Obestatin stimulates glucose-induced insulin secretion through ghrelin receptor GHS-R

AbstractOrexigenic hormone ghrelin and anorexic hormone obestatin are encoded by the same preproghrelin gene. While it is known that ghrelin inhibits glucose-stimulated insulin secretion (GSIS), the effect of obestatin on GSIS is unclear. Ghrelin’s effect is mediated by its receptor Growth Hormone Secretagogue Receptor (GHS-R), but the physiologically relevant receptor of obestatin remains debatable. Here we have investigated the effect of obestatin on GSIS in vitro, in vivo and ex vivo, and tested whether obestatin regulates insulin secretion through GHS-R. We found that under hyperglycemic condition, obestatin augments GSIS in rat insulinoma cells (INS-1) and in pancreatic islets from ghrelin−/− mice. Surprisingly, obestatin-induced GSIS was absent in β-cells in which GHS-R was suppressed. Obestatin-induced insulin secretion was abolished in the circulation of Ghsr−/− mice, and in pancreatic islets isolated from Ghsr−/− mice. We also found that obestatin-induced GSIS was attenuated in islets isolated from β-cell-specific Ghsr knockout MIP-Cre/ERT;Ghsrf/f mice. Our data collectively demonstrate that obestatin is a potent insulin secretagogue under hyperglycemic condition, and obestatin’s effect on insulin secretion is mediated by GHS-R in pancreatic β-cells. Our findings reveal an intriguing insight that obestatin and ghrelin have opposing effects on insulin secretion, and both are mediated through ghrelin receptor GHS-R.</jats:p

Perceção de mulheres grávidas relativamente à informação disponível acerca do consumo de álcool durante a gravidez

info:eu-repo/semantics/draf

Observation of whistler wave instability driven by temperature anisotropy of energetic electrons on EXL-50 spherical torus

Electromagnetic modes in the frequency range of 30-120MHz were observed in electron cyclotron wave (ECW) steady state plasmas on the ENN XuanLong-50 (EXL-50) spherical torus. These modes were found to have multiple bands of frequencies proportional to the Alfv\'en velocity. This indicates that the observed mode frequencies satisfy the dispersion relation of whistler waves. In addition, suppression of the whistler waves by the synergistic effect of Lower Hybrid Wave (LHW) and ECW was also observed. This suggests that the whistler waves were driven by temperature anisotropy of energetic electrons. These are the first such observations (not runaway discharge) made in magnetically confined toroidal plasmas and may have important implications for studying wave-particle interactions, RF wave current driver, and runaway electron control in future fusion devices

Solenoid-free current drive via ECRH in EXL-50 spherical torus plasmas

As a new spherical tokamak (ST) designed to simplify engineering requirements of a possible future fusion power source, the EXL-50 experiment features a low aspect ratio (A) vacuum vessel (VV), encircling a central post assembly containing the toroidal field coil conductors without a central solenoid. Multiple electron cyclotron resonance heating (ECRH) resonances are located within the VV to improve current drive effectiveness. Copious energetic electrons are produced and measured with hard X-ray detectors, carry the bulk of the plasma current ranging from 50kA to 150kA, which is maintained for more than 1s duration. It is observed that over one Ampere current can be maintained per Watt of ECRH power issued from the 28-GHz gyrotrons. The plasma current reaches Ip>80kA for high density (>5e18me-2) discharge with 150kW ECHR heating. An analysis was carried out combining reconstructed multi-fluid equilibrium, guiding-center orbits of energetic electrons, and resonant heating mechanisms. It is verified that in EXL-50 a broadly distributed current of energetic electrons creates smaller closed magnetic-flux surfaces of low aspect ratio that in turn confine the thermal plasma electrons and ions and participate in maintaining the equilibrium force-balance

From structure to function via complex supramolecular dendrimer systems

This tutorial review summarizes strategies elaborated for the discovery and prediction of programmed primary structures derived from quasi-equivalent constitutional isomeric libraries of self-assembling dendrons, dendrimers and dendronized polymers. These libraries demonstrate an 82% predictability, defined as the percentage of similar primary structures resulting in at least one conserved supramolecular shape with internal order. A combination of structural and retrostructural analysis that employs methodologies transplanted from structural biology, adapted to giant supramolecular assemblies was used for this process. A periodic table database of programmed primary structures was elaborated and used to facilitate the emergence of a diversity of functions in complex dendrimer systems via first principles. Assemblies generated by supramolecular and covalent polymer backbones were critically compared. Although by definition complex functional systems cannot be designed, this tutorial hints to a methodology based on database analysis principles to facilitate design principles that may help to mediate an accelerated emergence of chemical, physical and most probably also societal, political and economic complex systems on a shorter time scale and lower cost than by the current methods. This tutorial review is limited to the simplest, synthetically most accessible self-assembling minidendrons, minidendrimers and polymers dendronized with minidendrons that are best analyzed and elucidated at molecular, supramolecular and theoretical levels, and most used in other laboratories. These structures are all interrelated, and their principles expand in a simple way to their higher generations

Designated-Tailoring on {100} Facets of Cu2O Nanostructures: From Octahedral to Its Different Truncated Forms

A facile template-free controlled synthesis of Cu2O architectures from octahedral to its different truncated forms is successfully achieved. It is found that the precursor formation temperature is crucial to the designated-tailoring on the {100} facets of Cu2O crystals, which can modify the ratio (R) between the growth rates along the 〈100〉 and 〈111〉 directions, leading to the formation of the initial structures with different shapes. The multiple morphologies can be evolved from these varied initial structures via the synergic effect of oriented attachment and ripening mechanism. This template-free complex precursor-based solution route has provided an innovative approach to design the {100} facets with different sizes to further enrich the current morphologies of Cu2O crystals

Delta large-channel technique versus microscopy-assisted laminar fenestration decompression for lumbar spinal stenosis: a one-year prospective cohort study

Abstract Purpose When it comes to treating lumbar spinal stenosis (LSS), a procedure known as microscope-assisted fenestration decompression has expediently become the gold standard. With the advancement of spinal endoscopy, the Delta large-channel approach has shown promising clinical outcomes in the management of lumbar spinal stenosis. However, case studies of this method being used to treat lumbar spinal stenosis are still uncommon. The purpose of this research was to examine how well microscopy-assisted laminectomy and the Delta large-channel approach work in treating LSS in the clinic. Methods From May 2018 to June 2020, 149 patients diagnosed with LSS were divided into 80 patients in Delta large-channel technique groups (FE group) and 69 patients in microscope groups (Micro group). Lower back and lower limb pain were measured using the visual analogue scale (VAS-LBP and VAS-LP), while lower limb numbness was evaluated using the 11-point numerical rating scale (NRS-LN); modified Oswestry Disability Index (ODI) was used to evaluate the quality of life, and modified MacNab criteria were used to assess the clinical efficacy before surgery and at one week, three months, six months, and 12 months after surgery. All patients had single-level lumbar spinal stenosis, and clinical data such as hospital stay, operation time, intraoperative blood loss were statistically analyzed. Results Finally, 111 patients (62 in FE group and 49 in Micro group) completed follow-up. Compared with preoperative results, postoperative VAS-LBP, VAS-LP, NRS-LN score and modified ODI score were significantly improved in 2 groups (P  0.05), Except 1 week after surgery, VAS-LBP in FE group was lower than that in Micro group (P  0.05). Conclusions Both microscope-assisted laminar fenestration decompression and Delta large-channel procedures provide satisfactory treatment outcomes, however the Delta large-channel approach has some potential advantages for the treatment of LSS, including quicker recovery and sooner reduced VAS-LBP. Long-term consequences, however, will necessitate additional follow-up and research

GHS-R in brown fat potentiates differential thermogenic responses under metabolic and thermal stresses

In response to cold or diet, fatty acids are dissipated into heat through uncoupling protein 1 (UCP1) in brown adipose tissue (BAT). This process is termed non-shivering thermogenesis, which is important for body temperature maintenance and contributes to obesity pathogenesis. Thermogenic enhancement has been considered a promising anti-obesity strategy. Ghrelin and its receptor Growth Hormone Secretagogue Receptor (GHS-R) have critical roles in energy intake, nutrient sensing, and lipid metabolism. We previously reported that global Ghsr-knockout mice have increased energy expenditure due to enhanced thermogenesis. To determine the site of action for GHS-R mediated thermogenesis, we generated brown adipocyte-specific Ghsr knockout mice (UCP1-CreER/Ghsrf/f) and assessed thermogenic responses under regular diet (RD) fed homeostatic metabolic state or high-fat diet (HFD) fed metabolically-impaired obese state, under normal or cold housing environment. Under a RD-feeding, UCP1-CreER/Ghsrf/f mice showed increased body fat and a slightly elevated core body temperature under cold but not under normal temperature. Consistently, the expression of thermogenic genes in BAT of RD-fed UCP1-CreER/Ghsrf/f mice was increased in reposes to cold. Under HFD feeding, HFD-fed UCP1-CreER/Ghsrf/f mice showed no difference in body fat or body temperature under either normal or cold exposure. Interestingly, the expression of thermogenic genes in BAT of HFD-fed UCP1-CreER/Ghsrf/f mice was upregulated under normal temperature but downregulated under cold exposure. Overall, our data show that GHS-R has cell-autonomous effect in brown adipocytes, and GHS-R regulates BAT thermogenic activity in a temperature- and metabolic state-dependent manner. The thermogenic effect of GHS-R in BAT is more pronounced in cold environment and differentially variable based on metabolic state; under cold exposure, GHS-R inhibition in BAT activates thermogenesis under homeostatic state but suppresses thermogenesis under obese state. Our finding collectively suggests that GHS-R in BAT, acting as a “metabolic thermostat”, differentially regulates thermogenesis in response to different metabolic and thermal stimuli.ISSN:1932-620

Evolutionary, genomic, and biogeographic characterization of two novel xenobiotics-degrading strains affiliated with Dechloromonas

Xenobiotics are generally known as man-made refractory organic pollutants widely distributed in various environments. For exploring the bioremediation possibility of xenobiotics, two novel xenobiotics-degrading strains affiliated with Azonexaceae were isolated. We report here the phylogenetics, genome, and geo-distribution of a novel and ubiquitous Azonexaceae species that primarily joins in the cometabolic process of some xenobiotics in natural communities. Strains s22 and t15 could be proposed as a novel species within Dechloromonas based on genomic and multi-phylogenetic analysis. Pan-genome analysis showed that the 63 core genes in Dechloromonas include genes for dozens of metabolisms such as nitrogen fixation protein (nifU), nitrogen regulatory protein (glnK), dCTP deaminase, C4-dicarboxylate transporter, and fructose-bisphosphate aldolase. Strains s22 and t15 have the ability to metabolize nitrogen, including nitrogen fixation, NirS-dependent denitrification, and dissimilatory nitrate reduction. Moreover, the novel species possesses the EnvZ-OmpR two-component system for controlling osmotic stress and QseC-QseB system for quorum sensing to rapidly sense environmental changes. It is intriguing that this new species has a series of genes for the biodegradation of some xenobiotics such as azathioprine, 6-Mercaptopurine, trinitrotoluene, chloroalkane, and chloroalkene. Specifically, glutathione S-transferase (GST) and 4-oxalocrotonate tautomerase (praC) in this novel species play important roles in the detoxification metabolism of some xenobiotics like dioxin, trichloroethene, chloroacetyl chloride, benzo[a]pyrene, and aflatoxin B1. Using data from GenBank, DDBJ and EMBL databases, we also demonstrated that members of this novel species were found globally in plants (e.g. rice), guts (e.g. insect), pristine and contaminated regions. Given these data, Dechloromonas sp. strains s22 and t15 take part in the biodegradation of some xenobiotics through key enzymes