We’re Here, You Just Don’t Know How to Reach Us: Conducting Research with Citizens on the Socio-Economic Margins

In this paper, methodological challenges that emerged when conducting research with socially and economically disadvantaged young adults in a semi-rural community are examined. Recruitment and retention issues related to ethics protocols, trust, and economic disadvantage are addressed. Strategies governing bodies can employ to support research with difficult to reach populations are suggested

Youth Speaks Up: Perceived Communication Changes Experienced by Grade 6 Participants in a Personal Development Program

A nine-month program entitled Youth Speaks Up is delivered annually to grade 6 students from Sydney, Nova Scotia. One goal of the program is to provide an opportunity for the development of positive communication skills in participants. The purpose of this project was to determine if students participating in the program perceived changes in their communication ability and comfort level as a result of participation in the program. Qualitative focus groups were conducted, and responses suggest that many participants experienced positive changes in their communication comfort levels in public and interpersonal communication contexts, and specifically in their ability and willingness to express their ideas. Participants believed factors such as consistent practice and interaction with new people influenced the changes. Students’ recommendations for program development are also presented.À chaque année, les élèves de la 6e année à Sydney, en Nouvelle-Écosse, participent à un programme d’une durée de neuf mois intitulé Youth Speaks Up (La parole aux jeunes). Le programme vise, entre autres, le développement d’aptitudes en communication positives chez les participants. L’objectif de cette étude était de déterminer si les participants croyaient que le programme avait entraîné des changements dans leurs aptitudes en communication et leur sentiment de bien-être. Les conclusions tirées à partir de sessions qualitatives avec des groupes de discussion indiquent que plusieurs participants constataient des changements positifs dans le sentiment de bien-être qu’ils ressentaient dans des contextes de communication interpersonnelle et en public, plus précisément dans leur habileté et leur volonté d’exprimer leurs idées. Les participants étaient d’avis que ces changements étaient en partie attribuables à des facteurs tels la pratique régulière et l’interaction avec de nouvelles personnes. Nous présentons également les recommandations qu’ont faites les élèves pour le développement du programme

Estrogen-Astrocyte interactions: Implications for neuroprotection

BACKGROUND: Recent work has suggested that the ovarian steroid 17β-estradiol, at physiological concentrations, may exert protective effects in neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and acute ischemic stroke. While physiological concentrations of estrogen have consistently been shown to be protective in vivo, direct protection upon purified neurons is controversial, with many investigators unable to show a direct protection in highly purified primary neuronal cultures. These findings suggest that while direct protection may occur in some instances, an alternative or parallel pathway for protection may exist which could involve another cell type in the brain. PRESENTATION OF THE HYPOTHESIS: A hypothetical indirect protective mechanism is proposed whereby physiological levels of estrogen stimulate the release of astrocyte-derived neuroprotective factors, which aid in the protection of neurons from cell death. This hypothesis is attractive as it provides a potential mechanism for protection of estrogen receptor (ER)-negative neurons through an astrocyte intermediate. It is envisioned that the indirect pathway could act in concert with the direct pathway to achieve a more widespread global protection of both ER+ and ER- neurons. TESTING THE HYPOTHESIS: We hypothesize that targeted deletion of estrogen receptors in astrocytes will significantly attenuate the neuroprotective effects of estrogen. IMPLICATIONS OF THE HYPOTHESIS: If true, the hypothesis would significantly advance our understanding of endocrine-glia-neuron interactions. It may also help explain, at least in part, the reported beneficial effects of estrogen in neurodegenerative disorders. Finally, it also sets the stage for potential extension of the hypothetical mechanism to other important estrogen actions in the brain such as neurotropism, neurosecretion, and synaptic plasticity

Patch-Clamp Analysis of Voltage-Activated and Chemically Activated Currents in the Vomeronasal Organ Of Sternotherus Odoratus (Stinkpot/Musk Turtle)

The electrophysiological basis of chemical communication in the specialized olfactory division of the vomeronasal (VN) organ is poorly understood. In total, 198 patch-clamp recordings were made from 42 animals (Sternotherus odoratus, the stinkpot/musk turtle) to study the electrically and chemically activated properties of VN neurons. The introduction of tetramethylrhodamine-conjugated dextran into the VN orifice permitted good visualization of the vomeronasal neural epithelium prior to dissociating it into single neurons. Basic electrical properties of the neurons were measured (resting potential, -54.5 +/- 2.7 mV, N=11; input resistance, 6.7 +/- 1.4 G Omega, N=25; capacitance, 4.2 +/- 0.3 pF, N=22; means +/- S.E.M.). The voltage-gated K(+) current inactivation rate was significantly slower in VN neurons from males than in those from females, and K(+) currents in males were less sensitive (greater K(i)) to tetraethylammonium. Vomeronasal neurons were held at a holding potential of -60 mV and tested for their response to five natural chemicals, female urine, male urine, female musk, male musk and catfish extract. Of the 90 VN neurons tested, 33 (34 %) responded to at least one of the five compounds. The peak amplitude of chemically evoked currents ranged from 4 to 180 pA, with two-thirds of responses less than 25 pA. Urine-evoked currents were of either polarity, whereas musk and catfish extract always elicited only inward currents. Urine applied to neurons harvested from female animals evoked currents that were 2-3 times larger than those elicited from male neurons. Musk-evoked inward currents were three times the magnitude of urine- or catfish-extract-evoked inward currents. The calculated breadth of responsiveness for neurons presented with this array of five chemicals indicated that the mean response spectrum of the VN neurons is narrow (H metric 0.11). This patch-clamp study indicates that VN neurons exhibit sexual dimorphism in function and specificity in response to complex natural chemicals.io

Subtelomeric plasticity contributes to gene family expansion in the human parasitic flatworm Schistosoma mansoni

Background: The genomic region that lies between the telomere and chromosome body, termed the subtelomere, is heterochromatic, repeat-rich, and frequently undergoes rearrangement. Within this region, large-scale structural changes enable gene diversification, and, as such, large multicopy gene families are often found at the subtelomere. In some parasites, genes associated with proliferation, invasion, and survival are often found in these regions, where they benefit from the subtelomere's highly plastic, rapidly changing nature. The increasing availability of complete (or near complete) parasite genomes provides an opportunity to investigate these typically poorly defined and overlooked genomic regions and potentially reveal relevant gene families necessary for the parasite's lifestyle. Results: Using the latest chromosome-scale genome assembly and hallmark repeat richness observed at chromosome termini, we have identified and characterised the subtelomeres of Schistosoma mansoni, a metazoan parasitic flatworm that infects over 250 million people worldwide. Approximately 12% of the S. mansoni genome is classified as subtelomeric, and, in line with other organisms, we find these regions to be gene-poor but rich in transposable elements. We find that S. mansoni subtelomeres have undergone extensive interchromosomal recombination and that these sites disproportionately contribute to the 2.3% of the genome derived from segmental duplications. This recombination has led to the expansion of subtelomeric gene clusters containing 103 genes, including the immunomodulatory annexins and other gene families with unknown roles. The largest of these is a 49-copy plexin domain-containing protein cluster, exclusively expressed in the tegument-the tissue located at the host-parasite physical interface-of intramolluscan life stages. Conclusions: We propose that subtelomeric regions act as a genomic playground for trial-and-error of gene duplication and subsequent divergence. Owing to the importance of subtelomeric genes in other parasites, gene families implicated in this subtelomeric expansion within S. mansoni warrant further characterisation for a potential role in parasitism

Senolytic therapy is neuroprotective and improves functional outcome long-term after traumatic brain injury in mice

IntroductionChronic neuroinflammation can exist for months to years following traumatic brain injury (TBI), although the underlying mechanisms remain poorly understood.MethodsIn the current study, we used a controlled cortical impact mouse model of TBI to examine whether proinflammatory senescent cells are present in the brain long-term (months) after TBI and whether ablation of these cells via administration of senolytic drugs can improve long-term functional outcome after TBI. The results revealed that astrocytes and microglia in the cerebral cortex, hippocampus, corpus callosum and lateral posterior thalamus colocalized the senescent cell markers, p16Ink4a or p21Cip1/Waf1 at 5 weeks post injury (5wpi) and 4 months post injury (4mpi) in a controlled cortical impact (CCI) model. Intermittent administration of the senolytic drugs, dasatinib and quercetin (D + Q) beginning 1-month after TBI for 13 weeks significantly ablated p16Ink4a-positive- and p21Cip1/Waf1-positive-cells in the brain of TBI animals, and significantly reduced expression of the major senescence-associated secretory phenotype (SASP) pro-inflammatory factors, interleukin-1β and interleukin-6. Senolytic treatment also significantly attenuated neurodegeneration and enhanced neuron number at 18 weeks after TBI in the ipsilateral cortex, hippocampus, and lateral posterior thalamus. Behavioral testing at 18 weeks after TBI further revealed that senolytic therapy significantly rescued defects in spatial reference memory and recognition memory, as well as depression-like behavior in TBI mice.DiscussionTaken as a whole, these findings indicate there is robust and widespread induction of senescent cells in the brain long-term after TBI, and that senolytic drug treatment begun 1-month after TBI can efficiently ablate the senescent cells, reduce expression of proinflammatory SASP factors, reduce neurodegeneration, and rescue defects in reference memory, recognition memory, and depressive behavior

How to cope with "noise" social dilemmas: The benefits of communication

Interactions in social life may be seriously affected by negative noise, whereby actual or perceived behavior is less cooperative than was intended (e.g., arriving late due to an unforeseen traffic jam). The present research examines whether negative noise exerts detrimental effects on impressions and cooperation and whether such effects could be reduced by communication. Consistent with hypotheses, Study 1 revealed that negative noise exerts detrimental effects on both impressions of partners' benign intent and cooperation and that these detrimental effects could be effectively reduced by communication about noise. Study 2 replicated both findings but only for individuals with low trust. Mediation analysis revealed that impressions of benign intent and prosocial interaction goals underlie the positive effects of communication on cooperation