67 research outputs found

    Future Needs for Tribo-Corrosion Research and Testing

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    Tribo-corrosion is an emerging interdisciplinary subject that spans from basic research on the behavior of surfaces in mechanical contact in chemically active surroundings to the test methods needed to quantify its effects, and from the selection of materials for bio-implants to the minimization of surface degradation and wastage in advanced energy conversion systems. Such a diverse field brings with it many challenges in understanding, testing, standardization, and application to engineering practice. This paper summarizes a panel discussion and participant survey held at the Third International Symposium on Tribo-Corrosion in Atlanta, Georgia, USA, in April 2012. It reflects a sense of agreement on many of the key scientific challenges in the field and the fact that tribo-corrosion is still in its infancy in terms of broad industry recognition, education, and the ability of those who conduct tribo-corrosion research to connect their laboratory results and theories to applications. Some sub-fields, notably the bio-tribo-corrosion of medical implants, have witnessed active international research efforts, but the engineering community in many other important areas of technology may not yet be aware of the field despite numerous tribo-corrosion problems that may exist within their purview

    Early-life stress leads to sex-dependent changes in pubertal timing in rats that are reversed by a probiotic formulation.

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    Puberty marks the beginning of a period of dramatic physical, hormonal, and social change. This instability has made adolescence infamous as a time of "storm and stress" and it is well-established that stress during adolescence can be particularly damaging. However, prior stress may also shape the adolescent experience. In the present series of experiments, we observed sex-specific effects of early-life maternal separation stress on the timing of puberty onset in the rat. Specifically, stressed females exhibited earlier pubertal onset compared to standard-reared females, whereas stressed males matured later than their standard-reared counterparts. Further, we demonstrated that a probiotic treatment restores the normative timing of puberty onset in rodents of both sexes. These results are in keeping with previous findings that probiotics reverse stress-induced changes in learned fear behaviors and stress hormone levels, highlighting the remarkable and wide-ranging restorative effects of probiotics in the context of early-life stress

    A brief guide to studying fear in developing rodents: important considerations and common pitfalls.

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    Development is a time of rapid change that sets the pathway to adult functioning across all aspects of physical and mental health. Developmental studies can therefore offer insight into the unique needs of individuals at different stages of normal development as well as the etiology of various disease states. The aim of this overview is to provide an introduction to the practical implementation of developmental studies in rats and mice, with an emphasis on the study of learned fear. We first discuss how developmental factors may influence experimental outcomes for any study. This is followed by a discussion of methodological issues to consider when conducting studies of developing rodents, highlighting examples from the literature on learned fear. Throughout, we offer some recommendations to guide researchers on best practice in developmental studies

    Acute early-life stress results in premature emergence of adult-like fear retention and extinction relapse in infant rats

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    Recent studies have shown that chronic early life stress results in precocious expression of the adult-like phenotype of fear retention and inhibition. However, it is unknown whether the experience of acute early trauma has the same effects as exposure to chronic early stress. In the present study, a 24-hr period of maternal deprivation on postnatal day (P) 9 was used as an acute early life stressor. In infancy (P16-17), maternally deprived and standard-reared rats were conditioned to fear a noise paired with shock. In Experiments 1 and 2, fear to the noise was then extinguished before rats were tested for context-mediated fear renewal or stress-induced fear reinstatement. In Experiments 3a and 3b, conditioned rats were tested for fear retention 1, 7, or 14 days after training. Whereas standard-reared infants exhibited relapse-resistant extinction and infantile amnesia (i.e., behaviors typical of their age), maternally deprived infants exhibited the renewal and reinstatement effects (i.e., relapse-prone extinction) and showed good retention of fear over the 7- and 14-day intervals (i.e., infantile amnesia was reduced). In other words, similar to rats exposed to chronic early life stress, rats exposed to acute early stress expressed an adult-like profile of fear retention and inhibition during infancy. These findings suggest that similar mechanisms might be involved in the effects of acute and chronic stress on emotional development, and may have implications for our understanding and treatment of emotional disorders associated with early adversity

    The effects of a probiotic formulation (Lactobacillus rhamnosus and L. helveticus) on developmental trajectories of emotional learning in stressed infant rats.

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    Recently, scientific interest in the brain-gut axis has grown dramatically, particularly with respect to the link between gastrointestinal and psychiatric dysfunction. However, the role of gut function in early emotional dysregulation is yet to be examined, despite the prevalence and treatment resistance of early-onset psychiatric disorders. The present studies utilized a developmental rodent model of early-life stress (ELS) to explore this gap. Rats were exposed to maternal separation (MS) on postnatal days 2-14. Throughout MS, dams received either vehicle or a probiotic formulation (previously shown to reduce gastrointestinal dysfunction) in their drinking water. Replicating past research, untreated MS infants exhibited an adult-like profile of long-lasting fear memories and fear relapse following extinction. In contrast, probiotic-exposed MS infants exhibited age-appropriate infantile amnesia and resistance to relapse. These effects were not mediated by changes in pups' or dams' anxiety at the time of training, nor by maternal responsiveness. Overall, probiotics acted as an effective and non-invasive treatment to restore normal developmental trajectories of emotion-related behaviors in infant rats exposed to ELS. These results provide promising initial evidence for this novel approach to reduce the risk of mental health problems in vulnerable individuals. Future studies are needed to test this treatment in humans exposed to ELS and to elucidate mechanisms for the observed behavioral changes

    Treating generational stress: effect of paternal stress on development of memory and extinction in offspring is reversed by probiotic treatment

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    Early-life adversity is a potent risk factor for mental-health disorders in exposed individuals, and effects of adversity are exhibited across generations. Such adversities are also associated with poor gastrointestinal outcomes. In addition, emerging evidence suggests that microbiota-gut-brain interactions may mediate the effects of early-life stress on psychological dysfunction. In the present study, we administered an early-life stressor (i.e., maternal separation) to infant male rats, and we investigated the effects of this stressor on conditioned aversive reactions in the rats' subsequent infant male offspring. We demonstrated, for the first time, longer-lasting aversive associations and greater relapse after extinction in the offspring (F1 generation) of rats exposed to maternal separation (F0 generation), compared with the offspring of rats not exposed to maternal separation. These generational effects were reversed by probiotic supplementation, which was effective as both an active treatment when administered to infant F1 rats and as a prophylactic when administered to F0 fathers before conception (i.e., in fathers' infancy). These findings have high clinical relevance in the identification of early-emerging putative risk phenotypes across generations and of potential therapies to ameliorate such generational effects

    The lasting impact of early-life adversity on individuals and their descendants: potential mechanisms and hope for intervention

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    The adverse effects of early-life stress are pervasive, with well-established mental and physical health consequences for exposed individuals. The impact of early adverse experiences is also highly persistent, with documented increases in risk for mental illness across the life span that are accompanied by stable alterations in neural function and hormonal responses to stress. Here, we review some of these 'stress phenotypes', with a focus on intermediary factors that may signal risk for long-term mental health outcomes, such as altered development of the fear regulation system. Intriguingly, recent research suggests that such stress phenotypes may persist even beyond the life span of the individuals, with consequences for their offspring and grand-offspring. Phenotypic characteristics may be transmitted to future generations via either the matriline or the patriline, a phenomenon that has been demonstrated in both human and animal studies. In this review, we highlight behavioral and epigenetic factors that may contribute to this multigenerational transmission and discuss the potential of various treatment approaches that may halt the cycle of stress phenotypes

    Search for the standard model Higgs boson at LEP

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    Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

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    Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio
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