Morphogen-induced kinase condensates transduce Hh signal by allosterically activating Gli.

Hedgehog (Hh) morphogen governs embryonic development and tissue homeostasis through the Ci/Gli family transcription factors. Here we report that Hh induces phase separation of the fused (Fu)/Ulk family kinases to allosterically regulate Ci/Gli. We find that Hh-induced phosphorylation of Fu/Ulk3 promotes SUMOylation of their inverted phosphorylation-dependent SUMOylation motifs.

Perivascular cells function as key mediators of mechanical and structural changes in vascular capillaries.

A hallmark of chronic and inflammatory diseases is the formation of a fibrotic and stiff extracellular matrix (ECM), typically associated with abnormal, leaky microvascular capillaries. Mechanisms explaining how the microvasculature responds to ECM alterations remain unknown. Here, we used a microphysiological model of capillaries on a chip mimicking the characteristics of healthy or fibrotic collagen to test the hypothesis that perivascular cells mediate the response of vascular capillaries to mechanical and structural changes in the human ECM.

Ultrasensitive detection of intact SARS-CoV-2 particles in complex biofluids using microfluidic affinity capture.

Measuring virus in biofluids is complicated by confounding biomolecules coisolated with viral nucleic acids. To address this, we developed an affinity-based microfluidic device for specific capture of intact severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Our approach used an engineered angiotensin-converting enzyme 2 to capture intact virus from plasma and other complex biofluids.

Cpeb1 remodels cell type-specific translational program to promote fear extinction.

Protein translation is crucial for fear extinction, a process vital for adaptive behavior and mental health, yet the underlying cell-specific mechanisms remain elusive. Using a Tet-On 3G genetic approach, we achieved precise temporal control over protein translation in the infralimbic medial prefrontal cortex () during fear extinction. In addition, our results reveal that the disruption of cytoplasmic polyadenylation element binding protein 1 (Cpeb1) leads to notable alterations in cell type-specific translational programs, thereby affecting fear extinction.

Redesigning protonic ceramic electrochemical cells to lower the operating temperature.

Protonic ceramic electrochemical cells (PCECs) can operate at intermediate temperatures (450° to 600°C) for power generation and hydrogen production. However, the operating temperature is still too high to revolutionize ceramic electrochemical cell technology. Lowering the operating temperature to <450°C will enable a wider material choice and reduce system costs.

Flap endonuclease 1 repairs DNA-protein cross-links via ADP-ribosylation-dependent mechanisms.

DNA-protein cross-links (DPCs) are among the most detrimental genomic lesions. They are ubiquitously produced by formaldehyde (FA), and failure to repair FA-induced DPCs blocks chromatin-based processes, leading to neurodegeneration and cancer. The type, structure, and repair of FA-induced DPCs remain largely unknown.

Chromatin conformation, gene transcription, and nucleosome remodeling as an emergent system.

In single cells, variably sized nanoscale chromatin structures are observed, but it is unknown whether these form a cohesive framework that regulates RNA transcription. Here, we demonstrate that the human genome is an emergent, self-assembling, reinforcement learning system. Conformationally defined heterogeneous, nanoscopic packing domains form by the interplay of transcription, nucleosome remodeling, and loop extrusion.

Molecular dynamics at immune synapse lipid rafts influence the cytolytic behavior of CAR T cells.

Chimeric antigen receptor T cells (CART) targeting CD19 through CD28.ζ signaling induce rapid lysis of leukemic blasts, contrasting with persistent tumor control exhibited by 4-1BB.ζ-CART.

Reduced circulating sphingolipids and activity are linked to T2D risk and impaired insulin secretion.

Gestational diabetes mellitus (GDM), a transient form of diabetes that resolves postpartum, is a major risk factor for type 2 diabetes (T2D) in women. While the progression from GDM to T2D is not fully understood, it involves both genetic and environmental components. By integrating clinical, metabolomic, and genome-wide association study (GWAS) data, we identified associations between decreased sphingolipid biosynthesis and future T2D, in part through the allele of the gene in Hispanic women shortly after a GDM pregnancy.

Necrosis of pleomorphic adenoma of the lacrimal gland with acute and chronic arteriolar occlusion.

Pleomorphic adenoma of the lacrimal gland (PALG) is a benign neoplasm typically presenting with gradual, painless globe displacement and/or lid swelling. We report an atypical case of PALG in a 53-year old male presenting acutely, mimicking orbital cellulitis. Imaging demonstrated an extraconal rim-enhancing soft-tissue lesion medial to the left lacrimal gland, involving superior rectus and levator palpebrae superioris.

Multiomics dissection of human RAG deficiency reveals distinctive patterns of immune dysregulation but a common inflammatory signature.

Human recombination-activating gene (RAG) deficiency can manifest with distinct clinical and immunological phenotypes. By applying a multiomics approach to a large group of -mutated patients, we aimed at characterizing the immunopathology associated with each phenotype. Although defective T and B cell development is common to all phenotypes, patients with hypomorphic variants can generate T and B cells with signatures of immune dysregulation and produce autoantibodies to a broad range of self-antigens, including type I interferons.

TSLP acts on regulatory T cells to maintain their identity and limit allergic inflammation.

Thymic stromal lymphopoietin (TSLP) is a type I cytokine that promotes allergic responses and mediates type 2 immunity. A balance between effector T cells (T), which drive the immune response, and regulatory T cells (T), which suppress the response, is required for proper immune homeostasis. Here, we report that TSLP differentially acts on T versus T to balance type 2 immunity.

Obesity reshapes regulatory T cells in the visceral adipose tissue by disrupting cellular cholesterol homeostasis.

Regulatory T cells (T) accumulate in the visceral adipose tissue (VAT) to maintain systemic metabolic homeostasis but decline during obesity. Here, we explored the metabolic pathways controlling the homeostasis, composition, and function of VAT T under normal and high-fat diet feeding conditions. We found that cholesterol metabolism was specifically up-regulated in ST2 VAT T subsets.

Adult and pediatric orbital rhabdomyosarcoma: comparison of characteristics and outcomes.

Introduction: Rhabdomyosarcoma (RMS) is a common pediatric orbital malignancy but is extremely rare in adults. This study assesses clinical and radiographic features, management, and outcomes in adult orbital RMS patients with comparison to pediatric patients.

Methods: A retrospective chart review from 2000-2023 at Bascom Palmer Eye Institute was conducted evaluating patients aged 0 to 100-years-old with biopsy-confirmed orbital RMS.

Semi-Supervised Learning Allows for Improved Segmentation With Reduced Annotations of Brain Metastases Using Multicenter MRI Data.

Background: Deep learning-based segmentation of brain metastases relies on large amounts of fully annotated data by domain experts. Semi-supervised learning offers potential efficient methods to improve model performance without excessive annotation burden.

Purpose: This work tests the viability of semi-supervision for brain metastases segmentation.

Satisfaction, user experiences, and initial efficacy of a technology-supported self-management intervention (iSMART) to improve post-stroke functioning: a remoted randomized controlled trial.

Background: Self-management interventions empower individuals to manage their chronic conditions and daily life after stroke. However, traditional in-person self-management interventions often face transportation and geographical barriers. Digital interventions may offer a solution to address this gap.

Functions of the Bloom Syndrome Helicase N-terminal Intrinsically Disordered Region.

Bloom Syndrome helicase (Blm) is a RecQ family helicase involved in DNA repair, cell-cycle progression, and development. Pathogenic variants in human BLM cause the autosomal recessive disorder Bloom Syndrome, characterized by predisposition to numerous types of cancer. Prior studies of Drosophila Blm mutants lacking helicase activity or protein have shown sensitivity to DNA damaging agents, defects in repairing DNA double-strand breaks (DSBs), female sterility, and improper segregation of chromosomes in meiosis.

Characterization of fungal carbonyl sulfide hydrolase belonging to clade D β-carbonic anhydrase.

Carbonyl sulfide hydrolase (COSase) is a unique enzyme that exhibits high activity towards carbonyl sulfide (COS) but low carbonic anhydrase (CA) activity, despite belonging to the CA family. COSase was initially identified in a sulfur-oxidizing bacterium and later discovered in the ascomycete Trichoderma harzianum strain THIF08. The COSase from T.

Feasibility and Usage of a Virtual Assistant Device in Cognitively Impaired Homebound Older Adults.

Social technology in older adults can improve self-rated health; however, there can also be difficulties using it. Our study aimed to evaluate the feasibility and acceptance of virtual assistant device (VAD) use in cognitively impaired homebound older adults. 52 newly referred Meals on Wheels clients aged 60 and older were recruited for a three-phase study: 6 weeks of meals alone (control), followed by 6 weeks of meals+Alexa Echo Show 8 (AES8) basic usage, and lastly 6 weeks of meals+AES8 advanced usage.

Associations of Central Arterial Stiffness With Brain White Matter Integrity and Gray Matter Volume in MRI Across the Adult Lifespan.

Background: Central arterial stiffening is associated with brain white matter (WM) damage and gray matter (GM) volume loss in older adults, but little is known about this association from an adult lifespan perspective.

Purpose: To investigate the associations of central arterial stiffness with WM microstructural organization, WM lesion load, cortical thickness, and GM volume in healthy adults across the lifespan.

Study Type: This is a cross-sectional study.

Does Weekend Discharge Affect Readmission and Survival in Liver Transplant Patients? Insights From a Cohort Study.

Background: Weekend hospital discharges are often associated with reduced staffing, potentially impacting the quality of patient care. We studied the effects of weekend discharge after liver transplantation (LT) on early readmission rates, overall survival (OS), and graft survival (GS).

Method: We analyzed data from the Ohio State University Wexner Medical Center database (January 2016 to December 2023).

sp. nov., a bacterium isolated from the roots of the aquatic plant .

A polyphasic taxonomic study was carried out on strain T5W1, isolated from the roots of the aquatic plant . This isolate is Gram-negative, rod-shaped, motile, aerobic and non-pigmented. Nearly complete 16S rRNA gene sequence homology related the strain to , with 98.