Assessing the Mental Wellbeing and Help-Seeking Behaviors of Pre-Veterinary Undergraduates at a Land-Grant Institution.

Recent research conducted within the veterinary profession has reported higher rates of depression and stress than the general US population. While this decline in mental wellbeing has been documented in Doctor of Veterinary Medicine (DVM) students and veterinary professionals, there is a lack of research on the mental wellbeing of the pre-veterinary population. This gap led the authors to conduct a survey in the fall of 2021 utilizing the DASS-21 and ATSPPH-sf inventories to assess the levels of depression, anxiety, stress, and help-seeking stigma in pre-veterinary students to better understand when the decline in veterinary mental wellbeing begins. A pre-test survey was completed by 233 pre-veterinary students in September, and an identical post-test survey was completed by 184 pre-veterinary students in November. From the pre- and post-test data, depression, anxiety, and stress scores increased as students advanced in academic status during their undergraduate degree. Juniors reported the highest averages of depression, anxiety, and stress compared to their peers. In the post-test, sophomores and juniors exhibited higher rates of depression than freshmen, and juniors and seniors exhibited higher rates of stress than freshmen. Current VMCAS applicants exhibited higher levels of stress than non-VMCAS applicants in the pre-test, and lower levels of stress in the post-test. In both the pre-test and post-test data, respondents averaged a neutral attitude toward help-seeking. Based on these results, a decline in pre-veterinary mental wellbeing occurs as students' progress in their undergraduate career and should be further studied to assess its impact on Doctor of Veterinary Medicine and veterinary professional wellbeing.

HIV induced nitric oxide and lipid peroxidation, influences neonatal birthweight in a South African population.

HIV has been implicated in adverse birth outcomes, due to increased oxidative stress and inflammation. In addition, HIV has been reported to increase nitric oxide levels. Therefore the combined exposures to HIV and traffic-related air pollution, within South Durban, South Africa (SA), may lead to adverse birth outcomes. However, the exact mechanism is still unknown; this study aimed to identify a potential mechanism. First, the influence of HIV on oxidative and nitrosative stress markers in pregnant women was assessed. Secondly, the effect of these stress makers and exposure to oxides of nitrogen (NOx) on neonatal birthweight (BW) was evaluated. Finally, the effect HIV and traffic-related pollution exposure has on the oxidative and endoplasmic profile and epigenetic regulation of Nrf2-Keap1 pathway by miR-144 and miR-28 in pregnant women was determined. Women, in their third trimester with singleton pregnancies, who were HIV+ and HIV-, were recruited from Durban, SA. Biomarker levels of serum nitrites/nitrates (NO) and malondialdehyde (MDA) were analysed and mRNA expression levels of oxidative and endoplasmic stress response genes were assessed. Land regression modelling was performed to determine NOx exposure levels. HIV exposure during pregnancy was associated with increased NO levels. NO was shown to reduce neonatal BW. NO and MDA was found to reciprocally increase each other, with HIV differentially influencing MDA's effect on BW. HIV down-regulated miR-144 which was negatively associated with Nrf2, suggesting a potential mechanism for HIV associated chronic oxidative stress. This study proposes that NO plays a key role in neonatal BW reduction in response to HIV and traffic-related air pollution.

OGG1 Ser326Cys polymorphism, HIV, obesity and air pollution exposure influences adverse birth outcome susceptibility, within South African Women.

The global HIV and obesity epidemics are major public health concerns; particularly as both are associated with increased risk of adverse birth outcomes. Despite extensive research, their combined effect, in terms of birth outcomes, has not been investigated. A single-nucleotide polymorphism (SNP) within 8-oxoguanine glycosylase 1 (OGG1) (Ser326Cys) has been suggested to affect body mass indices and therefore could predispose South African (SA) women to adverse effects of obesity. This study investigated the associations of OGG1 Ser326Cys SNP in relation to HIV and obesity on the susceptibility of low-birthweight (LBW) and pre-term birth (PTB) in SA women exposed to ambient air-pollution living in Durban. In our study population, the OGG1 SNP was associated with HIV and obesity. Wild-type (CC)-carrying patients had increased susceptibility for HIV-associated LBW and PTB. Co-morbid HIV and obese patients delivered neonates with decreased birthweights. Living within the heavily-polluted south-Durban and carrying the CC-genotype increased the risk for PTB within our study population.

The Cytokinin Oxidase/Dehydrogenase CKX1 Is a Membrane-Bound Protein Requiring Homooligomerization in the Endoplasmic Reticulum for Its Cellular Activity.

Degradation of the plant hormone cytokinin is controlled by cytokinin oxidase/dehydrogenase (CKX) enzymes. The molecular and cellular behavior of these proteins is still largely unknown. In this study, we show that CKX1 is a type II single-pass membrane protein that localizes predominantly to the endoplasmic reticulum (ER) in Arabidopsis (Arabidopsis thaliana). This indicates that this CKX isoform is a bona fide ER protein directly controlling the cytokinin, which triggers the signaling from the ER. By using various approaches, we demonstrate that CKX1 forms homodimers and homooligomers in vivo. The amino-terminal part of CKX1 was necessary and sufficient for the protein oligomerization as well as for targeting and retention in the ER. Moreover, we show that protein-protein interaction is largely facilitated by transmembrane helices and depends on a functional GxxxG-like interaction motif. Importantly, mutations rendering CKX1 monomeric interfere with its steady-state localization in the ER and cause a loss of the CKX1 biological activity by increasing its ER-associated degradation. Therefore, our study provides evidence that oligomerization is a crucial parameter regulating CKX1 biological activity and the cytokinin concentration in the ER. The work also lends strong support for the cytokinin signaling from the ER and for the functional relevance of the cytokinin pool in this compartment.

The Effect of Nitric Oxide Pollution on Oxidative Stress in Pregnant Women Living in Durban, South Africa.

The purpose of the study was to evaluate the effect nitric oxide (NO x ) pollution had on maternal serum 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-OHdG) levels and neonatal outcomes in pregnant women living in Durban, South Africa (SA). Women, in their third trimester with singleton pregnancies, were recruited from the heavily industrialised south (n = 225) and less industrialised north (n = 152). Biomarker levels of serum 8-OHdG concentrations were analysed, and the women were genotyped for glutathione-S-transferases pi 1 (GSTP1) and glutathione-S-transferases mu 1 (GSTM1) polymorphisms. The level of NO x pollution in the two regions was determined by using land use regression modelling. The serum 8-OHdG was shown to correlate significantly with NO x levels; this relationship was strengthened in the south (p < 0.05). This relationship was still observed after adjusting for maternal characteristics. GSTP1 was significantly associated with the south region, where the variant (AG+GG) genotype was associated with increased 8-OHdG levels as a result of NO x exposure (p < 0.05). GSTM1 null genotype was associated with a positive correlation between NO x and 8-OHdG levels (p < 0.05). NO x levels were found marginally to reduce gestational age (p < 0.05) with mothers carrying male neonates. Variant GSTP1 and living in the north were factors that contributed to gestational age reduction (p < 0.05). Our study demonstrated that NO x exposure resulted in increased 8-OHdG levels in pregnant women living in Durban, SA, which led to gestational age reduction. The GSTP1 variant increased susceptibility of individuals to harmful effects of NO x .

Combination of Cα-H Hydrogen Bonds and van der Waals Packing Modulates the Stability of GxxxG-Mediated Dimers in Membranes.

The GxxxG motif is frequently found at the dimerization interface of a transmembrane structural motif called GASright, which is characterized by a short interhelical distance and a right-handed crossing angle between the helices. In GASright dimers, such as glycophorin A (GpA), BNIP3, and members of the ErbB family, the backbones of the helices are in contact, and they invariably display networks of 4 to 8 weak hydrogen bonds between Cα-H carbon donors and carbonyl acceptors on opposing helices (Cα-H···O═C hydrogen bonds). These networks of weak hydrogen bonds at the helix-helix interface are presumably stabilizing, but their energetic contribution to dimerization has yet to be determined experimentally. Here, we present a computational and experimental structure-based analysis of GASright dimers of different predicted stabilities, which show that a combination of van der Waals packing and Cα-H hydrogen bonding predicts the experimental trend of dimerization propensities. This finding provides experimental support for the hypothesis that the networks of Cα-H hydrogen bonds are major contributors to the free energy of association of GxxxG-mediated dimers. The structural comparison between groups of GASright dimers of different stabilities reveals distinct sequence as well as conformational preferences. Stability correlates with shorter interhelical distances, narrower crossing angles, better packing, and the formation of larger networks of Cα-H hydrogen bonds. The identification of these structural rules provides insight on how nature could modulate stability in GASright and finely tune dimerization to support biological function.

Polar localization of Escherichia coli chemoreceptors requires an intact Tol-Pal complex.

Subcellular biomolecular localization is critical for the metabolic and structural properties of the cell. The functional implications of the spatiotemporal distribution of protein complexes during the bacterial cell cycle have long been acknowledged; however, the molecular mechanisms for generating and maintaining their dynamic localization in bacteria are not completely understood. Here we demonstrate that the trans-envelope Tol-Pal complex, a widely conserved component of the cell envelope of Gram-negative bacteria, is required to maintain the polar positioning of chemoreceptor clusters in Escherichia coli. Localization of the chemoreceptors was independent of phospholipid composition of the membrane and the curvature of the cell wall. Instead, our data indicate that chemoreceptors interact with components of the Tol-Pal complex and that this interaction is required to polarly localize chemoreceptor clusters. We found that disruption of the Tol-Pal complex perturbs the polar localization of chemoreceptors, alters cell motility, and affects chemotaxis. We propose that the E. coli Tol-Pal complex restricts mobility of the chemoreceptor clusters at the cell poles and may be involved in regulatory mechanisms that co-ordinate cell division and segregation of the chemosensory machinery.