Projected 21st-century changes in marine heterotrophic bacteria under climate change.

Marine heterotrophic Bacteria (or referred to as bacteria) play an important role in the ocean carbon cycle by utilizing, respiring, and remineralizing organic matter exported from the surface to deep ocean. Here, we investigate the responses of bacteria to climate change using a three-dimensional coupled ocean biogeochemical model with explicit bacterial dynamics as part of the Coupled Model Intercomparison Project Phase 6. First, we assess the credibility of the century-scale projections (2015-2099) of bacterial carbon stock and rates in the upper 100 m layer using skill scores and compilations of the measurements for the contemporary period (1988-2011). Second, we demonstrate that across different climate scenarios, the simulated bacterial biomass trends (2076-2099) are sensitive to the regional trends in temperature and organic carbon stocks. Bacterial carbon biomass declines by 5-10% globally, while it increases by 3-5% in the Southern Ocean where semi-labile dissolved organic carbon (DOC) stocks are relatively low and particle-attached bacteria dominate. While a full analysis of drivers underpinning the simulated changes in all bacterial stock and rates is not possible due to data constraints, we investigate the mechanisms of the changes in DOC uptake rates of free-living bacteria using the first-order Taylor decomposition. The results demonstrate that the increase in semi-labile DOC stocks drives the increase in DOC uptake rates in the Southern Ocean, while the increase in temperature drives the increase in DOC uptake rates in the northern high and low latitudes. Our study provides a systematic analysis of bacteria at global scale and a critical step toward a better understanding of how bacteria affect the functioning of the biological carbon pump and partitioning of organic carbon pools between surface and deep layers.

Psychiatric Boarding of Transgender and Gender Diverse Youth Awaiting Treatment.

With increased prevalence and duration of pediatric mental health boarding that disparately impacts transgender and gender diverse (TGD) youth, it is critical to consider disparities that TGD youth experience in accessing mental health care. Although mental health care for TGD youth has long been considered specialty care, frontline, primary medical, and mental health clinicians must be equipped to serve TGD patients' psychiatric needs. Inequities that TGD youth face require examination and intervention at multiple levels, including societal discrimination, lack of culturally responsive primary mental health care, and barriers to gender-affirming care in emergency departments and psychiatric inpatient units.

Lysyl-tRNA synthetase, a target for urgently needed M. tuberculosis drugs.

Tuberculosis is a major global cause of both mortality and financial burden mainly in low and middle-income countries. Given the significant and ongoing rise of drug-resistant strains of Mycobacterium tuberculosis within the clinical setting, there is an urgent need for the development of new, safe and effective treatments. Here the development of a drug-like series based on a fused dihydropyrrolidino-pyrimidine scaffold is described. The series has been developed against M. tuberculosis lysyl-tRNA synthetase (LysRS) and cellular studies support this mechanism of action. DDD02049209, the lead compound, is efficacious in mouse models of acute and chronic tuberculosis and has suitable physicochemical, pharmacokinetic properties and an in vitro safety profile that supports further development. Importantly, preliminary analysis using clinical resistant strains shows no pre-existing clinical resistance towards this scaffold.

Psychological Benefits of Purchasing Home Meal Replacement in the Context of Eco-Friendly TV Home Shopping Broadcast: The Moderating Role of Personal Norm.

This study observed the relationship between psychological benefits and the theory of planned behavior (TPB) in the context of an eco-friendly TV home shopping broadcasts. The theoretical framework was enhanced even further by examining the moderating role of personal norm on proenvironmental attitudes in the TV home shopping context. An online survey was conducted with Korean customers who had purchased home meal replacement (HMR) products from a TV home shopping broadcast within the past 6 months. A total of 305 samples were collected and used for the data analysis. All six of the hypotheses in the psychological benefits and TPB model were supported, meaning all constructs of psychological benefits, including warm glow, self-expressive benefits, and nature experiences, impacted TPB and behavioral intentions. Furthermore, personal norm had a moderating role in the relationship between warm glow and attitude. This research provides significant theoretical and managerial implications for the home shopping industry.

A Novel CO2-Based Insect Sampling Device and Associated Field Method Evaluated in a Strawberry Agroecosystem.

There is high demand for accurate insect sampling methods to inform integrated pest management strategies. Despite widespread application, existing sampling methods, such as portable aspirating and sweep netting, can result in overrepresentation of prominent pests, underrepresentation of natural enemies, and damage to plants. In this study, we test a novel device for insect sampling via anesthetization. Specifically, we test the effect of CO2 (application pressure and duration of exposure) on Lygus hesperus Knight (Hemiptera: Miridae) anesthetization in the laboratory and on insect community density in a strawberry agroecosystem. Carbon dioxide application proves an effective means of anesthetization compared to negative controls, and an increase in net CO2 exposure results in a decrease in time until L. hesperus anesthetization. Field results indicate the CO2 method collects more parasitoids and thrips than a portable aspirator, and at the 50 PSI application pressure and 15-s exposure, the CO2 method results in a comparable number of pests collected as the research standard, a portable aspirator with 8-s aspiration time. Benefits of the CO2 method include minimal plant damage, highly explicit spatial and temporal data, and scalability.

Candida albicans Elicits Pro-Inflammatory Differential Gene Expression in Intestinal Peyer's Patches.

The details of how gut-associated lymphoid tissues such as Peyer's patches (PPs) in the small intestine play a role in immune surveillance, microbial differentiation and the mucosal barrier protection in response to fungal organisms such as Candida albicans are still unclear. We particularly focus on PPs as they are the immune sensors and inductive sites of the gut that influence inflammation and tolerance. We have previously demonstrated that CD11c+ phagocytes that include dendritic cells and macrophages are located in the sub-epithelial dome within PPs sample C. albicans. To gain insight on how specific cells within PPs sense and respond to the sampling of fungi, we gavaged naïve mice with C. albicans strains ATCC 18804 and SC5314 as well as Saccharomyces cerevisiae. We measured the differential gene expression of sorted CD45+ B220+ B-cells, CD3+ T-cells and CD11c+ DCs within the first 24 h post-gavage using nanostring nCounter® technology. The results reveal that at 24 h, PP phagocytes were the cell type that displayed differential gene expression. These phagocytes were able to sample C. albicans and discriminate between strains. In particular, strain ATCC 18804 upregulated fungal-specific pro-inflammatory genes pertaining to innate and adaptive immune responses. Interestingly, PP CD11c+ phagocytes also differentially expressed genes in response to C. albicans that were important in the protection of the mucosal barrier. These results highlight that the mucosal barrier not only responds to C. albicans, but also aids in the protection of the host.

Assessment of environmental and occupational exposure while working with multidrug resistant (MDR) fungus Candida auris in an animal facility.

In less than a decade since its identification in 2009, the emerging fungal pathogen Candida auris has become a major public health threat due to its multidrug resistant (MDR) phenotype, high transmissibility, and high mortality. Unlike other Candida species, C. auris has acquired high levels of resistance to an already limited arsenal of antifungals. As an emerging pathogen, there are currently a limited number of documented murine models of C. auris infection. These animal models use inoculums as high as 107-108 cells per mouse, and the environmental and occupational exposure of working with these models has not been clearly defined. Using real-time quantitative polymerase chain reaction (PCR) and culture, we monitored the animal holding room as well as the procedure room for up to 6 months while working with an intravenous model of C. auris infection. This study determined that shedding of the organism is dose-dependent, as detectable levels of C. auris were detected in the cage bedding when mice were infected with 107 and 108 cells, but not with doses of 105 and 106 cells. Autoclaving bedding in closed micro-isolator cages was found to be an effective way to minimize exposure for animal caretakers. We found that tissue necropsies of infected mice were also an important source of potential source exposure to C. auris. To mitigate these potential exposures, we implemented a rigorous "buddy system" workflow and a disinfection protocol that uses 10% bleach followed by 70% ethanol and can be used in any animal facility when using small animal models of C. auris infection.

Polydopamine Coating of Glucan Particles Increases Uptake into Peyer's Patches.

Glucan particles (GPs) are hollow, porous 3-4 µm microspheres derived from the cell walls of Baker's yeast (Saccharomyces cerevisiae). The ß-1,3-D glucan outer shell of GPs provides for receptor-mediated uptake by phagocytic cells expressing ß-glucan receptors. GPs have been used for efficient encapsulation of different types of payloads (DNA, siRNA, proteins, antigens, small molecules), and these payloads have been delivered in vivo by a variety of routes including oral delivery. It is known that GPs are transported across the intestinal epithelium by Peyer's patch M-cells and accumulate in a subset of CD11c+Langerin-positive dendritic cells (DC) in the subepithelial dome (SED). An increase in GP uptake in the intestinal epithelium is needed to improve our efforts to develop GPs for oral delivery of therapeutics and vaccines. In this Article, we report that polydopamine coating of GPs (PDA-GPs) increases transepithelial uptake. Synthesis of PDA-GPs was optimized to allow for encapsulation of payloads inside the hollow cavity of GPs. PDA-GPs and GP controls were orally administered to mice, and PDA-GPs showed a 42% increased uptake in SED phagocytes. PDA-GP uptake by SED phagocytes in control and M-cell-depleted mice demonstrated both M-cell-dependent and -independent mechanisms. In future studies, we will evaluate PDA-GPs for oral vaccine delivery and the use of PDA-functional groups for secondary surface derivatization to generate particles with ligands targeting other intestinal epithelium cell-surface receptors.