Conventional and Unconventional Mechanisms by which Exocytosis Proteins Oversee β-cell Function and Protection

Type 2 diabetes (T2D) is one of the prominent causes of morbidity and mortality in the United States and beyond, reaching global pandemic proportions. One hallmark of T2D is dysfunctional glucose-stimulated insulin secretion from the pancreatic β-cell. Insulin is secreted via the recruitment of insulin secretory granules to the plasma membrane, where the soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) and SNARE regulators work together to dock the secretory granules and release insulin into the circulation. SNARE proteins and their regulators include the Syntaxins, SNAPs, Sec1/Munc18, VAMPs, and double C2-domain proteins. Recent studies using genomics, proteomics, and biochemical approaches have linked deficiencies of exocytosis proteins with the onset and progression of T2D. Promising results are also emerging wherein restoration or enhancement of certain exocytosis proteins to β-cells improves whole-body glucose homeostasis, enhances β-cell function, and surprisingly, protection of β-cell mass. Intriguingly, overexpression and knockout studies have revealed novel functions of certain exocytosis proteins, like Syntaxin 4, suggesting that exocytosis proteins can impact a variety of pathways, including inflammatory signaling and aging. In this review, we present the conventional and unconventional functions of β-cell exocytosis proteins in normal physiology and T2D and describe how these insights might improve clinical care for T2D.     

Synthesis of Flexible Graphene/Polymer Composites for Supercapacitor Applications

In this paper, the graphene was synthesized using biocompatible cellulosic component from onions. Onion epidermal cells were chosen as raw material. During heating at high temperature, the bonding among atoms in material was rearranged and forms two-dimensional hexagonal carbon layer (graphene). The characterization of synthesized graphene was done by x-ray diffractometer, Raman spectrometer and field emission scanning electron microscopy, respectively. An attempt has been taken to form the capacitors with two different current collector electrodes, anticipating the performance of the supercapacitors. The observed capacitance values as-obtained for Al and Au current collector were 1.3 μF and 6.08 μF, respectively. However, when thermally exfoliated graphene was used as an electrode on Al and Au current collector, the capacitance value was drastically increased and found to be 1.6 and 41.25 μF, respectively.     

The effect of modifying an edge-plane pyrolytic graphite electrode with single-wall carbon nanotubes on its use for sensing diclofenac

A simple and highly sensitive sensor based on edge-plane pyrolytic graphite electrode (EPPGE) coated with single-wall carbon nanotubes is proposed for diclofenac determination in nanomolar concentrations. The oxidation of diclofenac occurred in two well-defined peaks having peak potentials ∼439 and ∼854 mV at pH 7.2. The modified electrode showed excellent catalytic activity presenting much higher peak currents than those measured on a bare EPPGE. Under the optimum conditions, the calibration curve was linear in the concentration range 1 × 10⁻⁹-500 × 10⁻⁹ M and 25 × 10⁻⁹-1500 × 10⁻⁹ M for peaks I and II, respectively. The limit of detection for peaks I and II was found as 0.82 × 10⁻⁹ and 22.5 × 10⁻⁹ M, respectively. The developed sensor was applied for the determination of diclofenac in biological and pharmaceutical samples using square-wave voltammetry and the validation of results using high performance liquid chromatography showed excellent agreement.     

Is the Jaw Bone Micro-Structure Altered in Response to Osteoporosis and Bisphosphonate Treatment? A Micro-CT Analysis

The aim of the study was to quantify the micro-architectural changes of the jaw bone in response to ovariectomy, exposed or not to bisphosphonate treatment. A total of 47 Wistar rats were ovariectomized (OVX) or sham-operated (shOVX) and exposed to osteoporosis preventive treatment for eight weeks either with bisphosphonates (alendronate, ALN; group OVX-ALN) three days/week at a dose of 2 mg/kg or with saline solution (untreated control condition; group OVX). The bone morphometric parameters of the trabecular jaw bone were assessed using ex vivo micro-computed tomography. The regions of interest investigated in the maxilla were the inter-radicular septum of the second molar and the tuber. The regions quantified in the mandible included the three molar regions and the condyle. A one-way analysis of variance followed by pairwise comparison using Tukey’s HSD and the Games–Howell test was conducted to explore significant differences between the groups. In the maxilla, OVX decreased the bone volume in the inter-radicular septum of the second molar. Bisphosphonate treatment was able to prevent this deterioration of the jaw bone. The other investigated maxillary regions were not affected by (un)treated ovariectomy. In the mandible, OVX had a significant negative impact on the jaw bone in the buccal region of the first molar and the inter-radicular region of the third molar. Treatment with ALN was able to prevent this jaw bone loss. At the condyle site, OVX significantly deteriorated the trabecular connectivity and shape, whereas preventive bisphosphonate treatment showed a positive effect on this trabecular bone region. No significant results between the groups were observed for the remaining regions of interest. In summary, our results showed that the effects of ovariectomy-induced osteoporosis are manifested at selected jaw bone regions and that bisphosphonate treatment is capable to prevent these oral bone changes.     

M- S-H formation in MgO-SiO2slurries via wet milling for magnesia based castables

It is believed that the formation of hydration phase, MgO-SiO₂-H₂O (M-S-H), contributes to good workability and reliable comprehensive properties for magnesia based castables. In order to stimulate the formation of M-S-H in magnesia based castables and understand the minimum introduction of microslica amount, wet milling process was used to promote the dissolution of MgO and SiO₂ in this work. The slurry containing different content of microsilica with wet milling technology and the castables with/without wet milling slurry were prepared. The effects of microsilica content on the formation of hydration phases were analyzed by XRD, FT-IR and TG/DSC and the properties of magnesia based castables were evaluated by explosion resistance, CMOR, HMOR and so on. The results showed that the formation of M-S-H was accelerated because of the dissolution of Mg²⁺ and HSiO₃^? in wet milling process. Higher amount of M-S-H led to a tight bonding in the early stage, and a denser structure after firing at high temperature due to the limited formation of brucite and in-situ formation of evenly distributed forsterite phase. In addition, much higher HMOR were obtained when less microsilica was added, attributing to the suppressed formation of low-melting-point liquid. Therefore, 2–3 wt% microsilica addition was recommended in this process.     

Synthesis,structure, CO oxidation,and H2 production activities of CaCu3−xMnxTi4−xMnxO12 (x = 0, 0.5, and 1.0)

Synthesis of nanocrystalline pristine and Mn-doped calcium copper titanate quadruple perovskites, CaCu_3?xMn_xTi_4?xMn_xO₁₂ (x = 0, 0.5, and 1.0) by modified citrate solution combustion method has been reported. Powder X-ray diffraction patterns attest the phase purity of the perovskite materials. Average particle sizes of all the materials obtained from the Scherrer's formula are in the range of 55–70 nm. The specific surface areas for all the perovskites obtained from BET isotherms are found to be low as expected for the condensed oxide systems and fall in the range of 13–17 m² g^?1. Transmission electron microscopy studies show a reduction in particle size of CaCu₃Ti₄O₁₂ with increase in Mn doping. Ca and Ti are present in +2 and +4 oxidation states in all the materials as demonstrated by X-ray photoelectron spectroscopy analyses. Cu²⁺ gets reduced in CaCu₃Ti₄O₁₂ with higher Mn content. Mn is observed to be present only in +3 oxidation state. All the materials have been examined to be active in CO oxidation as well as H₂ production from methanol steam reforming. CaCu₃Ti₄O₁₂ with ~14 at.% Mn is found to show best catalytic activities among these materials. A comprehensive analysis of the catalytic activities of these perovskites toward CO oxidation and H₂ production from MSR reveal the cooperative activity of copper-manganese in the doped perovskites and it is more effective at lower manganese content.     

Unimportance of geometric nonlinearity in analysis of flanged joints with metal-to-metal contact

Gasketless flanged joints with metal to metal contact offer some advantages over gasketed joints such as lower weight and better fatigue life. Design of such joints is often based on finite element analyses, and complicated by the fact that the area of contact between the flanges changes upon application of loads. Such analyses can be done using commercial software, which can incorporate geometrical nonlinearities as well as contact nonlinearities. Engineering intuition suggests that the role of geometrical nonlinearities might be small for such problems. However, many engineers continue to use the fully nonlinear analyses. Our aim in this paper is simply to put on record that significant savings in time can be obtained by “turning off” geometric nonlinearities in such analyses, with negligible loss of accuracy. To this end, a nonautomated implementation of the basic ideas is first demonstrated for a simple geometry; more automated analyses for a more general geometry follow.