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How Household Dogs Protect Aga!st Asth"a a!d I!#ecto!Dec. 16, 2013 Children's risk for developing allergies and asthma is reduced whenthey are exposed in early infancy to a dog in the household, and now researchers havediscovered a reason why.

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Exposure of mice to dust from houses where canine pets are permitted both indoors and outdoors can reshape the community ofmicrobes that live in the mouse gut -- collectively known as the gastrointestinal microbiome -- and also diminish immune systemreactivity to common allergens, according to a new study by researchers led by usan !ynch, "h#, associate 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 allergensand viral respiratory infection.)he study, funded by the ational *nstitute of +llergy and *nfectious #iseases *+*#, is published online this week intheProceedings 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 theresults 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 inflammatoryresponses in the lungs were greatly reduced in mice previously exposed to dog-associated dust, in comparison to mice that wereexposed 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, !actobacillus0ohnsonii. 1hen they fed it alone to mice, they found it could prevent airway inflammation due to allergens or even respiratorysyncytial 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 activityof 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 dogowners' 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 gutmicrobiome 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 ofthe gut microbiome strongly influence immune reactions and present a novel avenue for development of therapeutics for bothallergic asthma and a range of other diseases.3)he current study demonstrates that changes in the gut microbiome can have wide-reaching effects on immune function beyondthe 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 asignificantly 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 whetherbeing 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.33)he results of our study indicate that this is likely to be one mechanism through which the environment influences immuneresponses in early life, and it is something we are currently examining using human samples in a large multi-institutionalcollaborative study funded by the *+*#.33$ut microbiome manipulation represents a promising new therapeutic strategy to protect individuals against both pulmonaryinfection and allergic airway disease,3 !ynch said.

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http://www.sciencedaily.com/releases/2013/12/131216155042.htmhttp://www.sciencedaily.com/releases/2013/12/131216155042.htm


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Sce!ce News... from universities, ournals, and other research organi!ations

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L!' (etwee! Allerges) I!creased Rs' o# (lood Ca!cers ! *o"e!Nov. 22, 2013 + team of scientists looking into the interplay of the immune systemand cancer have found a link between a history of airborne allergies -- in particular toplants, grass and trees -- with risk of blood cancers in women.

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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 theAmerican "ournal of #ematology. 3)o the best of our knowledge, ours is the first study to suggestimportant gender differences in the association between allergies and hematologic malignancies,3 wrote first author (a5yarhadman, (.#., (.".., 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 scientificinterest. 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, canaffect survival of cells in developing tumors.3 &or the study, hadman, principal investigator Emily 1hite, "h.#., of the "ublic ealthciences #ivision at &red utch and their colleagues drew on a large, population-based sample of men and women from the2*)amins +nd !ifestyle 2*)+! cohort, which included people aged 78-9: years old from western 1ashington. )he studyparticipants answered a ; health history and cancer risk factors,medication and supplement use, and diet. "articipants provided information on age, race4ethnicity, education, smoking, diet fruitand vegetable intake, and other lifestyle characteristics, self-rated health, medical history, and family history of leukemia orlymphoma.

istory of asthma and allergies was also taken, including allergies to plants, grasses or trees6 mold or dust6 cats, dogs or otheranimals6 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 eliminatingthose who had a prior history of malignancies other than non-melanoma skin cancers and missing information on baseline cancerhistory. "articipants were followed for a median of eight years until they withdrew from the study, moved away, had a cancerdiagnosis other than hematologic malignancy or non-melanoma skin cancer, or died. *ncidence of hematologic malignancies andother 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 bemale, to have two or more first-degree relatives with a family history of leukemia or lymphoma, to be less active and rank theirhealth status as low. + history of allergies to airborne antigens was associated with a higher risk of hematologic malignancies. )hemost 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 thata history of allergies to plants, grass and trees was significantly associated with mature D-cell neoplasms, one of four ma0orcategories of lymphoma. )here was also an increased risk of plasma-cell neoplasms for participants who reported a history ofallergies 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 wasincreased in women but not in men. )he reason for this is as yet unknown.3*t is tempting to speculate that the additional effect of allergy may reach statistical significance in women because of their lowerbaseline risk for the development of hematologic malignancies compared to men,3 the authors wrote. 3owever, hormonal effectson the immune system and interactions with carcinogenesis may offer an alternative biological explanation that will re=uire furthermechanical 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. )ypesof 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,3hadman said.)he authors cite the study's strengths as its large population si5e, the comprehensive baseline data regarding cancer risk andmedical 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 eachsubset of allergy types.

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http://www.sciencedaily.com/releases/2013/11/131122165458.htmhttp://www.sciencedaily.com/releases/2013/11/131122165458.htmhttp://www.sciencedaily.com/releases/2013/11/131122165458.htmhttp://www.sciencedaily.com/releases/2013/11/131122165458.htmhttp://www.sciencedaily.com/releases/2013/11/131122165458.htmhttp://www.sciencedaily.com/releases/2013/11/131122165458.htmhttp://www.sciencedaily.com/releases/2013/11/131122165458.htmhttp://www.sciencedaily.com/releases/2013/11/131122165458.htm


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3$iven the limited number of cases within each subtype of hematologic cancer, the risk estimates need to be interpreted withcaution 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! Allerges$ct. 3, 2013 /esearchers have successfully tested treatments for people withallergies to grasses and to dust mites.

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)here are two treatments, one for grass allergy, which is commonly known as hay fever, and the other for dust mite allergy. )heyare 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. basedbiotechnology 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 ;7per cent of the population in orth +merica and Europe is sensitive to pollen from different grass species. ?ne in four people issensiti5ed 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 tograss pollen in a controlled environment, both before treatment and at the end of the hay fever season. tudy participants receivedone of three treatment regimens over three months, completed prior to the beginning of the pollen season. )hose who had theoptimal short course of therapy had significantly improved symptoms at the end of the season, compared to those who had aplacebo. )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 hadsignificantly improved allergy symptoms a year after the start of treatment, compared to patients who received a placebo. )hetreatment, 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 thedesign of the treatments. 3"ositive results, first with a cat allergy therapy and now with house dust mite and grass allergytreatments, 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 bypeople, and they thrive in warm, humid environments. %pholstered furniture, bedding and carpeting provide an ideal environmentfor dust mites.

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L!' (etwee! Red Cell Dstr.uto! *dth Le/els) De0resso!Nov. 1%, 2013 /esearchers at the *ntermountain (edical Center eart *nstitute havediscovered a link between elevated red cell distribution width levels and depression inpatients being treated for heart disease. )his new discovery can help physiciansprovide earlier diagnosis and treatment for possible depression in heart patients.

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/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


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Iro! Su00le"e!tato! Ca! Pro/de Cog!t/e) Phscal (e!e#ts to A!e"cChldre!

$ct. 1&, 2013 $iving daily iron supplements to anemic primary-school-aged childrencan have cognitive and physical benefits, according to a study publishedin '(A"'anadian (edical Association "ournal.

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$lobally, approximately ;7H of school-aged children are anemic, with iron deficiency the cause of about half of all cases. *rondeficiency, which has been associated with impaired cognitive and physical development, is caused by a lack of dietary iron and, indeveloping countries, by parasites such as hookworm and schistosomiasis. *n developed countries, newcomers, native people andsome ethnic populations can be anemic. +bout AH of primary-school-aged children in Canada are anemic. owever, concerns thatiron 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 scoresthan children in the control groups @ studies with ;A77 children. )hey also showed substantial improvement in *J scores andother cognitive tests. Children who received iron supplements were also slightly taller for their age and had improved weight-for-age compared with children who did not.31e found evidence of a benefit of iron supplementation on cognitive performance among primary-school-aged children, includingon *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 ironsupplementation 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 thegroups 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 cognitiveperformance in primary school children in developing settings where anemia is prevalent and testing hemoglobin before ironsupplementation 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 thatit =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 poorsettings 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 -utato!s -a'e (reast Ca!cers Treat"e!t2Ressta!t

Dec. 12, 2013 1omen with breast cancer characteri5ed by high levels of the proteinE/; and hormone receptors gained much less benefit from presurgery treatment withchemotherapy and E/;-targeted therapies if their cancer had one or more mutationsin the "*FAC+ gene, according to results presented at the ;8A an +ntonio DreastCancer ymposium, held #ec. 8-


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Lo!g2Last!g Ge!e Thera0 (e!e#ts Ad/a!ced Heart 3alure Pate!tsNov. 1), 2013 /esearchers from the Cardiovascular /esearch Center at *cahnchool of (edicine at (ount inai reported the long-term benefits of a single dose oftheir gene therapy ++24E/C+;a in advanced heart failure patients on ov. @ at the+merican eart +ssociation cientific essions ;8A.

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)he new long-term follow-up results from their initial Calcium %p-/egulation by "ercutaneous +dministration of $ene )herapy *nCardiac #isease C%"*# clinical trial found a one-time, high-dose in0ection of the ++24E/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 tothose patients receiving placebo. +lso, patients experienced no negative side effects following gene therapy delivery at three-yearfollow-up.3)his study shows ++24E/C+;a gene therapy has long-lasting and beneficial effects for congestive heart failure patientsallowing 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 (edicineat (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 in0ectedthrough 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 orreduced expression occurs in patients with heart failure. 1hen E/C+;a is down-regulated, calcium stays longer in the cells thanit 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 improvedheart function status and left ventricular function, along with a significant decrease in recurrent cardiovascular events. C%"*# wasthe first-in human clinical gene therapy randomi5ed, double-blind study which enrolled A@ patients with advanced heart failure.3++24E/C+;a gene therapy has been proven to be a safe and effective therapeutic intervention for advanced heart failure,3says #r. a00ar. 3?ur long-term results support the potential use of ++24E/C+;a gene therapy as a new important additionaltool 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 ++24E/C+;a. *n addition, on ov. @ #r. a00ar also presented at the ++cientific essions ;8A a "lenary talk entitled, 3ow the "ostgenome Era 1ill Change the "ractice of Cardiology3 and discussedhis 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 thatshow delivery of small ubi=uitin-related modifier %(?-, an important regulator of E/C+;a, in preclinical heart failure modelsimproves 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 thatdevelopment of novel cardiotropic vectors may render cardiovascular gene therapy easier and less-invasive in the near future.

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RNA (uld240 L!'ed to De"e!ta) -otor Neuro! Dsease$ct. 30, 2013 + new toxic entity associated with genetically inherited forms ofdementia 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 theproduction of /+ molecules which could be responsible for the diseases. )he findingsare published in the 0ournalActa Neuro*athologica.

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&rontotemporal dementia and motor neuron disease are related neurodegenerative diseases that affect approximately 7,888people in the %F. &rontotemporal dementia causes profound personality and behaviour changes. (otor neuron disease leads tomuscle weakness and eventual paralysis.)he most common known cause for both frontotemporal dementia and motor neuron disease is an unusual genetic mutation in theC@orf9; gene. )he mutation involves a small string of #+ letters at the beginning of the gene, which expand massively to producethousands of copies.)he new research, funded by +l5heimer's /esearch %F and the (edical /esearch Council, has shown that this #+ expansionacts 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 isnormally turned on in only one direction, termed the 'sense direction'. )he new research shows that the #+ expansion is turnedon 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 thanpeople with less /+ aggregates. )his correlation suggests that the build-up may be important in causing frontotemporal dementiaand 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 moleculesin diseases caused by #+ expansions. )he next steps will be to determine how they might kill neurons and how to stop thembuilding up.3#r imon /idley, ead of /esearch at +l5heimer's /esearch %F, the %F's leading dementia research charity, said> 3)he discoveryof the C@?/&9; gene was a ma0or step forward for research into frontotemporal dementia and motor neuron disease, and it'spositive 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 researchcould take us further on the road to new treatments that are so desperately needed by the thousands of people with thesedevastating diseases. &or these results to reach their full potential it's vital that we continue to invest in research.3

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TEXT N4TRITITI5N 1:



Det 6ualt L!'s 5ld) You!gDec. 1%, 2013 %nderstanding how dietary habits are connected through thegenerations could have valuable benefits for community health, a new study shows.

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)he )aiwanese study assessed the relationship between the =uality of children's diets and that of their elders in a wide range ofrepresentative 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 ;


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TEXT NER754S SYSTE- 1:



*ll Ste" Cell Thera0 Hel0 Cure S0!al Cord I!8ur9Dec. 1, 2013 + systematic survey of the scientific literature shows that stem celltherapy can have a statistically significant impact on animal models of spinal cord

in0ury, and points the way for future studies.Share Ths:

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pinal cord in0uries are mostly caused by trauma, often incurred in road traffic or sporting incidents, often with devastating andirreversible conse=uences, and unfortunately having a relatively high prevalence ;78,888 patients in the %+6 B8H of cases aremale. igh-profile campaigners like the late actor Christopher /eeve, himself a victim of sports-related spinal cord in0ury, haveplaced 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 iologyby +na +ntonic, #avidowells and colleagues from the &lorey *nstitute and the %niversity of (elbourne, +ustralia, and (alcolm (ac!eod and colleaguesfrom 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 cordin0uries, with the hope of improving the ability to move 3motor outcomes3 and to feel 3sensory outcomes3 beyond the site of thein0ury. (any studies have been performed that involve animal models of spinal cord in0ury mostly rats and mice, but these arelimited in scale by financial, practical and ethical considerations. )hese limitations hamper each individual study's statistical powerto 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 statisticalreappraisal of many previous laboratory experiments. *n this case the authors assessed 7: published studies that examined theeffects 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 inboth sensory and motor outcomes, though the results can vary widely between animals. &or sensory outcomes the degree ofimprovement tended to increase with the number of cells introduced -- scientists are often reassured by this sort of 3doseresponse,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 weretreated and which untreated, the way that the stem cells were cultured, the way that the spinal in0ury was generated, and the waythat outcomes were measured. *n each case, important lessons were learned that should help inform and refine the design of futureanimal studies. )he meta-analysis also revealed some surprises that should provoke further investigation -- there was littleevidence 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 researchers then used i"C technology to reprogram skin cells taken from patients with "arkinson's disease and convertedthe stem cells into the type of neuron that is defective in these patients. +fter exposure to progerin, these neurons recapitulateddisease-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 diseasein a dish,3 says first author Gustine (iller of the loan-Fettering *nstitute for Cancer /esearch. 31e hope that the strategy willenable mechanistic studies that could explain why a disease is late-onset. 1e also think that it could enable a more relevantscreening platform to develop new drugs that treat late-onset diseases and prevent degeneration.3

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New Clues to -e"or 3or"ato! -a Hel0 (etter Treat De"e!taNov. 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 themechanisms of "avlovian conditioning. )heir work will help them understand howmemories form and, ultimately, provide better treatments to improve memory in allages.

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$regg /oman, an associate professor of biology and biochemistry at %, and hixing Phang, his postdoctoral associate, describetheir findings in a paper titled 3"resynaptic *nhibition of $amma !obe eurons *s /e=uired for ?lfactory !earning in #rosophila,3appearing 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 sumof our experiences. 1hen memories can no longer be retrieved or we have difficulty in forming new memories, the effects arefre=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 flybrain, /oman says, there are nerve cells that play a role in olfactory learning and memory. ?lfactory learning, he says, is anexample of classical conditioning first described by "avlov in his experiment with dogs. *n their study, the flies were trained toassociate 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 activatedby odors. )raining the flies to associate an odor with an electric shock changed how these cells responded to odors by developinga modification in gamma lobe neuron activity, known as a memory trace,3 he said. 3*nterestingly, we found that training caused thegamma lobe neurons to be more weakly activated by odors that were not paired with an electric shock, while the odors paired withelectric shock maintained a strong activation of these neurons. )hus, the gamma lobe neurons responded more strongly to thetrained odor than to the untrained odor.3

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http://www.sciencedaily.com/releases/2013/11/131127122413.htmhttp://www.sciencedaily.com/releases/2013/11/131127122413.htmhttp://www.sciencedaily.com/releases/2013/11/131127122413.htmhttp://www.sciencedaily.com/releases/2013/11/131127122413.htmhttp://www.sciencedaily.com/releases/2013/11/131127122413.htmhttp://www.sciencedaily.com/releases/2013/11/131127122413.htm


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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 thebrain. 1e have released our data so that others can assess how any gene they are interested in is expressed differently betweenmen and women.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, theresearchers conducted interviews with the older healthy individuals of each affected family and spoke to genealogists andhistorians 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


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3+s this area begins to deteriorate, people begin to show the early signs of cognitive decline -- problems learning and rememberingthings, 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 monkeysfitted with electrodes to read out the activity of individual neurons in their brains. )heir task was akin to playing video games withtheir 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 anderror 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 andthe $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 followingcorrect and incorrect responses. )hey also altered the amount of 0uice dispensed in some cases, creating a sense of high-rewardand low-reward answers.*f the "CC actively dampened performance, the researchers would expect to see it active before a choice is made or the feedbackis 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 earnenough reward to keep motivated.)he researchers also ran the task after administering a drug, muscimol, that impaired the function of the "CC temporarily duringtesting. 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 rewardswere 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 roleis 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 ofpoor 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, particularlywhen 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 motivationinteracts with "CC abnormalities seen in +l5heimer's disease.

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TEXT 7ACCINES $:



New Tu.erculoss 7acc!e De/elo0ed$ct. 1, 2013 + tuberculosis vaccine developed at (c(aster %niversity offers newhopes for the global fight against tuberculosis.

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31e are the first to have developed such a vaccine for tuberculosis,3 said #r. &iona maill, professor and chair of the #epartmentof "athology and (olecular (edicine of the (ichael $. #e$roote chool of (edicine at (c(aster. he led the phase one clinicalstudy 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 andmolecular medicine and the (c(aster *mmunology /esearch Centre, who co-led the phase one study. Doth are also members ofthe (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 thatcauses tuberculosis, and it remains the top infectious killer of people only secondary to *26 yet, the current vaccine used toprevent 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 overtime diminish following DC$ vaccination.Currently the DC$ vaccine is part of the 1orld ealth ?rgani5ation's immuni5ation program in +sia, +frica, Eastern Europe andouth +merica, as well as unavut, the only Canadian 0urisdiction where the DC$ vaccine is routinely given because of the highrate 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 theimmune system.3Dy ;8; they established that the vaccine was safe and observed a robust immune response in most trial participants. (ore clinicaltrials 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 howimportant 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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