Seipin oligomers can interact directly with AGPAT2 and lipin 1, physically scaffolding critical regulators of adipogenesis

This work was supported by a Merit Scholarship from the Islamic Development Bank (to M.M.U.T.), The Agency for Science, Technology and Research, Singapore (A*STAR) (M.F.M.S), the Medical Research Council (MRC) [NIRG GO800203 and Research Grant MR/L002620/1 (to J.J.R.), Program GrantG09000554 (to S.O.R)], The Wellcome Trust [078986/Z/06/Z (to S.O.R.)], the MRC Centre for Obesity and Related Metabolic Disorders (MRC-CORD) [GO600717] and the NIHR Comprehensive Biomedical Research Centre [CG50826].Peer reviewedPublisher PD

Analysis of naturally occurring mutations in the human lipodystrophy protein seipin reveals multiple potential pathogenic mechanisms

Peer reviewedPublisher PD

Role of Mothers\u27 Nutritional Knowledge, Nutritional Factors on the School Performance

A cross sectional study was carried out to investigate the effects of mothers\u27 nutritional knowledge, health and nutritional factors and socio-economic parameters on school performance among class five students of University Laboratory School, Dhaka. All of the eighty students were selected for this study. This study found there is a strong relationship between mother\u27s knowledge score and school performance. It was found that mothers\u27 knowledge score was responsible for 91.1 percent change in school performance. The mean BMI of the mothers was 20.44. We found that the school performance measured by class roll number of the students is significantly related with mothers BMI. There was an imperfect negative association between socio-economic parameters and school performance. But the relationship between the school performances with socio-economic parameters was strongly significant. This study also observed the relationship between Individual Dietary Diversity Score (IDDS) of respondent and marks achieved in class 4 final exam. It is alarming that consumption percentage were low for eggs (30) and milk and milk products (37.5), but majority of the students who consumed milk and milk products (63.3%) and eggs (66.7%) got the highest marks

Regulation of elongation factor-1α expression by growth factors and anti-receptor blocking antibodies

The Epidermal Growth Factor (EGF) family and its receptors regulate normal and cancerous epithelial cell proliferation, a process that could be suppressed by anti-receptor blocking antibodies. Polypeptide elongation factor-1α (EF-1α) is a multifunctional protein whose levels are positively correlated with the proliferative state of cells. To identify genes, whose expression may be modulated by anti-receptor blocking antibodies, we performed a differential display screening and isolated differentially expressed cDNAs. Isolates from one clone were 100% identical to human EF-1α. Both EGF and heregulin-β1 (HRG) induced EF-1α promoter activity and mRNA and protein expression. Growth factor-mediated EF-1α expression was effectively blocked by pretreatment with humanized anti-EGF receptor antibody C225 or anti-human epidermal growth factor receptor-2 (HER2) antibody herceptin. Mutants and pharmacological inhibitors of p38MAPK and MEK, but not phosphatidylinositol 3-kinase, suppressed both constitutive and HRG-induced stimulation of EF-1α promoter activity in MCF-7 cells. Deletion analysis of the promoter suggested the requirement of the −393 to −204 region for growth factor-mediated transcription of EF-1α. Fine mapping and point mutation studies revealed a role of the SP1 site in the observed HRG-mediated regulation of the EF-1α promoter. In addition, we also provide new evidence to suggest that HRG stimulation of the EF-1α promoter involves increased physical interactions with acetylated histone H3 and histone H4. These results suggest that regulation of EF-1α expression by extracellular signals that function through human EGF receptor family members that are widely deregulated in human cancers and that growth factor regulation of EF-1α expression involve histone acetylation

A blind hierarchical coherent search for gravitational-wave signals from coalescing compact binaries in a network of interferometric detectors

We describe a hierarchical data analysis pipeline for coherently searching for gravitational wave (GW) signals from non-spinning compact binary coalescences (CBCs) in the data of multiple earth-based detectors. It assumes no prior information on the sky position of the source or the time of occurrence of its transient signals and, hence, is termed "blind". The pipeline computes the coherent network search statistic that is optimal in stationary, Gaussian noise, and allows for the computation of a suite of alternative statistics and signal-based discriminators that can improve its performance in real data. Unlike the coincident multi-detector search statistics employed so far, the coherent statistics are different in the sense that they check for the consistency of the signal amplitudes and phases in the different detectors with their different orientations and with the signal arrival times in them. The first stage of the hierarchical pipeline constructs coincidences of triggers from the multiple interferometers, by requiring their proximity in time and component masses. The second stage follows up on these coincident triggers by computing the coherent statistics. The performance of the hierarchical coherent pipeline on Gaussian data is shown to be better than the pipeline with just the first (coincidence) stage.Comment: 12 pages, 3 figures, accepted for publication in Classical and Quantum Gravit

Variation of pro‐vasopressin processing in parvocellular and magnocellular neurons in the paraventricular nucleus of the hypothalamus: Evidence from the vasopressin‐related glycopeptide copeptin

Arginine vasopressin (AVP) is synthesized in parvocellular‐ and magnocellular neuroendocrine neurons in the paraventricular nucleus (PVN) of the hypothalamus. Whereas magnocellular AVP neurons project primarily to the posterior pituitary, parvocellular AVP neurons project to the median eminence (ME) and to extrahypothalamic areas. The AVP gene encodes pre‐pro‐AVP that comprises the signal peptide, AVP, neurophysin (NPII), and a copeptin glycopeptide. In the present study, we used an N‐terminal copeptin antiserum to examine copeptin expression in magnocellular and parvocellular neurons in the hypothalamus in the mouse, rat, and macaque monkey. Although magnocellular NPII‐expressing neurons exhibited strong N‐terminal copeptin immunoreactivity in all three species, a great majority (~90%) of parvocellular neurons that expressed NPII was devoid of copeptin immunoreactivity in the mouse, and in approximately half (~53%) of them in the rat, whereas in monkey hypothalamus, virtually all NPII‐immunoreactive parvocellular neurons contained strong copeptin immunoreactivity. Immunoelectron microscopy in the mouse clearly showed copeptin‐immunoreactivity co‐localized with NPII‐immunoreactivity in neurosecretory vesicles in the internal layer of the ME and posterior pituitary, but not in the external layer of the ME. Intracerebroventricular administration of a prohormone convertase inhibitor, hexa‐d‐arginine amide resulted in a marked reduction of copeptin‐immunoreactivity in the NPII‐immunoreactive magnocellular PVN neurons in the mouse, suggesting that low protease activity and incomplete processing of pro‐AVP could explain the disproportionally low levels of N‐terminal copeptin expression in rodent AVP (NPII)‐expressing parvocellular neurons. Physiologic and phylogenetic aspects of copeptin expression among neuroendocrine neurons require further exploration

A comprehensive model of gain recovery due to unipolar electron transport after a short optical pulse in quantum cascade lasers

We have developed a comprehensive model of gain recovery due to unipolar electron transport after a short optical pulse in quantum cascade lasers (QCLs) that takes into account all the participating energy levels, including the continuum, in a device. This work takes into account the incoherent scattering of electrons from one energy level to another and quantum coherent tunneling from an injector level to an active region level or vice versa. In contrast to the prior work that only considered transitions to and from a limited number of bound levels, this work include transitions between all bound levels and between the bound energy levels and the continuum. We simulated an experiment of S. Liu et al., in which 438-pJ femtosecond optical pulses at the device’s lasing wavelength were injected into an In0:653Ga0:348As=In0:310Al0:690As QCL structure; we found that approximately 1% of the electrons in the bound energy levels will be excited into the continuum by a pulse and that the probability that these electrons will be scattered back into bound energy levels is negligible, 104. The gain recovery that is predicted is not consistent with the experiments, indicating that one or more phenomena besides unipolar electron transport in response to a short optical pulse play an important role in the observed gain recovery

Slow Light Propagation in a Thin Optical Fiber via Electromagnetically Induced Transparency

We propose a novel configuration that utilizes electromagnetically induced transparency (EIT) to tailor a fiber mode propagating inside a thin optical fiber and coherently control its dispersion properties to drastically reduce the group velocity of the fiber mode. The key to this proposal is: the evanescent-like field of the thin fiber strongly couples with the surrounding active medium, so that the EIT condition is met by the medium. We show how the properties of the fiber mode is modified due to the EIT medium, both numerically and analytically. We demonstrate that the group velocity of the new modified fiber mode can be drastically reduced (approximately 44 m/sec) using the coherently prepared orthohydrogen doped in a matrix of parahydrogen crystal as the EIT medium.Comment: 10 pages in two column RevTex4, 6 Figure

Reduction of Endothelial Nitric Oxide Increases the Adhesiveness of Constitutive Endothelial Membrane ICAM-1 through Src-Mediated Phosphorylation

Nitric oxide (NO) is a known anti-adhesive molecule that prevents platelet aggregation and leukocyte adhesion to endothelial cells (ECs). The mechanism has been attributed to its role in the regulation of adhesion molecules on leukocytes and the adhesive properties of platelets. Our previous study conducted in rat venules found that reduction of EC basal NO synthesis caused EC ICAM-1-mediated firm adhesion of leukocytes within 10–30min. This quick response occurred in the absence of alterations of adhesion molecules on leukocytes and also opposes the classical pattern of ICAM-1-mediated leukocyte adhesion that requires protein synthesis and occurs hours after stimulation. The objective of this study is to investigate the underlying mechanisms of reduced basal NO-induced EC-mediated rapid leukocyte adhesion observed in intact microvessels. The relative levels of ICAM-1 at different cell regions and their activation status were determined with cellular fractionation and western blot using cultured human umbilical vein ECs. ICAM-1 adhesiveness was determined by immunoprecipitation in non-denatured proteins to assess the changes in ICAM-1 binding to its inhibitory antibody, mAb1A29, and antibody against total ICAM-1 with and without NO reduction. The adhesion strength of EC ICAM-1 was assessed by atomic force microscopy (AFM) on live cells. Results showed that reduction of EC basal NO caused by the application of caveolin-1 scaffolding domain (AP-CAV) or NOS inhibitor, L-NMMA, for 30 min significantly increased phosphorylated ICAM-1 and its binding to mAb1A29 in the absence of altered ICAM-1 expression and its distribution at subcellular regions. The Src inhibitor, PP1, inhibited NO reduction-induced increases in ICAM-1 phosphorylation and adhesive binding. AFM detected significant increases in the binding force between AP-CAV-treated ECs and mAb1A29-coated probes. These results demonstrated that reduced EC basal NO lead to a rapid increase in ICAM-1 adhesive binding via Src-mediated phosphorylation without de novo protein synthesis and translocation. This study suggests that a NO-dependent conformational change of constitutive EC membrane ICAM-1 might be the mechanism of rapid ICAM-1 dependent leukocyte adhesion observed in vivo. This new mechanistic insight provides a better understanding of EC/leukocyte interaction-mediated vascular inflammation under many disease conditions that encounter reduced basal NO in the circulation system

Cis and Trans Effects of Human Genomic Variants on Gene Expression

This work was funded by the Louis-Jeantet Foundation (http://www.jeantet.ch/), the European Research Council (Grant ID: 260927 http://erc.europa.eu/), the Swiss National Foundation (Grant ID: 130342 http://www.snf.ch), NCCR Frontiers In Genetics (http://www.frontiers-in-genetics.org), the UK Medical Research Council (http://www.mrc.ac.uk) and the Wellcome Trust (Grant ID: 092731).