A stratified approach for modeling the distribution of a threatened ant species in the Swiss National Park

We present models predicting the potential distribution of a threatened ant species, Formica exsecta Nyl., in the Swiss National Park ( SNP). Data to fit the models have been collected according to a random-stratified design with an equal number of replicates per stratum. The basic aim of such a sampling strategy is to allow the formal testing of biological hypotheses about those factors most likely to account for the distribution of the modeled species. The stratifying factors used in this study were: vegetation, slope angle and slope aspect, the latter two being used as surrogates of solar radiation, considered one of the basic requirements of F. exsecta. Results show that, although the basic stratifying predictors account for more than 50% of the deviance, the incorporation of additional non-spatially explicit predictors into the model, as measured in the field, allows for an increased model performance (up to nearly 75%). However, this was not corroborated by permutation tests. Implementation on a national scale was made for one model only, due to the difficulty of obtaining similar predictors on this scale. The resulting map on the national scale suggests that the species might once have had a broader distribution in Switzerland. Reasons for its particular abundance within the SNP might possibly be related to habitat fragmentation and vegetation transformation outside the SNP boundaries.

Genetic variation at CHRNA5-CHRNA3-CHRNB4 interacts with smoking status to influence body mass index.

BACKGROUND: Cigarette smoking is associated with lower body mass index (BMI), and a commonly cited reason for unwillingness to quit smoking is a concern about weight gain. Common variation in the CHRNA5-CHRNA3-CHRNB4 gene region (chromosome 15q25) is robustly associated with smoking quantity in smokers, but its association with BMI is unknown. We hypothesized that genotype would accurately reflect smoking exposure and that, if smoking were causally related to weight, it would be associated with BMI in smokers, but not in never smokers. METHODS: We stratified nine European study samples by smoking status and, in each stratum, analysed the association between genotype of the 15q25 SNP, rs1051730, and BMI. We meta-analysed the results (n = 24 198) and then tested for a genotype × smoking status interaction. RESULTS: There was no evidence of association between BMI and genotype in the never smokers {difference per T-allele: 0.05 kg/m(2) [95% confidence interval (95% CI): -0.05 to 0.18]; P = 0.25}. However, in ever smokers, each additional smoking-related T-allele was associated with a 0.23 kg/m(2) (95% CI: 0.13-0.31) lower BMI (P = 8 × 10(-6)). The effect size was larger in current [0.33 kg/m(2) lower BMI per T-allele (95% CI: 0.18-0.48); P = 6 × 10(-5)], than in former smokers [0.16 kg/m(2) (95% CI: 0.03-0.29); P = 0.01]. There was strong evidence of genotype × smoking interaction (P = 0.0001). CONCLUSIONS: Smoking status modifies the association between the 15q25 variant and BMI, which strengthens evidence that smoking exposure is causally associated with reduced BMI. Smoking cessation initiatives might be more successful if they include support to maintain a healthy BMI.

Metabolic compartmentalization in the human cortex and hippocampus: evidence for a cell- and region-specific localization of lactate dehydrogenase 5 and pyruvate dehydrogenase.

BACKGROUND: For a long time now, glucose has been thought to be the main, if not the sole substrate for brain energy metabolism. Recent data nevertheless suggest that other molecules, such as monocarboxylates (lactate and pyruvate mainly) could be suitable substrates. Although monocarboxylates poorly cross the blood brain barrier (BBB), such substrates could replace glucose if produced locally.The two key enzymatiques systems required for the production of these monocarboxylates are lactate dehydrogenase (LDH; EC1.1.1.27) that catalyses the interconversion of lactate and pyruvate and the pyruvate dehydrogenase complex that irreversibly funnels pyruvate towards the mitochondrial TCA and oxydative phosphorylation. RESULTS: In this article, we show, with monoclonal antibodies applied to post-mortem human brain tissues, that the typically glycolytic isoenzyme of lactate dehydrogenase (LDH-5; also called LDHA or LDHM) is selectively present in astrocytes, and not in neurons, whereas pyruvate dehydrogenase (PDH) is mainly detected in neurons and barely in astrocytes. At the regional level, the distribution of the LDH-5 immunoreactive astrocytes is laminar and corresponds to regions of maximal 2-deoxyglucose uptake in the occipital cortex and hippocampus. In hippocampus, we observed that the distribution of the oxidative enzyme PDH was enriched in the neurons of the stratum pyramidale and stratum granulosum of CA1 through CA4, whereas the glycolytic enzyme LDH-5 was enriched in astrocytes of the stratum moleculare, the alveus and the white matter, revealing not only cellular, but also regional, selective distributions. The fact that LDH-5 immunoreactivity was high in astrocytes and occurred in regions where the highest uptake of 2-deoxyglucose was observed suggests that glucose uptake followed by lactate production may principally occur in these regions. CONCLUSION: These observations reveal a metabolic segregation, not only at the cellular but also at the regional level, that support the notion of metabolic compartmentalization between astrocytes and neurons, whereby lactate produced by astrocytes could be oxidized by neurons.

The role of LEKTI in fate determination of keratinocyte stem cells

SPINK5 (serine protease inhibitor Kazal-type 5) encodes the putative proteinase inhibitor LEKTI (lympho-epithelial Kazal-type related inhibitor). In skin, LEKTI expression is restricted to the stratum granulosum of the epidermis and the inner root sheath of hair follicles. Mutations that create premature termination codons in SPINK5 have been reported as the cause of Netherton syndrome (NS), a human autosomal recessive disorder characterized by congenital ichthyosis with defective cornification, a specific hair shaft defect known as trichorrexis invaginata or 'bamboo hair', and severe atopic manifestations, including atopic dermatitis and hayfever. Althought recombinant human LEKTI inhibits a battery of serine proteases including plasmin, trypsin, subtilisin A, cathepsin G, and elastase, the precise role of LEKTI in the physiopathology of NS remains unclear. Spink5−/− mice display a NS-like phenotype. Surprisingly, a psoriasis-like hyperplasia, basement membrane breakdown followed by evagination of spindle-shaped epidermal cells into the dermal compartment, and the presence of numerous sweat gland-like structures were also observed when the skin of Spink5−/− newborn mice, which die at birth, was transplanted onto the back of nude mice. Collectively, these observations suggest that LEKTI may play a role on cell proliferation and stem cell fate. Our current work aims at elucidating the mechanisms by which LEKTI impact these biological processes. Using keratinocyte stem cells obtained from NS patients, we have identified LEKTI as a regulator node in several signaling pathways involved in stem cell behavior.

Once-daily dolutegravir is superior to once-daily darunavir/ritonavir in treatment-naïve HIV-1-positive individuals: 96 week results from FLAMINGO.

INTRODUCTION: Dolutegravir (DTG) 50 mg once daily was superior to darunavir/ritonavir (DRV/r) 800 mg/100 mg once daily through Week 48, with 90% vs. 83% of participants achieving HIV RNA 50 c/mL (p=0.025) [1]. We present data through Week 96. MATERIAL AND METHODS: FLAMINGO is a multicentre, randomized, open-label, Phase IIIb non-inferiority study, in which HIV-1-positive ART-naïve adults with HIV-1 RNA≥1000 c/mL and no evidence of viral resistance were randomized 1:1 to receive DTG or DRV/r, with investigator-selected backbone NRTIs (TDF/FTC or ABC/3TC). Participants were stratified by screening HIV-1 RNA (≤100K c/mL) and NRTI backbone. RESULTS: A total of 484 adults were randomized and treated; 25% had baseline HIV RNA 100K c/mL. At Week 96, the proportion of participants with HIV RNA 50 c/mL was 80% in the DTG arm vs. 68% in the DRV/r arm (adjusted difference 12.4%; 95% CI 4.7, 20.2%; p=0.002). Secondary analyses supported primary results: per-protocol [(DTG 83% vs. DRV/r 70%), 95% CI 12.9 (5.3, 20.6)] and treatment-related discontinuation = failure [(98% vs. 95%), 95% CI 3.2 (-0.3, 6.7)]. Overall virologic non-response (DTG 8%; DRV/r 12%) and non-response due to other reasons (DTG 12%; DRV/r 21%) occurred less frequently on DTG. As at Week 48, the difference between arms was most pronounced in participants with high baseline viral load (82% vs. 52% response through Week 96) and in the TDF/FTC stratum (79% vs. 64%); consistent responses were seen in the ABC/3TC stratum (82% vs. 75%). Six participants (DTG 2, none post-Week 48; DRV/r 4, two post-Week 48) experienced protocol-defined virologic failure (PDVF; confirmed viral load 200 c/mL on or after Week 24); none had treatment-emergent resistance to study drugs. Most frequent drug-related adverse events (AEs) were diarrhoea, nausea and headache, with diarrhoea significantly more common on DRV/r (24%) than DTG (10%). Significantly more participants had Grade 2 fasting LDL toxicities on DRV/r (22%) vs. DTG (7%), p<0.001; mean changes in creatinine for DTG (~0.18 mg/dL) observed at Week 2 were stable through Week 96. CONCLUSIONS: Once-daily DTG was superior to once-daily DRV/r in treatment-naïve HIV-1-positive individuals, with no evidence of emergent resistance to DTG in virologic failure and relatively similar safety profiles for DTG and DRV/r through 96 Weeks.

On the immature stages and natural history of Gonioterma exquisita Duckworth (Lepidoptera, Elachistidae, Stenomatinae)

In the present work the natural history and immature stages of Gonioterma exquisita Duckworth, 1964 of the Brazilian cerrado region are described. The caterpillars are external folivorous feeders and present a diet restricted to pubescent-leaved host plants of the genus Byrsonima Rich. (Malpighiaceae). They are solitary caterpillars and they build a hard individual shelter that looks like a planorbid shell, made from silk and frass, covered with trichomes and silk, where they develop until the last larval instar on the host plant, and remain inside it until the adult emergence on herbaceous stratum. The larval development presented eight instars. Egg, larval head capsules, instar duration, pupa, shelter, and behavior are also described. Diapause is mentioned for the first time in this species.

Evaluación poblacional de concha de abanico Argopecten purpuratus (Lamarck, 1819) en la isla Lobos de Tierra, 2010

Entre el 14 y 23 de diciembre 2010, se efectuó la evaluación poblacional de la concha de abanico en la isla Lobos de Tierra, su distribución se registró entre 6°21’12,6”S y 6°24’12,6”S, (noreste de Cabo Cruz y sur de Juanchuquita) y entre 6°26’38,8”S y 6°27’18,4”S (sur de Roca Blanca y norte de El Ñopo) a profundidades de 14,3 a 26,3 m. La altura valvar varió entre 7 y 107 mm. El rango más amplio de tallas y la mayor talla media (69,9 mm), se presentó en el estrato III. Predominaron los ejemplares desovados (37,50%) y desovantes (28,41%). Las densidades fluctuaron entre 1 y 77 ejem.m-2, predominando el rango entre 1 a 10 ind.m-2. La biomasa total fue estimada en 4962,716 t y la población en 87,61 millones de individuos El stock de juveniles (≤25 mm) fue de 0,18 millones de ejemplares y 0,012 t. El stock explotable (≥65 mm) estuvo constituido por 53,81 millones de individuos (61,42%) y 3.725,81 t (75,08%) de la biomasa. Se observó alta mortandad de individuos entre 14 y 77 mm de altura valvar, distribuidos en áreas con niveles de oxígeno menores a 0,1 mL/L, que coincidieron con sustratos reducidos localizados frente a La Grama.

VGLUT1 is Present in Cortical, Hippocampal and Striatal Astrocytes

The last decade has presented studies providing evidence for astrocytic exocytosis of glutamate potentiating nerve signals. To make further investigations into this astrocytic attribute we investigated the localization of the vesicular glutamate transporter 1 (VGLUT1) in small processes of astrocytes close to glutamatergic terminals in frontal cortex, striatum, molecular layer of hippocampus and stratum radiatum of hippocampus. According to the importance of VGLUT1 in glutamate exocytosis the presence of VGLUT1 in astrocytic processes indicates the ability to exocytose glutamate. METHODS: For qualitative analysis we used immunoflourescence histochemistry. Sections from rat frontal cortex, striatum, molecular layer of hippocampus and stratum radiatum of hippocampus were labeled with antibodies against glutamine synthetase (an astrocytic marker) and VGLUT1. Z-stacks of 4.5-5 lm obtained by confocal microscopy from each section were deconvolved and 3D reconstructed in Amira. Small astrocytic processes were analysed for the presence of VGLUT1 inside the processes. The quantitative analysis was done by immunogold labeling. Ultrathin sections from each brain region were labeled for GLT (an astrocytic marker) and VGLUT1. Pictures obtained by electron microscopy were analysed and the point density (gold particles/nm2) for VGLUT1 in astrocytic processes was measured. RESULTS: Using confocal 3D reconstructions we were qualitatively able to identify VGLUT1 within small processes of astrocytes in all four brain regions. Reflecting our qualitative findings the electron microscopical immunogold quantifications showed a significant density of gold particles signaling VGLUT1 in astrocytic processes in all four brain regions. CONCLUSION: We extend the results of previous studies on glutamate release from astrocytes, which have focused on the hippocampus, proposing that astrocytic exocytosis of glutamate is a global phenomenon in the brain.

An index to identify stroke-related vs incidental patent foramen ovale in cryptogenic stroke.

OBJECTIVE: We aimed to create an index to stratify cryptogenic stroke (CS) patients with patent foramen ovale (PFO) by their likelihood that the stroke was related to their PFO. METHODS: Using data from 12 component studies, we used generalized linear mixed models to predict the presence of PFO among patients with CS, and derive a simple index to stratify patients with CS. We estimated the stratum-specific PFO-attributable fraction and stratum-specific stroke/TIA recurrence rates. RESULTS: Variables associated with a PFO in CS patients included younger age, the presence of a cortical stroke on neuroimaging, and the absence of these factors: diabetes, hypertension, smoking, and prior stroke or TIA. The 10-point Risk of Paradoxical Embolism score is calculated from these variables so that the youngest patients with superficial strokes and without vascular risk factors have the highest score. PFO prevalence increased from 23% (95% confidence interval [CI]: 19%-26%) in those with 0 to 3 points to 73% (95% CI: 66%-79%) in those with 9 or 10 points, corresponding to attributable fraction estimates of approximately 0% to 90%. Kaplan-Meier estimated stroke/TIA 2-year recurrence rates decreased from 20% (95% CI: 12%-28%) in the lowest Risk of Paradoxical Embolism score stratum to 2% (95% CI: 0%-4%) in the highest. CONCLUSION: Clinical characteristics identify CS patients who vary markedly in PFO prevalence, reflecting clinically important variation in the probability that a discovered PFO is likely to be stroke-related vs incidental. Patients in strata more likely to have stroke-related PFOs have lower recurrence risk.

Improvement of Granular Base Course Materials with Portland Cement, Special Report, HR-99

A highway base course may be defined as a layer of granular material which lies immediately below the wearing surface of a pavement and must possess high resistance to deformation in order to withstand pressures imposed by traffic. A material commonly used for base course construction is crushed limestone. Sources of limestone, acceptable for highway bases in the state of Iowa, occur almost entirely in the Pennsylvanian, Mississippian and Devonian strata. Performance records of the latter two have been quite good, while material from the Pennsylvanian stratum has failed on numerous occasions. The study reported herein is one segment of an extensive research program on compacted crushed limestone used for flexible highway base courses. The primary goals of the total study are: 1. Determination of a suitable and realistic laboratory method of compaction. 2. Effect of gradation, and mineralogy of the fines, on shearing strength. 3. Possible improvement of the shear strength with organic and inorganic chemical stabilization additives. Although the study reported herein deals primarily with the third goal, information gathered from work on the first two was required for this investigation. The primary goal of this study was the evaluation of various factors of stability of three crushed limestones when treated with small amounts of type I Portland cement. Investigation of the untreated materials has indicated that shear strength alone is not the controlling factor for stability of crushed stone bases. Thus the following observations were made in addition to shear strength parameters, to more adequately ascertain the stability of the cement treated materials: 1. Volume change during consolidation and shear testing. 2. Pore pressure during shear. The consolidated-undrained triaxial shear test was used for determination of the above factors.

Contribution à l'étude neuroanatomique de systèmes enzymatiques impliqués dans le métabolisme énergétique cérébral

RESUME Il a longtemps été admis que le glucose était le principal, sinon le seul substrat du métabolisme énergétique cérébral. Néanmoins, des études récentes indiquent que dans des situations particulières, d'autres substrats peuvent être employés. C'est le cas des monocarboxylates (lactate et pyruvate principalement). Bien que la barrière hématoencéphalique soit peu perméable à ces molécules, elles deviennent néanmoins des substrats possibles si elles sont produites localement. Les deux systèmes enzymatiques pivots des voies glycolytiques et oxydatives sont la lactate déshydrogénase (LDH, EC 1.1.1.27) qui catalyse l'interconversion du pyruvate et du lactate et le complexe pyruvate déshydrogénase qui catalyse la conversion irréversible du pyruvate en acétyl-CoA qui entre dans la respiration mitochondriale. Nous avons étudié la localisation, tant régionale que cellulaire, des isoformes LDH-1, LDH-5 et PDHEla dans le cerveau du chat et dé l'homme au moyen de diverses techniques histologiques. Dans un premier temps, des investigations par hybridation in situ au moyen d'oligosondes marquées au 33P sur de coupes de cerveau de chat ont permis de montrer une différence de l'expression des enzymes à vocation oxydative (LDH-1 et PDHA1, le gène codant pour la protéine PDHEIa) par rapport à LDH-5, isoforme qui catalyse préférentiellement la formation de lactate. LDH-1 et PDHA 1 ont des distributions similaires et sont enrichies dans de nombreuses structures cérébrales, comme l'hippocampe, de nombreux noyaux thalamiques et des structures pontiques. Le cortex cérébral exhibe également une expression importante de LDH-1 et PDH. LDH-5 a par contre une expression largement plus diffuse à travers le cerveau, bien que l'on trouve néanmoins un enrichissement plus important dans l'hippocampe. Ces résultats sont en accord avec les observations que nous avons précédemment publiées chez le rongeur pour LDH-1 et LDH-5 (Laughton et collaborateurs, 2000). Des analyses par PCR en temps réel ont confirmé que dans certaines régions, LDH-1 est exprimée de façon nettement plus importante que LDH-5. Dans un deuxième temps, nous avons appliqué sur des coupes histologiques d'hippocampe et de cortex occipital humain post-mortem des anticorps monoclonaux spécifiques de l'isoforme LDH-5 et la sous-unité PDHela du complexe pyruvate déshydrogénase. Là aussi, les immunoréactions révèlent une ségrégation régionale mais aussi cellulaire des deux enzymes. Dans les deux régions étudiées, LDH-5 est localisée exclusivement dans les astrocytes. Dans le cortex occipital, la matière blanche et également la couche I corticale sont immunopositives pour LDH-5. Dans l'hippocampe, le CA4 et l'alveus exhibe l'immunomarquage le plus intense pour LDH-5. Seuls des neurones (à de rares exceptions quelques astrocytes) sont immunopositifs à l'anticorps monoclonal dirigé contre PDHela. La couche IV du cortex occipital présente la plus forte immunoréaction. Dans l'hippocampe, une immunoréactivité est observée dans le stratum granulosum et à travers la région CA1 jusqu'à la région CA3. L'ensemble de ces résultats montre une hétérogénéité métabolique dans le cerveau et étaye l'hypothèse "astrocyte-neurone lactate shuttle" (ANL5) (Bittar et collaborateurs, 1996; Magistretti et Pellerin, 1999) qui propose que les astrocytes fournissent aux neurones activés du lactate comme substrat alternatif de leur métabolisme énergétique. ABSTRACT For a long time now, glucose has been thought to be the main, if not the sole substrate for brain energy metabolism. Recent data nevertheless suggest that other molecules, such as monocarboxylates (lactate and pyruvate mainly) could be suitable substrates. Although monocarboxylates poorly cross the blood brain barrier (BBB), such substrates could replace glucose if produced locally. The two key enzymatic systems required for the use and production of these substats are lactate dehydrogenase (LDH; EC 1.1.1.27) that catalyses the interconversion of lactate and pyruvate and the pyruvate dehydrogenase complex that irreversibly funnels pyruvate towards the mitochondrial TCA cycle and oxydative phosphorylation. Our study consisted in localizing these different systems with various histochemical procedures in the cat brain and two regions, i.e. hippocampus and primary visual cortex, of the human brain. First, by means of in situ hybridization with 33P labeled oligoprobes, we have demonstrated that the more oxidative enzymes (LDH-1 and PDHA1, the gene coding for PDHEla) are highly expressed in a variety of feline brain structures. These structures include the hippocampus, various thalamic nuclei and the pons. The cerebral cortex exhibits also a high LDH-1 and PDHAl expression. On the other hand, LDH-5 expression is poorer and more diffuse, although the hippocampus does seem to have a higher expression. These fmdings are consistent with our previous observation of the expression of LDH1 and LDH-5 in the rodent brain (Laughton et al, 2000). Real-time PCR (TagMan tm) revealed that, in various regions, LDH-1 is effectively more highly expressed than LDH-5. In a second set of experiments, monoclonal antibodies to LDH-5 and PDHeIa were applied to cryostat sections of post-mortem human hippocampus and occipital cortex. These procedures revealed not only that the two enzymes have different regional distributions, but also distinct cellular localisation. LDH-5 immunoreactivity is solely observed in astrocytes. In the occipital cortex, the white matter and layer I are immunopositive. In the hippocampus, the alveus and CA4 show LDH-5 immunoréactivity. PDHeIa has been detected, with few exceptions, only in neurons. Layer IV of the occipital cortex was most immmunoreactive. In the hippocampus, PDHela immunoreactivity is noticed in the stratum granulosum and through CA 1 to CA3 areas. The overall observations made in this study show that there is a metabolic heterogeneity in the brain and our findings support the hypothesis of an astrocyte-neuron lactate shuttle (ANLS)(Bittar et al., 1996; Magistretti & Pellerin, 1999) where astrocytes export to active neurons lactate to fuel their energy demands.

Endogenous protease nexin-1 protects against cerebral ischemia.

The serine protease thrombin plays a role in signalling ischemic neuronal death in the brain. Paradoxically, endogenous neuroprotective mechanisms can be triggered by preconditioning with thrombin (thrombin preconditioning, TPC), leading to tolerance to cerebral ischemia. Here we studied the role of thrombin's endogenous potent inhibitor, protease nexin-1 (PN-1), in ischemia and in tolerance to cerebral ischemia induced by TPC. Cerebral ischemia was modelled in vitro in organotypic hippocampal slice cultures from rats or genetically engineered mice lacking PN-1 or with the reporter gene lacZ knocked into the PN-1 locus PN-1HAPN-1-lacZ/HAPN-1-lacZ (PN-1 KI) exposed to oxygen and glucose deprivation (OGD). We observed increased thrombin enzyme activity in culture homogenates 24 h after OGD. Lack of PN-1 increased neuronal death in the CA1, suggesting that endogenous PN-1 inhibits thrombin-induced neuronal damage after ischemia. OGD enhanced β-galactosidase activity, reflecting PN-1 expression, at one and 24 h, most strikingly in the stratum radiatum, a glial cell layer adjacent to the CA1 layer of ischemia sensitive neurons. TPC, 24 h before OGD, additionally increased PN-1 expression 1 h after OGD, compared to OGD alone. TPC failed to induce tolerance in cultures from PN-1(-/-) mice confirming PN-1 as an important TPC target. PN-1 upregulation after TPC was blocked by the c-Jun N-terminal kinase (JNK) inhibitor, L-JNKI1, known to block TPC. This work suggests that PN-1 is an endogenous neuroprotectant in cerebral ischemia and a potential target for neuroprotection.

Genome-wide association study of virologic response with efavirenz-containing or abacavir-containing regimens in AIDS clinical trials group protocols.

BACKGROUND: Efavirenz and abacavir are components of recommended first-line regimens for HIV-1 infection. We used genome-wide genotyping and clinical data to explore genetic associations with virologic failure among patients randomized to efavirenz-containing or abacavir-containing regimens in AIDS Clinical Trials Group (ACTG) protocols. PARTICIPANTS AND METHODS: Virologic response and genome-wide genotype data were available from treatment-naive patients randomized to efavirenz-containing (n=1596) or abacavir-containing (n=786) regimens in ACTG protocols 384, A5142, A5095, and A5202. RESULTS: Meta-analysis of association results across race/ethnic groups showed no genome-wide significant associations (P<5×10) with virologic response for either efavirenz or abacavir. Our sample size provided 80% power to detect a genotype relative risk of 1.8 for efavirenz and 2.4 for abacavir. Analyses focused on CYP2B genotypes that define the lowest plasma efavirenz exposure stratum did not show associations nor did analysis limited to gene sets predicted to be relevant to efavirenz and abacavir disposition. CONCLUSION: No single polymorphism is associated strongly with virologic failure with efavirenz-containing or abacavir-containing regimens. Analyses to better consider context, and that minimize confounding by nongenetic factors, may show associations not apparent here.

Key locations for soybean genotype assessment in Central Brazil

The objective of this work was to identify key locations for the establishment of soybean (Glycine max) genetic breeding programs, in the Central Region of Brazil. Grain yield data of three maturity groups of soybean genotypes, from regional trials conducted over three years, at 18 locations in Brazilian Cerrado were used. A key location for the early phases of the breeding program was defined as the site that best classifies the winning genotypes in the region. Key locations for the final phases were defined as those sites that best represent each environmental stratum, in relation to the adaptability of the respective winning genotype. This adaptability was estimated by additive main effects and multiplicative interaction (AMMI) model analysis, using the distance between the score of each location in a stratum and the score of the winning genotype, which characterizes such stratum in an AMMI biplot. The locations that best classified the winning genotypes over space and time were Mineiros, Placas and Rio Verde. For the final phases of genotype selection, with data from the three maturity group, the recommended locations were: Buritis, Chapadão do Céu, Iraí, Pamplona, Placas, Planaltina, Rio Verde, Sacramento, Senador Canedo, Uberaba, and Uberlândia.

A genome-wide association study of anorexia nervosa.

Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome-wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2907 cases with AN from 14 countries (15 sites) and 14 860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery data sets. Seventy-six (72 independent) single nucleotide polymorphisms were taken forward for in silico (two data sets) or de novo (13 data sets) replication genotyping in 2677 independent AN cases and 8629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication data sets comprised 5551 AN cases and 21 080 controls. AN subtype analyses (1606 AN restricting; 1445 AN binge-purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P=3.01 × 10(-7)) in SOX2OT and rs17030795 (P=5.84 × 10(-6)) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P=5.76 × 10(-)(6)) between CUL3 and FAM124B and rs1886797 (P=8.05 × 10(-)(6)) near SPATA13. Comparing discovery with replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P=4 × 10(-6)), strongly suggesting that true findings exist but our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field.