Developmental function of PirB restricts adult ocular dominance plasticity

Early visual input induces changes in functional connectivity which can either lead to the stabilisation of appropriate synaptic connections or the elimination of inappropriate ones in the visual system. Monocular deprivation (MD) is a widely used paradigm to study changes in ocular dominance (OD) in the binocular visual cortex of higher mammals. Closure of one eye for several days leads to a shift in OD which re ects changes in the response kinetics of the deprived and the non-deprived eye. The molecular machinery which underlies this type of experience-dependent plasticity is still elusive. A recent genetic screen in the lab of Carla Shatz has identied that the family of MHCI receptors are expressed in the developing visual cortex and regulated upon neuronal activity. They hypothesized that MHC receptors might be required for consolidation of longlasting changes in synaptic strength. To investigate the role of MHCI in OD plasticity, I used a transgenic mouse lacking the MHCI receptor paired-immunoglobulin-like receptor B (PirB). To determine OD in the mouse visual cortex, I used optical imaging of intrinsic signals which measures the activity of neuronal populations elicited from either eye stimulation. Beforehand I investigated OD plasticity in adult mice (C57Bl6) which is still questioned to be present after MD. I conrmed earlier ndings which have shown robust MD induced changes of either eye in the visual cortex of adult mice. In the next chapter I explored eye specic kinetics during the critical period (postnatal days (P)19-32) in PirB KO mice. Closed eye depression occurred more rapidly and was stronger in KO mice in comparison to WT mice. I was also interested whether the mechanisms of OD plasticity in adult PirB KO (P90) mice diered from that juvenile PirB KO mice. Interestingly I observed a tendency for similar eye specic kinetics in adult PirB KO mice and in juvenile WT mice, which lead to the speculation that removal of PirB might reinduce juvenile like plasticity in adult mice. A recent study in the lab investigated the effect of prior experience and could show that OD plasticity in adult mice was enhanced due to an inital MD in juvenile mice and a subsequent MD of the same eye in adulthood. Would PirB play a role in this type of enhanced plasticity? Surprisingly I explored that OD plasticity in PirB KO mice is the same after a single or repeated exposure to MD, suggesting that the capacity for plasticity in these mice is near saturation. In the last chapter I addressed the question whether the representation of both eyes in the binocular visual cortex is dierent in PirB KO mice in comparison to WT mice. Therefore I showed stimuli in the central and peripheral visual field of adult non-deprived and deprived PirB KO mice. I found enhanced response strength in the open eye after peripheral visual eld stimulation in deprived PirB KO mice in contrast to WT mice. Overall I assessed stronger and more rapid functional plasticity in PirB KO mice during development and adulthood. Hence I postulate that PirB might act as a molecular brake limiting OD plasticity

Les conséquences du sida dans la vie des hémophiles et de leurs soignants familiaux au Québec : stress, réponse au stress et soutien social

Le présent article présente les résultats de l'échantillon québécois d'une enquête nationale sur les besoins de soutien des hémophiles atteints du sida ou du VIH. Portant aussi sur les besoins des soignants et des proches (endeuillés ou non) de ces personnes, cette enquête se fondait sur une problématique qui considère le soutien social comme un moyen de faire face au stress. Les participants ont signalé avoir éprouvé plus de stress à cause de l'absence de soutien ou d'un soutien négatif que par suite de la détérioration physique due à la maladie. La question de la confidentialité a été fréquemment soulevée. En général, les participants se sont déclarés satisfaits du soutien reçu, surtout de la part des membres de leurs familles.The following article focuses on the Québec portion of a national survey on the care needed by hemophiliacs with AIDS or having contracted the HIV virus. The survey was based on an approach that considers social support as a means to face stress. It also examined the needs of dispensers of care and relatives (whether mourning or not) of these persons. Participants revealed having experienced more stress because of an absence of support or simply negative support, than because of the physical deterioration caused by the disease. In addition, the question of confidentiality was often raised. In general, participants said they were satisfied with the support they had received, especially on the part of members of their family

Metabolic Engineering von Clostridium acetobutylicum: Steigerung der Butanolbildung durch homologe Genexpression

Eine Plasmid-vermittelte homologe Co-Expressionen der Chaperone GrpE und HtpG führten zu einer signifikant erhöhten Buntanolresistenz, jedoch nicht zu einer erhöhten Butanolproduktion in C. acetobutylicum. Zudem zeigten die untersuchten Expressionsstämme eine effizientere Adaption an sich wiederholende Butanolstress-Experimente. Eine plasmid-vermittelte homologe thlA-Expression - mit folgenden Aminosäuresubstitutionen: R133G, H156N und G222V - in C. acetobutylicum, führten zu einem Phänotypen mit erhöhter Butanolproduktion (vergleichend zu C. acetobutylicum ATCC 824)

Symptom burden and lived experiences of patients, caregivers and healthcare professionals on the management of malignant bowel obstruction: A qualitative systematic review

Background: Malignant bowel obstruction occurs in up to 50% of people with advanced ovarian and 15% of people with gastrointestinal cancers. Evaluation and comparison of interventions to manage symptoms are hampered by inconsistent evaluations of efficacy and lack of agreed core outcomes. The patient perspective is rarely incorporated. Aim: To synthesise the qualitative data regarding patient, caregiver and healthcare professionals’ views and experience of malignant bowel obstruction to inform the development of a core outcome set for the evaluation of malignant bowel obstruction. Design: A qualitative systematic review was conducted, with narrative synthesis. The review protocol was registered prospectively (https://www.crd.york.ac.uk/prospero, CRD42020176393). Data sources: MEDLINE, EMBASE, CINAHL, PsycINFO and Scopus databases were searched for studies published between 2010 and 2021. Reference lists were screened for further relevant publications, and citation tracking was performed. Results: Nine papers were included, reporting on seven studies which described the views and experiences of malignant bowel obstruction through the perspectives of 75 patients, 13 caregivers and 62 healthcare professionals. Themes across the papers included symptom burden, diverse experiences of interventions, impact on patient quality of life, implications and trajectory of malignant bowel obstruction, mixed experience of communication and the importance of realistic goals of care. Conclusion: Some of the most devastating sequelae of malignant bowel obstruction, such as pain and psychological distress, are not included routinely in its clinical or research evaluation. These data will contribute to a wider body of work to ensure the patient and caregiver perspective is recognised in the development of a core outcome set

The Arabidopsis class II sirtuin is a lysine deacetylase and interacts with mitochondrial energy metabolism

The posttranslational regulation of proteins by lysine (Lys) acetylation has recently emerged to occur not only on histones, but also on organellar proteins in plants and animals. In particular, the catalytic activities of metabolic enzymes have been shown to be regulated by Lys acetylation. The Arabidopsis (Arabidopsis thaliana) genome encodes two predicted sirtuin-type Lys deacetylases, of which only Silent Information Regulator2 homolog (SRT2) contains a predicted presequence for mitochondrial targeting. Here, we have investigated the function of SRT2 in Arabidopsis. We demonstrate that SRT2 functions as a Lys deacetylase in vitro and in vivo. We show that SRT2 resides predominantly at the inner mitochondrial membrane and interacts with a small number of protein complexes mainly involved in energy metabolism and metabolite transport. Several of these protein complexes, such as the ATP synthase and the ATP/ADP carriers, show an increase in Lys acetylation in srt2 loss-of-function mutants. The srt2 plants display no growth phenotype but rather a metabolic phenotype with altered levels in sugars, amino acids, and ADP contents. Furthermore, coupling of respiration to ATP synthesis is decreased in these lines, while the ADP uptake into mitochondria is significantly increased. Our results indicate that SRT2 is important in fine-tuning mitochondrial energy metabolism

Risk stratification in patients with acute chest pain using three high-sensitivity cardiac troponin assays

Aims Several high-sensitivity cardiac troponin (hs-cTn) assays have recently been developed. It is unknown which hs-cTn provides the most accurate prognostic information and to what extent early changes in hs-cTn predict mortality. Methods and results In a prospective, international multicentre study, cTn was simultaneously measured with three novel [high-sensitivity cardiac Troponin T (hs-cTnT), Roche Diagnostics; hs-cTnI, Beckman-Coulter; hs-cTnI, Siemens] and a conventional assay (cTnT, Roche Diagnostics) in a blinded fashion in 1117 unselected patients with acute chest pain. Patients were followed up 2 years regarding mortality. Eighty-two (7.3%) patients died during the follow-up. The 2-year prognostic accuracy of hs-cTn was most accurate for hs-cTnT [area under the receivers operating characteristic curve (AUC) 0.78 (95% CI: 0.73-0.83) and outperformed both hs-cTnI (Beckman-Coulter, 0.71 (95% CI: 0.65-0.77; P = 0.001 for comparison), hs-cTnI (Siemens) 0.70 (95% CI: 0.64-0.76; P < 0.001 for comparison)] and cTnT 0.67 (95% CI: 0.61-0.74; P < 0.001 for comparison). Absolute changes of hs-cTnT were more accurate than relative changes in predicting mortality, but inferior to presentation values of hs-cTnT. Combining changes of hs-cTnT within the first 6 h with their presentation values did not further improve prognostic accuracy. Similar results were obtained for both hs-cTnI assays regarding the incremental value of changes. Hs-cTn concentrations remained predictors of death in clinically challenging subgroups such as patients with pre-existing coronary artery disease, impaired renal function, and patients older than 75 years. Conclusion High-sensitivity cardiac Troponin T is more accurate than hs-cTnI in the prediction of long-term mortality. Changes of hs-cTn do not seem to further improve risk stratification beyond initial presentation value

The role of clathrin in post-golgi trafficking in toxoplasma gondii

Apicomplexan parasites are single eukaryotic cells with a highly polarised secretory system that contains unique secretory organelles (micronemes and rhoptries) that are required for host cell invasion. In contrast, the role of the endosomal system is poorly understood in these parasites. With many typical endocytic factors missing, we speculated that endocytosis depends exclusively on a clathrin-mediated mechanism. Intriguingly, in Toxoplasma gondii we were only able to observe the endogenous clathrin heavy chain 1 (CHC1) at the Golgi, but not at the parasite surface. For the functional characterisation of Toxoplasma gondii CHC1 we generated parasite mutants conditionally expressing the dominant negative clathrin Hub fragment and demonstrate that CHC1 is essential for vesicle formation at the trans-Golgi network. Consequently, the functional ablation of CHC1 results in Golgi aberrations, a block in the biogenesis of the unique secretory microneme and rhoptry organelles, and of the pellicle. However, we found no morphological evidence for clathrin mediating endocytosis in these parasites and speculate that they remodelled their vesicular trafficking system to adapt to an intracellular lifestyle

Priority strategies to improve gender equity in Canadian emergency medicine: proceedings from the CAEP 2021 Academic Symposium on leadership

Objectives: Gender inequities are deeply rooted in our society and have significant negative consequences. Female physicians experience numerous gender-related inequities (e.g., microaggressions, harassment, violence). These inequities have far-reaching consequences on health, well-being and career longevity and may result in the devaluing of various strengths that female emergency physicians bring to the table. This, in turn, has an impact on patient healthcare experience and outcomes. During the 2021 Canadian Association of Emergency Physicians (CAEP) Academic Symposium, a national collaborative sought to understand gender inequities in emergency medicine in Canada. Methods: We used a multistep stakeholder-engagement-based approach (harnessing both quantitative and qualitative methods) to identify and prioritize problems with gender equity in emergency medicine in Canada. Based on expert consultation and literature review, we developed recommendations to effect change for the higher priority problems. We then conducted a nationwide consultation with the Canadian emergency medicine community via online engagement and the CAEP Academic Symposium to ensure that these priority problems and solutions were appropriate for the Canadian context. Conclusion: Via the above process, 15 recommendations were developed to address five unique problem areas. There is a dearth of research in this important area and we hope this preliminary work will serve as a starting point to fuel further research. To facilitate these scholarly endeavors, we have appended additional documents identifying other key problems with gender equity in emergency medicine in Canada as well as proposed next steps for future research

Oceanic forcing of interannual and multidecadal climate variability in the southwestern Indian Ocean: evidence from a 160 year coral isotopic record (La Réunion, 55°E, 21°S)

We have developed a new 163-year bimonthly coral δ18O record from La Réunion (55°E, 21°S). Interannual variations in coral δ18O are coherent with the Southern Oscillation Index but not with regional sea surface temperature (SST). Correlations with the global SST field suggest more negative seawater δ18O (δ18Osw) during La Niña years. We propose that the signal results from changes in the strength of the South Equatorial Current and the Indonesian throughflow, which carry low salinity water. Multidecadal variations in coral δ18O are coherent with regional SST, but the sign is of opposite sense as expected from the coral δ18O-temperature relationship. This requires multidecadal changes in salinity large enough to overprint the SST contribution in the coral δ18O record. Our results suggest that multidecadal salinity variations result from modulations in the transport of the South Equatorial Current, which varies in response to the surface wind field and/or the Indonesian throughflow

Controlling Access to Suicide Means

Background: Restricting access to common means of suicide, such as firearms, toxic gas, pesticides and other, has been shown to be effective in reducing rates of death in suicide. In the present review we aimed to summarize the empirical and clinical literature on controlling the access to means of suicide. Methods: This review made use of both MEDLINE, ISI Web of Science and the Cochrane library databases, identifying all English articles with the keywords “suicide means”, “suicide method”, “suicide prediction” or “suicide prevention” and other relevant keywords. Results: A number of factors may influence an individual’s decision regarding method in a suicide act, but there is substantial support that easy access influences the choice of method. In many countries, restrictions of access to common means of suicide has lead to lower overall suicide rates, particularly regarding suicide by firearms in USA, detoxification of domestic and motor vehicle gas in England and other countries, toxic pesticides in rural areas, barriers at jumping sites and hanging, by introducing “safe rooms” in prisons and hospitals. Moreover, decline in prescription of barbiturates and tricyclic antidepressants (TCAs), as well as limitation of drugs pack size for paracetamol and salicylate has reduced suicides by overdose, while increased prescription of SSRIs seems to have lowered suicidal rates. Conclusions: Restriction to means of suicide may be particularly effective in contexts where the method is popular, highly lethal, widely available, and/or not easily substituted by other similar methods. However, since there is some risk of means substitution, restriction of access should be implemented in conjunction with other suicide prevention strategies