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The megadiversity of Peru, has many species framed in the genus Cinchona, Ladenbergia and Remijia, and that the inhabitants of the Andean-Amazonian Communities know them indistinctly as "quina trees", "quina" or "cascarillas" and which They attribute medicinal properties to them against malaria, broncho-respiratory diseases and especially Covid-19. However, the indiscriminate exploitation and the little interest of the investigation has contributed to the extinction and confusion in the identification of the species in different genera;In view of this, the research objective was to quantify the alkaloids of Ladenbergia oblongifolia "quina tree";in order to promote the revaluation of this species as a promising ethnobotanical resource that seeks to correlate its active principles or secondary metabolites with the consequent pharmacological actions attributed to it. For this, bark and leaves of L. oblongifolia were used, from Chiclin, Chicama, Ascope, La Libertad, Peru;the taxonomic determination was carried out in the Herbarium Truxillense (HUT);while the extraction and quantification of alkaloids in the Laboratory of Instrumental Methods, Department of Chemistry, Faculty of Chemical Engineering of the National University of Trujillo. It is concluded that the leaves of L. oblongifolia contain 0.1039 mmol alkaloids/g dry matter, and these metabolites can be extracted directly from the leaves, without the need to cut or destroy the trees, so it is urgent to implement mechanisms of use of the leaves instead of the bark, thus avoiding their extinction.

Studies have shown that the intracellular content of probiotic (postbiotics) has antioxidant properties, which can improve the antioxidant status in vivo. However, its absorption and mechanisms underlying the protective effects are still unknown. The antioxidant capacity of Lacticaseibacillus casei CRL431 (IC-431) postbiotics was determined after an in vitro simulated digestive process. Permeability of antioxidant constituents of IC-431 was determined by an ex vivo everted duodenum assay. Aflatoxin B1–induced oxidative stress rat models were established and treated with IC-431; biomarkers of hepatic mitochondrial function and H2O2 levels, oxidative stress, and oxidative stress index (OSi) were examined. The antioxidant capacity of IC-431 (477 ± 45.25 μmol Trolox Equivalent/L) was reduced by exposure to the simulated digestive process. No difference (p > 0.05) was found among digested and the permeate fraction of IC-431. A protective effect was observed by significantly lower OSi and higher liver glutathione peroxidase and catalase activities. Lower H2O2 production, a higher degree of mitochondrial uncoupling, and lower mitochondrial respiration coefficient were also observed (p

Background Exhausted sugar beet pulp pellets (ESBPP) were used as raw material for lactic acid (LA) fermentation. The enzymatic hydrolysis of ESBPP was performed with the solid obtained after the fungal solid-state fermentation of ESBPP as a source of hydrolytic enzymes. Subsequently, a medium rich in glucose and arabinose was obtained, which was used to produce LA by fermentation. For LA production, two Lactobacillus strains were assayed and the effect of the supplementation of the hydrolysate with a nitrogen source and the mode of pH regulation of the fermentation were investigated. Moreover, a kinetic model for lactic acid fermentation by Lactobacillus plantarum on ESBPP hydrolysates was developed. Results L. plantarum produced a LA concentration 34 % higher than Lactobacillus casei. The highest LA concentration (30 g L-1 ) was obtained with L. plantarum when the hydrolysate was supplemented with 5 g L-1 of yeast extract and the pH was controlled with CaCO3 . The concentration of acetic acid differed depending on the concentration of CaCO3 added, producing its maximum value with 27 g L-1 of CaCO3 . The proposed kinetic model was able to predict the evolution of substrates and products depending on the variation of the pH in the hydrolysate, according to the amount of CaCO3 added. Conclusion ESBPP can be revalorized to produce lactic acid. A pure LA stream or a mixture of lactic and acetic acid, depending on the pH control method of the fermentation, can be produced. Thus, this control shows a great interest depending on the destination of the effluent. This article is protected by copyright. All rights reserved.

There are many studies on the polymorphism of the HLA system in healthy donor populations, such as registries of unrelated bone marrow donors. Investigations on the characterization of the HLA complex in hematopoietic stem cell transplant (HSCT) patients, however, are scarce, at least in the Spanish population. This study presents a large-scale analysis of allelic diversity and HLA distribution at a high-resolution level in 2886 patients undergoing HSCT in Spanish centres of the "Grupo Español de Trasplante Hematopoyético y Terapia Celular" during a period of 11 years. Allelic diversity analysis identified 67 HLA-A, 133 HLA-B, 60 HLA-C, 63 HLA-DRB1, 24 HLA-DQB1 and 27 HLA-DPB1 different alleles. Rare alleles were detected among which 33 alleles had not been reported in the European catalog of common and well-documented HLA alleles. Regarding the distribution of five genes-haplotypes, it was observed that the five most frequent extended haplotypes found in our population were between the most common in other Spanish populations, both in patients and in healthy subjects. However, some particular haplotypes were also detected. Bilocus associations HLA-C ~ B and -DRB1 ~ DQB1 were analyzed in order to predict the probability of finding 10/10 matched donors in registries. We found HLA-B alleles showing a great diversity of combinations with HLA-C alleles and unusual associations involving a negative predicting factor. In the field of adoptive therapies, our work supports the necessity to expand further research of TCR-engineered cells, adoptive transfer of virus-specific T-cells and vaccines to target HLA alleles other than A*02:01. HLA alleles such as A*01:01, A*03:01, A*24:02, B*44:03, B*07:02 or B*51:01, might be considered new targets due to its high frequency in our population.

Prey detection and selection by birds can be influenced by prey coloration. Whereas certain colours can indicate to predators the unpalatability of prey (i.e. aposematism), other colours can render prey cryptic against the background. However, there are discrepancies in the response of birds to prey coloration reported in different studies. Such discrepancies can be the result of geographical or temporal (e.g. seasonal) differences between studies if birds in different regions respond differently to coloration or if responses vary seasonally due to changes in bird composition. Experimental studies aiming to understand bird responses to prey colour should consider the effect of geographical variation while accounting for seasonal as well as interannual variability. We investigated the effects of colour on attack rates by exposing plasticine caterpillars of different colours to bird communities in 13 Mediterranean forests in central Spain for a period from 17 weeks to 7 months. Overall, yellow and green dummy caterpillars suffered the lowest attack rates. We also observed a bimodal pattern of bird attack rates through time, with highest predation occurring in late winter and summer (June to September). Low attack rates on yellow dummies are probably a consequence of aposematism, while low attack rates on green dummies probably resulted from crypsis. Rapid decreases in attack rates over time are probably a result of avoidance learning, whereas the increase in attacks in summer could be explained by the increase in fledglings and migrant birds.

Se evaluó la eficiencia en fijación biológica de nitrógeno (FBN) de 27 cepas de Rhizobium spp. recolectadas en frijol silvestre y cultivado del occidente de México, al utilizar como hospedero la variedad de frijol Cuarenteño. El trabajo se realizó bajo malla sombra, se usó un diseño experimental completamente al azar con cinco repeticiones y se evaluaron longitud de vástago (LV) y de raíz (LR), peso seco de vástago (PSV) y de raíz (PSR), número de nódulos (NN) y peso seco de nódulos (PSN), nitrógeno total del vástago (NT) y contenido de clorofila (CL). Se realizaron análisis de varianza y de componentes principales; se obtuvieron índices de eficiencia por variable y por grupos de variables. Se detectaron diferencias altamente significativas (P ≤ 0.01) en seis de las ocho variables registradas. Por el valor per se de las variables, se seleccionaron Rhizojal VC3 colectada en frijol silvestre y Rhizojal ZCB3, Rhizojal ZCB1, Rhizojal TP2 y Rhizojal TP3 obtenidas en frijol cultivado. Por índices de eficiencia simples y por grupos de variables, se escogieron Rhizojal VC3, Rhizojal ZCB3 y Rhizojal TP2. El análisis de componentes principales separó a la mayoría de las cepas en dos grupos: cepas procedentes de la forma silvestre de frijol y cepas colectadas en frijol cultivado. Las cepas Rhizojal ZCB3, Rhizojal TP2 y Rhizojal TP3, mostraron los mayores valores en la escala del CP1; la cepa Rhizojal VC3, se ubicó del lado de los aislados de origen cultivado. Considerando los análisis realizados, las cepas identificadas como mejores en FBN fueron Rhizojal VC3 de frijol silvestre y Rhizojal ZCB3 y Rhizojal TP2 de origen cultivado. Los resultados indican que los índices de eficiencia contribuyen a la evaluación y selección de cepas por FBN y que existe potencial para identificar cepas de Rhizobium eficientes en FBN en la región occidente de México.

Los objetivos de esta investigación fueron caracterizar los descriptores ecológicos y evaluar los impactos del cambio climático en la distribución potencial del frijol lima Phaseolus lunatus L. en las regiones de Mesoamérica y Aridoamérica. Se integró una base de datos de sitios de ocurrencia tomando seis fuentes. A partir, de las coordenadas geográficas de dichos sitios de ocurrencia y mediante el uso de sistemas de información geográfica, se extrajeron valores de variables agroclimáticas derivados de rasters de los sistemas Worldclim, USGS/NASA SRTM y CGIAR. Así se integró una matriz de datos agroclimáticos mediante la cual se determinaron los descriptores ecológicos de Phaseolus lunatus. Se modeló la distribución de P. lunatus con el modelo Maxent. Los resultados mostraron que P. lunatus se adapta a una amplia gama de condiciones ambientales que incluye una condición hídrica que va de semiárida a húmeda, una condición térmica que oscila de templada a muy cálida, y tiene presencia en los rangos altitudinal, térmico y pluvial de 0-2 386 msnm, 13.2-29.9 °C y 400-4 250 mm, respectivamente. Estos descriptores señalan la existencia de poblaciones portadoras de genes resistentes a condiciones de estrés climático. El modelo Maxent modeló satisfactoriamente la distribución de Phaseolus lunatus en los diferentes escenarios climáticos evaluados (AUC= 0.94). El cambio climático proyectado por el modelo HADGEM-ES para 2050 y 2070 y RCPs 4.5 y 8.5 es desfavorable para la distribución de P. lunatus, mientras que según el modelo CCMS4 el clima 2050 y 2070 es favorable en la ruta RCP4.5 y desfavorable en la ruta RCP8.5.

Triatoma longipennis Usinger 1939, Triatoma pallidipennis (Stal, 1872), and Triatoma picturata Usinger 1939 are considered among the species with the highest transmission capacity of Chagas disease in Mexico, with an impact on health mainly in rural zones and places with worn-out dwellings. There have been previous studies on the phylogenetic relationship of these species of the Phyllosoma complex using molecular approaches, in addition to analyzing morphological characters. However, one of the problems in the field is the presence of hybrids that due to the short genetic distance between species, and such organisms have not yet been identified and could be confused with parental organisms. In this work, we analyzed genotypical and phenotypic characters, between the species and the three possible hybrids resulting from the cross between the species. In the analysis of wings morphology, we found that the dominant phenotype in hybrids was that of T. pallidipennis, having a higher dominance than T. longipennis. Besides, the use of the COI marker amplified in DNA of parentals and the three possible hybrids showed by neighbor-joining phylograms a greater association of the hybrids with T. longipennis, in agreement with the analysis of genetic distances and polymorphic sites. Thus, the morphological data demonstrate the high dominance of T. pallidipennis and the molecular data of T. longipennis in its hybrids, in such a way that it is possible to differentiate hybrids from parental species.

Prefoldin is a heterohexameric complex conserved from archaea to humans that plays a cochaperone role during the co-translational folding of actin and tubulin monomers. Additional functions of prefoldin have been described, including a positive contribution to transcription elongation and chromatin dynamics in yeast. Here we show that prefoldin perturbations provoked transcriptional alterations across the human genome. Severe pre-mRNA splicing defects were also detected, particularly after serum stimulation. We found impairment of co-transcriptional splicing during transcription elongation, which explains why the induction of long genes with a high number of introns was affected the most. We detected genome-wide prefoldin binding to transcribed genes and found that it correlated with the negative impact of prefoldin depletion on gene expression. Lack of prefoldin caused global decrease in Ser2 and Ser5 phosphorylation of the RNA polymerase II carboxy-terminal domain. It also reduced the recruitment of the CTD kinase CDK9 to transcribed genes, and the association of splicing factors PRP19 and U2AF65 to chromatin, which is known to depend on CTD phosphorylation. Altogether the reported results indicate that human prefoldin is able to act locally on the genome to modulate gene expression by influencing phosphorylation of elongating RNA polymerase II, and thereby regulating co-transcriptional splicing., Ministerio de Ciencia e Innovación-Agencia Estatal de Investigación [BFU2016-77728-C3-1-P to S.C. and BFU2017-85420-R to J.C.R.] co-financed with European Union funds (FEDER); Andalusian Government [P12-BIO1938MO, BIO271, US-1256285 to S.C., BIO321 to J.C.R.]; Junta de Andalucía (to L.P.-B.). Funding for open access charge: Ministerio de Ciencia e Innovación-Agencia Estatal de Investigación [BFU2016-77728-C3-1-P].

6 páginas, 2 figuras, 3 tablas. Se puede acceder al texto completo de este artículo desde PubMedCentral: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8490129 . Los datos de investigación utilizados en el mismo, se encuentran disponibles en: https://doi.org/10.1016/j.cmi.2021.09.031., Objectives: The current study was aimed at examining SARS-CoV-2 immune responses following two doses of Comirnaty® COVID-19 vaccine among elderly people in nursing homes. Methods: A prospective cohort study in a representative sample from nursing homes in Valencia (n = 881; males: 271, females 610; median age, 86 years) recruited residents using a random one-stage cluster sampling approach. A lateral flow immunochromatography device (LFIC) (OnSite COVID-19 IgG/IgM Rapid Test; CTK BIOTECH, Poway, CA, USA) was used as the front-line test for detecting SARS-CoV-2-Spike (S)-specific antibodies in whole blood obtained using a fingerstick. Residents returning negative LFIC results underwent venipuncture and testing for presence of SARS-CoV-2-S-reactive antibodies and T cells using the Roche Elecsys® Anti-SARS-CoV-2 S (Roche Diagnostics, Pleasanton, CA, USA), the LIAISON® SARS-CoV-2 TrimericS IgG assay (Diasorin S.p.A, Saluggia, Italy) and by flow cytometry, respectively. Results: The SARS-CoV-2-S antibody detection rate in nursing home residents was 99.6% (283/284) and 98.3% (587/597) for SARS-CoV-2 recovered and naïve residents, respectively, within a median of 99 days (range 17-125 days) after full vaccination. Three out of five residents lacking SARS-CoV-2-S antibodies had detectable S-reactive CD8+ and/or CD4+ T cells. In addition, 50/50 and 40/50 participants with detectable SARS-CoV-2 antibodies also had SARS-CoV-2-S-reactive interferon-γ-producing CD4+ and CD8+ T cells, respectively. Discussion: The Comirnaty® COVID-19 vaccine is highly immunogenic in nursing home residents. Keywords: Comirnaty®COVID-19 vaccine; Nursing home residents; SARS-CoV-2; SARS-CoV-2-S antibodies., Ignacio Torres (Río Hortega Contract; CM20/00090), Eliseo Albert (Juan Rodes Contract; JR20/00011) and Estela Gimenez (Juan Rod es Contract, JR18/00053) hold contracts funded by the Health Institute Carlos III (co-financed by the European Regional Development Fund, ERDF/FEDER).

On October 9, 2019, mosquito collections were conducted to update the mosquito species of medical importance in the Apurímac River Valley, Canayre, in the state of Ayacucho, Peru. Species collected included Culex (Carrollia) iridescens, which had been previously reported only in Colombia, Ecuador, and Brazil, this being the first national report of this species in Peru and the first species within the genus Culex in Ayacucho. With the addition of Cx. iridescens to the mosquito fauna of Peru, there are currently 182 species in the country. Specimens collected during this study were deposited in the Entomological Collection of the Natural History Museum of the National University of San Cristobal Huamanga in Ayacucho, Peru.

Background Communication between the gut microbiota and the brain is primarily mediated via soluble microbe-derived metabolites, but the details of this pathway remain poorly defined. Methylamines produced by microbial metabolism of dietary choline and l-carnitine have received attention due to their proposed association with vascular disease, but their effects upon the cerebrovascular circulation have hitherto not been studied. Results Here, we use an integrated in vitro/in vivo approach to show that physiologically relevant concentrations of the dietary methylamine trimethylamine N-oxide (TMAO) enhanced blood-brain barrier (BBB) integrity and protected it from inflammatory insult, acting through the tight junction regulator annexin A1. In contrast, the TMAO precursor trimethylamine (TMA) impaired BBB function and disrupted tight junction integrity. Moreover, we show that long-term exposure to TMAO protects murine cognitive function from inflammatory challenge, acting to limit astrocyte and microglial reactivity in a brain region-specific manner. Conclusion Our findings demonstrate the mechanisms through which microbiome-associated methylamines directly interact with the mammalian BBB, with consequences for cerebrovascular and cognitive function.

Refined foods are commonly depleted in certain bioactive components that are abundant in ‘natural’ (plant) foods. Identification and addition of these ‘missing’ bioactives in the diet is, therefore, necessary to counteract the deleterious impact of convenience food. In this study, multiomics approaches were employed to assess the addition of the popular supplementary soluble dietary fibers inulin and psyllium, both in isolation and in combination with a refined animal feed. A 16S rRNA sequencing and 1H NMR metabolomic investigation revealed that, whilst inulin mediated an increase in Bifidobacteria, psyllium elicited a broader microbial shift, with Parasutterella and Akkermansia being increased and Enterorhabdus and Odoribacter decreased. Interestingly, the combination diet benefited from both inulin and psyllium related microbial changes. Psyllium mediated microbial changes correlated with a reduction of glucose (R −0.67, −0.73, respectively, p < 0.05) and type 2 diabetes associated metabolites: 3-methyl-2-oxovaleric acid (R −0.72, −0.78, respectively, p < 0.05), and citrulline (R −0.77, −0.71, respectively, p < 0.05). This was in line with intestinal and hepatic carbohydrate response (e.g., Slc2a2, Slc2a5, Khk and Fbp1) and hepatic lipogenesis (e.g., Srebf1 and Fasn), which were significantly reduced under psyllium addition. Although established in the liver, the intestinal response associated with psyllium was absent in the combination diet, placing greater significance upon the established microbial, and subsequent metabolomic, shift. Our results therefore highlight the heterogeneity that exists between distinct dietary fibers in the context of carbohydrate uptake and metabolism, and supports psyllium containing combination diets, for their ability to negate the impact of a refined diet.

This work was supported by Junta de Andalucia (Spain) Research Group RNM 190. Funding for open access charge: Universidad de Granada/CBUA. We are grateful to Manuel Vicente Maestre Galindo for his helpful comments during development of this research and to Francisco Gonzalez Portillo and Lola Molina for their help with macrophotography. We thank Isabel Sanchez-Almazo and Nicolas Velilla for carrying out the elemental and XR analyses of fossil samples, respectively., Despite the abundance of seagrass-related deposits in the geological record, seagrass macrofossils are scattered in time and space, due to the low preservation potential of marine angiosperms. Fossil seagrass impressions, mainly rhizomes occur in Messinian (late Miocene) marl beds intercalated in cross-bedded bioclastic limestones in the Guadalquivir Basin near Alcala de Guadaira in southern Spain. Vegetative characters indicate that most remains can be attributed to Cymodocea cf. nodosa, to which also probably belong a few molds of fruits. Two other fossil fragments can only be assigned to Alismatales indet. The plants lived in sheltered ephemeral areas among shallow-water submarine dunes, in which deposition of fine-grained sediment favored their fossilization. During the late Miocene the Guadalquivir Basin was open to the Atlantic Ocean and, therefore, these fossil occurrences lie within the modern biogeographic distribution of C. nodosa, the only species of the genus out of the Indo-West Pacific region. At the moment, it is the only record of seagrass fossils in the Miocene of Europe., Junta de Andalucia RNM 190, Universidad de Granada/CBUA

Background Exhausted sugar beet pulp pellets (ESBPP), a sugar industry by-product generated after sugar extraction in the sugar production process, have been used as a raw material for lactic acid (LA) production via hydrolysis and fermentation by Lactobacillus casei. To design a more cost-effective process, simultaneous saccharification and fermentation (SSF) of ESBPP is proposed in the present study. The effects of pH control, nutrient supplementation and solid addition in fed-batch SSF on lactic acid production were investigated. Results The highest LA concentration (26.88 g L-1 ) was reached in fed-batch SSF at a solid/liquid loading of 0.2 g mL-1 , with pH control (by adding 30 g L-1 CaCO3 to the medium) and nutrient supplementation (by adding 20 mL of MRS medium per 100 mL of buffer). Under these conditions, a maximum productivity of 0.63 g L-1 h-1 was achieved, which is 2.7 times higher than that attained in the control experiment (SSF inoculated at time 0 h). However, a slightly lower LA yield was obtained, revealing the need of an increasing dose of enzymes at high solid loading SSF. Conclusion An efficient fed-batch SSF strategy with pH control and MRS supplementation is described in the present study, attaining higher LA productivity compared to separate hydrolysis and fermentation and SSF. © 2020 Society of Chemical Industry.

In this research, the capacity of biodegradation of phenolic compounds using the microalgae Chlamydomonas reinhardtii was evaluated, as well as the impact of the contaminant on the growth of the microalgae. The bioassays consisted on three phenol concentrations: 25 mgL/L, 50 mgL/L and 100 mg/L and a control solution. Bioremediation rates of approximately 99% were obtained, showing no significant difference between medium and high concentration bioassays. A good microalgae growth rate was obtained for the tests at low and medium concentration, they were above the control bioassay, but the high concentration bioassay showed an inhibition in the cell growth, this one presented growth below the control bioassay. The use of the microalgae Chlamydomonas reinhardtii in bioremediation processes of phenolic effluents, whose concentrations are below 100 mg/L, is proposed for future research.

The study aimed to evaluate the agronomic characteristics of elephant grass (Pennisetum purpureum Schum.) genotypes on energy production in the combustion form. A randomized block design with 3 repetitions was used. The treatments were arranged in subdivided plots scheme, considering as a plot the genotypes and as subplots, the harvest season. The agronomic characteristics plant height (H), leaf length (LL), leaf blade width (LBW), stem diameter (SD), tillers number (TN), stem percentage (SP), dry matter yield (DMY) were evaluated. The rainy season provided greater H to elephant grass genotypes with height above 3.5 m. The average SP obtained by the genotypes was 68.21% and 67.21% to the first and second year of cultivation, respectively, which gives the biomass good quality of burning. The rainy season provided greater DMY comparing to the dry season. In the first year of cultivation there were genotypes with annual dry matter yield (ADMY) above 50 ton ha-1 year-1, however, the non-maintenance of soil fertility promoted the reduction of 39.17% and 39.05% in the DMY and ADMY, respectively. Analyzing the agronomic characteristics, we conclude that the promising genotypes of elephant grass to produce energy in the form of direct combustion are CNPGL 91-25-1, Cubano Pinda, BRS Canará, Porto Rico and Mercker.

Dendritic cells (DCs) link innate and adaptive immunity. The microenvironment generated during the innate immunity affects DCs and the type of adaptive immunity generated. Lipid mediators are released early in inflammation and could modify the functional state of DCs. Leukotriene B 4 (LTB 4 ) has a wide range of effects on macrophages and in the present study we investigated if it also affects DCs. Murine bone marrow-derived DCs were employed and it was found that stimulation of DCs with LTB4 (10 nM) increased the gene expression of the high affinity receptor BLT-1 but not of BLT-2. It also increased the co-stimulatory molecule CD86 expression but did not affect CD80 and CD 40 . LTB 4 -stimulated DCs acquired the capacity to present antigen to T lymphocytes, evidenced by antigen-specific proliferation of CD4 + lymphocytes in co-cultures of ovalbumin-loaded DCs with DO11.10 splenocytes. LTB 4 -stimulated DCs induced Treg proliferation and increased Th2 cytokine IL-13 in the co-cultures. Expression of transcription factor genes, Gata3 and Fox p3 (Th2 and Treg, respectively) were also found increased. However, the expression of Th1 transcription factor (Tbet) and Th17 ( RorγT ) were not affected. These results indicate that LTB 4 affects DCs and modulates the type of adaptive immune response.

Hypothyroidism is an endocrine disorder whose management raises many challenges in clinical practice. Its standard treatment is levothyroxine (LT4). The goal of the treatment is to normalize signs and symptoms, as well as to achieve thyroid-stimulating hormone (TSH) concentrations within the reference range, on an individual basis. It is known that 5–10 % of hypothyroid patients remain to be symptomatic, despite achieving the target TSH levels, which, in turn, affects their quality of life. After ruling out other causes of non-thyroid origin for this persistence, it is suggested that these patients could benefit from the use of liothyronine (LT3), added to LT4, especially if polymorphism of the deiodinase 2 (D2) genes is documented. There exist a variety of LT3 preparations, whose concentrations vary from 5 to 50 ug, with the recommended LT4/LT3 ratio of 13:1–20:1. The goals of combination therapy should be to achieve a physiological ratio of free triiodothyronine/free thyroxine (FT3/FT4) and non-suppression of TSH. Since there is currently no guide that makes evidence-based recommendations on the use of LT3 in primary hypothyroidism, more clinical studies are needed to be able to identify hypothyroid patients who may benefit from the use of LT3, by identifying new biomarkers.

Autosomal dominant retinitis pigmentosa (adRP) is frequently caused by mutations in RHO, the gene for rhodopsin. In previous experiments in dogs with the T4R mutation in RHO, an AAV2/5 vector expressing both an shRNA directed to human and dog RHO mRNA and an shRNA-resistant human RHO cDNA (AAV-RHO820-shRNA820) prevented retinal degeneration for more than 8 months following injection. To confirm that this same vector could protect the retinas of a different species and bearing a different RHO mutation, we injected mice transgenic for human P23H RHO at postnatal day 30 in one eye. For nine months, we monitored their retinal structure using spectral- domain optical coherence tomography (SD-OCT) and retinal function using electroretinography (ERG). We compared these to P23H RHO transgenic mice injected with AAV-GFP. Though retinas continued to thin over time, compared to control injected eyes, AAV-RHO820-shRNA820 slowed the loss of photoreceptor cells and decreased ERG amplitudes in AAV-RHO820-shRNA820 eyes during the nine-month study period. Unexpectedly, we also observed preservation of retinal structure and function in the untreated contralateral eyes of AAV-RHO820-shRNA820 treated mice. PCR analysis and western blots provided evidence that a low amount of vector from injected eyes was present in uninjected eyes.

Summary Anaplastic thyroid cancer (ATC) is the type of thyroid cancer that has the worst prognosis. It usually presents as a rapidly growing cervical mass that generates compressive symptoms. Its association with thyrotoxicosis is rare. A 76-year-old woman, with no contributory history, presented with a 3-month course of fast-growing cervical tumor, associated with tenderness, cough, and weight loss. Physical examination revealed goiter, localized erythema, and a painful and stone tumor dependent on the right thyroid lobe. Due to the malignant findings of the thyroid ultrasound, the patient underwent a thyroid core needle biopsy, which indicated ATC. Laboratory tests revealed leukocytosis, decreased thyroid-stimulating hormone, elevated free thyroxine (fT4), and increased thyroperoxidase (TPO) antibodies. At the beginning, we considered that the etiology of thyrotoxicosis was secondary to subacute thyroiditis (SAT) after SARS-CoV-2 infection, due to the immunochromatography result and chest tomography findings. The result of markedly elevated TPO antibodies left this etiology more remote. Therefore, we suspected Graves’ disease as an etiology; however, thyroid histopathology and ultrasound did not show compatible findings. Therefore, we suspect that the main etiology of thyrotoxicosis in the patient was the destruction of the thyroid follicles caused by a rapid invasion of malignant cells, which is responsible for the consequent release of preformed thyroid hormone. ATC is a rare endocrine neoplasm with high mortality; it may be associated with thyrotoxicosis, whose etiology can be varied; therefore, differential diagnosis is important for proper management. Learning points Anaplastic thyroid cancer is the thyroid cancer with the worst prognosis and the highest mortality. The association of anaplastic thyroid cancer with thyrotoxicosis is rare, and a differential diagnosis is necessary to provide adequate treatment. Due to the current pandemic, in patients with thyrotoxicosis, it is important to rule out SARS-CoV-2 as an etiology. Anaplastic thyroid cancer, due to its aggressive behavior and rapid growth, can destroy thyroid follicular cells, generating preformed thyroid hormone release, being responsible for thyrotoxicosis.

Aedes aegypti control programs require more sensitive tools in order to survey domestic and peridomestic larval habitats for dengue and other arbovirus prevention areas. As a consequence of the COVID-19 pandemic, field technicians have faced a new occupational hazard during their work activities in dengue surveillance and control. Safer strategies to monitor larval populations, in addition to minimum householder contact, are undoubtedly urgently needed. Drones can be part of the solution in urban and rural areas that are dengue-endemic. Throughout this study, the proportion of larvae breeding sites found in the roofs and backyards of houses were assessed using drone images. Concurrently, the traditional ground field technician’s surveillance was utilized to sample the same house groups. The results were analyzed in order to compare the effectiveness of both field surveillance approaches. Aerial images of 216 houses from El Vergel village in Tapachula, Chiapas, Mexico, at a height of 30 m, were obtained using a drone. Each household was sampled indoors and outdoors by vector control personnel targeting all the containers that potentially served as Aedes aegypti breeding sites. The main results were that the drone could find 1 container per 2.8 found by ground surveillance, however, containers that were inaccessible by technicians in roofs and backyards, such as plastic buckets and tubs, disposable plastic containers and flowerpots were more often detected by drones than traditional ground surveillance. This new technological approach would undoubtedly improve the surveillance of Aedes aegypti in household environments, and better vector control activities would therefore be achieved in dengue-endemic countries.

Effective function of CD8+ T cells and enhanced innate activation of dendritic cells (DC) in response to HIV-1 is linked to protective antiviral immunity in controllers. Manipulation of DC targeting the master regulator TANK-binding Kinase 1 (TBK1) might be useful to acquire controller-like properties. Here, we evaluated the impact of TBK1-primed DC inducing protective CD8+ T cell responses in lymphoid tissue and peripheral blood and their association with reduced HIV-1 disease progression in vivo in the humanized bone marrow, liver and thymus (hBLT) mouse model. A higher proportion of hBLT-mice vaccinated with TBK1-primed DC exhibited less severe CD4+ T cell depletion following HIV-1 infection compared to control groups. This was associated with infiltration of CD8+ T cells in the white pulp from the spleen, reduced spread of infected p24+ cells to secondary lymphoid organs and with preserved abilities of CD8+ T cells from the spleen and blood of vaccinated animals to induce specific polyfunctional responses upon antigen stimulation. Therefore, TBK1-primed DC might be an useful tool for subsequent vaccine studies.Author summaryEmulating protective immunological characteristics from individuals capable of spontaneously controlling HIV-1 infection might be useful for the development of a protective vaccine. Enhanced function of dendritic cells (DC) in these HIV-1 controllers depends on the activation of TANK-binding Kinase 1 (TBK1) and might associate with protective T cells. Our study evaluated the ability of DCs trained through TBK1 activation inducing protective adaptive immune responses against HIV-1 and reducing disease progression in vivo, using a humanized mouse model. Our data indicate that mice vaccinated with tailored DC exhibit delayed disease progression, increased induction of protective CD8+ T lymphocyte subsets in the lymphoid tissue and blood upon antigen recognition. Therefore, trained-DC might be an useful tool for future HIV-1 vaccine designs.

ELTD1/ADGRL4 expression is increased in the vasculature of a number of tumor types and this correlates with a good prognosis. Expression has also been reported in some tumor cells with high expression correlating with a good prognosis in hepatocellular carcinoma (HCC) and a poor prognosis in glioblastoma. Here we show that 35% of primary human breast tumors stain positively for ELTD1, with 9% having high expression that correlates with improved relapse-free survival. Using immunocompetent, syngeneic mouse breast cancer models we found that tumors expressing recombinant murine Eltd1 grew faster than controls, with an enhanced ability to metastasize and promote systemic immune effects. The Eltd1-expressing tumors had larger and better perfused vessels and tumor–endothelial cell interaction led to the release of proangiogenic and immune-modulating factors. M2-like macrophages increased in the stroma along with expression of programmed death-ligand 1 (PD-L1) on tumor and immune cells, to create an immunosuppressive microenvironment that allowed Eltd1-regulated tumor growth in the presence of an NY-ESO-1–specific immune response. Eltd1-positive tumors also responded better to chemotherapy which could explain the relationship to a good prognosis observed in primary human cases. Thus, ELTD1 expression may enhance delivery of therapeutic antibodies to reverse the immunosuppression and increase response to chemotherapy and radiotherapy in this subset of tumors. ELTD1 may be useful as a selection marker for such therapies. Implications: ELTD1 expression in mouse breast tumors creates an immunosuppressive microenvironment and increases vessel size and perfusion. Its expression may enhance the delivery of therapies targeting the immune system.

Indoor and outdoor ovitraps were placed in 15 randomly selected houses in two rural villages in Chiapas, southern Mexico. In addition, ovitraps were placed in five transects surrounding each village, with three traps per transect, one at the edge, one at 50 m, and another at 100 m from the edge of the village. All traps were inspected weekly. A transect with eight traps along a road between the two villages was also included. Population fluctuations of Aedes aegypti and Ae. albopictus were examined during 2016&ndash, 2018 by counting egg numbers. A higher number of Aedes spp. eggs was recorded at Hidalgo village with 257,712 eggs (60.9%), of which 58.1% were present in outdoor ovitraps and 41.9% in indoor ovitraps, compared with 165,623 eggs (39.1%) collected in the village of R&iacute, o Florido, 49.0% in outdoor and 51.0% in indoor ovitraps. A total of 84,047 eggs was collected from ovitraps placed along transects around R&iacute, o Florido, compared to 67,542 eggs recorded from transects around Hidalgo. Fluctuations in egg counts were associated with annual variation in precipitation, with 2.3 to 3.2-fold more eggs collected from ovitraps placed in houses and 4.8 to 5.1-fold more eggs in ovitraps from the surrounding transects during the rainy season than in the dry season, respectively. Aedes aegypti was the dominant species during the dry season and at the start of the rainy season in both villages. Aedes albopictus populations were lower for most of the dry season, but increased during the rainy season and predominated at the end of the rainy season in both villages. Aedes albopictus was also the dominant species in the zones surrounding both villages. The numbers of eggs collected from intradomiciliary ovitraps were strongly correlated with the numbers of eggs in peridomiciliary ovitraps in both R&iacute, o Florido (R2adj = 0.92) and Hidalgo (R2adj = 0.94), suggesting that peridomiciliary sampling could provide an accurate estimate of intradomiciliary oviposition by Aedes spp. in future studies in these villages. We conclude that the feasibility of sterile insect technique (SIT)-based program of vector control could be evaluated in the isolated Ae. aegypti populations in the rural villages of our baseline study.

The capacity to learn new efficient systemic behavior is a fundamental issue of contemporary biology. We have recently observed, in a preliminary analysis, the emergence of conditioned behavior in some individual amoebae cells. In these experiments, cells were able to acquire new migratory patterns and remember them for long periods of their cellular cycle, forgetting them later on. Here, following a similar conceptual framework of Pavlov’s experiments, we have exhaustively studied the migration trajectories of more than 2000 individual cells belonging to three different species: Amoeba proteus, Metamoeba leningradensis, and Amoeba borokensis. Fundamentally, we have analyzed several relevant properties of conditioned cells, such as the intensity of the responses, the directionality persistence, the total distance traveled, the directionality ratio, the average speed, and the persistence times. We have observed that cells belonging to these three species can modify the systemic response to a specific stimulus by associative conditioning. Our main analysis shows that such new behavior is very robust and presents a similar structure of migration patterns in the three species, which was characterized by the presence of conditioning for long periods, remarkable straightness in their trajectories and strong directional persistence. Our experimental and quantitative results, compared with other studies on complex cellular responses in bacteria, protozoa, fungus-like organisms and metazoans that we discus here, allow us to conclude that cellular associative conditioning might be a widespread characteristic of unicellular organisms. This new systemic behavior could be essential to understand some key principles involved in increasing the cellular adaptive fitness to microenvironments., This work was supported by a grant of the University of Basque Country (UPV/EHU), GIU17/066, the Basque Government grant IT974-16, the UPV/EHU and Basque Center of Applied Mathematics, grant US18/21, and the Israel Science Foundation (536/19)

Background Wilson disease is an autosomal recessive disorder of copper metabolism caused by mutations in the ATP7B gene. An early diagnosis is crucial to prevent evolution of the disease, as implantation of early therapeutic measures fully prevents its symptoms. As population genetics data predict a higher than initially expected prevalence, it was important to define the basic diagnostic tools to approach population screening. Methods A highly genetically homogeneous cohort of 70 patients, belonging to 50 unrelated families, has been selected as a framework to analyze all their clinical, biochemical and genetic characteristics, to define the disease in our population, with an estimated prevalence of 1 in 12,369, and determine the most useful features that reach diagnostic value. Results Serum ceruloplasmin below 11.5 mg/dL and cupremia below 60 mu g/mL, were the best analytical predictors of the disease in asymptomatic individuals, while cupruria or hepatic copper determination were less powerful. Genetic analysis reached a conclusive diagnosis in all 65 patients available for complete testing. Of them, 48 were carriers of at least one p.Leu708Pro mutant allele, with 24 homozygotes. Nine patients carried a promoter deletion mutation, revealing that extended sequencing beyond the ATP7B gene-coding region is essential. All mutations caused hepatic damage since early ages, increasing its severity as diagnosis was delayed, and neurological symptoms appear. Conclusion Serum ceruloplasmin determination followed by genetic screening would reduce costs and favor the prioritization of non-invasive procedures to reach a definitive diagnosis, even for asymptomatic cases.

SARS‐CoV‐2 infection causes an abrupt response by the host immune system, which is largely responsible for the outcome of COVID‐19. We investigated whether the specific immune responses in the peripheral blood of 276 patients associated to severity and progression of COVID‐19. At admission, dramatic lymphopenia of T, B and NK cells associated to severity. Conversely, the proportion of B cells, plasmablasts, circulating follicular helper T cells (cTfh) and CD56‐CD16+ NK‐cells increased. Regarding humoral immunity, levels of IgM, IgA and IgG were unaffected, but when degrees of severity were considered, IgG was lower in severe patients. Compared to healthy donors, complement C3 and C4 protein levels were higher in mild and moderate, but not in severe patients, while the activation peptide of C5 (C5a) increased from the admission in every patient, regardless their severity. Moreover, total IgG, the IgG1 and IgG3 isotypes and C4 decreased from day 0 to day 10 in patients who were hospitalized for more than two weeks, but not in patients who were discharged earlier. Our study provides important clues to understand the immune response observed in COVID‐19 patients, associating severity with an imbalanced humoral response and identifying new targets for therapeutic intervention., The study was funded by grants SAF2017-82886-R to FS-M from the Ministerio de Economía y Competitividad, and from “La Caixa Banking Foundation” (HR17-00016) to FS-M. Grant PI018/01163 to CMC and grant PI19/00549 to AA were funded by Fondo de Investigaciones Sanitarias, Ministerio de Sanidad y Consumo, Spain. SAF2017-82886-R, PI018/01163 and PI19/00549 grants were also cofunded by European Regional Development Fund, ERDF/FEDER. This work has been funded by grants Fondo Supera COVID (CRUE-Banco de Santander) to FSM, and “Ayuda Covid 2019” from Comunidad de Madrid.

Cervical cancer, which main etiologic factor is Human Papillomavirus (HPV) infection, continues to be a burden for public health systems in developing countries. Our laboratory has been working with the hypothesis that signals generated in the tumor microenvironment can modulate local and systemic immune responses. In this context, it would be reasonable to think that tumors create pro-tumoral bias in immune cells, even before they are recruited to the tumor microenvironment. To understand if and how signaling started in the tumor microenvironment can influence cells within the tumor and systemically, we investigated the expression of key proteins in signaling pathways important for cell proliferation, viability, immune responses and tolerance. Besides, we used detection of specific phosphorylated residues, which are indicative of activation for Akt, CREB, p65 NFκB, and STAT3. Our findings included the observation of a significant STAT3 expression increase and p65 NFκB decrease in circulating leukocytes in correlation with lesion grade. In light of those observations, we started investigating the result of the inhibition of STAT3 in a tumor experimental model. STAT3 inhibition impaired tumor growth, increased anti-tumor T cell responses and decreased the accumulation of myeloid cells in the spleen. The concomitant inhibition of NFκB partially reversed these effects. This study indicates that STAT3 and NFκB are involved in immunomodulatory tumor effects and STAT3 inhibition could be considered as therapy for patients with cervical cancer.

Adeno-associated virus (AAV) is a helper-dependent single-stranded DNA parvovirus. Over the years, AAV has become the vector of choice in the gene therapy field due to its safety profile and low immunogenicity. With a carrying capacity of 4.2 kbp, these vectors have demonstrated their clinical value, especially in the field of ophthalmology. Herein we describe methods for the molecular design and packaging of AAV viral vectors. These methods apply to the design of single-stranded or self-complementary AAV vectors.

The capacity to learn new systemic behaviour is a fundamental issue to understand the adaptive mechanisms involved in cellular evolution. We have recently observed, in a preliminary analysis, the emergence of conditioned behaviour in individual amoebae cells. In these experiments, cells were able to acquire new migratory conduct and remember it for long periods of their cellular cycle, forgetting it later on. Here, following a similar conceptual framework of Pavlov’s experiments, we have exhaustively studied the migration trajectories of more than 2000 individual cells belonging to three different species: Amoeba proteus, Metamoeba leningradensis, and Amoeba borokensis. Fundamentally, we have analysed several properties of conditioned cells, such as the intensity of the responses, the directionality persistence, the total distance traveled, the directionality ratio, the average speed, and the persistence times. We have observed that these three species can modify the systemic response to a specific stimulus by associative conditioning. Our main analysis shows that such new behaviour is very robust and presents a similar structure of migration patterns in the three species, which was characterized by the presence of conditioning for long periods, remarkable straightness in their trajectories and strong directional persistence. Our quantitative results, compared with other studies on complex cellular responses in bacteria, protozoa, fungus-like organisms and metazoans, allow us to conclude that cellular associative conditioning might be a widespread characteristic of unicellular organisms. This finding could be essential to understand some key evolutionary principles involved in increasing the cellular adaptive fitness to microenvironments.

Retinitis pigmentosa (RP) is a group of blinding disorders caused by diverse mutations, including in rhodopsin (RHO). Effective therapies have yet to be discovered. The I307N Rho mouse is a light-inducible model of autosomal dominant RP. Our purpose was to describe the glial response in this mouse model to educate future experimentation. I307N Rho mice were exposed to 20,000 lx of light for thirty minutes to induce retinal degeneration. Immunofluorescence staining of cross-sections and flat-mounts was performed to visualize the response of microglia and Müller glia. Histology was correlated with spectral-domain optical coherence tomography imaging (SD-OCT). Microglia dendrites extended between photoreceptors within two hours of induction, withdrew their dendrites between twelve hours and one day, appeared ameboid by three days, and assumed a ramified morphology by one month. Glial activation was more robust in the inferior retina and modulated across the boundary of light damage. SD-OCT hyper-reflectivity overlapped with activated microglia. Finally, microglia transiently adhered to the RPE before which RPE cells appeared dysmorphic. Our data demonstrate the spatial and temporal pattern of glial activation in the I307N Rho mouse, and correlate these patterns with SD-OCT images, assisting in interpretation of SD-OCT images in preclinical models and in human RP.

In this study, the production of a hydrolysate rich in fermentable sugars, which could be used as a generic microbial culture medium, was carried out by using exhausted sugar beet pulp pellets (ESBPPs) as raw material. For this purpose, the hydrolysis was performed through the direct addition of the fermented ESBPPs obtained by fungal solid-state fermentation (SSF) as an enzyme source. By directly using this fermented solid, the stages for enzyme extraction and purification were avoided. The effects of temperature, fermented to fresh solid ratio, supplementation of fermented ESBPP with commercial cellulase, and the use of high-solid fed-batch enzymatic hydrolysis were studied to obtain the maximum reducing sugar (RS) concentration and productivity. The highest RS concentration and productivity, 127.3 g&middot, L&minus, 1 and 24.3 g&middot, 1&middot, h&minus, 1 respectively, were obtained at 50 &deg, C and with an initial supplementation of 2.17 U of Celluclast&reg, per gram of dried solid in fed-batch mode. This process was carried out with a liquid to solid ratio of 4.3 mL&middot, g&minus, 1 solid, by adding 15 g of fermented solid and 13.75 g of fresh solid at the beginning of the hydrolysis, and then the same amount of fresh solid 3 times every 2.5 h. By this procedure, ESBPP can be used to produce a generic microbial feedstock, which contains a high concentration of monosaccharides.

Spain has been hit hard by COVID-19, with more than 300 000 cases, 28 498 confirmed deaths,1 and around 44 000 excess deaths, as of Aug 4, 2020.2 More than 50 000 health workers have been infected, and nearly 20 000 deaths were in nursing homes.3 With a population of 47 million, these data place Spain among the worst affected countries. Spain is also reported to have one of the best performing health systems in the world4 and ranks 15th in the Global Health Security index.5 So how is it possible that Spain now finds itself in this position?

Cell migration is an essential systemic behavior, tightly regulated, of all living cells endowed with directional motility that is involved in the major developmental stages of all complex organisms such as morphogenesis, embryogenesis, organogenesis, adult tissue remodeling, wound healing, immunological cell activities, angiogenesis, tissue repair, cell differentiation, tissue regeneration as well as in a myriad of pathological conditions. However, how cells efficiently regulate their locomotion movements is still unclear. Since migration is also a crucial issue in cancer development, the goal of this narrative is to show the connection between basic findings in cell locomotion of unicellular eukaryotic organisms and the regulatory mechanisms of cell migration necessary for tumor invasion and metastases. More specifically, the review focuses on three main issues, (i) the regulation of the locomotion system in unicellular eukaryotic organisms and human cells, (ii) how the nucleus does not significantly affect the migratory trajectories of cells in two-dimension (2D) surfaces and (iii) the conditioned behavior detected in single cells as a primitive form of learning and adaptation to different contexts during cell migration. New findings in the control of cell motility both in unicellular organisms and mammalian cells open up a new framework in the understanding of the complex processes involved in systemic cellular locomotion and adaptation of a wide spectrum of diseases with high impact in the society such as cancer.

Today representatives of the giant cirolanid isopods of the genus Bathynomus inhabit tropical to warm-temperate waters of the West Atlantic and the Indo-West Pacific. In not so distant geological past, however, the genus was present also in the Mediterranean, as documented by numerous fossils from the Plio–Pleistocene of Italy. Herein, a somewhat older occurrence of the genus is reported, from the North-East Atlantic. Based on a single posterior moult from the upper Miocene (Tortonian) of southwestern Spain, a new species is described. Bathynomus civisi sp. nov. differs from its congeners by both uropod rami having the obtuse distolateral corner produced as a distinct tip and a wider gap between the second and third side distal spines than between others. The new species is so far known only from the type locality in close vicinity of Arroyo Trujillo, in the municipality of Cantillana (Seville, Spain), where the marls of the Écija Formation are exposed. At the time of deposition of these marls, the area represented a part of the Norbetic Strait, a corridor connecting the North-East Atlantic with the Mediterranean. The new occurrence reported herein further supports the environmental preferences of the genus throughout its geological past for deep-marine settings.

Bacterial kidney disease (BKD) is widespread in many areas of the world and can cause substantial economic losses for the salmon aquaculture industry. The objective of this study was to investigate the pathophysiological response and gene expression profiles related to the immune response at different water temperatures and to identify the best immunopathological biomarkers to define a phenotype of resistance to BKD. The abundance of msa transcripts of R. salmoninarum in the head kidney was significantly higher in infected fish at 11°C. R. salmoninarum induced significantly more severe kidney lesions, anemia and impaired renal function at 11°C. In addition, the expression pattern of the genes related to humoral and cell-mediated immune responses in infected fish at 11°C and 15°C was very similar, although R. salmoninarum induced a significantly greater downregulation of the adaptive immune response genes at the lower water temperature. These results could be due to a suppressed host response directly related to the lowest water temperature and/or associated with a delayed host response related to the lowest water temperature. Although no significant differences in survival rate were observed, fish infected at the lowest temperature showed a higher probability of death and delayed the mortality curve during the late stage of infection (35 days after infection). Thirty-three immunopathological biomarkers were identified for potential use in the search for a resistance phenotype for BKD, and eight were genes related specifically to the adaptive cell-mediated immune response.

BackgroundSARS-CoV-2 infection causes an abrupt response by the host immune system, which is largely responsible for the pathogenesis and outcome of COVID-19. We aimed to investigate which specific responses from either cellular or humoral immunity associate to severity and progression of COVID-19.MethodsA cohort of 276 patients classified in mild, moderate and severe, was studied. Peripheral blood lymphocyte subpopulations were quantified by flow cytometry, and immunoglobulins and complement proteins by nephelometry.ResultsAt admission, dramatic lymphopenia of T, B and NK cells associated to severity. However, only the proportion of B cells increased, while T and NK cells appeared unaffected. Accordingly, the number of plasma cells and circulating follicular helper T cells (cTfh) increased, but levels of IgM, IgA and IgG were unaffected. When degrees of severity were considered, IgG was lower in severe patients, suggesting an IgG consumption by complement activation or antibody-dependent cellular cytotoxicity (ADCC). Activated CD56-CD16+ NK-cells, which mediate ADCC, were increased. Regarding complement, C3 and C4 protein levels were higher in mild and moderate, but not in severe patients, compared to healthy donors. Moreover, IgG and C4 decreased from day 0 to day 10 in patients who were hospitalized for more than two weeks, but not in patients who were discharged earlier.ConclusionOur study provides important clues to understand the immune response observed in COVID-19 patients, which is probably related to viral clearance, but also underlies its pathogenesis and severity. This study associates for the first time COVID-19 severity with an imbalanced humoral immune response characterized by excessive consumption of IgG and C4, identifying new targets for therapeutic intervention.

Herein we report on the synthesis and characterization of new water-soluble complexes with the basic formula [Cu(O N)(N N)(ClO4)2], where O N = 4-aminoantipyrine and N N = 1,10-phenanthroline (1) or 2,2ʹ-bipyridine (2). Both complexes have distorted tetragonal geometry around each copper centre, which is coordinated to both bidentate ligands in equatorial sites with two perchlorate ions weakly bonded in the axial positions. The compounds bind to DNA and induce oxidative DNA damage mediated by reactive oxygen species (ROS). Both complexes inhibit the growth of K562 cells in a concentration-dependent manner with IC50 values lower than the corresponding free ligands. Significantly, the most cytotoxic agent (complex 1) presented high in vitro nucleolytic activity by generating single- and double-strand breaks, besides of inhibiting topoisomerase I enzymatic activity at low micromolar concentration.

Leishmania (Viannia) guyanensisis one species that causes cutaneous leishmaniasis in the New World. The incidence of infections with this parasite is probably underestimated and few studies exist on this species, despite its epidemiological importance. In particular, there are no studies concerningL. guyanensismetacyclogenesis and no technique for obtaining metacyclic promastigotes for this species is presently available. Here, we have studiedL. guyanensismetacyclogenesis in axenic culture, describing the main changes that occur during this process, namely, in morphology and size, sensitivity to complement-mediated lysis, surface carbohydrates and infectivity to macrophages. We have shown that metacyclogenesis inL. guyanensispromastigotes is basically complete on the 4thday of culture, as determined by decreased body size, increased flagellum length, resistance to complement-mediated lysis and infectivity. We have also found that only a fraction of the parasites is agglutinated byBauhinia purpurealectin. The non-agglutinated parasites, which also peaked on the 4thday of culture, had all morphological traits typical of the metacyclic stage. This is the first report describing metacyclogenesis inL. guyanensisaxenic promastigotes and a simple and efficient method for the purification of metacyclic forms. Furthermore, a model of human macrophage infection withL. guyanensiswas established.

First sampled in the late 1990s, Campamento Tortuguero La Gloria, in Jalisco, Mexico, was resampled for olive ridley sea turtle (Lepidochyles olivacea Eschscholtz) diversity 10 years later. A compa...

Nowadays, significant amounts of agro-industrial wastes are discarded by industries; however, they represent interesting raw materials for the production of high-added value products. In this regard, orange peels (ORA) and exhausted sugar beet cossettes (ESBC) have turned out to be promising raw materials for hydrolytic enzymes production by solid state fermentation (SSF) and also a source of sugars which could be fermented to different high-added value products. The maximum activities of xylanase and exo-polygalacturonase (exo-PG) measured in the enzymatic extracts obtained after the SSF of ORA were 31,000 U·kg-1 and 17,600 U·kg-1, respectively; while for ESBC the maximum values reached were 35,000 U·kg-1 and 28,000 U·kg-1, respectively. The enzymatic extracts obtained in the SSF experiments were also employed for the hydrolysis of ORA and ESBC. Furthermore, it was found that extracts obtained from SSF of ORA, supplemented with commercial cellulase, were more efficient for the hydrolysis of ORA and ESBC than a commercial enzyme cocktail typically used for this purpose. In this case, maximum reducing sugars concentrations of 57 and 47 g·L-1 were measured after the enzymatic hydrolysis of ESBC and ORA, respectively.

El conocimiento sobre inicio y duración de las etapas de desarrollo y producción de materia seca por estadio en variedades de frijol (Phaseolus vulgaris L.) es primordial para un buen manejo y producción del cultivo. El presente estudio se realizó para determinar la ocurrencia y duración de las etapas de desarrollo y la acumulación de materia seca en las variedades de frijol común de hábito de crecimiento determinado Bayomex, Canario Chiapas, Peruano 16 y Peruano Mostaza. El trabajo de campo se condujo en Zapopan, Jalisco, México bajo condiciones de secano bajo un diseño experimental de bloques completos al azar con tres repeticiones. Se registraron los días al inicio de cada etapa y la materia seca acumulada en cada etapa, así como el rendimiento de grano. Se determinó la duración en días de cada etapa y se elaboraron curvas de acumulación de materia seca; se obtuvo la tasa media de crecimiento diario por etapa fenológica. Las variedades mostraron diferencias en las etapas de desarrollo de la fase reproductiva y en la duración del ciclo biológico. Bayomex y Canario Chiapas llegaron a madurez a los 82 y 85 d, y Peruano 16 y Peruano Mostaza a los 92 y 94 d, respectivamente. Se detectaron diferencias entre variedades en producción de materia seca total. La acumulación de materia seca fue lenta en las etapas iniciales, más alta en estados intermedios y se redujo hacia la madurez fisiológica. Se observó incremento de materia seca en las estructuras vegetativas hasta la formación de vainas y descenso en madurez fisiológica; las estructuras reproductivas mostraron acumulación pronunciada de materia seca entre formación de vainas y madurez. La tasa media de crecimiento diario fue mayor en las etapas intermedias. Los cultivares Peruano 16 y Peruano Mostaza mostraron ciclo biológico más largo, mayor producción de materia seca y rendimiento de grano.

El objetivo fue generar mapas de casos de dengue mediante un Sistema de Informacion Geografica (SIG) en el area metropolitana de Monterrey (AMMty), Nuevo Leon, Mexico indicando las zonas de riesgo. Las muestras positivas a una de las pruebas para dengue, que realiza el Laboratorio Estatal de Salud Publica (LESP) se tomaron como casos. Los casos fueron agrupados en area geoestadistica basica (AGEB's). Se definieron AGEB's brote y semana brote. Se presentaron 114 AGEB's Brote y 33 Semanas Brote. Las AGEB's fueron ubicadas en cinco niveles de riesgo: Muy alto, Alto, Mediano, Bajo y en Riesgo. Las AGEB's incluidas en Muy alto y Alto Riesgo abarcaron el 7.9% de las AGEB's y 41.4% casos. Con mayor frecuencia durante las semanas 38–45, temporada de lluvia. En base a estos resultados el AMMty debe considerase endemica.

Significant advances have been made in the last years trying to identify regulatory pathways that control plant responses to boron (B) deficiency. Still, there is a lack of a deep understanding of how they act regulating growth and development under B limiting conditions. Here, we analyzed the impact of B deficit on cell division leading to root apical meristem (RAM) disorganization. Our results reveal that inhibition of cell proliferation under the regulatory control of cytokinins (CKs) is an early event contributing to root growth arrest under B deficiency. An early recovery of QC46:GUS expression after transferring B-deficient seedlings to control conditions revealed a role of B in the maintenance of QC identity whose loss under deficiency occurred at later stages of the stress. Additionally, the D-type cyclin CYCD3 overexpressor and triple mutant cycd3;1-3 were used to evaluate the effect on mitosis inhibition at the G1-S boundary. Overall, this study supports the hypothesis that meristem activity is inhibited by B deficiency at early stages of the stress as it does cell elongation. Likewise, distinct regulatory mechanisms seem to take place depending on the severity of the stress. The results presented here are key to better understand early signaling responses under B deficiency, This work was supported by the MINECO BIO2012-32796 Spanish grant, the Juan de la Cierva Fellowship Program (JCI-2012-14172) (MINECO, Spain) (to M.R), the Postgraduate Studies Scholarship Programme (UAM, Spain) (to L.P.V.) and the FPU Fellowship Program (AP2010-4786) (MECD, Spain) (to I.A)