Crh receptor priming in the bed nucleus of the stria terminalis induces tph2 gene expression in the dorsomedial dorsal raphe nucleus and chronic anxiety

The bed nucleus of the stria terminalis (BNST) is a nodal structure in neural circuits controlling anxiety-related defensive behavioral responses. It contains neurons expressing the stress- and anxiety-related neuropeptide corticotropin-releasing hormone (Crh) as well as Crh receptors. Repeated daily subthreshold activation of Crh receptors in the BNST is known to induce a chronic anxiety-like state, but how this affects neurotransmitter-relevant gene expression in target regions of the BNST is still unclear. Since the BNST projects heavily to the dorsal raphe nucleus (DR), the main source of brain serotonin, we here tested the hypothesis that such repeated, anxiety-inducing activation of Crh receptors in the BNST alters the expression of serotonergic genes in the DR, including tph2, the gene encoding the rate-limiting enzyme for brain serotonin synthesis, and slc6a4, the gene encoding the serotonin transporter (SERT). For 5 days, adult male Wistar rats received daily, bilateral, intra-BNST microinjections of vehicle (1% bovine serum albumin in 0.9% saline, n = 11) or behaviorally subthreshold doses of urocortin 1 (Ucn1, n = 11), a potent Crh receptor agonist. Priming with Ucn1 increased tph2 mRNA expression selectively within the anxiety-related dorsal part of the DR (DRD) and decreased social interaction (SI) time, a measure of anxiety-related defensive behavioral responses in rodents. Decreased social interaction was strongly correlated with increased tph2 mRNA expression in the DRD. Together with previous studies, our data are consistent with the hypothesis that Crh-mediated control of the BNST/DRD-serotonergic system plays a key role in the development of chronic anxiety states, possibly also contributing to stress-induced relapses in drug abuse and addiction behavior

Unveiling the collaborative effect at the cucurbit[8]urilMoS2 hybrid interface for electrochemical melatonin determination

Host-guest interactions are of paramount importance in supramolecular chemistry and in a wide range of applications. Particularly well known is the ability of cucurbit[n]urils (CB[n]) to selectively host small molecules. We show that the charge transfer and complexation capabilities of CB[n] are retained on the surface of 2D transition metal dichalcogenides (TMDs), allowing the development of efficient electrochemical sensing platforms. We unveil the mechanisms of host-guest recognition between the MoS2- CB[8] hybrid interface and melatonin (MLT), an important molecular regulator of vital constants in vertebrates. We find that CB[8] on MoS2 organizes the receptor portals perpendicularly to the surface, facilitating MLT complexation. This advantageous adsorption geometry is specific to TMDs and favours MLT electro-oxidation, as opposed to other 2D platforms like graphene, where one receptor portal is closed. This study rationalises the cooperative interaction in 2D hybrid systems to improve the efficiency and selectivity of electrochemical sensing platform

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion

Abstract: The B.1.617.2 (Delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha)1. In vitro, B.1.617.2 is sixfold less sensitive to serum neutralizing antibodies from recovered individuals, and eightfold less sensitive to vaccine-elicited antibodies, compared with wild-type Wuhan-1 bearing D614G. Serum neutralizing titres against B.1.617.2 were lower in ChAdOx1 vaccinees than in BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies to the receptor-binding domain and the amino-terminal domain. B.1.617.2 demonstrated higher replication efficiency than B.1.1.7 in both airway organoid and human airway epithelial systems, associated with B.1.617.2 spike being in a predominantly cleaved state compared with B.1.1.7 spike. The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralizing antibody, compared with that of wild-type spike. We also observed that B.1.617.2 had higher replication and spike-mediated entry than B.1.617.1, potentially explaining the B.1.617.2 dominance. In an analysis of more than 130 SARS-CoV-2-infected health care workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx1 vaccine effectiveness against B.1.617.2 relative to non-B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune-evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era

Augmented Reality Supported Learning Process for Operators

Abstract Intro: Conventional training methods are intended to teach and offer the most human way of teaching but is it the most effective and can another method improve or eliminate nonvalue adding activities. This master thesis tackles the difference between traditional training versus AR supported training, studying different aspects of training to see the advantages and disadvantages of the methods. The research questions were the following:  RQ1: Is the learning process improved with or without AR supported technology?   RQ2: What are the benefits of AR use in industry?  RQ3: Will the investment of AR implementation in the learning process pay off?  Method: To answer the research questions, a case study at a case company was conducted. The case study consisted of working with two companies, an external company for a theoretical answer based on experiences and an experimental study at the internal case company. In parallel to this case study a literature review was done to answer the research questions.  Theory and Literature Review: Literature for the frame of reference was gathered to support the thesis and give the perspectives of the investigated area. The literature review sought to find answers to the research questions and the search was systematically formed to focus on data gathering to answer the questions.  Analyses: The findings from this research shows that AR supported training is beneficial and has the potential to eliminate nonvalue adding activities. AR has many capabilities and research shows that AR in general has positive impact.  Conclusion: AR-applied training has both advantages and disadvantages, but the potential of improvements is high. It is difficult to conclude if it is economical to invest in AR, with the advances the technology holds on to now since the outcome can depend on several factors from different parameters. However, AR does contribute to more effective learning and further benefits within the applied area. It has been proven to reduce the error rate and thus may increase the quality of the product.

Augmented Reality Supported Learning Process for Operators

Abstract Intro: Conventional training methods are intended to teach and offer the most human way of teaching but is it the most effective and can another method improve or eliminate nonvalue adding activities. This master thesis tackles the difference between traditional training versus AR supported training, studying different aspects of training to see the advantages and disadvantages of the methods. The research questions were the following:  RQ1: Is the learning process improved with or without AR supported technology?   RQ2: What are the benefits of AR use in industry?  RQ3: Will the investment of AR implementation in the learning process pay off?  Method: To answer the research questions, a case study at a case company was conducted. The case study consisted of working with two companies, an external company for a theoretical answer based on experiences and an experimental study at the internal case company. In parallel to this case study a literature review was done to answer the research questions.  Theory and Literature Review: Literature for the frame of reference was gathered to support the thesis and give the perspectives of the investigated area. The literature review sought to find answers to the research questions and the search was systematically formed to focus on data gathering to answer the questions.  Analyses: The findings from this research shows that AR supported training is beneficial and has the potential to eliminate nonvalue adding activities. AR has many capabilities and research shows that AR in general has positive impact.  Conclusion: AR-applied training has both advantages and disadvantages, but the potential of improvements is high. It is difficult to conclude if it is economical to invest in AR, with the advances the technology holds on to now since the outcome can depend on several factors from different parameters. However, AR does contribute to more effective learning and further benefits within the applied area. It has been proven to reduce the error rate and thus may increase the quality of the product.

Inter-pregnancy interval and pregnancy outcomes among women with delayed childbearing: protocol for a systematic review

Background: Women in high resource nations are increasingly delaying childbearing until their thirties. Delayed childbearing poses challenges for the spacing of a woman’s pregnancies. Inter-pregnancy intervals <12 months are associated with risk for adverse pregnancy outcome, yet increased maternal age at delivery is linked with increased risk. The optimal inter-pregnancy interval for older mothers is uncertain. This systematic review will aim to assess the relation between inter-pregnancy interval and perinatal and maternal health outcomes in women who delay childbearing to age 30 and older. Methods: We will search MEDLINE, CINAHL, and EMBASE databases for peer-reviewed articles on the effects of inter-pregnancy interval on perinatal and maternal health outcomes among women over 29 years at the time of first birth, in high-income countries. To assess the quality of studies, the Cochrane’s Collaboration tool for assessing risk of bias will be used for randomized controlled trials, and the Newcastle-Ottawa tool to assess quality of case control and cross-sectional studies. The quality of the findings on each outcome will be assessed across studies, using the GRADE approach. The decision to conduct meta-analyses will be based on the concordance in definitions used for inter-pregnancy intervals, age groups studied, or outcomes measured among selected studies. We will report odds ratios and/or relative risks and/or risk differences for different inter-pregnancy intervals and perinatal and maternal outcomes as well as pregnancy complications. Discussion: This systematic review will summarize existing data on the relation between inter-pregnancy interval and perinatal and maternal health outcomes among women who delay childbearing to age 30 and older. Findings will inform clinical best practices to assist mothers over age 30 to space their pregnancies appropriately. Systematic review registration Prospero CRD42015019057Medicine, Faculty ofNon UBCFamily Practice, Department ofMedical Genetics, Department ofObstetrics and Gynaecology, Department ofReviewedFacult