Plasma proteome correlates of lipid and lipoprotein: biomarkers of metabolic diversity and inflammation in children of rural Nepal.

Proteins involved in lipoprotein metabolism can modulate cardiovascular health. While often measured to assess adult metabolic diseases, little is known about the proteomes of lipoproteins and their relation to metabolic dysregulation and underlying inflammation in undernourished child populations. The objective of this population study was to globally characterize plasma proteins systemically associated with HDL, LDL, and triglycerides in 500 Nepalese children. Abnormal lipid profiles characterized by elevated plasma triglycerides and low HDL-cholesterol (HDL-C) concentrations were common, especially in children with subclinical inflammation. Among 982 proteins analyzed, the relative abundance of 11, 12, and 52 plasma proteins was correlated with LDL-cholesterol (r = -0.43∼0.70), triglycerides (r = -0.39∼0.53), and HDL-C (r = -0.49∼0.79) concentrations, respectively. These proteins included apolipoproteins and numerous unexpected intracellular and extracellular matrix binding proteins, likely originating in hepatic and peripheral tissues. Relative abundance of two-thirds of the HDL proteome varied with inflammation, with acute phase reactants higher by 4∼40%, and proteins involved in HDL biosynthesis, cholesterol efflux, vitamin transport, angiogenesis, and tissue repair lower by 3∼20%. Untargeted plasma proteomics detects comprehensive sets of both known and novel lipoprotein-associated proteins likely reflecting systemic regulation of lipoprotein metabolism and vascular homeostasis. Inflammation-altered distributions of the HDL proteome may be predisposing undernourished populations to early chronic disease

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

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

Temporal variation in out-of-hospital cardiac arrest occurrence in individuals with or without diabetes

Objective: Out-of-hospital cardiac arrest (OHCA) occurrence has been shown to exhibit a circadian rhythm, following the circadian rhythm of acute myocardial infarction (AMI) occurrence. Diabetes mellitus (DM) is associated with changes in circadian rhythm. We aimed to compare the temporal variation of OHCA occurrence over the day and week between OHCA patients with DM and those without.Methods: In two population-based OHCA registries (Amsterdam Resuscitation Studies [ARREST] 2010-2016, n = 4163, and Danish Cardiac Arrest Registry [DANCAR], 2010-2014, n = 12,734), adults (≥18y) with presumed cardiac cause of OHCA and available medical history were included. Single and double cosinor analysis was performed to model circadian variation of OHCA occurrence. Stratified analysis of circadian variation was performed in patients with AMI as immediate cause of OHCA.Results: DM patients (22.8% in ARREST, 24.2% in DANCAR) were older and more frequently had cardiovascular risk factors or previous cardiovascular disease. Both cohorts showed 24 h-rhythmicity, with significant amplitudes in single and double cosinor functions (P-range &lt; 0.001). In both registries, a morning peak (10:00-11:00) and an evening peak (20:00-21:00) was observed in both DM and non-DM patients. No septadian variation was observed in either DM or non-DM patients (P-range 0.13-84).Conclusions: In these two population-based OHCA registries, we observed a similar circadian rhythm of OHCA occurrence in DM and non-DM patients.</p

A novel treatment strategy for preterm birth: Intra-vaginal progesterone-loaded fibrous patches

Progesterone-loaded poly(lactic) acid fibrous polymeric patches were produced using electrospinning and pressurized gyration for intra-vaginal application to prevent preterm birth. The patches were intravaginally inserted into rats in the final week of their pregnancy, equivalent to the third trimester of human pregnancy. Maintenance tocolysis with progesterone-loaded patches was elucidated by recording the contractile response of uterine smooth muscle to noradrenaline in pregnant rats. Both progesterone-loaded patches indicated similar results from release and thermal studies, however, patches obtained by electrospinning had smaller average diameters and more uniform dispersion compared to pressurized gyration. Patches obtained by pressurized gyration had better results in production yield and tensile strength than electrospinning; thereby pressurized gyration is better suited for scaled-up production. The patches did not affect cell attachment, viability, and proliferation on Vero cells negatively. Consequently, progesterone-loaded patches are a novel and successful treatment strategy for preventing preterm birth

Thrombospondin receptor α2δ-1 promotes synaptogenesis and spinogenesis via postsynaptic Rac1

Astrocytes control excitatory synaptogenesis by secreting thrombospondins (TSPs), which function via their neuronal receptor, the calcium channel subunit α2δ-1. α2δ-1 is a drug target for epilepsy and neuropathic pain; thus the TSP–α2δ-1 interaction is implicated in both synaptic development and disease pathogenesis. However, the mechanism by which this interaction promotes synaptogenesis and the requirement for α2δ-1 for connectivity of the developing mammalian brain are unknown. In this study, we show that global or cell-specific loss of α2δ-1 yields profound deficits in excitatory synapse numbers, ultrastructure, and activity and severely stunts spinogenesis in the mouse cortex. Postsynaptic but not presynaptic α2δ-1 is required and sufficient for TSP-induced synaptogenesis in vitro and spine formation in vivo, but an α2δ-1 mutant linked to autism cannot rescue these synaptogenesis defects. Finally, we reveal that TSP–α2δ-1 interactions control synaptogenesis postsynaptically via Rac1, suggesting potential molecular mechanisms that underlie both synaptic development and pathology

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.

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