Variations in the Abundances of Potassium and Thorium on the Surface of Mercury: Results from the MESSENGER Gamma-Ray Spectrometer

A technique for converting gamma-ray count rates measured by the Gamma-Ray Spectrometer on the MESSENGER spacecraft to spatially resolved maps of the gamma-ray emission from the surface of Mercury is utilized to map the surface distributions of the elements Si, O, and K over the planet's northern hemisphere. Conversion of the K gamma-ray count rates to elemental abundances on the surface reveals variations from 300 to 2400 ppm. A comparison of these abundances with models for the maximum surface temperature suggests the possibility that a temperature-related process is controlling the K abundances on the surface as well as providing K to the exosphere. The abundances of K and Th have been determined for several geologically distinct regions, including Mercury's northern smooth plains and the plains interior to the Caloris basin. The lack of a significant variation in the measured Th abundances suggests that there may be considerable variability in the K/Th abundance ratio over the mapped regions

Major-Element Abundances on the Surface of Mercury: Results from the MESSENGER Gamma-Ray Spectrometer

Orbital gamma-ray measurements obtained by the MESSENGER spacecraft have been analyzed to determine the abundances of the major elements Al, Ca, S, Fe, and Na on the surface of Mercury. The Si abundance was determined and used to normalize those of the other reported elements. The Na analysis provides the first abundance estimate of 2.9 plus or minus 0.1 wt% for this element on Mercury's surface. The other elemental results (S/Si = 0.092 plus or minus 0.015, Ca/Si = 0.24 plus or minus 0.05, and Fe/Si = 0.077 plus or minus 0.013) are consistent with those previously obtained by the MESSENGER X-Ray Spectrometer, including the high sulfur and low iron abundances. Because of different sampling depths for the two techniques, this agreement indicates that Mercury's regolith is, on average, homogenous to a depth of tens of centimeters. The elemental results from gamma-ray and X-ray spectrometry are most consistent with petrologic models suggesting that Mercury's surface is dominated by Mg-rich silicates. We also compare the results with those obtained during the MESSENGER flybys and with ground-based observations of Mercury's surface and exosphere

Outcomes Following Extracorporeal Membrane Oxygenation for Severe COVID-19 in Pregnancy or Post Partum

IMPORTANCE: Existing reports of pregnant patients with COVID-19 disease who require extracorporeal membrane oxygenation (ECMO) are limited, with variable outcomes noted for the maternal-fetal dyad. OBJECTIVE: To examine maternal and perinatal outcomes associated with ECMO used for COVID-19 with respiratory failure during pregnancy. DESIGN, SETTING, AND PARTICIPANTS: This retrospective multicenter cohort study examined pregnant and postpartum patients who required ECMO for COVID-19 respiratory failure at 25 hospitals across the US. Eligible patients included individuals who received care at one of the study sites, were diagnosed with SARS-CoV-2 infection during pregnancy or up to 6 weeks post partum by positive nucleic acid or antigen test, and for whom ECMO was initiated for respiratory failure from March 1, 2020, to October 1, 2022. EXPOSURES: ECMO in the setting of COVID-19 respiratory failure. MAIN OUTCOME AND MEASURES: The primary outcome was maternal mortality. Secondary outcomes included serious maternal morbidity, obstetrical outcomes, and neonatal outcomes. Outcomes were compared by timing of infection during pregnancy or post partum, timing of ECMO initiation during pregnancy or post partum, and periods of circulation of SARS-CoV-2 variants. RESULTS: From March 1, 2020, to October 1, 2022, 100 pregnant or postpartum individuals were started on ECMO (29 [29.0%] Hispanic, 25 [25.0%] non-Hispanic Black, 34 [34.0%] non-Hispanic White; mean [SD] age: 31.1 [5.5] years), including 47 (47.0%) during pregnancy, 21 (21.0%) within 24 hours post partum, and 32 (32.0%) between 24 hours and 6 weeks post partum; 79 (79.0%) had obesity, 61 (61.0%) had public or no insurance, and 67 (67.0%) did not have an immunocompromising condition. The median (IQR) ECMO run was 20 (9-49) days. There were 16 maternal deaths (16.0%; 95% CI, 8.2%-23.8%) in the study cohort, and 76 patients (76.0%; 95% CI, 58.9%-93.1%) had 1 or more serious maternal morbidity events. The largest serious maternal morbidity was venous thromboembolism and occurred in 39 patients (39.0%), which was similar across ECMO timing (40.4% pregnant [19 of 47] vs 38.1% [8 of 21] immediately postpartum vs 37.5% postpartum [12 of 32]; P \u3e .99). CONCLUSIONS AND RELEVANCE: In this multicenter US cohort study of pregnant and postpartum patients who required ECMO for COVID-19-associated respiratory failure, most survived but experienced a high frequency of serious maternal morbidity

PGRMC1 phosphorylation affects cell shape, motility, glycolysis, mitochondrial form and function, and tumor growth.

BackgroundProgesterone Receptor Membrane Component 1 (PGRMC1) is expressed in many cancer cells, where it is associated with detrimental patient outcomes. It contains phosphorylated tyrosines which evolutionarily preceded deuterostome gastrulation and tissue differentiation mechanisms.ResultsWe demonstrate that manipulating PGRMC1 phosphorylation status in MIA PaCa-2 (MP) cells imposes broad pleiotropic effects. Relative to parental cells over-expressing hemagglutinin-tagged wild-type (WT) PGRMC1-HA, cells expressing a PGRMC1-HA-S57A/S181A double mutant (DM) exhibited reduced levels of proteins involved in energy metabolism and mitochondrial function, and altered glucose metabolism suggesting modulation of the Warburg effect. This was associated with increased PI3K/AKT activity, altered cell shape, actin cytoskeleton, motility, and mitochondrial properties. An S57A/Y180F/S181A triple mutant (TM) indicated the involvement of Y180 in PI3K/AKT activation. Mutation of Y180F strongly attenuated subcutaneous xenograft tumor growth in NOD-SCID gamma mice. Elsewhere we demonstrate altered metabolism, mutation incidence, and epigenetic status in these cells.ConclusionsAltogether, these results indicate that mutational manipulation of PGRMC1 phosphorylation status exerts broad pleiotropic effects relevant to cancer and other cell biology

Melanoma Central Nervous System Metastases: An Update to Approaches, Challenges, and Opportunities

Brain metastases are the most common brain malignancy. This review discusses the studies presented at the third annual meeting of the Melanoma Research Foundation in the context of other recent reports on the biology and treatment of melanoma brain metastases (MBM). Although symptomatic MBM patients were historically excluded from immunotherapy trials, efforts from clinicians and patient advocates have resulted in more inclusive and even dedicated clinical trials for MBM patients. The results of checkpoint inhibitor trials were discussed in conversation with current standards of care for MBM patients, including steroids, radiotherapy, and targeted therapy. Advances in the basic scientific understanding of MBM, including the role of astrocytes and metabolic adaptations to the brain microenvironment, are exposing new vulnerabilities which could be exploited for therapeutic purposes. Technical advances including single-cell omics and multiplex imaging are expanding our understanding of the MBM ecosystem and its response to therapy. This unprecedented level of spatial and temporal resolution is expected to dramatically advance the field in the coming years and render novel treatment approaches that might improve MBM patient outcomes

The Mitotic Arrest Deficient Protein MAD2B Interacts with the Clathrin Light Chain A during Mitosis

Contains fulltext : 87811.pdf (publisher's version ) (Open Access)BACKGROUND: Although the mitotic arrest deficient protein MAD2B (MAD2L2) is thought to inhibit the anaphase promoting complex (APC) by binding to CDC20 and/or CDH1 (FZR1), its exact role in cell cycle control still remains to be established. METHODOLOGY/PRINCIPAL FINDINGS: Using a yeast two-hybrid interaction trap we identified the human clathrin light chain A (CLTA) as a novel MAD2B binding protein. A direct interaction was established in mammalian cells via GST pull-down and endogenous co-immunoprecipitation during the G2/M phase of the cell cycle. Through subsequent confocal laser scanning microscopy we found that MAD2B and CLTA co-localize at the mitotic spindle. Clathrin forms a trimeric structure, i.e., the clathrin triskelion, consisting of three heavy chains (CLTC), each with an associated light chain. This clathrin structure has previously been shown to be required for the function of the mitotic spindle through stabilization of kinetochore fibers. Upon siRNA-mediated MAD2B depletion, we found that CLTA was no longer concentrated at the mitotic spindle but, instead, diffusely distributed throughout the cell. In addition, we found a marked increase in the percentage of misaligned chromosomes. CONCLUSIONS/SIGNIFICANCE: Previously, we identified MAD2B as an interactor of the renal cell carcinoma (RCC)-associated protein PRCC. In addition, we found that fusion of PRCC with the transcription factor TFE3 in t(X;1)(p11;q21)-positive RCCs results in an impairment of this interaction and a concomitant failure to shuttle MAD2B to the nucleus. Our current data show that MAD2B interacts with CLTA during the G2/M phase of the cell cycle and that depletion of MAD2B leads to a marked increase in the percentage of misaligned chromosomes and a redistribution of CLTA during mitosis

Global change effects on plant communities are magnified by time and the number of global change factors imposed

Global change drivers (GCDs) are expected to alter community structure and consequently, the services that ecosystems provide. Yet, few experimental investigations have examined effects of GCDs on plant community structure across multiple ecosystem types, and those that do exist present conflicting patterns. In an unprecedented global synthesis of over 100 experiments that manipulated factors linked to GCDs, we show that herbaceous plant community responses depend on experimental manipulation length and number of factors manipulated. We found that plant communities are fairly resistant to experimentally manipulated GCDs in the short term (<10 y). In contrast, long-term (≥10 y) experiments show increasing community divergence of treatments from control conditions. Surprisingly, these community responses occurred with similar frequency across the GCD types manipulated in our database. However, community responses were more common when 3 or more GCDs were simultaneously manipulated, suggesting the emergence of additive or synergistic effects of multiple drivers, particularly over long time periods. In half of the cases, GCD manipulations caused a difference in community composition without a corresponding species richness difference, indicating that species reordering or replacement is an important mechanism of community responses to GCDs and should be given greater consideration when examining consequences of GCDs for the biodiversity–ecosystem function relationship. Human activities are currently driving unparalleled global changes worldwide. Our analyses provide the most comprehensive evidence to date that these human activities may have widespread impacts on plant community composition globally, which will increase in frequency over time and be greater in areas where communities face multiple GCDs simultaneously

Eleven strategies for making reproducible research and open science training the norm at research institutions

Across disciplines, researchers increasingly recognize that open science and reproducible research practices may accelerate scientific progress by allowing others to reuse research outputs and by promoting rigorous research that is more likely to yield trustworthy results. While initiatives, training programs, and funder policies encourage researchers to adopt reproducible research and open science practices, these practices are uncommon inmanyfields. Researchers need training to integrate these practicesinto their daily work. We organized a virtual brainstorming event, in collaboration with the German Reproducibility Network, to discuss strategies for making reproducible research and open science training the norm at research institutions. Here, weoutline eleven strategies, concentrated in three areas:(1)offering training, (2)adapting research assessment criteria and program requirements, and (3) building communities. We provide a brief overview of each strategy, offer tips for implementation,and provide links to resources. Our goal is toencourage members of the research community to think creatively about the many ways they can contribute and collaborate to build communities,and make reproducible research and open sciencetraining the norm. Researchers may act in their roles as scientists, supervisors, mentors, instructors, and members of curriculum, hiring or evaluation committees. Institutionalleadership and research administration andsupport staff can accelerate progress by implementing change across their institution

Electrochemical Nanoprobes for Single-Cell Analysis

The measurement of key molecules in individual cells with minimal disruption to the biological milieu is the next frontier in single-cell analyses. Nanoscale devices are ideal analytical tools because of their small size and their potential for high spatial and temporal resolution recordings. Here, we report the fabrication of disk-shaped carbon nanoelectrodes whose radius can be precisely tuned within the range 5–200 nm. The functionalization of the nanoelectrode with platinum allowed the monitoring of oxygen consumption outside and inside a brain slice. Furthermore, we show that nanoelectrodes of this type can be used to impale individual cells to perform electrochemical measurements within the cell with minimal disruption to cell function. These nanoelectrodes can be fabricated combined with scanning ion conductance microscopy probes, which should allow high resolution electrochemical mapping of species on or in living cells