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High-throughput identification of genes promoting neuron formation and lineage choice in mouse embryonic stem cells

The potential of embryonic stem cells to differentiate to all cell types makes them an attractive model for development and a potential source of cells for transplantation therapies. Candidate approaches have identified individual genes and proteins that promote the differentiation of embryonic stem cells to desired fates. Here, we describe a rapid large-scale screening strategy for the identifica

Functional Notch signaling is required for BMP4-induced inhibition of myogenic differentiation

The bone morphogenetic protein (BMP) and Notch signaling pathways are crucial for cellular differentiation. In many cases, the two pathways act similarly; for example, to inhibit myogenic differentiation. It is not known whether this inhibition is caused by distinct mechanisms or by an interplay between Notch and BMP signaling. Here we demonstrate that functional Notch signaling is required for BM

Cross-talk between the Notch and TGF-beta signaling pathways mediated by interaction of the Notch intracellular domain with Smad3

The Notch and transforming growth factor-beta (TGF-beta) signaling pathways play critical roles in the control of cell fate during metazoan development. However, mechanisms of cross-talk and signal integration between the two systems are unknown. Here, we demonstrate a functional synergism between Notch and TGF-beta signaling in the regulation of Hes-1, a direct target of the Notch pathway. Activa

Amphiregulin is a mitogen for adult neural stem cells

Neurons are continuously generated from stem cells in the hippocampus and along the lateral ventricles in the adult brain. Neural stem cells can be propagated in vitro in the presence of epidermal growth factor (EGF) or fibroblast growth factor-2. We report here that amphiregulin, a growth factor related to EGF, is a mitogen for adult mouse neural stem cells in vitro and displays potency similar t

Mechanism of Ganglioside Receptor Recognition by Botulinum Neurotoxin Serotype E

The botulinum neurotoxins are potent molecules that are not only responsible for the lethal paralytic disease botulism, but have also been harnessed for therapeutic uses in the treatment of an increasing number of chronic neurological and neuromuscular disorders, in addition to cosmetic applications. The toxins act at the cholinergic nerve terminals thanks to an efficient and specific mechanism of

Progress towards Clinical Use of iPS Cell Derived Therapies

A decade has passed since Shinya Yamanaka published his landmarking publication on how to produce pluripotent stem-cell-like cells and the term induced pluripotent stem cells, iPS cells, was coined. This past decade has been a decade devoted to pluripotent cells, scrutinizing molecular mechanisms in cell identity, and optimizing derivation methods, culture conditions and characterization methods t

Modeling psychiatric disorders : from genomic findings to cellular phenotypes

Major programs in psychiatric genetics have identified >150 risk loci for psychiatric disorders. These loci converge on a small number of functional pathways, which span conventional diagnostic criteria, suggesting a partly common biology underlying schizophrenia, autism and other psychiatric disorders. Nevertheless, the cellular phenotypes that capture the fundamental features of psychiatric diso

New neurons in old brains

The brain was traditionally viewed as a static organ, without turnover of neurons or significant capacity for self-repair after insults. Research in the last years has established that neurons are renewed in certain areas throughout life. The prospect of stimulation of endogenous neurogenesis as well as cell transplantation has raised hope for new therapies for neurological diseases.

4D-imaging of drip-line radioactivity by detecting proton emission from 54mNi pictured with ACTAR TPC

Proton radioactivity was discovered exactly 50 years ago. First, this nuclear decay mode sets the limit of existence on the nuclear landscape on the neutron-deficient side. Second, it comprises fundamental aspects of both quantum tunnelling as well as the coupling of (quasi)bound quantum states with the continuum in mesoscopic systems such as the atomic nucleus. Theoretical approaches can start ei

Professionals’ Views on the Comparatively Low Prevalence of Intimate Partner Violence Against Women in Spain. Violence Against Women

The aim of this study was to understand the reasons why Spain has one of the lowest prevalence rates of intimate partner violence against women (IPVAW) in the European Union. Using a qualitative and inductive research approach, a total of five focus groups (n = 19) and 10 unstructured interviews with key informants were conducted. Three main categories were identified as possible explanations of t

Functional role and potential therapeutic use of Reelin, Gas6 and Protein S in relation to adult neural stem or progenitor cells

The invention relates generally to methods of influencing central nervous system cells to produce progeny useful in the treatment of CNS disorders. More specifically, the invention includes methods of exposing a patient suffering from such a disorder to a reagent that modulates the proliferation, migration, differentiation and survival of central nervous system cells via PACAP, Maxadilan or VIP si

The advanced machine learner XGBoost did not reduce prehospital trauma mistriage compared with logistic regression : a simulation study

Background: Accurate prehospital trauma triage is crucial for identifying critically injured patients and determining the level of care. In the prehospital setting, time and data are often scarce, limiting the complexity of triage models. The aim of this study was to assess whether, compared with logistic regression, the advanced machine learner XGBoost (eXtreme Gradient Boosting) is associated wi