DELVE: feature selection for preserving biological trajectories in single-cell data.

Single-cell technologies can measure the expression of thousands of molecular features in individual cells undergoing dynamic biological processes. While examining cells along a computationally-ordered pseudotime trajectory can reveal how changes in gene or protein expression impact cell fate, identifying such dynamic features is challenging due to the inherent noise in single-cell data. Here, we present DELVE, an unsupervised feature selection method for identifying a representative subset of molecular features which robustly recapitulate cellular trajectories.

Integration of Untargeted Metabolomics and Microbial Community Analyses to Characterize Distinct Deep-Sea Methane Seeps.

Deep-sea methane seeps host highly diverse microbial communities whose biological diversity is distinct from other marine habitats. Coupled with microbial community analysis, untargeted metabolomics of environmental samples using high resolution tandem mass spectrometry provides unprecedented access to the unique specialized metabolisms of these chemosynthetic microorganisms. In addition, the diverse microbial natural products are of broad interest due to their potential applications for human and environmental health and well-being.

Advances in Magnetic Microbead Affinity Selection Screening: Discovery of Natural Ligands to the SARS-CoV-2 Spike Protein.

Affinity selection-mass spectrometry, which includes magnetic microbead affinity selection-screening (MagMASS), is ideal for the discovery of ligands in complex mixtures that bind to pharmacological targets. Therapeutic agents are needed to prevent or treat COVID-19, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Infection of human cells by SARS-CoV-2 involves binding of the virus spike protein subunit 1 (S1) to the human cell receptor angiotensin converting enzyme-2 (ACE2).

Xanthohumol Pyrazole Derivative Improves Diet-Induced Obesity and Induces Energy Expenditure in High-Fat Diet-Fed Mice.

The energy intake exceeding energy expenditure (EE) results in a positive energy balance, leading to storage of excess energy and weight gain. Here, we investigate the potential of a newly synthesized compound as an inducer of EE for the management of diet-induced obesity and insulin resistance. Xanthohumol (XN), a prenylated flavonoid from hops, was used as a precursor for the synthesis of a pyrazole derivative tested for its properties on high-fat diet (HFD)-induced metabolic impairments.

Mouse-INtraDuctal (MIND): an in vivo model for studying the underlying mechanisms of DCIS malignancy.

Due to widespread adoption of screening mammography, there has been a significant increase in new diagnoses of ductal carcinoma in situ (DCIS). However, DCIS prognosis remains unclear. To address this gap, we developed an in vivo model, Mouse-INtraDuctal (MIND), in which patient-derived DCIS epithelial cells are injected intraductally and allowed to progress naturally in mice.

Autophagy regulates the localization and degradation of p16.

The tumor suppressor protein p16 (p16) is a well-established hallmark of aging that induces cellular senescence in response to stress. Previous studies have focused primarily on p16 regulation at the transcriptional level; comparatively little is known about the protein's intracellular localization and degradation. The autophagy-lysosomal pathway has been implicated in the subcellular trafficking and turnover of various stress-response proteins and has also been shown to attenuate age-related pathologies, but it is unclear whether p16 is involved in this pathway.

Radiologic and Pathologic Features Associated With Upgrade of Atypical Ductal Hyperplasia at Surgical Excision.

Rationale And Objectives: To evaluate radiologic and pathologic features associated with upgrade of atypical ductal hyperplasia (ADH) to ductal carcinoma in situ or invasive breast cancer at surgical excision, in order to identify patients who may consider alternatives to excision.

Materials And Methods: This retrospective analysis examined patients who underwent surgical excision of biopsy-proven ADH at our institution. Imaging and pathology from biopsy were reviewed to determine radiologic (lesion size, radiologic abnormality, biopsy type, needle gauge, number of cores, percent of lesion removed) and pathologic features (histologic calcifications, presence of necrosis, micropapillary features, extent of ADH) associated with ADH upgrade.

Inheritance of OCT4 predetermines fate choice in human embryonic stem cells.

It is well known that clonal cells can make different fate decisions, but it is unclear whether these decisions are determined during, or before, a cell's own lifetime. Here, we engineered an endogenous fluorescent reporter for the pluripotency factor OCT4 to study the timing of differentiation decisions in human embryonic stem cells. By tracking single-cell OCT4 levels over multiple cell cycle generations, we found that the decision to differentiate is largely determined before the differentiation stimulus is presented and can be predicted by a cell's preexisting OCT4 signaling patterns.

Automated Breast Ultrasound Interpretation Times: A Reader Performance Study.

Rationale And Objectives: This study aimed to determine the average time for breast radiologists of varied experience to interpret automated breast ultrasound (ABUS) examinations.

Materials And Methods: A reader performance study was conducted on female patients, with ACR BI-RADS 4 breast density classifications of C or D, who received both an ABUS screening examination and a digital mammogram from 2013 to 2014 at an academic institution. Three faculty breast radiologists with varied levels of ABUS experience (advanced, intermediate, novice) read all ABUS examinations, with interpretation times and final impressions (categorized as "normal" or "abnormal") recorded for each examination.

NEMO, a Transcriptional Target of Estrogen and Progesterone, Is Linked to Tumor Suppressor PML in Breast Cancer.

The beneficial versus detrimental roles of estrogen plus progesterone (E+P) in breast cancer remains controversial. Here we report a beneficial mechanism of E+P treatment in breast cancer cells driven by transcriptional upregulation of the NFκB modulator NEMO, which in turn promotes expression of the tumor suppressor protein promyelocytic leukemia (PML). E+P treatment of patient-derived epithelial cells derived from ductal carcinoma (DCIS) increased secretion of the proinflammatory cytokine IL6.

NPP4 is a procoagulant enzyme on the surface of vascular endothelium.

Ap3A is a platelet-dense granule component released into the extracellular space during the second wave of platelet aggregation on activation. Here, we identify an uncharacterized enzyme, nucleotide pyrophosphatase/phosphodiesterase-4 (NPP4), as a potent hydrolase of Ap3A capable of stimulating platelet aggregation and secretion. We demonstrate that NPP4 is present on the surface of vascular endothelium, where it hydrolyzes Ap3A into AMP and ADP, and Ap4A into AMP and ATP.

Microcalcifications of the breast: a mammographic-histologic correlation study using a newly designed Path/Rad Tissue Tray.

The introduction of screening mammography has brought about a greater knowledge of early breast cancer characteristics. These improvements have led to a reduction in size of suspicious lesions and a shift from surgical to image-guided core needle biopsies (CNBs). Establishing correlation between histologic and imaging findings is required for accurate diagnosis.

New techniques for mammography screening: advantages and limitations.

Screening mammography is the primary method used for the detection of breast cancer. Computer assisted detection (CAD) systems, magnetic resonance imaging of the breast, and breast lymphoscintigraphy with sentinel lymph node biopsy are three new imaging techniques developed to assist in the detection and evaluation of breast cancer and will be described and discussed.

Comparison of iodixanol and ioxaglate for adult aortography and renal/visceral angiography: a phase III clinical trial.

Rationale And Objectives: We investigated whether iodixanol offers improved safety or tolerance compared with ioxaglate and evaluated whether iodixanol-enhanced radiographs are diagnostically comparable or superior to those produced with ioxaglate. Iodixanol is a new isosmotic hexa-iodinated nonionic contrast agent being evaluated for intravascular use.

Methods: Fifty-four adult patients undergoing renal or visceral angiography, aortography, or both were enrolled in a prospective, randomized, double-blind, two-center study in which iodixanol and ioxaglate were compared.

Characterization and use of monoclonal and polyclonal antibodies against the mouse interferon-gamma receptor.

To facilitate investigation of its physical and functional properties, 11 monoclonal antibodies (mAbs) and a goat polyclonal IgG specific for the mouse interferon- (IFN-gamma) receptor were characterized and their potential uses studied. Eight of the mAbs interacted with epitopes on the extracellular domain of the receptor, two interacted with epitopes on the intracellular domain, and one interacted with an epitope that could not be localized definitively to either region. Of the 11 mAbs, the majority (8) were IgGs, 2 were IgMs, and 1 was an IgA.

Quantitation of pulmonary neuroepithelial bodies in pre- and postnatal rabbits.

The size, density and total number of neuroepithelial bodies (NEB) in the lungs of late fetal, neonatal, and mature rabbits were determined using fluorescence microscopy. In this study lungs from 27-, 29-, 30-, and 31-day fetuses; neonates of ages 2, 7, and 30 days; and 4- and 7(+)-month-old rabbits, were used. The total number of NEB in the entire lung of rabbits from each age group was estimated based on measurements of collapsed lung volume, average NEB diameter, and NEB density (number/mm2).