37 research outputs found

    Hippocampus, Amygdala and Basal Ganglia Based Navigation Control

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    In this paper we present a novel robot navigation system aimed at testing hypotheses about the roles of key brain areas in foraging behavior of rats. The key components of the control network are: 1. a Hippocampus inspired module for spatial localization based on associations between sensory inputs and places; 2. an Amygdala inspired module for the association of values with places and sensory stimuli; 3. a Basal Ganglia inspired module for the selection of actions based on the evaluated sensory inputs. By implementing this Hippocampus-Amygdala-Basal Ganglia based control network with a simulated rat embodiment we intend to test not only our understanding of the individual brain areas but especially the interaction between them. Understanding the neural circuits that allows rats to efficiently forage for food will also help to improve the ability of robots to autonomously evaluate and select navigation targets

    Whole-genome sequencing reveals host factors underlying critical COVID-19

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    Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

    Effects of cage-cleaning frequency on laboratory rat reproduction, cannibalism, and welfare.

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    Regular cage-cleaning is important for health, but for breeding rats it disrupts the nest and removes olfactory signals important for parental care. To investigate how different cage-cleaning frequencies affect breeding rats' health and welfare, we monitored reproductive output, pup mortality, pup sex-ratios, parental chromodacryorrhoea and in-cage ammonia levels for rats in a commercial breeding facility. Cages were cleaned twice-weekly, once-weekly or every two weeks (18 cages/group), replicated in two buildings, for the entire 36-week reproductive period. Frequent cage-cleaning had no clear benefits or major negative effects, showing no significant reductions in ammonia levels, or affects on health or overall pup mortality. However, frequent cage-cleaning slightly but significantly increased cannibalistic behaviour. This was because: (i) vulnerable 0-2 day old pups were more likely to be exposed to a cage-cleaning event in the more frequent cage-cleaning regimes, physically disturbing them, and disrupting the nest and scent marks; and (ii) in the twice-weekly and weekly-cleaned groups, pups under 2 days old at their first cage cleaning were more likely to be cannibalised. Possible mechanisms behind these effects are discussed, including that cleaning might induce premature births, or stress the parents through noise or olfactory and physical disturbance. Finally, the cage cleaning frequency producing most pups differed between the two buildings – an interactive effect corroborating previous findings that same-strain rodents’ phenotypes can differ with environment. Overall, we suggest that for breeding rats, cage-cleaning regimes should minimise noise, dissemination of unfamiliar conspecific odours, and physical disturbance during very late pregnancy and the first days following birth

    Rats seem indifferent between their own scent-marked homecages and clean cages.

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    Previous large-scale, long-term studies suggest that rat welfare is little affected by cage-cleaning frequency. Here, we investigate this further using a preference test: arguably a more sensitive welfare indicator than those used previously. Nine pairs of rats were each housed in two interconnected cages of differing cleanliness. One cage was cleaned every 3–4 days, while the other remained uncleaned for 18 days. All rats were handled at each cage-cleaning (regardless of which cage they chose) so that this aspect of the cleaning routine remained consistent. Furthermore, ammonia build-up was negligible. We could thus see whether rats prefer their own scent-marks over clean bedding, without the confounds of differential handling or the potential harm induced by ammonia. Dwelling, resting, feeding, drinking, defecation, and ammonia concentrations were compared between the two cages. None were found to differ significantly between the cages over the course of the experiment. Power tests and confidence intervals support the conclusion that the rats had no meaningful preference for self-scented, familiar areas over clean areas. A weak preference cannot be ruled out, due to the small sample and the space limitations within laboratory cages. Also, the lack of ammonia means that the threshold at which rats would start to avoid soiled areas that do generate this compound remains undetermined. Nevertheless, together with previous studies showing no clear effects of cage-cleaning frequency on rat welfare, these choice tests indicate that it is unlikely that olfactory disruption during cage-cleaning is an important welfare concern for stable non-breeding groups of rats.# 2008 Elsevier B.V. All rights reserved

    Long-term effects of cage-cleaning frequency and bedding type on laboratory rat health, welfare, and handleability: a cross-laboratory study.

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    Cage-cleaning is necessary for a hygienic environment, but since rats communicate using scent, they might suffer if their cages are cleaned too frequently. Male rats (Sprague–Dawley and Wistar) were kept for five months across four animal units. Their cages were cleaned twice-weekly, weekly, or every two weeks, and contained either aspen woodchips or absorbent paper bedding. Aggression, injuries and general health, weight gain, chromodacryorrhoea (a stress-related Harderian gland secretion), handleability, and lung pathology were monitored, as was in-cage ammonia. Cleaning frequency had no clear impact on rat welfare, although frequent cleaning decreased ammonia concentrations and handleability, and non-aggressive skirmishing was highest in weekly cleaned rats. Surprisingly, bedding type did not affect ammonia, but all ammonia readings were unexpectedly low. However, rats kept on aspen had greater sneezing rates and lung pathology than those on paper bedding, but also had higher body weights. The results raise concerns about aspen bedding, which is relatively inert compared with other wood beddings, but nevertheless more harmful than paper. Animal unit significantly affected eight of the 11 variables tested, having interactive effects on five of them. The study also demonstrates the interactive effects of different animal units, casting doubt on the feasibility of standardization. We explored multiple variables of interest, so all findings require confirmation through further work. Nevertheless, cage-cleaning rates seem to affect socially housed male rats little, while bedding type has important effects on rat health

    Psychometric properties of the Trauma and Distress Scale, TADS, in an adult community sample in Finland

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    Background: There is increasing evidence that a history of childhood abuse and neglect is not uncommon among individuals who experience mental disorder and that childhood trauma experiences are associated with adult psychopathology. Although several interview and self-report instruments for retrospective trauma assessment have been developed, many focus on sexual abuse (SexAb) rather than on multiple types of trauma or adversity. Methods: Within the European Prediction of Psychosis Study, the Trauma and Distress Scale (TADS) was developed as a new self-report assessment of multiple types of childhood trauma and distressing experiences. The TADS includes 43 items and, following previous measures including the Childhood Trauma Questionnaire, focuses on five core domains: emotional neglect (EmoNeg), emotional abuse (EmoAb), physical neglect (PhyNeg), physical abuse (PhyAb), and SexAb.This study explores the psychometric properties of the TADS (internal consistency and concurrent validity) in 692 participants drawn from the general population who completed a mailed questionnaire, including the TADS, a depression self-report and questions on help-seeking for mental health problems. Inter-method reliability was examined in a random sample of 100 responders who were reassessed in telephone interviews. Results: After minor revisions of PhyNeg and PhyAb, internal consistencies were good for TADS totals and the domain raw score sums. Intra-class coefficients for TADS total score and the five revised core domains were all good to excellent when compared to the interviewed TADS as a gold standard. In the concurrent validity analyses, the total TADS and its all core domains were significantly associated with depression and help-seeking for mental problems as proxy measures for traumatisation. In addition, robust cutoffs for the total TADS and its domains were calculated. Conclusions: Our results suggest the TADS as a valid, reliable, and clinically useful instrument for assessing retrospectively reported childhood traumatisation
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