Hydraulic transmissivity inferred from ice-sheet relaxation following Greenland supraglacial lake drainages

© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Lai, C.-Y., Stevens, L. A., Chase, D. L., Creyts, T. T., Behn, M. D., Das, S. B., & Stone, H. A. Hydraulic transmissivity inferred from ice-sheet relaxation following Greenland supraglacial lake drainages. Nature Communications, 12(1), (2021): 3955, https://doi.org/10.1038/s41467-021-24186-6.Surface meltwater reaching the base of the Greenland Ice Sheet transits through drainage networks, modulating the flow of the ice sheet. Dye and gas-tracing studies conducted in the western margin sector of the ice sheet have directly observed drainage efficiency to evolve seasonally along the drainage pathway. However, the local evolution of drainage systems further inland, where ice thicknesses exceed 1000 m, remains largely unknown. Here, we infer drainage system transmissivity based on surface uplift relaxation following rapid lake drainage events. Combining field observations of five lake drainage events with a mathematical model and laboratory experiments, we show that the surface uplift decreases exponentially with time, as the water in the blister formed beneath the drained lake permeates through the subglacial drainage system. This deflation obeys a universal relaxation law with a timescale that reveals hydraulic transmissivity and indicates a two-order-of-magnitude increase in subglacial transmissivity (from 0.8 ± 0.3 mm3 to 215 ± 90.2 mm3) as the melt season progresses, suggesting significant changes in basal hydrology beneath the lakes driven by seasonal meltwater input.C.-Y.L. and L.A.S thank Lamont-Doherty Earth Observatory for funding through the Lamont Postdoctoral Fellowships. D.L.C acknowledges support from the National Science Foundation (NSF) Graduate Research Fellowship. T.T.C. was supported by NSF’s Office of Polar Programs (NSF-OPP) through OPP-1643970, the National Aeronautics and Space Administration (NASA) through NNX16AJ95G, and a grant from the Vetlesen Foundation. S.B.D. and M.D.B. acknowledge funding from NSF-OPP and NASA’s Cryospheric Sciences Program through OPP-1838410, ARC-1023364, ARC-0520077, and NNX10AI30G. H.A.S. thanks the High Meadows Environmental Institute and the Carbon Mitigation Initiative at Princeton University. This publication was supported by the Princeton University Library Open Access Fund

Hydrocarbons Are Essential for Optimal Cell Size, Division, and Growth of Cyanobacteria.

Cyanobacteria are intricately organized, incorporating an array of internal thylakoid membranes, the site of photosynthesis, into cells no larger than other bacteria. They also synthesize C15-C19 alkanes and alkenes, which results in substantial production of hydrocarbons in the environment. All sequenced cyanobacteria encode hydrocarbon biosynthesis pathways, suggesting an important, undefined physiological role for these compounds. Here, we demonstrate that hydrocarbon-deficient mutants of $\textit{Synechocystis }$ sp. PCC 7002 and $\textit{Synechocystis }$ sp. PCC 6803 exhibit significant phenotypic differences from wild type, including enlarged cell size, reduced growth, and increased division defects. Photosynthetic rates were similar between strains, although a minor reduction in energy transfer between the soluble light harvesting phycobilisome complex and membrane-bound photosystems was observed. Hydrocarbons were shown to accumulate in thylakoid and cytoplasmic membranes. Modeling of membranes suggests these compounds aggregate in the center of the lipid bilayer, potentially promoting membrane flexibility and facilitating curvature. In vivo measurements confirmed that $\textit{Synechocystis }$ sp. PCC 7002 mutants lacking hydrocarbons exhibit reduced thylakoid membrane curvature compared to wild type. We propose that hydrocarbons may have a role in inducing the flexibility in membranes required for optimal cell division, size, and growth, and efficient association of soluble and membrane bound proteins. The recent identification of C15-C17 alkanes and alkenes in microalgal species suggests hydrocarbons may serve a similar function in a broad range of photosynthetic organisms.T.L. was supported by BBSRC Research Grant BB/J016985/1 to C.W.M. D.J.L-S. was supported by the Environmental Services Association Education Trust. L.L.B was supported by a BBSRC Doctoral Training Grant (BB/F017464/1)

Another intermediate mass black hole in a starburst galaxy?: The luminous X-ray source in NGC 3628 reappears

In a 52 ks-long Chandra ACIS-S observation of the nearby starburst galaxy NGC 3628, obtained to study the starburst-driven outflow from this galaxy, we have detected a very luminous (L_X = 1.1e40 erg/s in the 0.3-8.0 keV energy band) point source located at least 20 arcsec (~970 pc) from the nucleus of the galaxy. No radio, optical or near-IR counterpart to this source has been found. This is most probably the reappearance of the strongly-variable X-ray-luminous source discovered by Dahlem et al (1995), which faded by a factor >27 between December 1991 and March 1994 (at which point it had faded below the detection limit in a ROSAT HRI observation). This source is clearly a member of an enigmatic class of X-ray sources that are considerably more luminous than conventional X-ray binaries but less luminous than AGN, and which are not found at the dynamical center of the host galaxy. The Chandra spectrum is best-fit by an absorbed power law model with a photon index of Gamma = 1.8+/-0.2, similar to that seen in Galactic BH binary candidates in their hard state. Bremsstrahlung models or multi-color disk models (the favored spectral model for objects in this class based on ASCA observations) can provide statistically acceptable fits only if the data at energies E > 5 keV is ignored. This is one of the first X-ray spectra of such an object that is unambiguously that of the source alone, free from the spectral contamination by X-ray emission from the rest of the galaxy that affects previous spectral studies of these objects using ASCA.Comment: Accepted for publication in the Ap

Microglia contribute to circuit defects in Mecp2 null mice independent of microglia-specific loss of Mecp2 expression

Microglia, the resident CNS macrophages, have been implicated in the pathogenesis of Rett Syndrome (RTT), an X-linked neurodevelopmental disorder. However, the mechanism by which microglia contribute to the disorder is unclear and recent data suggest that microglia do not play a causative role. Here, we use the retinogeniculate system to determine if and how microglia contribute to pathogenesis in a RTT mouse model, the Mecp2 null mouse (Mecp2tm1.1Bird/y). We demonstrate that microglia contribute to pathogenesis by excessively engulfing, thereby eliminating, presynaptic inputs at end stages of disease (≥P56 Mecp2 null mice) concomitant with synapse loss. Furthermore, loss or gain of Mecp2 expression specifically in microglia (Cx3cr1CreER;Mecp2fl/yor Cx3cr1CreER; Mecp2LSL/y) had little effect on excessive engulfment, synapse loss, or phenotypic abnormalities. Taken together, our data suggest that microglia contribute to end stages of disease by dismantling neural circuits rendered vulnerable by loss of Mecp2 in other CNS cell types. DOI: http://dx.doi.org/10.7554/eLife.15224.00

Evaluation and Recommendations on Good Clinical Laboratory Practice Guidelines for Phase I–III Clinical Trials

Marcella Sarzotti-Kelsoe and colleagues harmonize various approaches to Good Clinical Laboratory Practice for clinical trials into a single set of recommendations

Medication Adherence During Adjunct Therapy With Statins and ACE Inhibitors in Adolescents With Type 1 Diabetes.

OBJECTIVE: Suboptimal adherence to insulin treatment is a main issue in adolescents with type 1 diabetes. However, to date, there are no available data on adherence to adjunct noninsulin medications in this population. Our aim was to assess adherence to ACE inhibitors and statins and explore potential determinants in adolescents with type 1 diabetes. RESEARCH DESIGN AND METHODS: There were 443 adolescents with type 1 diabetes recruited into the Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial (AdDIT) and exposed to treatment with two oral drugs-an ACE inhibitor and a statin-as well as combinations of both or placebo for 2-4 years. Adherence was assessed every 3 months with the Medication Event Monitoring System (MEMS) and pill count. RESULTS: Median adherence during the trial was 80.2% (interquartile range 63.6-91.8) based on MEMS and 85.7% (72.4-92.9) for pill count. Adherence based on MEMS and pill count dropped from 92.9% and 96.3%, respectively, at the first visit to 76.3% and 79.0% at the end of the trial. The percentage of study participants with adherence ≥75% declined from 84% to 53%. A good correlation was found between adherence based on MEMS and pill count (r = 0.82, P < 0.001). Factors associated with adherence were age, glycemic control, and country. CONCLUSIONS: We report an overall good adherence to ACE inhibitors and statins during a clinical trial, although there was a clear decline in adherence over time. Older age and suboptimal glycemic control at baseline predicted lower adherence during the trial, and, predictably, reduced adherence was more prevalent in subjects who subsequently dropped out

Dissection of artifactual and confounding glial signatures by single-cell sequencing of mouse and human brain

A key aspect of nearly all single-cell sequencing experiments is dissociation of intact tissues into single-cell suspensions. While many protocols have been optimized for optimal cell yield, they have often overlooked the effects that dissociation can have on ex vivo gene expression. Here, we demonstrate that use of enzymatic dissociation on brain tissue induces an aberrant ex vivo gene expression signature, most prominently in microglia, which is prevalent in published literature and can substantially confound downstream analyses. To address this issue, we present a rigorously validated protocol that preserves both in vivo transcriptional profiles and cell-type diversity and yield across tissue types and species. We also identify a similar signature in postmortem human brain single-nucleus RNA-sequencing datasets, and show that this signature is induced in freshly isolated human tissue by exposure to elevated temperatures ex vivo. Together, our results provide a methodological solution for preventing artifactual gene expression changes during fresh tissue digestion and a reference for future deeper analysis of the potential confounding states present in postmortem human samples

GWAS for systemic sclerosis identifies multiple risk loci and highlights fibrotic and vasculopathy pathways

Systemic sclerosis (SSc) is an autoimmune disease that shows one of the highest mortality rates among rheumatic diseases. We perform a large genome-wide association study (GWAS), and meta-analysis with previous GWASs, in 26,679 individuals and identify 27 independent genome-wide associated signals, including 13 new risk loci. The novel associations nearly double the number of genome-wide hits reported for SSc thus far. We define 95% credible sets of less than 5 likely causal variants in 12 loci. Additionally, we identify specific SSc subtype-associated signals. Functional analysis of high-priority variants shows the potential function of SSc signals, with the identification of 43 robust target genes through HiChIP. Our results point towards molecular pathways potentially involved in vasculopathy and fibrosis, two main hallmarks in SSc, and highlight the spectrum of critical cell types for the disease. This work supports a better understanding of the genetic basis of SSc and provides directions for future functional experiments