Fragment-based development of small molecule inhibitors targeting cholesterol metabolism.

( ) is the world's most deadly infectious pathogen and new drugs are urgently required to combat the emergence of multi-(MDR) and extensively-(XDR) drug resistant strains. The bacterium specifically upregulates sterol uptake pathways in infected macrophages and the metabolism of host-derived cholesterol is essential for long-term survival Here, we report the development of antitubercular small molecules that inhibit the cholesterol oxidases CYP125 and CYP142, which catalyze the initial step of cholesterol metabolism. An efficient biophysical fragment screen was used to characterize the structure-activity relationships of CYP125 and CYP142, and identify a non-azole small molecule that can bind to the heme cofactor of both enzymes.

Cataract surgery has minimal effect on corneal shape.

Purpose: To quantify the effect of cataract surgery on cornea shape.

Methods: Patients undergoing cataract surgery with standardised 2.75 mm surgical incisions at 110 degrees with a side port at 50 degrees were included.

COVID-19 vaccine anxieties: exploring social and political drivers of vaccine attitudes in Kono District, Sierra Leone.

As COVID-19 spread rapidly during the early months of the pandemic, many communities around the globe anxiously waited for a vaccine. At the start of the pandemic, it was widely believed that Africa would be a significant source of infection, and thus, vaccinating African communities became a primary goal among local and global health authorities. However, when the COVID-19 vaccine became available in March 2021 in Sierra Leone, many people viewed it with scepticism and hesitation.

Perceptions of sexual assault perpetrators, victims, and event depend on system justification beliefs and perpetrator atonement.

When accused of wrongdoing, a sexual assault perpetrator may express atonement, i.e., he may acknowledge harm done, take responsibility, and make amends.

International Symposium on Ruminant Physiology: Paternal Nutrient Supply: Impacts on Physiological and Whole Animal Outcomes in Offspring.

Recent evidence suggests that environmental factors experienced by sires can be transmitted through the ejaculate (seminal plasma + sperm) into the female reproductive tract, influencing fertilization, embryo development, and postnatal offspring outcomes. This concept is termed paternal programming. In rodents, sire nutrition was shown to directly alter offspring outcomes through sperm epigenetic signatures, DNA damage/oxidative stress, cytokine profiles, and/or the seminal microbiome.

Revisiting the Plasmodium falciparum druggable genome using predicted structures and data mining.

The identification of novel drug targets for the purpose of designing small molecule inhibitors is key component to modern drug discovery. In malaria parasites, discoveries of antimalarial targets have primarily occurred retroactively by investigating the mode of action of compounds found through phenotypic screens. Although this method has yielded many promising candidates, it is time- and resource-consuming and misses targets not captured by existing antimalarial compound libraries and phenotypic assay conditions.

Methods to reduce fraudulent participation and highlight autistic voices in research.

Over the last decade, especially since the pandemic, more research has been happening online. Conducting research online can create opportunities to include autistic people across the world and make our studies more diverse. However, conducting research online had led to scammers, or people pretending to be autistic, participating in autism research studies.

Integrating systems of power and privilege in the study of resilience.

Although current approaches to the study of resilience acknowledge the role of context, rarely do those conceptualizations attend to societal systems and structures that include hierarchies of power and privilege-namely systems of racism, colonialism, patriarchy, and capitalism-nor do they articulate how these structural realities are embedded within individual experiences. We offer critiques of the current literature from this structural lens, using the concept of master narratives to articulate the incomplete and, at times, damaging story that the discipline of psychology has told about resilience. We then provide three models that center history, systems, and structures of society that can be employed in the study of resilience.

Implementation of digital remote postoperative monitoring in routine practice: a qualitative study of barriers and facilitators.

Introduction: Remote monitoring can strengthen postoperative care in the community and minimise the burden of complications. However, implementation requires a clear understanding of how to sustainably integrate such complex interventions into existing care pathways. This study aimed to explore perceptions of potential facilitators and barriers to the implementation of digital remote postoperative monitoring from key stakeholders and derive recommendations for an implementable service.

Challenges and Opportunities in Transitioning Autistic Individuals Into Adulthood.

Background And Objectives: Approximately 1.2 million autistic youth will reach the legal age of adulthood over the next decade. Given dynamic changes in the socioecological context of the transition to adulthood, we produced an updated transitions research agenda reflecting the perspectives of autistic young adults, care partners (parents), and professionals who use autism research.

Changes in vaginal cytokines concentrations during artificial insemination and natural service in beef heifers.

Objective: Heifer development is crucial for the optimization of reproductive efficiency in beef production. Heifer development is largely influenced by nutrition. Nutritional status of these heifers can influence immunological responses that are crucial for reproduction.

The story of 'us' is the story of 'me': A cross-sectional test of the influence of insecure attachment on narratives of romantic transgressions and high points.

Narratives play an important role in the development of the self-identity. Romantic relationships offer a powerful context in which to develop these narratives about the self through the good and the bad experiences people have with their partners. However, the stories we tell can also be colored by how we already see ourselves.

Emerging adults' journeys out of the shutdown: Longitudinal narrative patterns in a college career defined by COVID-19.

The COVID-19 pandemic has defined the college career for this generation of learners, threatening mental health, identity development, and college functioning. We began tracking the impacts of this pandemic for 633 first-year college students from four U.S.

Chronic Health Conditions Among Adults With Intellectual and Developmental Disabilities in a State Medicaid System.

Despite a growing number of adults with intellectual and developmental disabilities (IDD) and documented risk for adverse outcomes as they age, little is known about the health and healthcare patterns of adults with different IDD throughout adulthood. This study uses Wisconsin Medicaid claims data to characterize health conditions among adults with IDD. Results indicate high prevalence of asthma, diabetes, heart disease, and hypertension.

How do young men narrate the redemption story of a sexual assault perpetrator?

Little is known about how young men who have committed sexual assault might acknowledge wrongdoing and eventually change and make amends. There are practical barriers to seeking the real redemption stories of perpetrators. To explore hypothetical pathways to young men's accountability-taking and amends (i.

Avoidable admissions after minimally invasive hysterectomy.

Objective: To determine the rate of avoidable admissions following anticipated same-day discharge for patients undergoing minimally invasive hysterectomy and to identify risk factors associated with such admissions.

Methods: A retrospective review was performed of patients who underwent a minimally invasive hysterectomy between March 2019 and July 2021 for a suspected gynecologic malignancy at a single tertiary care center. Pre-operatively, patients were assessed for same-day discharge versus planned admission.

Validation of a Demography-Based Adaptive QTc Formula using Pediatric and Adult Datasets Acquired from Humans and Guinea Pigs.

Introduction: A variety of QT rate-correction (QTc) formulae have been utilized for both clinical and research purposes. However, these formulae are not universally effective, likely due to significant influences of demographic diversity on the QT-HR relationship. To address this limitation, we proposed an adaptive QTc (QTcAd) formula that adjusts to subject demographics (i.

Intergenerational Storytelling and Positive Psychosocial Development: Stories as Developmental Resources for Marginalized Groups.

Academic Abstract: We articulate an intergenerational model of positive psychosocial development that centers storytelling in an ecological framework and is motivated by an orientation toward social justice. We bring together diverse literature (e.g.

Research as resistance: Naming and dismantling the master narrative of "good" science.

The call for psychological science to make amends for "causing harm to communities of color and contributing to systemic inequities" (American Psychological Association, 2022a) requires a critical acknowledgment that science is not neutral but a sociopolitical and ideological endeavor. From its inception, psychology used science to produce what was framed as incontrovertible "hard" evidence of racial hierarchy, infallible "proof" that white people (i.e.

Promoting public engagement in interdisciplinary biological systems education by leveraging American sports-inspired bracket contests on social media and web.

The complexity of modern biology poses challenges in fostering interdisciplinary understanding, particularly between practicing scientists and the public. Furthermore, scientists often lack formal training in science communication, despite various motivations to engage the public. The science literacy of the public in the biological sciences can also vary across socio-economic and cultural backgrounds.

Genotyping-by-sequencing targets genic regions and improves resolution of genome-wide association studies in autotetraploid potato.

De novo genotyping in potato using methylation-sensitive GBS discovers SNPs largely confined to genic or gene-associated regions and displays enhanced effectiveness in estimating LD decay rates, population structure and detecting GWAS associations over 'fixed' SNP genotyping platform. Study also reports the genetic architectures including robust sequence-tagged marker-trait associations for sixteen important potato traits potentially carrying higher transferability across a wider range of germplasm. This study deploys recent advancements in polyploid analytical approaches to perform complex trait analyses in cultivated tetraploid potato.