Seasonal size variation in the predatory cladoceran Bythotrephes cederstroemii in Lake Michigan

1.  Dry weight, body length and spine length were measured for the exotic cladoceran Bythotrephes cederstroemii collected from offshore and inshore stations in southeastern Lake Michigan. Average dry weight of each developmental stage exhibited seasonal variation by a factor of more than 5. 2.  Mean dry weight of Bythotrephes was closely correlated with water temperature. Contrary to the inverse relationship between water temperature and body size frequently observed for other invertebrates, the dry weight of Bythotrephes increased at higher ambient temperatures. 3.  No significant correlation was observed between abundances of major zooplankton taxa and the dry weight of Bythotrephes . An indirect effect of temperature on prey consumption may cause seasonal variation in dry weight of Bythotrephes in Lake Michigan. 4.  Distances between adjacent pairs of barbs, added to the caudal spine with each moult, are significantly shorter in Bythotrephes which produce resting eggs. Less material investment in the exoskeleton of sexually reproducing females was observed in favour of growth and reproduction.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74641/1/j.1365-2427.1994.tb00842.x.pd

Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk

A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10−8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers

Bovine mature adipocytes readily return to a proliferative state

The dynamics of human and animal adipogenesis has been defined using several traditional cell systems including stromal vascular cells and adipocyte-related cell lines. But a relatively new cell system using progeny cells stemming from the dedifferentiation of purified cultures of mature adipocytes may be used for studying the development and biology of adipocytes. In this research, we show that isolated (and purified) mature adipocytes derived from Wagyu cattle dedifferentiate into progeny cells, and that these spindle-shaped, proliferative-competent daughter cells possess ability to proliferate. We outline the optimum cell culture system and offer precautionary thoughts for effective mature adipocyte culture. Collectively, this represents a novel cell model which may provide new insights into cell development, physiology and use as a model for animal production/composition, tissue engineering and disease treatment

Divergent chemokine receptor expression and the consequence for human IgG4 B cell responses

IgG4 antibodies are unique to humans. IgG4 is associated with tolerance during immunotherapy in allergy, but also with pathology, as in pemphigus vulgaris and IgG4-related disease. Its induction is largely restricted to nonmicrobial antigens, and requires repeated or prolonged antigenic stimulation, for reasons poorly understood. An important aspect in generating high-affinity IgG antibodies is chemokine receptor-mediated migration of B cells into appropriate niches, such as germinal centers. Here, we show that compared to IgG1 B cells, circulating IgG4 B cells express lower levels of CXCR3, CXCR4, CXCR5, CCR6, and CCR7, chemokine receptors involved in GC reactions and generation of long-lived plasma cells. This phenotype was recapitulated by in vitro priming of naive B cells with an IgG4-inducing combination of TFH/TH2 cytokines. Consistent with these observations, we found a low abundance of IgG4 B cells in secondary lymphoid tissues in vivo, and the IgG4 antibody response is substantially more short-lived compared to other IgG subclasses in patient groups undergoing CD20+ B cell depletion therapy with rituximab. These results prompt the hypothesis that factors needed to form IgG4 B cells restrain at the same time the induction of a robust migratory phenotype that could support a long-lived IgG4 antibody response