Post-Translational Modifications of H2A Histone Variants and Their Role in Cancer

Altres ajuts: Research leading to inventions at the IJC is supported by the 'La Caixa' Foundation, the Fundació Internacional Josep Carreras, Celgene Spain and the CERCA Programme/Generalitat de Catalunya.Histone variants are chromatin components that replace replication-coupled histones in a fraction of nucleosomes and confer particular characteristics to chromatin. H2A variants represent the most numerous and diverse group among histone protein families. In the nucleosomal structure, H2A-H2B dimers can be removed and exchanged more easily than the stable H3-H4 core. The unstructured N-terminal histone tails of all histones, but also the C-terminal tails of H2A histones protrude out of the compact structure of the nucleosome core. These accessible tails are the preferential target sites for a large number of post-translational modifications (PTMs). While some PTMs are shared between replication-coupled H2A and H2A variants, many modifications are limited to a specific histone variant. The present review focuses on the H2A variants H2A.Z, H2A.X, and macroH2A, and summarizes their functions in chromatin and how these are linked to cancer development and progression. H2A.Z primarily acts as an oncogene and macroH2A and H2A.X as tumour suppressors. We further focus on the regulation by PTMs, which helps to understand a degree of context dependency

An integration of slicing, NFV, and SDN for mobility management in corporate environments

Online access to information while on the move has conferred businesses with the capability to be constantly accessible and in operation, independently of geographical area or time zone. There are situations, however, that demand technical solutions for specific scenarios, such as controlled access to corporate-based content. Virtual Private Networks (VPNs) allow controlled remote access to con-tent, supporting scenarios such as teleworking. Nonetheless, such mechanisms are not commonly associated with the highly mobile users of today, which can traverse different types of access networks, while still keeping access to con-tent restricted to corporate network usage. In addition, as VPN mechanisms are disassociated from mobility procedures, service disruption can happen or specific mechanisms and clients can be required in end-user's equipment. This paper proposes a framework that leverages Network Slicing, enabled by Software Defined Networking and Network Function Virtualisation, to provide seamless and isolated access to corporate-based content while moving through heterogeneous networks. This solution allows Mobile Network Operators to dynamically instantiate isolated network slices for corporate users, and handover them between 3GPP and non-3GPP networks while users move away from the corporate network. In this way, they are able to keep access to corporate-based content in a transparent way, while maintaining access requirements for the servicebeing used. The framework was implemented and validated over an experimental testbed composed by mobile and Wi-Fi accesses, with results presenting improvements in terms of overhead signaling and data redirection without downtime nor stream reconnection.publishe

Matching random colored points with rectangles

Let S[0,1]2 be a set of n points, randomly and uniformly selected. Let RB be a random partition, or coloring, of S in which each point of S is included in R uniformly at random with probability 1/2. We study the random variable M(n) equal to the number of points of S that are covered by the rectangles of a maximum strong matching of S with axis-aligned rectangles. The matching consists of closed rectangles that cover exactly two points of S of the same color. A matching is strong if all its rectangles are pairwise disjoint. We prove that almost surely M(n)=0.83n for n large enough. Our approach is based on modeling a deterministic greedy matching algorithm, that runs over the random point set, as a Markov chain.Research supported by projects MTM2015-63791-R MINECO/FEDER and Gen. Cat. DGR 2017SGR1640Postprint (author's final draft

Dynamic Interdomain Network Slicing for verticals in the 5Growth project

Proceedings of: IEEE Conference on Network Function Virtualization and Software Defined Networks (NFV-SDN), 9-11 Nov. 2021, Heraklion, Greece.This paper proposes and validates a Interdomain Network Slicing framework for verticals, allowing them to directly participate in the establishment and control of end-to-end Communication Services deployment across multiple inter-operator domains. The framework progresses the means made available by different standards and research initiatives to enhance service requesting and provisioning interfaces for the stakeholders involved, namely operators and verticals. The framework is validated under two different use cases, showcasing effective end-to-end service instantiation and a first assessment towards dynamic service modification capability.This work has been supported by EC H2020 5GPPP 5Growth project (Grant 856709)

The Histone Variant MacroH2A1 Regulates Key Genes for Myogenic Cell Fusion in a Splice-Isoform Dependent Manner

Altres ajuts: This research project was supported by the Fundació La Marató de TV3 257/C/2019 (to MB). Research at the IJC is supported by the 'La Caixa' Foundation, the Fundació Internacional Josep Carreras, Celgene Spain.MacroH2A histone variants have functions in differentiation, somatic cell reprogramming and cancer. However, at present, it is not clear how macroH2As affect gene regulation to exert these functions. We have parted from the initial observation that loss of total macroH2A1 led to a change in the morphology of murine myotubes differentiated ex vivo. The fusion of myoblasts to myotubes is a key process in embryonic myogenesis and highly relevant for muscle regeneration after acute or chronic injury. We have focused on this physiological process, to investigate the functions of the two splice isoforms of macroH2A1. Individual perturbation of the two isoforms in myotubes forming in vitro from myogenic C2C12 cells showed an opposing phenotype, with macroH2A1.1 enhancing, and macroH2A1.2 reducing, fusion. Differential regulation of a subset of fusion-related genes encoding components of the extracellular matrix and cell surface receptors for adhesion correlated with these phenotypes. We describe, for the first time, splice isoform-specific phenotypes for the histone variant macroH2A1 in a physiologic process and provide evidence for a novel underlying molecular mechanism of gene regulation

Disruption of paternal circadian rhythm affects metabolic health in male offspring via nongerm cell factors

Circadian rhythm synchronizes each body function with the environment and regulates physiology. Disruption of normal circadian rhythm alters organismal physiology and increases disease risk. Recent epidemiological data and studies in model organisms have shown that maternal circadian disruption is important for offspring health and adult phenotypes. Less is known about the role of paternal circadian rhythm for offspring health. Here, we disrupted circadian rhythm in male mice by night-restricted feeding and showed that paternal circadian disruption at conception is important for offspring feeding behavior, metabolic health, and oscillatory transcription. Mechanistically, our data suggest that the effect of paternal circadian disruption is not transferred to the offspring via the germ cells but initiated by corticosterone-based parental communication at conception and programmed during in utero development through a state of fetal growth restriction. These findings indicate paternal circadian health at conception as a newly identified determinant of offspring phenotypes

MacroH2A1.1 regulates mitochondrial respiration by limiting nuclear NAD+ consumption

Histone variants are structural components of eukaryotic chromatin that can replace replication-coupled histones in the nucleosome. The histone variant macroH2A.1.1 contains a macrodomain able to bind NAD+ derived metabolites. Here, we report that macroH2A.1.1 is rapidly induced during myogenic differentiation through a switch in alternative splicing. Importantly, myotubes lacking macroH2A.1.1 display a defect in mitochondrial respiratory capacity. We find that the metabolite-interacting macrodomain is essential for sustaining optimal mitochondrial function, but dispensable for gene regulation. Through direct binding, macroH2A.1.1 inhibits basal poly-ADP ribose polymerase 1 activity and thus reduces nuclear NAD+ consumption. Consequentially, accumulation of the NAD+ precursor NMN allows the maintenance of mitochondrial NAD+ pools critical for respiration. Our data indicate that macroH2A.1.1-containing chromatin regulates mitochondrial respiration by limiting nuclear NAD+ consumption and establishing a buffer of NAD+ precursors in differentiated cells

Deliberate and Accidental Gas-Phase Alkali Doping of Chalcogenide Semiconductors: Cu(In,Ga)Se2

Alkali metal doping is essential to achieve highly efficient energy conversion in Cu(In,Ga)Se2 (CIGSe) solar cells. Doping is normally achieved through solid state reactions, but recent observations of gas phase alkali transport in the kesterite sulfide (Cu2ZnSnS4) system (re)open the way to a novel gas-phase doping strategy. However, the current understanding of gas-phase alkali transport is very limited. This work (i) shows that CIGSe device efficiency can be improved from 2% to 8% by gas-phase sodium incorporation alone, (ii) identifies the most likely routes for gas-phase alkali transport based on mass spectrometric studies, (iii) provides thermochemical computations to rationalize the observations and (iv) critically discusses the subject literature with the aim to better understand the chemical basis of the phenomenon. These results suggest that accidental alkali metal doping occurs all the time, that a controlled vapor pressure of alkali metal could be applied during growth to dope the semiconductor, and that it may have to be accounted for during the currently used solid state doping routes. It is concluded that alkali gas-phase transport occurs through a plurality of routes and cannot be attributed to one single source