Cholesterol Alters the Dynamics of Release in Protein Independent Cell Models for Exocytosis

Neurons communicate via an essential process called exocytosis. Cholesterol, an abundant lipid in both secretory vesicles and cell plasma membrane can affect this process. In this study, amperometric recordings of vesicular dopamine release from two different artificial cell models created from a giant unilamellar liposome and a bleb cell plasma membrane, show that with higher membrane cholesterol the kinetics for vesicular release are decelerated in a concentration dependent manner. This reduction in exocytotic speed was consistent for two observed modes of exocytosis, full and partial release. Partial release events, which only occurred in the bleb cell model due to the higher tension in the system, exhibited amperometric spikes with three distinct shapes. In addition to the classic transient, some spikes displayed a current ramp or plateau following the maximum peak current. These post spike features represent neurotransmitter release from a dilated pore before constriction and show that enhancing membrane rigidity via cholesterol adds resistance to a dilated pore to re-close. This implies that the cholesterol dependent biophysical properties of the membrane directly affect the exocytosis kinetics and that membrane tension along with membrane rigidity can influence the fusion pore dynamics and stabilization which is central to regulation of neurochemical release

Integrated climate-chemical indicators of diffuse pollution from land to water

Management of agricultural diffuse pollution to water remains a challenge and is influenced by the complex interactions of rainfall-runoff pathways, soil and nutrient management, agricultural landscape heterogeneity and biogeochemical cycling in receiving water bodies. Amplified cycles of weather can also influence nutrient loss to water although they are less considered in policy reviews. Here, we present the development of climate-chemical indicators of diffuse pollution in highly monitored catchments in Western Europe. Specifically, we investigated the influences and relationships between weather processes amplified by the North Atlantic Oscillation during a sharp upward trend (20102016) and the patterns of diffuse nitrate and phosphorus pollution in rivers. On an annual scale, we found correlations between local catchment-scale nutrient concentrations in rivers and the influence of larger, oceanic-scale climate patterns defined by the intensity of the North Atlantic Oscillation. These influences were catchment-specific showing positive, negative or no correlation according to a typology. Upward trends in these decadal oscillations may override positive benefits of local management in some years or indicate greater benefits in other years. Developing integrated climate-chemical indicators into catchment monitoring indicators will provide a new and important contribution to water quality management objectives

Perovskite solar cells using polymer electrolytes

This study deals with the characterization of methylammonium lead iodide (MAPbI3) material and the fabrication of perovskite solar cells using gel polymer electrolyte as the charge transport medium. The crystalline lead–based perovskite has been verified by x-ray diffraction (XRD). The [100], [200], [210], [211], [220], [300] and [222] reflection planes can be observed at 2θ angles of 14.10°, 28.35°, 31.90°, 34.95°, 40.40°, 43.15° and 50.20°, indicating a cubic crystal symmetry for CH3NH3PbI3. EDX spectrum showed a Pb:I ratio of approximately 1:3 as in CH3NH3PbI3. The band gap for lead-based perovskite is 1.45 eV estimated from UV-Vis absorption spectroscopy. The nanocrystalline MAPbI3 have been observed using field emission scanning electron microscopy (FESEM), where the average cuboid size of perovskite nanocrystals is 380 nm. The cell have been fabricated using gel polymer electrolyte with composition 17.02 wt.% PVA–13.93 wt.% TBAI–0.96 wt.% I2– 68.09 wt.% DMF. The cell exhibits a power conversion efficiency (PCE) of 1.28% with open circuit voltage (Voc) 0.58 mV, short circuit current density (Jsc) 3.74 mA cm−2 and fill factor (FF) 59.18%

Polyacrylonitrile gel polymer electrolyte based dye sensitized solar cells for a prototype solar panel

Polyacrylonitrile (PAN) based gel polymer electrolytes (GPE) were prepared using lithium iodide (LiI), 1-butyl-3-methylimidazolium iodide (BMII) and tetrapropyl ammonium iodide (TPAI). The LiI mass fraction in the electrolyte was varied while keeping the masses of other components constant in order to enhance the solar cell performance. The addition of 4.61 wt.% LiI in the GPE increased the electrolyte room temperature ionic conductivity from (2.32 ± 0.02) to (3.91 ± 0.04) mS cm−1. The increase in conductivity with the addition of LiI salts was attributed to the increase in diffusion coefficient, mobility and number density of charge carriers as determined from Nyquist plot fitting. The incorporation of LiI salts in PAN-based GPE has enhanced the efficiency of the DSSC as expected. The best cell performance was obtained with an electrolyte containing 4.61 wt.% LiI sandwiched between a single mesoporous layer of TiO2 soaked in N3 dye sensitizer and a platinum counter electrode, which showed a power conversion efficiency (PCE) of (5.4 ± 0.1) % with a short circuit current density (Jsc) of (21.0 ± 1.1) mA cm−2, an open circuit voltage (Voc) of (0.48 ± 0.02) V and a fill factor (FF) of (53.4 ± 0.9) %. The DSSCs with 4.61 wt.% of LiI have been used to fabricate prototype solar panels for operating small devices. The panels were assembled using a number of cells, each having an area of 2 cm × 2 cm, connected in series and parallel. The panel, consisting of a set of eight cells in series which was connected in parallel with another set of eight cells in series, produces an average power conversion efficiency of (3.7 ± 0.2)% with a maximum output power of (17.1 ± 0.9) mW

Adrenalectomy-Produced Facilitation of Pavlovian Conditioned Cardiodecelerations in Immobilized Rats

Previous evidence has suggested that both hormonal and behavioral aspects of adrenal stress activation may contribute to heart rate (HR) conditioning during physical/pharmacological immobilization. Accordingly, four studies were conducted to determine if bilateral adrenalectomy facilitates stimulus-control over Pavlovian conditioned cardiodecelerations in rats immobilized either through physical restraint or neuromuscular paralysis. Plasma corticosterone assays were used as an index of the effectiveness of adrenal removal. The results showed that adrenalectomy facilitated both simple and discriminated Pavlovian conditioned cardiodecelerations in rats paralyzed with d-tubocurarine chloride (dTC) without significantly altering the characteristics of EMG recovery from paralysis. Similarly, adrenalectomy facilitated simple Pavlovian HR conditioning in physically restrained rats. The results suggest that adrenal activation may disrupt the parasympathetically-mediated Pavlovian conditioned cardiodeceleration in the physically-and dTC-immobilized rat. However, the specific nature of neuroendocrine mechanisms underlying cardiovascular conditioning during immobilization remains problematical.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75069/1/j.1469-8986.1977.tb03371.x.pd

Selective IgA Deficiency

Immunoglobulin A (IgA) deficiency is the most common primary immunodeficiency defined as decreased serum level of IgA in the presence of normal levels of other immunoglobulin isotypes. Most individuals with IgA deficiency are asymptomatic and identified coincidentally. However, some patients may present with recurrent infections of the respiratory and gastrointestinal tracts, allergic disorders, and autoimmune manifestations. Although IgA is the most abundant antibody isotype produced in the body, its functions are not clearly understood. Subclass IgA1 in monomeric form is mainly found in the blood circulation, whereas subclass IgA2 in dimeric form is the dominant immunoglobulin in mucosal secretions. Secretory IgA appears to have prime importance in immune exclusion of pathogenic microorganisms and maintenance of intestinal homeostasis. Despite this critical role, there may be some compensatory mechanisms that would prevent disease manifestations in some IgA-deficient individuals. In IgA deficiency, a maturation defect in B cells to produce IgA is commonly observed. Alterations in transmembrane activator and calcium modulator and cyclophilin ligand interactor gene appear to act as disease-modifying mutations in both IgA deficiency and common variable immunodeficiency, two diseases which probably lie in the same spectrum. Certain major histocompatibility complex haplotypes have been associated with susceptibility to IgA deficiency. The genetic basis of IgA deficiency remains to be clarified. Better understanding of the production and function of IgA is essential in elucidating the disease mechanism in IgA deficiency

Arginine-vasopressin mediates counter-regulatory glucagon release and is diminished in type 1 diabetes.

Insulin-induced hypoglycemia is a major treatment barrier in type-1 diabetes (T1D). Accordingly, it is important that we understand the mechanisms regulating the circulating levels of glucagon. Varying glucose over the range of concentrations that occur physiologically between the fed and fuel-deprived states (8 to 4 mM) has no significant effect on glucagon secretion in the perfused mouse pancreas or in isolated mouse islets (in vitro), and yet associates with dramatic increases in plasma glucagon. The identity of the systemic factor(s) that elevates circulating glucagon remains unknown. Here, we show that arginine-vasopressin (AVP), secreted from the posterior pituitary, stimulates glucagon secretion. Alpha-cells express high levels of the vasopressin 1b receptor (V1bR) gene (Avpr1b). Activation of AVP neurons in vivo increased circulating copeptin (the C-terminal segment of the AVP precursor peptide) and increased blood glucose; effects blocked by pharmacological antagonism of either the glucagon receptor or V1bR. AVP also mediates the stimulatory effects of hypoglycemia produced by exogenous insulin and 2-deoxy-D-glucose on glucagon secretion. We show that the A1/C1 neurons of the medulla oblongata drive AVP neuron activation in response to insulin-induced hypoglycemia. AVP injection increased cytoplasmic Ca2+ in alpha-cells (implanted into the anterior chamber of the eye) and glucagon release. Hypoglycemia also increases circulating levels of AVP/copeptin in humans and this hormone stimulates glucagon secretion from human islets. In patients with T1D, hypoglycemia failed to increase both copeptin and glucagon. These findings suggest that AVP is a physiological systemic regulator of glucagon secretion and that this mechanism becomes impaired in T1D