Yersinia pestis YopJ and its impact on innate immunity

Yersinia pestis is one of the most virulent pathogens known to man, with the most impactful epidemics in human history. As the causative agent for the plague, Y. pestis has demonstrated its propensity to ravage through animal and human populations. As a zoonotic disease that can confer transmission between different species of mammals, this further illustrates the importance of plague research. Today, plague still has a foothold in several countries such as India and Madagascar. Worldwide outbreaks led to its ranking as number 5 in emerging zoonotic diseases by the Centers for Disease Control in 2019. Despite the gratuitous devastation it has displayed worldwide, Y. pestis has piqued interest in use for bioterrorism from multiple superpowers. Given the exhibition of its reach in the 14th century, and its conserved methods of pathogenesis in other pathogens, plague studies demonstrate a broader impact in elucidating the mechanisms of infectious diseases.Includes bibliographical references

Characterizing student engagement with hands-on, problem-based, and lecture activities in an introductory college course

This study examines the interest, motivation, and behavioral engagement of college students in an introductory course relative to three instructional formats used in the course: hands-on, problem-based laboratory stations; problem-based written case studies; and video lectures. Groups of five to seven students were assigned learning activities as treatments in a Latin Square design consisting of three experimental periods. At the beginning of selected laboratory sessions, students completed 10 minutes of the experimental activity immediately followed by a questionnaire. Students rated hands-on, problem-based laboratory stations as more challenging, novel, and attention-grabbing than they rated case studies or video lectures. Interest, intrinsic motivation, and behavioral engagement were greatest for groups completing laboratory stations followed by those completing case studies and lectures, respectively. Overall, the greater situational interest experienced during laboratory stations and case studies indicates that these activities can be leveraged to create learning environments that promote interest, engagement, and achievement

Proprotein convertase cleavage liberates a fibrillogenic fragment of a resident glycoprotein to initiate melanosome biogenesis

Lysosome-related organelles are cell type–specific intracellular compartments with distinct morphologies and functions. The molecular mechanisms governing the formation of their unique structural features are not known. Melanosomes and their precursors are lysosome-related organelles that are characterized morphologically by intralumenal fibrous striations upon which melanins are polymerized. The integral membrane protein Pmel17 is a component of the fibrils and can nucleate their formation in the absence of other pigment cell–specific proteins. Here, we show that formation of intralumenal fibrils requires cleavage of Pmel17 by a furin-like proprotein convertase (PC). As in the generation of amyloid, proper cleavage of Pmel17 liberates a lumenal domain fragment that becomes incorporated into the fibrils; longer Pmel17 fragments generated in the absence of PC activity are unable to form organized fibrils. Our results demonstrate that PC-dependent cleavage regulates melanosome biogenesis by controlling the fibrillogenic activity of a resident protein. Like the pathologic process of amyloidogenesis, the formation of other tissue-specific organelle structures may be similarly dependent on proteolytic activation of physiological fibrillogenic substrates

PROMOÇÃO DA SAÚDE SEXUAL E REPRODUTIVA DE ADOLESCENTES: EDUCAÇÃO POR PARES

O objetivo do estudo foi descrever o processo de educação por pares, desenvolvido por jovens católicos como promotores da saúde sexual e reprodutiva na adolescência. Trata-se de um estudo qualitativo, realizado com 17 participantes que foram capacitados para desenvolver o processo de educação por pares com outros adolescentes durante o período de um mês, em espaços de convivência escolhidos pelos próprios participantes. Os dados foram registrados em diário de campo e categorizados para análise. Foi realizado educação por pares com 54 amigos e parentes, os temas mais abordados foram sexualidade e IST, os espaços de maior abordagem foram domicílio, escola e rua. A estratégia foi considerada positiva, destacando-se o empenho dos jovens católicos em atuar como educadores. Descritores: Sexualidade, Adolescente, Saúde sexual, Saúde reprodutiva.

Parents\u27 Goals For ADHD Care In a Clinical Pediatric Sample

Objective. This report describes goals parents have for their children with attention deficit/hyperactivity disorder (ADHD) when coming for a pediatric visit. Method. Data were collected from 441 parents of children presenting to either a primary care pediatric practice or a developmental behavioral pediatric practice. Parents were asked to report their top 1 or 2 goals for improvement for their children, and responses were coded into 17 categories. These categories were further grouped into 7 goal composites and examined in relation to demographic characteristics of the families, office type, and symptomology. Results. Goals related to reducing symptoms of inattention were most common, but goals were heterogeneous in nature. Goals were meaningfully, but modestly, related to symptomology. In several instances, symptoms of comorbid conditions interacted with symptoms of ADHD in relation to specific goals being reported. Conclusions. Parents’ goals extended beyond ADHD symptoms. Pediatricians need an array of resources to address parents’ goals

Quantitative Analysis of Immune Infiltrates in Primary Melanoma.

Novel methods to analyze the tumor microenvironment (TME) are urgently needed to stratify melanoma patients for adjuvant immunotherapy. Tumor-infiltrating lymphocyte (TIL) analysis, by conventional pathologic methods, is predictive but is insufficiently precise for clinical application. Quantitative multiplex immunofluorescence (qmIF) allows for evaluation of the TME using multiparameter phenotyping, tissue segmentation, and quantitative spatial analysis (qSA). Given that CD3+CD8+ cytotoxic lymphocytes (CTLs) promote antitumor immunity, whereas CD68+ macrophages impair immunity, we hypothesized that quantification and spatial analysis of macrophages and CTLs would correlate with clinical outcome. We applied qmIF to 104 primary stage II to III melanoma tumors and found that CTLs were closer in proximity to activated (CD68+HLA-DR+) macrophages than nonactivated (CD68+HLA-DR-) macrophages (P < 0.0001). CTLs were further in proximity from proliferating SOX10+ melanoma cells than nonproliferating ones (P < 0.0001). In 64 patients with known cause of death, we found that high CTL and low macrophage density in the stroma (P = 0.0038 and P = 0.0006, respectively) correlated with disease-specific survival (DSS), but the correlation was less significant for CTL and macrophage density in the tumor (P = 0.0147 and P = 0.0426, respectively). DSS correlation was strongest for stromal HLA-DR+ CTLs (P = 0.0005). CTL distance to HLA-DR- macrophages associated with poor DSS (P = 0.0016), whereas distance to Ki67- tumor cells associated inversely with DSS (P = 0.0006). A low CTL/macrophage ratio in the stroma conferred a hazard ratio (HR) of 3.719 for death from melanoma and correlated with shortened overall survival (OS) in the complete 104 patient cohort by Cox analysis (P = 0.009) and merits further development as a biomarker for clinical application

Clinical, environmental, and genetic risk factors for substance use disorders : characterizing combined effects across multiple cohorts

Substance use disorders (SUDs) incur serious social and personal costs. The risk for SUDs is complex, with risk factors ranging from social conditions to individual genetic variation. We examined whether models that include a clinical/environmental risk index (CERI) and polygenic scores (PGS) are able to identify individuals at increased risk of SUD in young adulthood across four longitudinal cohorts for a combined sample of N = 15,134. Our analyses included participants of European (N-EUR = 12,659) and African (N-AFR = 2475) ancestries. SUD outcomes included: (1) alcohol dependence, (2) nicotine dependence; (3) drug dependence, and (4) any substance dependence. In the models containing the PGS and CERI, the CERI was associated with all three outcomes (ORs = 01.37-1.67). PGS for problematic alcohol use, externalizing, and smoking quantity were associated with alcohol dependence, drug dependence, and nicotine dependence, respectively (OR = 1.11-1.33). PGS for problematic alcohol use and externalizing were also associated with any substance dependence (ORs = 1.09-1.18). The full model explained 6-13% of the variance in SUDs. Those in the top 10% of CERI and PGS had relative risk ratios of 3.86-8.04 for each SUD relative to the bottom 90%. Overall, the combined measures of clinical, environmental, and genetic risk demonstrated modest ability to distinguish between affected and unaffected individuals in young adulthood. PGS were significant but added little in addition to the clinical/environmental risk index. Results from our analysis demonstrate there is still considerable work to be done before tools such as these are ready for clinical applications.Peer reviewe

Indigenous Peoples' Rights in Data: a contribution toward Indigenous Research Sovereignty

Indigenous Peoples' right to sovereignty forms the foundation for advocacy and actions toward greater Indigenous self-determination and control across a range of domains that impact Indigenous Peoples' communities and cultures. Declarations for sovereignty are rising throughout Indigenous communities and across diverse fields, including Network Sovereignty, Food Sovereignty, Energy Sovereignty, and Data Sovereignty. Indigenous Research Sovereignty draws in the sovereignty discourse of these initiatives to consider their applications to the broader research ecosystem. Our exploration of Indigenous Research Sovereignty, or Indigenous self-determination in the context of research activities, has been focused on the relationship between Indigenous Data Sovereignty and efforts to describe Indigenous Peoples' Rights in data

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy