bluuebunny/crossref_metadata_2025 huggingface dataset:
Some issues of civil law counteraction to raiding in the field of entrepreneurship
Authors:   L.N. Gumilyov Eurasian National University, Nurmagambetov A.A. , Nurmagambetov A.M. ,   L.N. Gumilyov Eurasian National University
Published: February 2021

Raiding, as an economic phenomenon, arose in the world practice in connection with the functioning of the securities market. At the initial stage of the formation of the securities market, the activities of the so-called “black” raiders were formed and intensified, which in a criminal way, using violent acts, seized enterprises and the business as a whole.Along with “black” raiding, there is a “white” raiding aimed at seizing the enterprise and business, guided primarily by civil law. At the same time, the division of raiding into “black” and “white” is conditional, since the methods of raider attacks on the target company have improved in their own way, and in some cases the “black” and “white” raiding are mixed.In the Republic of Kazakhstan, raiding, as an unlawful act, arose in the context of the transition of our country from a socialist economic system to a market economy. At the same time, medium and small businesses, which, unlike large businesses, do not have the corresponding economic, financial and organizational capabilities to counter raiding, are exposed to the negative impact of raiding.Civil law does not have a legal definition of raiding, but legal opposition to this phenomenon is enshrined in many of its norms. In practice, those companies that violate current legislation may be vulnerable to raider seizure, thereby creating a facilitated environment for raider attacks. In order to increase the effectiveness of opposing raiding, it is necessary to improve legislation in the field of banking, on real estate mortgages, on rehabilitation and bankruptcy.
Anticoagulation in COVID-19.
Authors: Ochoa Ximena Veloz , Ayo Chipantasig Gustavo , Zambrano Palma Dixon
Published: February 2021

In 2020 declared the COVID-19 pandemic. A new SARS-Cov-2 betacoronavirus transmitted through respiratory secretions of infected people, causing lesions in the pulmonary microvasculature, endothelial activation, massive release of pro-inflammatory substances "cytokine storm", which lead to a procoagulant state and on which it will depend the development of the serious disease. The management of coagulopathy induced by COVID-19 entails stratifying the risk of thrombosis, for which heparins are the treatment of choice, especially in hospitalized patients. Low molecular weight heparin (LMWH) is the first option since its administration implies longer times and less exposure of health personnel. Unfractionated heparin is another alternative but requires laboratory controls and is sometimes not available. Heparin-induced thrombocytopenia (HIT) and bleeding are serious adverse events secondary to the use of heparin anticoagulation.
Carcinoma Espinocelular da Cavidade Bucal: um Estudo Epidemiológico na Santa Casa de Misericórdia de Fortaleza
Authors: Teixeira Ana Karine Macedo , Almeida Maria Eneide Leitão de , Holanda Marcelo Esmeraldo , Sousa Fabrício Bitu , Almeida Paulo César de
Published: February 2021

O objetivo deste trabalho foi identificar o perfil epidemiológico dos pacientes portadores de carcinoma espinocelular de boca, atendidos na Santa Casa de Misericórdia de Fortaleza-CE, de 1999 a 2005. Trata-se de um estudo transversal, descritivo, a partir de informações secundárias. A população pesquisada foi de 225 casos. As informações foram coletadas nos livros de registros das cirurgias de cabeça e pescoço e nos prontuários dos pacientes da Santa Casa. Foram pesquisadas as variáveis: idade, sexo, procedência do paciente, estadiamento clínico e patológico, localização anatômica e tratamento. Observou-se que 69,2% dos casos prevaleceram em homens, com idade variando de 26 a 98 anos. Os sítios mais acometidos foram assoalho de boca (22,7%) e língua (21,8%). Sobre o estadiamento, 52,4% dos pacientes apresentaram-se em estágios III ou IV, sendo 40% com metástase regional. Cirurgia associada à radioterapia foi o tratamento mais realizado (57,2%). Encontrou-se relação estatisticamente significante (p<0,05) entre as variáveis sexo e idade, entre sexo e local acometido, e deste com idade. Os resultados sugerem a necessidade de implantação de uma política de prevenção e controle do câncer bucal no Estado do Ceará, no sentido de viabilizar a redução no número de novos casos, diagnóstico precoce e melhor prognóstico, e tratamento dessas neoplasias.
PELATIHAN MARKETPLACE BAGI KELOMPOK INFORMASI MASYARAKAT KABUPATEN BANTUL
Authors: Haryani Prita
Published: February 2021

Pemanfaatan teknologi informasi untuk meningkatkan nilai ekonomi dilakukan oleh Pemerintah Kabupaten Bantul dengan memberdayakan masyarakat Bantul khususnya pelaku UMKM yang tergabung pada KIM untuk memanfaatkan marketplace sebagai sarana pemasaran produk/jasa UMKM. Hal ini dilakukan agar promosi produk UMKM dapat menjangkau wilayah yang lebih luas dan transaksi jual beli bisa dilakukan secara mudah, cepat dan aman. Pelatihan marketplace ini dilaksanakan dengan langkah-langkah kegiatan seperti analisis kebutuhan dan permasalahan, pembuatan materi, pelaksanaan,dan evaluasi. Dari hasil pendampingan yang telah dilakukan, pelaku UMKM Kabupaten Bantul dapat memanfaatkan secara maksimal penggunaan marketplace sebagai sarana pemasaran produk/jasa. Diharapkan dengan meningkatnya transaksi jual beli produk UMKM melalui marketplace, akan meningkatkan kesejahteraan pelaku UMKM khususnya masyarakat Bantul.
Implementación de un sistema para evaluar la neurotoxicidad de los contaminantes ambientales en larvas de pez cebra (Danio rerio)
Authors: Valles Selma , Gutiérrez López Everardo , Bardullas Ulises
Published: February 2021

En la actualidad, una amplia gama de contaminantes son detectados en el ambiente con implicaciones en la salud y en la biodiversidad, su elevado número ha dificultado su estudio con métodos de experimentación in vitro e in vivo. Se implementó en el modelo del pez cebra un sistema de bajo costo para evaluar el efecto de los contaminantes ambientales, utilizando la actividad motora como marcador de neurotoxicidad. Embriones fueron expuestos a concentraciones de 0.05, 0.5, 5, 50 mg/l de arsénico inorgánico (Asi), 0.03, 0.3, 3, 10 mg/l de atrazina (ATR) y 14.5, 29.1, 43.6 mg/l de tiametoxam (TMX). La actividad motora aumentó en larvas expuestas a ATR y Asi y disminuyó con dosis altas de TMX. Estos datos sugieren que el sistema implementado es sensible para detectar cambios en la conducta motora en larvas del pez cebra, lo que puede contribuir positivamente al estudio de los contaminantes ambientales.
La familia Cactaceae en el Área Natural Protegida Monumento Natural Cerro del Muerto, Aguascalientes, México
Authors: Rivera-Martínez Ricardo , Ocampo Gilberto
Published: February 2021

El Área Natural Protegida (ANP) Monumento Natural Cerro del Muerto se encuentra ubicado en los municipios de Aguascalientes y Jesús María, Aguascalientes, México. El plan de manejo oficial de esta ANP reporta que 8% de la flora corresponde a la familia Cactaceae; no obstante, tal documento no proporciona un listado florístico. En el borrador del plan de manejo están registrados 14 taxones de cactáceas. Ambos documentos mencionan la presencia de especies incluidas en la NOM-059-SEMARNAT-2010; sin embargo, no existe evidencia física que avale esta información. En este trabajo se presenta un listado florístico conformado por 17 taxones que se encuentran en el Área Natural Protegida Monumento Natural Cerro del Muerto, de los cuales tres están incluidos dentro de la NOM-059-SEMARNAT-2010, así como la referencia de los ejemplares de herbario.
Gestión del conocimiento y su influencia sobre el desempeño organizacional en las empresas de Aguascalientes
Authors: Padilla-Ornelas Patricia Janet , Martínez-Serna Ma. del Carmen
Published: February 2021

Este estudio tiene como propósito analizar la influencia de la gestión del conocimiento sobre el desempeño de pequeñas, medianas y grandes organizaciones establecidas en el estado de Aguascalientes. Se realizó una investigación cuantitativa, exploratoria, no experimental a 206 empresas del sector industrial, comercio y servicios. Se aplicaron cuestionarios personales a directivos, gerentes o propietarios de las unidades económicas. El análisis de los datos se realizó mediante la técnica estadística de ecuaciones estructurales (SEM). Los resultados obtenidos permiten concluir que, si se tiene una cultura que permita políticas y estrategias para gestionar adecuadamente el conocimiento, se entrena a los empleados, mejora en consecuencia el desempeño de las organizaciones. Sin embargo, a los empleados no les gusta compartir sus conocimientos por temor a perder su trabajo.
Intención emprendedora en los productores de chile del estado de Aguascalientes: Perspectiva desde las relaciones de colaboración
Authors: Parga-Montoya Neftalí , Vega-Martínez Javier Eduardo , Miramontes-Acevedo Guillermo
Published: February 2021

Las redes de colaboración son un tópico relevante para el desarrollo económico, social e individual de los emprendedores. Se tiene como base la teoría de los recursos y capacidades para analizar las redes que tienen los productores de chile con otros actores del sector. El estudio tiene como objetivo principal medir los efectos de las redes de colaboración, tanto empresariales como institucionales sobre las intenciones emprendedoras. Se realizó un estudio empírico con 94 agricultores ubicados en el estado de Aguascalientes, México. Las hipótesis planteadas se contrastaron a partir de regresiones multivariantes. Los resultados obtenidos más relevantes se centran en las redes institucionales como detonantes de la intención emprendedora, teniendo efectos diferentes entre sí al conjuntar la escolaridad y la experiencia en el modelo. De la misma manera, las contribuciones teóricas recaen en el desarrollode una perspectiva de la intención emprendedora sustentada en la formación académica con implicaciones  importantes.
洋湖再生水厂（二期）池壁模板设计计算
Authors: 崔 欣
Published: February 2021

本工程主体由预处理池、MSBR池、微絮凝过滤池、中间提升泵站、紫外光消毒池组成。其中预处理池最大池壁高11.1m,最大池壁厚度为0.9m,C40P8;MSBR池最大池壁高9.1m,最大池壁厚度为0.9m, C30P6;微絮凝过滤池最大池壁高8.72m，最大池壁厚度为0.85m, C30P6。部分池壁顶端设计有0.15m厚，宽度为1.5m、1.0m、0.8m、0.55m的走道。池底板厚度0.5-1.1m。
METHODOLOGY FOR CALCULATING ELECTROMAGNETIC FIELDS GENERATED BY AN AUTOMATED WORKPLACE OF AN OBJECT OF INFORMATIZATION
Authors: Viktorov V. A.
Published: February 2021

A methodology for calculating electromagnetic fields generated by an automated workstation of an object of informatization has been developed. Using the presented methodology, it becomes possible to form a complete scheme of electromagnetic radia-tion of the space under study. Based on the output of the calculation of electromagnet-ic fields, the permissible time spent by the operator at each point of his workplace is calculated. For the first time, electromagnetic radiation sources are modeled by a com-bination of elementary electric dipoles powered by various harmonic components. The reliability of the illustrated methodology was carried out by comparing the calculated values of the parameters of electromagnetic fields with the measured values of the lev-els at given frequencies.
ON SOFTWARE IMPROVEMENT OF IMAGE CHANNEL SUPPRESSION IN SDR RECEIVERS WITH ANALOG CONVERSION TO A LOW INTERMEDIATE FREQUENCY
Authors: Yurkov A. S.
Published: February 2021

A method for digital signal processing in SDR receivers with analog conversion to a low intermediate frequency is proposed. In contrast to known systems, the proposed approach does not consider parasitic phase and amplitude distortions, but uses the direct method minimizing of the signal of the mirror reception channel. Generally speaking, this can be done simultaneously at several frequencies. It is shown that in computational terms, this is reduced to signal processing by an algorithm similar to a digital non-recursive filter, and to determine its coefficients, it is sufficient to solve a system of linear algebraic equations.
Development of Parameters for Standardization of Duckweed (Lemna Minor L.) Raw Material
Authors: Nikiforov L. N. , Krivoshchekov S. V. , Kolomiets N. E. , Kadyrova T. V. , Isaikina N. V. , Abramets N. Y. , Bezverkhniaia E. A. , Belousov M. V.
Published: February 2021

Introduction.Lemna minor L. (duckweed) refers to the duckweed subfamily (Lemnaceae S. F. Gray) and widely distributed in ponds of Russia. Literature data confirm the possibility of harvesting significant volumes of this raw material in natural habitat and grown in aquaculture. The process of biosynthetic accumulation in duckweed fronds provides a variety of compounds with a wide spectrum of biological activity. Therefore, the use of raw materials Lemna minor L. is promising for the development of drugs and parapharmaceutical products. Thus, it is an urgent task to quantify active components of duckweed and standardize (determination of criteria for identification, quality and safety) plant material.

Aim.Establish macro- and microscopic characteristics of raw materials and develop methods for the quantitative determination of the main groups of biologically active substances (BAS) for standardization of raw duckweed.

Materials and methods.Samples of duckweed was collected in natural habitats of Western Siberia. Macro- and microscopic assay, HPLC, UV-spectrometry were used in research process.

Results and discussion.Were established the criteria for identification of duckweed fronds by studying external (macroscopic) and microscopic features of raw material Lemna minor L. Was developed and validated the procedure of the quantitative determination of phenolcarboxylic acids in raw material Lemna minor L.

Conclusion.The study of external (macroscopic) and microscopic features provided the criteria for identification of the raw material Lemna minor L. The technique for the quantitative analysis of polysaccharides using gravimetry does not need validation, because is a direct method of substance measurement. Was validated quantification method of phenolcarboxylic acids (in terms of chlorogenic acid) by criteria of linearity, repeatability, in-laboratory precision and accuracy. Was established quality criteria for identification and quantitative assay, which can be used in the draft for normative documents for medicinal plant raw material of Lemna minor L. «Duckweed fronds».
Capacitação de agentes de ATER em processos de formação em agroecologia na Região Sudeste do Brasil
Authors: Gollo Alexandre Magno Lopes , Oliveira Marcelo Leles Romarco de
Published: February 2021

Este artigo tem por objetivo trazer reflexões sobre a formação de profissionais no campo da agroecologia para trabalhar nos serviços de Assistência Técnica e Extensão Rural (ATER) com base em uma nova perspectiva sociotécnica. Para isso, foi realizada uma pesquisa de campo entre os anos de 2016 a 2018 junto a profissionais vinculados a instituições públicas e organizações sociais com atuação na prestação de serviços de ATER nos estados da Região Sudestes do Brasil (Rio de Janeiro, Espírito Santo, Minas Gerais e São Paulo).  Os autores recorrem a um debate sobre Extensão Rural e suas conexões com a transição para a agroecologia, como um de seus princípios fundamentais, incorporado à Política Nacional de Assistência Técnica e Extensão Rural (PNATER), ainda que relativizado pela Lei 12.188/2010, que adotou o termo agricultura de base ecológica em substituição ao viés agroecológico. Os resultados alcançados através das diferentes estratégias de formação implementadas na região estudada são apresentados e discutidos em detalhe. No que tange à formação de agentes de Ater no âmbito da Agroecologia, observou-se que este referencial é tratado como uma abordagem científica, viva, interativa e interpelada, que busca reconhecer em seus protagonistas, sobretudo em agricultores familiares e suas organizações, um papel importante para o desenvolvimento rural do campo brasileiro.
Bioactive Cellulose Nanocrystal-Poly(ε-Caprolactone) Nanocomposites for Bone Tissue Engineering Applications
Authors: Hong Jung Ki , Cooke Shelley L. , Whittington Abby R. , Roman Maren
Published: February 2021

3D-printed bone scaffolds hold great promise for the individualized treatment of critical-size bone defects. Among the resorbable polymers available for use as 3D-printable scaffold materials, poly(ε-caprolactone) (PCL) has many benefits. However, its relatively low stiffness and lack of bioactivity limit its use in load-bearing bone scaffolds. This study tests the hypothesis that surface-oxidized cellulose nanocrystals (SO-CNCs), decorated with carboxyl groups, can act as multi-functional scaffold additives that (1) improve the mechanical properties of PCL and (2) induce biomineral formation upon PCL resorption. To this end, an in vitro biomineralization study was performed to assess the ability of SO-CNCs to induce the formation of calcium phosphate minerals. In addition, PCL nanocomposites containing different amounts of SO-CNCs (1, 2, 3, 5, and 10 wt%) were prepared using melt compounding extrusion and characterized in terms of Young's modulus, ultimate tensile strength, crystallinity, thermal transitions, and water contact angle. Neither sulfuric acid-hydrolyzed CNCs (SH-CNCs) nor SO-CNCs were toxic to MC3T3 preosteoblasts during a 24 h exposure at concentrations ranging from 0.25 to 3.0 mg/mL. SO-CNCs were more effective at inducing mineral formation than SH-CNCs in simulated body fluid (1x). An SO-CNC content of 10 wt% in the PCL matrix caused a more than 2-fold increase in Young's modulus (stiffness) and a more than 60% increase in ultimate tensile strength. The matrix glass transition and melting temperatures were not affected by the SO-CNCs but the crystallization temperature increased by about 5.5°C upon addition of 10 wt% SO-CNCs, the matrix crystallinity decreased from about 43 to about 40%, and the water contact angle decreased from 87 to 82.6°. The abilities of SO-CNCs to induce calcium phosphate mineral formation and increase the Young's modulus of PCL render them attractive for applications as multi-functional nanoscale additives in PCL-based bone scaffolds.
Tropoelastin and Elastin Assembly
Authors: Ozsvar Jazmin , Yang Chengeng , Cain Stuart A. , Baldock Clair , Tarakanova Anna , Weiss Anthony S.
Published: February 2021

Elastic fibers are an important component of the extracellular matrix, providing stretch, resilience, and cell interactivity to a broad range of elastic tissues. Elastin makes up the majority of elastic fibers and is formed by the hierarchical assembly of its monomer, tropoelastin. Our understanding of key aspects of the assembly process have been unclear due to the intrinsic properties of elastin and tropoelastin that render them difficult to study. This review focuses on recent developments that have shaped our current knowledge of elastin assembly through understanding the relationship between tropoelastin’s structure and function.
High-Throughput Metabolomics for Discovering Potential Biomarkers and Identifying Metabolic Mechanisms in Aging and Alzheimer’s Disease
Authors: Xie Kun , Qin Qi , Long Zhiping , Yang Yihui , Peng Chenghai , Xi Chunyang , Li Liangliang , Wu Zhen , Daria Volontovich , Zhao Yashuang , Wang Fan , Wang Maoqing
Published: February 2021

Alzheimer’s disease (AD) is an aging-related neurodegenerative disease. We aimed to investigate the metabolic mechanisms of aging and AD and to identify potential biomarkers for the early screening of AD in a natural aging population. To analyze the plasma metabolites related to aging, we conducted an untargeted metabolomics analysis using ultra-high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry in a two-stage cross-sectional study. Spearman’s correlation analysis and random forest were applied to model the relationship between age and each metabolite. Moreover, a systematic review of metabolomics studies of AD in the PubMed, Cochrane and Embase databases were searched to extract the differential metabolites and altered pathways from original studies. Pathway enrichment analysis was conducted using Mummichog. In total, 669 metabolites were significantly altered with aging, and 12 pathways were enriched and correlated with aging. Three pathways (purine metabolism, arginine and proline metabolism, and the TCA cycle) were shared between aging and AD. Arginine and proline metabolism play a key role in the progression from healthy to mild cognitive impairment and to AD in the natural aging population. Three metabolites, 16-a-hydroxypregnenolone, stearic acid and PC[16:0/22:5(4Z,7Z,10Z,13Z,16Z)] were finally proposed as potential markers of AD in the natural aging population. The underlying mechanism shared between aging and AD and the potential biomarkers for AD diagnosis were proposed based on multistep comparative analysis.
Perspectives on Organelle Interaction, Protein Dysregulation, and Cancer Disease
Authors: Díaz Paula , Sandoval-Bórquez Alejandra , Bravo-Sagua Roberto , Quest Andrew F. G. , Lavandero Sergio
Published: February 2021

In recent decades, compelling evidence has emerged showing that organelles are not static structures but rather form a highly dynamic cellular network and exchange information through membrane contact sites. Although high-throughput techniques facilitate identification of novel contact sites (e.g., organelle-organelle and organelle-vesicle interactions), little is known about their impact on cellular physiology. Moreover, even less is known about how the dysregulation of these structures impacts on cellular function and therefore, disease. Particularly, cancer cells display altered signaling pathways involving several cell organelles; however, the relevance of interorganelle communication in oncogenesis and/or cancer progression remains largely unknown. This review will focus on organelle contacts relevant to cancer pathogenesis. We will highlight specific proteins and protein families residing in these organelle-interfaces that are known to be involved in cancer-related processes. First, we will review the relevance of endoplasmic reticulum (ER)-mitochondria interactions. This section will focus on mitochondria-associated membranes (MAMs) and particularly the tethering proteins at the ER-mitochondria interphase, as well as their role in cancer disease progression. Subsequently, the role of Ca2+ at the ER-mitochondria interphase in cancer disease progression will be discussed. Members of the Bcl-2 protein family, key regulators of cell death, also modulate Ca2+ transport pathways at the ER-mitochondria interphase. Furthermore, we will review the role of ER-mitochondria communication in the regulation of proteostasis, focusing on the ER stress sensor PERK (PRKR-like ER kinase), which exerts dual roles in cancer. Second, we will review the relevance of ER and mitochondria interactions with other organelles. This section will focus on peroxisome and lysosome organelle interactions and their impact on cancer disease progression. In this context, the peroxisome biogenesis factor (PEX) gene family has been linked to cancer. Moreover, the autophagy-lysosome system is emerging as a driving force in the progression of numerous human cancers. Thus, we will summarize our current understanding of the role of each of these organelles and their communication, highlighting how alterations in organelle interfaces participate in cancer development and progression. A better understanding of specific organelle communication sites and their relevant proteins may help to identify potential pharmacological targets for novel therapies in cancer control.
HOXA5 Participates in Brown Adipose Tissue and Epaxial Skeletal Muscle Patterning and in Brown Adipocyte Differentiation
Authors: Holzman Miriam A. , Ryckman Abigail , Finkelstein Tova M. , Landry-Truchon Kim , Schindler Kyra A. , Bergmann Jenna M. , Jeannotte Lucie , Mansfield Jennifer H.
Published: February 2021

Brown adipose tissue (BAT) plays critical thermogenic, metabolic and endocrine roles in mammals, and aberrant BAT function is associated with metabolic disorders including obesity and diabetes. The major BAT depots are clustered at the neck and forelimb levels, and arise largely within the dermomyotome of somites, from a common progenitor with skeletal muscle. However, many aspects of BAT embryonic development are not well understood.Hoxa5patterns other tissues at the cervical and brachial levels, including skeletal, neural and respiratory structures. Here, we show thatHoxa5also positively regulates BAT development, while negatively regulating formation of epaxial skeletal muscle. HOXA5 protein is expressed in embryonic preadipocytes and adipocytes as early as embryonic day 12.5.Hoxa5null mutant embryos and rare, surviving adults show subtly reduced iBAT and sBAT formation, as well as aberrant marker expression, lower adipocyte density and altered lipid droplet morphology. Conversely, the epaxial muscles that arise from a common dermomyotome progenitor are expanded inHoxa5mutants. Conditional deletion ofHoxa5withMyf5/Crecan reproduce both BAT and epaxial muscle phenotypes, indicating that HOXA5 is necessary withinMyf5-positive cells for proper BAT and epaxial muscle development. However, recombinase-based lineage tracing shows thatHoxa5does not act cell-autonomously to repress skeletal muscle fate. Interestingly,Hoxa5-dependent regulation of adipose-associated transcripts is conserved in lung and diaphragm, suggesting a shared molecular role forHoxa5in multiple tissues. Together, these findings establish a role forHoxa5in embryonic BAT development.
Functional Role of Class III Myosins in Hair Cells
Authors: Cirilo Joseph A. , Gunther Laura K. , Yengo Christopher M.
Published: February 2021

Cytoskeletal motors produce force and motion using the energy from ATP hydrolysis and function in a variety of mechanical roles in cells including muscle contraction, cargo transport, and cell division. Actin-based myosin motors have been shown to play crucial roles in the development and function of the stereocilia of auditory and vestibular inner ear hair cells. Hair cells can contain hundreds of stereocilia, which rely on myosin motors to elongate, organize, and stabilize their structure. Mutations in many stereocilia-associated myosins have been shown to cause hearing loss in both humans and animal models suggesting that each myosin isoform has a specific function in these unique parallel actin bundle-based protrusions. Here we review what is known about the classes of myosins that function in the stereocilia, with a special focus on class III myosins that harbor point mutations associated with delayed onset hearing loss. Much has been learned about the role of the two class III myosin isoforms, MYO3A and MYO3B, in maintaining the precise stereocilia lengths required for normal hearing. We propose a model for how class III myosins play a key role in regulating stereocilia lengths and demonstrate how their motor and regulatory properties are particularly well suited for this function. We conclude that ongoing studies on class III myosins and other stereocilia-associated myosins are extremely important and may lead to novel therapeutic strategies for the treatment of hearing loss due to stereocilia degeneration.
A Simplified Amino Acidic Alphabet to Unveil the T-Cells Receptors Antigens: A Computational Perspective
Authors: Iannuzzi Raffaele , Rossetti Grazisa , Spitaleri Andrea , Bonnal Raoul J. P. , Pagani Massimiliano , Mollica Luca
Published: February 2021

The exposure to pathogens triggers the activation of adaptive immune responses through antigens bound to surface receptors of antigen presenting cells (APCs). T cell receptors (TCR) are responsible for initiating the immune response through their physical direct interaction with antigen-bound receptors on the APCs surface. The study of T cell interactions with antigens is considered of crucial importance for the comprehension of the role of immune responses in cancer growth and for the subsequent design of immunomodulating anticancer drugs. RNA sequencing experiments performed on T cells represented a major breakthrough for this branch of experimental molecular biology. Apart from the gene expression levels, the hypervariable CDR3α/β sequences of the TCR loops can now be easily determined and modelled in the three dimensions, being the portions of TCR mainly responsible for the interaction with APC receptors. The most direct experimental method for the investigation of antigens would be based on peptide libraries, but their huge combinatorial nature, size, cost, and the difficulty of experimental fine tuning makes this approach complicated time consuming, and costly. We have implemented in silico methodology with the aim of moving from CDR3α/β sequences to a library of potentially antigenic peptides that can be used in immunologically oriented experiments to study T cells’ reactivity. To reduce the size of the library, we have verified the reproducibility of experimental benchmarks using the permutation of only six residues that can be considered representative of all ensembles of 20 natural amino acids. Such a simplified alphabet is able to correctly find the poses and chemical nature of original antigens within a small subset of ligands of potential interest. The newly generated library would have the advantage of leading to potentially antigenic ligands that would contribute to a better understanding of the chemical nature of TCR-antigen interactions. This step is crucial in the design of immunomodulators targeted towards T-cells response as well as in understanding the first principles of an immune response in several diseases, from cancer to autoimmune disorders.
The Role of Group 3 Innate Lymphoid Cells in Lung Infection and Immunity
Authors: Yang Dan , Guo Xinning , Huang Tingxuan , Liu Chuntao
Published: February 2021

The lung is constantly exposed to environmental particulates such as aeroallergens, pollutants, or microorganisms and is protected by a poised immune response. Innate lymphoid cells (ILCs) are a population of immune cells found in a variety of tissue sites, particularly barrier surfaces such as the lung and the intestine. ILCs play a crucial role in the innate immune system, and they are involved in the maintenance of mucosal homeostasis, inflammation regulation, tissue remodeling, and pathogen clearance. In recent years, group 3 innate lymphoid cells (ILC3s) have emerged as key mediators of mucosal protection and repair during infection, mainly through IL-17 and IL-22 production. Although research on ILC3s has become focused on the intestinal immunity, the biology and function of pulmonary ILC3s in the pathogenesis of respiratory infections and in the development of chronic pulmonary inflammatory diseases remain elusive. In this review, we will mainly discuss how pulmonary ILC3s act on protection against pathogen challenge and pulmonary inflammation, as well as the underlying mechanisms.
Exogenous Coronavirus Interacts With Endogenous Retrotransposon in Human Cells
Authors: Yin Ying , Liu Xiao-zhao , He Ximiao , Zhou Li-quan
Published: February 2021

There is an increased global outbreak of diseases caused by coronaviruses affecting respiratory tracts of birds and mammals. Recent dangerous coronaviruses are MERS-CoV, SARS-CoV, and SARS-CoV-2, causing respiratory illness and even failure of several organs. However, profound impact of coronavirus on host cells remains elusive. In this study, we analyzed transcriptome of MERS-CoV, SARS-CoV, and SARS-CoV-2 infected human lung-derived cells, and observed that infection of these coronaviruses all induced increase of retrotransposon expression with upregulation of TET genes. Upregulation of retrotransposon was also observed in SARS-CoV-2 infected human intestinal organoids. Retrotransposon upregulation may lead to increased genome instability and enhanced expression of genes with readthrough from retrotransposons. Therefore, people with higher basal level of retrotransposon such as cancer patients and aged people may have increased risk of symptomatic infection. Additionally, we show evidence supporting long-term epigenetic inheritance of retrotransposon upregulation. We also observed chimeric transcripts of retrotransposon and SARS-CoV-2 RNA for potential human genome invasion of viral fragments, with the front and the rear part of SARS-CoV-2 genome being easier to form chimeric RNA. Thus, we suggest that primers and probes for nucleic acid detection should be designed in the middle of virus genome to identify live virus with higher probability. In summary, we propose our hypothesis that coronavirus invades human cells and interacts with retrotransposon, eliciting more severe symptoms in patients with underlying diseases. In the treatment of patients with coronavirus infection, it may be necessary to pay more attention to the potential harm contributed by retrotransposon dysregulation.
Detection of DENV-2 and Insect-Specific Flaviviruses in Mosquitoes Collected From Jeddah, Saudi Arabia
Authors: Fang Yuan , Tambo Ernest , Xue Jing-Bo , Zhang Yi , Zhou Xiao-Nong , Khater Emad I. M.
Published: February 2021

Background

Mosquito-borne diseases are rapidly spreading due to increasing international travel and trade. Routine mosquito surveillance and screening for mosquito-borne pathogens can be early indicators for local disease transmission and outbreaks. However, arbovirus detection in mosquito vectors has rarely been reported in Saudi Arabia.

Methods

A total of 769,541 Aedes and Culex mosquitoes were collected by Black Hole traps during routine mosquito surveillance in the first half of 2016. Culex. quinquefasciatus and Ae. aegypti were the most prevalent species observed. Twenty-five and 24 randomly selected pools of Ae. aegypti and Cx. quinquefasciatus, respectively, were screened for arboviruses by RT-PCR.

Results

Dengue 2 (DENV-2) and four strains of insect-specific flaviviruses, including one of cell-fusing agent virus (CFAV) and three of Phlebotomus-associated flavivirus (PAFV) were detected in pools of Ae. aegypti. We also detected 10 strains of Culex flavivirus (CxFV) in pools of Cx. quinquefasciatus. Phylogenetic analysis using whole genome sequences placed the DENV strain into the cosmopolitan 1 sub-DENV-2 genotype, and the CxFVs into the African/Caribbean/Latin American genotype. These analyses also showed that the DENV-2 strain detected in the present study was closely related to strains detected in China in 2014 and in Japan in 2018, which suggests frequent movement of DENV-2 strains among these countries. Furthermore, the phylogenetic analysis suggested at least five introductions of DENV-2 into Saudi Arabia from 2014 through 2018, most probably from India.

Conclusions

To our knowledge, this study reports the first detection of four arboviruses DENV, CFAV, PAFV, and CxFV in mosquitoes in Saudi Arabia, which shows that they are co-circulating in Jeddah. Our findings show a need for widespread mosquito-based arbovirus surveillance programs in Saudi Arabia, which will improve our understanding of the transmission dynamics of the mosquito-borne arboviruses within the country and help early predict and mitigate the risk of human infections and outbreaks.
Clinical Experience of Personalized Phage Therapy Against Carbapenem-Resistant Acinetobacter baumannii Lung Infection in a Patient With Chronic Obstructive Pulmonary Disease
Authors: Tan Xin , Chen Huaisheng , Zhang Min , Zhao Ying , Jiang Yichun , Liu Xueyan , Huang Wei , Ma Yingfei
Published: February 2021

Overuse of antibiotics in clinical medicine has contributed to the global spread of multidrug-resistant bacterial pathogens, includingAcinetobacter baumannii. We present a case of an 88-year-old Chinese man who developed hospital-acquired pneumonia caused by carbapenem-resistantA. baumannii(CRAB). A personalized lytic pathogen-specific single-phage preparation was nebulized to the patient continuously for 16 days in combination with tigecycline and polymyxin E. The treatment was well tolerated and resulted in clearance of the pathogen and clinical improvement of the patient’s lung function.
Rapid Detection of Enterocytozoon hepatopenaei Infection in Shrimp With a Real-Time Isothermal Recombinase Polymerase Amplification Assay
Authors: Ma Chao , Fan Shihui , Wang Yu , Yang Haitao , Qiao Yi , Jiang Ge , Lyu Mingsheng , Dong Jingquan , Shen Hui , Gao Song
Published: February 2021

Enterocytozoon hepatopenaei (EHP) infection has become a significant threat in shrimp farming industry in recent years, causing major economic losses in Asian countries. As there are a lack of effective therapeutics, prevention of the infection with rapid and reliable pathogen detection methods is fundamental. Molecular detection methods based on polymerase chain reaction (PCR) and loop-mediated isothermal amplification (LAMP) have been developed, but improvements on detection speed and convenience are still in demand. The isothermal recombinase polymerase amplification (RPA) assay derived from the recombination-dependent DNA replication (RDR) mechanism of bacteriophage T4 is promising, but the previously developed RPA assay for EHP detection read the signal by gel electrophoresis, which restricted this application to laboratory conditions and hampered the sensitivity. The present study combined fluorescence analysis with the RPA system and developed a real-time RPA assay for the detection of EHP. The detection procedure was completed in 3–7 min at 39°C and showed good specificity. The sensitivity of 13 gene copies per reaction was comparable to the current PCR- and LAMP-based methods, and was much improved than the RPA assay analyzed by gel electrophoresis. For real clinical samples, detection results of the real-time RPA assay were 100% consistent with the industrial standard nested PCR assay. Because of the rapid detection speed and the simple procedure, the real-time RPA assay developed in this study can be easily assembled as an efficient and reliable on-site detection tool to help control EHP infection in shrimp farms.
Quo vadis? Central Rules of Pathogen and Disease Tropism
Authors: McCall Laura-Isobel
Published: February 2021

Understanding why certain people get sick and die while others recover or never become ill is a fundamental question in biomedical research. A key determinant of this process is pathogen and disease tropism: the locations that become infected (pathogen tropism), and the locations that become damaged (disease tropism). Identifying the factors that regulate tropism is essential to understand disease processes, but also to drive the development of new interventions. This review intersects research from across infectious diseases to define the central mediators of disease and pathogen tropism. This review also highlights methods of study, and translational implications. Overall, tropism is a central but under-appreciated aspect of infection pathogenesis which should be at the forefront when considering the development of new methods of intervention.
Species-Specific Immunological Reactivities Depend on the Cell-Wall Organization of the Two Aspergillus, Aspergillus fumigatus and A. flavus
Authors: Wong Sarah Sze Wah , Venugopalan Lakshmi Prabha , Beaussart Audrey , Karnam Anupama , Mohammed Mohammed Razeeth Shait , Jayapal Jeya Maheshwari , Bretagne Stéphane , Bayry Jagadeesh , Prajna Lalitha , Kuppamuthu Dharmalingam , Latgé Jean-Paul , Aimanianda Vishukumar
Published: February 2021

Although belong to the same genus,Aspergillus fumigatusis primarily involved in invasive pulmonary infection, whereasAspergillus flavusis a common cause of superficial infection. In this study, we compared conidia (the infective propagules) of these twoAspergillusspecies. In immunocompetent mice, intranasal inoculation with conidia ofA. flavusresulted in significantly higher inflammatory responses in the lungs compared to mice inoculated withA. fumigatusconidia.In vitroassays revealed that the dormant conidia ofA. flavus, unlikeA. fumigatusdormant conidia, are immunostimulatory. The conidial surface ofA. fumigatuswas covered by a rodlet-layer, while that ofA. flavuswere presented with exposed polysaccharides.A. flavusharbored significantly higher number of proteins in its conidial cell wall compared toA. fumigatusconidia. Notably, β-1,3-glucan in theA. flavusconidial cell-wall showed significantly higher percentage of branching compared to that ofA. fumigatus. The polysaccharides ensemble ofA. flavusconidial cell wall stimulated the secretion of proinflammatory cytokines, and conidial cell wall associated proteins specifically stimulated IL-8 secretion from the host immune cells. Furthermore, the two species exhibited different sensitivities to antifungal drugs targeting cell wall polysaccharides, proposing the efficacy of species-specific treatment strategies. Overall, the species-specific organization of the conidial cell wall could be important in establishing infection by the twoAspergillusspecies.
EZH2 Dynamically Associates With Non-coding RNAs in Mouse Hearts After Acute Angiotensin II Treatment
Authors: Wang Shun , Guo Ningning , Li Shuangling , He Yuan , Zheng Di , Li Lili , Wang Zhihua
Published: February 2021

Enhancer of zeste 2 (EZH2) governs gene reprogramming during cardiac hypertrophy through epigenetic remodeling, a process regulated by numerous non-coding RNAs (ncRNAs). However, the dynamic interaction between EZH2 and ncRNAs upon hypertrophic stimulation remains elusive. Here we performed an unbiased profiling for EZH2-associated ncRNAs in mouse hearts treated with Angiotensin II (AngII) at different time points (0, 4, and 24 h). The interactions between EZH2 and long ncRNAs (lncRNAs), Chaer, Mirt1, Hotair, and H19, were validated by PCR. RIP-seq analysis identified a total of 126 ncRNAs to be significantly associated with EZH2. These ncRNAs covers all five categories including intergenic, antisense, intron-related, promoter-related and both antisense and promoter-related. According to their changing patterns after AngII treatment, these ncRNAs were clustered into four groups, constantly enhanced, transiently enhanced, constantly suppressed and transiently suppressed. Structural prediction showed that EZH2 bound to hairpin motifs in ncRNAs including snoRNAs. Interaction strength prediction and RNA pull-down assay confirmed the direct interaction between EZH2 and Snora33. Interestingly, two antisense lncRNAs of Malat1, Gm20417, and Gm37376, displayed different binding patterns from their host gene after AngII treatment, suggesting a crucial role of this genomic locus in modulating EZH2 behavior. Our findings reveal the profile of EZH2-associated ncRNAs upon hypertrophic stimulation, and imply a dynamic regulation of EZH2 function in cardiac hypertrophy.
Sex-Specific Patterns of Mortality Predictors Among Patients Undergoing Cardiac Resynchronization Therapy: A Machine Learning Approach
Authors: Tokodi Márton , Behon Anett , Merkel Eperke Dóra , Kovács Attila , Tősér Zoltán , Sárkány András , Csákvári Máté , Lakatos Bálint Károly , Schwertner Walter Richard , Kosztin Annamária , Merkely Béla
Published: February 2021

Background: The relative importance of variables explaining sex-related differences in outcomes is scarcely explored in patients undergoing cardiac resynchronization therapy (CRT). We sought to implement and evaluate machine learning (ML) algorithms for the prediction of 1- and 3-year all-cause mortality in CRT patients. We also aimed to assess the sex-specific differences in predictors of mortality utilizing ML.

Methods: Using a retrospective registry of 2,191 CRT patients, ML models were implemented in 6 partially overlapping patient subsets (all patients, females, or males with 1- or 3-year follow-up). Each cohort was randomly split into training (80%) and test sets (20%). After hyperparameter tuning in the training sets, the best performing algorithm was evaluated in the test sets. Model discrimination was quantified using the area under the receiver-operating characteristic curves (AUC). The most important predictors were identified using the permutation feature importances method.

Results: Conditional inference random forest exhibited the best performance with AUCs of 0.728 (0.645–0.802) and 0.732 (0.681–0.784) for the prediction of 1- and 3-year mortality, respectively. Etiology of heart failure, NYHA class, left ventricular ejection fraction, and QRS morphology had higher predictive power, whereas hemoglobin was less important in females compared to males. The importance of atrial fibrillation and age increased, while the importance of serum creatinine decreased from 1- to 3-year follow-up in both sexes.

Conclusions: Using ML techniques in combination with easily obtainable clinical features, our models effectively predicted 1- and 3-year all-cause mortality in CRT patients. Sex-specific patterns of predictors were identified, showing a dynamic variation over time.
Atmospheric and Oceanographic Forcing Impact Particle Flux Composition and Carbon Sequestration in the Eastern Mediterranean Sea: A Three-Year Time-Series Study in the Deep Ierapetra Basin
Authors: Pedrosa-Pamies Rut , Parinos Constantine , Sanchez-Vidal Anna , Calafat Antoni , Canals Miquel , Velaoras Dimitris , Mihalopoulos Nikolaos , Kanakidou Maria , Lampadariou Nikolaos , Gogou Alexandra
Published: February 2021

Sinking particles are a critical conduit for the export of organic material from surface waters to the deep ocean. Despite their importance in oceanic carbon cycling, little is known about the biotic composition and seasonal variability of sinking particles reaching abyssal depths. Herein, sinking particle flux data, collected in the deep Ierapetra Basin for a three-year period (June 2010 to June 2013), have been examined at the light of atmospheric and oceanographic parameters and main mass components (lithogenic, opal, carbonates, nitrogen, and organic carbon), stable isotopes of particulate organic carbon (POC) and source-specific lipid biomarkers. Our aim is to improve the current understanding of the dynamics of particle fluxes and the linkages between atmospheric dynamics and ocean biogeochemistry shaping the export of organic matter in the deep Eastern Mediterranean Sea. Overall, particle fluxes showed seasonality and interannual variability over the studied period. POC fluxes peaked in spring April–May 2012 (12.2 mg m−2 d−1) related with extreme atmospheric forcing. Summer export was approximately fourfold higher than mean wintertime, fall and springtime (except for the episodic event of spring 2012), fueling efficient organic carbon sequestration. Lipid biomarkers indicate a high relative contribution of natural and anthropogenic, marine- and land-derived POC during both spring (April–May) and summer (June–July) reaching the deep-sea floor. Moreover, our results highlight that both seasonal and episodic pulses are crucial for POC export, while the coupling of extreme weather events and atmospheric deposition can trigger the influx of both marine labile carbon and anthropogenic compounds to the deep Levantine Sea. Finally, the comparison of time series data of sinking particulate flux with the corresponding biogeochemical parameters data previously reported for surface sediment samples from the deep-sea shed light on the benthic–pelagic coupling in the study area. Thus, this study underscores that accounting the seasonal and episodic pulses of organic carbon into the deep sea is critical in modeling the depth and intensity of natural and anthropogenic POC sequestration, and for a better understanding of the global carbon cycle.