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The recent discovery that dairy cattle can be infected by highly pathogenic avian influenza (HPAI) virus of the H5N1 subtype (2,2), in combination with the virus's propensity to replicate in [...]

In March 2024, the US Department of Agriculture’s Animal and Plant Health Inspection Service reported detection of highly pathogenic avian influenza (HPAI) A(H5N1) virus in dairy cattle in the United States for the first time. One factor that determines susceptibility to HPAI H5N1 infection is the presence of specific virus receptors on host cells; however, little is known about the distribution of the sialic acid (SA) receptors in dairy cattle, particularly in mammary glands. We compared the distribution of SA receptors in the respiratory tract and mammary gland of dairy cattle naturally infected with HPAI H5N1. The respiratory and mammary glands of HPAI H5N1–infected dairy cattle are rich in SA, particularly avian influenza virus–specific SA α2,3-gal. Mammary gland tissues co-stained with sialic acids and influenza A virus nucleoprotein showed predominant co-localization with the virus and SA α2,3-gal. HPAI H5N1 exhibited epitheliotropism within the mammary gland, and we observed rare immunolabeling within macrophages.

Abstract Androgen deprivation therapy (ADT) targeting androgen/androgen receptor (AR)- signaling pathways is the main therapy for advanced prostate cancer (PCa). However, ADT eventually fails in most patients who consequently develop castration-resistant prostate cancer (CRPC). While more potent AR antagonists and blockers for androgen synthesis were developed to improve clinical outcomes, they also show to induce more diverse CRPC phenotypes. Specifically, the AR- and neuroendocrine-null PCa, DNPC, occurs in abiraterone and enzalutamide-treated patients. Here, we uncover that current ADT induces aberrant HGF/MET signaling activation that further elevates Wnt/β-catenin signaling in human DNPC samples. Co-activation of HGF/MET and Wnt/β-catenin axes in mouse prostates induces DNPC-like lesions. Single-cell RNA sequencing analyses identify increased expression and activity of XPO1 and ribosomal proteins in mouse DNPC-like cells. Elevated expression of XPO1 and ribosomal proteins is also identified in clinical DNPC specimens. Inhibition of XPO1 and ribosomal pathways represses DNPC growth in both in vivo and ex vivo conditions, evidencing future therapeutic targets.

Obesity, a complex condition that involves genetic, environmental, and behavioral factors, is a non-infectious pandemic that affects over 650 million adults worldwide with a rapidly growing prevalence. A major contributor is the consumption of high-fat diets, an increasingly common feature of modern diets. Maternal obesity results in an increased risk of offspring developing obesity and related health problems; however, the impact of maternal diet on the adipose tissue composition of offspring has not been evaluated. Here, we designed a generational diet-induced obesity study in female C57BL/6 mice that included maternal cohorts and their female offspring fed either a control diet (10% fat) or a high-fat diet (45% fat) and examined the visceral adipose proteome. Solubilizing proteins from adipose tissue is challenging due to the need for high concentrations of detergents; however, the use of a detergent-compatible sample preparation strategy based on suspension trapping (S-Trap) enabled label-free quantitative bottom-up analysis of the adipose proteome. We identified differentially expressed proteins related to lipid metabolism, inflammatory disease, immune response, and cancer, providing valuable molecular-level insight into how maternal obesity impacts the health of offspring. Data are available via ProteomeXchange with the identifier PXD042092.

Shallow groundwater is an important resource, especially in low- and middle-income countries; however, shallow groundwater is particularly vulnerable to point sources of pollution such as latrines or unlined waste disposal ponds. The objective of this paper is to derive a quantitative criterion for siting an extraction well and an upgradient point source of pollution to ensure that they are hydraulically disconnected, i.e., that no water flows from the point source to the well. To achieve this objective, we modeled the flow of shallow groundwater considering uniform regional flow, a single point source of pollution, and a single extraction well. For any set of flow rates and upgradient point source distance, we sought the minimum “off-center distance” ymin (i.e., the distance in the direction perpendicular to regional flow) that ensures the well and the point source are hydraulically disconnected. For constituencies with access to computing resources and coding expertise, we used a computer-based method for determining ymin that is exact to within the accuracy of a root-finding algorithm; this approach is recommended when computer access is available. For constituencies lacking these resources, we determined a simple, closed-form, approximate solution for ymin that has an average error of less than 3% for the conditions we tested. For a subset of scenarios in which the point source is sufficiently far upgradient of the well (n = 77), the root mean square relative error of the approximate solution is only 0.52%. We found that ymin depends on a length parameter (Qw + Qps)/QR, where Qw is the extraction rate of the well, Qps is the injection rate of the point source, and QR is the regional groundwater flow rate per unit of perpendicular length. Either the exact solution or the closed-form approximation can help to site wells near point sources of pollution, or to site point sources near wells, in a manner that protects the health of the well user. The approximate solution is valuable because many constituencies that rely on shallow wells for water supply and latrines for sanitation also lack access to the computer resources necessary to apply the exact solution.

The objective of this paper is to analyze the preferences and time of dedication to teaching and research activities of different types of academics from Mexico who have been exposed, unequally, to public and institutional policies oriented mainly to stimulate and recognizes scientific productivity and, to a lesser extent, teaching. Based on the results of the international survey Academic Profession in the Knowledge-based Society (APIKS) answered by 4,631 academics from 127 higher education institutions (HEIs), changes are noted in terms of preference and dedication of full-time scholars to the activities they perform, compared to the previous survey, in accordance with the aspirations to receive the benefits of public policy programs that are aimed at this population. This preference for research has also permeated those hired as part-time professor, and it was even identified that 7% of this type of academic has recognition as a researcher.

Latrines are an effective way for people in low- and middle-income countries to move away from open defecation. Guidelines are used to provide a recommended horizontal setback distance from a latrine to a downgradient well to ensure the safety of the well from subsurface contaminants. We collected 107 journal papers, books, and reports to critically review the recommended setback distances and how these recommendations are derived. It was discovered that the four most common guidelines/reviews are all based principally on just four field studies, all of which were conducted over 40 years ago, which casts doubt on a frequently used one-size-fits-all approach. More recent methods for latrine siting use both field data and some sort of modeling component to account for the different site conditions, but these models have not been verified for use outside their respective studies. They are also limited in how they consider the hydraulic connection between the latrine and the well. We recommend that future siting guidelines should focus more on vertical separation, include chemical contamination, and be based on models describing how latrines and wells are hydraulically connected, along with the fate and transport of potentially harmful contaminants. HIGHLIGHTS Most common guidelines are based on four field studies, conducted over 40 years ago.; Latrine-siting guidelines must account for the vertical transport of pollutants.; Siting guidelines should account for the distinct features of loadings and transport of bacteria and viruses.; In situ treatment technologies and resource recovery strategies may influence pollutant loadings.; Models can assist with site-specific siting.;

We report a case of a native knee septic arthritis and subsequent osteomyelitis due to a CO2-dependent (capnophilic) multidrug-resistant E. coli ST131 O25:H4 strain. Capnophilic phenotype made microbiology investigation challenging; susceptibility testing could not be performed and the organism did not grow in the urine culture using standard method. The combination of unique virotype and capnophilia may have contributed to the aggressiveness of this organism and the initial unsuccessful carbapenem course, leading to recurrent infection.

Angelman syndrome (AS) is a rare genetic disorder characterized by severe intellectual disability, seizures, lack of speech, and ataxia. The gene responsible for AS was identified as Ube3a and it encodes for E6AP, an E3 ubiquitin ligase. Currently, there is very little known about E6AP's mechanism of action in vivo or how the lack of this protein in neurons may contribute to the AS phenotype. Elucidating the mechanistic action of E6AP would enhance our understanding of AS and drive current research into new avenues that could lead to novel therapeutic approaches that target E6AP's various functions. To facilitate the study of AS, we have generated a novel rat model in which we deleted the rat Ube3a gene using CRISPR. The AS rat phenotypically mirrors human AS with loss of Ube3a expression in the brain and deficits in motor coordination as well as learning and memory. This model offers a new avenue for the study of AS. Autism Res 2020, 13: 397-409. © 2020 International Society for Autism Research,Wiley Periodicals, Inc. LAY SUMMARY: Angelman syndrome (AS) is a rare genetic disorder characterized by severe intellectual disability, seizures, difficulty speaking, and ataxia. The gene responsible for AS was identified as UBE3A, yet very little is known about its function in vivo or how the lack of this protein in neurons may contribute to the AS phenotype. To facilitate the study of AS, we have generated a novel rat model in which we deleted the rat Ube3a gene using CRISPR. The AS rat mirrors human AS with loss of Ube3a expression in the brain and deficits in motor coordination as well as learning and memory. This model offers a new avenue for the study of AS.

Prostate stromal cells can contribute to prostate tumorigenesis. Here the authors show that the loss of androgen receptor signalling in Gli1-lineage stromal cells diminishes prostate epithelial oncogenic transformation and tumor growth in mouse models and this is due to insulin-like growth factor binding protein 3-mediated inhibiting IGF1 and Wnt/β-catenin signalling activation.

Activation of the androgen receptor (AR) through androgen binding is essential for prostate tumorigenesis. Here the authors show that AR activation in a subpopulation of prostatic progenitor cells can initiate prostatic intraepithelial neoplasia formation and promotes prostate cancer development through activation of IGF1 and Wnt/β-catenin signalling pathways.

Shallow groundwater is an important resource, especially in low- and middle-income countries; however, shallow groundwater is particularly vulnerable to point sources of pollution such as latrines or unlined waste disposal ponds. The objective of this paper is to derive a quantitative criterion for siting an extraction well and an upgradient point source of pollution to ensure that they are hydraulically disconnected, i.e., that no water flows from the point source to the well. To achieve this objective, we modeled the flow of shallow groundwater considering uniform regional flow, a single point source of pollution, and a single extraction well. For any set of flow rates and upgradient point source distance, we sought the minimum "off-center distance" ymin (i.e., the distance in the direction perpendicular to regional flow) that ensures the well and the point source are hydraulically disconnected. For constituencies with access to computing resources and coding expertise, we used a computer-based method for determining ymin that is exact to within the accuracy of a root-finding algorithm; this approach is recommended when computer access is available. For constituencies lacking these resources, we determined a simple, closed-form, approximate solution for ymin that has an average error of less than 3% for the conditions we tested. For a subset of scenarios in which the point source is sufficiently far upgradient of the well (n = 77), the root mean square relative error of the approximate solution is only 0.52%. We found that ymin depends on a length parameter (Qw + Qps)/QR, where Qw is the extraction rate of the well, Qps is the injection rate of the point source, and QR is the regional groundwater flow rate per unit of perpendicular length. Either the exact solution or the closed-form approximation can help to site wells near point sources of pollution, or to site point sources near wells, in a manner that protects the health of the well user. The approximate solution is valuable because many constituencies that rely on shallow wells for water supply and latrines for sanitation also lack access to the computer resources necessary to apply the exact solution. [ABSTRACT FROM AUTHOR]

Obesity, a complex condition that involves genetic, environmental, and behavioral factors, is a non-infectious pandemic that affects over 650 million adults worldwide with a rapidly growing prevalence. A major contributor is the consumption of high-fat diets, an increasingly common feature of modern diets. Maternal obesity results in an increased risk of offspring developing obesity and related health problems; however, the impact of maternal diet on the adipose tissue composition of offspring has not been evaluated. Here, we designed a generational diet-induced obesity study in female C57BL/6 mice that included maternal cohorts and their female offspring fed either a control diet (10% fat) or a high-fat diet (45% fat) and examined the visceral adipose proteome. Solubilizing proteins from adipose tissue is challenging due to the need for high concentrations of detergents; however, the use of a detergent-compatible sample preparation strategy based on suspension trapping (S-Trap) enabled label-free quantitative bottom-up analysis of the adipose proteome. We identified differentially expressed proteins related to lipid metabolism, inflammatory disease, immune response, and cancer, providing valuable molecular-level insight into how maternal obesity impacts the health of offspring. Data are available via ProteomeXchange with the identifier PXD042092. [ABSTRACT FROM AUTHOR]

Veterans in the transition stage out of the military have an increased risk for negative mental health outcomes and suicide. Previous research has found that finding and retaining employment is the most challenging post-service adjustment for veterans. Job loss may have a greater impact on mental health for veterans than for civilians due to the myriad challenges often faced when transitioning to the civilian workplace, as well as preexisting vulnerabilities that are common among veterans such as trauma exposure or service-related injuries. Previous studies have demonstrated that low Future Self-Continuity (FSC), which refers to the sense of "psychological connectedness" that a person has between their present and future selves, has also been associated with the abovementioned mental health outcomes. 167 U.S. military veterans who exited the military 10 or fewer years prior to their participation in the study, of which 87 experienced subsequent job loss, completed a series of questionnaires to assess future self-continuity (FSC) and mental health outcomes. Results confirmed previous findings in that job loss, as well as low FSC, were individually associated with an increased risk for negative mental health outcomes. Findings suggest that FSC may act as a mediator, where levels of FSC mediate the effects of job loss on negative mental outcomes (depression, anxiety, stress, and suicidality) among veterans during their first 10 years out of the military. These findings may have implications for enhancing current clinical interventions for veterans experiencing job loss and mental health difficulties during the transition period. [ABSTRACT FROM AUTHOR]

In our research we examined the the relationship between the perception of scientific skills acquisition in Mexican graduate students with their awareness of scientific competences considered in the curriculum, mentoring practices and availability of institutional resources for conducting research. The study involved a conventional sample of 147 graduate students (M age = 28, DS = 6.52 years) in natural sciences and engineering from public higher education institutions from a northwest state of Mexico. The results of multiple linear regression show that the variables studied are significantly associated with the perceived acquisition of scientific skills during the program, the importance of scientific competence in the curriculum, mentoring practices and available resources for research. Implication for graduate programs are discussed in light of the results.

From the researchers' perspective, the study aimed to identify factors affecting the functionality of postgraduate programs in natural sciences and engineering in a north-western Mexican state. Through the typical cases method, 25 researchers who worked in six doctorate programs in the region were selected. From the perception of these participants, the functionality of the postgraduate program is affected by external factors, such as the weakness of other participants' actions in the scientific and technological innovation system in the region; and internal factors, in particular, difficulties concerning the formation processes and strategies for academic training and technology transfer into the region.