Genetic variants associated with breast cancer risk for Ashkenazi Jewish women with strong family histories but no identifiable BRCA1/2 mutation

The ability to establish genetic risk models is critical for early identification and optimal treatment of breast cancer. For such a model to gain clinical utility, more variants must be identified beyond those discovered in previous genome-wide association studies (GWAS). This is especially true for women at high risk because of family history, but without BRCA1/2 mutations. This study incorporates three datasets in a GWAS analysis of women with Ashkenazi Jewish (AJ) homogeneous ancestry. Two independent discovery cohorts comprised 239 and 238 AJ women with invasive breast cancer or preinvasive ductal carcinoma in situ and strong family histories of breast cancer, but lacking the three BRCA1/2 founder mutations, along with 294 and 230 AJ controls, respectively. An independent, third cohort of 203 AJ cases with familial breast cancer history and 263 healthy controls of AJ women was used for validation. A total of 19 SNPs were identified as associated with familial breast cancer risk in AJ women. Among these SNPs, 13 were identified from a panel of 109 discovery SNPs, including an FGFR2 haplotype. In addition, six previously identified breast cancer GWAS SNPs were confirmed in this population. Seven of the 19 markers were significant in a multivariate predictive model of familial breast cancer in AJ women, three novel SNPs [rs17663555(5q13.2), rs566164(6q21), and rs11075884(16q22.2)], the FGFR2 haplotype, and three previously published SNPs [rs13387042(2q35), rs2046210(ESR1), and rs3112612(TOX3)], yielding moderate predictive power with an area under the curve (AUC) of the ROC (receiver-operator characteristic curve) of 0.74. Population-specific genetic variants in addition to variants shared with populations of European ancestry may improve breast cancer risk prediction among AJ women from high-risk families without founder BRCA1/2 mutations.     

The ant community response to the arrival of Monomorium sydneyense forel (Hymenoptera: Formicidae) at sulphur point,Tauranga, New Zealand

Abstract

Impacts of highly invasive ants in new ecosystems are well documented, but many more ant species are establishing in new ranges for which there is little or no information. We studied the effects of the recently discovered Australian ant, Monomorium sydneyense Forel, on the ant community of Sulphur Point in Tauranga, New Zealand. At the community scale, the species composition in invaded areas was significantly different from that in areas free of M. sydneyense. However, no single ant species was significantly more or less abundant in the presence of M. sydneyense. Some resident ant species categorised in the same functional group as the invader appeared to be scarcer when sympatric with M. sydneyense, but the local abundances of these species were always spatially variable, so the effects were not statistically significant Patchy distribution of M. sydneyense, and other aspects of its behaviour, such as poor foraging abilities and a lack of unicoloniality (where there is little or no aggression between conspecific ants from spatially separate nests), appear to allow resident ant species to coexist with M. sydneyense at Sulphur Point.     

Competitive protein adsorption on polysaccharide and hyaluronate modified surfaces

Adsorption of bovine serum albumin (BSA) and fibrinogen (Fg) was measured on six distinct bare and dextran- and hyaluronate-modified silicon surfaces created using two dextran grafting densities and three hyaluronic acid (HA) sodium salts derived from human umbilical cord, rooster comb and Streptococcus zooepidemicus. Film thickness and surface morphology depended on the HA molecular weight and concentration. BSA coverage was enhanced on surfaces in competitive adsorption of BSA:Fg mixtures. Dextranization differentially reduced protein adsorption onto surfaces based on oxidation state. Hyaluronization was demonstrated to provide the greatest resistance to protein coverage, equivalent to that of the most resistant dextranized surface. Resistance to protein adsorption was independent of the type of HA utilized. With changing bulk protein concentration from 20 to 40 μg ml^?1 for each species, Fg coverage on silicon increased by 4x, whereas both BSA and Fg adsorption on dextran and HA were far less dependent on protein bulk concentration.     

The biostratigraphic and palaeoenvironmental significance of Lower Cambrian (Botomian) trilobites from the Ak-Kaya section of the Altai Mountains (southern Siberia,Russia)

The presence of one of the oldest records of polycystine Radiolaria in the Lower Cambrian sedimentary sequence of the Ak-Kaya section (Gorny Altai) requires a biostratigraphic dating. The trilobites found recently a few tens of meters below the radiolarian-bearing level belong to Calodiscus resimus Repina, Serrodiscus fossuliferus Repina and Alacephalus aff. contortus Repina; they suggest that this part of the Shashkunar Formation can be correlated with the lower part of the Botomian stage. The absence of eyes in the two former species suggests a mode of life buried in the fine pelagic sediments. Indications of the presence of a strongly developed musculature on the third species point to a palaeoenvironment characterized by a relatively high hydrodynamic regime.     

Whisker motor cortex ablation and whisker movement patterns

Previous studies, based on qualitative observations, reported that lesions of the whisker motor cortex produce no deficits in whisking behavior. We used high-resolution optoelectronic recording methods to compare the temporal organization and kinematics of whisker movements before and after unilateral lesions of whisker motor cortex in rats. We now report that while the lesion did not abolish whisking, it significantly disrupted whisking kinematics, coordination, and temporal organization. Lesioned animals showed significant increases in the velocity and amplitude of whisker protractions contralateral to the lesions, as well as a reduction in the synchrony of whisker movements on the two sides of the face. There was a marked shift in the distribution of whisking frequencies, with reduction of activity in the 5–7?Hz bandwidth and increased activity at <?2?Hz. Disruptions of the normal whisking pattern were evident on both sides of the face, and the magnitude of these effects was proportional to the extent of the cortical ablation. We suggest that the observed deficits reflect an imbalance in cortical inputs to a brainstem central pattern generator.     

Herbivory and drought interact to enhance spatial patterning and diversity in a savanna understory

The combination of abiotic stress and consumer stress can have complex impacts on plant community structure. Effective conservation and management of semi-arid ecosystems requires an understanding of how different stresses interact to structure plant communities. We explored the separate and combined impacts of episodic drought, livestock grazing, and wild ungulate herbivory on species co-occurrence and diversity patterns in a relatively productive, semi-arid Acacia savanna. Specifically, we analyzed 9 years of biannual plant community data from the Kenya long-term exclosure experiment, a broad-scale manipulative experiment that has excluded different combinations of large mammalian herbivores from 18 4-ha plots since 1995. During droughts, we observed low species diversity and random species co-occurrence patterns. However, when rain followed a major drought, areas exposed to moderate cattle grazing displayed high species diversity and evidence of significant species aggregation. These patterns were not apparent in the absence of cattle, even if other large herbivores were present. To explore possible mechanisms, we examined patterns separately for common and rare species. We found that aggregation patterns were likely driven by rare species responding similarly to the availability of open micro-sites. Our results indicate that in a productive, fire-suppressed savanna, the combination of periodic drought and moderate cattle grazing can enhance plant biodiversity and fine-scale spatial heterogeneity by opening up space for species that are otherwise rare or cryptic. Our findings also emphasize that domestic herbivores can have significantly stronger impacts on plant community dynamics than wild herbivores, even in an ecosystem with a long history of grazing.     

A closer look at the “Protopithecus” fossil assemblages: new genus and species from Bahia,Brazil

The recently extinct large-bodied New World monkey Protopithecus brasiliensis Lund 1836 was named based on a distal humerus and proximal femur found in the Lagoa Santa cave system in the southeastern Brazilian state of Minas Gerais. These bones are from an animal about twice the size of the largest extant platyrrhines. One hundred and seventy-five years later, a nearly complete skeleton was discovered in the Toca da Boa Vista caves in the neighboring state of Bahia and was allocated to the same taxon as it was the first platyrrhine fossil of comparable size found since the originals. Our detailed study of the equivalent elements, however, reveals important morphological differences that do not correspond to intraspecific variation as we know it in related platyrrhine taxa. The presence of both an expanded brachioradialis flange on the humerus and gluteal tuberosity on the femur of the Bahian skeleton distinguishes it from the Lagoa Santa fossil as well as from all other platyrrhines. Further cranial and postcranial evidence suggests a closer relationship of the former with the alouattine Alouatta, while the limited Lund material fits more comfortably with the ateline clade. Therefore, we propose to limit P. brasiliensis Lund to the distal humerus and proximal femur from Lagoa Santa and erect a new genus and species for the skeleton from Toca da Boa Vista. Cartelles coimbrafilhoi was a large-bodied frugivore with a relatively small brain and diverse locomotor repertoire including both suspension and climbing that expands the range of platyrrhine biodiversity beyond the dimensions of the living neotropical primates.     

Diet and feeding habits of the small catfish,Clarias liocephalus in wetlands of Western Uganda

Clarias liocephalus is an air‐breathing catfish inhabiting wetland and river systems in East Africa. This catfish is in high demand for sale as live bait in the Nile perch fishery of Lake Victoria and equally important in the diet of local communities in the lake basin. Wetland loss and increasing fishing pressure potentially threaten the persistence of C. liocephalus; however, little information exists on the ecology of this species to permit evaluation of current threats. This study quantified dietary characteristics of C. liocephalus from heavy and lightly fished wetlands in Western Uganda using numeric, gravimetric and volumetric indices on 492 stomach samples collected over one year. Clarias liocephalus was significantly smaller in three heavily fished sites, relative to the one in‐park site, likely a reflection of a size‐selective fishery. Across sites, C. liocephalus was a generalist feeder whose diet was dominated by aquatic dipteran larvae and plant material. The broad niche gives C. liocephalus an ecological advantage to forage effectively on a wide selection of prey. The significant presence of plant material shows that the species may utilize plant protein, an important consideration of diet requirements should the species be selected for aquaculture.     

CD147, CD44, and the Epidermal Growth Factor Receptor (EGFR) Signaling Pathway Cooperate to Regulate Breast Epithelial Cell Invasiveness

The immunoglobulin superfamily glycoprotein CD147 (emmprin; basigin) is associated with an invasive phenotype in various types of cancers, including malignant breast cancer. We showed recently that up-regulation of CD147 in non-transformed, non-invasive breast epithelial cells is sufficient to induce an invasive phenotype characterized by membrane type-1 matrix metalloproteinase (MT1-MMP)-dependent invadopodia activity (Grass, G. D., Bratoeva, M., and Toole, B. P. (2012) Regulation of invadopodia formation and activity by CD147. J. Cell Sci. 125, 777–788). Here we found that CD147 induces breast epithelial cell invasiveness by promoting epidermal growth factor receptor (EGFR)-Ras-ERK signaling in a manner dependent on hyaluronan-CD44 interaction. Furthermore, CD147 promotes assembly of signaling complexes containing CD147, CD44, and EGFR in lipid raftlike domains. We also found that oncogenic Ras regulates CD147 expression, hyaluronan synthesis, and formation of CD147-CD44-EGFR complexes, thus forming a positive feedback loop that may amplify invasiveness. Last, we showed that malignant breast cancer cells are heterogeneous in their expression of surface-associated CD147 and that high levels of membrane CD147 correlate with cell surface EGFR and CD44 levels, activated EGFR and ERK1, and activated invadopodia. Future studies should evaluate CD147 as a potential therapeutic target and disease stratification marker in breast cancer.