First passage times as a measure of hysteresis in stochastic gene regulatory circuits

GAIN Oportunius Grant from Xunta de Galicia.[Abstract]: In the context of phenotype switching and cell fate determination, numerousexperimental studies report hysteresis, despite the fact that the (forward) Chemical Master Equation governing the inherently stochastic underlying gene regulatory networks has a unique steady state (precluding memory effects and hysteresis). In previous works, we demonstrate thathysteresis is a transient phenomenon in systems far from the thermodynamic limit, using the convergence rates of the partial integro-differential equation associated to the forward master equation governing the stochastic process. Here, we make use of the backward master equationto quantify hysteresis and irreversibility based on First Passage Times. First, we derive the backward master equation for a gene regulatory network with protein production in bursts. Solving this equation, we obtain the probability distributions of the first times to reach some fixed final state from one starting state. The mean first passage time provides a measure to quantify how hysteresis and irreversibility in gene regulation at the singlecell level are transient effects that vanish at steady state. In addition, we provide a theoretical basis that reconciles phenotype coexistence and prevalence far from the thermodynamic limit. In fact, we substitute the notion of pseudo-potential (the so-called Waddington landscape) by a time evolving landscape built upon the Chemical Master Equation (CME) in which phenotypes,rather than prevail, persist with different intensities.Ministerio de Ciencia e Innovación/Agencia Estatal de Investigación; FJC2019-041397-

Development and Organization of the Lamprey Telencephalon with Special Reference to the GABAergic System

Lampreys, together with hagfishes, represent the sister group of gnathostome vertebrates. There is an increasing interest for comparing the forebrain organization observed in lampreys and gnathostomes to shed light on vertebrate brain evolution. Within the prosencephalon, there is now a general agreement on the major subdivisions of the lamprey diencephalon; however, the organization of the telencephalon, and particularly its pallial subdivisions, is still a matter of controversy. In this study, recent progress on the development and organization of the lamprey telencephalon is reviewed, with particular emphasis on the GABA immunoreactive cell populations trying to understand their putative origin. First, we describe some early general cytoarchitectonic events by searching the classical literature as well as our collection of embryonic and prolarval series of hematoxylin-stained sections. Then, we comment on the cell proliferation activity throughout the larval period, followed by a detailed description of the early events on the development of the telencephalic GABAergic system. In this context, lampreys apparently do not possess the same molecularly distinct subdivisions of the gnathostome basal telencephalon because of the absence of a Nkx2.1-expressing domain in the developing subpallium; a fact that has been related to the absence of a medial ganglionic eminence as well as of its derived nucleus in gnathostomes, the pallidum. Therefore, these data raise interesting questions such as whether or not a different mechanism to specify telencephalic GABAergic neurons exists in lampreys or what are their migration pathways. Finally, we summarize the organization of the adult lamprey telencephalon by analyzing the main proposed conceptions, including the available data on the expression pattern of some developmental regulatory genes which are of importance for building its adult shape

Diagnóstico ecográfico en un caso clínico de quiste paraprostático canino

El artículo describe el diagnóstico ecográfico de un caso clínico de quiste paraprostático en un perro, discutiendo la importancia de la imagen en el diagnóstico de afecciones prostáticas y mostrando imágenes radiológicas y ecográficas.This paper describes the ultrasonographic diagnosis in a case of paraprostatic cyst in a dog. Importance of imaging diagnostic methods in prostatic diseases are discussed. Radiologic and ultrasound images are shown

Equality in higher education in Spain and the UK: Mismatch between rhetoric and policy?

Making use of Grisay's typology of educational equality, the paper analyses rhetoric and policy on equality in higher education (HE) in Spain and the UK in the period 1996–2004, using electoral manifestos, policy papers, legislation and academic literature. We find that in both countries, and in spite of similar pressures and levels of access to HE, the prevailing notions of educational equality vary. We also find evidence of a good match between policy rhetoric and policy practice in terms of areas of intervention, but not in the strength of these interventions

Resource use efficiency is affected by phytoplankton community changes and geochemical shifts over time in a coastal upwelling area (NE Atlantic).

abstractTime series records are crucial to understand the dynamical processes that occur within phytoplankton communities. This is even more important in the context of the current global change that is already forcing alterations of unprecedented nature and might have unknown consequences for multiple ecosystem processes. Here we present time series analyses of the biogeochemical trends that occurred in the shelf of the Galician coast (station 2 off A Coruña, NE Atlantic) since late 1980s. Upwelling strength and sea temperature in the area have not changed substantially during the last decades. However, while nitrate fertilization from upwelled waters has remained relatively stable, phosphate concentration has increased leading to a negative trend in the N:P ratio. Those trends have impacted the phytoplankton resource use efficiency jointly with the evenness of the community. Phytoplankton used resources more efficiently at higher values of upwelling strength and at lower values of nutrient concentration and evenness. Phytoplankton communities that were more even had higher dinoflagellate diversity contrasting to dominance of diatoms that used resources more efficiently. Moreover, variability in resource use efficiency increased with evenness.IEO (RADIALES-11

New properties of a bioinspired pyridine benzimidazole compound as a novel differential staining agent for endoplasmic reticulum and Golgi apparatus in fluorescence live cell imaging

Indexación: Scopus.In this study, we explored new properties of the bioinspired pyridine benzimidazole compound B2 (2,4-di-tert-butyl-6-(3H-imidazo[4,5-c]pyridine-2-yl)phenol) regarding its potential use as a differential biomarker. For that, we performed 1D 1HNMR (TOCSY), UV-Vis absorption spectra in different organic solvents, voltammetry profile (including a scan-rate study), and TD-DFT calculations that including NBO analyses, to provide valuable information about B2 structure and luminescence. In our study, we found that the B2 structure is highly stable, where the presence of an intramolecular hydrogen bond (IHB) seems to have a crucial role in the stability of luminescence, and its emission can be assigned as fluorescence. In fact, we found that the relatively large Stokes Shift observed for B2 (around 175 nm) may be attributed to the stability of the B2 geometry and the strength of its IHB. On the other hand, we determined that B2 is biocompatible by cytotoxicity experiments in HeLa cells, an epithelial cell line. Furthermore, in cellular assays we found that B2 could be internalized by passive diffusion in absence of artificial permeabilization at short incubation times (15 min to 30 min). Fluorescence microscopy studies confirmed that B2 accumulates in the endoplasmic reticulum (ER) and Golgi apparatus, two organelles involved in the secretory pathway. Finally, we determined that B2 exhibited no noticeable blinking or bleaching after 1 h of continuous exposure. Thus, B2 provides a biocompatible, rapid, simple, and efficient way to fluorescently label particular organelles, producing similar results to that obtained with other well-established but more complex methods. © 2018 Llancalahuen, Fuentes, Carreño, Zúñiga, Páez-Hernández, Gacitúa, Polanco, Preite, Arratia-Pérez and Otero.https://www.frontiersin.org/articles/10.3389/fchem.2018.00345/ful

Net sea-air CO2 flux uncertainties in the Bay of Biscay based on the choice of wind speed products and gas transfer parameterizations

25 páginas, 4 figuras, 1 tablaThe estimation of sea-air CO2 fluxes are largely dependent on wind speed through the gas transfer velocity parameterization. In this paper, we quantify uncertainties in the estimation of the CO2 uptake in the Bay of Biscay resulting from using different sources of wind speed such as three different global reanalysis meteorological models (NCEP/NCAR 1, NCEP/DOE 2 and ERA-Interim), one regional high-resolution forecast model (HIRLAM-AEMet) and QuikSCAT winds, in combination with some of the most widely used gas transfer velocity parameterizations. Results show that net CO2 flux estimations during an entire seasonal cycle may differ up to 240% depending on the wind speed product and the gas exchange parameterization. The comparison of satellite and model derived winds with observations at buoys advises against the systematic overestimation of NCEP-2 and the underestimation of NCEP-1. In this region, QuikSCAT has the best performing, although ERA-Interim becomes the best choice in areas near the coastline or when the time resolution is the constraint.This work was developed and funded by the ECO project (MCyT REN2002-00503/MAR) and EU FP7 project CARBOCHANGE “Changes 5 in carbon uptake and emissions by oceans in a changing climate” under agreement no. 264879Peer reviewe

Populism and hegemony in Islamic State: The building of the caliphal State in the propagandistic Dabiq magazine

This paper studies the form and emergence of the construction and representation of the self-proclamed State of caliphate by Islamic State. Dabiq magazine, the bridge between the organization and its readers (allies and enemies) has been used completely in this paper (15 total issues) with the purpose of knowing and comprehending critically how ISIS uses a propagandist and its communicative line to construct and represent itself and its idea of State as safe and pious. Great quality visual and textual resources of the magazine reproduce the populist, hegemonic and antagonistic self-construction of the caliphate as a form of life and government. It will also show the self-projection of ISIS to the outside and the we-other equation. In short, this work aims to approach the propagandistic discourse of an organization that shapes itself as the savior of society, designed and self-proclaimed through social institutions and forms of government that reinforce its domination and particular cultural hegemony.El presente estudio analiza la construcción y de la representación del califato como Estado por parte del Estado Islámico. Para ello, se ha utilizado la revista Dabiq al completo. En el análisis se establecerá la forma en la que ISIS se autoproyecta hacia el exterior, incidiendo sobre todo en la ecuación nosotros-otros y nutriéndose de los imaginarios sociales y colectivos allegados a esta. En definitiva, este trabajo pretende acercarse al instrumento propagandístico de una organización que se plasma a sí misma como la salvadora de la sociedad y que, por ende, se ha diseñado y autoproclamado a través de unas instituciones sociales y unas formas de gobierno que refuerzan esa hegemonía cultural particular

Knowledge, perceptions, and perspectives of medical students regarding the use of antibiotics and antibiotic resistance: a qualitative research in Galicia, Spain

Antibiotic resistance is a significant public health concern, with numerous studies linking antibiotic consumption to the development of resistance. As medical students will play a pivotal role in prescribing antibiotics, this research aimed to identify their perceptions of current use and factors that could influence future inappropriate use of antibiotics. The study employed a qualitative research approach using Focus Group discussions (FGs) consisting of students from the final theoretical course of the Medicine degree. The FGs were conducted based on a pre-script developed from factors contributing to antibiotic misuse identified in previous studies. All sessions were recorded and transcribed for analysis by two independent researchers, with all participants signing informed consent. Seven focus groups were conducted, with a total of 35 participants. The study identified factors that could influence the future prescription of antibiotics, including the low applicability of knowledge, insecurity, clinical inertia, difficulties in the doctor-patient relationship, unawareness of available updates on the topic, and inability to assess their validity. The students did not perceive antibiotic resistance as a current problem. However, the study found several modifiable factors in medical students that could explain the misuse of antibiotics, and developing specific strategies could help improve their useThis research was supported in part by the Instituto de Salud Carlos III (ISCIII) (PI081239, PI09/90609) Spanish State Plan for Scientific and Technical Research and Innovation and co-funded by The European Union (ERDF)S