See-saw relationship of the Holocene East Asian-Australian summer monsoon

D.E. and N.M. acknowledge support by the Leibniz Association (WGL) under Grant No. SAW-2013-IZW-2. F.H.M.’s research is funded through an Australian Postgraduate Award. I.O. is financially supported from TUBITAK under 2214/A program and by Ege University under the Research Project number 2015FEN028. This study received funding from the European Union’s Horizon 2020 Research and Innovation programme under the Marie Skłodowska-Curie grant agreement No 691037. The publication of this article was funded by the Open Access Fund of the Leibniz Association. K.H.W. thank Rhawn F. Denniston for his wider involvement in the northwest Australian monsoon project and the Kimberley Foundation Australia for financial support for this project and Paul Wyrwoll for helpful comments. We are also grateful to Yanjun Cai for providing the Lake Qinghai record.Peer reviewedPublisher PD

Circuit-Selective Striatal Synaptic Dysfunction in the Sapap3 Knockout Mouse Model of Obsessive-Compulsive Disorder

Background: Synapse-associated protein 90/postsynaptic density protein 95-associated protein 3 (SAPAP3) is an excitatory postsynaptic protein implicated in the pathogenesis of obsessive-compulsive behaviors. In mice, genetic deletion of Sapap3 causes obsessive-compulsive disorder (OCD)-like behaviors that are rescued by striatal expression of Sapap3, demonstrating the importance of striatal neurotransmission for the OCD-like behaviors. In the striatum, there are two main excitatory synaptic circuits, corticostriatal and thalamostriatal. Neurotransmission defects in either or both of these circuits could potentially contribute to the OCD-like behaviors of Sapap3 knockout (KO) mice. Previously, we reported that Sapap3 deletion reduces corticostriatal alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid-type glutamate receptor-mediated synaptic transmission. Methods: Whole-cell electrophysiological recording techniques in acute brain slices were used to measure synaptic transmission in the corticostriatal and thalamostriatal circuits of Sapap3 KO mice and littermate control animals. Transgenic fluorescent reporters identified striatopallidal and striatonigral projection neurons. SAPAP isoforms at corticostriatal and thalamostriatal synapses were detected using immunostaining techniques. Results: I n contrast to corticostriatal synapses, thalamostriatal synaptic activity is unaffected by Sapap3 deletion. At the molecular level, we find that another SAPAP family member, SAPAP4, is present at thalamostriatal, but not corticostriatal, synapses. This finding provides a molecular rationale for the functional divergence we observe between thalamic and cortical striatal circuits in Sapap3 KO mice. Conclusions: These findings define the circuit-level neurotransmission defects in a genetic mouse model for OCD-related behaviors, focusing attention on the corticostriatal circuit for mediating the behavioral abnormalities. Our results also provide the first evidence that SAPAP isoforms may be localized to synapses according to circuit-selective principles.National Institute of Mental Health (U.S.) (Grant MH081201

Dehydration of potato slices following brief dipping in osmotic solutions: effect of conditions and understanding the mechanism of water loss

A novel variant of osmotic dehydration, named here as post-dipping dehydration – where a material is dipped in a salt or sugar solution for a very short time followed by simple exposure to ambient conditions was explored with the aim of lowering water content of potato slices but at the same time not gain a high level of sugar/salt. The rate of water loss, which was rapid initially, was found to approach equilibrium. This paper also explored whether the water loss process could subsequently be kick started once again, by employing a multi-stage process, where each stage consisted of osmotic solution dipping followed by ambient holding of the potato slices that had reached equilibrium in the earlier stage. Water loss values comparable to conventional osmotic dehydration could be achieved thus, but with significantly lower overall solid gain (less than 50%) – which can potentially yield a significantly healthy product option

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

Investigation into the use of histone deacetylase inhibitor MS-275 as a topical agent for the prevention and treatment of cutaneous squamous cell carcinoma in an SKH-1 hairless mouse model

<div><p>Cutaneous squamous cell carcinomas are a common form of highly mutated keratinocyte skin cancers that are of particular concern in immunocompromised patients. Here we report on the efficacy of topically applied MS-275, a clinically used histone deacetylase inhibitor, for the treatment and management of this disease. At 2 mg/kg, MS-275 significantly decreased tumor burden in an SKH-1 hairless mouse model of UVB radiation-induced skin carcinogenesis. MS-275 was cell permeable as a topical formulation and induced histone acetylation changes in mouse tumor tissue. MS-275 was also effective at inhibiting the proliferation of patient derived cutaneous squamous cell carcinoma lines and was particularly potent toward cells isolated from a regional metastasis on an immunocompromised individual. Our findings support the use of alternative routes of administration for histone deacetylase inhibitors in the treatment of high-risk squamous cell carcinoma which may ultimately lead to more precise delivery and reduced systemic toxicity.</p></div

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

Alcohol drinking in one's thirties and forties is associated with body mass index in men, but not in women: A longitudinal analysis of the 1970 British Cohort Study

Our objective was to investigate longitudinal associations between alcohol drinking and body mass index (BMI). Alcohol drinking (exposure), BMI (outcome), smoking habit, occupation, longstanding illness, and leisure time physical activity (potential confounders) were assessed at ages 30, 34, 42, and 46 in the 1970 British Birth Cohort Study. Multilevel models were used to cope with the problem of correlated observations. There were 15,708 observations in 5931 men and 14,077 observations in 5656 women. Drinking was associated with BMI in men. According to the regression coefficients, BMI was expected to increase by 0.36 (95% confidence interval: 0.11, 0.60) kg/m2 per year in men who drank once a week and by 0.40 (0.14, 0.15) kg/m2 per year in men who drank most days. In ten years, BMI was expected to increase by 5.4 kg/m2 in men who drank and by 2.9 kg/m2 in men who drank and were physically active. Drinking was not associated with BMI in women. Rather, BMI was expected to increase by 0.25 (0.07, 0.43) kg/m2 per year in women who were former smokers. In ten years, BMI was expected to increase by 4.3 kg/m2 in women who were former smokers and by 0.8 kg/m2 in women who were former smokers and who were physically active. Associations between drinking and BMI were similar after further adjustment for problematic drinking and diet. These longitudinal data suggest that drinking is associated with BMI in men and that drinking is not associated with BMI in women independent of other lifestyle risk factors