No abstract

Malignant peripheral nerve sheath tumour (MPNST) is a rare soft tissue sarcoma. In particular, primary MPNST of the breast is extremely rare. We report a case of a giant malignant peripheral nerve sheath tumour involving the entire right breast, which was not associated with neurofibromatosis type 1 (NF-1) or previous radiation therapy. A CT scan showed a huge heterogeneous soft tissue mass with well-enhanced nodules at its periphery and low-density internal necrosis, which was confirmed by modified radical mastectomy.

Trio family and case-control studies of next-generation sequencing data have proven integral to understanding the contribution of rare inherited and de novo single-nucleotide variants to the genetic architecture of complex disease. Ideally, such studies should identify individual risk genes of moderate to large effect size to generate novel treatment hypotheses for further follow-up. However, due to insufficient power, gene set enrichment analyses have come to be relied upon for detecting differences between cases and controls, implicating sets of hundreds of genes rather than specific targets for further investigation. Here, we present a Bayesian statistical framework, termed gTADA, that integrates gene-set membership information with gene-level de novo and rare inherited case-control counts, to prioritize risk genes with excess rare variant burden within enriched gene sets. Applying gTADA to available whole-exome sequencing datasets for several neuropsychiatric conditions, we replicated previously reported gene set enrichments and identified novel risk genes. For epilepsy, gTADA prioritized 40 risk genes (posterior probabilities > 0.95), 6 of which replicate in an independent whole-genome sequencing study. In addition, 30/40 genes are novel genes. We found that epilepsy genes had high protein-protein interaction (PPI) network connectivity, and show specific expression during human brain development. Some of the top prioritized EPI genes were connected to a PPI subnetwork of immune genes and show specific expression in prenatal microglia. We also identified multiple enriched drug-target gene sets for EPI which included immunostimulants as well as known antiepileptics. Immune biology was supported specifically by case-control variants from familial epilepsies rather than do novo mutations in generalized encephalitic epilepsy. meta-analyzing DNMs and rare case-control (CC) variants, an approach that has been particularly successful for autism spectrum disorders (ASD) 9,10 . For epilepsy (EPI), multiple associated genes have been identified through DN based studies 4,5,11 , and in recent years, a number of EPI significant genes have also been identified through CC studies 12,13 . We hypothesized that, as for ASD, additional significant EPI genes could be discovered through the integration of DN and CC data. EPI is a serious brain disorder which includes multiple subtypes. Studies of cases/controls and twins have shown that genetic components have played important roles in EPI [14][15][16] . Some of EPI's subtypes can be explained by single genes, but multiple subtypes might be caused by multiple genes 15 . It is still challenging to develop specific drugs for this disorder. There have been multiple antiepileptic drugs used for EPI treatments; however, 20-30% of EPI patients have not been successful in controlling their seizures by using current medications 17 . Identifying additional genes or gene sets might help better understand its etiology as well as better design drug targets for the disorder.Due to the high p...

Functional genomics networks are widely used to identify unexpected pathway relationships in large genomic datasets. However, it is challenging to quantitatively compare the signal-to-noise ratio of different networks, the biology they describe, and to identify the optimal network to interpret a particular genetic dataset. Via GeNets users can train a machine-learning model (Quack) to make such comparisons; and they can execute, store, and share analyses of genetic and RNA sequencing datasets.

Variation in floral displays, both between and within species, has been long known to be shaped by the mutualistic interactions that plants establish with their pollinators. However, increasing evidence suggests that abiotic selection pressures influence floral diversity as well. Here we analyze the genetic and environmental factors that underlie patterns of floral pigmentation in wild sunflowers. While sunflower inflorescences appear invariably yellow to the human eye, they display extreme diversity for patterns of ultraviolet pigmentation, which are visible to most pollinators. We show that this diversity is largely controlled by cis-regulatory variation at a single MYB transcription factor, HaMYB111, through accumulation of UV-absorbing flavonol glycosides. As expected, different patterns of ultraviolet pigments in flowers have a strong effect on pollinator preferences. However, variation for floral ultraviolet patterns is also associated with environmental variables, especially relative humidity, across populations of wild sunflowers. Larger ultraviolet patterns, which are found in drier environments, limit transpiration, therefore reducing water loss. The dual role of floral UV patterns in pollination attraction and abiotic responses reveals the complex adaptive balance underlying the evolution of floral traits.

P P Mad P Tkv Put Dpp P P Mad P Mad P Tkv Put Dpp Put Dpp P P Sax Put Dpp P Sax O Sxc Normal glucose and Sxc Low glucose or no Sxc Extracellular space Cytoplasm Graphical Abstract Moulton et al. p. 2 Summary Precise regulation of signal transduction is critical throughout organismal life, both for embryonic development and for adult homeostasis. To ensure proper spatio-temporal signal transduction, Bone Morphogenetic Protein (BMP) signaling pathways, like all other signaling pathways, are regulated by both agonists and antagonists. Here, we report identification of a previously unrecognized method of signal antagonism for Dpp (Decapentaplegic), a Drosophila BMP family member. We demonstrate that the BMP type I receptor Saxophone (Sax) functions as a Dpp receptor in the Drosophila embryonic epidermis, but that its activity is normally inhibited by the Olinked glycosyltransferase Super sex combs (Sxc). In wild-type embryos, inhibition of Saxophone (Sax) activity in the epidermis marks the BMP type I receptor Thickveins (Tkv) as the sole conduit for Dpp. In contrast, in sxc mutants, the Dpp signal is transduced by both Tkv and Sax, and elevated Dpp signaling induces errors in embryonic development that lead to embryonic death.We also demonstrate that Sax is the O-glycosylated target of Sxc and that O-glycosylation of Sax can be modulated by dietary sugar. Together, these findings link fertility to nutritive environment and point to Sax (activin receptor-like kinase [Alk] 1/2) signaling as the nutrient-sensitive branch of BMP signaling.

No abstract

Objectives Patients with cervical cancer have lower bone mass than women without cancer, whereas women with endometrial cancer have higher bone mineral density (BMD) than control subjects, possibly due to the prevalence of high body-fat mass. The aim of this study was to compare BMD in patients with cervical cancer, endometrial cancer and controls. Methods We analyzed and compared spinal and femoral BMD in 130 patients with cervical cancer, 68 with endometrial cancer, and 140 age-matched menopausal female control subjects. We also compared serum calcium, phosphorus, total alkaline phosphatase, osteocalcin, and urinary deoxypyridinoline levels. Results Compared with the control group, T-scores for some lumbar vertebrae (L4), the femoral neck, and Ward's triangle were lower in patients with cervical cancer, whereas only L4 T-scores were significantly lower in patients with endometrial cancer. Deoxypyridinoline levels were significantly lower in women with endometrial cancer (p < 0.002) than in women with cervical cancer, but no other biochemical variables differed among groups. Conclusions Cervical cancer was associated with lower BMD, especially in femoral BMD, and may be a risk factor for secondary osteoporosis. However, endometrial cancer generally seemed to have no damaging effect on bone except at L4. A further larger follow-up study in more populations is required to clarify these findings.