Oxygen pathway modeling estimates high Reactive oxygen species production above the highest permanent human habitation.

The production of reactive oxygen species (ROS) from the inner mitochondrial membrane is one of many fundamental processes governing the balance between health and disease. It is well known that ROS are necessary signaling molecules in gene expression, yet when expressed at high levels, ROS may cause oxidative stress and cell damage. Both hypoxia and hyperoxia may alter ROS production by changing mitochondrial Po2 (). Because depends on the balance between O2 transport and utilization, we formulated an integrative mathematical model of O2 transport and utilization in skeletal muscle to predict conditions to cause abnormally high ROS generation. Simulations using data from healthy subjects during maximal exercise at sea level reveal little mitochondrial ROS production. However, altitude triggers high mitochondrial ROS production in muscle regions with high metabolic capacity but limited O2 delivery. This altitude roughly coincides with the highest location of permanent human habitation. Above 25,000 ft., more than 90% of exercising muscle is predicted to produce abnormally high levels of ROS, corresponding to the "death zone" in mountaineering

Contrasting environmental preferences of photosynthetic and non‐photosynthetic soil cyanobacteria across the globe

Aim: Cyanobacteria have shaped the history of life on Earth and continue to play important roles as carbon and nitrogen fixers in terrestrial ecosystems. However, their global distribution and ecological preferences remain poorly understood, particularly for two recently discovered non‐photosynthetic cyanobacterial classes (Sericytochromatia and Melainabacteria). Location: Two hundred and thirty‐seven locations across six continents encompassing multiple climates (arid, temperate, tropical, continental and polar) and vegetation types (forests, grasslands and shrublands). Time period: Sampling was carried out between 2003 and 2015. Major taxa studied: Photosynthetic and non‐photosynthetic cyanobacterial taxa. Methods: We conducted a field survey and used co‐occurrence network analysis and structural equation modelling to evaluate the distribution and environmental preferences of soil cyanobacteria across the globe. These ecological preferences were used to create a global atlas (predictive distribution maps) of soil cyanobacteria. Results: Network analyses identified three major groups of cyanobacterial taxa, which resembled the three main cyanobacterial classes: the photosynthetic Oxyphotobacteria‐dominated cluster, which were prevalent in arid and semi‐arid areas, and the non‐photosynthetic Sericytochromatia‐ and Melainabacteria‐dominated clusters, which preferred hyper‐arid oligotrophic and acidic/humid environments, respectively. Main conclusions: This study provides new insights into the environmental preferences of non‐photosynthetic cyanobacteria in soils globally. Our findings highlight the contrasting environmental preferences among the three clusters of cyanobacteria and suggest that alterations in environmental conditions linked to climate change might result in important changes in the ecology and biogeography of these functionally important microorganisms.M.D.-B. is supported by a Ramón y Cajal grant from the Spanish Ministry of Science and Innovation (RYC2018-025483-I), and by the BES grant agreement No LRB17\1019 (MUSGONET). The work of C.C.-D. and F.T.M. and the global drylands database were supported by the European Research Council [ERC Grant Agreements 242658 (BIOCOM) and 647038 (BIODESERT)] and by the Spanish Ministry of Economy and Competitiveness (BIOMOD project, ref. CGL2013-44661-R). F.T.M. acknowledges support from Generalitat Valenciana (BIOMORES project, ref. CIDEGENT/2018/041). Research on biodiversity by B.K.S. is supported by the Australian Research Council (DP170104634). R.D.B. was supported by the U.K. Department of Environment, Food and Rural Affairs (DEFRA) project no. BD5003 and a Biotechnology and Biological Sciences Research Council (BBSRC) International Exchange Grant (BB/L026406/1)

Targeting SHIP-1 in Myeloid Cells Enhances Trained Immunity and Boosts Response to Infection

beta-Glucan-induced trained immunity in myeloid cells leads to long-term protection against secondary infections. Although previous studies have characterized this phenomenon, strategies to boost trained immunity remain undefined. We found that beta-glucan-trained macrophages from mice with a myeloid-specific deletion of the phosphatase SHIP-1 (LysM Delta SHIP-1) showed enhanced proinflammatory cytokine production in response to lipopolysaccharide. Following beta-glucan training, SHIP-1-deficient macrophages exhibited increased phosphorylation of Akt and mTOR targets, correlating with augmented glycolytic metabolism. Enhanced training in the absence of SHIP-1 relied on histone methylation and acetylation. Trained LysM Delta SHIP-1 mice produced increased amounts of proinflammatory cytokines upon rechallenge in vivo and were better protected against Candida albicans infection compared with control littermates. Pharmacological inhibition of SHIP-1 enhanced trained immunity against Candida infection in mouse macrophages and human peripheral blood mononuclear cells. Our data establish proof of concept for improvement of trained immunity and a strategy to achieve it by targeting SHIP-1.We thank the members of the Immunobiology Lab for useful discussions. We thank the CNIC facilities and personnel, particularly Santiago Rodriguez and Ruben Mota, for their support. P.S.-L. is funded by grant BES-2015-072699 (´´Ayudas para Contratos Predoctorales para la Formacion de Doctores 2015´´) from the Spanish Ministry of Economy, Industry and Competitiveness (MINECO). C.d.F. is supported by the Asociacion Espanola Contra el Cancer (AECC) Foundation as a recipient of an ``Ayuda Fundacion Cientifica AECC a Personal Investigador en Cancer´´ grant. Work in the Sancho laboratory is funded by CNIC and grant SAF2016-79040-R from MINECO, Agencia Estatal de Investigacion, and FEDER (European Fund for Regional Development); grant B2017/BMD-3733 Immunothercan-CM from Comunidad de Madrid; grant RD16/0015/0018-REEM from FIS-Instituto de Salud Carlos III, MINECO, and FEDER; Foundation Acteria; a Constantes y Vitales prize (Atresmedia); Foundation La Marato de TV3 (grant 201723); the European Commission (grant 635122-PROCROP H2020); and the European Research Council (ERC-2016-Consolidator Grant 725091). CNIC is supported by MINECO and the Pro-CNIC Foundation and is a Severo Ochoa Center of Excellence (MINECO award SEV-2015-0505). W.G.K. is an Empire Scholar of the State of New York, the Murphy Family Professor of Children's Oncology Research, and is supported by funds from the Paige Arnold Butterfly Run.S

A Case of Urogenital Human Schistosomiasis from a Non-endemic Area

© 2015 Calvo-Cano et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The attached file is the published version of the article

A mononucleotide repeat in PRRT2 is an important, frequent target of mismatch repair deficiency in cancer

The DNA mismatch repair (MMR) system corrects DNA replication mismatches thereby contributing to the maintenance of genomic stability. MMR deficiency has been observed in prostate cancer but its impact on the genomic landscape of these tumours is not known. In order to identify MMR associated mutations in prostate cancer we have performed whole genome sequencing of the MMR deficient PC346C prostate cancer cell line. We detected a total of 1196 mutations in PC346C which was 1.5-fold higher compared to a MMR proficient prostate cancer sample (G089). Of all different mutation classes, frameshifts in mononucleotide repeat (MNR) sequences were significantly enriched in the PC346C sample. As a result, a selection of genes with frameshift mutations in MNR was further assessed regarding its mutational status in a comprehensive panel of prostate, ovarian, endometrial and colorectal cancer cell lines. We identified PRRT2 and DAB2IP to be frequently mutated in MMR deficient cell lines, colorectal and endometrial cancer patient samples. Further characterization of PRRT2 revealed an important role of this gene in cancer biology. Both normal prostate cell lines and a colorectal cancer cell line showed increased proliferation, migration and invasion when expressing the mutated form of PRRT2 (ΔPRRT2). The wild-type PRRT2 (PRRT2wt) had an inhibitory effect in proliferation, consistent with the low expression level of PRRT2 in cancer versus normal prostate samples

Electromyography: a simple and accessible tool to assess physical performance and health during hypoxia training. A systematic review

Hypoxia causes reduced partial pressure of oxygen in arterial blood and induces adaptations in skeletal muscle that may affect individuals’ physical performance and muscular health. These muscular changes are detectable and quantifiable by electromyography (EMG), an instrument that assesses electrical activity during active contraction at rest. EMG is a relatively simple and accessible technique for all patients, one that can show the degree of the sensory and motor functions because it provides information about the status of the peripheral nerves and muscles. The main goal of this review is to evaluate the scientific evidence of EMG as an instrument for monitoring different responses of skeletal muscles subjected to external stimuli such as hypoxia and physical activity. A structured search was conducted following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines in Medline/PubMed, Scielo, Google Scholar, Web of Science, and Cochrane Library Plus. The search included articles published in the last 25 years until May 2020 and was restricted to English- and Spanish-language publications. As such, investigators identified nine articles that met the search criteria. The results determined that EMG was able to detect muscle fatigue from changes in the frequency spectrum. When a muscle was fatigued, high frequency components decreased and low frequency components increased. In other studies, EMG determined muscle activation increased during exercise by recruiting motor units and by increasing the intensity of muscle contractions. Finally, it was also possible to calculate the mean quadriceps quadratic activity used to obtain an image of muscle activation. In conclusion, EMG offers a suitable tool for monitoring the different skeletal muscle responses and has sufficient sensitivity to detect hypoxia-induced muscle changes produced by hypoxic stimuli. Moreover, EMG enhances an extension of physical examination and tests motor-system integrity

Giant Superfluorescent Bursts from a Semiconductor Magnetoplasma

Currently, considerable resurgent interest exists in the concept of superradiance (SR), i.e., accelerated relaxation of excited dipoles due to cooperative spontaneous emission, first proposed by Dicke in 1954. Recent authors have discussed SR in diverse contexts, including cavity quantum electrodynamics, quantum phase transitions, and plasmonics. At the heart of these various experiments lies the coherent coupling of constituent particles to each other via their radiation field that cooperatively governs the dynamics of the whole system. In the most exciting form of SR, called superfluorescence (SF), macroscopic coherence spontaneously builds up out of an initially incoherent ensemble of excited dipoles and then decays abruptly. Here, we demonstrate the emergence of this photon-mediated, cooperative, many-body state in a very unlikely system: an ultradense electron-hole plasma in a semiconductor. We observe intense, delayed pulses, or bursts, of coherent radiation from highly photo-excited semiconductor quantum wells with a concomitant sudden decrease in population from total inversion to zero. Unlike previously reported SF in atomic and molecular systems that occur on nanosecond time scales, these intense SF bursts have picosecond pulse-widths and are delayed in time by tens of picoseconds with respect to the excitation pulse. They appear only at sufficiently high excitation powers and magnetic fields and sufficiently low temperatures - where various interactions causing decoherence are suppressed. We present theoretical simulations based on the relaxation and recombination dynamics of ultrahigh-density electron-hole pairs in a quantizing magnetic field, which successfully capture the salient features of the experimental observations.Comment: 21 pages, 4 figure

Multiparametric renal magnetic resonance imaging: A reproducibility study in renal allografts with stable function

Monitoring renal allograft function after transplantation is key for the early detection of allograft impairment, which in turn can contribute to preventing the loss of the allograft. Multiparametric renal MRI (mpMRI) is a promising noninvasive technique to assess and characterize renal physiopathology; however, few studies have employed mpMRI in renal allografts with stable function (maintained function over a long time period). The purposes of the current study were to evaluate the reproducibility of mpMRI in transplant patients and to characterize normal values of the measured parameters, and to estimate the labeling efficiency of Pseudo-Continuous Arterial Spin Labeling (PCASL) in the infrarenal aorta using numerical simulations considering experimental measurements of aortic blood flow profiles. The subjects were 20 transplant patients with stable kidney function, maintained over 1 year. The MRI protocol consisted of PCASL, intravoxel incoherent motion, and T1 inversion recovery. Phase contrast was used to measure aortic blood flow. Renal blood flow (RBF), diffusion coefficient (D), pseudo-diffusion coefficient (D*), flowing fraction ( f ), and T1 maps were calculated and mean values were measured in the cortex and medulla. The labeling efficiency of PCASL was estimated from simulation of Bloch equations. Reproducibility was assessed with the within-subject coefficient of variation, intraclass correlation coefficient, and Bland-Altman analysis. Correlations were evaluated using the Pearson correlation coefficient. The significance level was p less than 0.05. Cortical reproducibility was very good for T1, D, and RBF, moderate for f , and low for D*, while medullary reproducibility was good for T1 and D. Significant correlations in the cortex between RBF and f (r = 0.66), RBF and eGFR (r = 0.64), and D* and eGFR (r = -0.57) were found. Normal values of the measured parameters employing the mpMRI protocol in kidney transplant patients with stable function were characterized and the results showed good reproducibility of the techniques