Protists as mediators of complex microbial and viral associations.

Microbial eukaryotes (aka protists) are known for their important roles in nutrient cycling across different ecosystems. However, the composition and function of protist-associated microbiomes remains largely elusive. Here, we employ cultivation-independent single-cell isolation and genome-resolved metagenomics to provide detailed insights into underexplored microbiomes and viromes of over 100 currently uncultivable ciliates and amoebae isolated from diverse environments.

Endocytosis of Wnt ligands from surrounding epithelial cells positions microtubule nucleation sites at dendrite branch points.

Microtubule nucleation is important for microtubule organization in dendrites and for neuronal injury responses. The core nucleation protein, γTubulin (γTub), is localized to dendrite branch points in Drosophila sensory neurons by Wnt receptors and scaffolding proteins on endosomes. However, whether Wnt ligands are important is unknown.

Luminal breast epithelial cells of BRCA1 or BRCA2 mutation carriers and noncarriers harbor common breast cancer copy number alterations.

The prevalence and nature of somatic copy number alterations (CNAs) in breast epithelium and their role in tumor initiation and evolution remain poorly understood. Using single-cell DNA sequencing (49,238 cells) of epithelium from BRCA1 and BRCA2 carriers or wild-type individuals, we identified recurrent CNAs (for example, 1q-gain and 7q, 10q, 16q and 22q-loss) that are present in a rare population of cells across almost all samples (n = 28). In BRCA1/BRCA2 carriers, these occur before loss of heterozygosity (LOH) of wild-type alleles.

Appropriateness Criteria for Radiation Therapy in the Setting of Presumed Early-Stage Lung Cancer.

Low-dose chest computed tomography imaging for lung cancer screening is revealing increasing numbers of radiographic early-stage lung cancers. This topic discussion describes when a clinical scenario merits radiation therapy without a histologic diagnosis, with an emphasis on pragmatic algorithms in settings without readily available advanced biopsy techniques.

Cluster Assembly Dynamics Drive Fidelity of Planar Cell Polarity Polarization.

The planar cell polarity (PCP) signaling pathway polarizes epithelial cells in the tissue plane by segregating distinct molecular subcomplexes to opposite sides of each cell, where they interact across intercellular junctions to form asymmetric clusters. The role of clustering in this process is unknown. We hypothesized that protein cluster size distributions could be used to infer the underlying molecular dynamics and function of cluster assembly and polarization.

Clinical, Pathologic, and Imaging Variables Associated with Prostate Cancer Detection by PSMA PET/CT and Multiparametric MRI.

Multiparametric MRI (mpMRI) and prostate-specific membrane antigen (PSMA) PET/CT are complementary imaging modalities used in the presurgical evaluation of patients with prostate cancer (PCa). The purpose of this study was to characterize clinically significant PCa (csPCa) detected and not detected by PSMA PET/CT and mpMRI, focusing on tumors detected solely by PSMA PET/CT and overlooked by mpMRI. We conducted a single-center, retrospective analysis of patients who underwent both PSMA PET/CT and mpMRI within 3 mo of each other and before radical prostatectomy.

Inferring replication timing and proliferation dynamics from single-cell DNA sequencing data.

Dysregulated DNA replication is a cause and a consequence of aneuploidy in cancer, yet the interplay between copy number alterations (CNAs), replication timing (RT) and cell cycle dynamics remain understudied in aneuploid tumors. We developed a probabilistic method, PERT, for simultaneous inference of cell-specific replication and copy number states from single-cell whole genome sequencing (scWGS) data. We used PERT to investigate clone-specific RT and proliferation dynamics in  >50,000 cells obtained from aneuploid and clonally heterogeneous cell lines, xenografts and primary cancers.

Disruption of immune responses by type 1 diabetes exacerbates SARS-CoV-2 mediated lung injury.

COVID-19 commonly presents as pneumonia, with those most severely affected progressing to respiratory failure. Patient responses to SARS-CoV-2 infection are varied, with comorbidities acting as major contributors to varied outcomes. Focusing on one such major comorbidity, we assessed whether pharmacological induction of type 1 diabetes mellitus (T1DM) would increase the severity of lung injury in a murine model of COVID-19 pneumonia utilizing wild-type mice infected with mouse-adapted SARS-CoV-2.

Molecular Hallmarks of Prostate-specific Membrane Antigen in Treatment-naïve Prostate Cancer.

Background And Objective: We characterized tumor prostate-specific membrane antigen (PSMA) levels as a reflection of cancer biology and treatment sensitivities for treatment-naïve prostate cancer.

Methods: We first correlated PSMA positron emission tomography (PET) maximum standardized uptake values (SUVmax) in primary prostate cancer with tumor FOLH1 (PSMA RNA abundance) to establish RNA as a proxy (n = 55). We then discovered and validated molecular pathways associated with PSMA RNA levels in two large primary tumor cohorts.

Silicon photonic microresonator-based high-resolution line-by-line pulse shaping.

Optical pulse shaping stands as a formidable technique in ultrafast optics, radio-frequency photonics, and quantum communications. While existing systems rely on bulk optics or integrated platforms with planar waveguide sections for spatial dispersion, they face limitations in achieving finer (few- or sub-GHz) spectrum control. These methods either demand considerable space or suffer from pronounced phase errors and optical losses when assembled to achieve fine resolution.

Divergent Evolution in Bilateral Prostate Cancer: a Case Study.

Multifocal prostate cancer is a prevalent phenomenon, with most cases remaining uncharacterized from a genomic perspective. A patient presented with bilateral prostate cancer. On systematic biopsy, two indistinguishable clinicopathologic lesions were detected.

Taxonomic and abundance biases affect the record of marine eukaryotic plankton communities in sediment DNA archives.

Environmental DNA (eDNA) preserved in marine sediments is increasingly being used to study past ecosystems. However, little is known about how accurately marine biodiversity is recorded in sediment eDNA archives, especially planktonic taxa. Here, we address this question by comparing eukaryotic diversity in 273 eDNA samples from three water depths and the surface sediments of 24 stations in the Nordic Seas.

Dissecting the impact of differentiation stage, replicative history, and cell type composition on epigenetic clocks.

Epigenetic clocks, built on DNA methylation patterns of bulk tissues, are powerful age predictors, but their biological basis remains incompletely understood. Here, we conducted a comparative analysis of epigenetic age in murine muscle, epithelial, and blood cell types across lifespan. Strikingly, our results show that cellular subpopulations within these tissues, including adult stem and progenitor cells as well as their differentiated progeny, exhibit different epigenetic ages.

Ongoing genome doubling promotes evolvability and immune dysregulation in ovarian cancer.

Whole-genome doubling (WGD) is a critical driver of tumor development and is linked to drug resistance and metastasis in solid malignancies. Here, we demonstrate that WGD is an ongoing mutational process in tumor evolution. Using single-cell whole-genome sequencing, we measured and modeled how WGD events are distributed across cellular populations within tumors and associated WGD dynamics with properties of genome diversification and phenotypic consequences of innate immunity.

Transcriptomic Profiling of Primary Prostate Cancers and Nonlocalized Disease on Prostate-Specific Membrane Antigen Positron Emission Tomography/Computed Tomography: A Multicenter Retrospective Study.

Purpose: To characterize the relationship between Decipher genomic classifier scores and prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT)-based metastatic spread.

Materials And Methods: We identified patients from four institutions who underwent PSMA PET/CT scans pretreatment for primary staging or postradical prostatectomy (RP) for suspected recurrence and had Decipher transcriptomic data available from biopsy or RP specimens. PSMA PET/CT-based patterns of spread were classified as localized (miT + N0M0) or nonlocalized (miN1M0 or miM1a-c).

IMMUNOTAR - Integrative prioritization of cell surface targets for cancer immunotherapy.

Cancer remains a leading cause of mortality globally. Recent improvements in survival have been facilitated by the development of less toxic immunotherapies; however, identifying targets for immunotherapies remains a challenge in the field. To address this challenge, we developed IMMUNOTAR, a computational tool that systematically prioritizes and identifies candidate immunotherapeutic targets.

A Health-Related Quality of Life Measure for Patients Who Undergo Minimally Invasive Glaucoma Surgery.

Purpose: To develop a patient-reported outcome measure to assess the impact of glaucoma and treatment, including minimally invasive glaucoma surgery (MIGS).

Design: Observational study before and after concomitant cataract and Food and Drug Administration-approved implantable MIGS device surgery.

Setting: Survey administration was on a computer, iPad, or similar device.

International Variations in Adherence to Quality Metrics for Locoregional Prostate Cancer.

Background And Objective: Adherence to guideline recommendations can improve the quality of care for patients with prostate cancer (PCa). Our aim was to assess adherence to guidelines for locoregional PCa by international region.

Methods: The study cohort comprised patients diagnosed with locoregional PCa in the 10-country Movember TrueNTH Global Registry (n = 62 688; 2013-2022).

Normal-Tension Glaucoma Complicated by a Giant Internal Carotid-Ophthalmic Artery Aneurysm.

. We describe a patient with normal tension glaucoma (NTG) of several years whose management was complicated by the presence of a giant internal carotid-ophthalmic artery aneurysm. .

Vascular endothelial-derived SPARCL1 exacerbates viral pneumonia through pro-inflammatory macrophage activation.

Inflammation induced by lung infection is a double-edged sword, moderating both anti-viral and immune pathogenesis effects; the mechanism of the latter is not fully understood. Previous studies suggest the vasculature is involved in tissue injury. Here, we report that expression of Sparcl1, a secreted matricellular protein, is upregulated in pulmonary capillary endothelial cells (EC) during influenza-induced lung injury.