Croton stipulaceus Kunth, a native Mexican medicinal plant with antioxidant and anti-inflammatory activities / Croton stipulaceus Kunth, planta medicinal mexicana con actividad antioxidante y antiinflamatoria

Leaves of Croton stipulaceuswere extracted (EHex, ECHCl3and EEtOH extracts) to assesstheir antioxidant potential, anti-inflammatory activity in murine models and acute toxicity. EEtOH showed the highest effect in DPPH (37.80% inhibition), FRAP (1065.00 ± 55.30 µmolFe2+) and total polyphenols (231.24 ± 9.05 meq AG/gM). EHex was the most active, ~ 50% inhibition of TPA-induced ear edema; while EEtOH (dose of 2 mg/ear) showed the highest inhibition in the chronic model (97% inhibition), and inhibited MPO activity (48%). In carrageenan-induced edema, ECHCl3(dose 500 mg/kg) was the most active. None of the extracts showed acute toxicity (LD50) at 2 g/kg (p.o.). This work is the first report that supports the traditional use of C. stipulaceusas an anti-inflammatory.

De las hojas de Croton stipulaceusse obtuvieron diferentes extractos (EHex, ECHCl3y EEtOH) evaluando el potencial antioxidante y la actividad antiinflamatoria en modelos murinos y la toxicidad aguda. El EEtOH mostró mayor efecto en DPPH (37.80% inhibición), FRAP (1065.00 ± 55.30 µmolFe2+) y polifenolestotales (231.24 ± 9.05 meq AG/gM). El EHex fue el más activo, cercano al 50% de inhibición del edema auricular inducido con TPA; mientras que el EEtOH (dosis de 2 mg/oreja) mostró la mayor inhibición en el modelo crónico (97% inhibición), e inhibió la actividad de la MPO (48%). En el edema inducido con carragenina, el ECHCl3(dosis 500 mg/kg) fue el más activo. Ninguno de los extractos mostró una toxicidad aguda (DL50) mayor a 2 g/kg (p.o). Este trabajo es el primer reporte que sustenta el uso tradicional de C. stipulaceuscomo antiinflamatorio.

ClC-1 Chloride Channel: Inputs on the Structure-Function Relationship of Myotonia Congenita-Causing Mutations.

Myotonia congenita is a hereditary muscle disease mainly characterized by muscle hyperexcitability, which leads to a sustained burst of discharges that correlates with the magnitude and duration of involuntary aftercontractions, muscle stiffness, and hypertrophy. Mutations in the chloride voltage-gated channel 1 (CLCN1) gene that encodes the skeletal muscle chloride channel (ClC-1) are responsible for this disease, which is commonly known as myotonic chloride channelopathy. The biophysical properties of the mutated channel have been explored and analyzed through in vitro approaches, providing important clues to the general function/dysfunction of the wild-type and mutated channels. After an exhaustive search for CLCN1 mutations, we report in this review more than 350 different mutations identified in the literature. We start discussing the physiological role of the ClC-1 channel in skeletal muscle functioning. Then, using the reported functional effects of the naturally occurring mutations, we describe the biophysical and structural characteristics of the ClC-1 channel to update the knowledge of the function of each of the ClC-1 helices, and finally, we attempt to point out some patterns regarding the effects of mutations in the different helices and loops of the protein.

Automated chronic wounds medical assessment and tracking framework based on deep learning.

Chronic wounds are a latent health problem worldwide, due to high incidence of diseases such as diabetes and Hansen. Typically, wound evolution is tracked by medical staff through visual inspection, which becomes problematic for patients in rural areas with poor transportation and medical infrastructure. Alternatively, the design of software platforms for medical imaging applications has been increasingly prioritized. This work presents a framework for chronic wound tracking based on deep learning, which works on RGB images captured with smartphones, avoiding bulky and complicated acquisition setups. The framework integrates mainstream algorithms for medical image processing, including wound detection, segmentation, as well as quantitative analysis of area and perimeter. Additionally, a new chronic wounds dataset from leprosy patients is provided to the scientific community. Conducted experiments demonstrate the validity and accuracy of the proposed framework, with up to 84.5% in precision.

Dyslipidemia in Muscular Dystrophy: A Systematic Review and Meta-Analysis.

BACKGROUND: Muscular dystrophies (MDs) are characterized by chronic muscle wasting but also poorly understood metabolic co-morbidities. We have recently shown that Duchenne MD (DMD) patients, dogs and asymptomatic carriers are affected by a new form of dyslipidemia that may exacerbate muscle damage. OBJECTIVE: We aimed to perform a systematic review and meta-analysis for evidence that other types of MDs are associated with dyslipidemia compared to healthy controls. METHODS: Search was conducted using MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials for reports that compare plasma/serum lipids from MD patients and controls, and meta-analysis of cross-sectional studies quantifying total cholesterol, high-density lipoprotein, low density lipoprotein and triglycerides was performed. RESULTS: Out of 749 studies, 17 met our inclusion criteria for meta-analysis. 14 of the 17 studies (82%) included investigated myotonic dystrophy (DM); other studies were on pseudohypertrophic MD (PMD) or DMD. As a whole, MD individuals had significantly higher levels of circulating total cholesterol (Hedges' g with 95% confidence interval [CI], 0.80 [0.03 - 1.56]; p = 0.04) and triglycerides (Hedges' g with 95% confidence interval [CI], 2.28[0.63 - 3.92]; p = 0.01) compared to controls. Meta-regression analysis showed the percentage of male gender was significantly associated with the difference in total cholesterol (beta = 0.05; 95% CI, - 0.02 to 0.11; p = 0.043) and high-density lipoprotein (beta = - 9.38; 95% CI, - 16.26 to - 2.50; p = 0.028). CONCLUSIONS: MD is associated with significantly higher circulating levels of total cholesterol and triglycerides. However, caution on the interpretation of these findings is warranted and future longitudinal research is required to better understand this relationship.

Individual-specific levels of CTG•CAG somatic instability are shared across multiple tissues in myotonic dystrophy type 1.

Myotonic dystrophy type 1 is a complex disease caused by a genetically unstable CTG repeat expansion in the 3'-untranslated region of the DMPK gene. Age-dependent, tissue-specific somatic instability has confounded genotype-phenotype associations, but growing evidence suggests that it also contributes directly toward disease progression. Using a well-characterized clinical cohort of DM1 patients from Costa Rica, we quantified somatic instability in blood, buccal cells, skin and skeletal muscle. Whilst skeletal muscle showed the largest expansions, modal allele lengths in skin were also very large and frequently exceeded 2000 CTG repeats. Similarly, the degree of somatic expansion in blood, muscle and skin were associated with each other. Notably, we found that the degree of somatic expansion in skin was highly predictive of that in skeletal muscle. More importantly, we established that individuals whose repeat expanded more rapidly than expected in one tissue (after correction for progenitor allele length and age) also expanded more rapidly than expected in other tissues. We also provide evidence suggesting that individuals in whom the repeat expanded more rapidly than expected in skeletal muscle have an earlier age at onset than expected (after correction for the progenitor allele length). Pyrosequencing analyses of the genomic DNA flanking the CTG repeat revealed that the degree of methylation in muscle was well predicted by the muscle modal allele length and age, but that neither methylation of the flanking DNA nor levels of DMPK sense and anti-sense transcripts could obviously explain individual- or tissue-specific patterns of somatic instability.

Morpho-agronomic evaluation of native maize races associated with Mexican tropical climate agroforestry systems.

Maize (Zea mays L.) is native to Mexico, in which wide genetic diversity can be found; however, maize is at risk of genetic erosion, and agroforestry systems (ASs) can be a strategy for conservation and sustainable use of this crop. The objective of this study was to evaluate the variation in the morpho-agronomic characteristics of three native maize races, Tuxpeño, Olotillo × Tuxpeño and Ratón × Tepecintle, cultivated in different AS in a tropical climate of Veracruz, Mexico, as well as its association with microclimatic conditions. In 2019, experiments were established in the localities La Gloria and La Luisa, Veracruz, where the three maize races are cultivated, in a randomized complete block design with three replications in a 3 × 4 factorial scheme (three native maize races and three AS arrrays, plus monoculture). Ten morpho-agronomic variables were recorded in each experiment and were analyzed by analysis of variance (ANOVA; Tukey's post-hoc test, all p ≤ 0.05) and principal component analysis (PCA). Six morpho-agronomic characteristics showed significant differences for the race × system interaction. Consistently standing out both in the Myroxylon with 2.8 m × 2.0 arrays and in the monoculture was the Olotillo × Tuxpeño race, as there were no variations (p ≥ 0.05) in 50% of its morpho-agronomic characteristics. The first three PCs explained 87.7% of the cumulative variance, determined by five variables of the ears, three of the grain and plant height, which were associated with temperature; therefore, the microclimatic conditions of the studied ASs are associated with the morpho-agronomic characteristics of the native maize races. The results show that ASs could be a strategy for the conservation and use of native corn germplasm and could allow the diversification of sustainable production for rural farmers.

Identificación de aberraciones cromosómicas en una población infantil costarricense con discapacidad intelectual idiopática / Identification of chromosomal aberrations in a Costa Rican children population with idiopathicintellectual disability

Resumen La prevalencia mundial de la discapacidad intelectual (DI) es del 3 %. Una de las causas más comunes de DI de origen genético son las aberraciones cromosómicas, las cuales resultan fácilmente detectables mediante un cariotipo. Sin embargo, muchas de estas pasan desapercibidas durante el análisis citogenético convencional debido a su tamaño. Estas pequeñas alteraciones se pueden localizar en los subtelómeros y se ha observado que, cuando es así, constituyen una razón importante de DI en pacientes que carecen de un diagnóstico de causalidad. En este estudio de tipo observacional, se utilizó la técnica MLPA con el objetivo de determinar la frecuencia de aberraciones cromosómicas submicroscópicas en los subtelómeros en una población infantil con DI de origen desconocido. Se examinaron 70 muestras de forma exitosa y se obtuvo un caso con una microduplicación en el subtelómero 17p, para una frecuencia del 1,4 %. También, se realizó el análisis citogenético en 33 muestras y se encontró un caso con una aberración cromosómica detectable al microscopio, para una frecuencia del 3 %. El porcentaje de aberraciones cromosómicas subteloméricas fue menor al esperado en comparación con estudios similares. Finalmente, se concluyó que el cariotipo y la técnica MLPA se complementan para el abordaje de personas con DI de origen desconocido.

Abstract The prevalence of intellectual disability (ID) in the global population is 3%. One of the most frequent cause of ID are chromosome aberrations, which are easily detected by a karyotype. However, many of these maygoundetected during a conventional cytogenetic analysis because of their length.These small alterations can be localized in the subtelomeres and it has been observed that when localized there, they are an important cause of ID in patients without a causality diagnostic. In this observational study, we use the MLPA technique for the purpose of identifying the frequency of submicroscopicsubtelomere chromosomal aberrations in a population of people with ID of unknown origin. 70 samples were successfully analyzed with MLPA and we found one case with a microduplication in the 17p subtelomere for a frequency of 1,4%. Also,the karyotype was performed in 33cases, and we foundone case with a chromosome aberration that can be detect by microscope for a frequency of 3%. The subtelomeric chromosome aberration frequency was lower than expected as we compare our results with similar studies. Finally, with this work we conclude that the karyotype and the MLPA technique complement each other for approaching people with ID of unknown origin.

Inicio de la Dosimetría Biológica en Costa Rica y su importancia en la atención de poblaciones sobreexpuestas a radiaciones / Beginning of Biological Dosimetry in Costa Rica and its importance in the care of populations overexposed to ionizing radiation

Resumen Introducción: el laboratorio de citogenética del Instituto de Investigaciones en Salud (INISA) de la Universidad de Costa Rica estableció un Servicio de Dosimetría Biológica en enero del 2020 utilizando biomarcadores citogenéticos de exposición a radiaciones ionizantes. Es el primero de su tipo en la región centroamericana. Objetivo: establecer un servicio de dosimetría biológica para Costa Rica, elaborando una curva de calibración dosis-efecto para rayos gamma. Metodología: para la realización de la curva de calibración se irradiaron muestras de sangre periférica in vitro con rayos gamma de dos voluntarios, uno femenino y otro masculino, en 11 puntos de dosis en el rango de 0 a 5 Gy. Se cultivó la sangre acorde a los protocolos internacionales durante 48 horas y se registraron las aberraciones inducidas. Los programas Dose Estimate V5.2 y R versión 4.03 se utilizaron para el cálculo de los coeficientes de la curva de calibración que correlaciona la frecuencia de cromosomas dicéntricos con la dosis. Resultados: los coeficientes de la curva son α: 0.02737±0.00658, ß: 0,05938±0,00450 y C: 0.00129±0.00084. Estos coeficientes tienen valores similares a los reportados internacionalmente. La curva se validó calculando dos dosis incógnitas, en la primera incógnita la dosis suministrada fue de 1,5 Gy y la dosis estimada fue 1,47 Gy y en la segunda la dosis suministrada fue de 4 Gy y la dosis estimada fue 3,616 Gy, para ambos casos no existen diferencias estadísticamente significativas entre las dosis suministradas y las estimadas. Conclusiones: actualmente El Servicio de Dosimetría Biológica del INISA puede estimar dosis absorbida en personas que se sospecha de una sobre exposición a rayos gamma en personal ocupacionalmente expuesto o personas involucradas en un accidente radiológico.

Abstract Introduction. The cytogenetics laboratory of the Health Research Institute (INISA) of the University of Costa Rica established a Biological Dosimetry Service in January 2020 using cytogenetic biomarkers of exposure to ionizing radiation. It is the first of its kind in the Central American region. Objective: establish a biological dosimetry service for Costa Rica, developing a dose-effect calibration curve for gamma rays. Methodology: to carry out the calibration curve, peripheral blood samples from two volunteers, one female and the other male, were irradiated in vitro with gamma rays, at 11 dose points in the range of 0 to 5 Gy. Blood was cultured according to international protocols for 48 hours and induced aberrations were recorded. The Dose Estimate V5.2 and R version 4.03 programs were used to calculate the coefficients of the calibration curve that correlates the frequency of dicentric chromosomes with the dose. Results: the coefficients of the curve are α: 0.02737 ± 0.00658, ß: 0.05938 ± 0.00450 and C: 0.00129 ± 0.00084. These coefficients have values similar to those reported internationally. The curve was validated by calculating two unknown doses, in the first unknown case the delivered dose was 1.5 Gy and the estimated dose was 1.47 Gy and in the second case the delivered dose was 4 Gy and the estimated dose was 3.616 Gy. for both cases there are no statistically significant differences between the delivered and estimated doses. Conclusions: the Biological Dosimetry Service of the INISA can estimate absorbed dose in persons suspected of overexposure to gamma rays in occupationally exposed personnel or persons involved in a radiological accident.Health is loaded with symbolisms and practical manifestations that differ according to social groups and sociocultural contexts. In order to make everyday life and needs visible, the Theoretical Paradigm of Social Representations provides the theoretical-methodological bases necessary to understand the common sense knowledge associated with health among the Nicaraguan migrant population in Costa Rica. Methodology: Qualitative study with ethnographic approach that aimed to identify the social representation of health, through the process of objectification, present among Nicaraguan migrants living in Costa Rica. Data collected through semi-structured interviews, participant observation, and field diaries. Processing according to Content Analysis. Results: The social representation of health found behaves analogously to a formula; where, the search for peaceful environments is added to the achievement of financial stability to result in two interdependent representations: 1) Health as physical-mental strength; and 2) Health as a future and abstract sensation of well-being, happiness and transcendence. The socio-political antecedents in Nicaragua, the migratory process, and the adaptation to Costa Rica play a preponderant role in shaping the representation on health. Conclusion: Social representations about health have direct practical implications on the ways of life and needs of migrant groups. Understanding their common sense knowledge allows to move towards more contextualized public policies. More integration of the thoughts, opinions and feelings of migrants in decision-making platforms is recommended.

Effect of Pulsed Light on Quality of Shelled Walnuts.

Shelled walnuts are considered a microbiologically low-risk food but have been linked to some outbreaks, and a treatment aiming to decrease this risk is desirable. Pulsed light (PL) may be an alternative, providing it does not seriously impair their quality. This work assessed the impact of PL on some quality attributes of walnuts. To do this, measurements of rancidity, volatiles, total phenols, antioxidant activity, and descriptive sensory analysis were carried out on untreated and PL (43 J/cm2)-treated kernels. PL had no statistically significant (p > 0.05) effects on TBARS, peroxide value, total phenols, and antioxidant activity but significantly increased the concentration of volatiles related to green/herbaceous odors and decreased compounds related to fruity and citrus odors. The descriptors nut overall, walnut odor and flavor, and aftertaste were given statistically significantly (p < 0.05) higher scores, while descriptors woody odor and sweet received lower scores; 16 other traits such as all those related to color, texture, and rancidity were unaffected. No significant (p > 0.05) effects on total phenols and antioxidant activity in general were observed during the course of PL treatment. It can be concluded that PL technology may be used in shelled walnuts with only mild effects on their quality; a storage study must be carried out in order to determine the effect of PL treatment on its shelf-life.

Synergy of the Tropical Earthworm Pontoscolex corethrurus and Oil Palm Bagasse in the Removal of Heavy Crude Oil.

The tropical endogeic earthworm Pontoscolex corethrurus, a non-standard species used in ecotoxicity, has been found in crude oil-contaminated habitats. We estimated the removal of total hydrocarbons from heavy crude "Maya" oil on an artificially contaminated soil with a median lethal concentration of P. corethrurus and an addition of oil palm bagasse. P. corethrurus had a high survival rate, and the addition of oil palm bagasse led to a greater growth and an increase in abundance of bacteria and fungi. The activity of P. corethrurus and the nutritional quality of oil palm bagasse had a significant impact on the removal of a larger amount of petroleum hydrocarbons from contaminated soil. We concluded that the endogeic earthworm P. corethrurus and oil palm bagasse acted synergistically to achieve a more effective removal of total petroleum hydrocarbons from soil. These results show the potential for using P. corethrurus to remove, either directly or indirectly, crude oil from soil.

Myotonic dystrophy type 1 (DM1) clinical subtypes and CTCF site methylation status flanking the CTG expansion are mutant allele length-dependent.

Myotonic dystrophy type 1 (DM1) is a complex disease with a wide spectrum of symptoms. The exact relationship between mutant CTG repeat expansion size and clinical outcome remains unclear. DM1 congenital patients (CDM) inherit the largest expanded alleles, which are associated with abnormal and increased DNA methylation flanking the CTG repeat. However, DNA methylation at the DMPK locus remains understudied. Its relationship to DM1 clinical subtypes, expansion size and age-at-onset is not yet completely understood. Using pyrosequencing-based methylation analysis on 225 blood DNA samples from Costa Rican DM1 patients, we determined that the size of the estimated progenitor allele length (ePAL) is not only a good discriminator between CDM and non-CDM cases (with an estimated threshold at 653 CTG repeats), but also for all DM1 clinical subtypes. Secondly, increased methylation at both CTCF sites upstream and downstream of the expansion was almost exclusively present in CDM cases. Thirdly, levels of abnormal methylation were associated with clinical subtype, age and ePAL, with strong correlations between these variables. Fourthly, both ePAL and the intergenerational expansion size were significantly associated with methylation status. Finally, methylation status was associated with ePAL and maternal inheritance, with almost exclusively maternal transmission of CDM. In conclusion, increased DNA methylation at the CTCF sites flanking the DM1 expansion could be linked to ePAL, and both increased methylation and the ePAL could be considered biomarkers for the CDM phenotype.

Functional and Structural Characterization of ClC-1 and Nav1.4 Channels Resulting from CLCN1 and SCN4A Mutations Identified Alone and Coexisting in Myotonic Patients.

Non-dystrophic myotonias have been linked to loss-of-function mutations in the ClC-1 chloride channel or gain-of-function mutations in the Nav1.4 sodium channel. Here, we describe a family with members diagnosed with Thomsen's disease. One novel mutation (p.W322*) in CLCN1 and one undescribed mutation (p.R1463H) in SCN4A are segregating in this family. The CLCN1-p.W322* was also found in an unrelated family, in compound heterozygosity with the known CLCN1-p.G355R mutation. One reported mutation, SCN4A-p.T1313M, was found in a third family. Both CLCN1 mutations exhibited loss-of-function: CLCN1-p.W322* probably leads to a non-viable truncated protein; for CLCN1-p.G355R, we predict structural damage, triggering important steric clashes. The SCN4A-p.R1463H produced a positive shift in the steady-state inactivation increasing window currents and a faster recovery from inactivation. These gain-of-function effects are probably due to a disruption of interaction R1463-D1356, which destabilizes the voltage sensor domain (VSD) IV and increases the flexibility of the S4-S5 linker. Finally, modelling suggested that the p.T1313M induces a strong decrease in protein flexibility on the III-IV linker. This study demonstrates that CLCN1-p.W322* and SCN4A-p.R1463H mutations can act alone or in combination as inducers of myotonia. Their co-segregation highlights the necessity for carrying out deep genetic analysis to provide accurate genetic counseling and management of patients.

Evaluator perceptions of NGO performance in disasters: meeting multiple institutional demands in humanitarian aid projects.

Providing aid in times of increasing humanitarian need, limited budgets, and mounting security risks is challenging. This paper explores in what organisational circumstances evaluators judge, positively and negatively, the performance of international non-governmental organisations (INGOs) in response to disasters triggered by natural hazards. It assesses whether and how, as perceived by expert evaluators, CARE and Oxfam successfully met multiple institutional requirements concerning beneficiary needs and organisational demands. It utilises the Competing Values Framework to analyse evaluator statements about project performance and organisational control and flexibility issues, using seven CARE and four Oxfam evaluation reports from 2005-11. The reports are compared using fuzzy-set Qualitative Comparative Analysis. The resulting configurations show that positive evaluations of an INGO's internal and external flexibility relate to satisfying beneficiary needs and organisational demands, whereas negative evaluations of external flexibility pertain to not meeting beneficiary needs and negative statements about internal control concerning not fulfilling organisational demands.

Yeast Surface Display System: Strategies for Improvement and Biotechnological Applications.

Yeast surface display (YSD) is a "whole-cell" platform used for the heterologous expression of proteins immobilized on the yeast's cell surface. YSD combines the advantages eukaryotic systems offer such as post-translational modifications, correct folding and glycosylation of proteins, with ease of cell culturing and genetic manipulation, and allows of protein immobilization and recovery. Additionally, proteins displayed on the surface of yeast cells may show enhanced stability against changes in temperature, pH, organic solvents, and proteases. This platform has been used to study protein-protein interactions, antibody design and protein engineering. Other applications for YSD include library screening, whole-proteome studies, bioremediation, vaccine and antibiotics development, production of biosensors, ethanol production and biocatalysis. YSD is a promising technology that is not yet optimized for biotechnological applications. This mini review is focused on recent strategies to improve the efficiency and selection of displayed proteins. YSD is presented as a cutting-edge technology for the vectorial expression of proteins and peptides. Finally, recent biotechnological applications are summarized. The different approaches described herein could allow for a better strategy cascade for increasing protein/peptide interaction and production.

Microbial prospection of communities that produce biosurfactants from the water column and sediments of the Gulf of Mexico.

Microbial communities capable of hydrocarbon degradation linked to biosurfactant (BS) and bioemulsifier (BE) production are basically unexplored in the Gulf of México (GOM). In this work, the BS and BE production of culturable marine bacterial hydrocarbonoclasts consortia isolated from two sites (the Perdido Fold Belt and Coatzacoalcos area) was investigated. The prospection at different locations and depths led to the screening and isolation of a wide variety of bacterial consortia with BS and BE activities, after culture enrichment with crude oil and glycerol as the carbon sources. At least 55 isolated consortia presented reduction in surface tension (ST) and emulsifying activity (EI24 ). After colony purification, bacteria were submitted to polyphasic analysis assays that resulted in the identification of different strains of cultivable Gammaproteobacteria Gram (-) Citrobacter, Enterobacter, Erwinia, Pseudomonas, Vibrio, Shewanella, Thalassospira, Idiomarina, Pseudoalteromonas, Photobacterium, and Gram (+) Staphylococcus, Bacillus, and Microbacterium. Overall, the best results for ST reduction and EI24 were obtained with consortia. Individually, Pseudomonas, Bacillus, and Enterobacter strains showed the best results for the reduction of ST after 6 days, while Thalassospira and Idiomarina strains showed the best results for EI24 (above 68% after 9 days). Consortia isolates from the GOM had the ability to degrade crude oil by up to 40-80% after 24 and 36 months, respectively. In all cases, biodegradation of crude oil was related to the reduction in ST and bioemulsifying activity and was independent from the depth in the water column.

Characterization of Enterobacter cloacae BAGM01 Producing a Thermostable and Alkaline-Tolerant Rhamnolipid Biosurfactant from the Gulf of Mexico.

The search for novel biosurfactants (Bs) requires the isolation of microorganisms from different environments. The Gulf of Mexico (GoM) is a geographical area active in the exploration and exploitation of hydrocarbons. Recent metagenomic and microbiologic studies in this area suggested a potential richness for novel Bs microbial producers. In this work, nineteen bacterial consortia from the GoM were isolated at different depths of the water column and marine sediments. Bs production from four bacterial consortia was detected by the CTAB test and their capacity to reduce surface tension (ST), emulsion index (EI24), and hemolytic activity. These bacterial consortia produced Bs in media supplemented with kerosene, diesel, or sucrose. Cultivable bacteria from these consortia were isolated and identified by bacterial polyphasic characterization. In some consortia, Enterobacter cloacae was the predominant specie. E. cloacae BAGM01 presented Bs activity in minimal medium and was selected to improve its Bs production using a Taguchi and Box-Behnken experimental design; this strain was able to grow and presented Bs activity at 35 g L-1 of NaCl. This Bs decreased ST to around 34.5 ± 0.56 mNm-1 and presented an EI24 of 71 ± 1.27%. Other properties of this Bs were thermal stability, stability in alkaline conditions, and stability at high salinity, conferring important and desirable characteristics in multiple industries. The analysis of the genome of E. cloacae BAGM01 showed the presence of rhlAB genes that have been reported in the synthesis of rhamnolipids, and alkAB genes that are related to the degradation of alkanes. The bioactive molecule was identified as a rhamnolipid after HPLC derivatization, 1H NMR, and UPLC-QTOF-MS analysis.

Male survival advantage on the Baja California peninsula.

A consistent finding from contemporary Western societies is that women outlive men. However, what is unclear is whether sex differences in survival are constant across varying socio-ecological conditions. We test the universality of the female survival advantage with mortality data from a nineteenth century population in the Baja California peninsula of Mexico. When examined simply, we find evidence for a male-biased survival advantage. However, results from Cox regression clearly show the importance of age intervals for variable survival patterns by sex. Our key findings are that males: (i) experience significantly lower mortality risk than females during the ages 15-30 (RR = 0.69), (ii) are at a significantly increased risk of dying in the 61+ category (RR = 1.30) and (iii) do not experience significantly different mortality risk at any other age interval (0-14, 31-45, 46-60). We interpret our results to stem from differing intrinsic and extrinsic risk factors for sex-biased mortality across age intervals, highlighting the relevance of a lifecourse approach to the study of survival advantage. Ultimately, our results make clear the need to more broadly consider variability in mortality risk factors across time and place to allow for a clearer understanding of human survival differences.

Community-wide HIV testing, linkage case management, and defaulter tracing in Bukoba, Tanzania: pre-intervention and post-intervention, population-based survey evaluation.

BACKGROUND: Community randomised trials have had mixed success in implementing combination prevention strategies that diagnose 90% of people living with HIV, initiate and retain on antiretroviral therapy (ART) 90% of those diagnosed, and achieve viral load suppression in 90% of those on ART (90-90-90). The Bukoba Combination Prevention Evaluation (BCPE) aimed to achieve 90-90-90 in Bukoba Municipal Council, Tanzania, by scaling up new HIV testing, linkage, and retention interventions. METHOD: We did population-based, cross-sectional surveys before and after our community-wide intervention in Bukoba-a mixed urban and rural council of approximately 150 000 residents located on the western shore of Lake Victoria in Tanzania. BCPE interventions were implemented in 11 government-supported health-care facilities throughout Bukoba from Oct 1, 2014, to March 31, 2017, when national ART-eligibility guidelines expanded from CD4 counts of less than 350 cells per µL (Oct 1, 2014-Dec 31, 2015) and 500 or less cells per µL (Jan 1, 2016-Sept 30, 2016) to any CD4 cell count (test and treat, Oct 1, 2016-March 31, 2017). We used pre-intervention (Nov 4, 2013-Jan 25, 2014) and post-intervention (June 21, 2017-Sept 20, 2017) population-based household surveys to assess population prevalence of undiagnosed HIV infection and ART coverage, and progress towards 90-90-90, among residents aged 18-49 years. FINDINGS: During the 2·5-year intervention, BCPE did 133 695 HIV tests, diagnosed and linked 3918 people living with HIV to HIV care at 11 Bukoba facilities, and returned to HIV care 604 patients who had stopped care. 4795 and 5067 residents aged 18-49 years participated in pre-intervention and post-intervention surveys. HIV prevalence before and after the intervention was similar: pre-intervention 8·9% (95% CI 7·5-10·4); post-intervention 8·4% (6·9-9·9). Prevalence of undiagnosed HIV infection decreased from 4·7% to 2·0% (prevalence ratio 0·42, 95% CI 0·31-0·57), and current ART use among all people living with HIV increased from 32·2% to 70·9% (2·20, 1·82-2·66) overall, 23·0% to 62·1% among men (2·70, 1·84-3·96), and 16·7% to 64·4% among people aged 18-29 years (3·87, 2·54-5·89). Of 436 and 435 people living with HIV aged 18-49 years who participated in pre-intervention and post-intervention surveys, previous HIV diagnosis increased from 47·4% (41·3-53·4) to 76·2% (71·8-80·6), ART use among diagnosed people living with HIV increased from 68·0% (60·9-75·2) to 93·1% (90·2-96·0), and viral load suppression of those on ART increased from 88·7% (83·6-93·8) to 91·3% (88·6-94·1). INTERPRETATION: BCPE findings suggest scaling up recommended HIV testing, linkage, and retention interventions can help reduce prevalence of undiagnosed HIV infection, increase ART use among all people living with HIV, and make substantial progress towards achieving 90-90-90 in a relatively short period. BCPE facility-based testing and linkage interventions are undergoing national scale up to help achieve 90-90-90 in Tanzania. FUNDING: US Presidents' Emergency Plan for AIDS Relief.

Longitudinal increases in somatic mosaicism of the expanded CTG repeat in myotonic dystrophy type 1 are associated with variation in age-at-onset.

In myotonic dystrophy type 1 (DM1), somatic mosaicism of the (CTG)n repeat expansion is age-dependent, tissue-specific and expansion-biased. These features contribute toward variation in disease severity and confound genotype-to-phenotype analyses. To investigate how the (CTG)n repeat expansion changes over time, we collected three longitudinal blood DNA samples separated by 8-15 years and used small pool and single-molecule PCR in 43 DM1 patients. We used the lower boundary of the allele length distribution as the best estimate for the inherited progenitor allele length (ePAL), which is itself the best predictor of disease severity. Although in most patients the lower boundary of the allele length distribution was conserved over time, in many this estimate also increased with age, suggesting samples for research studies and clinical trials should be obtained as early as possible. As expected, the modal allele length increased over time, driven primarily by ePAL, age-at-sampling and the time interval. As expected, small expansions <100 repeats did not expand as rapidly as larger alleles. However, the rate of expansion of very large alleles was not obviously proportionally higher. This may, at least in part, be a result of the allele length-dependent increase in large contractions that we also observed. We also determined that individual-specific variation in the increase of modal allele length over time not accounted for by ePAL, age-at-sampling and time was inversely associated with individual-specific variation in age-at-onset not accounted for by ePAL, further highlighting somatic expansion as a therapeutic target in DM1.

Highly selective Diels-Alder and Heck arylation reactions in a divergent synthesis of isoindolo- and pyrrolo-fused polycyclic indoles from 2-formylpyrrole.

A highly regio-, chemo- and stereoselective divergent synthesis of isoindolo- and pyrrolo-fused polycyclic indoles is herein described, starting from 2-formylpyrrole and employing Diels-Alder and Heck arylation reactions. 3-(N-Benzyl-2-pyrrolyl)acrylates and 4-(pyrrol-2-yl)butenones underwent a highly endo-Diels-Alder cycloaddition with maleimides to furnish octahydropyrrolo[3,4-e]indoles, which served as precursors in the regioselective synthesis of aza-polycyclic skeletons via an intramolecular Heck arylation reaction. Through the latter reaction, the 3-(N-benzyl-2-pyrrolyl)acrylates give rise to 3-(pyrrolo[2,1-a]isoindol-3-yl)acrylates. A further oxidative aromatization of the polycyclic intermediates provides the corresponding polycyclic pyrrolo-isoindoles and isoindolo-pyrrolo-indoles. A theoretical study on the stereoselective Diels-Alder reactions, carried out by calculating the endo/exo transition states, revealed the assistance of non-covalent interactions in governing the endo stereocontrol.