Human mitochondrial degradosome prevents harmful mitochondrial R loops and mitochondrial genome instability

R loops are nucleic acid structures comprising an DNA-RNA hybrid and a displaced single-stranded DNA. These structures may occur transiently during transcription, playing essential biological functions. However, persistent R loops may become pathological as they are important drivers of genome instability and have been associated with human diseases. The mitochondrial degradosome is a functionally conserved complex from bacteria to human mitochondria. It is composed of the ATP-dependent RNA and DNA helicase SUV3 and the PNPase ribonuclease, playing a central role in mitochondrial RNA surveillance and degradation. Here we describe a new role for the mitochondrial degradosome in preventing the accumulation of pathological R loops in the mitochondrial DNA, in addition to preventing dsRNA accumulation. Our data indicate that, similar to the molecular mechanisms acting in the nucleus, RNA surveillance mechanisms in the mitochondria are crucial to maintain its genome integrity by counteracting pathological R-loop accumulation.European Research Council ERC2014 AdG669898 TARLOOPMinisterio de Economía y Competitividad BFU2013-42918-P, BFU2016-75058-

Diagnosis and Prevalence of High-Risk Human Papillomavirus Infection in Heterosexual Men

A better understanding of human papillomavirus (HPV) infection in men is an essential component of prevention programs aimed to reduce cervical cancer and other HPV-related diseases. A screening test capable of detecting asymptomatic/subclinical genital HPV infection in men at a reasonable price and causing minimal discomfort to the patient would be very valuable. The following chapter focuses on acetowhite test usefulness in the detection of asymptomatic/subclinical genital high-risk (HR) HPV infection in high-risk men populations, HR-HPV prevalence in sexually active healthy male partners of women diagnosed of high-grade cervical intraepithelial neoplasia and genotype-specific concordance between partners, addressing the preventive strategies that would reduce HPV infection in men. We present data from 125 men, sexual partners of women with preneoplastic cervical lesions. Prevalence of HR-HPV infection in male was high (50, 24% HPV16) and genotype concordance within the 60 infected couples was remarkable (62% shared at least one genotype). Acetowhite (AW) test was positive in 27% patients, showing low sensitivity for the identification of HR-HPV infection but allowed the diagnosis of subclinical HPV-related lesions in more than 10%. Current smoking and genital warts were associated with an increased risk of HR-HPV infection in men (OR: 2.4 and 5.6, respectively)

Labour Managed Firms in Spain

There are at least two types of companies: conventional capitalist companies or Profit Maximizing Firms (PMFs) and, on the other hand, companies managed by their workforce or Labour-Managed Firms (LMFs). The entrepreneurial structures in Spain which include this second type are worker cooperatives (cooperativas de trabajo asociado) and public or limited liability worker-owned companies (sociedades laborales). This paper describes how this type of company has evolved using a set of indicators and offers a closer look at some of the reasons which explain the current difficult situation which, as will be shown, can be considered as critical in the case of cooperatives.Labour-Managed Firms, worker cooperatives, worker-owned companies, employment.

Conical spouted bed combustor to obtain clean energy from avocado waste

The advantages of spouted bed technology for waste treatment are linked to the high excess of renewable biomass waste generated by the large worldwide consumption of avocado. Therefore, the applicability of avocado waste as fuel in a novel conical spouted bed combustor was investigated. The solid cyclic movement in this reactor innovatively promotes better mass and heat transfer, as well as better energy exploitation of the waste. Local heat transfer coefficients were experimentally determined in the beds of avocado waste in the combustor to assess their heat transfer and determine their value as biofuels. The combustion of the avocado beds in the spouted bed regime was performed at 300–600 °C in a conical reactor at the minimum spouting velocity. The exhaust gas evolution was monitored over time, and the emission ratios were calculated. The combustion efficiencies of avocado seeds, skin, and their binary mixtures, determined from flue gas concentrations, were compared, and the effects of temperature and bed composition on combustion efficiency were analyzed.This work is part of the project Grant PID2021-126331OB-I00 and grant TED2021-130150B-I00 funded by MCIN/AEI/10.13039/501100011033 and by “ERDF A way of making Europe”. Open Access funding provided by the University of the Basque Country UPV/EHU

Molecular Mechanisms Regulating the DNA Repair Protein APE1: A Focus on Its Flexible N-Terminal Tail Domain

APE1 (DNA (apurinic/apyrimidinic site) endonuclease 1) is a key enzyme of one of the major DNA repair routes, the BER (base excision repair) pathway. APE1 fulfils additional functions, acting as a redox regulator of transcription factors and taking part in RNA metabolism. The mechanisms regulating APE1 are still being deciphered. Structurally, human APE1 consists of a well-characterized globular catalytic domain responsible for its endonuclease activity, preceded by a conformationally flexible N-terminal extension, acquired along evolution. This N-terminal tail appears to play a prominent role in the modulation of APE1 and probably in BER coordination. Thus, it is primarily involved in mediating APE1 localization, post-translational modifications, and protein–protein interactions, with all three factors jointly contributing to regulate the enzyme. In this review, recent insights on the regulatory role of the N-terminal region in several aspects of APE1 function are covered. In particular, interaction of this region with nucleophosmin (NPM1) might modulate certain APE1 activities, representing a paradigmatic example of the interconnection between various regulatory factors.This work was supported by a grant from the University of the Basque Country (GIU18/172

Regulation of NR4A by nutritional status, gender, postnatal development and hormonal deficiency

The NR4A is a subfamily of the orphan nuclear receptors (NR) superfamily constituted by three well characterized members: Nur77 (NR4A1), Nurr1 (NR4A2) and Nor 1 (NR4A3). They are implicated in numerous biological processes as DNA repair, arteriosclerosis, cell apoptosis, carcinogenesis and metabolism. Several studies have demonstrated the role of this subfamily on glucose metabolism, insulin sensitivity and energy balance. These studies have focused mainly in liver and skeletal muscle. However, its potential role in white adipose tissue (WAT), one of the most important tissues involved in the regulation of energy homeostasis, is not well-studied. The aim of this work was to elucidate the regulation of NR4A in WAT under different physiological and pathophysiological settings involved in energy balance such as fasting, postnatal development, gender, hormonal deficiency and pregnancy. We compared NR4A mRNA expression of Nur77, Nurr1 and Nor 1 and found a clear regulation by nutritional status, since the expression of the 3 isoforms is increased after fasting in a leptin-independent manner and sex steroid hormones also modulate NR4A expression in males and females. Our findings indicate that NR4A are regulated by different physiological and pathophysiological settings known to be associated with marked alterations in glucose metabolism and energy status.This work has been supported by grants from Fondo Investigaciones Sanitarias (ST: PI12/02842), Ministerio de Economia y Competitividad (RN: RYC-2008-02219 and BFU2012-35255; MMM: BFU2010-17116), Xunta de Galicia (ML: 10PXIB208164PR and 2012-CP070; RN: EM 2012/039 and 2012-CP069), Centro de Investigación Biomédica en Red (CIBER) de Fisiopatología de la Obesidad y Nutrición. CIBERobn is an initiative of the Instituto de Salud Carlos III (ISCIII) of Spain which is supported by FEDER funds. The research leading to these results has also received funding from the European Community's Seventh Framework Programme under the following grant: ML and RN: FP7/2007-2013: n° 245009: NeuroFASTS

Tax fraud detection through neural networks: An application using a sample of personal income taxpayers

The goal of the present research is to contribute to the detection of tax fraud concerning personal income tax returns (IRPF, in Spanish) filed in Spain, through the use of Machine Learning advanced predictive tools, by applying Multilayer Perceptron neural network (MLP) models. The possibilities springing from these techniques have been applied to a broad range of personal income return data supplied by the Institute of Fiscal Studies (IEF). The use of the neural networks enabled taxpayer segmentation as well as calculation of the probability concerning an individual taxpayer’s propensity to attempt to evade taxes. The results showed that the selected model has an efficiency rate of 84.3%, implying an improvement in relation to other models utilized in tax fraud detection. The proposal can be generalized to quantify an individual’s propensity to commit fraud with regards to other kinds of taxes. These models will support tax offices to help them arrive at the best decisions regarding action plans to combat tax frau

El emprendimiento colectivo como salida laboral de los jóvenes: análisis del caso de las empresas de trabajo asociado

La falta de oportunidades laborales como trabajadores asalariados para los jóvenes, y las elevadas tasas de desempleo que afectan a la población juvenil, que llegan a duplicar la media europea, han de ser indicadores suficientes para que los jóvenes valoren el emprendimiento como vía de inclusión, o mantenimiento, en el mercado laboral. En este sentido, la vocación emprendedora de los jóvenes españoles se sitúa por debajo de la media de sus homólogos europeos, por lo que se precisa la difusión de las bondades del emprendimiento, tales como la posibilidad de obtener empleos de calidad y estables que se adecúen en mayor medida a la formación obtenida, así como su apoyo. Pero no sólo ha de valorarse la alternativa de emprender en solitario, sino que también es posible el emprendimiento en colectivo, prestándose en este trabajo especial atención a las empresas de participación, y al papel que pueden desempeñar éstos en las mismas. Estas empresas requieren al menos tres socios para la constitución tanto de una sociedad laboral, como de una sociedad cooperativa de trabajo asociado. En este contexto, se estudia la percepción del emprendimiento, y de las empresas de trabajo asociado, entre los jóvenes universitarios de la Universidad Complutense de Madrid, así como las iniciativas que se están llevando a cabo desde esta institución para fomentar, difundir y apoyar estas iniciativas emprendedoras