Mammalian cells in culture actively export specific microRNAs

The discovery of microRNAs (miRNAs) as a new class of regulators of gene expression has triggered an explosion of research, but has left many unanswered questions about how this regulation works and how it is integrated with other regulatory mechanisms. A number of miRNAs have been found to be present in blood plasma and other body fluids of humans and mice in surprisingly high concentrations. This observation was unexpected in two respects: first, the fact that these molecules are present at all outside the cell at significant concentrations; and second, that these molecules appear to be stable outside of the cell. In light of this it has been suggested that the biological function of miRNAs may also extend outside of the cell and mediate cell-cell communication^[1-5]^. Such a system would be expected to export specific miRNAs from cells in response to specific biological stimuli. We report here that after serum deprivation several human cell lines tested do export a spectrum of miRNAs into the culture medium. The export response is substantial and prompt. The exported miRNAs are found both within and outside of microvesicles and exosomes. We have identified some candidate protein components of this system outside the cell, and found one exported protein that plays a role in protecting miRNA from degradation. Our results point to a hitherto unrecognized and uncharacterized miRNA trafficking system in mammalian cells that may involve cell-cell communication

Fork rotation and DNA precatenation are restricted during DNA replication to prevent chromosomal instability

Faithful genome duplication and inheritance require the complete resolution of all intertwines within the parental DNA duplex. This is achieved by topoisomerase action ahead of the replication fork or by fork rotation and subsequent resolution of the DNA precatenation formed. Although fork rotation predominates at replication termination, in vitro studies have suggested that it also occurs frequently during elongation. However, the factors that influence fork rotation and how rotation and precatenation may influence other replication-associated processes are unknown. Here we analyze the causes and consequences of fork rotation in budding yeast. We find that fork rotation and precatenation preferentially occur in contexts that inhibit topoisomerase action ahead of the fork, including stable protein–DNA fragile sites and termination. However, generally, fork rotation and precatenation are actively inhibited by Timeless/Tof1 and Tipin/Csm3. In the absence of Tof1/Timeless, excessive fork rotation and precatenation cause extensive DNA damage following DNA replication. With Tof1, damage related to precatenation is focused on the fragile protein–DNA sites where fork rotation is induced. We conclude that although fork rotation and precatenation facilitate unwinding in hard-to-replicate contexts, they intrinsically disrupt normal chromosome duplication and are therefore restricted by Timeless/Tipin

Who plays with whom: farrowing environment influences isolation of foster piglets in play

Cross fostering piglets is a common management practise in the pig industry to manage large and heterogeneous litters, whereby piglets are moved from their biological litter to be reared by another sow. At present research has focused on immediate survival consequences and time of cross fostering, with little attention given to positive aspects of welfare such as social affiliations and the potential for positive interactions for these piglets such as play behaviour. The focus of our study was purely observational to record behaviour of piglets reared in either impoverished (farrowing crates) or enriched neonatal environments (PigSAFE pens) where fostering was practised as part of normal husbandry routines to promote piglet survival. We employed social network analysis to understand more about the behaviour of foster piglets in these environments and their acceptance into their new litter. In line with previous work, piglets exposed to enriched neonatal farrowing pens demonstrated more play behaviour than piglets reared in farrowing crates. We showed that pen piglets received and initiated more play invitations (higher degree centrality) than piglets in crates. We also found effects of cross fostering irrespective of neonatal environment. Non-foster piglets received and initiated more play behaviours (higher degree centrality) 2–3 weeks post-farrowing compared to piglets fostered into the litter and as such, fostered piglets remained isolated from play for the first few weeks of life. However, our data suggests this may be mitigated by neonatal environment; foster piglets reared in pens were better connected (betweenness centrality) within their foster litter than those fostered in crates. Our findings highlight the importance of the neonatal environment and its potential influence on the isolation of cross-fostered piglets and suggest that rearing in enriched neonatal environments may help mitigate against social isolation in early life of cross-fostered piglets, having obvious immediate, and long-term consequences for piglet welfare and behaviour. We also highlight the importance and application of methodologies such as social network analysis, for gaining more insight and understanding about the sociality of animal behaviour and its potential for measuring indicators of positive welfare, thus highlighting its application for veterinary science and animal behaviour and welfare research

Une critique littéraire et psychanalytique des protagonistes féminins de l'enfance à la ménopause dans les oeuvres d'Ananda Devi

1 online resource (iv, 51 leaves)Includes abstract in English and French.Includes bibliographical references (leaf 51).This thesis examines three novels written by award-winning Francophone Mauritian author Ananda Devi. Through her works, Devi enables her readers to get a closer look at the three main stages of life experienced by her female protagonists: childhood, the innocent discovery of a woman’s sexuality; adolescence and young adulthood, which should be the peak of a woman’s sexuality; and menopause, the perceived decrease in a woman’s sexuality. It is evident that the stereotypes are not always the case, and these important stages in a woman’s life may not always go as planned, or as what is considered as socially acceptable. However, all things the women in these novels experience have an important psychoanalytic value, which contribute directly to the overall significance and literary value.Résumé: Cette thèse examine trois romans écrits par l’écrivaine francophone mauricienne primée à plusieurs reprises, Ananda Devi. Toutes les trois étapes de la vie des femmes sont présentées à travers ses oeuvres: l’enfance, ce qui est une découverte innocente de la sexualité; l’adolescence, ou la jeunesse, ce qui est le sommet de la sexualité; et la ménopause, ce qui est la mort de la sexualité. Ce qui est évident dans ces livres c’est que les stéréotypes de ces étapes de vie ne sont pas toujours la vérité, ni ce qui est considéré comme acceptable par la société. Néanmoins, tout ce que les femmes éprouvent dans ces romans apporte une valeur psychanalytique qui contribue directement à la valeur littéraire et à la signifiance

Training and cross-educational effects of a six-week isokinetic eccentric program on dorsiflexion range of motion, plantarflexor strength, and muscle-tendon mechanics dataset

This dataset in the excel spreadsheet depicts the raw data for all variables collected before and after a six-week eccentric resistance training programme. Data for each variable (column A) are separated into 3 groups: 1) the trained (right) lower-limb of the experimental group (columns B [pre-training] and C [post-training]), 2) the untrained (left) contralateral lower-limb of the experimental group (columns D [pre-training] and E [post-training]), and 3) the left lower-limb of the control group (columns F [pre-training] and G [post-training]). The equipment and software used to measure and collect the data for the variables listed in the spreadsheet are listed in the word document with all abbreviations reported in full

Military personnel with chronic symptoms following blast traumatic brain injury have differential expression of neuronal recovery and epidermal growth factor receptor genes

Objective: Approximately one-quarter of military personnel who deployed to combat stations sustained one or more blast-related, closed-head injuries. Blast injuries result from the detonation of an explosive device. The mechanisms associated with blast exposure that give rise to traumatic brain injury (TBI), and place military personnel at high risk for chronic symptoms of post-concussive disorder (PCD), post-traumatic stress disorder (PTSD), and depression are not elucidated. Methods: To investigate the mechanisms of persistent blast-related symptoms, we examined expression profiles of transcripts across the genome to determine the role of gene activity in chronic symptoms following blast-TBI. Active duty military personnel with (1) a medical record of a blast-TBI that occurred during deployment (n = 19) were compared to control participants without TBI (n = 17). Controls were matched to cases on demographic factors including age, gender, and race, and also in diagnoses of sleep disturbance, and symptoms of PTSD and depression. Due to the high number of PCD symptoms in the TBI+ group, we did not match on this variable. Using expression profiles of transcripts in microarray platform in peripheral samples of whole blood, significantly differentially expressed gene lists were generated. Statistical threshold is based on criteria of 1.5 magnitude fold-change (up or down) and p-values with multiple test correction (false discovery rate \u3c0.05). Results: There were 34 transcripts in 29 genes that were differentially regulated in blast-TBI participants compared to controls. Up-regulated genes included epithelial cell transforming sequence and zinc finger proteins, which are necessary for astrocyte differentiation following injury. Tensin-1, which has been implicated in neuronal recovery in pre-clinical TBI models, was down-regulated in blast-TBI participants. Protein ubiquitination genes, such as epidermal growth factor receptor, were also down-regulated and identified as the central regulators in the gene network determined by interaction pathway analysis. Conclusion: In this study, we identified a gene-expression pathway of delayed neuronal recovery in military personnel a blast-TBI and chronic symptoms. Future work is needed to determine if therapeutic agents that regulate these pathways may provide novel treatments for chronic blast-TBI-related symptoms

Response of neural reward regions to food cues in autism spectrum disorders

BACKGROUND: One hypothesis for the social deficits that characterize autism spectrum disorders (ASD) is diminished neural reward response to social interaction and attachment. Prior research using established monetary reward paradigms as a test of non-social reward to compare with social reward may involve confounds in the ability of individuals with ASD to utilize symbolic representation of money and the abstraction required to interpret monetary gains. Thus, a useful addition to our understanding of neural reward circuitry in ASD includes a characterization of the neural response to primary rewards. METHOD: We asked 17 children with ASD and 18 children without ASD to abstain from eating for at least four hours before an MRI scan in which they viewed images of high-calorie foods. We assessed the neural reward network for increases in the blood oxygenation level dependent (BOLD) signal in response to the food images RESULTS: We found very similar patterns of increased BOLD signal to these images in the two groups; both groups showed increased BOLD signal in the bilateral amygdala, as well as in the nucleus accumbens, orbitofrontal cortex, and insula. Direct group comparisons revealed that the ASD group showed a stronger response to food cues in bilateral insula along the anterior-posterior gradient and in the anterior cingulate cortex than the control group, whereas there were no neural reward regions that showed higher activation for controls than for ASD. CONCLUSION: These results suggest that neural response to primary rewards is not diminished but in fact shows an aberrant enhancement in children with ASD