Regulation of Peripheral Myelination through Transcriptional Buffering of Egr2 by an Antisense Long Non-coding RNA

Precise regulation of Egr2 transcription is fundamentally important to the control of peripheral myelination. Here, we describe a long non-coding RNA antisense to the promoter of Egr2 (Egr2-AS-RNA). During peripheral nerve injury, the expression of Egr2-AS-RNA is increased and correlates with decreased Egr2 transcript and protein levels. Ectopic expression of Egr2-AS-RNA in dorsal root ganglion (DRG) cultures inhibits the expression of Egr2 mRNA and induces demyelination. In vivo inhibition of Egr2-AS-RNA using oligonucleotide GapMers released from a biodegradable hydrogel following sciatic nerve injury reverts the EGR2-mediated gene expression profile and significantly delays demyelination. Egr2-AS-RNA gradually recruits H3K27ME3, AGO1, AGO2, and EZH2 on the Egr2 promoter following sciatic nerve injury. Furthermore, expression of Egr2-AS-RNA is regulated through ERK1/2 signaling to YY1, while loss of Ser184 of YY1 regulates binding to Egr2-AS-RNA. In conclusion, we describe functional exploration of an antisense long non-coding RNA in peripheral nervous system (PNS) biology. Keywords: nerve injury response; transcription; RNA epigenetics; antisense RNA; Egr2; myelination; YY1; neureguli

Human fluids alter DNA-acquisition in Acinetobacter baumannii

Transformation is one of the mechanisms of acquisition of foreign genetic material leading to the emergence of multidrug resistant (MDR) bacteria. Recently, human serum albumin (HSA) was shown to specifically increase transformation frequency in the nosocomial pathogen Acinetobacter baumannii. To further assess the relevance of HSA as a possible modulator of A. baumannii transformation in host-pathogen interactions, in this work we examined the effect of different human fluids. We observed a significant increase in transformation frequencies in the presence of pleural fluid, whole blood cells and liquid ascites, and to a lesser extent with urine. The observed effects correlate with both HSA and bacterial content found in the assayed patient fluids. Taken together, these results are in agreement with our previous findings that highlight HSA as a possible host signal with the ability to trigger natural transformation in A. baumannii.Fil: Martinez, Jasmine. California State University; Estados UnidosFil: Liu, Christine. California State University; Estados UnidosFil: Rodman, Nyah. California State University; Estados UnidosFil: Fernandez, Jennifer S.. California State University; Estados UnidosFil: Barberis, Claudia. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Sieira, Rodrigo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Perez, Federico. Louis Stokes Cleveland Department of Veterans Affairs Medical Center; Estados UnidosFil: Bonomo, Robert A.. Louis Stokes Cleveland Department of Veterans Affairs Medical Center; Estados Unidos. Case Western Reserve University; Estados UnidosFil: Ramirez, Maria Soledad. California State University; Estados Unido

Introducing the FAIR Principles for research software

Research software is a fundamental and vital part of research, yet significant challenges to discoverability, productivity, quality, reproducibility, and sustainability exist. Improving the practice of scholarship is a common goal of the open science, open source, and FAIR (Findable, Accessible, Interoperable and Reusable) communities and research software is now being understood as a type of digital object to which FAIR should be applied. This emergence reflects a maturation of the research community to better understand the crucial role of FAIR research software in maximising research value. The FAIR for Research Software (FAIR4RS) Working Group has adapted the FAIR Guiding Principles to create the FAIR Principles for Research Software (FAIR4RS Principles). The contents and context of the FAIR4RS Principles are summarised here to provide the basis for discussion of their adoption. Examples of implementation by organisations are provided to share information on how to maximise the value of research outputs, and to encourage others to amplify the importance and impact of this work

Atrial fibrosis identification with unipolar electrogram eigenvalue distribution analysis in multi-electrode arrays

Atrial fbrosis plays a key role in the initiation and progression of atrial fbrillation (AF). Atrial fbrosis is typically identifed by a peak-to-peak amplitude of bipolar electrograms (b-EGMs) lower than 0.5 mV, which may be considered as ablation targets. Nevertheless, this approach disregards signal spatiotemporal information and b-EGM sensitivity to catheter orientation. To overcome these limitations, we propose the dominant-to-remaining eigenvalue dominance ratio (EIGDR) of unipolar electrograms (u-EGMs) within neighbor electrode cliques as a waveform dispersion measure, hypothesizing that it is correlated with the presence of fbrosis. A simulated 2D tissue with a fbrosis patch was used for validation. We computed EIGDR maps from both original and time-aligned u-EGMs, denoted as R and RA, respectively, also mapping the gain in eigenvalue concentration obtained by the alignment, ΔRA. The performance of each map in detecting fbrosis was evaluated in scenarios including noise and variable electrode-tissue distance. Best results were achieved by RA, reaching 94% detection accuracy, versus the 86% of b-EGMs voltage maps. The proposed strategy was also tested in real u-EGMs from fbrotic and non-fbrotic areas over 3D electroanatomical maps, supporting the ability of the EIGDRs as fbrosis markers, encouraging further studies to confrm their translation to clinical settings

Type 2-Diabetes is Associated With Elevated Levels of TNF-alpha, IL-6 and Adiponectin and Low Levels of Leptin in a Population of Mexican American: A Cross-Sectional Study

The goal of the study was to determine the association between diabetes and inflammation in clinically diagnosed diabetes patients. We hypothesized that low-grade inflammation in diabetes is associated with the level of glucose control. Using a cross-sectional design we compared pro and anti-inflammatory cytokines in a community recruited cohort of 367 Mexican Americans with type 2-diabetes having a wide range blood glucose levels. Cytokines (IL-6, TNF-α, IL-1β, IL-8) and adipokines (adiponectin, resistin and leptin) were measured using multiplex ELISA. Our data indicated that diabetes as whole was strongly associated with elevated levels of IL-6, leptin, CRP and TNF-α, whereas worsening of glucose control was positively and linearly associated with high levels of IL-6, leptin. The associations remained statistically significant even after controlling for BMI and age (p = 0.01). The association between TNF-α, however, was attenuated when comparisons were performed based on glucose control. Strong interaction effects between age and BMI and diabetes were observed for IL-8, resistin, and CRP. The cytokine/adipokine profiles of Mexican Americans with diabetes suggest an association between low-grade inflammation and quality of glucose control. Unique to in our population is that the chronic inflammation is accompanied by lower levels of leptin

A Haploid Pseudo-Chromosome Genome Assembly for a Keystone Sagebrush Species of Western North American Rangelands

Increased ecological disturbances, species invasions, and climate change are creating severe conservation problems for several plant species that are widespread and foundational. Understanding the genetic diversity of these species and how it relates to adaptation to these stressors are necessary for guiding conservation and restoration efforts. This need is particularly acute for big sagebrush (Artemisia tridentata; Asteraceae), which was once the dominant shrub over 1,000,000 km2 in western North America but has since retracted by half and thus has become the target of one of the largest restoration seeding efforts globally. Here, we present the first reference-quality genome assembly for an ecologically important subspecies of big sagebrush (A. tridentata subsp. tridentata) based on short and long reads, as well as chromatin proximity ligation data analyzed using the HiRise pipeline. The final 4.2-Gb assembly consists of 5,492 scaffolds, with nine pseudo-chromosomal scaffolds (nine scaffolds comprising at least 90% of the assembled genome; n = 9). The assembly contains an estimated 43,377 genes based on ab initio gene discovery and transcriptional data analyzed using the MAKER pipeline, with 91.37% of BUSCOs being completely assembled. The final assembly was highly repetitive, with repeat elements comprising 77.99% of the genome, making the Artemisia tridentata subsp. tridentata genome one of the most highly repetitive plant genomes to be sequenced and assembled. This genome assembly advances studies on plant adaptation to drought and heat stress and provides a valuable tool for future genomic research

A Uniform Analysis of the Ly-alpha forest at z = 0 - 5: II. Measuring the mean intensity of the extragalactic ionizing background using the proximity effect

A homogeneous sample of 99 moderate resolution QSO spectra at z > 1.7 were presented in Paper I, including 39 previously unpublished spectra from the Multiple Mirror Telescope. The statistics of the Lyman alpha forest were discussed. In this analysis, we demonstrate that a proximity effect is present in the data, ie. there exists a significant (5.5$\sigma$) deficit of lines at $z_{abs} \approx z_{em}$. Within 1.5 $h^{-1}$ Mpc of the QSO emission redshift, the significance does depend on QSO luminosity, in accordance with the theory that this effect is caused by enhanced ionization of hydrogen in the vicinity of the QSO from UV photons from the QSO itself. The photoionization model of Bajtlik, Duncan, and Ostriker (1988) permits an estimate of the mean intensity of the extragalactic background radiation at the Lyman limit. We compare the results of this standard analysis with those obtained using a maximum likelihood technique. The best fit value for $J(\nu_{0})$ is 7.0$^{+3.4}_{-4.4}$ x 10$^{-22}$ ergs/s/cm$^{2}$/Hz/sr, over the redshift range 1.7 < z < 3.8, using QSO redshifts based on narrow emission lines. The best fit value for the HI ionization rate is 1.9$^{+1.2}_{-1.0}$ x 10$^{-12}$ s$^{-1}$, in good agreement with models of the background which incorporate QSOs only. This large absorption line sample and these techniques for measuring the background and understanding the systematics involved allow us to place what we believe are are the firmest limits on the background at these redshifts.Comment: revised figures 13 and 14, and other minor corrections, 42 Latex pages, 23 encapsulated Postscript figures, uses emulateapj.sty, To appear in the Sept. 2000 ApJ

Effect of starvation and subsequent feeding on glycogen concentration, behavior and mortality in the golden mussel Limnoperna Fortunei (Dunker, 1857) (Bivalvia: Mytilidae)

The success of Limnoperna fortunei as an invasive species is related to its physiological plasticity that allows them to endure adverse environmental conditions. Starvation tolerance is considered to be an important trait associated with bivalve invasiveness. In natural ecosystems, food resources can vary during the year, exposing mussels to variable periods of starvation or limited food availability. Thus, mussels have developed physiological strategies to tolerate fluctuations in food availability. Glycogen concentration has been used in different monitoring studies as an indicator of the nutritional condition of bivalves. The aim of this study was to investigate the physiological responses of L. fortunei based on the glycogen concentrations of specimens under four treatments, comprising differentcombinations of feeding and starvation, during 125 days. The experiment was carried out in two phases. In the phase I, mussels were divided in two treatments: starvation (S) and feeding (F). After 100 days, tissue samples were collected to quantify glycogen concentrations and, each phase I group was divided in two subgroups: starvation (S) and feeding (F), resulting in four treatments. In the phase II, that lasted 25 days, starvation specimens (S) from phase I were allowed to feed (starvation-feeding treatment, or S-F), or continued to undergo starvation (starvation-starvation treatment, or S-S) and the feeding specimens (F) continued feeding (feeding-feeding group, or F-F), or were subjected to starvation (feeding-starvation treatment, or F-S). Behavior (valve-closing) and mortality were recorded in 24 h intervals. After the 25 days (phase II) all specimens were killed, and thei r soft tissue was removed to quantify glycogen concentrations. The glycogen concentration of the S-F treatment was lower than that of the F-S treatment, which was initially allowed to feed (phase I) and then subjected to starvation (phase II). Stability in the glycogen concentrations was observed when the phase II feeding conditions were maintained during the experiments, as observed in the S-S (continued starvation) and F-F (continued feeding) treatments. Based on our glycogen concentrations results, the golden mussel shows a higher tolerance to starvation (125 days) than has previously been published, which suggests that its tolerance strongly influences its invasive behavior.Facultad de Ciencias Naturales y Muse

Effect of starvation and subsequent feeding on glycogen concentration, behavior and mortality in the golden mussel Limnoperna Fortunei (Dunker, 1857) (Bivalvia: Mytilidae)

The success of Limnoperna fortunei as an invasive species is related to its physiological plasticity that allows them to endure adverse environmental conditions. Starvation tolerance is considered to be an important trait associated with bivalve invasiveness. In natural ecosystems, food resources can vary during the year, exposing mussels to variable periods of starvation or limited food availability. Thus, mussels have developed physiological strategies to tolerate fluctuations in food availability. Glycogen concentration has been used in different monitoring studies as an indicator of the nutritional condition of bivalves. The aim of this study was to investigate the physiological responses of L. fortunei based on the glycogen concentrations of specimens under four treatments, comprising differentcombinations of feeding and starvation, during 125 days. The experiment was carried out in two phases. In the phase I, mussels were divided in two treatments: starvation (S) and feeding (F). After 100 days, tissue samples were collected to quantify glycogen concentrations and, each phase I group was divided in two subgroups: starvation (S) and feeding (F), resulting in four treatments. In the phase II, that lasted 25 days, starvation specimens (S) from phase I were allowed to feed (starvation-feeding treatment, or S-F), or continued to undergo starvation (starvation-starvation treatment, or S-S) and the feeding specimens (F) continued feeding (feeding-feeding group, or F-F), or were subjected to starvation (feeding-starvation treatment, or F-S). Behavior (valve-closing) and mortality were recorded in 24 h intervals. After the 25 days (phase II) all specimens were killed, and thei r soft tissue was removed to quantify glycogen concentrations. The glycogen concentration of the S-F treatment was lower than that of the F-S treatment, which was initially allowed to feed (phase I) and then subjected to starvation (phase II). Stability in the glycogen concentrations was observed when the phase II feeding conditions were maintained during the experiments, as observed in the S-S (continued starvation) and F-F (continued feeding) treatments. Based on our glycogen concentrations results, the golden mussel shows a higher tolerance to starvation (125 days) than has previously been published, which suggests that its tolerance strongly influences its invasive behavior.Facultad de Ciencias Naturales y Muse