STAG2 loss in Ewing sarcoma alters enhancer-promoter contacts dependent and independent of EWS::FLI1.

Cohesin complexes carrying STAG1 or STAG2 organize the genome into chromatin loops. STAG2 loss-of-function mutations promote metastasis in Ewing sarcoma, a pediatric cancer driven by the fusion transcription factor EWS::FLI1. We integrated transcriptomic data from patients and cellular models to identify a STAG2-dependent gene signature associated with worse prognosis.

Isolation and Total Synthesis of PM170453, a New Cyclic Depsipeptide Isolated from sp.

In our continuing search for biologically active new chemical entities from marine organisms, we have isolated a new cyclic depsipeptide, PM170453 (), from a cyanobacterium of the genus sp., collected in the Indo-Pacific Ocean. Structure elucidation of the isolated compound was determined by spectroscopic methods including MS, H, C and 2D-NMR.

Marine macroalgae in rabbit feed - Effects on meat quality.

The addition of macroalgae to livestock diets has demonstrated to enhance the quality of meat by improving the muscle stability, antioxidant capacity and fatty acid profile. However, information regarding rabbit meat is scarce. This study evaluated the effect of adding 1.

A rewiring of DNA replication mediated by MRE11 exonuclease underlies primed-to-naive cell de-differentiation.

Mouse embryonic stem cells (mESCs) in the primed pluripotency state, which resembles the post-implantation epiblast, can be de-differentiated in culture to a naive state that resembles the pre-implantation inner cell mass. We report that primed-to-naive mESC transition entails a significant slowdown of DNA replication forks and the compensatory activation of dormant origins. Using isolation of proteins on nascent DNA coupled to mass spectrometry, we identify key changes in replisome composition that are responsible for these effects.

Plitidepsin as an Immunomodulator against Respiratory Viral Infections.

Plitidepsin is a host-targeted compound known for inducing a strong anti-SARS-CoV-2 activity, as well as for having the capacity of reducing lung inflammation. Because IL-6 is one of the main cytokines involved in acute respiratory distress syndrome, the effect of plitidepsin in IL-6 secretion in different in vitro and in vivo experimental models was studied. A strong plitidepsin-mediated reduction of IL-6 was found in human monocyte-derived macrophages exposed to nonproductive SARS-CoV-2.

A comprehensive coding and microRNA transcriptome of vertebral bone in postlarvae and juveniles of Senegalese sole (Solea senegalensis).

Understanding vertebral bone development is essential to prevent skeletal malformations in farmed fish related to genetic and environmental factors. This is an important issue in Solea senegalensis, with special impact of spinal anomalies in postlarval and juvenile stages. Vertebral bone transcriptomics in farmed fish mainly comes from coding genes, and barely on miRNA expression.

Protocol to analyze chromatin-bound proteins through the cell cycle using Chromoflow flow cytometry.

Chromatin-bound proteins have been conventionally measured through subcellular fractionation followed by immunoblotting or by immunofluorescence microscopy. Here, we present Chromoflow, a protocol for the quantitative analyses of protein levels on chromatin in single cells and throughout the cell cycle using flow cytometry. We describe steps for harvesting cells and for nuclear extraction, and a barcoding strategy to multiplex samples from different conditions that reduces antibody staining variability and eliminates the need for normalization.

A case of lipogranulomatous conjunctivitis in a horse.

Objective: To describe a case of lipogranulomatous conjunctivitis in a horse.

Animal Studied: A client-owned 12-year-old Standardbred gelding presenting with chronic conjunctivitis and palpebral masses.

Methods: Complete ophthalmic examination, surgical excision, histopathology, and bacterial culture of biopsy samples were performed.

A protocol to study three-dimensional genome structure in individual mutant preimplantation mouse embryos.

Hi-C studies the three-dimensional structure of the genome by detecting genome-wide chromatin regions that are in spatial proximity within the nucleus. We developed single-blastocyst Hi-C in mutant mouse embryos to genotype them on sequence. We describe steps for embryo fixation and nuclei permeabilization, after which chromatin is digested and re-ligated having incorporated a biotin-labeled nucleotide at the ligation junction.

NIPBL and cohesin: new take on a classic tale.

Cohesin folds the genome in dynamic chromatin loops and holds the sister chromatids together. NIPBL is currently considered the cohesin loader, a role that may need reevaluation. NIPBL activates the cohesin ATPase, which is required for topological entrapment of sister DNAs and to fuel DNA loop extrusion, but is not required for chromatin association.

Patients with drug-abuse poisoning with and without HIV infection: differential characteristics.

Objectives: Persons with HIV infection who use illicit drugs have higher morbidity and mortality rates than nonusers with or without HIV infection. The objetive were to detect differences between acute poisoning from illicit drugs in patients with and without HIV infection who are attended in hospital emergency departments, and to identify independent factors associated with a worse prognosis, defined by hospital admission or death.

Material And Methods: Observational study in 2 hospitals between January 2017 and 31 December 2021.

Severe neurometabolic phenotype in zebrafish with a C-terminal mutation.

Niemann Pick disease type C (NPC) is an autosomal recessive neurodegenerative lysosomal disorder characterized by an accumulation of lipids in different organs. Clinical manifestations can start at any age and include hepatosplenomegaly, intellectual impairment, and cerebellar ataxia. is the most common causal gene, with over 460 different mutations with heterogeneous pathological consequences.

Different NIPBL requirements of cohesin-STAG1 and cohesin-STAG2.

Cohesin organizes the genome through the formation of chromatin loops. NIPBL activates cohesin's ATPase and is essential for loop extrusion, but its requirement for cohesin loading is unclear. Here we have examined the effect of reducing NIPBL levels on the behavior of the two cohesin variants carrying STAG1 or STAG2 by combining a flow cytometry assay to measure chromatin-bound cohesin with analyses of its genome-wide distribution and genome contacts.

Contribution of variant subunits and associated factors to genome-wide distribution and dynamics of cohesin.

Background: The cohesin complex organizes the genome-forming dynamic chromatin loops that impact on all DNA-mediated processes. There are two different cohesin complexes in vertebrate somatic cells, carrying the STAG1 or STAG2 subunit, and two versions of the regulatory subunit PDS5, PDS5A and PDS5B. Mice deficient for any of the variant subunits are embryonic lethal, which indicates that they are not functionally redundant.

Mammalian CDC14 phosphatases control exit from stemness in pluripotent cells.

Maintenance of stemness is tightly linked to cell cycle regulation through protein phosphorylation by cyclin-dependent kinases (CDKs). However, how this process is reversed during differentiation is unknown. We report here that exit from stemness and differentiation of pluripotent cells along the neural lineage are controlled by CDC14, a CDK-counteracting phosphatase whose function in mammals remains obscure.

Establishment of 3D chromatin structure after fertilization and the metabolic switch at the morula-to-blastocyst transition require CTCF.

The eukaryotic genome is organized in 3D at different scales. This structure is driven and maintained by different chromatin states and by architectural factors, such as the zinc finger protein CTCF. Zygotic genome structure is established de novo after fertilization, but its impact during the first stages of mammalian development is unclear.

Amphetamine-related intoxications in people living with HIV: An observational study in an emergency department in Barcelona (Spain) from 2018 to 2020.

Background: Stimulant drugs, particularly amphetamines, are more commonly implicated in drug-related deaths in people living with HIV; however, the clinical characteristics of amphetamine-related intoxication in people living with HIV are poorly described.

Material And Methods: We conducted a retrospective study in people living with HIV who were admitted for amphetamine-related intoxication to an emergency department of a teaching hospital between 2018 and 2021. Severe intoxication (SI) was arbitrarily defined as requiring admission to the emergency medical support unit and receiving medical treatment for ≥6 h.

Do caregiver interventions improve outcomes in relatives with dementia and mild cognitive impairment? A comprehensive systematic review and meta-analysis.

Some reviews suggest benefits of nonpharmacological interventions for informal caregivers of people with dementia and mild cognitive impairment. These benefits may transfer to the care-recipients (CRs) through increased caregiving capability, reduced burden and depression among caregivers, and decreased negative mood contagion. However, large-scale review on these effects on the CRs is lacking.

Guilt Focused Intervention for Family Caregivers. Preliminary Results of a Randomized Clinical Trial.

Objectives: A pilot randomized controlled trial study was conducted for testing the efficacy of a novel Guilt Focused Intervention (GFI), that was compared with a Cognitive Behavioral Intervention (CBI) for caregivers of people with dementia with high levels of guilt and distress.

Methods: Participants were 42 caregivers who were randomized assigned to the intervention conditions.

Results: Participants in the GFI showed significant reductions in depression, anxiety, and guilt at posttreatment and follow-up.

Unraveling the antiviral activity of plitidepsin against SARS-CoV-2 by subcellular and morphological analysis.

The pandemic caused by the new coronavirus SARS-CoV-2 has made evident the need for broad-spectrum, efficient antiviral treatments to combat emerging and re-emerging viruses. Plitidepsin is an antitumor agent of marine origin that has also shown a potent pre-clinical efficacy against SARS-CoV-2. Plitidepsin targets the host protein eEF1A (eukaryotic translation elongation factor 1 alpha) and affects viral infection at an early, post-entry step.

Compassion in dementia caregiving: Psychometric properties of the Caregiving Compassion Scale in Spanish caregivers.

Compassion has been suggested as a relevant variable for understanding dementia caregivers' psychological distress. The objectives were to analyse the psychometric properties of the Caregiving Compassion Scale (CCS) and to explore the association between caregivers' compassion and their emotional health. Two hundred and thirty-six dementia caregivers were evaluated for compassion, depressive symptoms, guilt, ambivalence, care-recipient's functional and cognitive status, frequency of behavioural problems and desire to institutionalise the care-recipient.

Internet-delivered guided self-help acceptance and commitment therapy for family carers of people with dementia (iACT4CARERS): a feasibility study.

Objectives: The feasibility of research into internet-delivered guided self-help Acceptance and Commitment Therapy (ACT) for family carers of people with dementia is not known. This study assessed this in an uncontrolled feasibility study.

Method: Family carers of people with dementia with mild to moderate anxiety or depression were recruited from primary and secondary healthcare services in the UK.

Disruption of NIPBL/Scc2 in Cornelia de Lange Syndrome provokes cohesin genome-wide redistribution with an impact in the transcriptome.

Cornelia de Lange syndrome (CdLS) is a rare disease affecting multiple organs and systems during development. Mutations in the cohesin loader, NIPBL/Scc2, were first described and are the most frequent in clinically diagnosed CdLS patients. The molecular mechanisms driving CdLS phenotypes are not understood.