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TEXTS SCIENCE DAILY: TEXT ALERGY 1: How Household Dogs Protect Aga!st Asth"a a!d I!#ecto! Dec. 16, 2013 — Children's risk for developing allergies and asthma is reduced when

they are exposed in early infancy to a dog in the household, and now researchers have discovered a reason why. Share Ths:

%$Exposure of mice to dust from houses where canine pets are permi tted both indoors and outdoors can reshape the community of microbes microbes that live in the mouse gut -- collectively collectively known as the gastrointestina gastrointestinall microbiome -- and also diminish immune system system reactivity reactivity to common common allergens, according according to a new study by researchers researchers led by usan !ynch, "h#, associate professor professor with the #ivision of $astroenterology at %C an &rancisco, and icholas !ukacs, "h#, professor with the #epartment of "athology at the % (ichigan. )he scientists also identified a specific bacterial species within the gut that is critical to protecting the airways against both allergens and viral respiratory infection. )he study, study, funded funded by the ation ational al *nstit *nstitute ute of +llerg +llergy y and *nfectio *nfectious us #isease #iseases s *+*# *+*#, , is publish published ed online online this week week in theProceedings of the National Academy of Sciences "+ and involves a multi-disciplinary group of researchers from %C&, the %niversity of (ichigan, enry &ord ealth ystem and $eorgia /egents %niversity. )he results were obtained in studies of mice challenged with allergens after earlier exposure to dust from homes with dogs, but the results also are likely to explain the reduced allergy risk among children raised with dogs from birth, according to the study leaders. *n their study the scientists exposed mice to cockroach or protein allergens. )hey discovered that asthma-associated inflammatory responses in the lungs were greatly reduced in mice previously exposed to dog-associated dust, in comparison to mice that were exposed to dust from homes without pets or mice not exposed to any dust.  +mong the bacterial species in the gut microbiome of these protected mice, the researchers homed in on one, !actobacillus  0ohnsonii. 1hen they fed it alone to mice, they found it could prevent airway inflammation due to allergens or even respiratory syncytial virus /2 infection. evere /2 infection in infancy is associated with elevated asthma risk. )he researchers showed in this experiment that protection of the lungs' airways was associated with reduced numbers and activity of asthma-associated immune cells. )he level of protection with this single species was less than that obtained with the full complement of dust microbes from dog owners' homes, indicating that other, environmentally sourced bacterial species probably are necessary for full airway protection, !ynch said. )his result suggests that !actobacillus 0ohnsonii or other species of 3good3 bacteria might one day be used to reshape the gut microbiome in ways that can prevent the development of asthma or allergies, or perhaps even to treat existing cases, she said. !ynch's own work and research by several others in the field has led her to become convinced that 3the composition and function of the gut microbiome strongly influence immune reactions and present a novel avenue for development of therapeutics for both allergic asthma and a range of other diseases.3 )he current study demonstrates demonstrates that changes changes in the gut microbiome can have wide-reachin wide-reaching g effects effects on immune function function beyond beyond the gut, at sites elsewhere in the body, !ynch said. )he team had previously demonstrated that the presence of a dog that roams both inside and outside was associated with a significantly more diverse house dust microbiome that was enriched for species found in the gastrointestinal tract of humans.  +fter teaming up with !ukacs, an expert on immune responses in lung disease, !ynch said, 31e set out to investigate whether being exposed to a distinct house dust microbiome associated with indoor4outdoor dogs mediated a protective effect through manipulation of the gut microbiome and, by extension, the host immune response.3 3)he results of our study indicate that this is likely to be one mechanism through which the environment influences immune respon responses ses in early early life, life, and it is somethi something ng we are currently currently examinin examining g using using human human samples samples in a large large multi-i multi-inst nstitu itutio tional nal collaborative study funded by the *+*#.3 3$ut microbiome manipulation represents a promising new therapeutic strategy to protect individuals against both pulmonary infection and allergic airway disease,3 !ynch said.

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L!' (etwee! Allerges) I!creased Rs' o# (lood Ca!cers ! *o"e! Nov. 22, 2013 — + team of scientists looking into the interplay of the immune system

and cancer have found a link between a history of airborne allergies -- in particular to plants, grass and trees -- with risk of blood cancers in women. Share Ths: $

otably, the study did not find the same association in men, which suggests a possible gender-specific role in chronic stimulation of the immune system that may lead to the development of hematologic cancers. )he findings are published online ahead of the #ecember print issue of the American "ournal of #ematology . 3)o the best of our knowledge, ours is the first study to suggest important important gender differences differences in the association association between between allergies allergies and hematologic hematologic malignancies,3 malignancies,3 wrote first author (a5yar hadman, (.#., (.".., a senior fellow in the Clinical /esearch #ivision at &red utchinson Cancer /esearch Center.  +ccording to hadman, who led the research, the immune system's potential role in cancer causation is a focus of intense scientific interest. 3*f your immune system is over-reactive, then you have problems6 if it's under-reactive, you're going to have problems. *ncreasing evidence indicates that dysregulation of the immune system, such as you find in allergic and autoimmune disorders, can affect survival of cells in developing tumors.3 &or the study, hadman, principal investigator Emily 1hite, "h.#., of the "ublic ealth ciences #ivision at &red utch and their colleagues drew on a large, population-based sample of men and women from the 2*)ami 2*)amins ns +nd !ifest !ifestyle yle 2*)+! 2*)+! cohort cohort,, which which includ included ed people people aged aged 78-9: 78-9: years years old from from wester western n 1ashin 1ashingto gton. n. )he study study partic participa ipants nts answe answered red a ;<-pag ;<-page e =uesti =uestionn onnair aire e that that focused focused on three three ma0or ma0or areas> areas> health health histor history y and cancer cancer risk risk factor factors, s, medication and supplement use, and diet. "articipants provided information on age, race4ethnicity, education, smoking, diet fruit and vegetable intake, and other lifestyle characteristics, self-rated health, medical history, and family history of leukemia or lymphoma. istory of asthma and allergies allergies was also taken, including including allergies to plants, grasses grasses or trees6 trees6 mold or dust6 cats, dogs or other animals6 insect bites or stings6 foods6 and medications. ?f the 9@,A88 2*)+! participants who filled out the =uestionnaires, more than ::,888 individuals were selected after eliminating those who had a prior history of malignancies other than non-melanoma skin cancers and missing information on baseline cancer history. "articipants were followed for a median of eight years until they withdrew from the study, moved away, had a cancer diagnosis other than hematologic malignancy or non-melanoma skin cancer, or died. *ncidence of hematologic malignancies and other cancers was identified via the urveillance, Epidemiology and End /esults EE/ cancer registry of western 1ashington. ?f the participants, :B developed a hematologic malignancy during the follow-up period. )hese participants were more likely to be male, to have two or more first-degree first-degree relatives relatives with a family history of leukemia or lymphoma, to be less active and rank their health status as low. + history of allergies to airborne antigens was associated with a higher risk of hematologic malignancies. )he most statistically significant association was seen with allergies to plants, grass and trees. &urther, the study looked at associations between the different subtypes of allergies and hematologic malignancies and found that a history of allergies to plants, grass and trees was significantly associated with mature D-cell neoplasms, one of four ma0or categories of lymphoma. )here was also an increased risk of plasma-cell neoplasms for participants who reported a history of allergies to cats, dogs or other animals. "lasma-cell neoplasms are conditions, both cancerous and noncancerous, in which the body makes too many plasma cells. 1hen stratified by gender, the incidence of blood cancers in response to these allergens was increased in women but not in men. )he reason for this is as yet unknown. 3*t is tempting tempting to speculate speculate that the additional additional effect of allergy may reach statistical statistical significance significance in women because of their lower baseline risk for the development of hematologic malignancies compared to men,3 the authors wrote. 3owever, hormonal effects on the immune system and interactions with carcinogenesis may offer an alternative biological explanation that will re=uire further mechanical studies, in particular if our findings are replicated in an independent study cohort.3 )he data analysis took into account potential confounding factors such as sex, race4ethnicity, education, history of smoking, consumption of vegetables and fruits, level of exercise, family history of leukemia4lymphoma and self-reported health status. )ypes of allergy medication participants used were not controlled for. 3*t's tough to eliminate allergy treatment as a confounder, because  0ust about everyone with allergies is on some medication. Dut none of the allergy medications are known to cause cancer,3 hadman said. )he authors cite the study's strengths as its large population si5e, the comprehensive baseline data regarding cancer risk and medical conditions, its prospective design and its use of the EE/ registry, an award-winning cancer registry program based at &red utch. (eanwhile the authors acknowledge the study's limitations, namely the reliance on self-reporting of allergies, the limitation of soliciting answers about current allergies only, and particularly the limited number of hematologic cancers for each subset of allergy types.

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3$iven the limited number of cases within each subtype of hematologic cancer, the risk estimates need to be interpreted with caution  and the possibility of chance finding due to multiple testing should be recogni5ed,3 hadman and colleagues wrote.

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Noth!+ to S!ee,e At: New Treat"e!t #or Co""o! Allerges $ct. 3, 2013 — /esearchers have successfully tested treatments for people with

allergies to grasses and to dust mites. Share Ths: 1$

)here are two treatments, one for grass allergy, which is commonly known as hay fever, and the other for dust mite allergy. )hey are expected to be helpful for the millions of people who, as a reaction to grass pollen or the tiny bugs that live in house dust, have snee5ing, itching eyes and a running nose that often significantly impacts their productivity at school or work. )he two studies were conducted by +diga !ife ciences, a 0oint venture between (c(aster %niversity and Circassia, a %.F. based biotechnology company, and was supported by t. Goseph's ealthcare amilton. *t is estimated that together, these allergens are responsible for more than 78H of allergic respiratory disease. Detween 7 and ;7 per cent of the population in orth +merica and Europe is sensitive to pollen from different grass species. ?ne in four people is sensiti5ed to house dust mites, more than any other common allergen, which includes millions of people in these regions. )he treatments are from a new class of therapy, known as 'synthetic peptide immuno-regulatory epitopes', or "*/Es. )he ;B8 patients in the phase two clinical trial for the grass allergy treatment recorded their allergy symptoms while exposed to grass pollen in a controlled environment, both before treatment and at the end of the hay fever season. tudy participants received one of three treatment regimens over three months, completed prior to the beginning of the pollen season. )hose who had the optimal short course of therapy had significantly improved symptoms at the end of the season, compared to those who had a placebo. )his treatment, called $rass-"*/E, was well tolerated. #uring the clinical trial for the dust mite treatment, 9; patients who received four doses of the treatment over ; weeks had significantly improved allergy symptoms a year after the start of treatment, compared to patients who received a placebo. )he treatment, called #(-"*/E, was well tolerated. 3)his result is an important validation of the approach we are taking to treat allergic diseases,3 said (ark !archI, who led the design of the treatments. 3"ositive results, first with a cat allergy therapy and now with house dust mite and grass allergy treatments, suggest that this approach may be used for many common allergies.3 !archI is a professor of medicine of the (ichael $. #e$roote chool of (edicine at (c(aster and member of the &irestone *nstitute for /espiratory ealth at t. Goseph's ealthcare amilton. ay fever is a seasonal response to many different grass pollens which are heaviest in the spring and fall. #ust mites are close relatives of spiders and ticks and are too small to see without a microscope. )hey eat skin cells shed by people, and they thrive in warm, humid environments. %pholstered furniture, bedding and carpeting provide an ideal environment for dust mites.

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L!' (etwee! Red Cell Dstr.uto! *dth Le/els) De0resso! Nov. 1%, 2013 — /esearchers at the *ntermountain (edical Center eart *nstitute have

discovered a link between elevated red cell distribution width levels and depression in patients being treated for heart disease. )his new discovery can help physicians provide earlier diagnosis and treatment for possible depression in heart patients. Share Ths:

/ed cell distribution width or /#1 is a parameter that measures variation in red blood cell si5e or red blood cell volume. + high /#1 over <.7H means that the red blood cells vary a lot in si5e. + normal /#1 is .: to <.:H, but researchers from the *ntermountain (edical Center eart *nstitute found that patients with a /#1 level greater than or e=ual to ;.@H had an increased risk for depression. )he new study found that the higher the /#1, the greater the risk for depression for patients. )his is the first time this association has been discovered. /esults of the study will be presented during the +merican eart +ssociation cientific essions in #allas, on (onday, ovember B at @>A8 am, E). 3Elevated red blood distribution widths are associated with anemia, but it also appears to be associated with other poor outcomes, like heart attacks, heart failure, death and now depression,3 said eidi (ay, "h#, (", the study's principal researcher at the *ntermountain (edical Center eart *nstitute in (urray, %tah. )his study looked at
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Iro! Su00le"e!tato! Ca! Pro/de Cog!t/e) Phscal (e!e#ts to A!e"c Chldre! $ct. 1&, 2013 — $iving daily iron supplements to anemic primary-school-aged children

can have cognitive and physical benefits, according to a study published in '(A"  'anadian (edical Association "ournal . Share Ths:

$lobally, approximately ;7H of school-aged children are anemic, with iron deficiency the cause of about half of all cases. *ron deficiency, which has been associated with impaired cognitive and physical development, is caused by a lack of dietary iron and, in developing countries, by parasites such as hookworm and schistosomiasis. *n developed countries, newcomers, native people and some ethnic populations can be anemic. +bout AH of primary-school-aged children in Canada are anemic. owever, concerns that iron supplementation may have negative health effects limit efforts to address iron deficiencies. )o understand the effects of iron supplementation, +ustralian researchers conducted an analysis of A; studies including 98B@ children mainly in low- and middle-income countries. +nemic children who received iron supplements had higher cognitive scores than children in the control groups @ studies with ;A77 children. )hey also showed substantial improvement in *J scores and other cognitive tests. Children who received iron supplements were also slightly taller for their age and had improved weight-forage compared with children who did not. 31e found evidence of a benefit of iron supplementation on cognitive performance among primary-school-aged children, including on *J among children with anemia,3 writes #r. ant-/ayn "asricha, )he /oyal (elbourne ospital and the &aculty of (edicine, #entistry and ealth ciences, )he %niversity of (elbourne, with coauthors. 3*ron may also improve growth. #aily iron supplementation decreased the prevalence of anemia by about 78H and reduced the prevalence of iron deficiency by [email protected] )here appeared to be no adverse effects, with no differences in the prevalence of malaria or gastrointestinal issues between the groups that received iron and the control groups. *n addition, some studies reported fewer respiratory tract infections. )he study is larger and broader than others, with a comprehensive analysis of benefits and safety of iron supplementation. 3*ron supplementation benefits global cognitive performance  ./outine daily iron supplementation is likely to benefit cognitive performance in primary school children in developing settings where anemia is prevalent and testing hemoglobin before iron supplementation may not be feasible,3 the authors conclude. *n a related commentary, #r. Fatherine $ray-#onald, (c$ill %niversity, (ontrIal, writes that this meta-analysis 3is important in that it =uantifies the robust effects of iron supplementation on cognitive performance among anemic children who are iron deficient. )he next challenge is to determine how to safely, economically and sustainably provide better iron nutrition to children in many poor settings of the world. Clearly anemic children will benefit, but the risks of iron for all remain to be elucidated.3

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Cerat! Ge!e -utato!s -a'e (reast Ca!cers Treat"e!t2Ressta!t Dec. 12, 2013 — 1omen with breast cancer characteri5ed by high levels of the protein

E/; and hormone receptors gained much less benefit from presurgery treatment with chemotherapy and E/;-targeted therapies if their cancer had one or more mutations in the "*FAC+ gene, according to results presented at the ;8A an +ntonio Dreast Cancer ymposium, held #ec. 8-<. Share Ths:

)reatment given to shrink or eliminate a tumor before surgery is called neoad0uvant therapy. *n some women with breast cancer treated with neoad0uvant therapy, no residual invasive cancer can be detected in breast tissue samples and lymph nodes removed during surgery. Emerging data suggest that these women, who are said to have had a pathologic complete response, have a greater chance of long-term survival compared with women who do not have a pathologic complete response. 3(utations in the "*FAC+ gene are among the most common genetic aberrations in breast cancer,3 said ibylle !oibl, (.#., professor at the $erman Dreast $roup in eu-*senburg, $ermany. 31e found that very few women with E/;- and hormone receptor-positive breast cancer with a "*FAC+ mutation experienced a pathologic complete response after receiving neoad0uvant therapy. 31e need to identify new treatment options for this group of patients and evaluate them in clinical trials,3 continued !oibl. 31e also need to integrate "*FAC+ mutation analysis of breast tumors into routine practice so that we can ensure women receive the most appropriate neoad0uvant therapy for their tumor type.3 !oibl and colleagues investigated whether the presence of a "*FAC+ mutation affected patients enrolled in the $eparixto $: clinical trial in experiencing a pathologic complete response after neoad0uvant therapy. )here were 7@7 participants in the $: clinical trial, and information on the presence or absence of "*FAC+ gene mutations was available for 7;,;<8 with E/;-postive breast cancer and ;9; with triple-negative breast cancer. "articipants in the $: clinical trial received neoad0uvant chemotherapy paclitaxel and nonpegylated-liposomal doxorubicin and were randomly assigned the chemotherapy carboplatin or no additional chemotherapy. "atients with E/;-positive disease also received neoad0uvant trastu5umab and lapatinib, two E/;-targeted therapies, while patients with triple-negative disease also received neoad0uvant bevaci5umab. !oibl and colleagues found that patients with E/;-postive breast cancer were more likely to have at least one "*FAC+ mutation in their tumor compared with women with triple-negative breast cancer. ?verall, the pathologic complete response rate was lower among women with at least one "*FAC+ mutation in their tumor compared with women without a "*FAC+ mutation, but the effect was only significant among the group of women with E/;- and hormone receptor-positive breast cancer. +mong these women, patients with a "*FAC+ mutation had a pathologic complete response rate of only :.7 percent compared with A8.B percent for those without a "*FAC+ mutation. 3)o evaluate these findings in a group with only one E/; treatment, we are currently analy5ing data from another clinical trial, the $eparJuinto clinical trial, which is a randomi5ed, phase *** clinical trial evaluating two different neoad0uvant therapy regimens with a single anti-E/; treatment Ktrastu5umab or lapatinibL for women with E/;-positive breast cancer,3 said !oibl. 31e hope to present these results together with those from the $: clinical trial in an +ntonio.3

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Lo!g2Last!g Ge!e Thera0 (e!e#ts Ad/a!ced Heart 3alure Pate!ts Nov. 1), 2013 — /esearchers from the Cardiovascular /esearch Center at *cahn

chool of (edicine at (ount inai reported the long-term benefits of a single dose of their gene therapy ++24E/C+;a in advanced heart failure patients on ov. @ at the  +merican eart +ssociation cientific essions ;8A. Share Ths: 1

)he new long-term follow-up results from their initial Calcium %p-/egulation by "ercutaneous +dministration of $ene )herapy *n Cardiac #isease C%"*#  clinical trial found a one-time, high-dose in0ection of the ++24E/C+;a gene therapy results in the presence of the delivered E/C+;a gene up to A months in the cardiac tissue of heart failure patients. *n addition, study results show clinical event rates in gene therapy patients are significantly lower three years later compared to those patients receiving placebo. +lso, patients experienced no negative side effects following gene therapy delivery at three-year follow-up. 3)his study shows ++24E/C+;a gene therapy has long-lasting and beneficial effects for congestive heart failure patients allowing us to block the downward spiral of patients with severe heart failure, 3 says principal investigator /oger G. a00ar, (#, #irector of the Cardiovascular /esearch Center and the +rthur M Ganet C. /oss "rofessor of (edicine at *cahn chool of (edicine at (ount inai, who developed the gene therapy approach. )he gene therapy uses a modified adeno-associated viral-vector derived from a parvovirus. )he one-time gene therapy is in0ected through the coronary arteries of heart failure patients using catheters. *t works by introducing healthy E/C+;a genes into cells. )he delivery of the E/C+;a gene produces E/C+;a en5ymes, which helps heart cells restore their proper use of calcium. E/C+;a is an en5yme critical for proper pumping of calcium in calcium compartments within cells. E/C+;a dysfunction or reduced expression occurs in patients with heart failure. 1hen E/C+;a is down-regulated, calcium stays longer in the cells than it should, and it induces pathways that lead to overgrowth of new and enlarged cells. )his contributes to an enlarged heart in heart failure patients. "reviously, C%"*#  study results showed the gene therapy to be clinically safe and effective for over ; months with improved heart function status and left ventricular function, along with a significant decrease in recurrent cardiovascular events. C%"*#  was the first-in human clinical gene therapy randomi5ed, double-blind study which enrolled A@ patients with advanced heart failure. 3++24E/C+;a gene therapy has been proven to be a safe and effective therapeutic intervention for advanced heart failure,3 says #r. a00ar. 3?ur long-term results support the potential use of ++24E/C+;a gene therapy as a new important additional tool for treating and managing advanced heart failure patients.3 )his study was presented as an ?ral ession +bstract 8::9> !ong )erm &ollow-up of "atients with +dvanced eart &ailure &ollowing a ingle *ntracoronary *nfusion of ++24E/C+;a. *n addition, on ov. @ #r. a00ar also presented at the ++ cientific essions ;8A a "lenary talk entitled, 3ow the "ostgenome Era 1ill Change the "ractice of Cardiology3 and discussed his work on targeted gene therapy for human heart failure. *n his "lenary talk, #r a00ar presented his new findings 0ust published in the 0ournal cience )ranslational (edicine on ov. A that show delivery of small ubi=uitin-related modifier  %(?-, an important regulator of E/C+;a, in preclinical heart failure models improves cardiac contractility and prevents left ventricular dilatation -- two ma0or aspects of heart failure. +ccording to #r. a00ar, the transition of this %(?- gene therapy from pigs to humans seems likely in the short-term. +lso, #r. a00ar revealed that development of novel cardiotropic vectors may render cardiovascular gene therapy easier and less-invasive in the near future.

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RNA (uld240 L!'ed to De"e!ta) -otor Neuro! Dsease $ct. 30, 2013 — + new toxic entity associated with genetically inherited forms of

dementia and motor neuron disease has been identified by scientists at the %C! *nstitute of eurology. )he toxin is the result of a genetic mutation that leads to the production of /+ molecules which could be responsible for the diseases. )he findings are published in the 0ournal Acta Neuro*athologica. Share Ths: 1

&rontotemporal dementia and motor neuron disease are related neurodegenerative diseases that affect approximately 7,888 people in the %F. &rontotemporal dementia causes profound personality and behaviour changes. (otor neuron disease leads to muscle weakness and eventual paralysis. )he most common known cause for both frontotemporal dementia and motor neuron disease is an unusual genetic mutation in the C@orf9; gene. )he mutation involves a small string of #+ letters at the beginning of the gene, which expand massively to produce thousands of copies. )he new research, funded by +l5heimer's /esearch %F and the (edical /esearch Council, has shown that this #+ expansion acts in a peculiar way, leading to the generation of unexpected /+ molecules that could cause the disease. 1hen a gene is turned on, an /+ copy of the gene's #+ is generated. )he gene's #+ code has directionality, so that it is normally turned on in only one direction, termed the 'sense direction'. )he new research shows that the #+ expansion is turned on in both directions. )his leads to the normal sense /+ being produced, as well as /+ in the opposite direction, termed 'antisense /+'. Doth /+ types accumulate into aggregates in the neurons of people with frontotemporal dementia. *ntriguingly, the research showed that people with more of these aggregates in their brains developed the disease earlier than people with less /+ aggregates. )his correlation suggests that the build-up may be important in causing frontotemporal dementia and motor neuron disease, making the C@orf9; #+ expansion a potential target for therapy. #r +drian *saacs, lead researcher at the %C! *nstitute of eurology, said> 33)hese findings identify new, potentially toxic molecules in diseases caused by #+ expansions. )he next steps will be to determine how they might kill neurons and how to stop them building up.3 #r imon /idley, ead of /esearch at +l5heimer's /esearch %F, the %F's leading dementia research charity, said> 3)he discovery of the C@?/&9; gene was a ma0or step forward for research into frontotemporal dementia and motor neuron disease, and it's positive to see researchers beginning to untangle how this gene may cause these diseases in some people. +l5heimer's /esearch %F is delighted to have supported this promising study. Dy unravelling some of the biological mechanisms at play, this research could take us further on the road to new treatments that are so desperately needed by the thousands of people with these devastating diseases. &or these results to reach their full potential it's vital that we continue to invest in research.3

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Det 6ualt L!'s 5ld) You!g Dec. 1%, 2013 — %nderstanding how dietary habits are connected through the

generations could have valuable benefits for community health, a new study shows. Share Ths:

)he )aiwanese study assessed the relationship between the =uality of children's diets and that of their elders in a wide range of representative communities, generating findings that have international relevance. !ed by Emeritus "rofessor (ark 1ahl=vist from (onash %niversity's #epartment of Epidemiology and "reventive (edicine and the (onash +sia *nstitute, the research used national survey information on health and nutrition for more than ;<88 students aged from six to A, and nearly B88 elderly people. 3)he groups of children who scored highest on dietary =uality showed a correlation with high dietary scores among their respective elders,3 "rofessor 1ahl=vist said. )his was seen within the context of a range of factors that were shown to influence the =uality of children's diets. 3&actors from level of household income and parental education to the amount of time children spend watching television were all found to be significant determinants of dietary =uality in children,3 "rofessor 1ahl=vist said. 1hen the overall findings were ad0usted for these aspects, the =uality of elders' diets was still significantly associated with that of young people's. )he researchers believe grandparents may be even more likely than parents to influence food habits. 3*t is likely that the grandparent generation is transmitting what the cultural group has ac=uired over several generations, modulated by their children and grandchildren,3 "rofessor 1ahl=vist said. )he research also raised the possibility that the association works both ways, with children's familiarity with information technology, for example, boosting their influence over their elders. $iven the links between diet and health issues such as obesity and longevity, the intergenerational associations are particularly relevant, "rofessor 1ahl=vist said. 3?ur findings suggest that a decline in nutritional capacity in communities, represented by intergenerational transfer of food patterns, may place community health at risk. +t the same time, the observations suggest that intervening with healthy eating measures in one generation may benefit other generations as well.3 )he study, which also involved the ational ealth /esearch *nstitutes, )aiwan, will be published later this month in the+cology of ood and Nutrition 0ournal.

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Stud L!'s Slee0 to -ood Dstur.a!ce) Poor 6ualt o# L#e ! 5.ese Dec. -, 2013 — + new study shows that poor sleep =uality is strongly associated with

mood disturbance and lower =uality of life among people with extreme obesity. Share Ths:

/esults show that 9<.B percent of participants were poor sleepers, and their mean self-reported sleep duration was only six hours and ;8 minutes. &ifty-two percent of study sub0ects were anxious, and
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*ll Ste" Cell Thera0 Hel0 Cure S0!al Cord I!8ur9 Dec. 1, 2013 — + systematic survey of the scientific literature shows that stem cell

therapy can have a statistically significant impact on animal models of spinal cord in0ury, and points the way for future studies. Share Ths: 1

pinal cord in0uries are mostly caused by trauma, often incurred in road traffic or sporting incidents, often with devastating and irreversible conse=uences, and unfortunately having a relatively high prevalence ;78,888 patients in the %+6 B8H of cases are male. igh-profile campaigners like the late actor Christopher /eeve, himself a victim of sports-related spinal cord in0ury, have placed high hopes in stem cell transplantation. Dut how likely is it to workO )his =uestion is addressed in a paper published 9th #ecember in the open access 0ournal P/$S iology   by +na +ntonic, #avid owells and colleagues from the &lorey *nstitute and the %niversity of (elbourne, +ustralia, and (alcolm (ac!eod and colleagues from the %niversity of Edinburgh, %F. tem cell therapy aims to use special regenerative cells stem cells to repopulate areas of damage that result from spinal cord in0uries, with the hope of improving the ability to move 3motor outcomes3 and to feel 3sensory outcomes3 beyond the site of the in0ury. (any studies have been performed that involve animal models of spinal cord in0ury mostly rats and mice, but these are limited in scale by financial, practical and ethical considerations. )hese limitations hamper each individual study's statistical power to detect the true effects of the stem cell implantation. )his new study gets round this problem by conducting a 3meta-analysis3 -- a sophisticated and systematic cumulative statistical reappraisal of many previous laboratory experiments. *n this case the authors assessed 7: published studies that examined the effects of stem cell treatment for experimental spinal in0ury in a total of about :888 animals. ?verall, they found that stem cell treatment results in an average improvement of about ;7H over the post-in0ury performance in both sensory and motor outcomes, though the results can vary widely between animals. &or sensory outcomes the degree of improvement tended to increase with the number of cells introduced -- scientists are often reassured by this sort of 3dose response,3 as it suggests a real underlying biologically plausible effect. )he authors went on to use their analysis to explore the effects of bias whether the experimenters knew which animals were treated and which untreated, the way that the stem cells were cultured, the way that the spinal in0ury was generated, and the way that outcomes were measured. *n each case, important lessons were learned that should help inform and refine the design of future animal studies. )he meta-analysis also revealed some surprises that should provoke further investigation -- there was little evidence of any beneficial sensory effects in female animals, for example, and it didn't seem to matter whether immunosuppressive drugs were administered or not.

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)he authors conclude> 3Extensive recent preclinical literature suggests that stem cell-based therapies may offer promise6 however the impact of compromised internal validity and publication bias means that efficacy is likely to be somewhat lower than reported here.3

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Sce!tsts Accelerate Ag!g ! Ste" Cells to Stud Age2Related Dseases L'e Par'!so!+s Dec. &, 2013 — tem cells hold promise for understanding and treating

neurodegenerative diseases, but so far they have failed to accurately model disorders that occur late in life. + study published by Cell "ress #ecember 7th in the 0ournal'ell Stem 'ell  has revealed a new method for converting induced pluripotent stem cells i"Cs into nerve cells that recapitulate features associated with aging as well as "arkinson's disease. )he simple approach, which involves exposing i"C-derived cells to a protein associated with premature aging called progerin, could enable scientists to use stem cells to model a range of late-onset disorders, opening new avenues for preventing and treating these devastating diseases. Share Ths:

31ith current techni=ues, we would typically have to grow pluripotent stem cell-derived cells f or :8 or more years in order to model a late-onset disease,3 says senior study author !oren5 tuder of the loan-Fettering *nstitute for Cancer /esearch. 3ow, with progerin-induced aging, we can accelerate this process down to a period of a few days or weeks. )his should greatly simplify the study of many late-onset diseases that are of such great burden to our aging society.3 (odeling a specific patient's disease in a dish is possible with i"C approaches, which involve taking skin cells from patients and reprogramming them to embryonic-like stem cells capable of turning into other disease-relevant cell types like neurons or blood cells. Dut i"C-derived cells are immature and often take months to become functional, similar to the slow development of the human embryo. +s a result of this slow maturation process, i"C-derived cells are too young to model diseases that emerge late in life. )o overcome this hurdle, tuder and his team exposed i"C-derived skin cells and neurons, originating from both young and old donors, to progerin. +fter short-term exposure to this protein, these cells showed age-associated markers that are normally present in old cells.

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)he researchers then used i"C technology to reprogram skin cells taken from patients with "arkinson's disease and converted the stem cells into the type of neuron that is defective in these patients. +fter exposure to progerin, these neurons recapitulated disease-related features, including neuronal degeneration and cell death as well as mitochondrial defects. 31e could observe novel disease-related phenotypes that could not be modeled in previous efforts of studying "arkinson's disease in a dish,3 says first author Gustine (iller of the loan-Fettering *nstitute for Cancer /esearch. 31e hope that the strategy will enable mechanistic studies that could explain why a disease is late-onset. 1e also think that it could enable a more relevant screening platform to develop new drugs that treat late-onset diseases and prevent degeneration.3

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New Clues to -e"or 3or"ato! -a Hel0 (etter Treat De"e!ta Nov. 2, 2013 — #o fruit flies hold the key to treating dementiaO /esearchers at the

%niversity of ouston % have taken a significant step forward in unraveling the mechanisms of "avlovian conditioning. )heir work will help them understand how memories form and, ultimately, provide better treatments to improve memory in all ages. Share Ths:

$regg /oman, an associate professor of biology and biochemistry at %, and hixing Phang, his postdoctoral associate, describe their findings in a paper titled 3"resynaptic *nhibition of $amma !obe eurons *s /e=uired for ?lfactory !earning in #rosophila,3 appearing ov. ;9 in 'urrent iology , a scientific bimonthly 0ournal published by Cell "ress. 3(emory is essential to our daily function and is also central to our sense of self,3 /oman said. 3)o a large degree, we are the sum of our experiences. 1hen memories can no longer be retrieved or we have difficulty in forming new memories, the effects are fre=uently tragic. *n the future, our work will enable us to have a better understanding of how human memories form.3 /oman and Phang set about to unravel some of these mysteries by studying the brains of fruit flies #rosophila. 1ithin the fly brain, /oman says, there are nerve cells that play a role in olfactory learning and memory. ?lfactory learning, he says, is an example of classical conditioning first described by "avlov in his experiment with dogs. *n their study, the flies were trained to associate a weak electric shock with an odor. +fter training, the flies avoided that odor. 31e found that these particular nerve cells -- the gamma lobe neurons of the mushroom bodies in the insect brain -- are activated by odors. )raining the flies to associate an odor with an electric shock changed how these cells responded to odors by developing a modification in gamma lobe neuron activity, known as a memory trace,3 he said. 3*nterestingly, we found that training caused the gamma lobe neurons to be more weakly activated by odors that were not paired with an electric shock, while the odors paired with electric shock maintained a strong activation of these neurons. )hus, the gamma lobe neurons responded more strongly to the trained odor than to the untrained odor.3

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)he team also showed that a specific protein -- the heterotrimeric $o protein -- is naturally involved in inhibiting gamma lobe neurons. /oman says removing the activity of this protein only within the gamma lobe neurons resulted in a loss of the memory trace and, thus, poor learning. )herefore, inhibiting the release of neurotransmitters from these neurons through the actions of the $o protein is key to forming the memory trace and associative memories. )he significance of using fruit flies is that while their brain structure is much simpler with far fewer neurons, the mushroom body is analogous to the perirhinal cortex in humans, which serves the same function of sensory integration and learning. )his simplicity allows scientists to gain insights into how memories are ac=uired, stored and retrieved. 3#rosophila represents the $oldilocks principle of neural research, with sufficient behavioral complexity, while maintaining a huge advantage in neural simplicity,3 /oman said. 3)he complex behaviors allow us to examine many behavioral processes like learning, attention, aggression and addiction-like behaviors, while the simplicity allows us to dissect the crucial neural activities down to single cells. +dditionally, #rosophila has the most powerful genetic toolkit available for behavioral experimentation. *n using these tools, we are genetically identifying the molecules necessary to perform these behaviors and dissecting the logic of the neural circuits that allow for changes in behavior to occur.3 )he pair says all their experience to date suggests the molecules and logic will translate to most animals, including humans, leading to a more complete understanding of how memories form in humans, both at the level of molecules and through the activity of neural circuits.

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D##ere!t Ge!e E;0resso! ! -ale) 3e"ale (ra!s -a Hel0 E;0la! (ra! Dsorder D##ere!ces Nov. 22, 2013 — %C! scientists have shown that there are widespread differences in

how genes, the basic building blocks of the human body, are expressed in men and women's brains. Share Ths: &

Dased on post-mortem adult human brain and spinal cord samples from over 88 individuals, scientists at the %C! *nstitute of eurology were able to study the expression of every gene in ; brain regions. )he results are published inNature 'ommunications. )hey found that the way that the genes are expressed in the brains of men and women were different in all ma0or brain regions and these differences involved ;.7H of all the genes expressed in the brain.  +mong the many results, the researchers specifically looked at the gene /QA, which has been implicated in autism. )he gene is transcribed into two ma0or forms and the study results show that although one form is expressed similarly in both men and women, the other is produced at lower levels in women in the area of the brain called the thalamus. )his observation could be important in understanding the higher incidence of autism in males. ?verall, the study suggests that there is a sex-bias in the way that genes are expressed and regulated, leading to different functionality and differences in susceptibility to brain diseases observed by neurologists and psychiatrists. #r. (ina /yten, %C! *nstitute of eurology and senior author of the paper, said> 3)here is strong evidence to show that men and women differ in terms of their susceptibility to neurological diseases, but up until now the basis of that difference has been unclear.

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3?ur study provides the most complete information so far on how the sexes differ in terms of how their genes are expressed in the brain. 1e have released our data so that others can assess how any gene they are interested in is expressed differently between men and women.3

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5rg! o# Al,he"er+s Ge!e -utato! Dsco/ered Dec. -, 2013 — )he age and origin of the E;B8+ gene mutation responsible for early-

onset +l5heimer's in a Colombian family with an unusually high incidence of the disease has been traced to a single founder dating from the :th century. Share Ths: &

Fenneth . Fosik, arriman "rofessor in euroscience at %C anta Darbara and co-director of the campus's euroscience /esearch *nstitute /*, conducted the study. )he findings appear in the 0ournal  Al!heimers  Dementia. 3ome mutations 0ust increase your risk, but this mutation is not a risk,3 Fosik said. 3)his mutation is highly penetrant, which means that if you carry the mutation, you will get early-onset +l5heimer's disease.3 Fosik's team se=uenced the genomes of more than 88 family members and applied identity-by-descent analysis to identify regions of common ancestry. #+ is inherited from both the parents and recombined in chunks. &rom these pieces, scientists can identify which parent -- and sometimes which grandparent or great-grandparent -- is the source of the #+. +s time goes by, sections of #+ recombine into smaller and smaller segments, each representing a history of its ancestry. e=uencing the genomes came about because the researchers knew that while most family members with the mutation develop early-onset +l5heimer's at age <7, there were a small number of outliers. 3+ few people got it a decade later, a few got it a decade earlier and we wondered if there was a gene that was protecting those who got the disease later,3 Fosik explained. 3)hat protective gene -- even though this mutation exists only in this Colombian family -- might be useful for all of us. )hat research is still ongoing.3

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?ut of the genome se=uencing came the idea of determining where the gene mutation originated. *n addition to #+ analysis, the researchers conducted interviews with the older healthy individuals of each affected family and spoke to genealogists and historians in Colombia's +ntio=uian region. Fosik's co-author &rancisco !opera examined local historical and genealogical books, last wills and ecclesiastical records dating as far back as 7<8. 1hen the scientists examined the #+ patterns around the gene mutation site, they found markers from the *berian peninsula. )hey estimated the age and geographic origin of E;B8+ to be consistent with a single founder dating from the time of the panish Con=uistadors who began coloni5ing Colombia during the early :th century. 3)his doesn't have big medical implications, but it shows that genetics is a very powerful tool and can be used to reconstruct history,3 Fosik said. 31hat we've done here might be called 'neuroarchaeology.' 3

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(ra! Area Attac'ed . Al,he"er+s L!'s Lear!!g) Rewards Dec. 1%, 2013 — ?ne of the first areas of the brain to be attacked by +l5heimer's

disease is more active when the brain isn't working very hard, and =uiets down during the brain's peak performance. Share Ths: 1

)he =uestion that #uke %niversity graduate student arah eilbronner wanted to resolve was whether this brain region, called the posterior cingulate cortex, or "CC, actively dampens cognitive performance, say by allowing the mind to wander, or is instead monitoring performance and trying to improve it when needed. *f the "CC were monitoring and improving performance, increased activity there would be the result of poor performance, not the cause of it. )he "CC connects to both learning and reward systems, eilbronner said, and is a part of the 3default mode network.3 *t lies along a mid-line between the ears, where many structures related to rewards can be found. 3*t's kind of a nexus for multiple systems,3 said eilbronner, who is currently a postdoctoral researcher in neuroanatomy at the %niversity of /ochester.

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3+s this area begins to deteriorate, people begin to show the early signs of cognitive decline -- problems learning and remembering things, getting lost, trouble planning -- that ultimately manifest as outright dementia,3 said (ichael "latt, director of the #uke *nstitute for Drain ciences, who supervised eilbronner's ;8; dissertation. )heir findings appear #ec. B in the 0ournal Neuron. eilbronner's experiment to better understand the "CC's role in learning and remembering relied on two rhesus maca=ue monkeys fitted with electrodes to read out the activity of individual neurons in their brains. )heir task was akin to playing video games with their eyes. )he monkeys were shown a series of photographs each day marked with dots at the upper left and lower right corners. )o get a rewarding s=uirt of 0uice, they had to move their ga5e to the correct target dot on a photo, and they learned by trial and error which dot would yield the reward for each photo. Each day, they were shown up to ; photos from an assortment of eilbronner's vacation snaps at Rellowstone ational "ark and the $rand Canyon. ome of each day's images were familiar with a known reward target, and others were new. +s the monkeys responded with their ga5e, the researchers watched the activity of do5ens of neurons in each monkey's brain immediately following correct and incorrect responses. )hey also altered the amount of 0uice dispensed in some cases, creating a sense of high-reward and low-reward answers. *f the "CC actively dampened performance, the researchers would expect to see it active before a choice is made or the feedback is received. *nstead, they saw it working after the feedback, lasting sometimes until the next image was presented. eurons in the "CC responded strongly when the monkeys needed to learn something new, especially when they made errors or didn't earn enough reward to keep motivated. )he researchers also ran the task after administering a drug, muscimol, that impaired the function of the "CC temporarily during testing. 1ith the center inactivated by the drug, the monkeys could recall earlier learning regardless of the si5e of the reward. !earning a new item was still possible when the reward was large, but the monkeys couldn't learn anything new when rewards were small. 3(aybe it didn't seem worth it,3 eilbronner said. )he dampening experiment also reinforced what the researchers had seen in the timing of the "CC's response. *f this center's role is to let the mind wander, performance should have improved when the muscimol was administered, but the opposite was true. eilbronner concludes that the "CC summons more resources for a challenging cognitive task. o rather than being the cause of poor performance on a task, "CC actually steps in during a challenge to improve the situation. 3)his study tells us that a healthy "CC is re=uired for monitoring performance and keeping motivated during learning, particularly when problems are challenging,3 "latt said. eilbronner is now interested in finding out whether the "CC is more important to learning than it is to recall, and how motivation interacts with "CC abnormalities seen in +l5heimer's disease.

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A!"al 7acc!e Stud Yelds I!sghts That -a Ad/a!ce HI7 7acc!e Research Dec. 1%, 2013 — + vaccine study in monkeys designed to identify measurable signs

that the animals were protected from infection by *2, the monkey version of *2, as well as the mechanism of such protection has yielded numerous insights that may advance *2 vaccine research. even laboratories collaborated on the study led by (ario /oederer, "h.#., and Gohn /. (ascola, (.#., at the 2accine /esearch Center of the ational *nstitute of +llergy and *nfectious #iseases *+*#, part of the ational *nstitutes of ealth. 33

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Dy examining both viral amino-acid se=uences and the animals' immune responses, the scientists could determine the mechanisms of protection from *2 infection. )he study demonstrated that antibodies to the virus spikes that *2 uses to infect cells are necessary and sufficient to prevent *2 infection. )he study also identified clear measures of immune responses in monkeys that predict protection from *2 infection.  +mid the genetically heterogeneous mix of *2 to which the vaccinated monkeys were exposed, vaccine-induced immune responses tended to block infection by those viruses sensitive to neutrali5ation by *2 antibodies, while neutrali5ation-resistant forms of *2 tended to cause infection. + two-amino-acid change to the spikes on *2 converted neutrali5ation-sensitive *2 to neutrali5ation-resistant *2, and vice versa. + similar change to the spikes on *2 had a related effect. )hus, *2 and *2 escape the immune system in similar ways, the scientists discovered. )hey concluded that the reasons why future human *2 vaccine trials fail or succeed will become clearer if scientists integrate information on the amino-acid se=uence and neutrali5ation sensitivity or resistance of the infecting virus together with information about volunteers' immune responses to the vaccine.

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New -ethod #or Sta.l,!g He"oglo.! Could Lead to Sta.le 7acc!es) Art#cal (lood Dec. -, 2013 — + %Conn research team has found a way to stabili5e hemoglobin, the

oxygen carrier protein in the blood, a discovery that could lead to the development of stable vaccines and affordable artificial blood substitutes. Share Ths: 1

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)he team's novel approach involves wrapping the polymer polyacrylic acid around hemoglobin, protecting it from the intense heat used in sterili5ation and allowing it to maintain its biological function and structural integrity. *n addition to having potential applications in the stabili5ation of vaccines and development of inexpensive artificial blood, the stabili5ing polymer also allows vaccines and other biomedical products to be stored for longer periods without refrigeration. *t could also have applications in biomaterials, biosensors, and biofuels. 3"rotein stability is a ma0or issue in biotechnology,3 says Challa 2. Fumar, %Conn professor of chemistry and biochemistry and the primary investigator on the pro0ect. 31hat we've done is taken this protein molecule and wrapped it up in a polymer chain in order to stabili5e it. *n thermodynamics terms, we have restricted the entropy of the denatured state of the protein and stabili5ed it beyond our expectations. )he system also exhibits a high degree of reversibility. )he protein can be denatured and renatured many, many times. )his is the very first example of its kind in the literature of all protein science. o one has ever been able to achieve this kind of stability for proteins.3  + popular example of denaturation can be found in the protein present in eggs. +s the egg is cooked and the protein around the yolk turns white, the protein in the egg is denatured and cannot return to its prior, natural state. !ikewise, when proteins in a living cell are exposed to heat they become denatured, which disrupts their activity and can lead to cell death. 1hen protein is a critical element in a vaccine and breaks down, the product becomes useless. *n searching for a viable material to serve as a protein stabili5er, Fumar's team found one that is readily available, inexpensive, and can be modified chemically for further improvements. )he polyacrylic acid used in the study is the same material found in disposable diapers, and one of the most abundant synthetic polymers on the planet. )his particular polymer, says Fumar, is very hydrophilic, meaning it likes water. )he polymer naturally binds to hemoglobin, creating a tight seal that protects the protein molecule and allows it to retain its structural integrity even after heating it to ;8SC for extended periods of time steam sterili5ation. Goining him on the pro0ect was /a0eswari Fasi, associate professor of chemistry, an expert in synthetic polymers and hybrid materials. )he research team also included graduate students> 2amsi (udhivarthi, Fyle Cole, *noka #eshapriya, Caterina /iccardi, and Ruxiang Phou, as well as undergraduate students (arc ovak and 1estley Fipphut. Fumar is proud of the fact that undergraduates participated in such a ma0or research endeavor. 3?ne of our missions at the %niversity is to train undergraduates in research,3 he says, 3and we take that very seriously.3 )he team tested various protein-polymer compositions using transmission electron microscopy )E( and optical spectroscopy techni=ues. )he research was supported by multiple grants from the ational cience &oundation, topping NA million over the past 8 years. *n a paper published last year in the "ournal of (aterials 'hemistry , Fumar and his team showed how hemoglobin wrapped in low molecular weight polyacrylic acid formed nanoparticles that retained their natural state and structure, even after they were sub0ected to the harsh conditions of steam sterili5ation. %nder the same conditions, hemoglobin samples that were not wrapped in the polymer lost the ma0ority of their structure and function. Fumar said these test results signaled the pro0ect's breakthrough moment.  +s part of its research, the team chose to examine the feasibility of using hemoglobin as an artificial blood substitute. emoglobin, when extracted from blood, breaks down and is toxic in its pure form. ince hemoglobin is the critical oxygen carrier protein in blood, Fumar and his team are looking at ways of stabili5ing hemoglobin in its natural form so that it retains its activity and stays harmless when administered as a transfusion agent. )his could lead to a new substitute for human blood, which is fre=uently in short supply. Dlood shortages are expected to get worse in coming years, as more and more people in the world are likely to need blood transfusions, Fumar said. )he research has caught the attention of scientists at (erck, a global leader in prescription medicine, vaccines, and biologic therapies. 3Deing able to control the placement of proteins in polymer matrices of defined si5e brings exciting opportunities for producing potent and heat-stable vaccine antigens,3 says enryk (ach, a senior investigator with (erck's vaccine drug product development division. 3"rof. Fumar's work may well provide technologies for vaccine delivery in the developing world.3 )he abundance of the polymer, the flexibility of the process, and the simplicity of the approach enhances its potential for mass production, Fumar says.

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New Tu.erculoss 7acc!e De/elo0ed $ct. 1, 2013 — + tuberculosis vaccine developed at (c(aster %niversity offers new

hopes for the global fight against tuberculosis. Share Ths: 

37

31e are the first to have developed such a vaccine for tuberculosis,3 said #r. &iona maill, professor and chair of the #epartment of "athology and (olecular (edicine of the (ichael $. #e$roote chool of (edicine at (c(aster. he led the phase one clinical study published today in the 0ournal Science ranslational (edicine. )he vaccine, based on a genetically modified cold virus, was developed in the lab of Phou Qing, professor of pathology and molecular medicine and the (c(aster *mmunology /esearch Centre, who co-led the phase one study. Doth are also members of the (ichael $. #e$roote *nstitute for *nfectious #isease /esearch. 3)uberculosis is a serious public health threat,3 maill said. 3?ne-third of world's population is infected with the organism that causes tuberculosis, and it remains the top infectious killer of people only secondary to *26 yet, the current vaccine used to prevent it is ineffective.3 )he control of tuberculosis )D has met with further challenge from high incidence of multi-drug resistant tuberculosis, she added. )he new vaccine was developed to act as a booster to Dacille Calmette $uerin DC$, currently the only )D vaccine available. DC$ was developed in the @;8s and has been used worldwide. )he new 3booster3 would reactivate immune elements that over time diminish following DC$ vaccination. Currently the DC$ vaccine is part of the 1orld ealth ?rgani5ation's immuni5ation program in +sia, +frica, Eastern Europe and outh +merica, as well as unavut, the only Canadian 0urisdiction where the DC$ vaccine is routinely given because of the high rate of tuberculosis in the territory. *t is typically given in the first year of life. )he (c(aster vaccine has been more than a decade in the making. (c(aster researchers began the first human clinical trial in ;88@ with ;< healthy human volunteers, including ; who were previously DC$-immuni5ed. 3)he primary goal was to look at the safety of a single dose vaccine in0ection,3 said Qing, 3as well as its potency to engage the immune system.3 Dy ;8; they established that the vaccine was safe and observed a robust immune response in most trial participants. (ore clinical trials are needed to measure the vaccine's real potential, Qing added. maill added> 3+s a doctor who looks after patients who have tuberculosis, including those who are *2 infected, * reali5e how important it is going to be to control this infection with a good vaccine. 31e are probably one of a few groups in the world who are actually doing bench-to-human tuberculosis vaccine work, and we are excited to be part of this and thrilled that it started at (c(aster.3

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New I!sght ! 6uest #or S!gle 7acc!e Aga!st -ult0le 3lus 39

$ct. 21, 2013 — + study led by t. Gude Children's /esearch ospital scientists

highlights a new approach for developing a universal influen5a vaccine that could protect against multiple flu strains, including deadly pandemic strains. )he research appears today in the advance online edition of the scientific 0ournalNature 4mmunology . Share Ths:

/esearchers used the immune suppressing drug rapamycin to shift the immune response following flu vaccination to favor production of antibodies that broadly target flu viruses. )he result was a more diverse antibody response to the vaccination that expanded protection to include pandemic strains not targeted by the vaccine. 2accination is the most effective strategy against flu, particularly the pandemic strains that emerge periodically, but efforts to develop a single, universal vaccine against all flu strains have been unsuccessful. )he findings highlight a novel way to generate antibodies that recogni5e and target proteins shared by most influen5a + strains rather than those uni=ue to each strain. +ntibodies are produced by D cells to recogni5e and defend against viruses. )he same strategy might aid efforts to design vaccines against other viruses, researchers said. Current flu vaccines emphasi5e production of highly specific antibodies. )hey target and bind tightly to strain-specific regions of hemagglutinin + and neuraminidase + proteins on the virus. )hat approach re=uires developing and administering a new flu vaccine each year to keep up with changes in those uni=ue and highly variable + and + proteins. *nvestigators showed the new strategy protected mice -- vaccinated against the A; influen5a + flu strain, which causes mild disease -- from succumbing to the more dangerous 7 and 9@ strains weeks later. 1hen researchers transferred antibodyrich serum from vaccinated to unvaccinated mice, the unvaccinated animals were also protected from later 7 infection, an indication that the protection came from antibodies rather than from other immune system components. 3)his study has changed our approach to developing a universal flu vaccine,3 said corresponding author (aureen (c$argill, "h.#., an assistant member of the t. Gude #epartment of *mmunology. 3*nstead of trying to enhance a highly specific, targeted immune response, our results show that a more diverse, less focused response provides a broader repertoire of antibodies that target different flu strains.3 *nfluen5a -- particularly pandemic strains that emerge periodically as flu viruses mix and form novel strains -- remains a global health threat. )he influen5a + 7 avian pandemic strain has a mortality rate of nearly :8 percent. )he 1orld ealth ?rgani5ation estimates that each year flu and flu-related complications kill more than ;78,888 individuals worldwide. 2accination is the most effective strategy to combat the infection. Dut existing vaccines protect against 0ust the dominant seasonal flu strain and not emerging flu strains. )his study also advanced understanding of the role a protein named m)?/ plays in generating the highly specific antibodies. /apamycin works by inhibiting m)?/, which is involved in cell survival and proliferation. /esearchers used the drug to track how blocking m)?/ affected the immune response of mice following A; vaccination. *nhibiting m)?/ disrupted generation of the antibodies that target specific regions of the + proteins that are uni=ue to each flu strain. /esearchers showed that loss of m)?/ delayed the formation of the immune structure called a germinal center. )hat is where antibodies are reshaped through a process called class switching. )he process hones their focus and primes them to target flu viruses based on the uni=ue, rather than shared, surface proteins. )he finding was surprising because previous research had highlighted a likely role for white blood cells known as C#BT and C#
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7ruses Are as S"0le as The Are +S"art+ Nov. 2&, 2013 — 2iruses are as simple as they are 3smart3> too elementary to be able

to reproduce by themselves, they exploit the reproductive 3machinery3 of cells, by inserting pieces of their own #+ so that it is transcribed by the host cell. )o do this, they first have to in0ect their own genetic material into the cells they infect. +n international team of researchers, including Cristian (icheletti from *+ the *nternational chool for +dvanced tudies in )rieste, has studied how this occurs and how long it takes for this process to be completed. Share Ths:

(icheletti and colleagues constructed a computer model of viral #+ and then simulated the release of genetic material from the viral capsid into the host cell nucleus. &ar from being a fluid process, this e0ection is sub0ect to frictional forces that depend on the conformation of the #+ strand. 3&luidity of the process depends on how and how tightly the viral #+ is entangled,3 explains (icheletti. 3)he more topologically ordered is the double strand of the genome, the f aster it is e0ected from the virus. )he situation is somewhat similar to the behaviour of an anchor line that has been correctly coiled> when the anchor is thrown overboard, the line uncoils neatly without stops or 0erks due to tangles.3 #+ has an intrinsic characteristic that makes its pattern of spontaneous arrangement very singular. Decause it has two strands, #+ has a tendency to form highly ordered coils, 0ust like anchor lines or thread spools. )his isn't the case with generic polymers, which form complex and chaotic tangles. )he simulations by (icheletti and colleagues compared the behaviour of a model strand of #+ and a simple strand of generic polymer. 3*n @7H of cases the model #+ slid through the exit pore of the virus much faster than the simple polymer, as a result of the greater spontaneous order of its conformation,3 comments (icheletti. 3)he simple strands may be even ten times slower than the #+ strands. +nother interesting thing is that, although much more slowly, the simple strands in our observations always succeeded in leaving the virus completely. Dy contrast, in a small minority of cases, the #+ remained totally blocked, and this too is related to its tendency to form a spool that may sometimes present such complex torus knots -- i.e., doughnut-like -- to completely block e0ection from the virus.3 )he process timescales observed by (icheletti and colleagues are perfectly consistent with empirical observations, 3including all cases of complete #+ stalling that have been reported, though not explained, in some experiments,3 concludes (icheletti. 3?ur study, which estimated the time it takes viral #+ to leave the capsid in relation to its length and degree of packing could provide the starting point for designing artificial viral vectors.3 )he study has 0ust been published in the Proceedings of the National Academy of Sciences 5PNAS.

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Sce!tsts Dsco/er *h New.or!s Get Sc' So 5#te! $ct. 31, 2013 — *f you think cold and flu season is tough, trying being an infant. + new research finding published in the ovember ;8A issue of the "ournal of /eu7ocyte iology  sheds new light on why newborns appear to be so prone to getting sick with

viruses -- they are born without one of the key proteins needed to protect them. )his protein, called 3toll-like receptor A3 or 3)!/A,3 is involved in the recognition of different viruses and mediates the immune response to them. 1ithout this protein, newborn immune cells are not e=uipped to recogni5e and react appropriately to certain viruses, in particular, the herpes simplex virus known as 2. Share Ths: $

3)his study helps to understand the molecular basis for the immaturity of the immune system of newborns, which we believe will contribute to development of therapeutic interventions to protect this vulnerable population group,3 said !uci0a lavica, a researcher involved in the work from the #epartment of /heumatology and *nflammation /esearch at the %niversity of $othenburg in $othenburg, weden. )o make this discovery, scientists compared cells from the cord blood of newborns with the same type of blood cells from adults. )he cells from newborns did not contain the protein )!/A, which was present in adult cells. )hese cells rid the body of viralinfected cells, ultimately eliminating viral infections. 1hen researchers treated both cell groups with a synthetic component mimicking a viral presence, the adult immune cells reacted by secreting substances involved in immune reaction against viruses interferon-gamma and killed cells infected with virus, while cells from newborns could not do this or were impaired in performing this function. 3)his study adds to the growing body of research stemming from the obel-winning discovery in ;8 on how the immune system recogni5es microbes by shedding light on how these pathways develop over time after birth,3 said Gohn 1herry, "h.#., #eputy Editor of the "ournal of /eu7ocyte iology . 3)his report is particularly important -- as any new parent can attest, infants are particularly susceptible to infections and understanding which pathways are not yet functional could lead to novel therapies.3

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*hat the S"allest I!#ectous Age!ts Re/eal A.out E/oluto! (ay 23, 2013 — /adically different viruses share genes and are likely to share

ancestry, according to research published in Dio(ed Central's open access  0ournal 8irology "ournal this week. )he comprehensive phylogenomic analysis compares giant viruses that infect amoeba with tiny viruses known as virophages and to several groups of transposable elements. )he complex network of evolutionary relationships the authors describe suggests that viruses evolved from non-viral mobile genetic elements and vice versa, on more than one occasion. Share Ths: &1

)he recent discovery of virophages inside the giant viruses, which in turn infect amoeba, has led to speculation about their origin and their relationship to other viruses and small transposable genetic elements. )o try to answer this =uestion a research team including Eugene Foonin from the * and #idier /aoult from %/(*)E compared the genetic material from virophages, such as the (avirus, putnik, or ?!2 which was isolated from an +ntarctic organic lake, to eukaryotic self replicating transposable elements known as "olintons or (avericks. Eugene Foonin explains> 3Detween the known virophages there are six conserved genes, arranged in a similar way. &ive of these have counterparts in the "olintons, but their se=uence and arrangement are sufficiently different to discount suggestions that "olintons evolved directly from a (aviruse-like ancestor. /ather our data suggests that (aviruses have evolved from a fusion between a "oliton4(averick-like transposable element and an unknown virus.3 *ncluding information about other viruses and virus-like elements> adenoviruses that infect animals and are one of the causes of the common cold6 certain bacteriophages that infect bacteria6 transpovirons which infect giant viruses6 and a )etrahymena transposable element )lr, the virus 3evolutionary tree3 appears as a network of swapped genes. #idier /aoult, whose team discovered the transpovirons, says> 3*t appears that viruses have evolved from non-viral genetic elements and vice versa on more than one occasion. 2iral evolution is more complex than we thought.3

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Hgh Cholesterol 3uels Growth) S0read o# (reast Ca!cer  Nov. 2%, 2013 — + byproduct of cholesterol functions like the hormone estrogen to fuel

the growth and spread of the most common types of breast cancers, researchers at the #uke Cancer *nstitute report. Share Ths: 1&

)he researchers also found that anti-cholesterol drugs such as statins appear to diminish the effect of this estrogen-like molecule. "ublished in the ov. ;@, ;8A, edition of the 0ournal Science, the findings are early, using mouse models and tumor cells. Dut the research for the first time explains the link between high cholesterol and breast cancer, especially in post-menopausal women, and suggests that dietary changes or therapies to reduce cholesterol may also offer a simple, accessible way to reduce breast cancer risk. 3+ lot of studies have shown a connection between obesity and breast cancer, and specifically that elevated cholesterol is associated with breast cancer risk, but no mechanism has been identified,3 said senior author #onald (c#onnell, "h.#., chair of the #epartment of "harmacology and Cancer Diology at #uke. 31hat we have now found is a molecule -- not cholesterol itself, but an abundant metabolite of cholesterol -- called ;9C that mimics the hormone estrogen and can independently drive the growth of breast cancer.3 )he hormone estrogen feeds an estimated 97 percent of all breast cancers. *n a key earlier finding from (c#onnell's lab, researchers determined that ;9-hydroxycholesterol -- or ;9C -- behaved similarly to estrogen in animals. &or their current work, the researchers set out to determine whether this estrogen activity was sufficient on its own to promote breast cancer growth and metastasis, and whether controlling it would have a converse effect. %sing mouse models that are highly predictive of what occurs in humans, (c#onnell and colleagues demonstrated the direct involvement of ;9C in breast tumor growth, as well as the aggressiveness of the cancer to spread to other organs. )hey also noted that the activity of this cholesterol metabolite was inhibited when the animals were treated with antiestrogens or when supplementation of ;9C was stopped. )he studies were substantiated using human breast cancer tissue. +n additional finding in the human tissue showed a direct correlation between the aggressiveness of the tumor and an abundance of the en5yme that makes the ;9C molecule. )hey also noted that ;9C could be made in other places in the body and transported to the tumor. 3)he worse the tumors, the more they have of the en5yme,3 said lead author Erik elson, "h.#., a post-doctoral associate at #uke. elson said gene expression studies revealed a potential association between ;9C exposure and the development of resistance to the antiestrogen tamoxifen. )heir data also highlights how increased ;9C may reduce the effectiveness of aromatase inhibitors, which are among the most commonly used breast cancer therapeutics. 3)his is a very significant finding,3 (c#onnell said. 3uman breast tumors, because they express this en5yme to make ;9C, are making an estrogen-like molecule that can promote the growth of the tumor. *n essence, the tumors have developed a mechanism to use a different source of fuel.3 (c#onnell said the findings suggest there may be a simple way to reduce the risk of breast cancer by keeping cholesterol in check, either with statins or a healthy diet. +dditionally, for women who have breast cancer and high cholesterol, taking statins may delay or prevent resistance to endocrine therapies such as tamoxifen or aromatase inhibitors. )he next steps for research include clinical studies to verify those potential outcomes, as well as studies to determine if ;9C plays a role in other cancers, (c#onnell said.

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Sce!tsts Dsco/er How I""u!e Cells De Dur!g HI7 I!#ecto!= Ide!t# Pote!tal Drug to (loc' AIDS Dec. 1), 2013 — /esearch led by scientists at the $ladstone *nstitutes has identified

the precise chain of molecular events in the human body that drives the death of most of the immune system's C#< ) cells as an *2 infection leads to +*#. &urther, they have identified an existing anti-inflammatory drug that in laboratory tests blocks the death of these cells -- and now are planning a "hase ; clinical trial to determine if this drug or a similar drug can prevent *2-infected people from developing +*# and related conditions. Share Ths: 1>

)wo separate 0ournal articles, published simultaneously today in Nature andScience, detail the research from the laboratory of 1arner C. $reene, (#, "h#, who directs virology and immunology research at $ladstone, an independent biomedical-research nonprofit. is lab's Science paper reveals how, during an *2 infection, a protein known as *&*: senses fragments of *2 #+ in abortively infected immune cells. )his triggers the activation of the human en5yme caspase- and leads to pyroptosis, a fiery and highly inflammatory form of cell death. +s revealed in the ature paper, this repetitive cycle of abortive infection, cell death, inflammation and recruitment of additional C#< ) cells to the infection 3hot 5one3 ultimately destroys the immune system and causes +*#. )he ature paper further describes laboratory tests in which an existing anti-inflammatory inhibits caspase-, thereby preventing pyroptosis and breaking the cycle of cell death and inflammation. 3$ladstone has made two important discoveries, first by showing how the body's own immune response to *2 causes C#< ) cell death via a pathway triggering inflammation, and secondly by identifying the host #+ sensor that detects the viral #+ and triggers this death response,3 said /obert &. iliciano, (#, "h#, a professor of medicine at Gohns opkins %niversity, and a oward ughes (edical *nstitute investigator. 3)his one-two punch of discoveries underscores the critical value of basic science -by uncovering the ma0or cause of C#< ) cell depletion in +*#, #r. $reene's lab has been able to identify a potential new therapy for blocking the disease's progression and improving on current antiretroviral medications.3 )he research comes at a critical time, as so-called +*# fatigue leads many to think that *24+*# is solved. *n fact, *2 infected an additional ;.A million people last year, according to %+*# estimates, bringing the global total of *2-positive people to A7.A million. +ntiretroviral medications +/2s can prevent *2 infections from causing +*#, but they do not cure +*#. &urther, those taking +/2s risk both a latent version of the virus, which can rebound if +/2s are discontinued, and the premature onset of diseases that normally occur in aging populations. "lus, some : million people who carry the virus do not have access to +/2s, according to 1orld ealth ?rgani5ation estimates. eeking solutions for all these challenges, the new $ladstone discovery builds on earlier research from #r. $reene's lab, published in Cell in ;88. )his study showed how *2 attempts, but fails, to productively infect most of the immune system's C#< ) cells. *n an attempt to protect the body from the spreading virus, these immune cells then commit 3cellular suicide,3 leading to the collapse of the immune system -- and +*#.  +fter that research, the $ladstone scientists began to look for ways to prevent this process by studying exactly how the suicidal response is initiated. 1orking in the laboratory with human spleen and tonsil tissue, as well as lymph-node tissue from *2-infected patients, the researchers found that these so-called abortive infections leave fragments of *2's #+ in the immune cells. +s described in ature, pyroptosis ensues as immune cells rupture and release inflammatory signals that attract still more cells to repeat the death cycle. 3?ur studies have investigated and identified the root cause of +*# -- how C#< ) cells die,3 said $ladstone taff /esearch *nvestigator $ilad #oitsh, "h#, who is the ature paper's lead author, along with icole $alloway and Qin $eng, "h#. 3#espite some A8 years of *2 research, this key *24+*# process has remained pretty much a black box.3 ?nce the scientists discovered this key process, as described in ature, they began to investigate how the body senses the fragments of *2's #+ in the first place, before alerting the en5yme caspase- to launch an immune response in the C#< ) cells. )o identify the so-called #+ sensor, the scientists found a way to genetically manipulate C#< ) cells in spleen and tonsil tissue. *n doing so, they discovered that reducing the activity of a protein known as *&*: inhibited pyroptosis, explained Phiyuan Rang, "h#, a $ladstone postdoctoral fellow who is one of the paper's two lead authors. 3)his identified *&*: as the #+ sensor, which then sends signals to caspase- and triggers pyroptosis,3 says Fathryn (. (onroe, "h#, the Science paper's other lead author, who completed the research while a postdoctoral fellow at $ladstone. 31e can't block a process until we understand all of its steps -- so this discovery is critical to devising ways to inhibit the body's own destructive response to *2. 1e have high hopes for the upcoming clinical trial.3 )he "hase ; trial -- which will test an existing anti-inflammatory's ability to block inflammation and pyroptosis in *2-infected people -- promises to validate a variety of expected advantages to this therapy. &or example, by targeting the human body, or host, instead of the virus, the drug is likely to avoid the rapid emergence of drug resistance that often plagues the use of +/2s. )he anti-

50

inflammatory may also provide a bridge therapy for the millions without access to +/2s, while also reducing persistent inflammation in *2-infected people already on +/2s. (any suspect this inflammation drives the early onset of aging-related conditions such as dementia and cardiovascular disease. Dy reducing inflammation, the drug might also prevent expansion of a reservoir of latent virus that hides in the body where it thwarts a cure for *24+*#. 3)his has been an absolutely fascinating voyage of discovery,3 said #r. $reene, who is also a professor of medicine, microbiology and immunology at the %niversity of California, an &rancisco, with which $ladstone is affiliated. 3Every time we turned over an 'experimental rock' in the studies, a new surprise 0umped out.3

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I"ag!g Tech!olog Could 4!loc' -steres o# Chldhood Dsease Dec. 30, 2013 — Dy the time they're two, most children have had respiratory syncytial

virus /2 and suffered symptoms no worse than a bad cold. Dut for some children, especially premature babies and those with underlying health conditions, /2 can lead to pneumonia and bronchitis -- which can re=uire hospitali5ation and have long-term conse=uences. Share Ths:

 + new techni=ue for studying the structure of the /2 virion and the activity of /2 in living cells could help researchers unlock the secrets of the virus, including how it enters cells, how it replicates, how many genomes it inserts into its hosts -- and perhaps why certain lung cells escape the infection relatively unscathed. )hat could provide scientists information they need to develop new antiviral drugs and perhaps even a vaccine to prevent severe /2 infections. 31e want to develop tools that would allow us to get at how the virus really works,3 said "hilip antangelo, an associate professor in the 1allace . Coulter #epartment of Diomedical Engineering at $eorgia )ech and Emory %niversity. 31e really need to be able to follow the infection in a single living cell without affecting how the virus infects its hosts, and this technology should allow us to do that.3 )he research was supported by the ational *nstitutes of ealth's ational *nstitute of $eneral (edical ciences and published online ahead of print in the 0ournal A'S Nano  on #ecember A8, ;8A. 1hile /2 will be the first target for the work, the researchers believe the imaging techni=ue they developed could be used to study other /+ viruses, including influen5a and Ebola. 31e've shown that we can tag the genome using our probes,3 explained antangelo. 31hat we've learned from this is that the genome does get incorporated into the virion, and that the virus particles created are infectious. 1e were able to characteri5e some aspects of the virus particle itself at super-resolution, down to ;8 nanometers, using direct stochastic optical reconstruction microscopy d)?/( imaging.3 /2 can be difficult to study. &or one thing, the infectious particle can take different forms, ranging from 8-micron filaments to ordinary spheres. )he virus can insert more than one genome into the host cells and the /+ orientation and structure are disordered, which makes it difficult to characteri5e. )he research team, which included scientists from 2anderbilt %niversity and Emory %niversity, used a probe technology that =uickly attaches to /+ within cells. )he probe uses multiple fluorophores to indicate the presence of the viral /+, allowing the researchers to see where it goes in host cells -- and to watch as infectious particles leave the cells to spread the infection. 3Deing able to see the genome and the progeny /+ that comes from the genome with the probes we use really give us much more insight into the replication cycle,3 antangelo said. 3)his gives us much more information about what the virus is really doing. *f we can visuali5e the entry, assembly and replication of the virus, that would allow us to decide what to go after to fight the virus.3 )he research depended on a new method for labelling /+ viruses using multiply-labeled tetravalent /+ imaging probes ()/*". )he probes consist of a chimeric combination of #+ and /+ oligonucleotide labeled internally with fluorophores tetravelently complexed to neutravidin. )he chimeric combination was used to help the probes evade cellular defenses. 3)here are lots of sensors in the cell that look for foreign /+ and foreign #+, but to the cell, this probe doesn't look like anything,3 antangelo explained. 3)he cell doesn't see the nucleic acid as foreign.3 *ntroduced into cells, the probes =uickly diffuse through a cell infected with /2 and bind to the virus's /+. )hough binding tightly, the probe doesn't affect the normal activities of the virus and allows researchers to follow the activity for days using standard microscopy techni=ues. )he ()/*" can be used to complement other probe technology, such as $&" and gold nanoparticles. 1ork done by graduate student Eric +lonas to concentrate the virus was essential to the pro0ect, antangelo said. )he concentration had to be done without adversely affecting the infectivity of the virus, which would have impacted its ability to enter host cells. 3*t took =uite a bit of work to get the right techni=ues to concentrate the /2,3 he said. 3ow we can make lots of infectious virus that's labelled and can be stored so we can use it when we want to.3 )o study the infection's progress in individual cells, the researchers faced another challenge> living cells move around, and following them complicates the research. )o address that movement, the laboratory of )homas Darker -- also in the Coulter #epartment -- used micro-patterned fibronectin on glass to create 78-micron 3islands3 that contained the cells during the study.  +mong the mysteries that the researchers would like to tackle is why certain lung cells are severely infected -- while others appear to escape ill effects.

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3*f you look at a field of cells, you see huge differences from cell to cell, and that is something that's not understood at all,3 antangelo said. 3*f we can figure out why some cells are exploding with virus while others are not, perhaps we can figure out a way to help the bad ones look more like the good ones.3 *n addition to those already mentioned, the research team included Games Crowe, professor of pediatrics at 2anderbilt %niversity6 Eli5abeth 1right, assistant professor in the chool of (edicine at Emory %niversity6 #aryll 2anover, Geenah Gung, Chiara Purla, Gonathan Firschman, 2incent &iore, and +lison #ouglas from the 1allace . Coulter #epartment of Diomedical Engineering at $eorgia )ech and Emory %niversity6 +aron !ifland and (anasa $udheti from 2utara *nc. in alt !ake City, and ong Ri from the Emory %niversity chool of (edicine. ?ne of the challenges of studying /2 is maintaining its activity in the laboratory setting -- a problem parents of young children don't share. 31hen you handle this virus in the lab, you have to always be careful about it losing infectivity,3 antangelo noted. 3Dut if you take a room full of children who have not been infected and let one infected child into the room, 7 minutes later all of the children will be infected.3

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Sce!tsts E;0la! Age2Related 5.est: (row! 3at 3als "an. 2, 201- — +s most people resolve themselves to lose weight this ew Rear,

here's why it seems to get easier and easier to pack on unwanted pounds> ew research published in the Ganuary ;8< issue of he AS+ "ournal , shows that as we age, the thermogenic activity of brown fat is reduced. Drown fat is a 3good3 fat located in the backs of our necks that helps burn 3bad3 white fat around our bellies.  +dditionally, the researchers also discovered a possible metabolic on4off switch that could reactivate brown fat. Share Ths: $

3&uture studies on how "+&4"+&/ signaling controls %C" levels through betaA-+/ production in the D+) of animals and humans may reveal new therapeutic targets to treat metabolic disorders associated with obesity,3 said Gunko ugatani, "h.#., a researcher involved in the work from the #epartment of "harmaco-Diochemistry at the chool of "harmaceutical ciences at the %niversity of hi5uoka in hi5uoka, Gapan. )o make this discovery, scientists analy5ed two groups of mice. )he first group had the platelet-activating factor receptors "+&/ gene knocked out. )he second group was normal. "+&/-deficient mice developed a more severe obese state characteri5ed by higher body and epididymal fat mass with age than that of wild-type littermates. &indings from the "+&/-F? genetic model reveal that "+&/-deficiency causes brown adipose tissue D+) dysfunction, which converges to induce the development of obesity, due to impaired thermogenic activity of D+). )his study could elucidate the molecular mechanism underlying the "+&4"+& receptormediated anti-obesity, leading to the development of new targets for the treatment of obesity and related disorders, such as diabetes, high blood pressure, heart disease, cancer, infertility and ulcers. 3+ common complaint is that older people have to work twice as hard with their diets and exercise to get half of the results of younger people,3 said $erald 1eissmann, (.#., Editor-in-Chief of he AS+ "ournal . 3ow we have a much better idea why this is the case> ?ur brown fat stops working as we age. %nfortunately, until a way to turn it back on is developed, we'll have to be prepared to eat more salads and lean proteins, while logging more miles on the treadmill than our younger counterparts.3

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Adults) Es0ecall *o"e!) Ha/e Calore2(ur!!g +(row! 3at+ "une 12, 200) — Feeping your baby fat turns out to be a good thing, as long as it is

3brown fat3—the kind that burns calories, according to a study that found adults have much more of this type of fat than previously thought. )he results, which suggest a new way to treat obesity, were presented at )he Endocrine ociety's @st +nnual (eeting in 1ashington, #.C. Share Ths: $?

Drown fat burns off calories and generates heat in babies and small mammals. (ost of our body fat is white fat, which also provides insulation but stores calories. *t becomes 3bad3 fat when you have too much. )he 3good3 fat—brown fat—was considered essentially nonexistent in human adults. 31e now know that it is present and functional in adults,3 said the study's lead author, +aron Cypess, (#, "h#, ((c, of the Goslin #iabetes Center in Doston. 3)hree ounces of brown fat can burn several hundred calories a day.3 &or the first time, the researchers were able to measure patches of brown adipose tissue—brown fat—in people, thanks to a hightech imaging method that combines positron emission tomography and computed tomography, called "E)4C). Dy evaluating biopsy tissue of what appeared to be brown fat on "E)4C) scans in some patients who had neck surgery, the authors confirmed that they were, indeed, looking at stores of brown fat. (ore than ,@98 study participants had "E)4C) scans, from mid-skull to midthigh. Drown fat when it could be detected was located in an area extending from the front of the neck to the chest. ?f the sub0ects who had detectable brown fat, about : percent had A ounces or more of the fat. 31e believe that this percentage greatly underestimates the number of adults in the population who have a large amount of brown fat,3 said Cypess, whose results were published in the +pril @ issue of the ew England Gournal of (edicine, along with those of two other independent studies of brown fat in adults. )hat is because one of the other studies found that "E)4C) can detect much more brown fat if people are in a room cooled to :U&. !ikewise, Cypess and his colleagues found that people who underwent "E)4C) in the winter had more brown fat activity than those scanned in the summer. )hey also discovered that brown fat is most abundant in young women and least fre=uent in older, overweight men. *n fact, women were more than twice as likely as men to have substantial amounts of brown fat. 3?ne theory for this is that women may have less muscle mass overall, so they need more brown fat to generate heat and keep warm,3 Cypess said. Drown fat provides a new focus for developing treatments protecting against obesity and its complications, according to Cypess. owever, it may not be enough to lose weight to 0ust have brown fat. )he researcher said, 31e may have to turn it on and make sure it burns calories in a regulated, safe manner.3

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Sch,o0hre!a L!'ed to A.!or"al (ra! *a/es: Neurologcal H0eract/t Produces Dsordered Th!'!g $ct. 16, 2013 — chi5ophrenia patients usually suffer from a breakdown of organi5ed

thought, often accompanied by delusions or hallucinations. &or the first time, (*) neuroscientists have observed the neural activity that appears to produce this disordered thinking. Share Ths: %

)he researchers found that mice lacking the brain protein calcineurin have hyperactive brain-wave oscillations in the hippocampus while resting, and are unable to mentally replay a route they have 0ust run, as normal mice do. (utations in the gene for calcineurin have previously been found in some schi5ophrenia patients. )en years ago, (*) researchers led by usumu )onegawa, the "icower "rofessor of Diology and euroscience, created mice lacking the gene for calcineurin in the forebrain6 these mice displayed several behavioral symptoms of schi5ophrenia, including impaired short-term memory, attention deficits, and abnormal social behavior. *n the new study, which appears in the ?ct. : issue of the 0ournal Neuron, )onegawa and colleagues at the /*FE-(*) Center for eural Circuit $enetics at (*)'s "icower *nstitute for !earning and (emory recorded the electrical activity of individual neurons in the hippocampus of these knockout mice as they ran along a track. "revious studies have shown that in normal mice, 3place cells3 in the hippocampus, which are linked to specific locations along the track, fire in se=uence when the mice take breaks from running the course. )his mental replay also occurs when the mice are sleeping. )hese replays occur in association with very high fre=uency brain-wave oscillations known as ripple events. *n mice lacking calcineurin, the researchers found that brain activity was normal as the mice ran the course, but when they paused, their ripple events were much stronger and more fre=uent. &urthermore, the firing of the place cells was abnormally augmented and in no particular order, indicating that the mice were not replaying the route they had 0ust run. )his pattern helps to explain some of the symptoms seen in schi5ophrenia, the researchers say. 31e think that in this mouse model, we may have some kind of indication that there's a disorgani5ed thinking process going on,3 says Gunghyup uh, a research scientist at the "icower *nstitute and one of the paper's lead authors. 3#uring ripple events in normal mice we know there is a se=uential replay event. )his mutant mouse doesn't seem to have that kind of replay of a previous experience.3 )he paper's other lead author is #avid &oster, a former (*) postdoc. ?ther authors are eydar #avoudi and (atthew 1ilson, the herman &airchild "rofessor of euroscience at (*) and a member of the "icower *nstitute. )he researchers speculate that in normal mice, the role of calcineurin is to suppress the connections between neurons, known as synapses, in the hippocampus. *n mice without calcineurin, a phenomenon known as long-term potentiation !)" becomes more prevalent, making synapses stronger. +lso, the opposite effect, known as long-term depression !)#, is suppressed. 3*t looks like this abnormally high !)" has an impact on activity of these cells specifically during resting periods, or post exploration periods. )hat's a very interesting specificity,3 )onegawa says. 31e don't know why it's so specific.3 )he researchers believe the abnormal hyperactivity they found in the hippocampus may represent a disruption of the brain's 3default mode network3 -- a communication network that connects the hippocampus, prefrontal cortex where most thought and planning occurs, and other parts of the cortex. )his network is more active when a person or mouse is resting between goal-oriented tasks. 1hen the brain is focusing on a specific goal or activity, the default mode network gets turned down. owever, this network is hyperactive in schi5ophrenic patients before and during tasks that re=uire the brain to focus, and patients do not perform well in these tasks. &urther studies of these mice could help reveal more about the role of the default mode network in schi5ophrenia, )onegawa says.

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Could Poor Slee0 Co!tr.ute to S"0to"s o# Sch,o0hre!a9 Nov. 1-, 2012  — euroscientists studying the link between poor sleep and

schi5ophrenia have found that irregular sleep patterns and desynchronised brain activity during sleep could trigger some of the disease's symptoms. )he findings, published in the 0ournal Neuron, suggest that these prolonged disturbances might be a cause and not 0ust a conse=uence of the disorder's debilitating effects. Share Ths: @

)he possible link between poor sleep and schi5ophrenia prompted the research team, led by scientists from the %niversity of Dristol, the !illy Centre for Cognitive euroscience and funded by the (edical /esearch Council (/C, to explore the impact of irregular sleep patterns on the brain by recording electrical brain activity in multiple brain regions during sleep. &or many people, sleep deprivation can affect mood, concentration and stress levels. *n extreme cases, prolonged sleep deprivation can induce hallucinations, memory loss and confusion all of which are also symptoms associated with schi5ophrenia. #r %llrich Dartsch, one of the study's researchers, said> 3leep disturbances are well-documented in the disease, though often regarded as side effects and poorly understood in terms of their potential to actually trigger its symptoms.3 %sing a rat model of the disease, the team's recordings showed desynchronisation of the waves of activity which normally travel from the front to the back of the brain during deep sleep. *n particular the information flow between the hippocampus -- involved in memory formation, and the frontal cortex -- involved in decision-making, appeared to be disrupted. )he team's findings reported distinct irregular sleep patterns very similar to those observed in schi5ophrenia patients. #r (att Gones, the lead researcher from the %niversity's chool of "hysiology and "harmacology, added> 3#ecoupling of brain regions involved in memory formation and decision-making during wakefulness are already implicated in schi5ophrenia, but decoupling during sleep provides a new mechanistic explanation for the cognitive deficits observed in both the animal model and patients> sleep disturbances might be a cause, not 0ust a conse=uence of schi5ophrenia. *n fact, abnormal sleep patterns may trigger abnormal brain activity in a range of conditions.3 Cognitive deficits -- reduced short term memory and attention span, are typically resistant to medication in patients. )he findings from this study provide new angles for neurocognitive therapy in schi5ophrenia and related psychiatric diseases.

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Chldre! *th Auts" (e!e#t #ro" Peer Solctato! Dec. 12, 2013 — "eer solicitation -- a child inviting another to play -- can improve

reciprocal social interaction among children with autism, according to a 2anderbilt %niversity study released today in the"ournal of 'hild Psychology and Psychiatry . Share Ths: %

/esearchers studied playground interactions between children with autism and typically developing peers and found the two groups play similarly when engaged in independent play with kids they 0ust met. 1hile the children with autism initiated and engaged in less play overall than typically developing children, the researchers found that other children can facilitate and increase interactions by simple re=uests. )hese findings highlight the pivotal role that peers have in social interaction, noting that it only takes a single child to prompt other children -- with or without autism -- to interact. 3(ost children consider playgrounds a fun place to interact with other kids, but for children with autism, this may be a very challenging and stressful environment,3 said lead author Dlythe Corbett, "h.#., associate professor of "sychiatry and 2anderbilt Fennedy Center investigator. 3?ne of the key places we learn about social rules growing up is during play, but if you don't participate, chances are you're not going to learn the rules or be motivated to interact with other children.3 Corbett and colleagues studied more than A8 peer interactions in children ages B-; on an actual playground by using state-of-theart technology including four remotely operated cameras and battery-operated microphones. )hree children were on the playground for the observations -- a typically developing child trained as a research assistant, called a 3confederate63 another typically developing child there for play only6 and a child with autism. )he confederate was trained to invite the other two children to play and wore an ear microphone in order to receive directions from the researchers, who observed from a nearby lab overlooking the playground. )he stress hormone cortisol was measured through saliva samples taken both at home and several times after the playground interactions to compare the stress level of participants in a typical environment vs. playtime with peers. )he children with autism demonstrated elevated stress during social interactions, with higher cortisol levels observed in children who showed less motivation to play with the other children. 3+lthough children with autism may experience increased stress in social interactions, it was encouraging to see that reciprocal sociali5ation can be facilitated by peer solicitation,3 Corbett said. 3*t all starts with a simple bid to play.3

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Poor Slee0 #or 5.ese Adolesce!ts  A*r. 11, 2010  — ?bese adolescents go to bed later and sleep less than their lighter contemporaries. )his is the finding of a study published in the +pril issue of Australian and Ne9 :ealand "ournal of Pu;lic #ealth. Share Ths: @1

"rofessor )im ?lds and his colleagues at the %niversity of outh +ustralia explored the sleep patterns of @-B year old +ustralians on different days of the week. )he poor sleep among obese students was particularly evident on undays -- the night before school resumed after a weekend off. ?ther findings that may help parents understand their adolescent children included> V ?n average, girls slept more, because of earlier bedtimes. V +s adolescents grow older, they sleep less. V %nderweight children went to bed significantly earlier than those of normal weight. "rof. ?lds said the 'cause and effect' between sleep patterns and weight was unclear. 3)he sleep patterns we found sit comfortably with the theory that short sleep duration predisposes towards obesity,3 he said. 3owever, there may also be some third factor that contributes to both overweight and short sleep duration.3 )his third factor may be linked to the time adolescents spend in front of computer or )2 screens or low physical activity. 3leep intervention studies examining the relationship between screen time, weight status and sleep would help to clarify these issues.

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New De/ce A"s To G/e Slee0 A0!ea Su##erers Rele# A!d Rest $ct. 6, 200%  — &or some, a full nightWs rest can be anything but restful. )hatWs because

they have sleep apnea, which causes them to struggle for breath in bouts throughout the night. ix percent of the population is affected by the condition—but many donWt even know they have it. Share Ths: ?

X)hey donWt make the connection between the fact that they snore loudly at night and they complain about being tired during the day,Y says amuel Frachman, #.?. , professor of medicine and director of the leep #isorders Center at )emple %niversity chool of (edicine and ospital. X)hey think that theyWre 0ust tired, not getting enough sleep or 0ust working too hard. Dut in reality, itWs related to the sleep apnea.Y Frachman is leading research on an experimental device to help patients who suffer from positional sleep apnea. "ositional sleep apnea refers to patients who have episodes where they stop breathing when theyWre on their back, but when they are on their side, the abnormal breathing resolves. &ifty percent of patients with mild sleep apnea those who experience anywhere from five to 7 events an hour and ;8 percent of people with moderate sleep apnea 7 to A8 events an hour have positional sleep apnea. Frachman explains how wearing the device, called P5oma, works to reduce those episodes. XP5oma is a device which is worn around the chest area like a belt, with a device on the back, which is a firm, foam material wrapped in canvas to keep them from moving on their backs. ?ver the last year, weWve been studying its use in treating patients with mild to moderate positional sleep apnea.Y )he device was created by former )emple &ellow Goseph $. Crocetti. e and Frachman have worked together to treat positional sleep apnea. )heir research has shown that the P5oma device is less obtrusive and easier to use than the leading alternative, a continuous positive airway pressure machine or C"+", a mask that blows air on a personWs face to keep the airway open. X+lthough C"+" is very effective, the best studies have shown itWs only used correctly 78 percent of the time,Y says Frachman. X)hat leaves many diagnosed with sleep apnea but not treated.Y %ntreated sleep apnea can lead to a host of other medical problems. Gust having sleep apnea is an independent risk factor for developing high blood pressure, coronary disease and heart failure. )hatWs why Frachman hopes the &#+ approves P5oma to treat positional sleep apnea, to give sufferers an effective alternative to the burden of C"+".

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Se; -atters #or -cro.es "an. 3, 201- — Caught in the actZ /esearchers from the %niversity of Dristol have

observed mating for the first time in the microbes responsible for +frican sleeping sickness. )his tropical disease is caused by trypanosomes, single-celled parasites that are found in the blood of those afflicted. Share Ths:

)he Dristol team were able to see what the trypanosomes were getting up to inside the tsetse flies that carry the disease by using fluorescent markers Ksee image -- link belowL. )he microscopic beasts were seen twirling and gyrating together before 0oining up into one hybrid cell. )o tell which was which, individual trypanosomes were tagged with different colours, with the result that the hybrid cells had both colours. "rofessor 1endy $ibson, who led the research, commented> 3*t's not only bigger animals that have intricate courtship -- but you need a powerful microscope to see thisZ3 ex matters for microbes because it enables genes to be swapped between different strains, leading to new combinations of genes. *n the case of disease-causing microbes like the trypanosome, sex can potentially lead to a lot of harmful genes being combined in one strain. )hese new results suggest that sex is not an optional or rare part of this microbe's life cycle, but probably happens every time two different trypanosomes find themselves together in the same tsetse fly. )rypanosomes belong to a strange group of proto5oa that includes several other medically important parasites such as/eishmania, richomonas and
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New Surgcal Tech!ue #or (ell+s Pals 3acal Paralss "une 11, 2013 — + !oyola %niversity (edical Center surgeon is using electrical

stimulation as part of an advanced surgical techni=ue to treat Dell's palsy. Dell's palsy is a condition that causes paralysis on one side of a patient's face. Share Ths: &@

#uring surgery, #r. Gohn !eonetti stimulates the patient's damaged facial nerve with an electric current, helping to 0ump-start the nerve in an effort to restore improved facial movement more =uickly. !eonetti said some patients who have received electrical stimulation have seen muscle movement return to their face after one or two months -- rather than the four-to-six months it typically takes for movement to return following surgery.  + virus triggered Dell's palsy in +udrey /ex, 7, of !emont, *ll. er right eye could not close and her smile was lopsided, making her feel self-conscious. he had to drink from a straw, and eating was frustrating -- she would accidentally bite her bottom lip when it got stuck on her teeth. he was treated with steroids, but after six weeks, there were no improvements. o +udrey's mother did further research and made an appointment appointment with !eonett !eonett !eonetti !eonetti recommended recommended surgery with electrical electrical stimulation, stimulation, followed followed by physical physical therapy. therapy. )oday, )oday,  +udrey's appearance has returned to normal, and she has regained nearly all of the facial muscle movements she had lost. 3* feel very blessed that we were referred to #r. !eonetti,3 said #eborah /ex, +udrey's mother. Dell's palsy is classified as an idiopathic disorder, meaning its cause is not definitely known. owever, most physicians believe Dell's palsy is caused by a viral-induce viral-induced d swelling of the facial nerve within within its bony covering. covering. ymptoms include include paralysis paralysis on one side of the face6 inability to close one eye6 drooling6 dryness of the eye6 impaired taste6 and a complete inability to express emotion on one side of the face. Dell's palsy occurs when the nerve that controls muscles on one side of the face becomes swollen, inflamed or compressed. )he nerve runs through a narrow, bony canal called the &allopian canal. &ollowing &ollowing a viral infection, infection, the nerve swells inside the canal, restricting the flow of blood and oxygen to nerve cells. (ost cases can be successfully treated with oral steroids, and B7 percent of patients experience good recovery within one month. Dut if symptoms persist for longer than a month, the patient may need surgery, !eonetti said. *f surgery is delayed for longer than three months, the nerve damage from Dell's palsy can be permanent. )hus, the optimal window for surgery is between one and three months after onset of symptoms. )he surgery is called microscopic decompression of the facial nerve. )he surgeon removes the bony covering of the facial nerve, then slits open the outer covering of the nerve. )his gives the nerve room to swell. *n addition to this standard procedure, !eonetti uses an electric stimulator to send a current through the nerve. )his 0ump starts the nerve to speed its recovery. #ecompression #ecompression of the facial nerve is an established established techni=ue techni=ue for treating treating Dell's palsy, and electric stimulation stimulation is an established established techni=ue used in other surgeries involving the nerve. 31e are combining two standard treatments to create an exceptional treatment,3 !eonetti said. &ollowing surgery, +udrey worked with !oyola physical therapist !isa Durkman, who used a mirror and biofeedback to teach  +udrey individuali5ed exercises of her mouth, eye, forehead, cheek and chin. !eonetti said +udrey's case illustrates that the road back from Dell's palsy is a multidisciplinary effort that involves the surgeon, physical therapist and patient.

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!eonetti is a "rofessor and 2ice Chairman in the department of ?tolaryngology, ead and eck urgery, and Co-#irector of the !oyola Center for Cranial Dase )umors at !oyola %niversity Chicago tritch chool of (edicine. *n addition to facial nerve disorders, his special interests include parotid gland tumors, ear disorders and skull base tumors.

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I!!o/at/e Scree!!g Strateg Sw#tl 4!co/ers New Drug Ca!ddates) New (olog Dec. 22, 2013 — cientists at )he cripps /esearch *nstitute )/* have

demonstrated a drug-discovery strategy with a double payoff -- it enables the rapid selection of chemical compounds that have a desired effect on cells and also highlights how the compounds work. Share Ths: $

)o illustrate the power of the innovative techni=ue, the )/* researchers used it to identify a compound that shows promise for treating treating obesity-linked obesity-linked diabetes. diabetes. +t the same time, they were able to identify the fat-cell en5yme that the compound compound inhibits -- an en5yme that has not yet been a focus of diabetes drug development. 3)his integrated strategy we've developed has the potential to accelerate the discovery of important biological pathways and may lead to faster development of new drugs for multiple diseases,3 said )/* +ssociate "rofessor Enri=ue ae5. ae5 and his colleague colleague Den0amin &. Cravatt, chair of )/*'s #epartment #epartment of Chemical Chemical "hysiology, "hysiology, were the senior authors authors of the new study, which is reported #ecember ;;, ;8A, in an advance online issue of Nature 'hemical iology. 3acltat!g Drug Dsco/er )he new strategy has great potential to streamline drug discovery, a process whose importance to human health can hardly be overemphasi5ed. )ypically, pharmaceutical scientists start the discovery process by 3screening3 large libraries of chemical compounds in search of one or a few that might treat disease. )he dominant strategy of recent decades has been to screen compounds for a specific activity against a known target, for example, inhibiting the function of a certain en5yme thought to be critical for the disease in =uestion. + key advantage of this 3target-based3 screening is that it uses biochemical tests that can be done relatively simpl y in a test-tube -- or rather, in a large array of tiny test tubes via automated, rapid screening systems that sort through hundreds of thousands of different compounds. )arget-based screening has enabled scientists to discover many useful new drugs, but some wonder whether this basic discovery strategy has already taken all the 3low hanging fruit.3 *n recent years, compounds selected with target-based in vitro tests have seemed to be failing increasingly often when tested in the more realistic biological environments of cells and animals.  +n older strategy, 3phenotypic3 screening, avoids much of this problem by testing compounds for their ability to produce a desired effect directly on living cells. %nfortunately, such cell-based tests often leave open the =uestion of how a useful compound works. 3*f you don't know what its relevant molecular target is, then developing that compound into a drug -- optimi5ing its potency, its selectivity, its half-life in the bloodstream and so on -- is going to be difficult,3 said ae5. *dentifying the molecular targets of compounds selected by phenotypic screens is typically burdensome and time-consuming. Dut in their new study, ae5, Cravatt and their colleagues were able to speed up the process dramatically. *ndeed, their combined

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phenotypic screening and target-identification approach enabled them to =uickly discover, characteri5e and carry out preclinical tests of a potential new drug for obesity-linked diabetes> a complex metabolic disorder that affects A<9 million people worldwide. A New Da.etes Drug Ca!ddate) Plus I!sghts !to the Dsease )he strategy makes use of the increasing availability of special libraries of related compounds that act as inhibitors of entire en5yme classes. *n this case, the researchers used a set of compounds, recently synthesi5ed by Cravatt's laboratory, that tend to inhibit serine hydrolases -- a vast en5yme family whose members participate in most biological processes in mammals. )he scientists started with a phenotypic screen, testing their library of compounds for the ability to make young fat cells mature faster and store more fat. Detter fat storage means that less fat leaks from fat cells into the liver, muscles and pancreas -- a process that fre=uently occurs with obesity, often interfering with insulin signaling enough to bring on diabetes. )he screen =uickly yielded several compounds that had a strong effect in promoting fat-cell fat storage. )he researchers then used a method called 3activity-based profiling3 to identify the fat-cell serine hydrolases that the compounds inhibited most strongly. ?ne of the most potent compounds, 11!A, turned out to work principally by inhibiting CesA, a serine hydrolase en5yme that scientists have not studied in the context of obesity or diabetes. )he researchers =uickly demonstrated 11!A's effectiveness in two different mouse models of obesity-linked diabetes -- one in which the mice are genetically programmed to become obese and diabetic, and another in which normal mice are made obese and diabetic with a high-fat diet. 3)he treated animals showed resistance to weight gain -- they were not putting on as much weight as the controls,3 said ae5. 3)heir blood biochemistry also was getting normali5ed6 their glucose, triglyceride and cholesterol levels were coming down towards normal levels.3 *n these mouse tests, 11!A -- without any optimi5ation for use as a drug -- performed about as well as the &#+-approved diabetes treatment rosiglita5one +vandia. otably, the new compound lacked one of the side effects that drugs in rosiglita5one's class have in mice> the toxic accumulation of lipids in the li ver. 3?ur compound clears lipids from the diabetic mouse liver, whereas rosiglita5one has the opposite effect,3 said ae5. )o explore the relevance of these results to humans, the )/* team worked with collaborating researchers in +ustralia to test fat samples from obese humans and diabetics. )he tests confirmed that the human version of CesA also is unusually active in such patients. )his suggests that an inhibitor may also work as a diabetes treatment in people. ae5 and his colleagues will next focus on using the new screening strategy to uncover more biological pathways that c ould yield new mechanisms to develop potential therapies. Contributors to the study, 3*ntegrated phenotypic and activity-based profiling links CesA to obesity and diabetes,3 also included first author Eduardo #omingue5, then a postdoctoral fellow in the ae5 !aboratory6 as well as )/*'s +ndrea $almo55i, Gae 1on Chang, Fu-!ung su, Goanna "awlak, 1eiwei !i, Cristina $odio, Gason )homas, #avid "artida, herry iessen and #aniel F. omura6 and +ustralian researchers "aul E. ?'Drien and (atthew G. 1att of (onash %niversity, and +aron ". /ussell of #eakin %niversity. )he study was funded in part by the ational *nstitutes for ealth #F8B88A, #F8@@B8, the +merican #iabetes +ssociation, )he (c#onald's Center for )ype ; #iabetes and ?besity, the ational ealth and (edical /esearch Council of +ustralia, the ewitt &oundation for (edical /esearch and the Qunta de $alicia, pain.

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