Optimizing Nervous System-Specific Gene Targeting with Cre Driver Lines: Prevalence of Germline Recombination and Influencing Factors.

The Cre-loxP system is invaluable for spatial and temporal control of gene knockout, knockin, and reporter expression in the mouse nervous system. However, we report varying probabilities of unexpected germline recombination in distinct Cre driver lines designed for nervous system-specific recombination. Selective maternal or paternal germline recombination is showcased with sample Cre lines. Collated data reveal germline recombination in over half of 64 commonly used Cre driver lines, in most cases with a parental sex bias related to Cre expression in sperm or oocytes. Slight differences among Cre driver lines utilizing common transcriptional control elements affect germline recombination rates. Specific target loci demonstrated differential recombination; thus, reporters are not reliable proxies for another locus of interest. Similar principles apply to other recombinase systems and other genetically targeted organisms. We hereby draw attention to the prevalence of germline recombination and provide guidelines to inform future research for the neuroscience and broader molecular genetics communities

Large-Area (over 50 cm × 50 cm) Freestanding Films of Colloidal InP/ZnS Quantum Dots

Cataloged from PDF version of article.We propose and demonstrate the fabrication of flexible, freestanding films of InP/ZnS quantum dots (QDs) using fatty acid ligands across very large areas (greater than 50 cm x 50 cm), which have been developed for remote phosphor applications in solid-state lighting. Embedded in a poly(methyl methacrylate) matrix, although the formation of stand alone films using other QDs commonly capped with trioctylphosphine oxide (TOPO) and oleic acid is not efficient, employing myristic acid as ligand in the synthesis of these QDs, which imparts a strongly hydrophobic character to the thin film, enables film formation and ease of removal even on surprisingly large areas, thereby avoiding the need for ligand exchange. When pumped by a blue LED, these Cd-free QD films allow for high color rendering, warm white light generation with a color rendering index of 89.30 and a correlated color temperature of 2298 K. In the composite film, the temperature-dependent emission kinetics and energy transfer dynamics among different-sized InP/ZnS QDs are investigated and a model is proposed. High levels of energy transfer efficiency (up to 80%) and strong donor lifetime modification (from 18 to 4 ns) are achieved. The suppression of the nonradiative channels is observed when the hybrid film is cooled to cryogenic temperatures. The lifetime changes of the donor and acceptor InP/ZnS QDs in the film as a result of the energy transfer are explained well by our theoretical model based on the exciton-exciton interactions among the dots and are in excellent agreement with the experimental results. The understanding of these excitonic interactions is essential to facilitate improvements in the fabrication of photometrically high quality nanophosphors. The ability to make such large-area, flexible, freestanding Cd-free QD films pave the way for environmentally friendly phosphor applications including flexible, surface-emitting light engines

Systematic study of trace radioactive impurities in candidate construction materials for EXO-200

The Enriched Xenon Observatory (EXO) will search for double beta decays of 136Xe. We report the results of a systematic study of trace concentrations of radioactive impurities in a wide range of raw materials and finished parts considered for use in the construction of EXO-200, the first stage of the EXO experimental program. Analysis techniques employed, and described here, include direct gamma counting, alpha counting, neutron activation analysis, and high-sensitivity mass spectrometry.Comment: 32 pages, 6 figures. Expanded introduction, added missing table entry. Accepted for publication in Nucl. Instrum. Meth.

Abnormal degradation of the neuronal stress-protective transcription factor HSF1 in Huntington’s disease

Huntington’s Disease (HD) is a neurodegenerative disease caused by poly-glutamine expansion in the Htt protein, resulting in Htt misfolding and cell death. Expression of the cellular protein folding and pro-survival machinery by heat shock transcription factor 1 (HSF1) ameliorates biochemical and neurobiological defects caused by protein misfolding. We report that HSF1 is degraded in cells and mice expressing mutant Htt, in medium spiny neurons derived from human HD iPSCs and in brain samples from patients with HD. Mutant Htt increases CK2α′ kinase and Fbxw7 E3 ligase levels, phosphorylating HSF1 and promoting its proteasomal degradation. An HD mouse model heterozygous for CK2α′ shows increased HSF1 and chaperone levels, maintenance of striatal excitatory synapses, clearance of Htt aggregates and preserves body mass compared with HD mice homozygous for CK2α′. These results reveal a pathway that could be modulated to prevent neuronal dysfunction and muscle wasting caused by protein misfolding in HD.This work was supported by National Institutes of Health grant R01 NS065890 to D.J.T., R01 DA031833 and R01 NS096352 to C.E., R01GM070977 to A.A., U24NS069422/U24NS078378 and R21NS083365 to C.A.R., a Holland Trice Scholar Award to C.E. and D.J.T., NIH Predoctoral Fellowship F31GM119375 to E.T.B. and a Postdoctoral Fellowship from the Huntington’s Disease Society of America to R.G.P

A Large Hadron Electron Collider at CERN

This document provides a brief overview of the recently published report on the design of the Large Hadron Electron Collider (LHeC), which comprises its physics programme, accelerator physics, technology and main detector concepts. The LHeC exploits and develops challenging, though principally existing, accelerator and detector technologies. This summary is complemented by brief illustrations of some of the highlights of the physics programme, which relies on a vastly extended kinematic range, luminosity and unprecedented precision in deep inelastic scattering. Illustrations are provided regarding high precision QCD, new physics (Higgs, SUSY) and electron-ion physics. The LHeC is designed to run synchronously with the LHC in the twenties and to achieve an integrated luminosity of O(100) fb$^{-1}$. It will become the cleanest high resolution microscope of mankind and will substantially extend as well as complement the investigation of the physics of the TeV energy scale, which has been enabled by the LHC

Local differences of the position of the mental foramen

The mental foramen has been reported to vary in position in different ethnic groups. Repeated failures during injections and operative procedures involving the mental foramen suggest the presence of local differences in a given population. The aim of the present study was to investigate possible local differences of the mental foramen in Eastern Anatolian individuals in the Turkish population. The present investigation is based on the examination of 70 adult mandibles. The study consisted of three measurements, to include the relations of the mental foramen to the following: 1) the lower teeth; 2) the body of mandible; 3) the mandibular symphysis and posterior border of the ramus of the mandible. The most common position of the foramen was in line with the longitudinal axis of the second premolar tooth (relation IV), at the midpoint of the mandibular body height and at 1/3.5 of the distance from the mandibular symphysis to the posterior border of the ramus. Local differences of the mental foramen may occur in a population. Prior to surgery knowledge of the most common location of the foramen peculiar to a local population may enable effective mental block anaesthesia to be provided. (Folia Morphol 2008; 67: 32-35)

A highly sensitive and specific enzyme-linked immunosorbent assay of antibodies to hepatitis C virus

In this study, a 178 amino acids long portion of the hepatitis C virus (HCV) core gene was cloned, sequenced, expressed in Escherichia coli, and purified. The resulting antigen (C178) was tested with human sera enzyme-linked immunosorbent assay (ELISA) in order to assess its ability to diagnose HCV. It was shown by ELISA that 92% of the patients sera, diagnosed previously by a 3(rd) generation enzyme immunoassay (EIA) as HCV-positive, had antibodies against the C178 antigen. This antigen gave no false positive results when tested with anti-HCV-negative sera