DNA Hydroxymethylation in the Regulation of Gene Expression in Human Solid Cancer

Chromatin in cancer undergoes chemical and structural changes that alter gene expression patterns. One of the chemical modifications that impacts gene regulation is 5-hydroxymethylcytosine (5hmC), also called DNA hydroxymethylation. 5hmC is a stable mark that is commonly associated with transcriptional activation. In cancer, the global loss of 5hmC is a hallmark. In addition, the deregulation of 5hmC in specific regions of the genome, such as enhancers, promoters, and body of the gene, alters the expression of genes in cancer. These alterations have been detected by the improvement in the mapping of 5hmC at genomic scale, which has allowed us to evaluate the sites where 5hmC alterations occur and the genes that are affected. In this chapter, the recent knowledge about the status of 5hmC in genome specific sites of human solid cancers, the relationship with enzymes ten-eleven translocation (TET) and isocitrate dehydrogenase (IDH) involved in the dynamic regulation of 5hmC levels, and the impact of the 5hmC aberrant changes on the genic expression in these malignances is reviewed

Dengue virus NS1 protein interacts with the ribosomal protein RPL18: This interaction is required for viral translation and replication in Huh-7 cells

AbstractGiven dengue virus (DENV) genome austerity, it uses cellular molecules and structures for virion entry, translation and replication of the genome. NS1 is a multifunctional protein key to viral replication and pathogenesis. Identification of cellular proteins that interact with NS1 may help in further understanding the functions of NS1. In this paper we isolated a total of 64 proteins from DENV infected human hepatic cells (Huh-7) that interact with NS1 by affinity chromatography and immunoprecipitation assays. The subcellular location and expression levels during infection of the ribosomal proteins RPS3a, RPL7, RPL18, RPL18a plus GAPDH were determined. None of these proteins changed their expression levels during infection; however, RPL-18 was redistributed to the perinuclear region after 48hpi. Silencing of the RPL-18 does not affect cell translation efficiency or viability, but it reduces significantly viral translation, replication and viral yield, suggesting that the RPL-18 is required during DENV replicative cycle

The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies

Despite the clinical significance of balanced chromosomal abnormalities (BCAs), their characterization has largely been restricted to cytogenetic resolution. We explored the landscape of BCAs at nucleotide resolution in 273 subjects with a spectrum of congenital anomalies. Whole-genome sequencing revised 93% of karyotypes and demonstrated complexity that was cryptic to karyotyping in 21% of BCAs, highlighting the limitations of conventional cytogenetic approaches. At least 33.9% of BCAs resulted in gene disruption that likely contributed to the developmental phenotype, 5.2% were associated with pathogenic genomic imbalances, and 7.3% disrupted topologically associated domains (TADs) encompassing known syndromic loci. Remarkably, BCA breakpoints in eight subjects altered a single TAD encompassing MEF2C, a known driver of 5q14.3 microdeletion syndrome, resulting in decreased MEF2C expression. We propose that sequence-level resolution dramatically improves prediction of clinical outcomes for balanced rearrangements and provides insight into new pathogenic mechanisms, such as altered regulation due to changes in chromosome topology

Search for new particles in events with energetic jets and large missing transverse momentum in proton-proton collisions at root s=13 TeV

A search is presented for new particles produced at the LHC in proton-proton collisions at root s = 13 TeV, using events with energetic jets and large missing transverse momentum. The analysis is based on a data sample corresponding to an integrated luminosity of 101 fb(-1), collected in 2017-2018 with the CMS detector. Machine learning techniques are used to define separate categories for events with narrow jets from initial-state radiation and events with large-radius jets consistent with a hadronic decay of a W or Z boson. A statistical combination is made with an earlier search based on a data sample of 36 fb(-1), collected in 2016. No significant excess of events is observed with respect to the standard model background expectation determined from control samples in data. The results are interpreted in terms of limits on the branching fraction of an invisible decay of the Higgs boson, as well as constraints on simplified models of dark matter, on first-generation scalar leptoquarks decaying to quarks and neutrinos, and on models with large extra dimensions. Several of the new limits, specifically for spin-1 dark matter mediators, pseudoscalar mediators, colored mediators, and leptoquarks, are the most restrictive to date.Peer reviewe

Probing effective field theory operators in the associated production of top quarks with a Z boson in multilepton final states at root s=13 TeV

Peer reviewe

COVID-19 in hospitalized HIV-positive and HIV-negative patients : A matched study

CatedresObjectives: We compared the characteristics and clinical outcomes of hospitalized individuals with COVID-19 with [people with HIV (PWH)] and without (non-PWH) HIV co-infection in Spain during the first wave of the pandemic. Methods: This was a retrospective matched cohort study. People with HIV were identified by reviewing clinical records and laboratory registries of 10 922 patients in active-follow-up within the Spanish HIV Research Network (CoRIS) up to 30 June 2020. Each hospitalized PWH was matched with five non-PWH of the same age and sex randomly selected from COVID-19@Spain, a multicentre cohort of 4035 patients hospitalized with confirmed COVID-19. The main outcome was all-cause in-hospital mortality. Results: Forty-five PWH with PCR-confirmed COVID-19 were identified in CoRIS, 21 of whom were hospitalized. A total of 105 age/sex-matched controls were selected from the COVID-19@Spain cohort. The median age in both groups was 53 (Q1-Q3, 46-56) years, and 90.5% were men. In PWH, 19.1% were injecting drug users, 95.2% were on antiretroviral therapy, 94.4% had HIV-RNA < 50 copies/mL, and the median (Q1-Q3) CD4 count was 595 (349-798) cells/μL. No statistically significant differences were found between PWH and non-PWH in number of comorbidities, presenting signs and symptoms, laboratory parameters, radiology findings and severity scores on admission. Corticosteroids were administered to 33.3% and 27.4% of PWH and non-PWH, respectively (P = 0.580). Deaths during admission were documented in two (9.5%) PWH and 12 (11.4%) non-PWH (P = 0.800). Conclusions: Our findings suggest that well-controlled HIV infection does not modify the clinical presentation or worsen clinical outcomes of COVID-19 hospitalization

Measurements of jet multiplicity and jet transverse momentum in multijet events in proton-proton collisions at s= \sqrt{s}= 13 TeV

Multijet events at large transverse momentum ($p_{\mathrm{T}}$) are measured at $\sqrt{s}=$ 13 TeV using data recorded with the CMS detector at the LHC, corresponding to an integrated luminosity of 36.3 fb$^{-1}$. The multiplicity of jets with $p_{\mathrm{T}} >$ 50 GeV that are produced in association with a high-$p_{\mathrm{T}}$ dijet system is measured in various ranges of the $p_{\mathrm{T}}$ of the jet with the highest transverse momentum and as a function of the azimuthal angle difference $\Delta\phi_{1,2}$ between the two highest $p_{\mathrm{T}}$ jets in the dijet system. The differential production cross sections are measured as a function of the transverse momenta of the four highest $p_{\mathrm{T}}$ jets. The measurements are compared with leading and next-to-leading order matrix element calculations supplemented with simulations of parton shower, hadronization, and multiparton interactions. In addition, the measurements are compared with next-to-leading order matrix element calculations combined with transverse-momentum dependent parton densities and transverse-momentum dependent parton shower.Multijet events at large transverse momentum ($p_{\textrm{T}}$) are measured at $\sqrt{s}=13\,\text {Te\hspace{-.08em}V}$ using data recorded with the CMS detector at the LHC, corresponding to an integrated luminosity of $36.3{\,\text {fb}^{-1}}$. The multiplicity of jets with $p_{\textrm{T}} >50\,\text {Ge\hspace{-.08em}V}$ that are produced in association with a high-$p_{\textrm{T}}$ dijet system is measured in various ranges of the $p_{\textrm{T}}$ of the jet with the highest transverse momentum and as a function of the azimuthal angle difference $\varDelta \phi _{1,2}$ between the two highest $p_{\textrm{T}}$ jets in the dijet system. The differential production cross sections are measured as a function of the transverse momenta of the four highest $p_{\textrm{T}}$ jets. The measurements are compared with leading and next-to-leading order matrix element calculations supplemented with simulations of parton shower, hadronization, and multiparton interactions. In addition, the measurements are compared with next-to-leading order matrix element calculations combined with transverse-momentum dependent parton densities and transverse-momentum dependent parton shower.Multijet events at large transverse momentum ($p_\mathrm{T}$) are measured at $\sqrt{s}$ = 13 TeV using data recorded with the CMS detector at the LHC, corresponding to an integrated luminosity of 36.3 fb$^{-1}$. The multiplicity of jets with $p_\mathrm{T}$$>$ 50 GeV that are produced in association with a high-$p_\mathrm{T}$ dijet system is measured in various ranges of the $p_\mathrm{T}$ of the jet with the highest transverse momentum and as a function of the azimuthal angle difference $\Delta\phi_{1,2}$ between the two highest $p_\mathrm{T}$ jets in the dijet system. The differential production cross sections are measured as a function of the transverse momenta of the four highest $p_\mathrm{T}$ jets. The measurements are compared with leading and next-to-leading order matrix element calculations supplemented with simulations of parton shower, hadronization, and multiparton interactions. In addition, the measurements are compared with next-to-leading order matrix element calculations combined with transverse-momentum dependent parton densities and transverse-momentum dependent parton shower

Strange hadron collectivity in pPb and PbPb collisions

International audienceThe collective behavior of ${\textrm{K}}_{\textrm{S}}^0$ and $\Lambda /\overline{\Lambda}$ strange hadrons is studied by measuring the elliptic azimuthal anisotropy (v$_{2}$) using the scalar-product and multiparticle correlation methods. Proton-lead (pPb) collisions at a nucleon-nucleon center-of-mass energy $\sqrt{s_{\textrm{NN}}}$ = 8.16 TeV and lead-lead (PbPb) collisions at $\sqrt{s_{\textrm{NN}}}$ = 5.02 TeV collected by the CMS experiment at the LHC are investigated. Nonflow effects in the pPb collisions are studied by using a subevent cumulant analysis and by excluding events where a jet with transverse momentum greater than 20 GeV is present. The strange hadron v$_{2}$ values extracted in pPb collisions via the four- and six-particle correlation method are found to be nearly identical, suggesting the collective behavior. Comparisons of the pPb and PbPb results for both strange hadrons and charged particles illustrate how event-by-event flow fluctuations depend on the system size.[graphic not available: see fulltext