A common coding variant in CASP8 is associated with breast cancer risk

The Breast Cancer Association Consortium (BCAC) has been established to conduct combined case-control analyses with augmented statistical power to try to confirm putative genetic associations with breast cancer. We genotyped nine SNPs for which there was some prior evidence of an association with breast cancer: CASP8 D302H (rs1045485), IGFBP3 -202 C --> A (rs2854744), SOD2 V16A (rs1799725), TGFB1 L10P (rs1982073), ATM S49C (rs1800054), ADH1B 3' UTR A --> G (rs1042026), CDKN1A S31R (rs1801270), ICAM5 V301I (rs1056538) and NUMA1 A794G (rs3750913). We included data from 9-15 studies, comprising 11,391-18,290 cases and 14,753-22,670 controls. We found evidence of an association with breast cancer for CASP8 D302H (with odds ratios (OR) of 0.89 (95% confidence interval (c.i.): 0.85-0.94) and 0.74 (95% c.i.: 0.62-0.87) for heterozygotes and rare homozygotes, respectively, compared with common homozygotes; P(trend) = 1.1 x 10(-7)) and weaker evidence for TGFB1 L10P (OR = 1.07 (95% c.i.: 1.02-1.13) and 1.16 (95% c.i.: 1.08-1.25), respectively; P(trend) = 2.8 x 10(-5)). These results demonstrate that common breast cancer susceptibility alleles with small effects on risk can be identified, given sufficiently powerful studies.     

Breeding biology of the threatened Campo Miner Geositta poeciloptera (Aves: Scleruridae), a Neotropical grassland specialist

The Campo Miner is a threatened grassland passerine endemic to the South American Cerrado, whose life history is almost unknown. In this paper, we studied during three breeding seasons (2014 to 2016) the breeding biology of a colour banded population of the species found in the Upper Rio Grande Grasslands, south-eastern Brazil. We found 98 nests, 81 of which became active and were monitored. The Campo Miner breeds in frequently burnt-and-grazed natural grasslands, successfully nesting in highly disturbed sites, such as dirt banks along roads and even in mine pits. The species is socially monogamous and both parents build the nest, which is a cavity/with-tunnel/simple/platform type. The nest chamber is lined with a platform made of grass fragments, charcoal, hairs, and mammal faeces. The most common clutch size is three eggs (n = 66), with some nests containing one (n = 1), two (n = 12) or four eggs (n = 2). The egg is white and pyriform and the incubation, performed by both parents, lasts 17.5 days. Mean nestling period is 15.5 days, with both parents feeding the young. Breeding season lasted for about 125 days (August to December) and multiple breeding attempts in a single season were common, with a maximum of three attempts recorded. All species of Scleruridae built their nests inside cavities dug in the soil with an access tunnel to it, where they lay a small clutch (usually 2–3 white eggs), but no other species in the family has been studied in detail to date. Further studies are required to understand why a species apparently tolerant to anthropogenic impacts such as G. poeciloptera can be so rare, patchily distributed and threatened throughout its range.     

Architecture,composition and placement of nests of the Cipo Canastero Asthenes luizae (Aves: Furnariidae), a bird endemic to Brazilian mountaintops

Cipo Canastero (Asthenes luizae) is a bird endemic to Brazilian mountaintops, inhabiting rock outcrop habitats of the campos rupestres in the southern Espinhaço Range. Available data about Cipo Canastero’s breeding biology are scarce, incomplete or inconsistent. All nests found to date were built in the plant Vellozia nivea. Based on 84 nests found from 2009 to 2017 in four sites at Serra do Cipó, we described in detail their nesting habits focusing on three groups of characters: nest architecture, composition, and placement. Also, we described nest building. Our major new findings on the nesting habits of A. luizae were: three nest layers distinguishable, inner lining covering the entire nest interior, tunnels and tubes are absent, and the nest sites are not restricted to V. nivea. We recorded a wide range of nest sites, from ground, grasses and rupicolous bromeliads to shrubs and trees, including at least 30 supporting-plant species. Nest supports varied among study sites. Nest building lasted 22 days (one nest) and was done by both members of the pair. Our data can be useful for species conservation and contribute to the knowledge of the natural history of the genus Asthenes.     

First record of Monobrachium parasitum Mereschkowsky, 1877 (Cnidaria: Hydrozoa) from Brazil,in the tropical southwestern Atlantic,and its implication for bipolarity concepts

Project HABITATS was recently initiated in the Campos Basin (20.5–24° S), state of Rio de Janeiro, to assess biological impacts of petroleum exploration and exploitation on the continental shelf and slope of Brazil. Among species discovered in benthic samples from the area is the hydroid Monobrachium parasitum Mereschkowsky, 1877, occurring in an epibiotic association with the pelecypod mollusc Mendicula ferruginosa (Forbes, 1844): this is the first report of an association between the two species. Monobrachium parasitum has always been reported from cold waters, and is generally considered bipolar. This report records the occurrence of M. parasitum at lower latitudes, where they have seldom been collected: it is also the first account of this species from South America and the southwestern Atlantic. Moreover, the bathymetric distribution of M. parasitum is extended to a depth of 998 m. No previous records exist of hydroids from the Brazilian continental slope.     

Genome-wide association study identifies three new susceptibility loci for adult asthma in the Japanese population

Bronchial asthma is a common inflammatory disease caused by the interaction of genetic and environmental factors. Through a genome-wide association study and a replication study consisting of a total of 7,171 individuals with adult asthma (cases) and 27,912 controls in the Japanese population, we identified five loci associated with susceptibility to adult asthma. In addition to the major histocompatibility complex and TSLP-WDR36 loci previously reported, we identified three additional loci: a USP38-GAB1 locus on chromosome 4q31 (combined P = 1.87 × 10(-12)), a locus on chromosome 10p14 (P = 1.79 × 10(-15)) and a gene-rich region on chromosome 12q13 (P = 2.33 × 10(-13)). We observed the most significant association with adult asthma at rs404860 in the major histocompatiblity complex region (P = 4.07 × 10(-23)), which is close to rs2070600, a SNP previously reported for association with FEV(1)/FVC in genome-wide association studies for lung function. Our findings offer a better understanding of the genetic contribution to asthma susceptibility.     

Common variants in ZNF365 are associated with both mammographic density and breast cancer risk

High-percent mammographic density adjusted for age and body mass index is one of the strongest risk factors for breast cancer. We conducted a meta analysis of five genome-wide association studies of percent mammographic density and report an association with rs10995190 in ZNF365 (combined P = 9.6 × 10(-10)). Common variants in ZNF365 have also recently been associated with susceptibility to breast cancer.     

Oncogenic IL7R gain-of-function mutations in childhood T-cell acute lymphoblastic leukemia

Interleukin 7 (IL-7) and its receptor, formed by IL-7Rα (encoded by IL7R) and γc, are essential for normal T-cell development and homeostasis. Here we show that IL7R is an oncogene mutated in T-cell acute lymphoblastic leukemia (T-ALL). We find that 9% of individuals with T-ALL have somatic gain-of-function IL7R exon 6 mutations. In most cases, these IL7R mutations introduce an unpaired cysteine in the extracellular juxtamembrane-transmembrane region and promote de novo formation of intermolecular disulfide bonds between mutant IL-7Rα subunits, thereby driving constitutive signaling via JAK1 and independently of IL-7, γc or JAK3. IL7R mutations induce a gene expression profile partially resembling that provoked by IL-7 and are enriched in the T-ALL subgroup comprising TLX3 rearranged and HOXA deregulated cases. Notably, IL7R mutations promote cell transformation and tumor formation. Overall, our findings indicate that IL7R mutational activation is involved in human T-cell leukemogenesis, paving the way for therapeutic targeting of IL-7R-mediated signaling in T-ALL.     

Revisiting the metabolic syndrome: the emerging role of aquaglyceroporins

The metabolic syndrome (MetS) includes a group of medical conditions such as insulin resistance (IR), dyslipidemia and hypertension, all associated with an increased risk for cardiovascular disease. Increased visceral and ectopic fat deposition are also key features in the development of IR and MetS, with pathophysiological sequels on adipose tissue, liver and muscle. The recent recognition of aquaporins (AQPs) involvement in adipose tissue homeostasis has opened new perspectives for research in this field. The members of the aquaglyceroporin subfamily are specific glycerol channels implicated in energy metabolism by facilitating glycerol outflow from adipose tissue and its systemic distribution and uptake by liver and muscle, unveiling these membrane channels as key players in lipid balance and energy homeostasis. Being involved in a variety of pathophysiological mechanisms including IR and obesity, AQPs are considered promising drug targets that may prompt novel therapeutic approaches for metabolic disorders such as MetS. This review addresses the interplay between adipose tissue, liver and muscle, which is the basis of the metabolic syndrome, and highlights the involvement of aquaglyceroporins in obesity and related pathologies and how their regulation in different organs contributes to the features of the metabolic syndrome.     

A mutation of human cytochrome c enhances the intrinsic apoptotic pathway but causes only thrombocytopenia

We report the first identified mutation in the gene encoding human cytochrome c (CYCS). Glycine 41, invariant throughout eukaryotes, is substituted by serine in a family with autosomal dominant thrombocytopenia caused by dysregulated platelet formation. The mutation yields a cytochrome c variant with enhanced apoptotic activity in vitro. Notably, the family has no other phenotypic indication of abnormal apoptosis, implying that cytochrome c activity is not a critical regulator of most physiological apoptosis.