Isolation of PCSK9-specific nanobodies from synthetic libraries using a combined protein selection strategy.

Nanobodies (Nbs) hold great potential to replace conventional antibodies in various biomedical applications. However, conventional methods for their discovery can be time-consuming and expensive. We have developed a reliable protein selection strategy that combines magnetic activated cell sorting (MACS)-based screening of yeast surface display (YSD) libraries and functional ligand-binding identification by Tat-based recognition of associating proteins (FLI-TRAP) to isolate antigen-specific Nbs from synthetic libraries.

Large language models improve the identification of emergency department visits for symptomatic kidney stones.

Recent advancements of large language models (LLMs) like generative pre-trained transformer 4 (GPT-4) have generated significant interest among the scientific community. Yet, the potential of these models to be utilized in clinical settings remains largely unexplored. In this study, we investigated the abilities of multiple LLMs and traditional machine learning models to analyze emergency department (ED) reports and determine if the corresponding visits were due to symptomatic kidney stones.

SARS-CoV-2 S-protein expression drives syncytia formation in endothelial cells.

SARS-CoV-2 is a viral infection, best studied in the context of epithelial cell infection. Epithelial cells, when infected with SARS-CoV-2 express the viral S-protein, which causes host cells to fuse together into large multi-nucleated cells known as syncytia. Because SARS-CoV-2 infections also frequently present with cardiovascular phenotypes, we sought to understand if S-protein expression would also result in syncytia formation in endothelial cells.

Activation of Wnt/β-catenin in neural progenitor cells regulates blood-brain barrier development and promotes neuroinflammation.

The central nervous system (CNS) requires specialized blood vessels to support neural function within specific microenvironments. During neurovascular development, endothelial Wnt/β-catenin signaling is required for BBB development within the brain parenchyma, whereas fenestrated blood vessels that lack BBB properties do not require Wnt/β-catenin signaling. Here, we used zebrafish to further characterize this phenotypic heterogeneity of the CNS vasculature.

Merging metabolic modeling and imaging for screening therapeutic targets in colorectal cancer.

Cancer-associated fibroblasts (CAFs) play a key role in metabolic reprogramming and are well-established contributors to drug resistance in colorectal cancer (CRC). To exploit this metabolic crosstalk, we integrated a systems biology approach that identified key metabolic targets in a data-driven method and validated them experimentally. This process involved a novel machine learning-based method to computationally screen, in a high-throughput manner, the effects of enzyme perturbations predicted by a computational model of CRC metabolism.

Biological correlates associated with high-risk breast cancer patients identified using a computational method.

Using a novel unsupervised method to integrate multi-omic data, we previously identified a breast cancer group with a poor prognosis. In the current study, we characterize the biological features of this subgroup, defined as the high-risk group, using various data sources. Assessment of three published hypoxia signatures showed that the high-risk group exhibited higher hypoxia scores (p < 0.

Decreased nitric oxide production is a novel therapeutic target for salt-induced nocturnal polyuria in aging.

Nocturnal polyuria is a major cause of nocturia, which affects quality of life. Aging-related decreases in nitric oxide production have been reported to contribute to salt-induced nocturnal polyuria. We posited that enhanced nitric oxide production from exercise could mitigate salt-induced nocturnal polyuria.

Enhanced phosphorus weathering contributed to Late Miocene cooling.

Late Miocene climate evolution provides an opportunity to assess Earth's climate sensitivity to carbon cycle perturbation under warmer-than-modern conditions. Despite its relevance for understanding the climate system, the driving mechanisms underlying profound climate and carbon cycle changes - including the enigmatic Late Miocene cooling from 7 to 5.4 million years ago - remain unclear.

α-Copaene is a potent repellent against the Asian Citrus Psyllid Diaphorina citri.

The Asian Citrus Psyllid (ACP), Diaphorina citri, severely threatens citrus production worldwide by transmitting the greening (= Huanglongbing)-causing bacterium Candidatus Liberibacter asiaticus. There is growing evidence that the push-pull strategy is suitable to partially mitigate HLB by repelling ACP with transgenic plants engineered to produce repellents and attracting the vector to plants with a minimal disease transmission rate. Species that pull ACP away from commercial citrus plants have been identified, and transgenic plants that repel ACP have been developed.

A mutation in LXRα uncovers a role for cholesterol sensing in limiting metabolic dysfunction-associated steatohepatitis.

Liver x receptor alpha (LXRα) functions as an intracellular cholesterol sensor that regulates lipid metabolism at the transcriptional level in response to the direct binding of cholesterol derivatives. We have generated mice with a mutation in LXRα that reduces activity in response to endogenous cholesterol derived LXR ligands while still allowing transcriptional activation by synthetic agonists. The mutant LXRα functions as a dominant negative that shuts down cholesterol sensing.

Convergent evolution of oxidized sugar metabolism in commensal and pathogenic microbes in the inflamed gut.

Inflammation-associated perturbations of the gut microbiome are well characterized, but poorly understood. Here, we demonstrate that disparate taxa recapitulate the metabolism of the oxidized sugars glucarate and galactarate, utilizing enzymatically divergent, yet functionally equivalent, gud/gar pathways. The divergent pathway in commensals includes a putative 5-KDG aldolase (GudL) and an uncharacterized ABC transporter (GarABC) that recapitulate the function of their non-homologous counterparts in pathogens.

Greater residential greenness is associated with reduced epigenetic aging in adults.

Potential pathways linking urban green spaces to improved health include relaxation, stress alleviation, and improved immune system functioning. Epigenetic age acceleration (EAA) is a composite biomarker of biological aging based on DNA methylation measurements; it is predictive of morbidity and mortality. This cross-sectional study of 116 adult residents of a metropolitan area in central North Carolina investigated associations between exposure to residential green spaces and EAA using four previously developed epigenetic age formulas.

Polygenic burden of short tandem repeat expansions promotes risk for Alzheimer's disease.

Studies of the genetics of Alzheimer's disease (AD) have largely focused on single nucleotide variants and short insertions/deletions. However, most of the disease heritability has yet to be uncovered, suggesting that there is substantial genetic risk conferred by other forms of genetic variation. There are over one million short tandem repeats (STRs) in the genome, and their link to AD risk has not been assessed.

Morphological and functional decline of the SNc in a model of progressive parkinsonism.

The motor symptoms of Parkinson's Disease are attributed to the degeneration of dopamine neurons in the substantia nigra pars compacta (SNc). Previous work in the MCI-Park mouse model has suggested that the loss of somatodendritic dopamine transmission predicts the development of motor deficits. In the current study, brain slices from MCI-Park mice were used to investigate dopamine signaling in the SNc prior to and through the onset of movement deficits.

Platelet-white cell ratio is more strongly associated with mortality than other common risk ratios derived from complete blood counts.

Complete blood count indices and their ratios are associated with adverse clinical outcomes for many acute illnesses, but the mechanisms generating these associations are not fully understood. Recent identification of a consistent pattern of white blood cell and platelet count co-regulation during acute inflammatory recovery provides a potentially unifying explanation. Here we show that the platelet-to-white-cell ratio, which was selected based on this conserved recovery pattern, is more strongly associated with mortality than other blood count markers and ratios in four important illnesses involving acute inflammation: COVID-19, acute heart failure, myocardial infarction, and stroke.

Half of land use carbon emissions in Southeast Asia can be mitigated through peat swamp forest and mangrove conservation and restoration.

Southeast Asia (SEA) contributes approximately one-third of global land-use change carbon emissions, a substantial yet highly uncertain part of which is from anthropogenically-modified peat swamp forests (PSFs) and mangroves. Here, we report that between 2001-2022 land-use change impacting PSFs and mangroves in SEA generate approximately 691.8±97.

One state's journey with a reflective supervision professional development series: Development, implementation, and adaptation.

Reflective supervision (RS) has been viewed as best practice and is therefore incorporated-and often mandated-as a key feature of many relationship-based infant and early childhood serving programs. To promote the implementation of high-quality RS for infant and early childhood professionals, it is critical that a focus is placed on how infant and early childhood professionals are trained to build RS capacities. To this end, we describe Rhode Island, United States's journey developing, implementing, and iteratively adapting an RS professional development series.

Metabolic syndrome and associated components among police officers: A 7 and 12-year longitudinal analysis.

Objective: This study estimated risk of metabolic syndrome (MetSyn) and its components among police officers including differences by sex.

Methods: Police officers were examined at baseline and two follow-up examinations after 7 and 12 years. MetSyn was defined using the 2005 guidelines from AHA/NHLBI.

Vaccine effectiveness against influenza-associated hospitalizations in adults with liver disease, 2015-2020: US Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN).

Influenza causes 100,000-710,000 hospitalizations annually in the U.S. Patients with liver disease are at higher risk of severe outcomes following influenza infection.

Radiological safety atlas of minimally invasive midfoot fusion: A cadaver study.

Purpose: The popularity of minimally invasive (MIS) foot surgery continues to grow. However, it comes with certain limitations that present notable challenges. One significant hurdle is the absence of direct visualization of neurovascular structures and tendons.

Take your PIC (Program Improvement Committee): The benefits of a resident-run initiative to improve graduate medical education.

The evolving landscape of graduate medical education (GME) necessitates innovative approaches to residency program evaluation and improvement. At Detroit Medical Center/Wayne State University, a novel resident-led Program Improvement Committee (PIC) was established in June 2022 within the Diagnostic Radiology Residency Program. The PIC serves as a flexible, resident-driven structure designed to enhance engagement, provide continuous feedback, and implement actionable solutions in collaboration with residency leadership.

The number of central nervous system-driven symptoms predicts subsequent chronic primary pain: evidence from UK Biobank.

Background: Chronic primary pain describes conditions where pain is the principal problem rather than a consequence of another disease. Primary pain is thought to be primarily owing to nociplastic pain (i.e.

Overcoming the technical challenge of venous resection with pancreatectomy: Which factors determine survival?

Background: Pancreatectomy with venous resection (PVR) is nowadays considered standard. However, there is still concern about increased postoperative morbidity and impaired long-term outcome depending on the type of venous resection and reconstruction. The aim was to investigate the predictors of morbidity and long-term survival in patients undergoing PVR in a high-volume center.

The Role of Nutrition in Managing Muscle Disorders.

Many myopathies in horses can be managed by exercise regimes and dietary modifications. This includes modifying the amount of nonstructural carbohydrate, fat, amino acids, vitamin E, and selenium based on the horse's specific myopathy, metabolic status, exercise program, and optimal body weight. Because dietary recommendations differ substantially between myopathies, it is imperative to establish a specific diagnosis.