Inhibition of prandial and waterspray-induced rat grooming by 8-OH-DPAT

The effects of 8-OH-DPAT treatment on rat grooming behaviour, elicited either prandially or in response to spraying with water were investigated. Dose (≤0.1 mg/kg s.c.) response studies employed momentary time sampling over 30 or 60 min with behaviour being scored in one of 6 or 7 (depending on food availability) mutually exclusive categories (feeding, active, scratching, face-grooming, body grooming, genital-grooming and resting) at 15 s intervals. In non-deprived rats, tested with wet mash available, feeding and activity frequencies were increased, but resting and total grooming were inhibited by 8-OH-DPAT. Face-, body- and genital-grooming occurred at higher levels than scratching, but all categories were reduced with reductions in scratching occurring at a lower dose (0.01 mg/kg). Misting rats with a fine water spray selectively increased body grooming and decreased activity without altering feeding, while 8-OH-DPAT increased feeding and reduced face-, body- and genital-grooming, without affecting already low levels of scratching. In misted rats, tested without food, 8-OH-DPAT reduced face-, body- and genital-grooming and increased resting. These results confirm i) that the water spray technique is a useful method for increasing grooming and ii) that 8-OH-DPAT has a suppressant effect on grooming independent of response competition from enhanced feeding

Mitochondrial echoes of first settlement and genetic continuity in El Salvador

Background: From Paleo-Indian times to recent historical episodes, the Mesoamerican isthmus played an important role in the distribution and patterns of variability all around the double American continent. However, the amount of genetic information currently available on Central American continental populations is very scarce. In order to shed light on the role of Mesoamerica in the peopling of the New World, the present study focuses on the analysis of the mtDNA variation in a population sample from El Salvador. Methodology/Principal Findings: We have carried out DNA sequencing of the entire control region of the mitochondrial DNA (mtDNA) genome in 90 individuals from El Salvador. We have also compiled more than 3,985 control region profiles from the public domain and the literature in order to carry out inter-population comparisons. The results reveal a predominant Native American component in this region: by far, the most prevalent mtDNA haplogroup in this country (at ~90%) is A2, in contrast with other North, Meso- and South American populations. Haplogroup A2 shows a star-like phylogeny and is very diverse with a substantial proportion of mtDNAs (45%; sequence range 16090–16365) still unobserved in other American populations. Two different Bayesian approaches used to estimate admixture proportions in El Salvador shows that the majority of the mtDNAs observed come from North America. A preliminary founder analysis indicates that the settlement of El Salvador occurred about 13,400±5,200 Y.B.P.. The founder age of A2 in El Salvador is close to the overall age of A2 in America, which suggests that the colonization of this region occurred within a few thousand years of the initial expansion into the Americas. Conclusions/Significance: As a whole, the results are compatible with the hypothesis that today's A2 variability in El Salvador represents to a large extent the indigenous component of the region. Concordant with this hypothesis is also the observation of a very limited contribution from European and African women (~5%). This implies that the Atlantic slave trade had a very small demographic impact in El Salvador in contrast to its transformation of the gene pool in neighbouring populations from the Caribbean facade

EFHC1 variants in juvenile myoclonic epilepsy: reanalysis according to NHGRI and ACMG guidelines for assigning disease causality

Peer reviewe

Feedback as intervention for team learning in virtual teams: the role of team cohesion and personality

Scholars and practitioners agree that virtual teams (VTs) have become commonplace in today's digital workplace. Relevant literature argues that learning constitutes a significant contributor to team member satisfaction and performance, and that, at least in face-to-face teams, team cohesion fosters team learning. Given the additional challenges VTs face, e.g. geographical dispersion, which are likely have a negative influence on cohesion, in this paper we shed light on the relationship between team cohesion and team learning. We adopted a quantitative approach and studied 54 VTs in our quest to understand the role of feedback in mediating this relationship and, more specifically, the role of personality traits in moderating the indirect effect of team feedback and guided reflection intervention on TL through team cohesion within the VT context. Our findings highlight the importance of considering aspects related to the team composition when devising intervention strategies for VTs, and provide empirical support for an interactionist model between personality and emergent states such as cohesion. Implications for theory and practice are also discussed

Tuber shape and eye depth variation in a diploid family of Andean potatoes.

BACKGROUND: Tuber appearance is highly variable in the Andean cultivated potato germplasm. The diploid backcross mapping population ‘DMDD’ derived from the recently sequenced genome ‘DM’ represents a sample of the allelic variation for tuber shape and eye depth present in the Andean landraces. Here we evaluate the utility of morphological descriptors for tuber shape for identification of genetic loci responsible for the shape and eye depth variation. RESULTS: Subjective morphological descriptors and objective tuber length and width measurements were used for assessment of variation in tuber shape and eye depth. Phenotypic data obtained from three trials and male–female based genetic maps were used for quantitative trait locus (QTL) identification. Seven morphological tuber shapes were identified within the population. A continuous distribution of phenotypes was found using the ratio of tuber length to tuber width and a QTL was identified in the paternal map on chromosome 10. Using toPt-437059, the marker at the peak of this QTL, the seven tuber shapes were classified into two groups: cylindrical and non-cylindrical. In the first group, shapes classified as ‘compressed’, ‘round’, ‘oblong’, and ‘long-oblong’ mainly carried a marker allele originating from the male parent. The tubers in this group had deeper eyes, for which a strong QTL was found at the same location on chromosome 10 of the paternal map. The non-cylindrical tubers classified as ‘obovoid’, ‘elliptic’, and ‘elongated’ were in the second group, mostly lacking the marker allele originating from the male parent. The main QTL for shape and eye depth were located in the same genomic region as the previously mapped dominant genes for round tuber shape and eye depth. A number of candidate genes underlying the significant QTL markers for tuber shape and eye depth were identified. CONCLUSIONS: Utilization of a molecular marker at the shape and eye depth QTL enabled the reclassification of the variation in general tuber shape to two main groups. Quantitative measurement of the length and width at different parts of the tuber is recommended to accompany the morphological descriptor classification to correctly capture the shape variation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12863-015-0213-0) contains supplementary material, which is available to authorized users

CD47 plays a critical role in T-cell recruitment by regulation of LFA-1 and VLA-4 integrin adhesive functions

CD47 plays an important but incompletely understood role in the innate and adaptive immune responses. CD47, also called integrin-associated protein, has been demonstrated to associate in cis with β1 and β3 integrins. Here we test the hypothesis that CD47 regulates adhesive functions of T-cell α4β1 (VLA-4) and αLβ2 (LFA-1) in in vivo and in vitro models of inflammation. Intravital microscopy studies reveal that CD47(−/−) Th1 cells exhibit reduced interactions with wild-type (WT) inflamed cremaster muscle microvessels. Similarly, murine CD47(−/−) Th1 cells, as compared with WT, showed defects in adhesion and transmigration across tumor necrosis factor-α (TNF-α)–activated murine endothelium and in adhesion to immobilized intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion protein 1 (VCAM-1) under flow conditions. Human Jurkat T-cells lacking CD47 also showed reduced adhesion to TNF-α–activated endothelium and ICAM-1 and VCAM-1. In cis interactions between Jurkat T-cell β2 integrins and CD47 were detected by fluorescence lifetime imaging microscopy. Unexpectedly, Jurkat CD47 null cells exhibited a striking defect in β1 and β2 integrin activation in response to Mn(2+) or Mg(2+)/ethylene glycol tetraacetic acid treatment. Our results demonstrate that CD47 associates with β2 integrins and is necessary to induce high-affinity conformations of LFA-1 and VLA-4 that recognize their endothelial cell ligands and support leukocyte adhesion and transendothelial migration

Integrins as therapeutic targets: lessons and opportunities.

The integrins are a large family of cell adhesion molecules that are essential for the regulation of cell growth and function. The identification of key roles for integrins in a diverse range of diseases, including cancer, infection, thrombosis and autoimmune disorders, has revealed their substantial potential as therapeutic targets. However, so far, pharmacological inhibitors for only three integrins have received marketing approval. This article discusses the structure and function of integrins, their roles in disease and the chequered history of the approved integrin antagonists. Recent advances in the understanding of integrin function, ligand interaction and signalling pathways suggest novel strategies for inhibiting integrin function that could help harness their full potential as therapeutic targets

Molecular Mechanisms Associated with Nicotine Pharmacology and Dependence.

Tobacco dependence is a leading cause of preventable disease and death worldwide. Nicotine, the main psychoactive component in tobacco cigarettes, has also been garnering increased popularity in its vaporized form, as derived from e-cigarette devices. Thus, an understanding of the molecular mechanisms underlying nicotine pharmacology and dependence is required to ascertain novel approaches to treat drug dependence. In this chapter, we review the field's current understanding of nicotine's actions in the brain, the neurocircuitry underlying drug dependence, factors that modulate the function of nicotinic acetylcholine receptors, and the role of specific genes in mitigating the vulnerability to develop nicotine dependence. In addition to nicotine's direct actions in the brain, other constituents in nicotine and tobacco products have also been found to alter drug use, and thus, evidence is provided to highlight this issue. Finally, currently available pharmacotherapeutic strategies are discussed, along with an outlook for future therapeutic directions to achieve to the goal of long-term nicotine cessation

Circulating microRNAs as novel biomarkers for diabetes mellitus.

Diabetes mellitus is characterized by insulin secretion from pancreatic β cells that is insufficient to maintain blood glucose homeostasis. Autoimmune destruction of β cells results in type 1 diabetes mellitus, whereas conditions that reduce insulin sensitivity and negatively affect β-cell activities result in type 2 diabetes mellitus. Without proper management, patients with diabetes mellitus develop serious complications that reduce their quality of life and life expectancy. Biomarkers for early detection of the disease and identification of individuals at risk of developing complications would greatly improve the care of these patients. Small non-coding RNAs called microRNAs (miRNAs) control gene expression and participate in many physiopathological processes. Hundreds of miRNAs are actively or passively released in the circulation and can be used to evaluate health status and disease progression. Both type 1 diabetes mellitus and type 2 diabetes mellitus are associated with distinct modifications in the profile of miRNAs in the blood, which are sometimes detectable several years before the disease manifests. Moreover, circulating levels of certain miRNAs seem to be predictive of long-term complications. Technical and scientific obstacles still exist that need to be overcome, but circulating miRNAs might soon become part of the diagnostic arsenal to identify individuals at risk of developing diabetes mellitus and its devastating complications

DNA aneuploidy as a topographic malignant transformation pattern in a pleomorphic adenoma of long-term evolution: a case report

<p>Abstract</p> <p>Introduction</p> <p>We present a case of long-term evolution of a submandibular pleomorphic adenoma. There is little information about topographic malignant transformation patterns of pleomorphic adenomas.</p> <p>Case presentation</p> <p>We extensively analyze a giant submandibular mixed tumor of 25-year evolution in a 57-year-old Caucasian woman. Deoxyribonucleic acid ploidy was evaluated in different superficial and deep areas using flow cytometry analysis and correlated with pathological and immunohistochemical characteristics. Superficial areas exhibited a typical histological pleomorphic adenoma pattern and were deoxyribonucleic acid diploid. Deep samples showed deoxyribonucleic acid aneuploidy, atypical histological benign features and expression of markers involved at an early-stage of malignant transformation, such as tumor protein 53 and antigen Ki67.</p> <p>Conclusion</p> <p>These findings revealed that deep tumor compartments may be involved in the initial stages of malignant transformation. Deoxyribonucleic acid ploidy analysis may provide an additional diagnosis tool and indicate 'uncertain' areas that require careful study to avoid diagnostic errors. Larger studies are needed to confirm our results and to evaluate the usefulness of the technique.</p