Cortical neurons exhibit extreme diversity in gene expression as well as in morphological and electrophysiological properties
. Most existing neural taxonomies are based on either transcriptomic
or ...morpho-electric
criteria, as it has been technically challenging to study both aspects of neuronal diversity in the same set of cells
. Here we used Patch-seq
to combine patch-clamp recording, biocytin staining, and single-cell RNA sequencing of more than 1,300 neurons in adult mouse primary motor cortex, providing a morpho-electric annotation of almost all transcriptomically defined neural cell types. We found that, although broad families of transcriptomic types (those expressing Vip, Pvalb, Sst and so on) had distinct and essentially non-overlapping morpho-electric phenotypes, individual transcriptomic types within the same family were not well separated in the morpho-electric space. Instead, there was a continuum of variability in morphology and electrophysiology, with neighbouring transcriptomic cell types showing similar morpho-electric features, often without clear boundaries between them. Our results suggest that neuronal types in the neocortex do not always form discrete entities. Instead, neurons form a hierarchy that consists of distinct non-overlapping branches at the level of families, but can form continuous and correlated transcriptomic and morpho-electrical landscapes within families.
The high activity of metallic magnesium and alloys limits its potential in biomedical applications; in recent years, extensive efforts have been devoted to modulating this reactivity. In this work, ...we present Mg(OH)2 and TiO2 barrier coatings to reduce the degradation of magnesium alloy (Mg-Ca-Zn) surfaces. These coatings were deposited by the anodization method and the spin-coating technique, respectively. The anodized layer was coated with TiO2 generated from the hydrolysis of 3% weight of TTIP (TiOCH(CH3)24, Titanium(IV) isopropoxide) in 2-Propanol deposited by the spin-coating method. Studying the degradation in Ringer's solution by electrochemical impedance spectroscopy and OCP revealed a 98% reduction in pittings in uncoated samples after 14 days of immersion. The pH measurements revealed that the TiO2 coating reduced the alkalization of the physiological environment, keeping the pH at 6.0 values. In vitro studies of two types of bacteria (E. coli and S. aureus) exhibited zones of inhibition in the agar and activity bactericidal (kill time test). The mechanisms behind the improved degradation resistance and enhanced antibacterial activity are presented and discussed here. Surface modification with Mg(OH)2/TiO2 coatings is a promising strategy to control the biodegradation of magnesium implants for bone regeneration.
•Melipona honey proteins had antibacterial activity against foodborne pathogens.•The non-glycosylated fraction possessed the highest antimicrobial activity.•The least-glycosylated Melipona honey ...Proteins had highest antioxidant activity.
Proteins from Melipona beecheii honey were purified by concanavalin A (conA) affinity chromatography and eluted with a stepwise glucose gradient into fractions named F2-F5. The conA-unbound fraction (F1) was further separated by molecular exclusion into fractions named MbF1-1,2 and MbF1-3. All fractions were evaluated for antibacterial activity against foodborne pathogens and antioxidant capacity. F1 fraction possessed highest antimicrobial activity against S. aureus, L. monocytogenes, S. Typhimurium, E. coli and P. aeruginosa with MIC’s 1.4 ± 0.2, 15 ± 1, 39 ± 2, 1 ± 0.1, and 75 ± 2 µg/mL, respectively. F1, MbF1-1,2 and MbF1-3 had bactericidal effect except against P. aeruginosa. When the antioxidant capacity of the fractions was determined, F2 had the highest antioxidant activity measured by DPPH radical scavenging activity (IC50 = 2.4 ± 0.4 µg/µL) and reducing power of Fe(III) (IC50 = 1.8 ± 0.2 µg/µL). We provide evidence that M. beecheii honey proteins possess broad spectrum antibacterial and antioxidant activity, the latter probably through their reducing agent and free radical scavenger properties.
Objetivo: En este artículo se realiza el cálculo y análisis del índice por riesgo térmico, y el concepto del Índice Sintetizado de la Temperatura (SRT), que equivale a un promedio del índice de ...estrés térmico (WBGT), calculado en diferentes frentes de trabajo de una mina subterránea de carbón. Métodos: Los datos de campo incluyeron medidas de variables climatológicas como la Temperatura Seca (TS) y la Humedad Relativa (HR), y el tiempo de exposición de los trabajadores a dichas condiciones; estas medidas fueron tomadas en la Mina de carbón San José. Resultados: se evidenció que aunque el promedio SRT de la mina clasifica el ambiente como cálido moderado aceptable, existen frentes donde el índice de calor que experimentan los trabajadores es alto y riesgoso. Conclusiones: Se logra concluir que la humedad relativa es la variable que más influye en el calentamiento de los ambientes subterráneos de las minas de la región; de igual forma, se concluye que no es suficiente con determinar el WBGT, sino que se hace necesario establecer la sensación térmica que padecen los trabajadores, a partir del cálculo del índice de calor.
El diagnóstico del cáncer de pulmón (CP) se realiza en estados avanzados. En este sentido la Tomografía Computarizada de Alta Resolución (TCAR), permite demostrar la presencia de la enfermedad en ...casos con radiografía normal. El presente artículo tiene como objetivo caracterizar los patrones pulmonares asociados al CP por TCAR, en pacientes atendidos en el Instituto Nacional de Oncología y Radiobiología de Cuba (INOR), durante el periodo 2017-2018. El tipo de estudio fue descriptivo, de cohorte retrospectiva. Fueron estudiados 53 pacientes con CP. La información fue obtenida de la base de datos del Departamento de Imagenología y de la Historia Clínica. Los datos fueron procesados de forma automatizada (SPSS versión 22.0). Se utilizó análisis de distribución de frecuencias y el test de independencia. En los principales resultados se destaca que la mayor parte de los tumores pulmonares presentó localización central (64.2%). Predominaron los patrones de alta atenuación (67.9%). No se encontraron diferencias significativas, al comparar las frecuencias de las variedades histológicas entre cada uno de los patrones, con el resto de ellos (valores p>0.05). Se concluyo que la alta frecuencia de presentación radiológica central de los tumores pulmonares en nuestro estudio, no coincide con los reportes nacionales e internacionales. Este estudio no aporta las evidencias suficientes para poder plantear que exista relación de los patrones imagenológicos, con las formas de presentación radiológica, ni con las variedades histológicas del cáncer de pulmón.
GalNAc-glycopeptides derived from mucin MUC1 are an important class of tumor-associated antigens. α-O-glycosylation forces the peptide to adopt an extended conformation in solution, which is far from ...the structure observed in complexes with a model anti-MUC1 antibody. Herein, we propose a new strategy for designing potent antigen mimics based on modulating peptide/carbohydrate interactions by means of O → S/Se replacement at the glycosidic linkage. These minimal chemical modifications bring about two key structural changes to the glycopeptide. They increase the carbohydrate–peptide distance and change the orientation and dynamics of the glycosidic linkage. As a result, the peptide acquires a preorganized and optimal structure suited for antibody binding. Accordingly, these new glycopeptides display improved binding toward a representative anti-MUC1 antibody relative to the native antigens. To prove the potential of these glycopeptides as tumor-associated MUC1 antigen mimics, the derivative bearing the S-glycosidic linkage was conjugated to gold nanoparticles and tested as an immunogenic formulation in mice without any adjuvant, which resulted in a significant humoral immune response. Importantly, the mice antisera recognize cancer cells in biopsies of breast cancer patients with high selectivity. This finding demonstrates that the antibodies elicited against the mimetic antigen indeed recognize the naturally occurring antigen in its physiological context. Clinically, the exploitation of tumor-associated antigen mimics may contribute to the development of cancer vaccines and to the improvement of cancer diagnosis based on anti-MUC1 antibodies. The methodology presented here is of general interest for applications because it may be extended to modulate the affinity of biologically relevant glycopeptides toward their receptors.
The structural features of MUC1‐like glycopeptides bearing the Tn antigen (α‐O‐GalNAc‐Ser/Thr) in complex with an anti MUC‐1 antibody are reported at atomic resolution. For the α‐O‐GalNAc‐Ser ...derivative, the glycosidic linkage adopts a high‐energy conformation, barely populated in the free state. This unusual structure (also observed in an α‐S‐GalNAc‐Cys mimic) is stabilized by hydrogen bonds between the peptidic fragment and the sugar. The selection of a particular peptide structure by the antibody is thus propagated to the carbohydrate through carbohydrate/peptide contacts, which force a change in the orientation of the sugar moiety. This seems to be unfeasible in the α‐O‐GalNAc‐Thr glycopeptide owing to the more limited flexibility of the side chain imposed by the methyl group. Our data demonstrate the non‐equivalence of Ser and Thr O‐glycosylation points in molecular recognition processes. These features provide insight into the occurrence in nature of the APDTRP epitope for anti‐MUC1 antibodies.
Spot the difference: The structures of two Tn antigen glycopeptides, with N‐acetylgalactosamine (GalNAc, green hexagon) attached to either Ser or Thr, in complex with an anti‐MUC1 antibody are reported. The results reveal significant differences in the conformational behavior of the two glycopeptides in the bound state and demonstrate the non‐equivalence of Ser and Thr O‐glycosylation points in molecular recognition processes.
This research aimed to examine the potential alleviative effects of beta-glucan administration on fatigue, unrefreshing sleep, anxiety/depression symptoms and health-related quality of life in ...ME/CFS. A 36-week unicenter, randomized, double-blind, placebo-controlled trial was conducted in 65 ME/CFS patients, who were randomly allocated to one of two arms to receive four capsules each one of 250 mg beta-glucan, 3.75 µg vitamin D3, 1.05 mg vitamin B6, and 7.5 mg zinc (n = 35), or matching placebo including only microcrystalline cellulose as an excipient (n = 30) once daily. The findings showed that the beta-glucan supplementation significantly improved cognitive fatigue (assessed with FIS-40 scores) after the 36-week treatment compared to the baseline (p = 0.0338). Taken together, this study presents the novel finding that yeast-derived beta-glucan may alleviate cognitive fatigue symptoms in ME/CFS. Thus, it offers valuable scientific insights into the potential use of yeast beta-glucan as a nutritional supplement and/or functional food to prevent or reduce cognitive dysfunction in patients with ME/CFS. Further interventions are warranted to validate these findings and also to delve deeper into the possible immunometabolic pathomechanisms of beta-glucans in ME/CFS.
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