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Effects of anaerobic digestion on the dewaterability of sonicated biosludge

1 day ago
Studies on the impact of anaerobic digestion on biosludge dewatering are conflicting and mechanisms are poorly understood, with significant implications to both wastewater costs and environmental impact. To identify the mechanisms that improve dewaterability and to amplify the impacts of anaerobic digestion, biosludge was first sonicated to deteriorate dewaterability. Sonicated biosludge was next anaerobically digested under mesophilic conditions in three experiments, and the roles of...
Sergio Luna Nino

Personalized survival benefit estimation from living donor liver transplantation with a novel machine learning method for confounding adjustment

2 days ago
CONCLUSIONS: DPSM provides an effective approach for creating RCT-like comparability from observational data to predict which patients will benefit most from LDLT. This novel ML-based methodology enables personalized survival predictions while minimizing confounders and offers clinicians a new tool to more confidently evaluate treatment effects.
Anirudh Gangadhar

RETINA: Reconstruction-based pre-trained enhanced TransUNet for electron microscopy segmentation on the CEM500K dataset

4 days ago
Electron microscopy (EM) has revolutionized our understanding of cellular structures at the nanoscale. Accurate image segmentation is required for analyzing EM images. While manual segmentation is reliable, it is labor-intensive, incentivizing the development of automated segmentation methods. Although deep learning-based segmentation has demonstrated expert-level performance, it lacks generalizable performance across diverse EM datasets. Current approaches usually use either convolutional or...
Cheng Xing

Importin-alpha transports Norrin to the nucleus to promote proliferation and Notch signaling in glioblastoma stem cells

5 days ago
Norrin, a secreted protein encoded by NDP gene, is recognized for its established role as a paracrine canonical Frizzled-4/Wnt ligand that mediates angiogenesis and barrier function in the brain. However, emerging evidence suggests that Norrin possesses Frizzled-4-independent functions, notably impacting Notch activation and proliferation of cancer stem cells. We conducted a BioID protein-proximity screen to identify Norrin-interacting proteins. Surprisingly, a significant proportion of the...
Ahmed El-Sehemy

The IL-18 receptor is expressed on murine small-intestinal enterochromaffin cells and executes a recovery program upon injury

5 days ago
Upon injury, epithelial-derived IL-18 is released and induces an inflammatory response in underlying IL18R1^(+) lamina propria cells. Notably, Il18r1 is also predicted to be expressed and functional in intestinal epithelial cells (IECs), since epithelial IL18R1 deficiency contributes to worsened outcomes upon inflammatory challenge. However, the nature of Il18r1^(+) IECs, and their subsequent role in epithelial-intrinsic IL-18 signaling is poorly characterized. Here, we show that, in the murine...
Nathaniel J Winsor

Tegavivint triggers TECR-dependent nonapoptotic cancer cell death

6 days ago
Small molecules that induce nonapoptotic cell death are of fundamental mechanistic interest and may be useful to treat certain cancers. Here we report that tegavivint, a drug candidate undergoing human clinical trials, can activate a unique mechanism of nonapoptotic cell death in sarcomas and other cancer cells. This lethal mechanism is distinct from ferroptosis, necroptosis and pyroptosis and requires the lipid metabolic enzyme trans-2,3-enoyl-CoA reductase (TECR). TECR is canonically involved...
Logan Leak

At-RS31 orchestrates hierarchical cross-regulation of splicing factors and integrates alternative splicing with TOR-ABA pathways

6 days ago
Alternative splicing is essential for plants, enabling a single gene to produce multiple transcript variants to boost functional diversity and fine-tune responses to environmental and developmental cues. Arabidopsis thaliana At-RS31, a plant-specific splicing factor in the Serine/Arginine-rich (SR) protein family, responds to light and the Target of Rapamycin (TOR) signalling pathway, yet its downstream targets and regulatory impact remain unknown. To identify At-RS31 targets, we applied...
Tino Köster

Increased GABA<sub>A</sub> receptor open probability: Adaptive mechanisms to cope with anoxia in the painted turtle

1 week 1 day ago
The western painted turtle is the most anoxia-tolerant tetrapod known, surviving ∼ 4 months at 3 °C without oxygen. In the mammalian brain, absence of oxygen leads to hyper-excitability and cell death within minutes. A major mechanism by which painted turtles survive anoxia is a large increase of γ-aminobutyric acid (GABA) in the brain leading to a dominating Cl^(-) conductance that clamps membrane potential near the reversal potential of the GABA(A) receptor. Whole-cell GABA(A) receptor...
Haushe Suganthan

Impact of unequal testing on vaccine effectiveness estimates across two study designs: a simulation study

1 week 1 day ago
Observational studies are essential for measuring vaccine effectiveness. Recent research has raised concerns about how a relationship between testing and vaccination may affect estimates of vaccine effectiveness against symptomatic infection (symptomatic VE). Using an agent-based network model and SARS-CoV-2 as an example, we investigated how differences in the likelihood of testing by vaccination could influence estimates of symptomatic VE across two common study designs: retrospective cohort...
Korryn Bodner

A constellation of dysfunctional hybrid phenotypes enforces reproductive isolation between Caenorhabditis nematode species

1 week 1 day ago
The evolution of complete reproductive isolation hinges on the cumulative action of reproductive isolating barriers that can manifest throughout the life cycle of an organism. Consequently, a comprehensive understanding of the features underlying the origin and maintenance of species requires assessing the relative contributions of distinct barriers to overall reproductive isolation. Here we characterize multiple interrelated isolating barriers for the nematode sister species Caenorhabditis...
Maia N Dall'Acqua

Global, Regional, and National Burden of Nontraumatic Subarachnoid Hemorrhage: The Global Burden of Disease Study 2021

1 week 2 days ago
CONCLUSIONS AND RELEVANCE: Although the global age-standardized burden rates of SAH more than halved over the last 3 decades, SAH remained one of the most common cardiovascular and neurological causes of death and disabilities in the world, with increasing absolute case numbers. These findings suggest evidence for the potential health benefits of proactive public health planning and resource allocation toward the prevention of SAH.
GBD 2021 Global Subarachnoid Hemorrhage Risk Factors Collaborators

Genome-wide association study of long COVID

1 week 4 days ago
Infections can lead to persistent symptoms and diseases such as shingles after varicella zoster or rheumatic fever after streptococcal infections. Similarly, severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) infection can result in long coronavirus disease (COVID), typically manifesting as fatigue, pulmonary symptoms and cognitive dysfunction. The biological mechanisms behind long COVID remain unclear. We performed a genome-wide association study for long COVID including up to 6,450...
Vilma Lammi

A multimorphic variant in ThPOK causes an inborn error of immunity with T cell defects and fibrosis

1 week 5 days ago
ThPOK is a transcription factor that acts as a master regulator of CD4+ T cell lineage commitment. We report the first human disease caused by a genetic alteration in ThPOK, specifically, a damaging heterozygous de novo variant in ThPOK (NM_001256455.2:c.1080A>C, p.K360N). This patient exhibited the unusual constellation of persistent CD4+ T cell deficiency, allergy, interstitial lung disease, corneal vascularization and scarring, developmental delay, and growth failure. The ThPOKK360N variant...
Maryam Vaseghi-Shanjani

Genome-wide association studies of binge eating behaviour and anorexia nervosa yield insights into the unique and shared biology of eating disorder phenotypes

1 week 6 days ago
Eating disorders -including anorexia nervosa (AN), bulimia nervosa, and binge eating disorder-are clinically distinct but exhibit symptom overlap and diagnostic crossover. Genomic analyses have mostly examined AN. We conducted the first genomic meta-analysis of binge eating behaviour (BE; 39,279 cases, 1,227,436 controls), alongside new analyses of AN (24,223 cases, 1,243,971 controls) and its subtypes (all European ancestries). We identified six loci associated with BE, including loci...
Jet D Termorshuizen

Highly specific Immunoproteasome inhibitor M3258 induces proteotoxic stress and apoptosis in KMT2A::AFF1 driven acute lymphoblastic leukemia

1 week 6 days ago
Proteasome inhibitors (PIs) bortezomib, carfilzomib and ixazomib are approved for the treatment of multiple myeloma and mantle cell lymphoma and have clinical activity in acute lymphoblastic leukemia (ALL). The predominant form of proteasome in these hematologic malignancies is the lymphoid tissue-specific immunoproteasome. FDA-approved PIs inhibit immunoproteasomes and ubiquitously expressed constitutive proteasomes causing on-target toxicities in non-hematological tissues. Replacing PIs with...
Tyler W Jenkins

Neurodevelopmental hijacking of oligodendrocyte lineage programs drives glioblastoma infiltration

2 weeks 1 day ago
Glioblastoma (GBM) is an aggressive brain tumor with a highly invasive nature. Despite the clinical relevance of this behavior, the molecular underpinnings of infiltrating GBM cells in the peritumoral zone remain underexplored in patients. Here, we show that peritumoral progenitor-like GBM cells activate transcriptional programs associated with increased invasivity, synaptic activity, and NOTCH signaling. These cells spatially colocalize with neurons and exhibit an increased propensity for...
Yiyan Wu

Dominant variants in major spliceosome U4 and U5 small nuclear RNA genes cause neurodevelopmental disorders through splicing disruption

2 weeks 2 days ago
The major spliceosome contains five small nuclear RNAs (snRNAs; U1, U2, U4, U5 and U6) essential for splicing. Variants in RNU4-2, encoding U4, cause a neurodevelopmental disorder called ReNU syndrome. We investigated de novo variants in 50 snRNA-encoding genes in a French cohort of 23,649 individuals with rare disorders and gathered additional cases through international collaborations. Altogether, we identified 145 previously unreported probands with (likely) pathogenic variants in RNU4-2 and...
Caroline Nava
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