Nucleus incertus projections to rat medial septum and entorhinal cortex: rare collateralization and septal-gating of temporal lobe theta rhythm activity

Nucleus incertus (NI) neurons in the pontine tegmentum give rise to ascending forebrain projections and express the neuropeptide relaxin-3 (RLN3) which acts via the relaxin-family peptide 3 receptor (RXFP3). Activity in the hippocampus and entorhinal cortex can be driven from the medial septum (MS), and the NI projects to all these centers, where a prominent pattern of activity is theta rhythm, which is related to spatial memory processing. Therefore, we examined the degree of collateralization of NI projections to the MS and the medial temporal lobe (MTL), comprising medial and lateral entorhinal cortex (MEnt, LEnt) and dentate gyrus (DG), and the ability of the MS to drive entorhinal theta in the adult rat. We injected fluorogold and cholera toxin-B into the MS septum and either MEnt, LEnt or DG, to determine the percentage of retrogradely labeled neurons in the NI projecting to both or single targets, and the relative proportion of these neurons that were RLN3-positive ( +). The projection to the MS was threefold stronger than that to the MTL. Moreover, a majority of NI neurons projected independently to either MS or the MTL. However, RLN3 + neurons collateralize significantly more than RLN3-negative (–) neurons. In in vivo studies, electrical stimulation of the NI induced theta activity in the MS and the entorhinal cortex, which was impaired by intraseptal infusion of an RXFP3 antagonist, R3(BΔ23-27)R/I5, particularly at ~ 20 min post-injection. These findings suggest that the MS plays an important relay function in the NI-induced generation of theta within the entorhinal cortex.Funding for open access charge: CRUE-Universitat Jaume IThis research was funded by the Postdoctoral Program of the UJI POSDOC/2021/19 (IG-M); UJI Predoctoral Program PREDOC/2021/19 (MN-S); Fundación Alicia Koplowitz, Spain, grant number 19I436 (FEO-B, FR-B, EC-G); the Spanish Ministerio de Ciencia, Innovación y Universidades, grant number RTI2018-095698-B-I00 (FEO-B, IG-M, FR-B, EC-G); AICO Generalitat Valenciana, grant number AICO/2021/246 (EC-G, FO-B, FR-B), National Health and Medical Research Council of Australia, grant number (ALG), the Spanish Ministerio de Ciencia, Innovación y Universidades, grant number PID2019-107809RB-I00 (AN-M) and Universitat Jaume I, grant numbers UJI-A2017-17 (FR-B) and UJI-B2019-54 (FEO-B).Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. Funding was provided by the Universitat Jaume I, POSDOC/2021/19, PREDOC/2021/19, UJI-A2017-17, Ministerio de Ciencia, Innovación y Universidades, PID2019-107809RB-I00, RTI2018-095698-B-I00, Fundación Alicia Koplowitz, 19I436, Conselleria de Innovación, Universidades, Ciencia y Sociedad Digital, Generalitat Valenciana, AICO/2021/246, National Health and Medical Research Council of Australia, 1067522

Genetic differentiation in the Agave deserti (Agavaceae) complex of the Sonoran desert

The Agave deserti complex, comprising A. deserti, A. cerulata and A. subsimplex, represents a group of species and subspecies with a near allopatric distribution and clear differences in morphology. Genetic differentiation and taxonomic status with respect to spatial distribution of 14 populations of the complex were analyzed in an effort to understand the evolution and speciation process within the genus. Allelic frequencies, levels of genetic variation, expected heterozygosity (H S ), proportion of polymorphic loci (P), and genetic differentiation (y and Nei's genetic distance) were estimated using 41 putative RAPD loci. All three species show high levels of genetic variation (H S ¼ 0.12-0.29, P ¼ 63.4-95.1), and low genetic differentiation between populations and species (y populations ¼ 0.1470.02 (SE); G st ¼ 0.1170.02). Accordingly, gene flow among populations was estimated as high by three different methods (N m ¼ 2.91-6.14). Nei's genetic distances between the three species were low compared to the values obtained from other Agavaceae, and there was no clear correlation with taxonomic divisions. In a UPGMA analysis, A. subsimplex and A. cerulata formed exclusive monospecific clusters, whereas the A. deserti populations appear in more than one cluster together with other species. The results were consistent with a pattern of genetic isolation by distance

Variable Stars in the Quintuplet stellar cluster with the VVV Survey

This article has been accepted for publication in Monthly Notices of the Royal Astronomical Society, © : 2016 C Navarro Molina et al., published by Oxford University Press on behalf of the Royal Astronomical Society. All rights reserved.The Quintuplet cluster is one of the most massive star clusters in the Milky Way, situated very close to the Galactic center. We present a new search for variable stars in the vicinity of the cluster, using the five-year database of the Vista Variables in the Via Lactea (VVV) ESO Public Survey in the near-infrared. A total of 7586 objects were identified in the zone around $2'$ from the cluster center, using 55 $K_S$-band epochs. Thirty-three stars show $K_S$-band variability, 24 of them being previously undiscovered. Most of the variable stars found are slow/semiregular variables, long-period variables of the Mira type, and OH/IR stars. In addition, a good number of our candidates show variations in a rather short timescale. We also propose four Young Stellar Object (YSO) candidates, which could be cluster members.Peer reviewedFinal Published versio

Air temperature measurements using autonomous self-recording dataloggers in mountainous and snow covered areas

High mountain areas are poorly represented by official weather observatories. It implies that new instruments must be evaluated over snow-covered and strongly insolated environments (i.e. mid-latitude mountain areas). We analyzed uncertainty sources over snow covered areas including: 1) temperature logger accuracy and bias of two widely used temperature sensors (Tinytag and iButton); 2) radiation shield performance under various radiation, snow, and wind conditions; 3) appropriate measurement height over snow covered ground; and 4) differences in air temperature measured among nearby devices over a horizontal band. The major results showed the following. 1) Tinytag performance device (mean absolute error: MAE≈ 0.1–0.2°C in relation to the reference thermistor) was superior to the iButton (MAE≈ 0.7°C), which was subject to operating errors. 2) Multi-plate radiation shield showed the best performance under all conditions (> 90% samples has bias between ±0.5°C). The tube shield required wind (> 2.5ms⁠−1) for adequate performance, while the funnel shield required limited radiation (< 400Wm⁠−2). Snow cover causes certain overheating. 3) Air temperatures were found to stabilize at 75–100cm above the snow surface. Air temperature profile was more constant at night, showing a considerable cooling on near surface at midday. 4) Horizontal air temperature differences were larger at midday (0.5°C). These findings indicate that to minimize errors air temperature measurements over snow surfaces should be carried out using multi-plate radiation shields with high-end thermistors such as Tinytags, and be made at a minimum height above the snow covered ground.This study was funded by the research projects “El papel de la nieve en la hidrología de la peninsula ibérica y su respuesta a procesos de cambio global-HIDROIBERNIEVE-CGL2017-82216-R” and CLIMPY “Characterization of the evolution of climate and provision of information for adaptation in the Pyrenees” (FEDER-POCTEFA)

ATP synthase subunit alpha and LV mass in ischaemic human hearts

Mitochondrial dysfunction plays a critical role in the development of ischaemic cardiomyopathy (ICM). In this study, the mitochondrial proteome in the cardiac tissue of ICM patients was analysed by quantitative differential electrophoresis (2D‐DIGE) and mass spectrometry (MS) for the first time to provide new insights into cardiac dysfunction in this cardiomyopathy. We isolated mitochondria from LV samples of explanted hearts of ICM patients (n = 8) and control donors (n = 8) and used a proteomic approach to investigate the variations in mitochondrial protein expression. We found that most of the altered proteins were involved in cardiac energy metabolism (82%). We focused on ATPA, which is involved in energy production, and dihydrolipoyl dehydrogenase, implicated in substrate utilization, and observed that these molecules were overexpressed and that the changes detected in the processes mediated by these proteins were closely related. Notably, we found that ATPA overexpression was associated with reduction in LV mass (r = −0.74, P < 0.01). We also found a substantial increase in the expression of elongation factor Tu, a molecule implicated in protein synthesis, and PRDX3, involved in the stress response. All of these changes were validated using classical techniques and by using novel and precise selected reaction monitoring analysis and an RNA sequencing approach, with the total heart samples being increased to 24. This study provides key insights that enhance our understanding of the cellular mechanisms related to the pathophysiology of ICM and could lead to the development of aetiology‐specific heart failure therapies. ATPA could serve as a molecular target suitable for new therapeutic interventions

Gene expression network analysis reveals new transcriptional regulators as novel factors in human ischemic cardiomyopathy

BACKGROUND: Ischemic cardiomyopathy (ICM) is characterized by transcriptomic changes that alter cellular processes leading to decreased cardiac output. Because the molecular network of ICM is largely unknown, the aim of this study was to characterize the role of new transcriptional regulators in the molecular mechanisms underlying the responses to ischemia. METHODS: Myocardial tissue explants from ICM patients and control (CNT) subjects were analyzed by RNA-Sequencing (RNA-Seq) and quantitative Real-Time PCR. RESULTS: Enrichment analysis of the ICM transcriptomic profile allowed the characterization of novel master regulators. We found that the expression of the transcriptional regulators SP100 (-1.5-fold, p < 0.05), CITED2 (-3.8-fold, p < 0.05), CEBPD (-4.9-fold, p < 0.05) and BCL3 (-3.3-fold, p < 0.05) were lower in ICM than in CNT. To gain insights into the molecular network defined by the transcription factors, we identified CEBPD, BCL3, and HIF1A target genes in the RNA-Seq datasets. We further characterized the biological processes of the target genes by gene ontology annotation. Our results suggest that CEBPD-inducible genes with roles in the inhibition of apoptosis are downregulated and that BCL3-repressible genes are involved in the regulation of cellular metabolism in ICM. Moreover, our results suggest that CITED2 downregulation causes increased expression of HIF1A target genes. Functional analysis of HIF1A target genes revealed that hypoxic and stress response genes are activated in ICM. Finally, we found a significant correlation between the mRNA levels of BCL3 and the mRNA levels of both CEBPD (r = 0.73, p < 0.001) and CITED2 (r = 0.56, p < 0.05). Interestingly, CITED2 mRNA levels are directly related to ejection fraction (EF) (r = 0.54, p < 0.05). CONCLUSIONS: Our data indicate that changes in the expression of SP100, CITED2, CEBPD, and BCL3 affect their transcription regulatory networks, which subsequently alter a number of biological processes in ICM patients. The relationship between CITED2 mRNA levels and EF emphasizes the importance of this transcription factor in ICM. Moreover, our findings identify new mechanisms used to interpret gene expression changes in ICM and provide valuable resources for further investigation of the molecular basis of human cardiac ischemic response.National Institute of Health "Fondo de Investigaciones Sanitarias del Instituto de Salud Carlos III"European Commissio

Air and wet bulb temperature lapse rates and their impact on snowmaking in a Pyrenean ski resort

A set of 17 air temperature and relative humidity sensors were used to analyze the temporal variability of surface air temperature (Tair), wet bulb temperature (Twb), and daily snowmaking hours (SM, number of hours per day with Twb < − 2 °C), lapse rates, and the occurrence of thermal inversions at the Formigal ski resort (Spanish Pyrenees) from December to March during three consecutive ski seasons (2012–2013, 2013–2014, and 2014–2015). The Tair and Twb lapse rates showed strong hourly and daily variability, with both exhibiting almost identical temporal fluctuations. The Twb exhibited average lapse rates that were slightly steeper (− 5.2 °C/km) than those observed for Tair (− 4.9 °C/km). The less steep lapse rates and most thermal inversions were observed in December. Days having less (more) steep Tair and Twb lapse rates were observed under low (high) wind speeds and high (low) relative humidity and air pressure. The temporal dynamics of the SM lapse rates was more complex, as this involved consideration of the average Tair in the ski resort, in addition to the driving factors of the spatio-temporal variability of Twb. Thus, on a number of cold (warm) days, snowmaking was feasible at all elevations at the ski resort, independently of the slopes of the lapse rates. The SM exhibited an average daily lapse rate of 8.2 h/km, with a progressive trend of increase from December to March. Weather types over the Iberian Peninsula tightly control the driving factors of the Tair, Twb, and SM lapse rates (wind speed, relative humidity, and Tair), so the slopes of the lapse rates and the frequency of inversions in relation to elevation for the three variables are very dependent on the occurrence of specific weather types. The less steep lapse rates occurred associated with advections from the southeast, although low lapse rates also occurred during advections from the east and south, and under anticyclonic conditions. The steepest Tair and Twb lapse rates were observed during north and northwest advections, while the steepest rates for SM were observed during days of cyclonic circulation and advections from the northeast.This study was funded by the research project CGL2014-52599-P "Estudio del manto de nieve en la montaña española y su respuesta a la variabilidad y cambio climatico" (Ministry of Economy and Development, MINECO)

Phenotypic and genotypic characteristics of Escherichia coli strains isolated during a longitudinal follow-up study of chronic urinary tract infections

Worldwide, Urinary Tract Infections (UTIs) are an important health problem with many cases reported annually, women being the most affected. UTIs are relevant because they can become a recurrent condition, associated with different factors that contribute to the chronicity of the disease (cUTI). cUTI can be classified as persistent (peUTI) when the causative agent is the same each time the infection occurs or as reinfection (reUTI) when the associated microorganism is different. The purpose of this work was to characterize Escherichia coli isolates obtained in two prospective studies of patients with cUTI, to define which of them corresponded to peUTI and which to reUTI. A total of 394 isolates of E. coli were analyzed by agglutination with specific sera, antimicrobial susceptibility by diffusion disc test, and the phylogroups and presence of genes associated with virulence by PCR assays. Additionally, in some characterized strains adherence, invasiveness, and biofilm formation were analyzed by in vitro assays. The results showed that the peUTI strains belonged mainly to the classical UPEC serogroups (O25, O75, O6), were included in the B2 phylogroup, carried a great number of virulence genes, and were adherent, invasive, and biofilm-forming. Meanwhile, reUTI strains showed great diversity of serogroups, belonged mainly in the A phylogroup, and carried fewer virulence genes. Both peUTI and reUTI strains showed extensively drug-resistant (XDR) and multidrug-resistant (MDR) profiles in the antimicrobial susceptibility test. In conclusion, it appears that peUTIs are caused principally by classical UPEC strains, while reUTIs are caused by strains that appear to be a part of the common E. coli intestinal biota. Moreover, although both peUTI and reUTI strains presented different serotypes and phylogroups, their antimicrobial resistance profile (XDR and MDR) was similar, confirming the importance of regulating prophylactic treatments and seeking alternatives for the treatment and control of cUTI. Finally, it was possible to establish the features of the E. coli strains responsible for peUTI and reUTI which could be helpful to develop a fast diagnostic methodology