Secondary sulfur metabolism in cellular signalling and oxidative stress responses.

The sulfur metabolism pathway in plants produces a variety of compounds that are central to the acclimation response to oxidative stresses such as drought and high light. Primary sulfur assimilation provides the amino acid cysteine, which is utilized in protein synthesis and as a precursor for the cellular redox buffer glutathione. In contrast, the secondary sulfur metabolism pathway produces sulfated compounds such as glucosinolates and sulfated peptides, as well as a corresponding by-product 3'-phosphoadenosine 5'-phosphate (PAP). Emerging evidence over the past decade has shown that secondary sulfur metabolism also has a crucial engagement during oxidative stress. This occurs across various cellular, tissue, and organismal levels including chloroplast-to-nucleus retrograde signalling events mediated by PAP, modulation of hormonal signalling by sulfated compounds and PAP, control of physiological responses such as stomatal closure, and potential regulation of plant growth. In this review, we examine the contribution of the different components of plant secondary metabolism to oxidative stress homeostasis, and how this pathway is metabolically regulated. We further outline the key outstanding questions in the field that are necessary to understand how and why this 'specialized' metabolic pathway plays significant roles in plant oxidative stress tolerance.

The transcription factor HNF1α induces expression of angiotensin-converting enzyme 2 (ACE2) in pancreatic islets from evolutionarily conserved promoter motifs.

Pancreatic angiotensin-converting enzyme 2 (ACE2) has previously been shown to be critical for maintaining glycemia and ß-cell function. Efforts to maintain or increase ACE2 expression in pancreatic ß-cells might therefore have therapeutic potential for treating diabetes. In our study, we investigated the transcriptional role of hepatocyte nuclear factor 1α (HNF1α) and hepatocyte nuclear factor 1ß (HNF1ß) in induction of ACE2 expression in insulin-secreting cells. A deficient allele of HNF1α or HNF1ß causes maturity-onset diabetes of the young (MODY) types 3 and 5, respectively, in humans. We found that ACE2 is primarily transcribed from the proximal part of the ACE2 promoter in the pancreas. In the proximal part of the human ACE2 promoter, we further identified three functional HNF1 binding sites, as they have binding affinity for HNF1α and HNF1ß and are required for induction of promoter activity by HNF1ß in insulinoma cells. These three sites are well-conserved among mammalian species. Both HNF1α and HNF1ß induce expression of ACE2 mRNA and lead to elevated levels of ACE2 protein and ACE2 enzymatic activity in insulinoma cells. Furthermore, HNF1α dose-dependently increases ACE2 expression in primary pancreatic islet cells. We conclude that HNF1α can induce the expression of ACE2 in pancreatic islet cells via evolutionarily conserved HNF1 binding sites in the ACE2 promoter. Potential therapeutics aimed at counteracting functional HNF1α depletion in diabetes and MODY3 will thus have ACE2 induction in pancreatic islets as a likely beneficial effect.

The Acinetobacter baumannii K239 capsular polysaccharide includes heptasaccharide units that are structurally related to K86 but joined by different linkages formed by different Wzy polymerases.

The K239 type capsular polysaccharide (CPS) isolated from Acinetobacter baumannii isolate MAR19-4435 was studied by sugar analysis, one- and two-dimensional 1H and 13C NMR spectroscopy. K239 consists of branched heptasaccharide repeats (K-units) comprised of five residues of l-rhamnose (l-Rhap), and one residue each of d-glucuronic acid (d-GlcpA) and N-acetyl-d-glucosamine (d-GlcpNAc). The structure of K239 is closely related to that of the A. baumannii K86 CPS type, though the two differ in the 2,3-substitution patterns on the l-Rhap residue that is involved in the linkage between K-units in the CPS polymer. This structural difference was attributed to the presence of a gtr221 glycosyltransferase gene and a wzyKL239 polymerase gene in KL239 that replaces the gtr80 and wzyKL86 genes in the KL86 CPS biosynthesis gene cluster. Comparison of the two structures established the role of a novel WzyKL239 polymerase encoded by KL239 that forms the ß-d-GlcpNAc-(1→2)-l-Rhap linkage between K239 units. A. baumannii MAR19-4435 was found to be non-susceptible to infection by the APK86 bacteriophage, which encodes a depolymerase that specifically cleaves the linkage between K-units in the K86 CPS, indicating that the difference in 2,3-substitution of l-Rhap influences the susceptibility of this isolate to bacteriophage activity.

Characterization of a (p)ppApp Synthetase Belonging to a New Family of Polymorphic Toxin Associated with Temperate Phages.

Polymorphic toxins (PTs) are a broad family of toxins involved in interbacterial competition and pathogenesis. PTs are modular proteins that are comprised of a conserved N-terminal domain responsible for its transport, and a variable C-terminal domain bearing toxic activity. Although the mode of transport has yet to be elucidated, a new family of putative PTs containing an N-terminal MuF domain, resembling the Mu coliphage F protein, was identified in prophage genetic elements. The C-terminal toxin domains of these MuF PTs are predicted to bear nuclease, metallopeptidase, ADP-ribosyl transferase and RelA_SpoT activities. In this study, we characterized the MuF-RelA_SpoT toxin associated with the temperate phage of Streptococcus pneumoniae SPNA45. We show that the RelA_SpoT domain has (p)ppApp synthetase activity, which is bactericidal under our experimental conditions. We further determine that the two genes located downstream encode two immunity proteins, one binding to and inactivating the toxin and the other detoxifying the cell via a pppApp hydrolase activity. Finally, based on protein sequence alignments, we propose a signature for (p)ppApp synthetases that distinguishes them from (p)ppGpp synthetases.

Loss of a Branch Sugar in the Acinetobacter baumannii K3-Type Capsular Polysaccharide Due To Frameshifts in the gtr6 Glycosyltransferase Gene Leads To Susceptibility To Phage APK37.1.

The type of capsular polysaccharide (CPS) on the cell surface of Acinetobacter baumannii can determine the specificity of lytic bacteriophage under consideration for therapeutic use. Here, we report the isolation of a phage on an extensively antibiotic resistant ST2 A. baumannii isolate AB5001 that carries the KL3 CPS biosynthesis gene cluster predicting a K3-type CPS. As the phage did not infect isolates carrying KL3 or KL22 and known to produce K3 CPS, the structure of the CPS isolated from A. baumannii AB5001 was determined. AB5001 produced a variant CPS form, K3-v1, that lacks the ß-d-GlсpNAc side chain attached to the d-Galp residue in the K3 structure. Inspection of the KL3 sequence in the genomes of AB5001 and other phage-susceptible isolates with a KL3 locus revealed single-base deletions in gtr6, causing loss of the Gtr6 glycosyltransferase that adds the missing d-GlсpNAc side chain to the K3 CPS. Hence, the presence of this sugar profoundly restricts the ability of the phage to digest the CPS. The 41-kb linear double-stranded DNA (dsDNA) phage genome was identical to the genome of a phage isolated on a K37-producing isolate and thus was named APK37.1. APK37.1 also infected isolates carrying KL116. Consistent with this, K3-v1 resembles the K37 and K116 structures. APK37.1 is a Friunavirus belonging to the Autographiviridae family. The phage-encoded tail spike depolymerase DpoAPK37.1 was not closely related to Dpo encoded by other sequenced Friunaviruses, including APK37 and APK116. IMPORTANCE Lytic bacteriophage have potential for the treatment of otherwise untreatable extensively antibiotic-resistant bacteria. For Acinetobacter baumannii, most phage exhibit specificity for the type of capsular polysaccharide (CPS) produced on the cell surface. However, resistance can arise via mutations in CPS genes that abolish this phage receptor. Here, we show that single-base deletions in a CPS gene result in alteration of the final structure rather than deletion of the capsule layer and hence affect the ability of a newly reported podophage to infect strains producing the K3 CPS.

Aplicación móvil para el análisis estadístico en Android / Mobile application for statistics analysis on Android

El uso de dispositivos móviles en la vida moderna es imprescindible debido a las ventajas que brindan al ofrecer nuevas posibilidades e implementar de manera virtual servicios ya establecidos. La mayor existencia de móviles que computadoras en los estudiantes de Cuba nos motivó a la realización de esta aplicación. El objetivo de este artículo es describir la aplicación nombrada Cálculos estadísticos y tasas en salud (Calc. Tasas versión 1.7) construida para realizar cálculos en un curso de Bioestadística, cubriendo gran parte del contenido de esta asignatura en la enseñanza de pregrado de las universidades médicas, así como otros contenidos de interés en esta materia. También incorpora una base de datos con información demográfica y sanitaria de Cuba y sus provincias en el período 2013-2020. Como resultado se logró independencia tecnológica al dejar de usar programas foráneos y se logró una mayor portabilidad pues funciona tanto en móviles como en computadoras utilizando un emulador de Android(AU)

The use of mobile devices in modern life is essential due to the advantages they provide, offering new possibilities and implementing virtual services. The existence of greater number of mobiles phones than computers in Cuban students motivated the realization of this application. The objective of the article is to describe the application Statistical calculations and rates in health (Calc. Rates version 1.7) built to perform calculations in a Biostatistics course, covering a large part of the content of this subject in the undergraduate teaching of medical universities, as well as other content related with this topic. It also incorporates a database with demographic and health information on Cuba and its provinces in the period 2013-2020. As a result, technological independence was achieved by stopping using foreign programs and a greater portability, since it works on both mobile phones and computers through an Android emulator(AU)

CO-RADS: aplicación móvil para la estandarización del informe radiológico en el contexto de la COVID 19 / CO-RADS: Mobile Application for Standardization of the Radiological Report in the Context of COVID 19

El nuevo coronavirus denominado SARS-COV2 causa diversas manifestaciones clínicas englobadas bajo el término COVID-19. El sistema de informe y datos conocidos por sus siglas en inglés como RADS, determinadas a partir del consenso de expertos producido por un grupo de trabajo multidisciplinario con el objetivo de mejorar la comunicación de los resultados, establece un enfoque estándar para la notificación de manifestaciones imagenológicas. El presente trabajo presenta el prototipo de aplicación CO-RADS que propone una herramienta digital sobre la base de una revisión actualizada del papel y la idoneidad de los estudios de imagenología para el diagnóstico y seguimiento de pacientes con sospecha o infección conocida de COVID-19, proporcionando terminología estandarizada de imágenes para lograr comunicar los resultados al médico de asistencia de manera clara y consistente. CO-RADS es una aplicación gratuita que se encuentra disponible en: htttps://www.aplikis.cu/es/application/cu.sld.hlucia.corads(AU)

The new coronavirus called SARS-COV2 causes various clinical manifestations encompassed under the term COVID-19. The data and reporting system known by its acronym in English as RADS, establishes a standard approach for the notification of imaging manifestations with the aim of improving the communication of results; was determined from the consensus of experts produced by a multidisciplinary working group. This paper presents the CO-RADS application prototype that proposes a digital tool based on an updated review of the role and suitability of imaging studies for the diagnosis and follow-up of patients with suspected or known COVID-19 infection, providing standardized imaging terminology to achieve clear and consistent communication of results to the attending physician. CO-RADS is a free application that is available at: htttps://www.aplikis.cu/es/application/cu.sld.hlucia.corads(AU)

Determining the Enzymatic Activity of Angiotensin-Converting Enzyme 2 (ACE2) in Brain Tissue and Cerebrospinal Fluid Using a Quenched Fluorescent Substrate.

Angiotensin-converting enzyme 2 (ACE2) is a component of the renin-angiotensin system (RAS) which plays an important role in the regulation of blood pressure and volume homeostasis. Accumulating evidence shows alterations in ACE2 expression and activity in several hypertensive animal models, as well as in patients with hypertension. In order to assess the role of brain ACE2 in hypertension, a specific ACE2 assay is required. Based on a quenched fluorescent substrate, we describe an easy-to-use method for determining ACE2 activity in brain tissue and cerebrospinal fluid. The method can further be adapted for other tissues, plasma, cell extracts, and cell culture supernatants.

Mikros, aplicación androide para Microbiología y Parasitología en la Universidad de Ciencias Médicas de Camagüey / Mikros, an Android Application for the Microbiology and Parasitology Subject in the University of Medical Sciences of Camagüey

Introducción: El aprendizaje móvil (m-learning) es la inclusión de dispositivos móviles en las actividades de aprendizaje. En la enseñanza de Microbiología y Parasitología médica estos ofrecen un alto poder de ilustración y contribuyen al aprendizaje de la asignatura de los estudiantes de la carrera de medicina; además, sirven de apoyo a otros perfiles como Tecnología de la Salud. Objetivo: Exponer la actualización del curso de Microbiología y Parasitología en la Universidad de Ciencias Médicas de Camagüey mediante una aplicación androide. Métodos: Se realizó una aplicación optimizada para androide 4.4 o superior con el lenguaje de programación Java. Esta investigación se desarrolló en la Universidad de Ciencias Médicas Carlos J. Finlay y se aplicó a estudiantes de la carrera de medicina en los cursos 2018-2019 y 2019-2020. El universo del estudio fueron 1446 estudiantes de los cursos de 2016-2020. Se realizó una encuesta validada por expertos a una muestra probabilística de 88 estudiantes de la Universidad de Ciencias Médicas de Camagüey, en el período comprendido entre noviembre y diciembre de 2020. Se calculó el coeficiente concordancia general W de Kendall en cuanto a las respuestas a las preguntas. Resultados: Mikros fue una herramienta de apoyo a la docencia, fruto de un proyecto de colaboración entre el Centro de Inmunología y Productos Biológicos de la Universidad de Ciencias Médicas y la Facultad de Ingeniería Informática de la Universidad Ignacio Agramonte, de Camagüey, que permitió introducir al profesor en una modalidad de enseñanza muy a tono con estos tiempos. Conclusiones: La aplicación Mikros incluyó conceptos básicos y un alto nivel de actualización. También contribuyó a elevar el índice académico y a una mayor satisfacción del alumno en el aprendizaje, y resultó una herramienta de consulta práctica para estudiantes de años posteriores de la carrera en rotación por el área clínica y útil para el aprendizaje a distancia en tiempos de COVID-19(AU)

Introduction: Mobile learning (m-learning) consists in the inclusion of mobile devices into learning activities. In the teaching of medical parasitology and microbiology, such devices offer a high power of illustration and contribute to medical students' learning of the subject; in addition, they serve as support to other profiles such as health technology. Objective: To present the update, by means of an android application, of the Microbiology and Parasitology course at the University of Medical Sciences of Camagüey. Methods: An optimized application for android 4.4 or higher was created with the Java programming language. This research was carried out at Carlos J. Finlay University of Medical Sciences and applied to medical students in the 2018-2019 and 2019-2020 academic years. The study universe was made up of 1446 students from the academic years from 2016 to 2020. A survey validated by experts was carried out, in the period between November and December 2020, with a probabilistic sample of 88 students from the University of Medical Sciences of Camagüey. Kendall's coefficient of general concordance (W) was calculated for the answers to the questions. Results: Mikros was a teaching support tool, the result of a collaborative project between the Center of Immunology and Biological Products at the University of Medical Sciences and the School of Computer Engineering at Ignacio Agramonte University, in Camagüey, which allowed to present the professor in a teaching modality much in tune with the current times. Conclusions: The Mikros application included basic concepts and a high update level. It also contributed to raising the student's academic index and satisfaction with learning. It turned out to be a practical consultation tool for students of higher academic years of the major who are rotating through the clinical area, as well as a useful tool for distance learning in COVID-19 times(AU)

Soy isoflavones and prostate cancer: a review of molecular mechanisms.

Soy isoflavones are dietary components for which an association has been demonstrated with reduced risk of prostate cancer (PCa) in Asian populations. However, the exact mechanism by which these isoflavones may prevent the development or progression of PCa is not completely understood. There are a growing number of animal and in vitro studies that have attempted to elucidate these mechanisms. The predominant and most biologically active isoflavones in soy products, genistein, daidzein, equol, and glycetin, inhibit prostate carcinogenesis in some animal models. Cell-based studies show that soy isoflavones regulate genes that control cell cycle and apoptosis. In this review, we discuss the literature relevant to the molecular events that may account for the benefit of soy isoflavones in PCa prevention or treatment. These reports show that although soy isoflavone-induced growth arrest and apoptosis of PCa cells are plausible mechanisms, other chemo protective mechanisms are also worthy of consideration. These possible mechanisms include antioxidant defense, DNA repair, inhibition of angiogenesis and metastasis, potentiation of radio- and chemotherapeutic agents, and antagonism of estrogen- and androgen-mediated signaling pathways. Moreover, other cells in the cancer milieu, such as the fibroblastic stromal cells, endothelial cells, and immune cells, may be targeted by soy isoflavones, which may contribute to soy-mediated prostate cancer prevention. In this review, these mechanisms are discussed along with considerations about the doses and the preclinical models that have been used.

Comparative analysis of human and bovine protein kinases reveals unique relationship and functional diversity.

Reversible protein phosphorylation by protein kinases and phosphatases is a common event in various cellular processes. The eukaryotic protein kinase superfamily, which is one of the largest superfamilies of eukaryotic proteins, plays several roles in cell signaling and diseases. We identified 482 eukaryotic protein kinases and 39 atypical protein kinases in the bovine genome, by searching publicly accessible genetic-sequence databases. Bovines have 512 putative protein kinases, each orthologous to a human kinase. Whereas orthologous kinase pairs are, on an average, 90.6% identical, orthologous kinase catalytic domain pairs are, on an average, 95.9% identical at the amino acid level. This bioinformatic study of bovine protein kinases provides a suitable framework for further characterization of their functional and structural properties.

Comparative analysis of human and bovine protein kinases reveals unique relationship and functional diversity

Reversible protein phosphorylation by protein kinases and phosphatases is a common event in various cellular processes. The eukaryotic protein kinase superfamily, which is one of the largest superfamilies of eukaryotic proteins, plays several roles in cell signaling and diseases. We identified 482 eukaryotic protein kinases and 39 atypical protein kinases in the bovine genome, by searching publicly accessible genetic-sequence databases. Bovines have 512 putative protein kinases, each orthologous to a human kinase. Whereas orthologous kinase pairs are, on an average, 90.6 percent identical, orthologous kinase catalytic domain pairs are, on an average, 95.9 percent identical at the amino acid level. This bioinformatic study of bovine protein kinases provides a suitable framework for further characterization of their functional and structural properties.