Corticosterone Potentiation of Cocaine-Induced Reinstatement of Conditioned Place Preference in Mice is Mediated by Blockade of the Organic Cation Transporter 3

The mechanisms by which stressful life events increase the risk of relapse in recovering cocaine addicts are not well understood. We previously reported that stress, via elevated corticosterone, potentiates cocaine-primed reinstatement of cocaine seeking following self-administration in rats and that this potentiation appears to involve corticosterone-induced blockade of dopamine clearance via the organic cation transporter 3 (OCT3). In the present study, we use a conditioned place preference/reinstatement paradigm in mice to directly test the hypothesis that corticosterone potentiates cocaine-primed reinstatement by blockade of OCT3. Consistent with our findings following self-administration in rats, pretreatment of male C57/BL6 mice with corticosterone (using a dose that reproduced stress-level plasma concentrations) potentiated cocaine-primed reinstatement of extinguished cocaine-induced conditioned place preference. Corticosterone failed to re-establish extinguished preference alone but produced a leftward shift in the dose–response curve for cocaine-primed reinstatement. A similar potentiating effect was observed upon pretreatment of mice with the non-glucocorticoid OCT3 blocker, normetanephrine. To determine the role of OCT3 blockade in these effects, we examined the abilities of corticosterone and normetanephrine to potentiate cocaine-primed reinstatement in OCT3-deficient and wild-type mice. Conditioned place preference, extinction and reinstatement of extinguished preference in response to low-dose cocaine administration did not differ between genotypes. However, corticosterone and normetanephrine failed to potentiate cocaine-primed reinstatement in OCT3-deficient mice. Together, these data provide the first direct evidence that the interaction of corticosterone with OCT3 mediates corticosterone effects on drug-seeking behavior and establish OCT3 function as an important determinant of susceptibility to cocaine use

Knee joint kinetics in response to multiple three-dimensional printed, customised foot orthoses for the treatment of medial compartment knee osteoarthritis

The knee adduction moment is consistently used as a surrogate measure of medial compartment loading. Foot orthoses are designed to reduce knee adduction moment via lateral wedging. The 'dose' of wedging required to optimally unload the affected compartment is unknown and variable between individuals. This study explores a personalised approach via three-dimensional printed foot orthotics to assess the biomechanical response when two design variables are altered: orthotic length and lateral wedging. Foot orthoses were created for 10 individuals with symptomatic medial knee osteoarthritis and 10 controls. Computer-aided design software was used to design four full and four three-quarter-length foot orthoses per participant each with lateral posting of 0° 'neutral', 5° rearfoot, 10° rearfoot and 5° forefoot/10° rearfoot. Three-dimensional printers were used to manufacture all foot orthoses. Three-dimensional gait analyses were performed and selected knee kinetics were analysed: first peak knee adduction moment, second peak knee adduction moment, first knee flexion moment and knee adduction moment impulse. Full-length foot orthoses provided greater reductions in first peak knee adduction moment (p = 0.038), second peak knee adduction moment (p = 0.018) and knee adduction moment impulse (p = 0.022) compared to three-quarter-length foot orthoses. Dose effect of lateral wedging was found for first peak knee adduction moment (p < 0.001), second peak knee adduction moment (p < 0.001) and knee adduction moment impulse (p < 0.001) indicating greater unloading for higher wedging angles. Significant interaction effects were found for foot orthosis length and participant group in second peak knee adduction moment (p = 0.028) and knee adduction moment impulse (p = 0.036). Significant interaction effects were found between orthotic length and wedging condition for second peak knee adduction moment (p = 0.002). No significant changes in first knee flexion moment were found. Individual heterogeneous responses to foot orthosis conditions were observed for first peak knee adduction moment, second peak knee adduction moment and knee adduction moment impulse. Biomechanical response is highly variable with personalised foot orthoses. Findings indicate that the tailoring of a personalised intervention could provide an additional benefit over standard interventions and that a three-dimensional printing approach to foot orthosis manufacturing is a viable alternative to the standard methods.Full Tex

Having a lot of a good thing: multiple important group memberships as a source of self-esteem.

Copyright: © 2015 Jetten et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedMembership in important social groups can promote a positive identity. We propose and test an identity resource model in which personal self-esteem is boosted by membership in additional important social groups. Belonging to multiple important group memberships predicts personal self-esteem in children (Study 1a), older adults (Study 1b), and former residents of a homeless shelter (Study 1c). Study 2 shows that the effects of multiple important group memberships on personal self-esteem are not reducible to number of interpersonal ties. Studies 3a and 3b provide longitudinal evidence that multiple important group memberships predict personal self-esteem over time. Studies 4 and 5 show that collective self-esteem mediates this effect, suggesting that membership in multiple important groups boosts personal self-esteem because people take pride in, and derive meaning from, important group memberships. Discussion focuses on when and why important group memberships act as a social resource that fuels personal self-esteem.This study was supported by 1. Australian Research Council Future Fellowship (FT110100238) awarded to Jolanda Jetten (see http://www.arc.gov.au) 2. Australian Research Council Linkage Grant (LP110200437) to Jolanda Jetten and Genevieve Dingle (see http://www.arc.gov.au) 3. support from the Canadian Institute for Advanced Research Social Interactions, Identity and Well-Being Program to Nyla Branscombe, S. Alexander Haslam, and Catherine Haslam (see http://www.cifar.ca)

The freshwater Sponge Ephydatia Fluviatilis harbours diverse pseudomonas species (Gammaproteobacteria, Pseudomonadales) with broad-spectrum antimicrobial activity

Bacteria are believed to play an important role in the fitness and biochemistry of sponges (Porifera). Pseudomonas species (Gammaproteobacteria, Pseudomonadales) are capable of colonizing a broad range of eukaryotic hosts, but knowledge of their diversity and function in freshwater invertebrates is rudimentary. We assessed the diversity, structure and antimicrobial activities of Pseudomonas spp. in the freshwater sponge Ephydatia fluviatilis. Polymerase Chain Reaction - Denaturing Gradient Gel Electrophoresis (PCR-DGGE) fingerprints of the global regulator gene gacA revealed distinct structures between sponge-associated and free-living Pseudomonas communities, unveiling previously unsuspected diversity of these assemblages in freshwater. Community structures varied across E. fluviatilis specimens, yet specific gacA phylotypes could be detected by PCR-DGGE in almost all sponge individuals sampled over two consecutive years. By means of whole-genome fingerprinting, 39 distinct genotypes were found within 90 fluorescent Pseudomonas isolates retrieved from E. fluviatilis. High frequency of in vitro antibacterial (49%), antiprotozoan (35%) and anti-oomycetal (32%) activities was found among these isolates, contrasting less-pronounced basidiomycetal (17%) and ascomycetal (8%) antagonism. Culture extracts of highly predation-resistant isolates rapidly caused complete immobility or lysis of cells of the protozoan Colpoda steinii. Isolates tentatively identified as P. jessenii, P. protegens and P. oryzihabitans showed conspicuous inhibitory traits and correspondence with dominant sponge-associated phylotypes registered by cultivation-independent analysis. Our findings suggest that E. fluviatilis hosts both transient and persistent Pseudomonas symbionts displaying antimicrobial activities of potential ecological and biotechnological value.European Regional Development Fund (ERDF) through the COMPETE (Operational Competitiveness Programme); national funds through FCT (Foundation for Science and Technology) [PEst-C/MAR/LA0015/2011]; FCT-funded project [PTDC/BIA-MIC/3865/2012]; Federation of European Microbiological Societies (FEMS)info:eu-repo/semantics/publishedVersio

First report on dung beetles in intra-Amazonian savannahs in Roraima, Brazil

This is the first study to address the dung beetle (Coleoptera: Scarabaeidae: Scarabaeinae) diversity in intra-Amazonian savannahs in the state of Roraima, Brazil. Our aim was to survey the dung beetle fauna associated with these savannahs (regionally called 'lavrado'), since little is known about the dung beetles from this environment. We conducted three field samples using pitfall traps baited with human dung in savannah areas near the city of Boa Vista during the rainy seasons of 1996, 1997, and 2008. We collected 383 individuals from ten species, wherein six have no previous record in intra-Amazonian savannahs. The most abundant species were Ontherus appendiculatus (Mannerheim, 1829), Canthidium aff. humerale (Germar, 1813), Dichotomius nisus (Olivier, 1789), and Pseudocanthon aff. xanthurus (Blanchard, 1846). We believe that knowing the dung beetles diversity associated with the intra-Amazonian savannahs is ideal for understanding the occurrence and distribution of these organisms in a highly threatened environment, it thus being the first step towards conservation strategy development

HPV infection and p53 and p16 expression in esophageal cancer: are they prognostic factors?

Background: Esophageal squamous cell carcinoma (ESCC) is a highly lethal malignant tumor. Currently, Human papillomavirus (HPV) is suggested as a potential risk factor for esophageal cancer (EC) in addition to the classic risk factors, alcohol and tobacco, but this hypothesis still remains contradictory. We sought to investigate wether HPV and well-known biomarkers (p16 and p53) and patient-related factors that may have impact on survival of ESCC. Methods: We conducted a prospective cohort study. By using multiplex PCR, we determined the prevalence of high risk HPV in ESCC, and evaluated the immunohistochemical expression of p16 and p53, molecular markers related to esophageal carcinogenesis in order to verify the potential influence of these variables in patients's survival. Survival rates were estimated using Kaplan-Meier methods. A multivariate confirmatory model was performed using Cox proportional hazards regression. Results: Twelve (13.8%) of 87 patients were HPV-DNA positive. Positive reactions of p16 and p53 were 10.7% and 68.6%, respectively. Kaplan-Meier analysis indicated that men (p = 0.025) had poor specific-cancer survival and a shorter progression-free survival (p = 0.050) as compared to women; III or IV clinical stage (p < 0.019) had poor specific-cancer survival and a shorter progression-free survival (p < 0.001) compared to I and II clinical stage; not submitted to surgery (< 0.001) and not submitted to chemoradiotherapy (p = 0.039) had a poor specific-cancer survival, as well. The multivariate analysis showed that HPV, p16 and p53 status are not predictive parameters of progression-free and specific-cancer survival. Conclusion: HPV infection and p53 and p16 expression are not prognostic factors in ESCC.CNPq Universal for providing supplies to the largest study, of which this study is a part of, entitled “The role of human papillomavirus (HPV) as the etiologic agent of esophageal cancer. A cross-sectional study, case-control and longitudinal at Barretos Cancer Hospital”; (Grant number 482666/2012–9 to ALF); INCT HPV [Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) [Grant number 08/57889–1 to LLV]; Conselho Nacional de Desenvolvimento Científico e Tencnológico (CNPq) (Grant number 573799/ 2008–3 to LLV)].info:eu-repo/semantics/publishedVersio

Translational models for vascular cognitive impairment: a review including larger species.

BACKGROUND: Disease models are useful for prospective studies of pathology, identification of molecular and cellular mechanisms, pre-clinical testing of interventions, and validation of clinical biomarkers. Here, we review animal models relevant to vascular cognitive impairment (VCI). A synopsis of each model was initially presented by expert practitioners. Synopses were refined by the authors, and subsequently by the scientific committee of a recent conference (International Conference on Vascular Dementia 2015). Only peer-reviewed sources were cited. METHODS: We included models that mimic VCI-related brain lesions (white matter hypoperfusion injury, focal ischaemia, cerebral amyloid angiopathy) or reproduce VCI risk factors (old age, hypertension, hyperhomocysteinemia, high-salt/high-fat diet) or reproduce genetic causes of VCI (CADASIL-causing Notch3 mutations). CONCLUSIONS: We concluded that (1) translational models may reflect a VCI-relevant pathological process, while not fully replicating a human disease spectrum; (2) rodent models of VCI are limited by paucity of white matter; and (3) further translational models, and improved cognitive testing instruments, are required

Oestrogen receptor-α variant mRNA expression in primary human breast tumours and matched lymph node metastases

We have shown previously that the relative expression of a truncated oestrogen receptor-α variant mRNA (ER clone 4) is significantly increased in axillary node-positive primary breast tumours compared with node-negative tumours. In this study, we have examined the relative expression of clone 4-truncated, exon 5-deleted and exon 7-deleted oestrogen receptor-α variant mRNAs in 15 primary breast tumour samples and in synchronous axillary lymph node metastases. Overall, there were no significant differences between the primary tumours and the matched metastases in the relative expression of these three specific variant mRNAs. Furthermore, the pattern of all deleted oestrogen receptor-α variant mRNAs appeared conserved between any primary and its matched secondary tumour. © 1999 Cancer Research Campaig

Charged-particle distributions at low transverse momentum in √s=13 13 TeV pp interactions measured with the ATLAS detector at the LHC

Measurements of distributions of charged particles produced in proton–proton collisions with a centre-of-mass energy of 13 TeV are presented. The data were recorded by the ATLAS detector at the LHC and correspond to an integrated luminosity of 151 μb −1 μb−1 . The particles are required to have a transverse momentum greater than 100 MeV and an absolute pseudorapidity less than 2.5. The charged-particle multiplicity, its dependence on transverse momentum and pseudorapidity and the dependence of the mean transverse momentum on multiplicity are measured in events containing at least two charged particles satisfying the above kinematic criteria. The results are corrected for detector effects and compared to the predictions from several Monte Carlo event generators