Enhanced CREB and DARPP-32 phosphorylation in the nucleus accumbens and CREB, ERK, and GluR1 phosphorylation in the dorsal hippocampus is associated with cocaine-conditioned place preference behavior

Environment-induced relapse is a major concern in drug addiction because of the strong associations formed between drug reward and environment. Cocaine-conditioned place preference is an ideal experimental tool to examine adaptations in the molecular pathways that are activated upon re-exposure to an environment previously paired with drug reward. To better understand the mechanism of cocaine-conditioned place preference we have used western blot analysis to examine changes in phosphorylation of cAMP-response element binding protein (CREB), dopamine- and cyclic AMP-regulated phosphoprotein 32 (DARPP-32), extracellular signal-regulated kinase (ERK) and GluR1, key molecular substrates altered by cocaine, in the nucleus accumbens (NAc) and dorsal hippocampus (DHC) of C57BL/6 mice. Our studies revealed that re-exposing mice to an environment in which they were previously given cocaine resulted in increased levels of Ser133 phospho-CREB and Thr34 phospho-DARPP-32 with a corresponding decrease in Thr75 phospho-DARPP-32 in the NAc. In DHC there were increased levels of phospho-CREB, Thr183/Tyr185 phospho-ERK, and Ser845 phospho-GluR1. These data suggest that the formation of contextual drug reward associations involves recruitment of the DHC-NAc circuit with activation of the DARPP-32/CREB pathway in the NAc and the ERK/CREB pathway in the DHC.     

RAPD analysis of induced mutants of groundnut (Arachis hypogaea L.)

Radiation-induced mutants of groundnut cv. Spanish Improved showing distinct morphological differences and the parent were screened for RAPD variability. The analysis revealed characteristic band differences among the 12 mutants and the parent. The polymorphic RAPD bands were dominant in the F₁ and segregated in a Mendelian fashion in the F₂. The RAPD technique brought out greater genome variability than RFLP.     

Genetic evidence for landscape effects on dispersal in the army ant Eciton burchellii

Inhibited dispersal, leading to reduced gene flow, threatens populations with inbreeding depression and local extinction. Fragmentation may be especially detrimental to social insects because inhibited gene flow has important consequences for cooperation and competition within and among colonies. Army ants have winged males and permanently wingless queens; these traits imply male‐biased dispersal. However, army ant colonies are obligately nomadic and have the potential to traverse landscapes. Eciton burchellii, the most regularly nomadic army ant, is a forest interior species: colony raiding activities are limited in the absence of forest cover. To examine whether nomadism and landscape (forest clearing and elevation) affect population genetic structure in a montane E. burchellii population, we reconstructed queen and male genotypes from 25 colonies at seven polymorphic microsatellite loci. Pairwise genetic distances among individuals were compared to pairwise geographical and resistance distances using regressions with permutations, partial Mantel tests and random forests analyses. Although there was no significant spatial genetic structure in queens or males in montane forest, dispersal may be male‐biased. We found significant isolation by landscape resistance for queens based on land cover (forest clearing), but not on elevation. Summed colony emigrations over the lifetime of the queen may contribute to gene flow in this species and forest clearing impedes these movements and subsequent gene dispersal. Further forest cover removal may increasingly inhibit Eciton burchellii colony dispersal. We recommend maintaining habitat connectivity in tropical forests to promote population persistence for this keystone species.     

Shape Covariation (or the Lack Thereof) Between Vertebrae and Other Skeletal Traits in Felids: The Whole is Not Always Greater than the Sum of Parts

Within carnivorans, cats show comparatively little disparity in overall morphology, with species differing mainly in body size. However, detailed shape analyses of individual osteological structures, such as limbs or skulls, have shown that felids display significant morphological differences that correlate with their observed ecological and behavioural ranges. Recently, these shape analyses have been extended to the felid axial skeleton. Results demonstrate a functionally-partitioned vertebral column, with regions varying greatly in level of correlation between shape and ecology. Moreover, a clear distinction is evident between a phylogenetically-constrained neck region and a selection-responsive posterior spine. Here, we test whether this regionalisation of function reflected in vertebral column shape is also translated into varying levels of phenotypic integration between this structure and most other skeletal elements. We accomplish this comparison by performing pairwise tests of integration between vertebral and other osteological units, quantified with 3D geometric morphometric data and analysed both with and without phylogenetic correction. To our knowledge, this is the first study to test for integration across a comprehensive sample of whole-skeleton elements. Our results show that, prior to corrections, strong covariation is present between vertebrae across the vertebral column and all other elements, with the exception of the femur. However, most of these significant correlations disappear after correcting for phylogeny, which is a significant influence on cranial and limb morphology of felids and other carnivorans. Our results thus suggest that the vertebral column of cats displays relative independence from other skeletal elements and may represent several distinct evolutionary morphological modules.     

Synthesis and evaluation of aminobenzothiazoles as blockers of N- and T-type calcium channels

Both N- and T-type calcium ion channels have been implicated in pain transmission and the N-type channel is a well-validated target for the treatment of neuropathic pain. An SAR investigation of a series of substituted aminobenzothiazoles identified a subset of five compounds with comparable activity to the positive control Z160 in a FLIPR-based intracellular calcium response assay measuring potency at both Ca_V2.2 and Ca_V3.2 channels. These compounds may form the basis for the development of drug leads and tool compounds for assessing in vivo effects of variable modulation of Ca_V2.2 and Ca_V3.2 channels.     

Exploring how patients understand and assess their diabetes control

Background

Poor understanding of diabetes management targets is associated with worse disease outcomes. Patients may use different information than providers to assess their diabetes control. In this study, we identify the information patients use to gauge their current level of diabetes control and explore patient-perceived barriers to understanding the hemoglobin A1c value (HbA1c).

Methods

Adults who self-reported a diagnosis of diabetes were recruited from outpatient, academically-affiliated, Internal Medicine clinics. Semi-structured interviews were conducted with participants and collected data were analyzed using thematic analysis.

Results

The mean age of the 25 participants was 56.8 years. HbA1c was one of several types of information participants used to assess diabetes control. Other information included perceived self-efficacy and adherence to self-care, the type and amount of medications taken, the presence or absence of symptoms attributed to diabetes, and feedback from self-monitoring of blood glucose. Most participants reported familiarity with the HbA1c (22 of 25), though understanding of the value’s meaning varied significantly. Inadequate diabetes education and challenges with patient-provider communication were cited as common barriers to understanding the HbA1c.

Conclusions

In addition to the HbA1c, several categories of information influenced participants’ assessments of their diabetes control. Increased provider awareness of the factors that influence patients’ perceptions of diabetes control can inform effective, patient-centered approaches for communicating vital diabetes-related information, facilitating behavior change towards improved patient outcomes.

     

Inhibition of Endosteal Vascular Niche Remodeling Rescues Hematopoietic Stem Cell Loss in AML

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