Perceived Feasibility,Acceptability, and Cultural Adaptation for a Mental Health Intervention in Rural Haiti

Culture, Medicine, and Psychiatry - Mental healthcare is largely unavailable throughout Haiti, particularly in rural areas. The aim of the current study is to explore perceived feasibility,...     

A search for overlapping genetic susceptibility loci between non-Hodgkin lymphoma and autoimmune diseases

Non-Hodgkin lymphoma (NHL) is a hematological malignancy of the immune system, and, as with autoimmune and inflammatory diseases (ADs), is influenced by genetic variation in the major histocompatibility complex (MHC). Persons with a history of specific ADs also have increased risk of NHL. As the coexistence of ADs and NHL could be caused by factors common to both diseases, here we examined whether some of the associated genetic signals are shared. Overlapping risk loci for NHL subytpes and several ADs were explored using data from genome-wide association studies. Several common genomic regions and susceptibility loci were identified, suggesting a potential shared genetic background. Two independent MHC regions showed the main overlap, with several alleles in the human leukocyte antigen (HLA) class II region exhibiting an opposite risk effect for follicular lymphoma and type I diabetes. These results support continued investigation to further elucidate the relationship between lymphoma and autoimmune diseases.     

Effect of the leukotriene A4 hydrolase aminopeptidase augmentor 4-methoxydiphenylmethane in a pre-clinical model of pulmonary emphysema

The leukotriene A(4) hydrolase enzyme is a dual functioning enzyme with the following two catalytic activities: an epoxide hydrolase function that transforms the lipid metabolite leukotriene A(4) to leukotriene B(4) and an aminopeptidase function that hydrolyzes short peptides. To date, all drug discovery efforts have focused on the epoxide hydrolase activity of the enzyme, because of extensive biological characterization of the pro-inflammatory properties of its metabolite, leukotriene B(4). Herein, we have designed a small molecule, 4-methoxydiphenylmethane, as a pharmacological agent that is bioavailable and augments the aminopeptidase activity of the leukotriene A(4) hydrolase enzyme. Pre-clinical evaluation of our drug showed protection against intranasal elastase-induced pulmonary emphysema in murine models.     

Synthesis and SAR of a novel metabotropic glutamate receptor 4 (mGlu4) antagonist: unexpected 'molecular switch' from a closely related mGlu4 positive allosteric modulator

Herein we report the discovery and SAR of a novel antagonist of metabotropic glutamate receptor 4 (mGlu(4)). The antagonist was discovered via a molecular switch from a closely related mGlu(4) positive allosteric modulator (PAM). This antagonist (VU0448383) displays an IC(50) value of 8.2±0.4 μM and inhibits an EC(80) glutamate response by 63.1±6.6%.     

Synthesis and SAR of centrally active mGlu5 positive allosteric modulators based on an aryl acetylenic bicyclic lactam scaffold

This Letter describes the hit-to-lead progression and SAR of a series of biphenyl acetylene compounds derived from an HTS screening campaign targeting the mGlu₅ receptor. ‘Molecular switches’ were identified that modulated modes of pharmacology, and several compounds within this series were shown to be efficacious in reversal of amphetamine induced hyperlocomotion in rats after ip dosing, a preclinical model that shows similar positive effects with known antipsychotic agents.     

Integrin-mediated type IV secretion by Helicobacter: what makes it tick?

Helicobacter pylori (Hp) employs a multi-component type IV secretion system (T4SS) to secrete the effector protein CagA into the cytosol of infected host cells. A longstanding challenge has been to identify the host cell receptor(s) involved. Two recent studies have independently unveiled human β(1) integrin as the receptor but are divided over which T4SS proteins bind to β(1) integrin. Here we revisit the two models in light of previous findings and recent progress in the field. More concerted efforts are required to fully understand the complex T4SS mechanisms that underpin Hp pathogenesis.     

Cutting edge: transplant tolerance induced by anti-CD45RB requires B lymphocytes

Selective interference with the CD45RB isoform by mAb (anti-CD45RB) reliably induces donor-specific tolerance. Although previous studies suggest participation of regulatory T cells, a mechanistic understanding of anti-CD45RB-induced tolerance is lacking. We report herein the unexpected finding that tolerance induced by this agent is not established in B cell-deficient mice but can be recovered by preemptive B lymphocyte transfer to B cell-deficient hosts. Using B cells from genetically modified donors to reconstitute B cell-deficient recipients, we evaluate the role of B lymphocyte-expressed CD45RB, T cell costimulatory molecules, and the production of Abs in this novel tolerance mechanism. Our data document an Ab-induced tolerance regimen that is uniquely B lymphocyte-dependent and suggest mechanistic contributions to tolerance development from the B cell compartment through interactions with T cells.     

Alterations of endophytic microbial community function in Spartina alterniflora as a result of crude oil exposure

Biodegradation - The 2010 Deepwater Horizon disaster remains one of the largest oil spills in history. This event caused significant damage to coastal ecosystems, the full extent of which has yet...     

Survival and growth of northern bobwhite offspring post-translocation

Continual population declines in northern bobwhites (Colinus virginianus) have prompted the use of population restoration techniques in conjunction with habitat management to restore their populations. We tested the site familiarity hypothesis to determine if translocation to new environments affected offspring survival and growth rates of bobwhites. We used bobwhites from north Florida and translocated them to a study site in Brunswick County, North Carolina, USA, and monitored birds during April−October 2016 and April−October 2017. We used the corral capture method and modified-suture technique to capture and radio-tag chicks to evaluate offspring growth and survival rates of resident and translocated bobwhites. Offspring survival varied by year and age. We did not find any difference in offspring survival rates of resident and translocated individuals, lending no support to the site familiarity hypothesis with regards to survival. Offspring of resident bobwhites did not grow at a faster rate than offspring of translocated bobwhites, indicating a lack of support for the site familiarity hypothesis in terms of physiological development. Survival, however, is a more important metric for determining post-translocation population dynamics, and our results indicated that translocated bobwhites can reproduce and raise offspring similar to resident counterparts, but both had low survival. © 2019 The Wildlife Society.