The Next Generation Virgo Cluster Survey. IX. Estimating the Efficiency of Galaxy Formation on the Lowest-Mass Scales

The Next Generation Virgo Cluster Survey has recently determined the luminosity function of galaxies in the core of the Virgo cluster down to unprecedented magnitude and surface brightness limits. Comparing simulations of cluster formation to the derived central stellar mass function, we attempt to estimate the stellar-to-halo-mass ratio (SHMR) for dwarf galaxies, as it would have been before they fell into the cluster. This approach ignores several details and complications, e.g., the contribution of ongoing star formation to the present-day stellar mass of cluster members, and the effects of adiabatic contraction and/or violent feedback on the subhalo and cluster potentials. The final results are startlingly simple, however; we find that the trends in the SHMR determined previously for bright galaxies appear to extend down in a scale-invariant way to the faintest objects detected in the survey. These results extend measurements of the formation efficiency of field galaxies by two decades in halo mass, or five decades in stellar mass, down to some of the least massive dwarf galaxies known, with stellar masses of $\sim 10^5 M_\odot$.Comment: 18 pages, 12 figures; published in ApJ July 1st 201

Identification of novel epithelial ovarian cancer loci in women of African ancestry.

Women of African ancestry have lower incidence of epithelial ovarian cancer (EOC) yet worse survival compared to women of European ancestry. We conducted a genome-wide association study in African ancestry women with 755 EOC cases, including 537 high-grade serous ovarian carcinomas (HGSOC) and 1,235 controls. We identified four novel loci with suggestive evidence of association with EOC (p < 1 × 10-6 ), including rs4525119 (intronic to AKR1C3), rs7643459 (intronic to LOC101927394), rs4286604 (12 kb 3' of UGT2A2) and rs142091544 (5 kb 5' of WWC1). For HGSOC, we identified six loci with suggestive evidence of association including rs37792 (132 kb 5' of follistatin [FST]), rs57403204 (81 kb 3' of MAGEC1), rs79079890 (LOC105376360 intronic), rs66459581 (5 kb 5' of PRPSAP1), rs116046250 (GABRG3 intronic) and rs192876988 (32 kb 3' of GK2). Among the identified variants, two are near genes known to regulate hormones and diseases of the ovary (AKR1C3 and FST), and two are linked to cancer (AKR1C3 and MAGEC1). In follow-up studies of the 10 identified variants, the GK2 region SNP, rs192876988, showed an inverse association with EOC in European ancestry women (p = 0.002), increased risk of ER positive breast cancer in African ancestry women (p = 0.027) and decreased expression of GK2 in HGSOC tissue from African ancestry women (p = 0.004). A European ancestry-derived polygenic risk score showed positive associations with EOC and HGSOC in women of African ancestry suggesting shared genetic architecture. Our investigation presents evidence of variants for EOC shared among European and African ancestry women and identifies novel EOC risk loci in women of African ancestry

Increased Inter-Colony Fusion Rates Are Associated with Reduced COI Haplotype Diversity in an Invasive Colonial Ascidian Didemnum vexillum

Considerable progress in our understanding of the population genetic changes associated with biological invasions has been made over the past decade. Using selectively neutral loci, it has been established that reductions in genetic diversity, reflecting founder effects, have occurred during the establishment of some invasive populations. However, some colonial organisms may actually gain an ecological advantage from reduced genetic diversity because of the associated reduction in inter-colony conflict. Here we report population genetic analyses, along with colony fusion experiments, for a highly invasive colonial ascidian, Didemnum vexillum. Analyses based on mitochondrial cytochrome oxidase I (COI) partial coding sequences revealed two distinct D. vexillum clades. One COI clade appears to be restricted to the probable native region (i.e., north-west Pacific Ocean), while the other clade is present in widely dispersed temperate coastal waters around the world. This clade structure was supported by 18S ribosomal DNA (rDNA) sequence data, which revealed a one base-pair difference between the two clades. Recently established populations of D. vexillum in New Zealand displayed greatly reduced COI genetic diversity when compared with D. vexillum in Japan. In association with this reduction in genetic diversity was a significantly higher inter-colony fusion rate between randomly paired New Zealand D. vexillum colonies (80%, standard deviation ±18%) when compared with colonies found in Japan (27%, standard deviation ±15%). The results of this study add to growing evidence that for colonial organisms reductions in population level genetic diversity may alter colony interaction dynamics and enhance the invasive potential of newly colonizing species

Evaluation of vitamin D biosynthesis and pathway target genes reveals UGT2A1/2 and EGFR polymorphisms associated with epithelial ovarian cancer in African American Women.

An association between genetic variants in the vitamin D receptor (VDR) gene and epithelial ovarian cancer (EOC) was previously reported in women of African ancestry (AA). We sought to examine associations between genetic variants in VDR and additional genes from vitamin D biosynthesis and pathway targets (EGFR, UGT1A, UGT2A1/2, UGT2B, CYP3A4/5, CYP2R1, CYP27B1, CYP24A1, CYP11A1, and GC). Genotyping was performed using the custom-designed 533,631 SNP Illumina OncoArray with imputation to the 1,000 Genomes Phase 3 v5 reference set in 755 EOC cases, including 537 high-grade serous (HGSOC), and 1,235 controls. All subjects are of African ancestry (AA). Logistic regression was performed to estimate odds ratios (OR) and 95% confidence intervals (CI). We further evaluated statistical significance of selected SNPs using the Bayesian False Discovery Probability (BFDP). A significant association with EOC was identified in the UGT2A1/2 region for the SNP rs10017134 (per allele OR = 1.4, 95% CI = 1.2-1.7, P = 1.2 × 10-6 , BFDP = 0.02); and an association with HGSOC was identified in the EGFR region for the SNP rs114972508 (per allele OR = 2.3, 95% CI = 1.6-3.4, P = 1.6 × 10-5 , BFDP = 0.29) and in the UGT2A1/2 region again for rs1017134 (per allele OR = 1.4, 95% CI = 1.2-1.7, P = 2.3 × 10-5 , BFDP = 0.23). Genetic variants in the EGFR and UGT2A1/2 may increase susceptibility of EOC in AA women. Future studies to validate these findings are warranted. Alterations in EGFR and UGT2A1/2 could perturb enzyme efficacy, proliferation in ovaries, impact and mark susceptibility to EOC.Includes NIHR and CRUK

The instructive roles of muscle cells in planarian regeneration

This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Thesis: Ph. D., Massachusetts Institute of Technology, Department of Biology, 2019Cataloged from student-submitted PDF version of thesis. Vita.Includes bibliographical references.Regeneration requires both new cell production and patterning information to correctly place new tissue. Planarians are flatworms with remarkable capacity to regenerate after nearly any injury and to indefinitely maintain tissue homeostasis. Dividing cells, neoblasts, are the source of all new tissue, whereas positional information is hypothesized to be harbored by post-mitotic muscle, including the subepidermal body wall musculature. Single-muscle-cell mRNA sequencing along the anterior-posterior axis revealed regional gene expression within muscle cells. The resulting axial gene expression map included FGF receptor-like (FGFRL) homologs and genes encoding components of Wnt signaling. Two distinct FGFRL-Wnt circuits, involving juxtaposed anterior FGFRL and posterior Wnt expression domains, controlled head and trunk patterning.Inhibition of FGFRL-Wnt circuit components led to the formation of ectopic posterior eyes or secondary pharynges, indicating their importance in maintaining the anterior-posterior axis. Inhibition of different myogenic transcription factors specifically ablated orthogonal subsets of the body wall musculature. Longitudinal fibers, oriented along the anterior-posterior axis, are required for regeneration initiation. Circular fibers maintained medial-lateral patterning during head regeneration. During early regeneration, transcriptional changes in muscle cells comprised part of a generic wound response displayed by all injuries, from incisions to decapitations. The sole exception to this generic response was the expression in body-wall muscle of the Wnt inhibitor notum, which occurs preferentially at anterior-facing wounds in longitudinal muscle fibers. Therefore, anterior-posterior polarity, the choice of head or tail regeneration, involves longitudinal body wall muscle fibers.Planarian muscle were found to be highly secretory. Combining an in silico definition of the planarian matrisome and recent whole animal single-cell transcriptome data revealed that muscle is a major source of extracellular matrix (ECM). Inhibition of hemicentin-1 (hmcn-1), which encodes a highly conserved ECM glycoprotein expressed in body wall muscle, resulted in ectopic localization of internal cells, including neoblasts, outside of the muscle fiber layer. ECM secretion and maintenance of tissue separation indicated that muscle functions as planarian connective tissue. Whereas muscle is often viewed as a strictly contractile tissue, these findings reveal that planarian muscle has specific regulatory roles in axial patterning, wound signaling, and tissue architecture to enable correct regeneration.by Lauren E. Cote.Ph. D.Ph.D. Massachusetts Institute of Technology, Department of Biolog

Local ecological knowledge and multidisciplinary approach lead to discovery of hidden biodiversity in the deep ocean of Labrador, Canada

International commitments to preserve global biodiversity target the protection of 30% of marine habitats by 2030. The lack of even basic knowledge of many marine areas (e.g., deep oceans) combined with short timelines require integrative knowledge and multidisciplinary techniques to be used to efficiently identify areas worthy of protection. Here we outline a case study of the discovery of the Makkovik Hanging Gardens found in a deep-water trough in coastal Labrador, Canada. The area is of ecological significance because it supports high densities of vulnerable marine ecosystem indicator taxa, including the gorgonian coral Primnoa resedaeformis on portions of its vertical submarine walls. This study illustrates the exploratory process initiated by Nunatsiavut, which integrated local knowledge, scientific models, and a variety of technologies (such as remotely operated vehicles and multibeam sonar) to discover deep-water hidden biodiversity toward the advancement of both local Indigenous and global conservation goals