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Integrated single-cell analysis defines the epigenetic basis of castration-resistant prostate luminal cells

1 day 23 hours ago
Understanding prostate response to castration and androgen receptor signaling inhibitors (ARSI) is critical to improving long-term prostate cancer (PCa) patient survival. Here, we use a multi-omics approach on 229,794 single cells to create a mouse single-cell reference atlas for interpreting mouse prostate biology and castration response. Our reference atlas refines single-cell annotations and provides a chromatin context, which, when coupled with mouse lineage tracing, demonstrates that...
Jason S Kirk

Search for Nearly Mass-Degenerate Higgsinos Using Low-Momentum Mildly Displaced Tracks in pp Collisions at sqrt[s]=13  TeV with the ATLAS Detector

1 day 23 hours ago
Higgsinos with masses near the electroweak scale can solve the hierarchy problem and provide a dark matter candidate, while detecting them at the LHC remains challenging if their mass splitting is O(1 GeV). This Letter presents a novel search for nearly mass-degenerate Higgsinos in events with an energetic jet, missing transverse momentum, and a low-momentum track with a significant transverse impact parameter using 140 fb^{-1} of proton-proton collision data at sqrt[s]=13 TeV collected by the...
G Aad

The effector-triggered immunity landscape of tomato against Pseudomonas syringae

2 days 23 hours ago
Tomato (Solanum lycopersicum) is one of the world's most important food crops, and as such, its production needs to be protected from infectious diseases that can significantly reduce yield and quality. Here, we survey the effector-triggered immunity (ETI) landscape of tomato against the bacterial pathogen Pseudomonas syringae. We perform comprehensive ETI screens in five cultivated tomato varieties and two wild relatives, as well as an immunodiversity screen on a collection of 149 tomato...
Fabien Lonjon

Design and Characterization of a Generalist Biosensor for Indole Derivatives

2 days 23 hours ago
Transcription factor (TF)-based biosensors are useful synthetic biology tools for applications in a variety of areas of biotechnology. A major challenge of biosensor circuits is the limited repertoire of identified and well-characterized TFs for applications of interest, in addition to the challenge of optimizing selected biosensors. In this work, we implement the IclR family repressor TF TtgV from Pseudomonas putida DOT-T1E as an indole-derivative biosensor in Escherichia coli. We optimize the...
Chester Pham

Temperature dependence of the rain-gas and snow-gas partition coefficients for nearly a thousand chemicals

3 days 23 hours ago
Compared to the particle-gas partition coefficients (K(PG)), the rain-gas (K(RG)) and snow-gas (K(SG)) partition coefficients are also essential in studying the environmental behavior and fate of chemicals in the atmosphere. While the temperature dependence for the K(PG) have been extensively studied, the study for K(RG) and K(SG) are still lacking. Adsorption coefficients between water surface-air (K(IA)) and snow surface-air (K(JA)), as well as partition coefficients between water-air (K(WA))...
Pu-Fei Yang

Prostate cancer reshapes the secreted and extracellular vesicle urinary proteomes

3 days 23 hours ago
Urine is a complex biofluid that reflects both overall physiologic state and the state of the genitourinary tissues through which it passes. It contains both secreted proteins and proteins encapsulated in tissue-derived extracellular vesicles (EVs). To understand the population variability and clinical utility of urine, we quantified the secreted and EV proteomes from 190 men, including a subset with prostate cancer. We demonstrate that a simple protocol enriches prostatic proteins in urine....
Amanda Khoo

K29-linked free polyubiquitin chains affect ribosome biogenesis and direct ribosomal proteins to the intranuclear quality control compartment

3 days 23 hours ago
Ribosome assembly requires precise coordination between the production and assembly of ribosomal components. Mutations in ribosomal proteins that inhibit the assembly process or ribosome function are often associated with ribosomopathies, some of which are linked to defects in proteostasis. In this study, we examine the interplay between several yeast proteostasis enzymes, including deubiquitylases (DUBs) Ubp2 and Ubp14, and E3 ligases Ufd4 and Hul5, and we explore their roles in the regulation...
Harsha Garadi Suresh

Depression-Anxiety Coupling Strength as a predictor of relapse in major depressive disorder: A CAN-BIND wellness monitoring study report

4 days 23 hours ago
CONCLUSIONS: DACS may offer opportunities for developing novel strategies for personalized monitoring, early detection, and intervention. Future studies should replicate our findings in larger, diverse patient populations, develop individual patient prediction models, and explore the underlying mechanisms that govern the relationship of DACS and relapse.
Abraham Nunes

Crowd-sourced benchmarking of single-sample tumor subclonal reconstruction

5 days 23 hours ago
Subclonal reconstruction algorithms use bulk DNA sequencing data to quantify parameters of tumor evolution, allowing an assessment of how cancers initiate, progress and respond to selective pressures. We launched the ICGC-TCGA (International Cancer Genome Consortium-The Cancer Genome Atlas) DREAM Somatic Mutation Calling Tumor Heterogeneity and Evolution Challenge to benchmark existing subclonal reconstruction algorithms. This 7-year community effort used cloud computing to benchmark 31...
Adriana Salcedo

Evolution of rhodopsin in flatfishes (Pleuronectiformes) is associated with depth and migratory behavior

5 days 23 hours ago
Visual signals are involved in many fitness-related tasks and are therefore essential for survival in many species. Aquatic organisms are ideal systems to study visual evolution, as the high diversity of spectral properties in aquatic environments generates great potential for adaptation to different light conditions. Flatfishes are an economically important group, with over 800 described species distributed globally, including halibut, flounder, sole, and turbot. The diversity of flatfish...
Esme S B Macpherson

High-throughput screening of 222 pesticides in road environments in a megacity of northern China: A new approach to urban population exposure

1 week 1 day ago
A large number of pesticides have been widely manufactured and applied, and are released into the environment with negative impact on human health. Pesticides are largely used in densely populated urban environments, in green zones, along roads and on private properties. In order to characterize the potential exposure related health effects of pesticide and their occurrence in the urban environment, 222 pesticides were screened and quantified in 228 road dust and 156 green-belt soil samples in...
Ye Zhang

Better Respiratory Function in Heart Failure Patients With Use of Central-Acting Therapeutics

1 week 2 days ago
CONCLUSIONS: Central-acting drugs were associated with better respiratory function as measured by CPET parameters in HF patients. This could extend to clinically meaningful composite outcomes and hospitalizations but required more power to be definitive in linking to drug effect. Central-acting HF drugs show a role in mitigating diaphragm weakness.
Julie K K Vishram-Nielsen

HIF-1α and MIF enhance neutrophil-driven type 3 immunity and chondrogenesis in a murine spondyloarthritis model

1 week 4 days ago
The hallmarks of spondyloarthritis (SpA) are type 3 immunity-driven inflammation and new bone formation (NBF). Macrophage migration inhibitory factor (MIF) was found to be a key driver of the pathogenesis of SpA by amplifying type 3 immunity, yet MIF-interacting molecules and networks remain elusive. Herein, we identified hypoxia-inducible factor-1 alpha (HIF1A) as an interacting partner molecule of MIF that drives SpA pathologies, including inflammation and NBF. HIF1A expression was increased...
Akihiro Nakamura

Genome Sequencing for Diagnosing Rare Diseases

1 week 4 days ago
CONCLUSIONS: The diagnostic yield of genome sequencing in a large, diverse research cohort and in a small clinical cohort of persons who had previously undergone genetic testing was approximately 8% and included several types of pathogenic variation that had not previously been detected by means of exome sequencing or other techniques. (Funded by the National Human Genome Research Institute and others.).
Monica H Wojcik

Tracking the neurodevelopmental trajectory of beta band oscillations with optically pumped magnetometer-based magnetoencephalography

1 week 5 days ago
Neural oscillations mediate the coordination of activity within and between brain networks, supporting cognition and behaviour. How these processes develop throughout childhood is not only an important neuroscientific question but could also shed light on the mechanisms underlying neurological and psychiatric disorders. However, measuring the neurodevelopmental trajectory of oscillations has been hampered by confounds from instrumentation. In this paper, we investigate the suitability of a...
Lukas Rier

Large Individual Differences in Functional Connectivity in the Context of Major Depression and Antidepressant Pharmacotherapy

1 week 6 days ago
Clinical studies of major depression (MD) generally focus on group effects, yet interindividual differences in brain function are increasingly recognized as important and may even impact effect sizes related to group effects. Here, we examine the magnitude of individual differences in relation to group differences that are commonly investigated (e.g., related to MD diagnosis and treatment response). Functional MRI data from 107 participants (63 female, 44 male) were collected at baseline, 2, and...
Gwen van der Wijk

Azimuthal Angle Correlations of Muons Produced via Heavy-Flavor Decays in 5.02 TeV Pb+Pb and pp Collisions with the ATLAS Detector

1 week 6 days ago
Angular correlations between heavy quarks provide a unique probe of the quark-gluon plasma created in ultrarelativistic heavy-ion collisions. Results are presented of a measurement of the azimuthal angle correlations between muons originating from semileptonic decays of heavy quarks produced in 5.02 TeV Pb+Pb and pp collisions at the LHC. The muons are measured with transverse momenta and pseudorapidities satisfying p_{T}^{μ}>4 GeV and |η^{μ}|<2.4, respectively. The distributions of azimuthal...
G Aad

Asciminib in Newly Diagnosed Chronic Myeloid Leukemia

2 weeks 2 days ago
CONCLUSIONS: In this trial comparing asciminib with investigator-selected TKIs and imatinib, asciminib showed superior efficacy and a favorable safety profile in patients with newly diagnosed chronic-phase CML. Direct comparison between asciminib and second-generation TKIs was not a primary objective. (Funded by Novartis; ASC4FIRST ClinicalTrials.gov number, NCT04971226).
Andreas Hochhaus

From <em>mec</em> cassette to <em>rdhA</em>: a key <em>Dehalobacter</em> genomic neighborhood in a chloroform and dichloromethane-transforming microbial consortium

2 weeks 2 days ago
Chloroform (CF) and dichloromethane (DCM) are groundwater contaminants of concern due to their high toxicity and inhibition of important biogeochemical processes such as methanogenesis. Anaerobic biotransformation of CF and DCM has been well documented but typically independently of one another. CF is the electron acceptor for certain organohalide-respiring bacteria that use reductive dehalogenases (RDases) to dechlorinate CF to DCM. In contrast, known DCM degraders use DCM as their electron...
Olivia Bulka
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