Effects of stimulation of the satiety and feeding centers on gastric, cecal and rectal motility in the rat.

The effects of electrical stimulation of the satiety and feeding centers (SC, FC) on gastric, cecal and rectal motility were studied in rats anesthetized with urethane. Each center produced excitatory, inhibitory and biphasic responses in these organs. Cecal and rectal responses to stimulation of SC or FC were usually the opposite of the gastric response; for example, the gastric response was excitatory, whereas cecal and rectal responses were inhibitory. Gastric and cecal excitatory responses were abolished by vagotomy and the rectal response by severance of parasympathetic branches of the pudendal plexus (PSB). Gastric and ceca inhibitory responses were fairly depressed by vagotomy and abolished by successive splanchnicotomy, while the rectal inhibitory response was abolished by severance of inferior mesenteric nerves (IMN) and PSB. It was concluded that the satiety and feeding centers modulate not only gastric motility but also cecal and rectal motility, and that the excitatory response is conveyed through vagus nerves to the stomach and cecum and through PSB to the rectum. The inhibitory response is mediated mainly through vagus nerves, partially through splanchnic nerves to the stomach and cecum, and through IMN and PSB to the rectum. The characteristics of efferent terminal neurons eliciting excitatory and inhibitory responses were studied pharmacologically.</p

On the gastrocecal inhibitory reflex in the rat.

In rats anesthetized with urethane, the effects of distention of the stomach upon cecal motility and neural mechanisms which generate this effect were studied. Cecal motility was inhibited which generate this effect were studied. Cecal motility was inhibited when the pars glandularis of the stomach was distended by pressure ranging from 25 to 30 cm H2O. This inhibitory reflex was not affected by bilateral cervical vagotomy, but completely abolished following bilateral severance of the greater splanchnic nerves or after intravenous administration of guanethidine. After transection of the spinal cord at the level of the 5th thoracic segment the inhibitory reflex remained intact, but was abolished following pithing of the 6th thoracic segment and below. It may be concluded that the afferent and efferent path of the gastrocecal inhibitory reflex mainly pass through the greater splanchnic nerves and the reflex center is located in thoracic segments caudal to the 6th thoracic segment.</p

Molybdenum Disulfide-Coated Lithium Vanadium Fluorophosphate Anode: Experiments and First-Principles Calculations

To develop a new anode material to meet the increasing demands of lithium-ion battery, MoS2 is used for the first time to modify the C/LiVPO4F anode to improve its lithium-storage performance between 3 and 0.01 V. Morphological observations reveal that the MoS2-modified C/LiVPO4F particles (M-LVPF) are wrapped by an amorphous carbon as interlayer and layered MoS2 as external surface. Charge–discharge tests show that M-LVPF delivers a high reversible capacity of 308 mAh g−1 at 50 mA g−1. After 300 cycles at 1.0 A g−1, a capacity retention of 98.7 % is observed. Moreover, it exhibits high rate capability with a specific capacity of 199 mAh g−1 at 1.6 A g−1. Electrochemical impedance spectroscopy tests indicate that the lithium-ion diffusion and charge-exchange reaction at the surface of M-LVPF are greatly enhanced. First-principles calculations for the MoS2 (001)/C/LiVPO4F (010) system demonstrate that the absorption of MoS2 on C/LiVPO4F is exothermic and spontaneous and that the electron transfer at the MoS2-absorbed C/LiVPO4F surface is enhanced.postprin

Enhanced inhibition of Avian leukosis virus subgroup J replication by multi-target miRNAs

<p>Abstract</p> <p>Background</p> <p>Avian leukosis virus (ALV) is a major infectious disease that impacts the poultry industry worldwide. Despite intensive efforts, no effective vaccine has been developed against ALV because of mutations that lead to resistant forms. Therefore, there is a dire need to develop antiviral agents for the treatment of ALV infections and RNA interference (RNAi) is considered an effective antiviral strategy.</p> <p>Results</p> <p>In this study, the avian leukosis virus subgroup J (ALV-J) proviral genome, including the <it>gag </it>genes, were treated as targets for RNAi. Four pairs of miRNA sequences were designed and synthesized that targeted different regions of the <it>gag </it>gene. The screened target (i.e., the <it>gag </it>genes) was shown to effectively suppress the replication of ALV-J by 19.0-77.3%. To avoid the generation of escape variants during virus infection, expression vectors of multi-target miRNAs were constructed using the multi-target serial strategy (against different regions of the <it>gag</it>, <it>pol</it>, and <it>env </it>genes). Multi-target miRNAs were shown to play a synergistic role in the inhibition of ALV-J replication, with an inhibition efficiency of viral replication ranging from 85.0-91.2%.</p> <p>Conclusion</p> <p>The strategy of multi-target miRNAs might be an effective method for inhibiting ALV replication and the acquisition of resistant mutations.</p

Emergent properties of neural repair: elemental biology to therapeutic concepts

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137471/1/ana24653_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137471/2/ana24653.pd

The Groebke-Blackburn-Bienayme Reaction

Imidazo[1,2a]pyridine is a well‐known scaffold in many marketed drugs, such as Zolpidem, Minodronic acid, Miroprofen and DS‐1 and it also serves as a broadly applied pharmacophore in drug discovery. The scaffold revoked a wave of interest when Groebke, Blackburn and Bienaymé reported independently a new three component reaction resulting in compounds with the imidazo[1,2‐a]‐heterocycles as a core structure. During the course of two decades the Groebke Blackburn Bienaymé (GBB‐3CR) reaction has emerged as a very important multicomponent reaction (MCR), resulting in over a hundred patents and a great number of publications in various fields of interest. Now two compounds derived from GBB‐3CR chemistry received FDA approval. To celebrate the first 20 years of GBB‐chemistry , we present an overview of the chemistry of the GBB‐3CR, including an analysis of each of the three starting material classes, solvents and catalysts. Additionally, a list of patents and their applications and a more in‐depth summary of the biological targets that were addressed, including structural biology analysis, is given

No Reliable Association between Runs of Homozygosity and Schizophrenia in a Well-Powered Replication Study

It is well known that inbreeding increases the risk of recessive monogenic diseases, but it is less certain whether it contributes to the etiology of complex diseases such as schizophrenia. One way to estimate the effects of inbreeding is to examine the association between disease diagnosis and genome-wide autozygosity estimated using runs of homozygosity (ROH) in genome-wide single nucleotide polymorphism arrays. Using data for schizophrenia from the Psychiatric Genomics Consortium (n = 21,868), Keller et al. (2012) estimated that the odds of developing schizophrenia increased by approximately 17% for every additional percent of the genome that is autozygous (β = 16.1, CI(β) = [6.93, 25.7], Z = 3.44, p = 0.0006). Here we describe replication results from 22 independent schizophrenia case-control datasets from the Psychiatric Genomics Consortium (n = 39,830). Using the same ROH calling thresholds and procedures as Keller et al. (2012), we were unable to replicate the significant association between ROH burden and schizophrenia in the independent PGC phase II data, although the effect was in the predicted direction, and the combined (original + replication) dataset yielded an attenuated but significant relationship between Froh and schizophrenia (β = 4.86,CI(β) = [0.90,8.83],Z = 2.40,p = 0.02). Since Keller et al. (2012), several studies reported inconsistent association of ROH burden with complex traits, particularly in case-control data. These conflicting results might suggest that the effects of autozygosity are confounded by various factors, such as socioeconomic status, education, urbanicity, and religiosity, which may be associated with both real inbreeding and the outcome measures of interest

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders