Comparative Genomics Identifies Conserved and Variable TAL Effectors in African Strains of the Cotton Pathogen Xanthomonas citri pv. malvacearum.

Strains of Xanthomonas citri pv. malvacearum cause bacterial blight of cotton, a potentially serious threat to cotton production worldwide, including in sub-Saharan countries. Development of disease symptoms, such as water soaking, has been linked to the activity of a class of type 3 effectors, called transcription activator-like (TAL) effectors, which induce susceptibility genes in the host's cells. To gain further insight into the global diversity of the pathogen, to elucidate their repertoires of TAL effector genes, and to better understand the evolution of these genes in the cotton-pathogenic xanthomonads, we sequenced the genomes of three African strains of X. citri pv. malvacearum using nanopore technology. We show that the cotton-pathogenic pathovar of X. citri is a monophyletic lineage containing at least three distinct genetic subclades, which appear to be mirrored by their repertoires of TAL effectors. We observed an atypical level of TAL effector gene pseudogenization, which might be related to resistance genes that are deployed to control the disease. Our work thus contributes to a better understanding of the conservation and importance of TAL effectors in the interaction with the host plant, which can inform strategies for improving resistance against bacterial blight in cotton.

Resistance and susceptibility QTL identified in a rice MAGIC population by screening with a minor-effect virulence factor from Xanthomonas oryzae pv. oryzae.

Effective and durable disease resistance for bacterial blight (BB) of rice is a continuous challenge due to the evolution and adaptation of the pathogen, Xanthomonas oryzae pv. oryzae (Xoo), on cultivated rice varieties. Fundamental to this pathogens' virulence is transcription activator-like (TAL) effectors that activate transcription of host genes and contribute differently to pathogen virulence, fitness or both. Host plant resistance is predicted to be more durable if directed at strategic virulence factors that impact both pathogen virulence and fitness. We characterized Tal7b, a minor-effect virulence factor that contributes incrementally to pathogen virulence in rice, is a fitness factor to the pathogen and is widely present in geographically diverse strains of Xoo. To identify sources of resistance to this conserved effector, we used a highly virulent strain carrying a plasmid borne copy of Tal7b to screen an indica multi-parent advanced generation inter-cross (MAGIC) population. Of 18 QTL revealed by genome-wide association studies and interval mapping analysis, six were specific to Tal7b (qBB-tal7b). Overall, 150 predicted Tal7b gene targets overlapped with qBB-tal7b QTL. Of these, 21 showed polymorphisms in the predicted effector binding element (EBE) site and 23 lost the EBE sequence altogether. Inoculation and bioinformatics studies suggest that the Tal7b target in one of the Tal7b-specific QTL, qBB-tal7b-8, is a disease susceptibility gene and that the resistance mechanism for this locus may be through loss of susceptibility. Our work demonstrates that minor-effect virulence factors significantly contribute to disease and provide a potential new approach to identify effective disease resistance.

Functional analysis of African Xanthomonas oryzae pv. oryzae TALomes reveals a new susceptibility gene in bacterial leaf blight of rice.

Most Xanthomonas species translocate Transcription Activator-Like (TAL) effectors into plant cells where they function like plant transcription factors via a programmable DNA-binding domain. Characterized strains of rice pathogenic X. oryzae pv. oryzae harbor 9-16 different tal effector genes, but the function of only a few of them has been decoded. Using sequencing of entire genomes, we first performed comparative analyses of the complete repertoires of TAL effectors, herein referred to as TALomes, in three Xoo strains forming an African genetic lineage different from Asian Xoo. A phylogenetic analysis of the three TALomes combined with in silico predictions of TAL effector targets showed that African Xoo TALomes are highly conserved, genetically distant from Asian ones, and closely related to TAL effectors from the bacterial leaf streak pathogen Xanthomonas oryzae pv. oryzicola (Xoc). Nine clusters of TAL effectors could be identified among the three TALomes, including three showing higher levels of variation in their repeat variable diresidues (RVDs). Detailed analyses of these groups revealed recombination events as a possible source of variation among TAL effector genes. Next, to address contribution to virulence, nine TAL effector genes from the Malian Xoo strain MAI1 and four allelic variants from the Burkinabe Xoo strain BAI3, thus representing most of the TAL effector diversity in African Xoo strains, were expressed in the TAL effector-deficient X. oryzae strain X11-5A for gain-of-function assays. Inoculation of the susceptible rice variety Azucena lead to the discovery of three TAL effectors promoting virulence, including two TAL effectors previously reported to target the susceptibility (S) gene OsSWEET14 and a novel major virulence contributor, TalB. RNA profiling experiments in rice and in silico prediction of EBEs were carried out to identify candidate targets of TalB, revealing OsTFX1, a bZIP transcription factor previously identified as a bacterial blight S gene, and OsERF#123, which encodes a subgroup IXc AP2/ERF transcription factor. Use of designer TAL effectors demonstrated that induction of either gene resulted in greater susceptibility to strain X11-5A. The induction of OsERF#123 by BAI3Δ1, a talB knockout derivative of BAI3, carrying these designer TAL effectors increased virulence of BAI3Δ1, validating OsERF#123 as a new, bacterial blight S gene.

Genomic Acquisitions in Emerging Populations of Xanthomonas vasicola pv. vasculorum Infecting Corn in the United States and Argentina.

Xanthomonas vasicola pv. vasculorum is an emerging bacterial plant pathogen that causes bacterial leaf streak on corn. First described in South Africa in 1949, reports of this pathogen have greatly increased in the past years in South America and in the United States. The rapid spread of this disease in North and South America may be due to more favorable environmental conditions, susceptible hosts and/or genomic changes that favored the spread. To understand whether genetic mechanisms exist behind the recent spread of X. vasicola pv. vasculorum, we used comparative genomics to identify gene acquisitions in X. vasicola pv. vasculorum genomes from the United States and Argentina. We sequenced 41 genomes of X. vasicola pv. vasculorum and the related sorghum-infecting X. vasicola pv. holcicola and performed comparative analyses against all available X. vasicola genomes. Time-measured phylogenetic analyses showed that X. vasicola pv. vasculorum strains from the United States and Argentina are closely related and arose from two introductions to North and South America. Gene content comparisons identified clusters of genes enriched in corn X. vasicola pv. vasculorum that showed evidence of horizontal transfer including one cluster corresponding to a prophage found in all X. vasicola pv. vasculorum strains from the United States and Argentina as well as in X. vasicola pv. holcicola strains. In this work, we explore the genomes of an emerging phytopathogen population as a first step toward identifying genetic changes associated with the emergence. The acquisitions identified may contain virulence determinants or other factors associated with the spread of X. vasicola pv. vasculorum in North and South America and will be the subject of future work.

Diagnostic challenges of Brugada Syndrome in pediatric patients.

Although most cases of Brugada syndrome have been described in adults, pediatric patients with the disease have been reported since the original article from Josep and Pedro Brugada. Herein is presented the case series of Brugada syndrome in pediatric population of the National Institute of Cardiology Ignacio Chavez. One boy and two adolescent males had palpitations as clinical presentation of the disease. Atrial arrhythmias were documented in two, in the third case there was a high clinical suspicion and quinidine abolished symptoms. The aim of this report is to highlight the importance of performing a detailed clinical history as well as the usefulness of high precordial leads for the diagnosis of this entity.

Andersen-Tawil Syndrome with High Risk of Sudden Cardiac Death in Four Mexican Patients. Cardiac and Extra-Cardiac Phenotypes.

BACKGROUND: Andersen-Tawil syndrome (ATS) is a cardiac channelopathy that is inherited in an autosomal dominant way, and it is characterized by a triad of periodic paralysis, ventricular arrhythmias, and includes some dysmorphic features with incom- plete penetrance and variable expression that result in a challenging diagnosis. OBJECTIVE: The objective of the study was to describe the cardiac and extra-cardiac phenotype in a cohort of patients with ATS at risk of sudden cardiac death (SCD) to improve its early clinical identification. METHODS: In an observational, transversal study, with a deviant case sampling, four female patients with ATS at high risk of SCD were included in the study. They carried the heterozygous pathogenic variants c.407C>T [p.Ser136Phe], c.652C>T [p.Arg218Trp] (n=2), and c.431G>C [p.Gly144Ala] in the KCNJ2 gene. Patients were evaluated by a cardiologist, a clinical geneticist, and a physiatrist. RESULTS: One patient had the classical facial phenotype and the other three had subtle manifestations. The group of patients presented a diverse set of clinical data such as: triangular face, broad forehead, broadening of medial eyebrows, auricular pits, low-set ears, eyelid ptosis, thin lips, mandibular hypoplasia, and diverse types of dental alterations, single transverse palmar crease, camptodactyly, and syndactyly. Long-exercise test showed a decrement in the percentage amplitude up to 44%, classifying patients in IV or V types according to Fournier's scale. CONCLUSIONS: Extra- cardiac manifestations were a common finding in this series of ATS type1 at high risk of SCD. Its recognition could help the clinician in the early identification of patients with ATS, especially for the cardiologist since they are commonly referred only for evaluation of ventricular arrhythmias.

daTALbase: A Database for Genomic and Transcriptomic Data Related to TAL Effectors.

Transcription activator-like effectors (TALEs) are proteins found in the genus Xanthomonas of phytopathogenic bacteria. These proteins enter the nucleus of cells in the host plant and can induce the expression of susceptibility genes (S genes), triggering disease. TALEs bind the promoter region of S genes following a specific code, which allows the prediction of binding sites based on TALEs amino acid sequences. New candidate S genes can then be discovered by finding the intersection between genes induced in the presence of TALEs and genes containing predicted effector binding elements. By contrasting differential expression data and binding site predictions across different datasets, patterns of TALE diversification or convergence may be unveiled, but this requires the seamless integration of different genomic and transcriptomic data. With this in mind, we present daTALbase, a curated relational database that integrates TALE-related data including bacterial TALE sequences, plant promoter sequences, predicted TALE binding sites, transcriptomic data of host plants in response to TALE-harboring bacteria, and other associated data. The database can be explored to uncover new candidate S genes as well as to study variation in TALE repertories and their corresponding targets. The first version of the database here presented includes data for Oryza sp.-Xanthomonas pv. oryzae interactions. Future versions of the database will incorporate information for other pathosystems involving TALEs.

Perturbation of maize phenylpropanoid metabolism by an AvrE family type III effector from Pantoea stewartii.

AvrE family type III effector proteins share the ability to suppress host defenses, induce disease-associated cell death, and promote bacterial growth. However, despite widespread contributions to numerous bacterial diseases in agriculturally important plants, the mode of action of these effectors remains largely unknown. WtsE is an AvrE family member required for the ability of Pantoea stewartii ssp. stewartii (Pnss) to proliferate efficiently and cause wilt and leaf blight symptoms in maize (Zea mays) plants. Notably, when WtsE is delivered by a heterologous system into the leaf cells of susceptible maize seedlings, it alone produces water-soaked disease symptoms reminiscent of those produced by Pnss. Thus, WtsE is a pathogenicity and virulence factor in maize, and an Escherichia coli heterologous delivery system can be used to study the activity of WtsE in isolation from other factors produced by Pnss. Transcriptional profiling of maize revealed the effects of WtsE, including induction of genes involved in secondary metabolism and suppression of genes involved in photosynthesis. Targeted metabolite quantification revealed that WtsE perturbs maize metabolism, including the induction of coumaroyl tyramine. The ability of mutant WtsE derivatives to elicit transcriptional and metabolic changes in susceptible maize seedlings correlated with their ability to promote disease. Furthermore, chemical inhibitors that block metabolic flux into the phenylpropanoid pathways targeted by WtsE also disrupted the pathogenicity and virulence activity of WtsE. While numerous metabolites produced downstream of the shikimate pathway are known to promote plant defense, our results indicate that misregulated induction of phenylpropanoid metabolism also can be used to promote pathogen virulence.

RNAseq analysis of cassava reveals similar plant responses upon infection with pathogenic and non-pathogenic strains of Xanthomonas axonopodis pv. manihotis.

KEY MESSAGE: An RNAseq-based analysis of the cassava plants inoculated with Xam allowed the identification of transcriptional upregulation of genes involved in jasmonate metabolism, phenylpropanoid biosynthesis and putative targets for a TALE. Cassava bacterial blight, a disease caused by the gram-negative bacterium Xanthomonas axonopodis pv. manihotis (Xam), is a major limitation to cassava production worldwide and especially in developing countries. The molecular mechanisms underlying cassava susceptibility to Xam are currently unknown. To identify host genes and pathways leading to plant susceptibility, we analyzed the transcriptomic responses occurring in cassava plants challenged with either the non-pathogenic Xam strain ORST4, or strain ORST4(TALE1 Xam ) which is pathogenic due to the major virulence transcription activator like effector TALE1 Xam . Both strains triggered similar responses, i.e., induction of genes related to photosynthesis and phenylpropanoid biosynthesis, and repression of genes related to jasmonic acid signaling. Finally, to search for TALE1 Xam virulence targets, we scanned the list of cassava genes induced upon inoculation of ORST4(TALE1 Xam ) for candidates harboring a predicted TALE1 Xam effector binding element in their promoter. Among the six genes identified as potential candidate targets of TALE1 Xam a gene coding for a heat shock transcription factor stands out as the best candidate based on their induction in presence of TALE1 Xam and contain a sequence putatively recognized by TALE1 Xam .

Bioinformatic identification of cassava miRNAs differentially expressed in response to infection by Xanthomonas axonopodis pv. manihotis.

BACKGROUND: microRNAs (miRNAs) are short RNA molecules that control gene expression by silencing complementary mRNA. They play a crucial role in stress response in plants, including biotic stress. Some miRNAs are known to respond to bacterial infection in Arabidopsis thaliana but it is currently unknown whether these responses are conserved in other plants and whether novel species-specific miRNAs could have a role in defense. RESULTS: This work addresses the role of miRNAs in the Manihot esculenta (cassava)-Xanthomonas axonopodis pv. manihotis (Xam) interaction. Next-generation sequencing was used for analyzing small RNA libraries from cassava tissue infected and non-infected with Xam. A full repertoire of cassava miRNAs was characterized, which included 56 conserved families and 12 novel cassava-specific families. Endogenous targets were predicted in the cassava genome for many miRNA families. Some miRNA families' expression was increased in response to bacterial infection, including miRNAs known to mediate defense by targeting auxin-responding factors as well as some cassava-specific miRNAs. Some bacteria-repressed miRNAs included families involved in copper regulation as well as families targeting disease resistance genes. Putative transcription factor binding sites (TFBS) were identified in the MIRNA genes promoter region and compared to promoter regions in miRNA target genes and protein coding genes, revealing differences between MIRNA gene transcriptional regulation and other genes. CONCLUSIONS: Taken together these results suggest that miRNAs in cassava play a role in defense against Xam, and that the mechanism is similar to what's known in Arabidopsis and involves some of the same families.

Mining of miRNAs and potential targets from gene oriented clusters of transcripts sequences of the anti-malarial plant, Artemisia annua.

miRNAs involved in the biosynthesis of artemisinin, an anti-malarial compound form the plant Artemisia annua, have been identified using computational approaches to find conserved pre-miRNAs in available A. annua UniGene collections. Eleven pre-miRNAs were found from nine families. Targets predicted for these miRNAs were mainly transcription factors for conserved miRNAs. No target genes involved in artemisinin biosynthesis were found. However, miR390 was predicted to target a gene involved in the trichome development, which is the site of synthesis of artemisinin and could be a candidate for genetic transformation aiming to increase the content of artemisinin. Phylogenetic analyses were carried out to determinate the relation between A. annua and other plant pre-miRNAs: the pre-miRNA-based phylogenetic trees failed to correspond to known phylogenies, suggesting that pre-miRNA primary sequences may be too variable to accurately predict phylogenetic relations.

Soluble concentrations of the terminal complement complex C5b-9 correlate with end-organ injury in preeclampsia.

OBJECTIVE: We sought to determine if soluble levels of C5b-9, the terminal complement complex, correlate with end-organ injury in preeclampsia. STUDY DESIGN: Project COPA (Complement and Preeclampsia in the Americas), a multi-center observational study in Colombia from 2015 to 2016, enrolled hypertensive pregnant women into four groups: chronic hypertension, gestational hypertension, preeclampsia, and preeclampsia with severe features. Trained coordinators collected clinical data, blood and urine. End-organ injury was defined by serum creatinine ≥ 1.0 mg/dl, aspartate transaminase ≥ 70U/L, platelet count < 150,000/µl, or lactate dehydrogenase ≥ 500 U/L. Data were analyzed by χ2 or Fisher's exact test with significance at P < 0.05. MAIN OUTCOME MEASURE: C5b-9 concentrations in plasma and urine, using enzyme linked immunosorbent assays. RESULTS: In total, 298 hypertensive participants were enrolled. Plasma and urine C5b-9 levels were measured in all participants and stratified by quartile (Q1-4), from lowest to highest C5b-9 concentration. Participants with low plasma C5b-9 levels (Q1) were more likely to have end-organ injury compared to those with higher levels (Q2-Q4) [platelet count < 150,000/µl (20.8% vs. 8.4%, P = 0.01); elevated serum creatinine ≥ 1.0 mg/dl (14.9% vs. 4.5%, P = 0.009)]. In contrast, participants with high urinary C5b-9 levels (Q4) were more likely to have end-organ injury compared to those with lower levels (Q1-Q3) [platelet count < 150,000/µl (19.7% vs. 7.4%, P = 0.003); elevated serum creatinine ≥ 1.0 mg/dl (12.3% vs. 4.4%, P = 0.025)]. CONCLUSION: We identified a pattern of increased urine and low plasma C5b-9 levels in patients with preeclampsia and end-organ injury. Soluble C5b-9 levels may be used to identify complement-mediated end-organ injury in preeclampsia.

Ablation in Brugada Syndrome: A Review of Two Cases.

Brugada syndrome (BrS) is characterized by ventricular arrhythmias in patients without structural cardiac alteration. Some patients present repeated episodes of ventricular tachycardia. Epicardial catheter ablation makes it possible to decrease arrhythmic recurrence in these patients.

Artificial microRNAs (amiRNAs) engineering - On how microRNA-based silencing methods have affected current plant silencing research.

In recent years, endogenous microRNAs have been described as important regulators of gene expression in eukaryotes. Artificial microRNAs (amiRNAs) represent a recently developed miRNA-based strategy to silence endogenous genes. amiRNAs can be created by exchanging the miRNA/miRNA(∗) sequence within a miRNA precursor with a sequence designed to match the target gene, this is possible as long as the secondary RNA structure of the precursor is kept intact. In this review, we summarize the basic methodologies to design amiRNAs and detail their applications in plants genetic functional studies as well as their potential for crops genetic improvement.

Accumulating candidate genes for broad-spectrum resistance to rice blast in a drought-tolerant rice cultivar.

Biotic stresses, including diseases, severely affect rice production, compromising producers' ability to meet increasing global consumption. Understanding quantitative responses for resistance to diverse pathogens can guide development of reliable molecular markers, which, combined with advanced backcross populations, can accelerate the production of more resistant varieties. A candidate gene (CG) approach was used to accumulate different disease QTL from Moroberekan, a blast-resistant rice variety, into Vandana, a drought-tolerant variety. The advanced backcross progeny were evaluated for resistance to blast and tolerance to drought at five sites in India and the Philippines. Gene-based markers were designed to determine introgression of Moroberekan alleles for 11 CGs into the progeny. Six CGs, coding for chitinase, HSP90, oxalate oxidase, germin-like proteins, peroxidase and thaumatin-like protein, and 21 SSR markers were significantly associated with resistance to blast across screening sites. Multiple lines with different combinations, classes and numbers of CGs were associated with significant levels of race non-specific resistance to rice blast and sheath blight. Overall, the level of resistance effective in multiple locations was proportional to the number of CG alleles accumulated in advanced breeding lines. These disease resistant lines maintained tolerance to drought stress at the reproductive stage under blast disease pressure.

Clinical Spectrum of SCN5A Channelopathy in Children with Primary Electrical Disease and Structurally Normal Hearts.

Sodium voltage-gated channel α subunit 5 (SCN5A)-mutations may cause an array of arrhythmogenic syndromes most frequently as an autosomal dominant trait, with incomplete penetrance, variable expressivity and male predominance. In the present study, we retrospectively describe a group of Mexican patients with SCN5A-disease causing variants in whom the onset of symptoms occurred in the pediatric age range. The study included 17 patients with clinical diagnosis of primary electrical disease, at least one SCN5A pathogenic or likely pathogenic mutation and age of onset <18 years, and all available first- and second-degree relatives. Fifteen patients (88.2%) were male, and sixteen independent variants were found (twelve missense, three truncating and one complex inframe deletion/insertion). The frequency of compound heterozygosity was remarkably high (3/17, 17.6%), with early childhood onset and severe disease. Overall, 70.6% of pediatric patients presented with overlap syndrome, 11.8% with isolated sick sinus syndrome, 11.8% with isolated Brugada syndrome (BrS) and 5.9% with isolated type 3 long QT syndrome (LQTS). A total of 24/45 SCN5A mutation carriers were affected (overall penetrance 53.3%), and penetrance was higher in males (63.3%, 19 affected/30 mutation carriers) than in females (33.3%, 5 affected/15 carriers). In conclusion, pediatric patients with SCNA-disease causing variants presented mainly as overlap syndrome, with predominant loss-of-function phenotypes of sick sinus syndrome (SSS), progressive cardiac conduction disease (PCCD) and ventricular arrhythmias.

TAL Effector Repertoires of Strains of Xanthomonas phaseoli pv. manihotis in Commercial Cassava Crops Reveal High Diversity at the Country Scale.

Transcription activator-like effectors (TALEs) play a significant role for pathogenesis in several xanthomonad pathosystems. Xanthomonas phaseoli pv. manihotis (Xpm), the causal agent of Cassava Bacterial Blight (CBB), uses TALEs to manipulate host metabolism. Information about Xpm TALEs and their target genes in cassava is scarce, but has been growing in the last few years. We aimed to characterize the TALE diversity in Colombian strains of Xpm and to screen for TALE-targeted gene candidates. We selected eighteen Xpm strains based on neutral genetic diversity at a country scale to depict the TALE diversity among isolates from cassava productive regions. RFLP analysis showed that Xpm strains carry TALomes with a bimodal size distribution, and affinity-based clustering of the sequenced TALEs condensed this variability mainly into five clusters. We report on the identification of 13 novel variants of TALEs in Xpm, as well as a functional variant with 22 repeats that activates the susceptibility gene MeSWEET10a, a previously reported target of TAL20Xam668. Transcriptomics and EBE prediction analyses resulted in the selection of several TALE-targeted candidate genes and two potential cases of functional convergence. This study provides new bases for assessing novel potential TALE targets in the Xpm-cassava interaction, which could be important factors that define the fate of the infection.

An atypical class of non-coding small RNAs is produced in rice leaves upon bacterial infection.

Non-coding small RNAs (sRNA) act as mediators of gene silencing and regulate plant growth, development and stress responses. Early insights into plant sRNAs established a role in antiviral defense and they are now extensively studied across plant-microbe interactions. Here, sRNA sequencing discovered a class of sRNA in rice (Oryza sativa) specifically associated with foliar diseases caused by Xanthomonas oryzae bacteria. Xanthomonas-induced small RNAs (xisRNAs) loci were distinctively upregulated in response to diverse virulent strains at an early stage of infection producing a single duplex of 20-22 nt sRNAs. xisRNAs production was dependent on the Type III secretion system, a major bacterial virulence factor for host colonization. xisRNA loci overlap with annotated transcripts sequences, with about half of them encoding protein kinase domain proteins. A number of the corresponding rice cis-genes have documented functions in immune signaling and xisRNA loci predominantly coincide with the coding sequence of a conserved kinase motif. xisRNAs exhibit features of small interfering RNAs and their biosynthesis depend on canonical components OsDCL1 and OsHEN1. xisRNA induction possibly mediates post-transcriptional gene silencing but they do not broadly suppress cis-genes expression on the basis of mRNA-seq data. Overall, our results identify a group of unusual sRNAs with a potential role in plant-microbe interactions.

[Management of heart failure with His bundle pacing in right bundle branch block: case report]. / Manejo de la insuficiencia cardiaca con estimulación hisiana en bloqueo de rama derecha: reporte de caso.

La terapia de resincronización cardiaca mediante estimulación hisiana ha demostrado ser efectiva en pacientes con bloqueo de rama izquierda del haz de His e insuficiencia cardiaca. Paciente masculino, con 47 años de edad, con insuficiencia cardiaca, fracción de expulsión del 17% y miocardio dilatada idiopática, electrocardiograma en ritmo sinusal, bloqueo auriculoventricular de 1.er grado, intervalo PR 400 ms, bloqueo completo de rama derecha del haz de His, bloqueo del fascículo anterior de la rama izquierda del haz de His, duración del QRS 200 ms. Se decidió realizar estimulación selectiva del haz de His. La resincronización cardiaca biventricular convencional en pacientes con presencia de bloqueo completo de la rama derecha del haz de His no está indicada debido a la pobre respuesta al tratamiento. La estimulación hisiana permite reclutar la rama bloqueada y reestablecer la conducción a través de ella, de tal forma que, en ausencia de necrosis, se logre sincronía biventricular. En el caso presentado el reclutamiento de la rama derecha mediante estimulación hisiana se reflejó en el restablecimiento de la sincronía biventricular, medida por rastreo de marcas (speckle tracking) e incremento significativo de la fracción de expulsión del ventrículo izquierdo del 17 al 36.6%, con un incremento absoluto del 19.6%.Cardiac resynchronization therapy has proven to be an effective therapy in patients with left bundle branch block and heart failure. Male, 47 years old, heart failure with a left ventricle ejection fraction of 17%, idiopathic heart failure. ECG with sinus rhythm, 1st degree AV block, PR 400 ms, complete right bundle branch block, anterior hemi-fascicle of the left bundle of His, and QRS duration 200 ms. We decided to perform a selective His bundle pacing. In patients with right bundle branch block the biventricular cardiac resynchronization is not indicated due to low treatment response. His bundle pacing allows recruiting the blocked branch and restoring conduction throughout it, therefore, in the absence of necrosis the biventricular synchrony is achieved. We presented a case of His bundle pacing with recruitment of the right bundle branch, which reestablish biventricular synchrony measured by speckle tracking, and with a significant increase of the left ventricle ejection fraction from 17 to 36.6%, with an absolute increase of 19.6%.

Plant microRNAs and their role in defense against viruses: a bioinformatics approach.

BACKGROUND: microRNAs (miRNAs) are non-coding short RNAs that regulate gene expression in eukaryotes by translational inhibition or cleavage of complementary mRNAs. In plants, miRNAs are known to target mostly transcription factors and are implicated in diverse aspects of plant growth and development. A role has been suggested for the miRNA pathway in antiviral defense in plants. In this work, a bioinformatics approach was taken to test whether plant miRNAs from six species could have antiviral activity by targeting the genomes of plant infecting viruses. RESULTS: All plants showed a repertoire of miRNAs with potential for targeting viral genomes. The viruses were targeted by abundant and conserved miRNA families in regions coding for cylindrical inclusion proteins, capsid proteins, and nuclear inclusion body proteins. The parameters for our predicted miRNA:target pairings in the viral genomes were similar to those for validated targets in the plant genomes, indicating that our predicted pairings might behave in-vivo as natural miRNa-target pairings. Our screening was compared with negative controls comprising randomly generated miRNAs, animal miRNAs, and genomes of animal-infecting viruses. We found that plant miRNAs target plant viruses more efficiently than any other sequences, but also, miRNAs can either preferentially target plant-infecting viruses or target any virus without preference. CONCLUSIONS: Our results show a strong potential for antiviral activity of plant miRNAs and suggest that the miRNA pathway may be a support mechanism to the siRNA pathway in antiviral defense.