A Partially Protective Vaccine for Fasciola hepatica Induced Degeneration of Adult Flukes Associated to a Severe Granulomatous Reaction in Sheep

Fasciolosis is an important economic disease of livestock. There is a global interest in the development of protective vaccines since current anthelmintic therapy is no longer sustainable. A better knowledge of the host-parasite interaction is needed for the design of effective vaccines. The present study evaluates the microscopical hepatic lesions in sheep immunized with a partially protective vaccine (VAC1), a non-protective vaccine (VAC2), and an infected control group (IC). The nature of granulomatous inflammation associated with degeneration of adult flukes found in the VAC1 group was characterized by immunohistochemistry. Hepatic lesions (fibrous perihepatitis, chronic tracts, bile duct hyperplasia, infiltration of eosinophils and lymphocytes and plasma cells) were significantly less severe in the VAC1 group than in the IC group. Dead adult flukes within bile ducts were observed only in the VAC1 group and were surrounded by a severe granulomatous inflammation composed by macrophages and multinucleate giant cells with a high expression of lysozyme, CD163 and S100 markers, and a low expression of CD68. Numerous CD3+ T lymphocytes and scarce infiltrate of FoxP3+ Treg and CD208+ dendritic cells were present. This is the first report describing degenerated flukes associated to a severe granulomatous inflammation in bile ducts in a F. hepatica vaccine trial

PARTOGRAMA EN MUJERES MULTÍPARAS CON MANEJO MÉDICO DEL TRABAJO DE PARTO

Antecedentes. La evaluación gráfica del parto fue descrito originalmente por Friedman, sin embargo, una descripción de la evolución del trabajo de parto con un manejo médico contemporáneo no ha sido completamente evaluado. Objetivo: Analizar el efecto de un manejo médico estandarizado del trabajo de parto, que incluye anestesia regional, rotura artificial de membranas y conducción ocitócica, sobre la fase activa del trabajo de parto en multíparas. Método. Análisis retrospectivo de 130 multíparas en trabajo de parto espontáneo, que ingresaron con 3 a 4 cm de dilatación. Resultados. Se observó una duración de la fase activa del trabajo de parto de aproximadamente 3,5 horas, con una progresión promedio de 1,5 cm/ h, produciéndose la mayor progresión entre los 7 y 9 cm de dilatación con 1,9 cm/h. La segunda fase del trabajo de parto presento una duración promedio de 28 minutos. Conclusiones. Nuestros resultados muestran que el manejo "médico estandarizado" del trabajo de parto no reduce los tiempos de la fase activa ni de la segunda fase en multíparas. Creemos que es necesario implementar estudios randomizados para determinar la influencia de este tipo manejo del trabajo de parto en la incidencia de cesárea

2 cerebrospinal fluid levels are a potential biomarker for microglia activity in early-stage Alzheimer's disease and associate with neuronal injury markers

2 is an innate immune receptor expressed on the surface of microglia. Loss-of-function mutations of 2 are associated with increased risk of Alzheimer's disease (). 2 is a type-1 protein with an ectodomain that is proteolytically cleaved and released into the extracellular space as a soluble variant (2), which can be measured in the cerebrospinal fluid (). In this cross-sectional multicenter study, we investigated whether levels of 2 are changed during the clinical course of , and in cognitively normal individuals with suspected non- pathology (). 2 levels were higher in mild cognitive impairment due to than in all other groups and controls. individuals also had significantly increased 2 compared to controls. Moreover, increased 2 levels were associated with higher total tau and phospho-tau, which are markers of neuronal degeneration and tau pathology. Our data demonstrate that 2 levels are increased in the early symptomatic phase of , probably reflecting a corresponding change of the microglia activation status in response to neuronal degeneration

Benzimidazole derivatives as new and selective inhibitors of arginase from leishmania mexicana with biological activity against promastigotes and amastigotes

17 pags, 6 figs, 3 tabs, 2 schs. -- Supplementary materials are available online at https://www.mdpi.com/article/10 .3390/ijms222413613/s1.Leishmaniasis is a disease caused by parasites of the Leishmania genus that affects 98 countries worldwide, 2 million of new cases occur each year and more than 350 million people are at risk. The use of the actual treatments is limited due to toxicity concerns and the apparition of resistance strains. Therefore, there is an urgent necessity to find new drugs for the treatment of this disease. In this context, enzymes from the polyamine biosynthesis pathway, such as arginase, have been considered a good target. In the present work, a chemical library of benzimidazole derivatives was studied performing computational, enzyme kinetics, biological activity, and cytotoxic effect characterization, as well as in silico ADME-Tox predictions, to find new inhibitors for arginase from Leishmania mexicana (LmARG). The results show that the two most potent inhibitors (compounds 1 and 2) have an I50 values of 52 μM and 82 μM, respectively. Moreover, assays with human arginase 1 (HsARG) show that both compounds are selective for LmARG. According to molecular dynamics simulation studies these inhibitors interact with important residues for enzyme catalysis. Biological activity assays demonstrate that both compounds have activity against promastigote and amastigote, and low cytotoxic effect in murine macrophages. Finally, in silico prediction of their ADME-Tox properties suggest that these inhibitors support the characteristics to be considered drug candidates. Altogether, the results reported in our study suggest that the benzimidazole derivatives are an excellent starting point for design new drugs against leishmanisis.This research was funded by the Consejo Nacional de Ciencia y Tecnología (CONACyT), grants 257848 (A.T.-V.) and 258694 (C.A.-D.). The work in Spain was funded by a grant from the Spanish Ministry of Science, Innovation and Competitiveness PID2020-115331GB-100 to J.A.-H.Peer reviewe

Deep drilling at the Chalco lake:A technical report

En este artículo se presenta un resumen de las actividades realizadas para la recuperación de la totalidad de la secuencia lacustre del lago de Chalco. Mediante estudios geofísicos se determinó la distribución y espesor de los sedimentos lacustres con base en lo cual se seleccionó el sitio de perforación. Con datos de los espectros H/V de sísmica pasiva se hizo un mapa de isofrecuencias que definieron una región con sedimentos lacustres y material volcánico granulado de hasta 300 m de espesor. El uso de métodos electromagnéticos mostró cambios en la resistividad eléctrica relacionados con variaciones en la composición de la columna sedimentaria; entre 100 – 120 m de profundidad hay un primer aumento en la resistividad asociado al incremento de materiales volcaniclásticos, y entre 330 – 400 m de profundidad un segundo aumento asociado a la presencia de coladas de basalto. Fueron perforados tres pozos con recuperación continua, llegando a profundidades de 420 m en el pozo A, 310 m en el B y 520 en el C. Durante el trabajo de perforación se tomaron muestras para el análisis geomicrobiológicos y de metagenómica. Durante el proceso de perforación se recuperó un total de 1152 m de sedimentos con una profundidad máxima de 520 m. El porcentaje de recuperación de la columna sedimentaria varió entre 88 a 92 % en los tres sondeos. Los resultados del análisis de susceptibilidad magnética en las tres secuencias indica que los primeros 260 m son sedimentos lacustres, entre 260 y 300 m los sedimentos son más gruesos y debajo de los 300 m son predominantemente volcaniclásticos. El análisis de la secuencia sedimentaria del lago de Chalco de los últimos ~300000 años, permitirá documentar y ampliar el conocimiento acerca de la variabilidad climática de la zona, la historia paleoambiental, la historia del cierre de la cuenca, el desarrollo del sistema lacustre y la recurrencia de la actividad volcánica en la cuenca. Además, el estudio de las propiedades físicas de esta secuencia sedimentaria es importante para la modelación de la propagación de ondas sísmicas y de la estructura de la cuenca, así como para mejorar la capacidad de modelación del proceso de subsidencia del terreno que experimenta esta región. This paper presents a short description of the coring operations undertaken to recover the full lacustrine sedimentary sequence from Chalco. Geophysical techniques were used to determine the distribution and thickness of the sediments in order to select the drilling site. Resonance frequencies determined from H/V spectral ratios were used to determine an area where lake sediments reached 300 m thickness. Electromagnetic survey showed two changes in electric resistivity which were related to changes in sediment composition, the first from 100 to 120 m, related to an increase in volcanoclastic sediments and the second from 330 to 400 m related to the presence of a basaltic flows. Three wells were drilled with continuous recovery, reaching depths of 420 m in well A, 310 in B and 520 in C. Samples for geomicrobiological and metagenomics studies were collected during drilling operations. A total of 1152 m of core sediments were recovered reaching a maximum depth of 520 m. Recovery percentages were between 88 and 92 % in the three wells. Magnetic susceptibility analyses in the three sequences show that the first 260 m are mostly lake sediments, between 260 and 300 m sediments are coarser and below 300 m they are mostly volcaniclastic. Analysis of the sedimentary sequence of Lake Chalco that covers the last ~300000 years will allow documenting and extending the knowledge of climate variability in area, the paleoenvironmental history, basin closure history, lacustrian system development and volcanic activity recurrence. Studies of the physical properties of this sequence will be important for seismic propagation and basin structure modeling, and also will improve modeling of the subsidence process that this region experiences

A candidate super-Earth planet orbiting near the snow line of Barnard’s star

Barnard’s star is a red dwarf, and has the largest proper motion (apparent motion across the sky) of all known stars. At a distance of 1.8 parsecs, it is the closest single star to the Sun; only the three stars in the α Centauri system are closer. Barnard’s star is also among the least magnetically active red dwarfs known and has an estimated age older than the Solar System. Its properties make it a prime target for planetary searches; various techniques with different sensitivity limits have been used previously, including radial-velocity imaging, astrometry and direct imaging, but all ultimately led to negative or null results. Here we combine numerous measurements from high-precision radial-velocity instruments, revealing the presence of a low-amplitude periodic signal with a period of 233 days. Independent photometric and spectroscopic monitoring, as well as an analysis of instrumental systematic effects, suggest that this signal is best explained as arising from a planetary companion. The candidate planet around Barnard’s star is a cold super-Earth, with a minimum mass of 3.2 times that of Earth, orbiting near its snow line (the minimum distance from the star at which volatile compounds could condense). The combination of all radial-velocity datasets spanning 20 years of measurements additionally reveals a long-term modulation that could arise from a stellar magnetic-activity cycle or from a more distant planetary object. Because of its proximity to the Sun, the candidate planet has a maximum angular separation of 220 milliarcseconds from Barnard’s star, making it an excellent target for direct imaging and astrometric observations in the future. © 2018, Springer Nature Limited.The results are based on observations made with the CARMENES instrument at the 3.5-m telescope of the Centro Astronomico Hispano-Aleman de Calar Alto (CAHA, Almeria, Spain), funded by the German Max-Planck-Gesellschaft (MPG), the Spanish Consejo Superior de Investigaciones Cientificas (CSIC), the European Union and the CARMENES Consortium members; the 90-cm telescope at the Sierra Nevada Observatory (Granada, Spain) and the 40-cm robotic telescope at the SPACEOBS observatory (San Pedro de Atacama, Chile), both operated by the Instituto de Astrofisica de Andalucia (IAA); and the 80-cm Joan Oro Telescope (TJO) of the Montsec Astronomical Observatory (OAdM), owned by the Generalitat de Catalunya and operated by the Institute of Space Studies of Catalonia (IEEC). This research was supported by the following institutions, grants and fellowships: Spanish MINECO ESP2016-80435-C2-1-R, ESP2016-80435-C2-2-R, AYA2016-79425-C3-1-P, AYA2016-79245-C3-2-P, AYA2016-79425-C3-3-P, AYA2015-69350-C3-2-P, ESP2014-54362-P, AYA2014-56359-P, RYC-2013-14875; Generalitat de Catalunya/CERCA programme; Fondo Europeo de Desarrollo Regional (FEDER); German Science Foundation (DFG) Research Unit FOR2544, project JE 701/3-1; STFC Consolidated Grants ST/P000584/1, ST/P000592/1, ST/M001008/1; NSF AST-0307493; Queen Mary University of London Scholarship; Perren foundation grant; CONICYT-FONDECYT 1161218, 3180405; Swiss National Science Foundation (SNSF); Koshland Foundation and McDonald-Leapman grant; and NASA Hubble Fellowship grant HST-HF2-51399.001. J.T. is a Hubble Fellow

Focus on collagen: in vitro systems to study fibrogenesis and antifibrosis _ state of the art

Fibrosis represents a major global disease burden, yet a potent antifibrotic compound is still not in sight. Part of the explanation for this situation is the difficulties that both academic laboratories and research and development departments in the pharmaceutical industry have been facing in re-enacting the fibrotic process in vitro for screening procedures prior to animal testing. Effective in vitro characterization of antifibrotic compounds has been hampered by cell culture settings that are lacking crucial cofactors or are not holistic representations of the biosynthetic and depositional pathway leading to the formation of an insoluble pericellular collagen matrix. In order to appreciate the task which in vitro screening of antifibrotics is up against, we will first review the fibrotic process by categorizing it into events that are upstream of collagen biosynthesis and the actual biosynthetic and depositional cascade of collagen I. We point out oversights such as the omission of vitamin C, a vital cofactor for the production of stable procollagen molecules, as well as the little known in vitro tardy procollagen processing by collagen C-proteinase/BMP-1, another reason for minimal collagen deposition in cell culture. We review current methods of cell culture and collagen quantitation vis-à-vis the high content options and requirements for normalization against cell number for meaningful data retrieval. Only when collagen has formed a fibrillar matrix that becomes cross-linked, invested with ligands, and can be remodelled and resorbed, the complete picture of fibrogenesis can be reflected in vitro. We show here how this can be achieved. A well thought-out in vitro fibrogenesis system represents the missing link between brute force chemical library screens and rational animal experimentation, thus providing both cost-effectiveness and streamlined procedures towards the development of better antifibrotic drugs

HTLV-1 infection in solid organ transplant donors and recipients in Spain

HTLV-1 infection is a neglected disease, despite infecting 10-15 million people worldwide and severe illnesses develop in 10% of carriers lifelong. Acknowledging a greater risk for developing HTLV-1 associated illnesses due to immunosuppression, screening is being widely considered in the transplantation setting. Herein, we report the experience with universal HTLV testing of donors and recipients of solid organ transplants in a survey conducted in Spain. All hospitals belonging to the Spanish HTLV network were invited to participate in the study. Briefly, HTLV antibody screening was performed retrospectively in all specimens collected from solid organ donors and recipients attended since the year 2008. A total of 5751 individuals were tested for HTLV antibodies at 8 sites. Donors represented 2312 (42.2%), of whom 17 (0.3%) were living kidney donors. The remaining 3439 (59.8%) were recipients. Spaniards represented nearly 80%. Overall, 9 individuals (0.16%) were initially reactive for HTLV antibodies. Six were donors and 3 were recipients. Using confirmatory tests, HTLV-1 could be confirmed in only two donors, one Spaniard and another from Colombia. Both kidneys of the Spaniard were inadvertently transplanted. Subacute myelopathy developed within 1 year in one recipient. The second recipient seroconverted for HTLV-1 but the kidney had to be removed soon due to rejection. Immunosuppression was stopped and 3 years later the patient remains in dialysis but otherwise asymptomatic. The rate of HTLV-1 is low but not negligible in donors/recipients of solid organ transplants in Spain. Universal HTLV screening should be recommended in all donor and recipients of solid organ transplantation in Spain. Evidence is overwhelming for very high virus transmission and increased risk along with the rapid development of subacute myelopathy