Dopamine Signaling Attenuates a Recurrent Neuronal Network during C. elegans Copulation

Neuro-modulation of self-amplifying circuits drives the execution of behaviors to their appropriate context. These recursive networks are found throughout the Caenorhabditis elegans connectome, however the mechanism that fine-tunes reciprocal neural activity during complex behaviors is unknown. Here I dissect the cellular and molecular components involved in male copulation, a goal oriented behavior that entails initiation and termination under appropriate circumstances. The C. elegans mating circuit integrates sensory-motor cues resulting in copulatory spicule insertion into the hermaphrodite vulva. As the male tail presses against the hermaphrodite’s genitalia, cholinergic and glutamatergic reciprocal innervations of post-cloaca sensilla (PCS) neurons (PCA, PCB and PCC), hook neurons (HOA, HOB) and their post-synaptic sex muscles execute rhythmic spicule thrusts. These repetitive spicule movements continue until the male shifts off the vulva or genital penetration. However, the signaling mechanism that temporally and spatially restricts intromission attempts to vulva cues was unclear. My results suggest that dopamine (DA) neuromodulation delimits spicule insertion attempts to the hermaphrodite vulva by dampening stimulus-independent spicule circuit activity. I found that upon vulval contact, DA signaling from male specific sensory neurons stimulates D2-like receptors, DOP-2 and DOP-3, to decrease cholinergic induced sex muscle contractions. Through pharmacology and targeted optogenetics I demonstrate that D2-like pathways act coincidentally, and as a consequence of cholinergic signaling, to reduce spicule intromission attempts with non-productive mating partners. During spicule intromission attempts, DA up-regulates gap-junctions among PCB and a hook neuron to decrease self-amplifying PCS properties. Through forward genetics I isolated a missense mutation in an UNC-7L gap-junction isoform, which perturbs DOP-2 signaling in PCB and its electrical partner, HOA. Additional pharmacogenetic analysis suggests that the AVR-14 glutamate-gated channel partially introduces chloride ions into HOA to mediate DA downmodulation of the spicule circuit. Consistently, my analysis of the unc-7(rg396) allele indicates that when DOP-2 promotes UNC-7 electrical communication, AVR-14-mediated inhibitory signals pass from HOA to PCB. Consequently, the cholinergic PCB neuron is less receptive to stimulation by its recurrent glutamatergic synaptic partner, PCA. Furthermore, behavioral observations suggest that DA neuromodulation of UNC-7 ensures attenuation of recursive intromission attempts when the male disengages or is dislodged from the hermaphrodite genitali

Extractos vegetales con actividad sobre cepas mutadas de saccharomyces cerevisiae con deficiencia en el mecanismo de reparacion del adn

Ciento treinta y ocho extractos obtenidos de plantas pertenecientes a las familias botánicas Asteraceae, Euphorbiaceae, Melastomataceae, Podocarpaceae, Rubiaceae y Solanaceae recolectadas en reservas naturales de la Ecorregión del Eje Cafetero (EEC) fueron evaluadas contra cepas de la levadura Saccharomyces cerevisiae RS 322N, R52Y y RS 321 por el método de difusión en agar, con el propósito de identificar nuevos extractos bioactivos que dañen el ADN y/o que inhiban las topoisomerasas I o II. Los extractos metanólicos de las especies pertenecientes a la familia Solanaceae: Browallia speciosa, Cestrum olivaceum y Solanum brevifolium mostraron selectividad para el ensayo de la levadura Saccharomyces cerevisiae mutada, presentando actividad como inhibidor de la topoisomerasa I. Adicionalmente, el extracto de diclorometano deSolanum deflexiflorum perteneciente a la misma familia presentó actividad inhibidora de la topoisomerasa II

Extractos vegetales con actividad sobre cepas mutadas de saccharomyces cerevisiae con deficiencia en el mecanismo de reparacion del adn

Ciento treinta y ocho extractos obtenidos de plantas pertenecientes a las familias botánicas Asteraceae, Euphorbiaceae, Melastomataceae, Podocarpaceae, Rubiaceae y Solanaceae recolectadas en reservas naturales de la Ecorregión del Eje Cafetero (EEC) fueron evaluadas contra cepas de la levadura Saccharomyces cerevisiae RS 322N, R52Y y RS 321 por el método de difusión en agar, con el propósito de identificar nuevos extractos bioactivos que dañen el ADN y/o que inhiban las topoisomerasas I o II. Los extractos metanólicos de las especies pertenecientes a la familia Solanaceae: Browallia speciosa, Cestrum olivaceum y Solanum brevifolium mostraron selectividad para el ensayo de la levadura Saccharomyces cerevisiae mutada, presentando actividad como inhibidor de la topoisomerasa I. Adicionalmente, el extracto de diclorometano deSolanum deflexiflorum perteneciente a la misma familia presentó actividad inhibidora de la topoisomerasa II

Risk Association of TOX3 and MMP7 Gene Polymorphisms with Sporadic Breast Cancer in Mexican Women

Breast cancer (BC) has one of the highest incidences and mortality worldwide. Single nucleotide polymorphisms (SNPs) in TOX3 rs3803662 and MMP7 rs1943779 have been associated with susceptibility to BC. In this case-control study, we evaluated the association of rs3803662 (TOX3)/rs1943779 (MMP7) SNPs with clinical features, immunohistochemical reactivity, and risk association with BC in women from northeastern Mexico. We compared 212 BC cases and 212 controls. DNA was isolated from peripheral blood to perform the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. We calculated genotype frequencies, odds ratios, and 95% confidence intervals. We found that CT (Cytocine-Thymine) and TT (Thymine -Thymine) genotypes, and T alleles of TOX3 rs3803662, were associated with BC risk (p = 0.034, p = 0.011, respectively). SNP TOX3 rs3803662 was associated with positive progesterone receptors (PR) and triple-negative BC (TNBC) but not with estrogen receptor (ER) or HER2 reactivity. CT and TT genotypes (p = 0.006) and T alleles (p = 0.002) of SNP MMP7 rs1943779 were associated with risk of BC. We found that T alleles of TOX3 rs3803662 and MMP7 rs1943779 SNPs are associated with BC risk. These findings contribute to personalized medicine in Mexican women

APLICACIÓN DEL SOFTWARE TURNITIN Y SU ÍNDICE DE SIMILITUD FINAL, COMO UN INDICADOR DE ORIGINALIDAD EN TESIS DE MEDICINA HUMANA, URP

Objetivos: Presentamos un estudio para determinar el índice de similitud final con el uso del software Turnitin® como un indicador de originalidad de las tesis de Medicina Humana de la Universidad Ricardo Palma. Métodos: Se realizó un estudio transversal con enfoque cuantitativo. Se seleccionaron de manera aleatoria 100 tesis realizadas con el Curso Taller de Titulación por Tesis organizado por la Facultad de Medicina Humana-Instituto de Investigación en Ciencias Biomédicas, de la Universidad Ricardo Palma, durante su primera edición año 2015. Las tesis fueron analizadas con el software Turnitin con el fin de detectar el índice de similitud final (ISF). Resultados: De las 100 tesis evaluadas, según sexo de los autores se encontró que el 46% eran hombres y el 54% correspondió a mujeres. Los temas preferidos de las tesis, correspondió a las áreas clínicas en un 60% (Medicina Interna, Salud Publica y Pediatría) y luego las áreas quirúrgicas 40% (Cirugía y Ginecología). La media obtenida del ISF fue de 8.41. De manera interesante el 65% de las tesis evaluadas obtuvo un Índice menor a 10%. Solo el 15% de las tesis correspondió a un ISF grado IV (>15%). Cuando revisamos las calificaciones de los jurados de tesis, el 90% correspondió a las tesis calificadas como buenas, muy buenas y sobresalientes. Conclusión: El software Turnitin® es adecuado para reportar el grado de similitud en las tesis de medicina. El índice de similitud final, constituye un indicador de originalidad, y el software puede ser útil para ayudar a detectar los niveles de originalidad y por lo tanto mejorar la integridad académica en el pregrado. El grado de originalidad hallado en las tesis de medicina humana del curso taller de titulación por tesis 2,015 de la Universidad Ricardo Palma es satisfactorio. DOI:https://doi.org/10.25176/RFMH.v16.n2.66

Precision mapping of COVID-19 vulnerable locales by epidemiological and socioeconomic risk factors, developed using South Korean data

COVID-19 has severely impacted socioeconomically disadvantaged populations. To support pandemic control strategies, geographically weighted negative binomial regression (GWNBR) mapped COVID-19 risk related to epidemiological and socioeconomic risk factors using South Korean incidence data (January 20, 2020 to July 1, 2020). We constructed COVID-19-specific socioeconomic and epidemiological themes using established social theoretical frameworks and created composite indexes through principal component analysis. The risk of COVID-19 increased with higher area morbidity, risky health behaviours, crowding, and population mobility, and with lower social distancing, healthcare access, and education. Falling COVID-19 risks and spatial shifts over three consecutive time periods reflected effective public health interventions. This study provides a globally replicable methodological framework and precision mapping for COVID-19 and future pandemics

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Study protocol for the multicentre cohorts of Zika virus infection in pregnant women, infants, and acute clinical cases in Latin America and the Caribbean: The ZIKAlliance consortium

Background: The European Commission (EC) Horizon 2020 (H2020)-funded ZIKAlliance Consortium designed a multicentre study including pregnant women (PW), children (CH) and natural history (NH) cohorts. Clinical sites were selected over a wide geographic range within Latin America and the Caribbean, taking into account the dynamic course of the ZIKV epidemic. Methods: Recruitment to the PW cohort will take place in antenatal care clinics. PW will be enrolled regardless of symptoms and followed over the course of pregnancy, approximately every 4 weeks. PW will be revisited at delivery (or after miscarriage/abortion) to assess birth outcomes, including microcephaly and other congenital abnormalities according to the evolving definition of congenital Zika syndrome (CZS). After birth, children will be followed for 2 years in the CH cohort. Follow-up visits are scheduled at ages 1-3, 4-6, 12, and 24 months to assess neurocognitive and developmental milestones. In addition, a NH cohort for the characterization of symptomatic rash/fever illness was designed, including follow-up to capture persisting health problems. Blood, urine, and other biological materials will be collected, and tested for ZIKV and other relevant arboviral diseases (dengue, chikungunya, yellow fever) using RT-PCR or serological methods. A virtual, decentralized biobank will be created. Reciprocal clinical monitoring has been established between partner sites. Substudies of ZIKV seroprevalence, transmissio