Investigating Protein Degradability through Site-Specific Ubiquitin Ligase Recruitment.

We report targeted protein degradation through the site-specific recruitment of native ubiquitin ligases to a protein of interest via conjugation of E3 ligase ligands. Direct comparison of degradation ability of proteins displaying the corresponding bioconjugation handle at different regions of protein surfaces was explored. We demonstrate the benefit of proximal lysine residues and investigate flexibility in linker length for the design of optimal degraders.

Mitigating the Stigma of Mental Illness: The Impact of Story-Telling in the Black Community.

Racial/ethnic minorities, including the Black community, experience stigma as a significant barrier to mental health care, with fears of being devalued or discriminated against deterring individuals from seeking help. Racial stigma further exacerbates mental health issues and negatively influences perceptions of service utilization. To address this, our research team partnered with a national non-profit storytelling organization to develop and evaluate a virtual narrative storytelling intervention series that amplifies the voices and experiences of Black Americans living with mental illness and addiction.

Development of Priority Assistive Product Lists in Three African Countries.

National Assistive Product Lists (APLs) play an important role in improving access to assistive products (APs). Assistive products are critical to enhancing the health, well-being, and quality of life of persons with disabilities and other functional limitations, including those associated with aging. Comparing national APL development across Malawi, Liberia, and Sierra Leone may provide insight into the differences between the resulting national APLs and how to enhance AP service delivery systems.

Hydrogel-Enhanced Autologous Chondrocyte Implantation for Cartilage Regeneration-An Update on Preclinical Studies.

Autologous chondrocyte implantation (ACI) and matrix-induced ACI (MACI) have demonstrated improved clinical outcomes and reduced revision rates for treating osteochondral and chondral defects. However, their ability to achieve lasting, fully functional repair remains limited. To overcome these challenges, scaffold-enhanced ACI, particularly utilizing hydrogel-based biomaterials, has emerged as an innovative strategy.

CT-Derived Features as Predictors of Clot Burden and Resolution.

: To evaluate the prognostic utility of CT-imaging-derived biomarkers in distinguishing acute pulmonary embolism (PE) resolution and its progression to chronic PE, as well as their association with clot burden. : We utilized a cohort of 45 patients (19 male (42.2%)) and 96 corresponding CT scans with exertional dyspnea following an acute PE.

TomoPicker: Annotation-Efficient Particle Picking in cryo-electron Tomograms.

Particle picking in cryo-electron tomograms (cryo-ET) is crucial for in situ structure detection of macromolecules and protein complexes. The traditional template-matching-based approaches for particle picking suffer from template-specific biases and have low throughput. Given these problems, learning-based solutions are necessary for particle picking.

Inhibitory Control in Late Childhood as a Predictor of Antisocial Behavior in Adolescence and the Role of Social Context.

Understanding the factors contributing to adolescent antisocial behavior is crucial for effective interventions. Protracted development of cognitive control systems supporting inhibitory control may be linked to increases in adolescent antisocial behavior, suggesting the promotion of inhibitory control as a potential preventative strategy. Concurrently, social contextual factors, including peer relationships, parent-child dynamics, and the neighborhood environment, may exacerbate or buffer the risk posed by low inhibitory control.

Alternative splicing modulates chromatin interactome and phase separation of the RIF1 C-terminal domain.

RIF1 (RAP1 interacting factor) fulfills diverse roles in DNA double-strand break repair, DNA replication, and nuclear organization. RIF1 is expressed as two splice variants, RIF1-Long (RIF1-L) and RIF1-Short (RIF1-S), from the alternative splicing (AS) of Exon 32 (Ex32) which encodes a 26 aa Ser/Lys-rich cassette peptide in the RIF1 C-terminal domain (CTD). Here we demonstrate that Ex32 inclusion was repressed by DNA damage and oncogenesis but peaked at G/M phase of the cell cycle.

Two fitness inference schemes compared using allele frequencies from 1068 391 sequences sampled in the UK during the COVID-19 pandemic.

Throughout the course of the SARS-CoV-2 pandemic, genetic variation has contributed to the spread and persistence of the virus. For example, various mutations have allowed SARS-CoV-2 to escape antibody neutralization or to bind more strongly to the receptors that it uses to enter human cells. Here, we compared two methods that estimate the fitness effects of viral mutations using the abundant sequence data gathered over the course of the pandemic.

Challenges faced by women and persons excluded because of their ethnicity and race in physics learning environments: review of the literature and recommendations for departments and instructors.

Physics, as a discipline, has long struggled with pervasive stereotypes and biases about who is capable and can excel in it. Physics also ranks among the least diverse among all science, technology, engineering, and mathematics (STEM) disciplines, often cultivating and fostering learning environments that lack inclusivity and equity. Moreover, stereotypes about brilliance, inequitable physics learning environments and the overall physics culture not only impact the experiences and outcomes of students who major in physics, but also those from other STEM disciplines who must take physics courses.

Assays to measure small molecule Hsp70 agonist activity in vitro and in vivo.

Hsp70 prevents protein aggregation and is cytoprotective, but sustained Hsp70 overexpression is problematic. Therefore, we characterized small molecule agonists that augment Hsp70 activity. Because cumbersome assays were required to assay agonists, we developed cell-based and in vivo assays in which disease-associated consequences of Hsp70 activation can be quantified.

Targeted Polariton Flow Through Tailored Photonic Defects.

In non-Hermitian open quantum systems, such as polariton condensates, the local tailoring of gains and losses opens up an interesting possibility to realize functional optical elements. Here, we demonstrate that deliberately introducing losses via a photonic defect, realized by reducing the quality factor of a DBR mirror locally within an ultrahigh-quality microcavity, may be utilized to create directed polariton currents towards the defect. We discuss the role of polariton-polariton interactions in the process and how to tailor the effective decay time of a polariton condensate by coupling it to the defect.

Evaluation of a continuing education course on guideline-concordant management of acute dental pain.

Background: The purpose of the present study was to evaluate the use of a free online continuing education (CE) course that sought to address barriers of capability by training dental team members in the specific recommendations of the American Dental Association (ADA)-endorsed adult guideline for the pharmacologic management of acute dental pain, shared decision-making, and the adoption of the guideline into practice.

Methods: In 2022 and 2023, dentists completed an online, asynchronous CE course on the guideline-concordant pharmacologic management of acute dental pain. They completed 11-item knowledge tests before and after completing the course.

Assessing mechanical agency during apical apoptotic cell extrusion.

Homeostasis is necessary for epithelia to maintain barrier function and prevent the accumulation of defective cells. Unfit, excess, and dying cells in the larval zebrafish tail fin epidermis are removed via controlled cell death and extrusion. Extrusion coincides with oscillations of cell area, both in the extruding cell and its neighbors.

Temporal dynamics of nucleus accumbens neurons in male mice during reward seeking.

The nucleus accumbens (NAc) regulates reward-motivated behavior, but the temporal dynamics of NAc neurons that enable "free-willed" animals to obtain rewards remain elusive. Here, we recorded Ca activity from individual NAc neurons when mice performed self-paced lever-presses for sucrose. NAc neurons exhibited three temporally-sequenced clusters, defined by times at which they exhibited increased Ca activity: approximately 0, -2.

Interpretable Spatio-Temporal Embedding for Brain Structural-Effective Network with Ordinary Differential Equation.

The MRI-derived brain network serves as a pivotal instrument in elucidating both the structural and functional aspects of the brain, encompassing the ramifications of diseases and developmental processes. However, prevailing methodologies, often focusing on synchronous BOLD signals from functional MRI (fMRI), may not capture directional influences among brain regions and rarely tackle temporal functional dynamics. In this study, we first construct the brain-effective network via the dynamic causal model.

Unpacking unstructured data: A pilot study on extracting insights from neuropathological reports of Parkinson's Disease patients using large language models.

The aim of this study was to make unstructured neuropathological data, located in the NeuroBioBank (NBB), follow Findability, Accessibility, Interoperability, and Reusability principles and investigate the potential of large language models (LLMs) in wrangling unstructured neuropathological reports. By making the currently inconsistent and disparate data findable, our overarching goal was to enhance research output and speed. The NBB catalog currently includes information from medical records, interview results, and neuropathological reports.

Molecular basis of interchain disulfide-bond formation in BMP-9 and BMP-10.

BMP-9 and BMP-10 are TGF-β family signaling ligands naturally secreted into blood. They act on endothelial cells and are required for proper development and maintenance of the vasculature. In hereditary hemorrhagic telangiectasia, regulation is disrupted due to mutations in the BMP-9/10 pathway, namely in the type I receptor ALK1 or the co-receptor endoglin.

Co-option of the trichome-forming network initiated the evolution of a morphological novelty in Drosophila eugracilis.

Identifying the molecular origins by which new morphological structures evolve is one of the long-standing problems in evolutionary biology. To date, vanishingly few examples provide a compelling account of how new morphologies were initially formed, thereby limiting our understanding of how diverse forms of life derived their complex features. Here, we provide evidence that the large projections on the Drosophila eugracilis phallus that are implicated in sexual conflict have evolved through the partial co-option of the trichome genetic network.

A Pilot Study of the Role of Semaphorin 4A (sema4A) and 3C (sema3C) in Non-Muscle-Invasive Bladder Cancer (NMIBC).

Bladder cancer is a very important issue in contemporary urology. The aim of this pilot study was to assess for the first time the clinical utility of semaphorin 3C (sema3C) and 4A (sema4A) in patients with non-muscle-invasive bladder cancer (NMIBC). The experiment involved 15 patients with NMIBC and 5 patients without malignancies as the control group.