Genetic mapping of the p47 L.3.2 mutation in Drosophilamelanogaster.

An EMS-based forward genetic screen was conducted in an apoptotic null background to identify genetic aberrations that contribute to regulation of cell growth in Drosophila melanogaster . The current work maps the genomic location of one of the identified mutants, L.3.2 . Genetic crosses conducted through the Fly-CURE consortium determined that the gene locus for the L.3.2 mutation is p47 on chromosome 2R.

Proceedings of a Workshop to Promote Community Health Worker Interventions in Nephrology.

ABSTRACT: Latinx populations face a higher burden of kidney failure and associated negative outcomes compared with non-Latinx White populations, despite sharing a similar prevalence of CKD. Community health worker (CHW) interventions have been shown to improve outcomes for Latinx individuals, but they are largely underutilized in kidney disease. We convened a workshop of four ongoing kidney disease CHW programs to identify successes, challenges, potential solutions, and needed research to promote CHW programs for Latinx individuals with kidney disease. Key points from the workshop and recommendations for intervention and research are highlighted. Facilitators of program success included prioritizing trust-building with participants, enabling participants to determine what aspects of the intervention were needed, providing participants with tools to help themselves and others after the intervention, and taking a trauma-informed approach to relationships. Challenges included persistent systemic barriers despite successful care navigation and low recruitment and retention. Research is needed to capture the effect of CHW interventions on outcomes and to determine how to implement CHW interventions for people with kidney disease nationwide.

A leaky integrate-and-fire computational model based on the connectome of the entire adult Drosophila brain reveals insights into sensorimotor processing.

The forthcoming assembly of the adult Drosophila melanogaster central brain connectome, containing over 125,000 neurons and 50 million synaptic connections, provides a template for examining sensory processing throughout the brain. Here, we create a leaky integrate-and-fire computational model of the entire Drosophila brain, based on neural connectivity and neurotransmitter identity, to study circuit properties of feeding and grooming behaviors. We show that activation of sugar-sensing or water-sensing gustatory neurons in the computational model accurately predicts neurons that respond to tastes and are required for feeding initiation. Computational activation of neurons in the feeding region of the Drosophila brain predicts those that elicit motor neuron firing, a testable hypothesis that we validate by optogenetic activation and behavioral studies. Moreover, computational activation of different classes of gustatory neurons makes accurate predictions of how multiple taste modalities interact, providing circuit-level insight into aversive and appetitive taste processing. Our computational model predicts that the sugar and water pathways form a partially shared appetitive feeding initiation pathway, which our calcium imaging and behavioral experiments confirm. Additionally, we applied this model to mechanosensory circuits and found that computational activation of mechanosensory neurons predicts activation of a small set of neurons comprising the antennal grooming circuit that do not overlap with gustatory circuits, and accurately describes the circuit response upon activation of different mechanosensory subtypes. Our results demonstrate that modeling brain circuits purely from connectivity and predicted neurotransmitter identity generates experimentally testable hypotheses and can accurately describe complete sensorimotor transformations.

CYCLON and NPM1 Cooperate within an Oncogenic Network Predictive of R-CHOP Response in DLBCL.

R-CHOP immuno-chemotherapy significantly improved clinical management of diffuse large B-cell lymphoma (DLBCL). However, 30-40% of DLBCL patients still present a refractory disease or relapse. Most of the prognostic markers identified to date fail to accurately stratify high-risk DLBCL patients. We have previously shown that the nuclear protein CYCLON is associated with DLBCL disease progression and resistance to anti-CD20 immunotherapy in preclinical models. We also recently reported that it also represents a potent predictor of refractory disease and relapse in a retrospective DLBCL cohort. However, only sparse data are available to predict the potential biological role of CYCLON and how it might exert its adverse effects on lymphoma cells. Here, we characterized the protein interaction network of CYCLON, connecting this protein to the nucleolus, RNA processing, MYC signaling and cell cycle progression. Among this network, NPM1, a nucleolar multi-functional protein frequently deregulated in cancer, emerged as another potential target related to treatment resistance in DLBCL. Immunohistochemistry evaluation of CYCLON and NPM1 revealed that their co-expression is strongly related to inferior prognosis in DLBCL. More specifically, alternative sub-cellular localizations of the proteins (extra-nucleolar CYCLON and pan-cellular NPM1) represent independent predictive factors specifically associated to R-CHOP refractory DLBCL patients, which could allow them to be orientated towards risk-adapted or novel targeted therapies.

Genome Sequences of Microbacteriophages Zada and Ioannes.

Microbacteriophages Zada and Ioannes were isolated from soil and characterized. Genomes were then sequenced and annotated. This was done using the host bacterium Microbacterium foliorum Zada and Ioannes are both lytic phages with a Siphoviridae morphotype.

Differences in attitude toward prevention of suicide between nursing and medicine students: A study in Mexican population.

The aim of the present study was to evaluate the attitude toward suicide prevention in medicine and nursing students attending University in south Mexico, considering their family and personal history of suicide. Demographic features and self-reported personal and family history of suicide were evaluated in 355 Mexican students at the Health Sciences School. Their views toward suicide prevention was assessed using the Attitude Toward Suicide Prevention scale. Comparisons between medicine and nursing students were performed, as well as between had or had-not previous personal or family history of suicide. Our results support that nursing students showed the most negative attitude toward suicide prevention. Therefore, training programs and strategies encouraging a better attitude in suicide prevention are necessary to be implemented. It is also necessary to consider cultural, ethnic and family backgrounds of the students/of the population when developing new strategies.

Complete Genome Sequences of Cluster G Mycobacteriophage Darionha, Cluster A Mycobacteriophage Salz, and Cluster J Mycobacteriophage ThreeRngTarjay.

Mycobacteriophages Darionha, Salz, and ThreeRngTarjay are mycobacteriophages isolated using the host Mycobacterium smegmatis mc2155. Following isolation from soil samples, all three siphoviridae phages were characterized, and their genomes were sequenced and annotated.

Prevalencia de helicobacter pylori en un grupo de pacientes pediátricos infectados por el virus de la inmunodeficiencia humana / Prevalence of helicobacter pylori in a sample of pediatric patients infected by human inmunodeficiency virus

Se realizó un estudio cuantitativo, descriptivo transversal y no experimental sobre la prevalencia de Helicobacter pylori en pacientes pediátricos infectados por el virus de inmunodeficiencia humana (VIH), internados en el Hospicio San José, Santa Lucía Milpas Altas, Sacatepéquez, Guatemala, durante los meses de noviembre 2012 a enero 2013. La población completa fue conformada por 40 pacientes pediátricos de ambos sexos, entre los 3 y 12 años de edad, que padecen infección por VIH. Para el diagnóstico de infección por H. pylori se utilizó la detección de antígeno en heces por inmunocromatografía. Se encontró un resultado positivo en el 35%, con una mayor incidencia en varones, correspondiendo al 71.4% de los casos. En cuanto a la distribución por edades, el rango de edad con más casos positivos fue el comprendido entre los 7 y 8 años, con un 66.7% de los casos. La prevalencia de H. pylori en la población pediátrica VIH positiva estudiada fue mayor que la reportada en poblaciones similares, pero menor a la reportada en la población pediátrica VIH negativo. Se recomienda realizar un estudio multicéntrico para confirmar la prevalencia de H. pylori en la población pediátrica guatemalteca VIH positivo.

Aquantitative, descriptive, transversal, non experimental study was conducted on the prevalence of Helicobacter pylori in pediatric patients infected with the human immunodeficiency virus (HIV), who were admitted in the Hospice San Jose, Santa Lucia Milpas Altas, Sacatepequez, Guatemala, during November 2012 through January 2013. The study population included pediatric patients of both sexes, aged 3 to 12 years, who are infected with HIV. For the diagnosis of H. pylori infection an antigen stool test by immunochromatography was used. The population in the study period amounted to 40 patients in whom a positive result of 35% was found, 71.4% from male patients. In the age distribution it was found that the age range with more positive cases (66.7%) was between 7 and 8 years. The prevalence of H. pylori in the studied HIV positive pediatric population was higher than reported in similar populations, yet lower than reported in the HIV negative pediatric population. It is recommended that a multicenter study confirm the prevalence of H. pylori in the HIV positive Guatemalan pediatric population.

Malignant conversion of benign right ventricular outflow track ventricular tachycardia 18 years post-ablation.

This case report describes the rare phenomenon of malignant conversion of benign right ventricular outflow tract ventricular tachycardia into idiopathic ventricular fibrillation 18 years after successful ablation, in the absence of any type of heart disease. We review the current literature looking at predictors for this event, with the conclusion that there are no reliable risk predictors available. Until clear guidelines exist, we suggest patients be informed and monitored for the possibility of "malignant conversion" following ablation for benign idiopathic outflow tract ventricular tachycardia.

IR and electrochemical synthesis and characterization of thin films of PEDOT grown on platinum single crystal electrodes in [EMMIM]Tf2N ionic liquid.

Thin films of PEDOT synthesized on platinum single electrodes in contact with the ionic liquid 1-ethyl-2,3-dimethylimidazolium triflimide ([EMMIM]Tf2N) were studied by cyclic voltammetry, chronoamperometry, infrared spectroscopy and atomic force microscopy. It was found that the polymer grows faster on Pt(111) than on Pt(110) or Pt(100) and that the redox reactions associated with the PEDOT p-doping process are much more reversible in [EMMIM]Tf2N than in acetonitrile. Finally, the ion exchange and charge carriers' formation during the p-doping reaction of PEDOT were studied using in situ FTIR spectroscopy.

Barry shunt for treatment of a 76-hour stuttering priapism without subsequent erectile dysfunction.

INTRODUCTION: This paper reports treatment of a 76-hour low-flow priapism with a shunting procedure that was first described by Barry in 1976. We were able to observe the preservation of erectile function despite the long period of ischemia. A review of the literature shows that there are few reports of erectile function recovery after a priapism of similar duration. MATERIALS AND METHODS: A 42-year-old patient presented with a 76-hour priapism, probably caused by consumption of alcohol and illegal drugs. A Barry Shunt procedure was performed. The erectile function of the patient was assessed by means of International Index of Erectile Function score over a follow-up period of 30 months. Moreover, we reviewed different surgical options for treatment of priapism in the literature. RESULTS: Partial return of erection without sexual arousal occurred on two occasions during the 10-day hospitalization, but was treated by manipulation of the penis, ie, by milking the tumescence into the shunt. After 3 months, the shunt was still palpable as a subcutaneous swelling. Six months postoperatively, the residual swelling had disappeared. The International Index of Erectile Function score was of 21 without phosphodiesterase type 5 inhibitors after a follow-up of 2.5 years. CONCLUSION: Barry shunt is an effective alternative surgical option for the treatment of low-flow priapism. In the case of our patient, it was also effective after a 76-hour-lasting priapism.

IS-seq: a novel high throughput survey of in vivo IS6110 transposition in multiple Mycobacterium tuberculosis genomes.

BACKGROUND: The insertion element IS6110 is one of the main sources of genomic variability in Mycobacterium tuberculosis, the etiological agent of human tuberculosis. Although IS 6110 has been used extensively as an epidemiological marker, the identification of the precise chromosomal insertion sites has been limited by technical challenges. Here, we present IS-seq, a novel method that combines high-throughput sequencing using Illumina technology with efficient combinatorial sample multiplexing to simultaneously probe 519 clinical isolates, identifying almost all the flanking regions of the element in a single experiment. RESULTS: We identified a total of 6,976 IS6110 flanking regions on the different isolates. When validated using reference strains, the method had 100% specificity and 98% positive predictive value. The insertions mapped to both coding and non-coding regions, and in some cases interrupted genes thought to be essential for virulence or in vitro growth. Strains were classified into families using insertion sites, and high agreement with previous studies was observed. CONCLUSIONS: This high-throughput IS-seq method, which can also be used to map insertions in other organisms, extends previous surveys of in vivo interrupted loci and provides a baseline for probing the consequences of disruptions in M. tuberculosis strains.

[Comparative analysis of six Mycobacterium tuberculosis complex genomes]. / Análisis comparativo de seis genomas del complejo Mycobacterium tuberculosis.

INTRODUCTION: A growing number of sequenced genomes belonging to the Mycobacterium tuberculosis complex has enabled a comparison of strain traits and genomic constitution. These analyses may reveal mechanisms of evolution and genomic variation relevant to tuberculosis pathogenesis. OBJECTIVE: Multiple alignments were used to analyze the differences between six genomes of the M. tuberculosis complex and to locate regions of variation that may lead to improvements in species identification or in their treatment. MATERIALS AND METHODS: The Mauve software package was used to perform a multiple alignment of 6 genomes belonging to the M. tuberculosis complex. Regions exclusive to each genome were annotated using the TB database. RESULTS: Percent similarity among the six genomes ranged between 96.1% and 97.8%. The annotation identified intergenic regions, regions associated with transposable elements of the PE-PGRS and PPE families, and regions associated with resistance against bacteriophage. CONCLUSIONS: In spite of the high genetic similarity among the tuberculosis strains, genomic variations were elucidated that may be relevant to differences in behavior and virulence, as well as for improvement of strain diagnosis. Regions encoding membrane-associated proteins, possibly related with antigenic variation and immune response, are particularly interesting for studies aimed at seeking tuberculosis treatments.

Genomic signatures of the haarlem lineage of Mycobacterium tuberculosis: implications of strain genetic variation in drug and vaccine development.

Tuberculosis is the world's leading cause of death due to a single infectious agent, and efforts aimed at its control require a better understanding of host, environmental, and bacterial factors that govern disease outcome. Growing evidence indicates that certain Mycobacterium tuberculosis strains of distinct phylogeographic lineages elicit unique immunopathological events. However, identifying the genetic basis of these phenotypic peculiarities has proven difficult. Here we report the presence of six large sequence polymorphisms which, together with two single-nucleotide changes previously described by our group, consistently differentiate Haarlem strains from the remaining M. tuberculosis lineages. The six newly found Haarlem-specific genetic events are four deletions, which altogether involve more than 13 kb, and two intragenic insertions of the element IS6110. The absence of the genes involved in these polymorphisms could have an important physiological impact on Haarlem strains, i.e., by affecting key genes, such as Rv1354c and cyp121, which have been recently proposed as plausible drug targets. These lineage-specific polymorphisms can serve as genetic markers for the rapid PCR identification of Haarlem strains, providing a useful tool for strain surveillance and molecular epidemiology studies. Strain variability such as that described here underscores the need for the definition of a core set of essential genes in M. tuberculosis that are ubiquitously present in all circulating lineages, as a requirement in the development of effective antituberculosis drugs and vaccines.

Análisis comparativo de seis genomasdel complejo Mycobacterium tuberculosis / Comparative analysis of six Mycobacterium tuberculosis complex genomes

Introducción. El creciente número de genomas secuenciados pertenecientes al complejo Mycobacterium tuberculosis hace posible la comparación y el análisis genómico, que puede revelar importantes mecanismos de evolución y variación para entender la patogénesis de esta especie. Objetivo. Mediante el uso de alineamientos múltiples se pretendió analizar las diferencias entre seis genomas del complejo M. tuberculosis, para encontrar regiones de variación que conduzcan a mejoras en la identificación de estas especies o en el tratamiento. Materiales y métodos. Mediante el programa bioinformático Mauve, se realizaron alineamientos múltiples de seis genomas pertenecientes a especies del complejo M. tuberculosis. Las regiones genómicas exclusivas para cada genoma se anotaron usando la base de datos Tuberculosis Database.Resultados. El porcentaje de similitud entre los seis genomas analizados estuvo entre 96,1% y 97,8%. La anotación de las regiones exclusivas reveló la presencia de elementos de transposición, familias de proteínas PPE y PE-PGRS, regiones asociadas a resistencia contra bacteriófagos y regiones intergénicas. Conclusiones. A pesar de la gran similitud entre las cepas analizadas, existen variaciones entre ellas que pueden ser importantes para entender diferencias en comportamiento y virulencia, así como para mejorar los diagnósticos de cepas específicas. Regiones como aquéllas con genes para proteínas de membrana, posiblemente, relacionadas con la variación y la respuesta antigénica, son de particular interés para estudios futuros orientados a buscar tratamientos nuevos para el control de esta enfermedad.

Introduction. A growing number of sequenced genomes belonging to the Mycobacterium tuberculosis complex has enabled a comparison of strain traits and genomic constitution. These analyses may reveal mechanisms of evolution and genomic variation relevant to tuberculosis pathogenesis.Objective. Multiple alignments were used to analyze the differences between six genomes of the M. tuberculosis complex and to locate regions of variation that may lead to improvements in species identification or in their treatment. Materials and methods. The Mauve software package was used to perform a multiple alignment of 6 genomes belonging to the M. tuberculosis complex. Regions exclusive to each genome were annotated using the TB database.Results. Percent similarity among the six genomes ranged between 96.1% and 97.8%. The annotation identified intergenic regions, regions associated with transposable elements of the PE-PGRS and PPE families, and regions associated with resistance against bacteriophage. Conclusions. In spite of the high genetic similarity among the tuberculosis strains, genomic variations were elucidated that may be relevant to differences in behavior and virulence, as well as for improvement of strain diagnosis. Regions encoding membrane-associated proteins, possibly related with antigenic variation and immune response, are particularly interesting for studies aimed at seeking tuberculosis treatments.