The RNA-binding protein RBP33 dampens non-productive transcription in trypanosomes

In-depth analysis of the transcriptomes of several model organisms has revealed that genomes are pervasively transcribed, giving rise to an abundance of non-canonical and mainly antisense RNA polymerase II-derived transcripts that are produced from almost any genomic context. Pervasive RNAs are degraded by surveillance mechanisms, but the repertoire of proteins that control the fate of these non-productive transcripts is still incomplete. Trypanosomes are single-celled eukaryotes that show constitutive RNA polymerase II transcription and in which initiation and termination of transcription occur at a limited number of sites per chromosome. It is not known whether pervasive transcription exists in organisms with unregulated RNA polymerase II activity, and which factors could be involved in the process. We show here that depletion of RBP33 results in overexpression of similar to 40% of all annotated genes in the genome, with a marked accumulation of sense and antisense transcripts derived from silenced regions. RBP33 loss does not result in a significant increase in chromatin accessibility. Finally, we have found that transcripts that increase in abundance upon RBP33 knockdown are significantly more stable in RBP33-depleted trypanosomes, and that the exosome complex is responsible for their degradation. Our results provide strong evidence that RBP33 dampens non-productive transcription in trypanosomes

The effectiveness of manual therapy on pain, physical function, and nerve conduction studies in carpal tunnel syndrome patients: a systematic review and meta-analysis

Producción CientíficaAim of the study Systematic review and meta-analysis to assess the effectiveness of manual therapy in improving carpal tunnel syndrome (CTS) symptoms, physical function, and nerve conduction studies. Method MEDLINE, Web of Science, SCOPUS, Cochrane Library, TRIP database, and PEDro databases were searched from the inception to September 2021. PICO search strategy was used to identify randomized controlled trials applying manual therapy on patients with CTS. Eligible studies and data extraction were conducted independently by two reviewers. Methodology quality and risk of bias were assessed by PEDro scale. Outcomes assessed were pain intensity, physical func- tion, and nerve conduction studies. Results Eighty-one potential studies were identified and six studies involving 401 patients were finally included. Pain inten- sity immediately after treatment showed a pooled standard mean difference (SMD) of − 2.13 with 95% confidence interval (CI) (− 2.39, − 1.86). Physical function with Boston Carpal Tunnel Syndrome Questionnaire (BCTS-Q) showed a pooled SMD of − 1.67 with 95% CI (− 1.92, − 1.43) on symptoms severity, and a SMD of − 0.89 with 95% CI (− 1.08, − 0.70) on functional status. Nerve conduction studies showed a SMD of− 0.19 with 95% CI (−0.40, − 0.02) on motor conduction and a SMD of − 1.15 with 95% CI (− 1.36, − 0.93) on sensory conduction. Conclusions This study highlights the effectiveness of manual therapy techniques based on soft tissue and neurodynamic mobilizations, in isolation, on pain, physical function, and nerve conduction studies in patients with CTS.Publicación en abierto financiada por el Consorcio de Bibliotecas Universitarias de Castilla y León (BUCLE), con cargo al Programa Operativo 2014ES16RFOP009 FEDER 2014-2020 DE CASTILLA Y LEÓN, Actuación:20007-CL - Apoyo Consorcio BUCL

Blastic plasmacytoid dendritic cell neoplasm frequently shows occult central nervous system involvement at diagnosis and benefits from intrathecal therapy

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare aggressive myeloid neoplasm which shows a high rate of central nervous system (CNS) recurrence and overall survival (OS) of <1 year. Despite this, screening for CNS involvement is not routinely performed at diagnosis and intrathecal (IT) prophylaxis is not regularly administered in BPDCN. Here, we prospectively evaluated 13 consecutive BPDCN patients for the presence of CNS involvement by flow cytometry. Despite none of the patients presented with neurological symptoms, occult CNS involvement was detected in 6/10 cases evaluated at diagnosis and 3/3 studied at relapse/progression. BPDCN patients evaluated at diagnosis received IT treatment -either CNS prophylaxis (n = 4) or active therapy (n = 6)- and all but one remain alive (median follow-up of 20 months). In contrast, all three patients assessed at relapse/progression died. The potential benefit of IT treatment administered early at diagnosis on OS and CNS recurrence-free survival of BPDCN was further confirmed in a retrospective cohort of another 23 BPDCN patients. Our results show that BPDCN patients studied at diagnosis frequently display occult CNS involvement; moreover, they also indicate that treatment of occult CNS disease might lead to a dramatically improved outcome of BPDCN

Nivel de independencia en la vida diaria y plasticidad cognitiva en la vejez

Recent research provides evidence that an active lifestyle is associated with a high level of plasticity, which in turn is related to a reduced probability of cognitive deterioration and decline (Calero, Navarro &amp; Muñoz, 2007). Activities of daily living (ADL) constitute one of the variables currently considered to be an indicator of dependence/independence in old age and which is associated with cognitive and physical decline. The aim of the present study was to analyse the relation between ADL and cognitive plasticity in old age. Sixtythree elderly participants were evaluated using diverse measures of ADL levels and two techniques for evaluating learning potential. Results showed that a higher level of cognitive plasticity was associated with greater functional independence in daily living.En la actualidad, un estilo de vida activo se asocia con un alto nivel de plasticidad cognitiva que a su vez se relaciona con una menor probabilidad de deterioro y declive cognitivo (Calero, Navarro y Muñoz, 2007). Las actividades de la vida diaria (AVD) es una de las variables consideradas indicadoras de dependenciaindependencia en la vejez que se asocia al deterioro cognitivo y físico. El objetivo de esta investigación es analizar la relación entre las AVD y la plasticidad cognitiva en la vejez. Han participado 63 ancianos evaluados con distintas medidas de autonomía/dependencia y con dos técnicas de evaluación del potencial de aprendizaje. Los resultados muestran que un mayor nivel de plasticidad cognitiva se asocia a una mayor independencia funcional en la vida diaria

A Parasite Biomarker Set for Evaluating Benznidazole Treatment Efficacy in Patients with Chronic Asymptomatic Trypanosoma cruzi Infection

One of the current greatest challenges of Chagas disease is the establishment of biomarkers to assess the efficacy of drugs in a short period of time. In this context, the reactivity of sera from 66 adults with chronic indeterminate Chagas disease (IND) for a set of four Trypanosoma cruzi antigens (KMP11, PFR2, HSP70, and 3973d) was analyzed before and after benznidazole treatment. The results showed that the reactivity against these antigens decreased at 9, 24, and 48 months after treatment. Moreover, the 42.4% and 68.75% of IND patients met the established standard criteria of therapeutic efficacy (STEC) at 24 and 48 months posttreatment, respectively. Meeting the STEC implied that there was a continuous decrease in the reactivity of the patient sera against the four antigens after treatment and that there was a substantial decrease in the reactivity for at least two of the antigens. This important decrease in reactivity may be associated with a drastic reduction in the parasite load, but it is not necessarily associated with a parasitological cure. After treatment, a positive PCR result was only obtained in patients who did not meet the STEC. The percentage of granzyme B+/perforin+ CD8+ T cells was significantly higher in patients who met the STEC than in those who did not meet the STEC (35.2% versus 2.2%; P < 0.05). Furthermore, the patients who met the STEC exhibited an increased quality of the multifunctional response of the antigen-specific CD8+ T cells compared with that in the patients who did not meet the STE

Quality traits and tissue anatomy of pepper fruits as influenced by the variety and ripening

Comunicación oral presentada en: III congreso CAOS, Granada EEZ, España. 4 mayo 2023This research was supported by European Regional Development Fund (ERDF)-cofinanced grants from the Ministry of Science and Innovation (PID2019-103924GB-I00, PID2020-113324GB-I00 and TED2021-130015B-C22) and by the Junta de Andalucía (P18-FR-1359), Spain.

Novel genes and sex differences in COVID-19 severity

[EN] Here, we describe the results of a genome-wide study conducted in 11 939 coronavirus disease 2019 (COVID-19) positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (P < 5 × 10−8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (P = 1.3 × 10−22 and P = 8.1 × 10−12, respectively), and for variants in 9q21.32 near TLE1 only among females (P = 4.4 × 10−8). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (P = 2.7 × 10−8) and ARHGAP33 (P = 1.3 × 10−8), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative (HGI) confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, P = 4.1 × 10−8). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (<60 or ≥60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided.S

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality