A high-throughput microfabricated platform for rapid quantification of metastatic potential.

Assays that measure morphology, proliferation, motility, deformability, and migration are used to study the invasiveness of cancer cells. However, native invasive potential of cells may be hidden from these contextual metrics because they depend on culture conditions. We created a micropatterned chip that mimics the native environmental conditions, quantifies the invasive potential of tumor cells, and improves our understanding of the malignancy signatures.

Low-frequency ERK and Akt activity dynamics are predictive of stochastic cell division events.

Understanding the dynamics of intracellular signaling pathways, such as ERK1/2 (ERK) and Akt1/2 (Akt), in the context of cell fate decisions is important for advancing our knowledge of cellular processes and diseases, particularly cancer. While previous studies have established associations between ERK and Akt activities and proliferative cell fate, the heterogeneity of single-cell responses adds complexity to this understanding. This study employed a data-driven approach to address this challenge, developing machine learning models trained on a dataset of growth factor-induced ERK and Akt activity time courses in single cells, to predict cell division events.

A contact binary satellite of the asteroid (152830) Dinkinesh.

Asteroids with diameters less than about 5 km have complex histories because they are small enough for radiative torques (that is, YORP, short for the Yarkovsky-O'Keefe-Radzievskii-Paddack effect) to be a notable factor in their evolution. (152830) Dinkinesh is a small asteroid orbiting the Sun near the inner edge of the main asteroid belt with a heliocentric semimajor axis of 2.19 AU; its S-type spectrum is typical of bodies in this part of the main belt.

Open-Source System for Real-Time Functional Assessment of In Vitro Filtration Barriers.

The integrity of the barrier between blood and the selective filtrate of solutes is important for homeostasis and its disruption contributes to many diseases. Microphysiological systems that incorporate synthetic or natural membranes with human cells can mimic biological filtration barriers, such as the glomerular filtration barrier in the kidney, and they can readily be used to study cellular filtration processes as well as drug effects and interactions. We present an affordable, open-source platform for the real-time monitoring of functional filtration status in engineered microphysiological systems.

Relating individual cell division events to single-cell ERK and Akt activity time courses.

Biochemical correlates of stochastic single-cell fates have been elusive, even for the well-studied mammalian cell cycle. We monitored single-cell dynamics of the ERK and Akt pathways, critical cell cycle progression hubs and anti-cancer drug targets, and paired them to division events in the same single cells using the non-transformed MCF10A epithelial line. Following growth factor treatment, in cells that divide both ERK and Akt activities are significantly higher within the S-G2 time window (~ 8.

Large-scale cryovolcanic resurfacing on Pluto.

The New Horizons spacecraft returned images and compositional data showing that terrains on Pluto span a variety of ages, ranging from relatively ancient, heavily cratered areas to very young surfaces with few-to-no impact craters. One of the regions with very few impact craters is dominated by enormous rises with hummocky flanks. Similar features do not exist anywhere else in the imaged solar system.

Functional Effects of Cardiomyocyte Injury in COVID-19.

COVID-19 affects multiple organs. Clinical data from the Mount Sinai Health System show that substantial numbers of COVID-19 patients without prior heart disease develop cardiac dysfunction. How COVID-19 patients develop cardiac disease is not known.

Physiology of cardiomyocyte injury in COVID-19.

COVID-19 affects multiple organs. Clinical data from the Mount Sinai Health System shows that substantial numbers of COVID-19 patients without prior heart disease develop cardiac dysfunction. How COVID-19 patients develop cardiac disease is not known.

Transcriptomic profiling of human cardiac cells predicts protein kinase inhibitor-associated cardiotoxicity.

Kinase inhibitors (KIs) represent an important class of anti-cancer drugs. Although cardiotoxicity is a serious adverse event associated with several KIs, the reasons remain poorly understood, and its prediction remains challenging. We obtain transcriptional profiles of human heart-derived primary cardiomyocyte like cell lines treated with a panel of 26 FDA-approved KIs and classify their effects on subcellular pathways and processes.

A Multi-center Study on the Reproducibility of Drug-Response Assays in Mammalian Cell Lines.

Evidence that some high-impact biomedical results cannot be repeated has stimulated interest in practices that generate findable, accessible, interoperable, and reusable (FAIR) data. Multiple papers have identified specific examples of irreproducibility, but practical ways to make data more reproducible have not been widely studied. Here, five research centers in the NIH LINCS Program Consortium investigate the reproducibility of a prototypical perturbational assay: quantifying the responsiveness of cultured cells to anti-cancer drugs.

The derivation of a Reference Dose (RfD) for perfluorooctane sulfonate (PFOS) based on immune suppression.

Exposure to perfluorooctane sulfonate (PFOS) is ubiquitous in populations and environments worldwide. Its long half-life in humans, indefinite persistence in the environment, and awareness of its widespread presence in drinking water make the human health assessment of PFOS a priority. While developmental, endocrine, and hepatic effects, and increased serum cholesterol are among the outcomes resulting from PFOS exposure, immunosuppression has also consistently emerged as an adverse effect.

Fluorescence Multiplexing with Spectral Imaging and Combinatorics.

Ultraviolet-to-infrared fluorescence is a versatile and accessible assay modality but is notoriously hard to multiplex due to overlap of wide emission spectra. We present an approach for fluorescence called multiplexing using spectral imaging and combinatorics (MuSIC). MuSIC consists of creating new independent probes from covalently linked combinations of individual fluorophores, leveraging the wide palette of currently available probes with the mathematical power of combinatorics.

Validating Antibodies for Quantitative Western Blot Measurements with Microwestern Array.

Fluorescence-based western blots are quantitative in principal, but require determining linear range for each antibody. Here, we use microwestern array to rapidly evaluate suitable conditions for quantitative western blotting, with up to 192 antibody/dilution/replicate combinations on a single standard size gel with a seven-point, two-fold lysate dilution series (~100-fold range). Pilot experiments demonstrate a high proportion of investigated antibodies (17/24) are suitable for quantitative use; however this sample of antibodies is not yet comprehensive across companies, molecular weights, and other important antibody properties, so the ubiquity of this property cannot yet be determined.

Dunes on Pluto.

The surface of Pluto is more geologically diverse and dynamic than had been expected, but the role of its tenuous atmosphere in shaping the landscape remains unclear. We describe observations from the New Horizons spacecraft of regularly spaced, linear ridges whose morphology, distribution, and orientation are consistent with being transverse dunes. These are located close to mountainous regions and are orthogonal to nearby wind streaks.

A mechanistic pan-cancer pathway model informed by multi-omics data interprets stochastic cell fate responses to drugs and mitogens.

Most cancer cells harbor multiple drivers whose epistasis and interactions with expression context clouds drug and drug combination sensitivity prediction. We constructed a mechanistic computational model that is context-tailored by omics data to capture regulation of stochastic proliferation and death by pan-cancer driver pathways. Simulations and experiments explore how the coordinated dynamics of RAF/MEK/ERK and PI-3K/AKT kinase activities in response to synergistic mitogen or drug combinations control cell fate in a specific cellular context.

Charon tectonics.

New Horizons images of Pluto's companion Charon show a variety of terrains that display extensional tectonic features, with relief surprising for this relatively small world. These features suggest a global extensional areal strain of order 1% early in Charon's history. Such extension is consistent with the presence of an ancient global ocean, now frozen.

An Improved Method of Predicting Extinction Coefficients for the Determination of Protein Concentration.

Concentration determination is an important method of protein characterization required in the development of protein therapeutics. There are many known methods for determining the concentration of a protein solution, but the easiest to implement in a manufacturing setting is absorption spectroscopy in the ultraviolet region. For typical proteins composed of the standard amino acids, absorption at wavelengths near 280 nm is due to the three amino acid chromophores tryptophan, tyrosine, and phenylalanine in addition to a contribution from disulfide bonds.

Cell size assays for mass cytometry.

Mass cytometry offers the advantage of allowing the simultaneous measurement of a greater number parameters than conventional flow cytometry. However, to date, mass cytometry has lacked a reliable alternative to the light scatter properties that are commonly used as a cell size metric in flow cytometry (forward scatter intensity-FSC). Here, we report the development of two plasma membrane staining assays to evaluate mammalian cell size in mass cytometry experiments.

Correction: Sparse sampling methods in multidimensional NMR.

Correction for 'Sparse sampling methods in multidimensional NMR' by Mehdi Mobli et al., Phys. Chem.

The atmosphere of Pluto as observed by New Horizons.

Observations made during the New Horizons flyby provide a detailed snapshot of the current state of Pluto's atmosphere. Whereas the lower atmosphere (at altitudes of less than 200 kilometers) is consistent with ground-based stellar occultations, the upper atmosphere is much colder and more compact than indicated by pre-encounter models. Molecular nitrogen (N2) dominates the atmosphere (at altitudes of less than 1800 kilometers or so), whereas methane (CH4), acetylene (C2H2), ethylene (C2H4), and ethane (C2H6) are abundant minor species and likely feed the production of an extensive haze that encompasses Pluto.

The geology of Pluto and Charon through the eyes of New Horizons.

NASA's New Horizons spacecraft has revealed the complex geology of Pluto and Charon. Pluto's encounter hemisphere shows ongoing surface geological activity centered on a vast basin containing a thick layer of volatile ices that appears to be involved in convection and advection, with a crater retention age no greater than ~10 million years. Surrounding terrains show active glacial flow, apparent transport and rotation of large buoyant water-ice crustal blocks, and pitting, the latter likely caused by sublimation erosion and/or collapse.

A post-remediation assessment in Jersey City of the association of hexavalent chromium in house dust and urinary chromium in children.

Although all chromite ore processing residue (COPR) sites near residential neighborhoods in Jersey City, New Jersey have undergone remediation, recent studies found widespread, but low levels of hexavalent chromium (Cr(+6)) in house dust both in Jersey City and in communities with no known sources of Cr(+6). This study was designed as a follow-up to determine whether there is an association between current Cr(+6) levels in house dust and urinary chromium concentrations in young children. Dust samples (N=369) were collected from 123 homes.