Rest-Mediated Regulation of Extracellular Matrix Is Crucial for Neural Development

Neural development from blastocysts is strictly controlled by intricate transcriptional programmes that initiate the down-regulation of pluripotent genes, Oct4, Nanog and Rex1 in blastocysts followed by up-regulation of lineage-specific genes as neural development proceeds. Here, we demonstrate that the expression pattern of the transcription factor Rest mirrors those of pluripotent genes during neural development from embryonic stem (ES) cells and an early abrogation of Rest in ES cells using a combination of gene targeting and RNAi approaches causes defects in this process. Specifically, Rest ablation does not alter ES cell pluripotency, but impedes the production of Nestin+ neural stem cells, neural progenitor cells and neurons, and results in defective adhesion, decrease in cell proliferation, increase in cell death and neuronal phenotypic defects typified by a reduction in migration and neurite elaboration. We also show that these Rest-null phenotypes are due to the dysregulation of its direct or indirect target genes, Lama1, Lamb1, Lamc1 and Lama2 and that these aberrant phenotypes can be rescued by laminins

Secondary Metabolites of Marine Microbes: From Natural Products Chemistry to Chemical Ecology

Marine natural products (MNPs) exhibit a wide range of pharmaceutically relevant bioactivities, including antibiotic, antiviral, anticancer, or anti-inflammatory properties. Besides marine macroorganisms such as sponges, algae, or corals, specifically marine bacteria and fungi have shown to produce novel secondary metabolites (SMs) with unique and diverse chemical structures that may hold the key for the development of novel drugs or drug leads. Apart from highlighting their potential benefit to humankind, this review is focusing on the manifold functions of SMs in the marine ecosystem. For example, potent MNPs have the ability to exile predators and competing organisms, act as attractants for mating purposes, or serve as dye for the expulsion or attraction of other organisms. A large compilation of literature on the role of MNPs in marine ecology is available, and several reviews evaluated the function of MNPs for the aforementioned topics. Therefore, we focused the second part of this review on the importance of bioactive compounds from crustose coralline algae (CCA) and their role during coral settlement, a topic that has received less attention. It has been shown that certain SMs derived from CCA and their associated bacteria are able to induce attachment and/or metamorphosis of many benthic invertebrate larvae, including globally threatened reef-building scleractinian corals. This review provides an overview on bioactivities of MNPs from marine microbes and their potential use in medicine as well as on the latest findings of the chemical ecology and settlement process of scleractinian corals and other invertebrate larvae

Search for excited leptons in final states in proton-proton collisions at root s=13 TeV

A search is presented for excited electrons and muons in ℓℓγ final states at the LHC. The search is based on a data sample corresponding to an integrated luminosity of 35.9 fb−1 of proton-proton collisions at a center-of-mass energy of 13 TeV, collected with the CMS detector in 2016. This is the first search for excited leptons at s√ = 13 TeV. The observation is consistent with the standard model background prediction, and the most stringent exclusion limits to date are set on the excited lepton mass and the compositeness scale, at 95% confidence level. Excited electrons and muons are excluded for masses below 3.9 and 3.8 TeV, respectively, under the assumption that the excited lepton mass equals the compositeness scale. The best observed limit on the compositeness scale is obtained with an excited lepton mass of around 1.0 TeV, excluding values below 25 TeV for both excited electrons and muons

Measurement of nuclear modification factors of ϒ(1S), ϒ(2S), and ϒ(3S) mesons in PbPb collisions at √sNN = 5.02 TeV

The cross sections for ϒ(1S), ϒ(2S), and ϒ(3S) production in lead–lead (PbPb) and proton–proton (pp) collisions at √sNN = 5.02 TeV have been measured using the CMS detector at the LHC. The nuclear modification factors, RAA, derived from the PbPb-to-pp ratio of yields for each state, are studied as functions of meson rapidity and transverse momentum, as well as PbPb collision centrality. The yields of all three states are found to be significantly suppressed, and compatible with a sequential ordering of the suppression, RAA(ϒ(1S)) > RAA(ϒ(2S)) > RAA(ϒ(3S)). The suppression of ϒ(1S) is larger than that seen at √sNN = 2.76 TeV, although the two are compatible within uncertainties. The upper limit on the RAA of ϒ(3S) integrated over pT, rapidity and centrality is 0.096 at 95% confidence level, which is the strongest suppression observed for a quarkonium state in heavy ion collisions to date

Effect of dietary supplementation with conjugated linoleic acid on markers of calcium and bone metabolism in healthy adult men.

INTRODUCTION: Conjugated linoleic acid (CLA) has been shown to positively influence calcium and bone metabolism in experimental animals and cells in culture, but there are limited human data available. OBJECTIVE: To investigate the effect of CLA supplementation on biomarkers of calcium and bone metabolism in healthy adult males. DESIGN: The study consisted of a double-blind, placebo-controlled trial in which 60 healthy adult males (aged 39-64 y) were randomly assigned to receive daily either 3.0 g CLA isomer blend (50:50% cis-9,trans-11:trans-10,cis-12 isomers) or a palm/bean oil blend (placebo) for 8 weeks. Urine and blood samples were collected at weeks 0 and 8 and were analysed for biomarkers of calcium and bone metabolism. RESULTS: Supplementation with CLA or placebo for 8 weeks had no significant effects on markers of bone formation (serum osteocalcin and bone-specific alkaline phosphatase) or bone resorption (serum C-telopeptide-related fraction of type 1 collagen degradation products, urinary N-telopeptide-related fraction of type 1 collagen degradation products, urinary pyridinoline and deoxypyridinoline), or on serum or urinary calcium levels. Baseline levels of these biochemical parameters were similar in both groups of subjects. While the placebo had no effect, CLA supplementation resulted in a three-fold increase (P<0.00001) in cis-9,trans-11 CLA isomer in total plasma lipids. CONCLUSION: Under the conditions tested in this double-blind, placebo-controlled trial in adult men, a CLA supplement of mixed isomers did not affect markers of calcium or bone metabolism. Further investigation of the effects of CLA on calcium and bone metabolism in other gender- and age-groups is warranted

Introduction: A welcome to the first special animal health issue of AAPS PharmSci

The goal of this special volume is to provide veterinary scientists with state-of-the art reviews in animal health and to inform human health scientists of the various challenges and collaborative opportunities associated with their animal health counterparts. The contributors are highly respected experts, providing invaluable insights into current issues and state-of-the-art advances within veterinary medicine