Germline-somatic liaison dictates cancer subtype via de novo steroid biosynthesis.

The biological mechanisms underlying the cooperation between germline genetic variants and somatic mutations during carcinogenesis are rarely elucidated. Here, characterizing isogenic prostate cancer cell lines, we dissected the interplay between a germline variant at the 7p14.3 locus (rs1376350, G>A) and early recurrent prostate cancer-specific mutation in the Speckle-Type POZ protein (SPOP) gene across human prostate adenocarcinomas.

Signaling mechanisms that direct cell fate specification and morphogenesis in human embryonic stem cells-based models of human gastrulation.

During mammalian gastrulation, a mass of pluripotent cells surrounded by extraembryonic tissues differentiates into germ layers, mesoderm, endoderm, and ectoderm. The three germ layers are then organized into a body plan with organ rudiments via morphogenetic gastrulation movements of emboly, epiboly, convergence, and extension. Emboly is the most conserved gastrulation movement, whereby mesodermal and endodermal progenitors undergo epithelial-to-mesenchymal transition (EMT) and move via a blastopore/primitive streak beneath the ectoderm.

Dissecting cell identity via network inference and in silico gene perturbation.

Cell identity is governed by the complex regulation of gene expression, represented as gene-regulatory networks. Here we use gene-regulatory networks inferred from single-cell multi-omics data to perform in silico transcription factor perturbations, simulating the consequent changes in cell identity using only unperturbed wild-type data. We apply this machine-learning-based approach, CellOracle, to well-established paradigms-mouse and human haematopoiesis, and zebrafish embryogenesis-and we correctly model reported changes in phenotype that occur as a result of transcription factor perturbation.

A short Mindfulness retreat can improve biological markers of stress and inflammation.

Objective: Mindfulness practice, a form of meditation, has shown benefit for psychological and physical health. In this study, we investigated the effect of an intensive period of Mindfulness practice on some biological mediators of stress and inflammation during a 3-day residential retreat.

Methods: A total of 95 healthy individuals (aged 18-67) were recruited and randomized to a Mindfulness retreat arm or an active control arm.

F-isoprostanes can mediate bleomycin-induced lung fibrosis.

F-isoprostanes (F-IsoPs) have been considered markers of oxidative stress in various pulmonary diseases, but little is known about their possible role in pulmonary fibrosis. In this study, we have investigated the potential key role of F-IsoPs as markers and mediators of bleomycin (BLM)-induced pulmonary fibrosis in rats. During the in vivo study, plasma F-IsoPs showed a peak at 7 days and remained elevated for the entire experimental period.

Inherited determinants of early recurrent somatic mutations in prostate cancer.

Prostate cancer is a highly heritable molecularly and clinically heterogeneous disease. To discover germline events involved in prostate cancer predisposition, we develop a computational approach to nominate heritable facilitators of somatic genomic events in the context of the androgen receptor signaling. Here, we use a ranking score and benign prostate transcriptomes to identify a non-coding polymorphic regulatory element at 7p14.

Animal models for anti-emphysema drug discovery.

Introduction: Emphysema is characterized by an abnormal and permanent enlargement of airspaces accompanied by destruction of their walls. Up to now, there is no cure for emphysema, and animal models may be important for new drug discovery.

Areas Covered: Herein, the authors review animal models of emphysema since the protease-antiprotease hypothesis as well as the results obtained with compounds tested in these models.