Codon Usage of Chloroplast Gene rbcL in Laurencia sensu lato (Rhodophyta) species

Recent advances in molecular biology make it possible to sequence not only genes or genomes, but also to understand codon dynamics. For the organelle genes of these organisms, a small set of preferred codons are used for encoding proteins. For the first time, this paper treats the divergence of synonymous codon usage and its bias in the rbcL gene within the Laurencia complex of red algae. We observed that the synonymous codon preference biases in rbcL are large and differ among species. A clear distinction in codon usage between genera is evident: the genera Dasya and Delesseria use a set that fluctuated between 53 and 58 codons. Whereas, in the genera Ceramium, Chondrophycus, Chlamydomonas, Chlorella, Laurencia s.s, Osmundea, and Palisada codon usage indicates a higher restriction fluctuating between 40 to 51 codons. Laurencia complex genera and other representative algae showed a defined composition pattern, with lower percentage values of NNC/G (7-24.9%). Dasya and Delesseria showed a selective pattern tendency because of high percentage values of NNC/G (54-55%). The estimated codon bias parameters were tested to infer systematic relationships and match suitable codons with the NNC / G codon percentages. Cluster analysis based on Codon Usage supports phylogenetic relationships between Chondrophycus, Palisada, Laurencia, Osmundea, and Yuzurua species

A Single Nucleotide Polymorphism in the Il17ra Promoter Is Associated with Functional Severity of Ankylosing Spondylitis

The aim of this study was to identify new genetic variants associated with the severity of ankylosing spondylitis (AS). We sequenced the exome of eight patients diagnosed with AS, selected on the basis of the severity of their clinical parameters. We identified 27 variants in exons and regulatory regions. The contribution of candidate variants found to AS severity was validated by genotyping two Spanish cohorts consisting of 180 cases/300 controls and 419 cases/656 controls. Relationships of SNPs and clinical variables with the Bath Ankylosing Spondylitis Disease Activity and Functional Indices BASDAI and BASFI were analyzed. BASFI was standardized by adjusting for the duration of the disease since the appearance of the first symptoms. Refining the analysis of SNPs in the two cohorts, we found that the rs4819554 minor allele G in the promoter of the IL17RA gene was associated with AS (p<0.005). This variant was also associated with the BASFI score. Classifying AS patients by the severity of their functional status with respect to BASFI/disease duration of the 60th, 65th, 70th and 75th percentiles, we found the association increased from p60 to p75 (cohort 1: p<0.05 to p<0.01; cohort 2: p<0.01 to p<0.005). Our findings indicate a genetic role for the IL17/ILRA axis in the development of severe forms of AS

A serum microRNA signature associated with complete remission and progression after autologous stem-cell transplantation in patients with multiple myeloma

We have examined serum microRNA expression in multiple myeloma (MM) patients at diagnosis and at complete response (CR) after autologous stem-cell transplantation (ASCT), in patients with stable monoclonal gammopathy of undetermined significance, and in healthy controls. MicroRNAs were first profiled using TaqMan Human MicroRNA Arrays. Differentially expressed microRNAs were then validated by individual TaqMan MicroRNA assays and correlated with CR and progression-free survival (PFS) after ASCT. Supervised analysis identified a differentially expressed 14-microRNA signature. The differential expression of miR-16 (P = 0.028), miR-17 (P = 0.016), miR-19b (P = 0.009), miR-20a (P = 0.017) and miR-660 (P = 0.048) at diagnosis and CR was then confirmed by individual assays. In addition, high levels of miR-25 were related to the presence of oligoclonal bands (P = 0.002). Longer PFS after ASCT was observed in patients with high levels of miR-19b (6 vs. 1.8 years; P < 0.001) or miR-331 (8.6 vs. 2.9 years; P = 0.001). Low expression of both miR-19b and miR-331 in combination was a marker of shorter PFS (HR 5.3; P = 0.033). We have identified a serum microRNA signature with potential as a diagnostic and prognostic tool in MM

CAR density influences antitumoral efficacy of BCMA CAR T cells and correlates with clinical outcome

Identification of new markers associated with long-term efficacy in patients treated with CAR T cells is a current medical need, particularly in diseases such as multiple myeloma. In this study, we address the impact of CAR density on the functionality of BCMA CAR T cells. Functional and transcriptional studies demonstrate that CAR T cells with high expression of the CAR construct show an increased tonic signaling with up-regulation of exhaustion markers and increased in vitro cytotoxicity but a decrease in in vivo BM infiltration. Characterization of gene regulatory networks using scRNA-seq identified regulons associated to activation and exhaustion up-regulated in CARHigh T cells, providing mechanistic insights behind differential functionality of these cells. Last, we demonstrate that patients treated with CAR T cell products enriched in CARHigh T cells show a significantly worse clinical response in several hematological malignancies. In summary, our work demonstrates that CAR density plays an important role in CAR T activity with notable impact on clinical response

Tenemos mucho que contar: narraciones de mujeres privadas de la libertad del Centro de Detención Provisional de Guayaquil

La experiencia de trabajar durante varios meses con treinta mujeres privadas de la libertad, en compañia de diez alumnos de la carrera de Comunicación de la UPS sede Guayaquil, fue todo un desafío y una hermosa propuesta. Pudimos escuchar y apreciar las reflexiones y pensamientos de mujeres que son madres, abuelas, tías, primas, hijas, sobrinas. Mujeres que viven lejos de sus familiares y que esperan ansiosas el día para salir de ahi y estar junto a sus seres queridos

Frecuencia de prolongación del intervalo QTc en adultos infectados con VIH de Paraguay en 2020

Introduction: the prolonged QTc interval predisposes to serious arrhythmias. Various medications, including antiretrovirals, can prolong it. The objectives were to determine the demographic, clinical characteristics and the frequency of the prolonged QTc interval in patients with HIV. Methods: we conducted a prospective, observational study with a control group. Men and women, over 18 years of age, with HIV infection, who attended the National Hospital (Itauguá, Paraguay) during 2020, were included. Medical students acted as a control group. All subjects who did not give their consent and those with arrhythmias were excluded. Demographic, clinical, laboratory variables and 12-channel electrocardiogram at rest were measured. The study was approved by the Ethics Committee of the Universidad Privada del Este (Paraguay). Results: 39 HIV patients and 39 healthy controls entered the study. The mean age of the cases was 37 ± 11 years, being 59% male. The most frequent comorbidity in the cases was obesity (7.6%). The mean values ​​of urea, creatinine, K, Ca and Mg in the cases were in the normal range. Prolonged QTc was detected in 18% of the cases and in 0% of the controls. The subjects with the electrocardiographic alteration were all on antiretroviral and multiple antibiotic treatment known to be associated with prolonged Qtc. Conclusion: the frequency of prolonged QTc in HIV patients was 18% and in healthy controls it was 0%. Regular monitoring of the electrocardiogram is recommended in HIV patients receiving drugs that prolong the QT interval.Introducción: el intervalo QTc prolongado predispone a arritmias graves. Diversos medicamentos, entre ellos los antirretrovirales, pueden prolongarlo. Los objetivos fueron determinar las características demográficas, clínicas y la frecuencia del intervalo QTc prolongado en pacientes con VIH. Métodos: estudio observacional, prospectivo, con grupo control. Se incluyeron varones y mujeres, mayores de 18 años, portadores de infección por VIH, que acudieron al Hospital Nacional (Itauguá, Paraguay) durante 2020. Actuaron como grupo control los estudiantes de Medicina. Se excluyeron todos los sujetos que no dieron su consentimiento y los portadores de arritmias. Se midieron variables demográficas, clínicas, laboratoriales y electrocardiograma de 12 canales en reposo. El estudio contó con la aprobación del Comité de Ética de la Universidad Privada del Este (Paraguay). Resultados: ingresaron al estudio 39 pacientes con VIH y 39 controles sanos. La edad media de los casos fue 37 ± 11 años, siendo 59% del sexo masculino. La comorbilidad más frecuente en los casos fue la obesidad (7,6%). Los valores medios de urea, creatinina, K, Ca y Mg en los casos se hallaban en rango normal. Se detectó 18% de QTc prolongado en casos y 0% en los controles. Estos sujetos con alteración electrocardiográfica se hallaban todos en tratamiento antirretroviral y antibiótico múltiple de conocida asociación con QTc prolongado. Conclusión: la frecuencia de QTc prolongado en pacientes con VIH fue del 18% y en controles sanos fue del 0%. Se recomienda el control periódico del electrocardiograma en pacientes con VIH en tratamiento con fármacos que prolongan el intervalo QT

RICORS2040 : The need for collaborative research in chronic kidney disease

Chronic kidney disease (CKD) is a silent and poorly known killer. The current concept of CKD is relatively young and uptake by the public, physicians and health authorities is not widespread. Physicians still confuse CKD with chronic kidney insufficiency or failure. For the wider public and health authorities, CKD evokes kidney replacement therapy (KRT). In Spain, the prevalence of KRT is 0.13%. Thus health authorities may consider CKD a non-issue: very few persons eventually need KRT and, for those in whom kidneys fail, the problem is 'solved' by dialysis or kidney transplantation. However, KRT is the tip of the iceberg in the burden of CKD. The main burden of CKD is accelerated ageing and premature death. The cut-off points for kidney function and kidney damage indexes that define CKD also mark an increased risk for all-cause premature death. CKD is the most prevalent risk factor for lethal coronavirus disease 2019 (COVID-19) and the factor that most increases the risk of death in COVID-19, after old age. Men and women undergoing KRT still have an annual mortality that is 10- to 100-fold higher than similar-age peers, and life expectancy is shortened by ~40 years for young persons on dialysis and by 15 years for young persons with a functioning kidney graft. CKD is expected to become the fifth greatest global cause of death by 2040 and the second greatest cause of death in Spain before the end of the century, a time when one in four Spaniards will have CKD. However, by 2022, CKD will become the only top-15 global predicted cause of death that is not supported by a dedicated well-funded Centres for Biomedical Research (CIBER) network structure in Spain. Realizing the underestimation of the CKD burden of disease by health authorities, the Decade of the Kidney initiative for 2020-2030 was launched by the American Association of Kidney Patients and the European Kidney Health Alliance. Leading Spanish kidney researchers grouped in the kidney collaborative research network Red de Investigación Renal have now applied for the Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS) call for collaborative research in Spain with the support of the Spanish Society of Nephrology, Federación Nacional de Asociaciones para la Lucha Contra las Enfermedades del Riñón and ONT: RICORS2040 aims to prevent the dire predictions for the global 2040 burden of CKD from becoming true