Commentary: Granins, Secretory Granule Biogenesis, and Transport

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Neurotrophic, Gene Regulation, and Cognitive Functions of Carboxypeptidase E-Neurotrophic Factor-α1 and Its Variants

Carboxypeptidase E, also known as neurotrophic factor-α1 (CPE-NFα1), was first discovered as an exopeptidase and is known to work by cleaving C-terminal basic amino acids from prohormone intermediates to produce mature peptide hormones and neuropeptides in the endocrine and central nervous systems, respectively. CPE-NFα1 also plays a critical role in prohormone sorting and secretory vesicle transportation. Recently, emerging studies have indicated that CPE-NFα1 exerts multiple non-enzymatic physiological roles in maintaining normal central nervous system function and in neurodevelopment. This includes potent neuroprotective and anti-depressant activities, as well as stem cell differentiation functions. In addition, N-terminal truncated variants of CPE-NFα1 have been identified to regulate expression of important neurodevelopmental genes. This mini-review summarizes recent advances in understanding the mechanisms underlying CPE-NFα1’s function in neuroprotection during stress and aspects of neurodevelopment

The Leu34Phe ProCART Mutation Leads to Cocaine- and Amphetamine-Regulated Transcript (CART) Deficiency: A Possible Cause for Obesity in Humans

Cocaine- and amphetamine-regulated transcript (CART) is an anorexigenic neuropeptide synthesized in the hypothalamus. A Leu34Phe missense mutation in proCART has been found in an obese family in humans. Here we show that humans bearing the Leu34Phe mutation in proCART have severely diminished levels of bioactive CART, but elevated amounts of partially processed proCART in their serum. Expression of wild-type proCART in AtT-20 cells showed that it was sorted to the regulated secretory pathway, a necessity for proper processing to bioactive CART. However, expressed Leu34Phe proCART was missorted, poorly processed, and secreted constitutively. The defective intracellular sorting of Leu34Phe proCART would account for the reduced levels of bioactive CART in affected humans. These results suggest that the obesity observed in humans bearing the Leu34Phe mutation could be due to a putative deficiency in hypothalamic bioactive CART

Nutritional load in post-prandial oxidative stress and the pathogeneses of diabetes mellitus

Diabetes mellitus affected more than 500 million of people globally, with an annual mortality of 1.5 million directly attributable to diabetic complications. Oxidative stress, in particularly in post-prandial state, plays a vital role in the pathogenesis of the diabetic complications. However, oxidative status marker is generally poorly characterized and their mechanisms of action are not well understood. In this work, we proposed a new framework for deep characterization of oxidative stress in erythrocytes (and in urine) using home-built micro-scale NMR system. The dynamic of post-prandial oxidative status (against a wide variety of nutritional load) in individual was assessed based on the proposed oxidative status of the red blood cells, with respect to the traditional risk-factors such as urinary isoprostane, reveals new insights into our understanding of diabetes. This new method can be potentially important in drafting guidelines for sub-stratification of diabetes mellitus for clinical care and management

Micro-manufacturing : research, technology outcomes and development issues

Besides continuing effort in developing MEMS-based manufacturing techniques, latest effort in Micro-manufacturing is also in Non-MEMS-based manufacturing. Research and technological development (RTD) in this field is encouraged by the increased demand on micro-components as well as promised development in the scaling down of the traditional macro-manufacturing processes for micro-length-scale manufacturing. This paper highlights some EU funded research activities in micro/nano-manufacturing, and gives examples of the latest development in micro-manufacturing methods/techniques, process chains, hybrid-processes, manufacturing equipment and supporting technologies/device, etc., which is followed by a summary of the achievements of the EU MASMICRO project. Finally, concluding remarks are given, which raise several issues concerning further development in micro-manufacturing

New measurement of θ13\theta_{13} via neutron capture on hydrogen at Daya Bay

This article reports an improved independent measurement of neutrino mixing angle $\theta_{13}$ at the Daya Bay Reactor Neutrino Experiment. Electron antineutrinos were identified by inverse $\beta$-decays with the emitted neutron captured by hydrogen, yielding a data-set with principally distinct uncertainties from that with neutrons captured by gadolinium. With the final two of eight antineutrino detectors installed, this study used 621 days of data including the previously reported 217-day data set with six detectors. The dominant statistical uncertainty was reduced by 49%. Intensive studies of the cosmogenic muon-induced $^9$Li and fast neutron backgrounds and the neutron-capture energy selection efficiency, resulted in a reduction of the systematic uncertainty by 26%. The deficit in the detected number of antineutrinos at the far detectors relative to the expected number based on the near detectors yielded $\sin^22\theta_{13} = 0.071 \pm 0.011$ in the three-neutrino-oscillation framework. The combination of this result with the gadolinium-capture result is also reported.Comment: 26 pages, 23 figure

Improved Measurement of the Reactor Antineutrino Flux and Spectrum at Daya Bay

A new measurement of the reactor antineutrino flux and energy spectrum by the Daya Bay reactor neutrino experiment is reported. The antineutrinos were generated by six 2.9~GW$_{\mathrm{th}}$ nuclear reactors and detected by eight antineutrino detectors deployed in two near (560~m and 600~m flux-weighted baselines) and one far (1640~m flux-weighted baseline) underground experimental halls. With 621 days of data, more than 1.2 million inverse beta decay (IBD) candidates were detected. The IBD yield in the eight detectors was measured, and the ratio of measured to predicted flux was found to be $0.946\pm0.020$ ($0.992\pm0.021$) for the Huber+Mueller (ILL+Vogel) model. A 2.9~$\sigma$ deviation was found in the measured IBD positron energy spectrum compared to the predictions. In particular, an excess of events in the region of 4-6~MeV was found in the measured spectrum, with a local significance of 4.4~$\sigma$. A reactor antineutrino spectrum weighted by the IBD cross section is extracted for model-independent predictions.Comment: version published in Chinese Physics

Evolution of the Reactor Antineutrino Flux and Spectrum at Daya Bay

The Daya Bay experiment has observed correlations between reactor core fuel evolution and changes in the reactor antineutrino flux and energy spectrum. Four antineutrino detectors in two experimental halls were used to identify 2.2 million inverse beta decays (IBDs) over 1230 days spanning multiple fuel cycles for each of six 2.9 GW$_{\textrm{th}}$ reactor cores at the Daya Bay and Ling Ao nuclear power plants. Using detector data spanning effective $^{239}$Pu fission fractions, $F_{239}$, from 0.25 to 0.35, Daya Bay measures an average IBD yield, $\bar{\sigma}_f$, of $(5.90 \pm 0.13) \times 10^{-43}$ cm$^2$/fission and a fuel-dependent variation in the IBD yield, $d\sigma_f/dF_{239}$, of $(-1.86 \pm 0.18) \times 10^{-43}$ cm$^2$/fission. This observation rejects the hypothesis of a constant antineutrino flux as a function of the $^{239}$Pu fission fraction at 10 standard deviations. The variation in IBD yield was found to be energy-dependent, rejecting the hypothesis of a constant antineutrino energy spectrum at 5.1 standard deviations. While measurements of the evolution in the IBD spectrum show general agreement with predictions from recent reactor models, the measured evolution in total IBD yield disagrees with recent predictions at 3.1$\sigma$. This discrepancy indicates that an overall deficit in measured flux with respect to predictions does not result from equal fractional deficits from the primary fission isotopes $^{235}$U, $^{239}$Pu, $^{238}$U, and $^{241}$Pu. Based on measured IBD yield variations, yields of $(6.17 \pm 0.17)$ and $(4.27 \pm 0.26) \times 10^{-43}$ cm$^2$/fission have been determined for the two dominant fission parent isotopes $^{235}$U and $^{239}$Pu. A 7.8% discrepancy between the observed and predicted $^{235}$U yield suggests that this isotope may be the primary contributor to the reactor antineutrino anomaly.Comment: 7 pages, 5 figure