bluuebunny/crossref_metadata_2025 huggingface dataset:
Activity of loggerhead turtles during the U-shaped dive: insights using angular velocity metrics
Authors: Gunner RM , Wilson RP , Holton MD , Scott R , Arkwright A , Fahlman A , Ulrich M , Hopkins P , Duarte C , Eizaguirre C
Published: March 2021

Understanding the behavioural ecology of endangered taxa can inform conservation strategies. The activity budgets of the loggerhead turtle Caretta caretta are still poorly understood because many tracking methods show only horizontal displacement and ignore dives and associated behaviours. However, time-depth recorders have enabled researchers to identify flat, U-shaped dives (or type 1a dives) and these are conventionally labelled as resting dives on the seabed because they involve no vertical displacement of the animal. Video- and acceleration-based studies have demonstrated this is not always true. Focusing on sea turtles nesting on the Cabo Verde archipelago, we describe a new metric derived from magnetometer data, absolute angular velocity, that integrates indices of angular rotation in the horizontal plane to infer activity. Using this metric, we evaluated the variation in putative resting behaviours during the bottom phase of type 1a dives for 5 individuals over 13 to 17 d at sea during a single inter-nesting interval (over 75 turtle d in total). We defined absolute resting within the bottom phase of type 1a dives as periods with no discernible acceleration or angular movement. Whilst absolute resting constituted a significant proportion of each turtle’s time budget for this 1a dive type, turtles allocated 16-38% of their bottom time to activity, with many dives being episodic, comprised of intermittent bouts of rest and rotational activity. This implies that previously considered resting behaviours are complex and need to be accounted for in energy budgets, particularly since energy budgets may impact conservation strategies.
The effect of plant density on seed yield and quality of carrot (Daucus carota L.)
Authors: Merfield C.N. , Hampton J.G. , Wratten S.D. , Prapanoppasin P. , Yeeransiri P.
Published: March 2021

The hypothesis that by increasing carrot (Daucus carota) plant density the contribution to seed yield by the primary umbels would increase, and that therefore both seed yield and seed quality would increase, was examined in two experiments in different years in Canterbury. A radial trial design provided plant densities from 2 to 84 plants/m2 and from 4 to 100 plants/m2 in experiments one and two respectively. Seed yield increased with increasing plant density in both experiments, and at the highest density the primary umbels contributed 90% (experiment one) and 60% (experiment two) of the seed yield. In both experiments seeds from the primary umbels had a greater thousand seed weight and higher germination than those from the other order umbels, and for the second experiment they also had higher seed vigour. The quality of seeds from the primary umbels was consistently higher than that of seeds from the secondary umbels across all plant densities, and for the latter, both germination and seed vigour declined as plant density increased. These results therefore support the hypothesis, and densities higher than the 20 plants/m2 currently used commercially have the potential to increase both seed yield and quality. Keywords: seed production, primary umbels, germination, vigour, plants/m2
Mexico Inside Out: People, Politics and Culture
Authors:   Latin America Bureau, Caistor Nick
Published: March 2021

Mexico Inside Out provides an introduction to the country for the student and traveller alike, people who want to know more about the real Mexico than is found in an ordinary guidebook.
INFLUÊNCIA DO MEIO SALINO NA RESISTÊNCIA MECÂNICA E TENACIDADE DO AÇO INOXIDÁVEL FERRITICO K39MD
Authors: Andrade Gabriel Zangrande De , Virgens Rosivaldo Pereira Das , Angeloni Mauricio , Bosquetti Péricles
Published: March 2021

A busca pela eficiência é uma vertente em praticamente todos os setores da economia. Não é diferente para o setor industrial, cada dia mais competitivo e tecnológico, a procura constante por novos produtos e por novas formas de se produzir ganha cada vez mais espaço desde o chão de fábrica até a alta diretoria das empresas. A relação custo por benefício é um fator fundamental para as empresas sobreviverem no mercado globalizado. O aço inoxidável ferrítico K39MD, produzido pela ArcelorMittal, traz novas possibilidades e promessas de durabilidade aos componentes e peças com ele fabricados. Um estudo detalhado deste aço, levando-se em consideração as reais solicitações a que estará submetido, torna-se imperativo para uma aplicação segura e confiável do produto. Este trabalho teve por objetivo o estudo do aço inoxidável ferrítico K39MD quanto as intempéries do meio. Após a realização de ensaios de Salt Spray, as amostras foram ensaiadas para a verificação da influência do meio salino nas propriedades mecânicas do aço em estudo, que se mostrou altamente resistente a degradação em função dos tempos de exposição.
INVESTIGAÇÕES SOBRE FUNÇÕES LUCRO DE 3º GRAU GENÉRICA
Authors: Bosquetti Diógenes , Bosquetti Péricles , Angeloni Maurício , Maluf Omar , Silva Roberta Ângela Da
Published: March 2021

Uma generalização da função lucro é estudada, considerando que a mesma possa ser expressa por função polinomial do terceiro grau L(x) = ax3 + bx2 + cx + d, com coeficientes reais “a”, “b”, “c” e “d” arbitrários e “a” não nulo. Neste cenário, uma dada função lucro poderá conter pontos de máximo e mínimo local, sendo sua região de validade investigada. A ordem de aparecimento dos pontos de máximo e mínimo local varia de acordo com o sinal do parâmetro “a”. Para a > 0, o ponto de máximo precede o de mínimo local, sendo tal ordem invertida para a < 0. Igualmente se considera os comportamentos da função lucro quando a mesma está submetida a restrição adicional que diz que o parâmetro “x”, o qual é o alicerce da função lucro só poderá assumir valores positivos ou nulos. Igualmente são investigados os pontos de equilíbrio desta função, a qual a ocorrem quando a função receita R(x) e a função custo C(x) se equivalham.
INFLUÊNCIA DA MICROESTRUTURA DE UM AÇO SAE 1095 NA RESISTÊNCIA AO DESGASTE ABRASIVO
Authors: Farah Alessandro Fraga , Farah Solange Pereira dos Santos , Gomes Márcia Aparecida , Santos Vinicius Henrique Dos , Oliveira Anderson Luís De
Published: March 2021

O objetivo deste trabalho foi estudar um aço SAE 1095, fundido, com diferentes tratamentos térmicos para verificar a influência da microestrutura na resistência ao desgaste abrasivo. Os corpos de prova foram submetidos a tratamentos térmicos, ensaios de dureza e ensaios de desgaste abrasivo e caracterização microestrutural. Foram realizados tratamentos térmicos de normalização a 900°C seguido de resfriamento ao ar; têmpera partindo de 900°C de austenitização e resfriado em água; têmpera partindo de 800°C de austenitização e resfriado em água; revenimento em duas temperaturas diferentes sendo a primeira a 205°C e a segunda a 420°C, sendo o resfriamento realizado ao ar. Posteriormente, as medidas de dureza foram efetuadas, e em seguida foram realizados os ensaios de desgaste abrasivo do tipo roda de borracha (ASTM G65). A caracterização microestrutural foi feita por microscopia ótica, utilizando diferentes ataques químicos para melhor identificação das fases. Os resultados obtidos neste trabalho mostraram um material com boa resistência ao desgaste abrasivo, dependendo da sua condição microestrutural.
O PERFIL DE BIG DATA
Authors: Bergamo Luciano , Teixeira Sabrina dos Santos
Published: March 2021

O profissional de Big Data, engenheiro, é responsável por automatizar os processos de grande quatidades de dados e tratá-los de forma correta para tomadas de decisões e coloca em função áreas de programação que ajuda no cruzamento dos dados, limpeza e geração de resultados. O contexto Big Data engloba muitos setores da área de TI, tornando hoje um dos segmentos da Tecnologia da Informação em grande crescimento e sempre buscando profissionais de alto nível. Além de Cientistas de Dados e Engenheiros de Dados existem os Engenheiros de Machine Learning, que são profissionais responsáveis pelo aprendizado das máquinas. O objetivo desta pesquisa é identificar profissões emergentes relacionadas ao contexto da Ciência de Dados de forma a oferecer aos públicos, acadêmico e empresarial, alternativas de formação e capacitação nesta área e apresentar algumas obras e autores relacionados ao assunto. Os procedimentos metodológicos estão associados a uma pesquisa bibliográfica com a finalidade de identificar as profissões emergentes no mercado de Tecnologia da Informação voltado para a valorização dos dados. Entre as profissões pesquisadas e discutidas, nota-se que Cientistas e Engenheiros de Dados têm funções similares, porém, o Engenheiro de Dados é mais envolvido com o estudo da estrutura de suporte aos dados, incluindo hardware e software. Já o Cientista de Dados trabalha no quesito de linguagem de máquina “Machine Learning”, onde os processos são automatizados para filtrar grandes volumes de dados e obter os melhores resultados possíveis, também denominados como dados limpos.
A NOVA POLÍTICA DE DESENVOLVIMENTO ECONÔMICO PAULISTA E O POLO METALOMECÂNICO DE SERTÃOZINHO-SP
Authors: Bosquetti Diógenes , Maluf Omar , Marinho Clésio Aparecido , Sordan Juliano Endrigo , Farah Alessandro Fraga
Published: March 2021

O arranjo produtivo local das indústrias de Sertãozinho foi alvo de pesquisa da Faculdade de Tecnologia “Deputado Waldyr Alceu Trigo”. Nesta pesquisa, diversas características e particularidades das empresas foram obtidas, permitindo obter dados e informações de seu atual estado, bem como conhecendo suas aspirações, anseios e medos. Recentemente, o governo do Estado de São Paulo anunciou a implantação de uma política de desenvolvimento, o qual tal polo se encontra inserido. Os principais pilares desta ação governamental são: Simplificação Tributária, Redução de Impostos, Incentivos Fiscais, Novas Linhas de Crédito, Investimentos em Tecnologia e Inovação, Qualificação de mão de obra, Investimentos em Infraestrutura e serviços, Desburocratização. Assim sendo, investiga-se como tais fatores podem influenciar tal parque tecnológico, tendo em vista sua modernização, desenvolvimento e diversificação de sua produção. A metodologia de prospecção de dados adotada foi a de envio e coleta de questionários individualizados nas empresas de Sertãozinho/SP, bem como a realização de visitas técnicas às corporações da localidade.
LOGÍSTICA VERDE
Authors: Oliveira Alana Naiara Conrado , Melo Janayna Coelho de , Teixeira Cassia Regina Bianchini , Moya Murilo Tomazini Munhoz
Published: March 2021

A logística desempenha um importante papel dentro da empresa em relação aos custos e, também, em relação à emissão de poluentes no meio ambiente. Diante desta importância, a presente pesquisa tem o objetivo de analisar à logística verde como importante alternativa para o desenvolvimento sustentável, abordando seus benefícios e, também, descrever os processos necessários à aplicação da logística verde. A metodologia aplicada ao trabalho foi o estudo exploratório-descritivo, de natureza qualitativa, para tanto foi utilizado como meio a revisão bibliográfica, documental, artigos científicos, livros e revistas especializadas. Apurou-se que as legislações desempenham um papel muito importante na adequação ambiental, neste sentido, o mercado externo é o mais exigente. A busca por uma fatia do mercado externo contribui de forma significativa para a evolução dos pilares da sustentabilidade empresarial. Conclui-se que embora a logística verde seja um conceito novo no mercado brasileiro, algumas empresas já utilizam essa ferramenta logística. As práticas da logística verde comprovadamente melhoram o desempenho ambiental e organizacional.
DEMOCRACIA NAS ETECS BASEADA NA LEGISLAÇÃO
Authors: Santos Silvania Soares da Silva , Meirelles Raquel Gomes , Ventura Junior Antonio Carlos Muniz
Published: March 2021

As discussões sobre o conceito de gestão democrática na escola, o processo de democratização do acesso ao ensino público, a estrutura burocrática na instituição e a participação da comunidade, faz do diretor escolar um administrador e/ou gestor da unidade, pautada em ações burocráticas e técnicas em que são questionadas as condições de administrar a estrutura e a inter-relação com a comunidade, para que o desenvolvimento educacional ocorra com transparência e qualidade nas escolas técnicas estaduais, alimentando o interesse dos alunos na sua capacitação e posicionamento profissional no mercado de trabalho. Assim, a legislação vem de encontro com a democracia nas instituições e questiona a postura do diretor ou legislador educacional na gestão democrática das escolas técnicas estaduais, em função do seu gerenciamento e sua capacidade na formação dos pilares da participação do corpo docente, comunidade e poder público nas demandas do mercado profissionalizante. Analisar a forma de provimento da direção das Escolas Técnicas Estaduais é o objetivo da presente pesquisa. Esse objetivo se desdobrará na discussão em torno de eleição, indicação ou concurso para o provimento do cargo, contextualizando historicamente as formas utilizadas pelo centro para o exercício dessa função/cargo, desde 1980 até 2018, que servirá de pano de fundo para a análise da problemática em torno das questões que envolve o papel do gestor escolar na direção das escolas técnicas estaduais.
Konya Ekolojik Koşullarında Farklı Şeker Mısır (Zea mays saccharata Sturt) Genotiplerinin Verim ve Verim Komponentlerinin Belirlenmesi
Authors: TEZEL Mehmet , GÖNÜLAL Erdal , ARICI Ramazan Çağatay , ÖZCAN Gazi
Published: March 2021

Bu çalışma Konya ekolojik koşullarında bazı şeker mısır genotiplerinin verim ve tarımsal özelliklerini belirlemek amacıyla iki yıl (2018-2019) süreyle yürütülmüştür. Tesadüf blokları deneme desenine göre üç tekerrürlü olarak yürütülen çalışmada 3 ticari çeşit (Batem Tatlı, Merit, Caramelo) ve 4 aday melez (ŞADA-1, ŞADA-12, ŞADA-16, ŞADA 42) olmak üzere toplam yedi genotip kullanılmıştır.

Çalışmada iki yılın ortalamaları üzerinden tane verimi 329 kg/da (Caramelo) - 690 kg/da (ŞADA-42), taze koçan verimi 847 kg/da (Caramelo) - 1259 kg /da (ŞADA-42), bitki boyu 128 cm (Caramelo) - 236 cm (ŞADA-42), çiçeklenme gün sayısı 69 gün (ŞADA-42)- 72.7 gün (BATEM Tatlı), koçan çapı 43.9 mm (ŞADA-12) -48.5 (Merit), koçan uzunluğu 15.2 cm (Merit)-19.6 cm (ŞADA-42), ilk koçan yüksekliği 35.2 cm (Caramelo)-79.8 cm (ŞADA-42), tane/koçan oranı % 80 (ŞADA-42)-% 84.9 (ŞADA-12), ve hasatta tane nemi% 12.6 (Caramelo)- % 14.9 (Batem Tatlı) aralığında elde edilmiştir. Çalışma sonucunda Orta Anadolu bölgesi için tane verimi ve yeşil koçan verimi açısından ŞADA-42 ve ŞADA-12 aday melezlerinin ön plana çıktığı görülmüştür.
Changes in the Leaf Physiological Characteristics and Tissue-Specific Distribution of Ginsenosides in Panax ginseng During Flowering Stage Under Cold Stress
Authors: Zhang Tao , Chen Changbao , Chen Yuqiu , Zhang Qinghe , Li Qiong , Qi Weichen
Published: March 2021

Panax ginseng is a valuable traditional herbal medicine material with numerous applications. Ginsenosides are the key bioactive compounds in ginseng. Cold stress can activate stress tolerance mechanisms that regulate biomass and biosynthesis in ginseng tissue. In this study, the effects of short- and long-term cold stress (5°C) on the physiological characteristics, tissue-specific ginsenoside distributions, and ginsenoside synthesis gene expressions of 3-year-old P. ginseng during the flowering period were investigated. Short-term cold stress significantly reduced ginseng biomass (root fresh weight and dry weight), and increased malondialdehyde, proline, soluble sugar, and soluble protein concentrations. Superoxide dismutase, peroxidase, and catalase activities also increased significantly under cold stress. With prolongation of the cold stress period, all antioxidant enzyme activity decreased. The protopanaxatriol-type ginsenoside concentrations in the taproots (phloem and xylem) and fibrous roots, as well as the protopanaxadiol-type ginsenoside concentrations in the leaves, increased significantly under short-term cold stress. The key genes (SE, DS-II, CYP716A52v2, and CYP716A53v2) involved in the ginsenoside biosynthesis pathway were significantly positively correlated with the ginsenoside accumulation trends. Thus, short-term cold stress can stimulate membrane lipid peroxidation, in turn stimulating the antioxidant enzyme system to alleviate oxidative damage and increasing the expression of key enzyme genes involved in ginsenoside biosynthesis. During agricultural production, protopanaxadiol/protopanaxatriol ratios could be manipulated by low-temperature storage or treatments.
Mitochondrial Dysfunction: Cause or Consequence of Vascular Calcification?
Authors: Phadwal Kanchan , Vrahnas Christina , Ganley Ian G. , MacRae Vicky E.
Published: March 2021

Mitochondria are crucial bioenergetics powerhouses and biosynthetic hubs within cells, which can generate and sequester toxic reactive oxygen species (ROS) in response to oxidative stress. Oxidative stress-stimulated ROS production results in ATP depletion and the opening of mitochondrial permeability transition pores, leading to mitochondria dysfunction and cellular apoptosis. Mitochondrial loss of function is also a key driver in the acquisition of a senescence-associated secretory phenotype that drives senescent cells into a pro-inflammatory state. Maintaining mitochondrial homeostasis is crucial for retaining the contractile phenotype of the vascular smooth muscle cells (VSMCs), the most prominent cells of the vasculature. Loss of this contractile phenotype is associated with the loss of mitochondrial function and a metabolic shift to glycolysis. Emerging evidence suggests that mitochondrial dysfunction may play a direct role in vascular calcification and the underlying pathologies including (1) impairment of mitochondrial function by mineral dysregulation i.e., calcium and phosphate overload in patients with end-stage renal disease and (2) presence of increased ROS in patients with calcific aortic valve disease, atherosclerosis, type-II diabetes and chronic kidney disease. In this review, we discuss the cause and consequence of mitochondrial dysfunction in vascular calcification and underlying pathologies; the role of autophagy and mitophagy pathways in preventing mitochondrial dysfunction during vascular calcification and finally we discuss mitochondrial ROS, DRP1, and HIF-1 as potential novel markers and therapeutic targets for maintaining mitochondrial homeostasis in vascular calcification.
Inhibition of TGF-β/Smad3 Signaling Disrupts Cardiomyocyte Cell Cycle Progression and Epithelial–Mesenchymal Transition-Like Response During Ventricle Regeneration
Authors: Peng Yuanyuan , Wang Wenyuan , Fang Yunzheng , Hu Haichen , Chang Nannan , Pang Meijun , Hu Ye-Fan , Li Xueyu , Long Han , Xiong Jing-Wei , Zhang Ruilin
Published: March 2021

Unlike mammals, zebrafish can regenerate injured hearts even in the adult stage. Cardiac regeneration requires the coordination of cardiomyocyte (CM) proliferation and migration. The TGF-β/Smad3 signaling pathway has been implicated in cardiac regeneration, but the molecular mechanisms by which this pathway regulates CM proliferation and migration have not been fully illustrated. Here, we investigated the function of TGF-β/Smad3 signaling in a zebrafish model of ventricular ablation. Multiple components of this pathway were upregulated/activated after injury. Utilizing a specific inhibitor of Smad3, we detected an increased ratio of unrecovered hearts. Transcriptomic analysis suggested that the TGF-β/Smad3 signaling pathway could affect CM proliferation and migration. Further analysis demonstrated that the CM cell cycle was disrupted and the epithelial–mesenchymal transition (EMT)-like response was impaired, which limited cardiac regeneration. Altogether, our study reveals an important function of TGF-β/Smad3 signaling in CM cell cycle progression and EMT process during zebrafish ventricle regeneration.
Changes in the Cystic Fibrosis Airway Microbiome in Response to CFTR Modulator Therapy
Authors: Yi Buqing , Dalpke Alexander H. , Boutin Sébastien
Published: March 2021

The development of CFTR modulator therapies significantly changed the treatment scheme of people with cystic fibrosis. However, CFTR modulator therapy is still a life-long treatment, which is not able to correct the genetic defect and cure the disease. Therefore, it becomes crucial to understand the effects of such modulation of CFTR function on the airway physiology, especially on airway infections and inflammation that are currently the major life-limiting factors in people with cystic fibrosis. In this context, understanding the dynamics of airway microbiome changes in response to modulator therapy plays an essential role in developing strategies for managing airway infections. Whether and how the newly available therapies affect the airway microbiome is still at the beginning of being deciphered. We present here a brief review summarizing the latest information about microbiome alterations in light of modern cystic fibrosis modulator therapy.
Transcriptomic and Metabolomic Analysis Revealed Roles of Yck2 in Carbon Metabolism and Morphogenesis of Candida albicans
Authors: Liboro Karl , Yu Seong-Ryong , Lim Juhyeon , So Yee-Seul , Bahn Yong-Sun , Eoh Hyungjin , Park Hyunsook
Published: March 2021

Candida albicans is a part of the normal microbiome of human mucosa and is able to thrive in a wide range of host environments. As an opportunistic pathogen, the virulence of C. albicans is tied to its ability to switch between yeast and hyphal morphologies in response to various environmental cues, one of which includes nutrient availability. Thus, metabolic flexibility plays an important role in the virulence of the pathogen. Our previous study has shown that C. albicans Yeast Casein Kinase 2 (CaYck2) regulates the yeast-to-hyphal switch, but its regulatory mechanisms remain unknown. This study further elucidated the role of Yck2 in governing morphology and carbon metabolism by analyzing the transcriptome and metabolome of the C. albicans YCK2 deletion mutant strain (yck2Δ strain) in comparison to the wild type strain. Our study revealed that loss of CaYck2 perturbs carbon metabolism, leading to a transcriptional response that resembles a transcriptional response to glucose starvation with coinciding intracellular accumulation of glucose and depletion of TCA cycle metabolites. This shift in the metabolome is likely mediated by derepression of glucose-repressed genes in the Mig1/2-mediated glucose sensing pathway and by downregulation of glycolytic genes, possibly through the Rgt1-mediated SRR pathway. In addition, genes involved in beta-oxidation, glyoxylate cycle, oxidative stress response, and arginine biosynthesis were upregulated in the yck2Δ strain, which is highly reminiscent of C. albicans engulfment by macrophages. This coincides with an increase in arginine degradation intermediates in the yck2Δ strain, suggesting arginine catabolism as a potential mechanism of CaYck2-mediated filamentation as seen during C. albicans escape from macrophages. Transcriptome analysis also shows differential expression of hyphal transcriptional regulators Nrg1 and Ume6. This suggests dysregulation of hyphal initiation and elongation in the yck2Δ strain which may lead to the constitutive pseudohyphal phenotype of this strain. Metabolome analysis also detected a high abundance of methyl citrate cycle intermediates in the yck2Δ strain, suggesting the importance of CaYck2 in this pathway. Taken together, we discovered that CaYck2 is an integral piece of carbon metabolism and morphogenesis of C. albicans.
Modeling of Urinary Microbiota Associated With Cystitis
Authors: Ceprnja Marina , Oros Damir , Melvan Ena , Svetlicic Ema , Skrlin Jasenka , Barisic Karmela , Starcevic Lucija , Zucko Jurica , Starcevic Antonio
Published: March 2021

A decade ago, when the Human Microbiome Project was starting, urinary tract (UT) was not included because the bladder and urine were considered to be sterile. Today, we are presented with evidence that healthy UT possesses native microbiota and any major event disrupting its “equilibrium” can impact the host also. This dysbiosis often leads to cystitis symptoms, which is the most frequent lower UT complaint, especially among women. Cystitis is one of the most common causes of antimicrobial drugs prescriptions in primary and secondary care and an important contributor to the problem of antimicrobial resistance. Despite this fact, we still have trouble distinguishing whether the primary cause of majority of cystitis cases is a single pathogen overgrowth, or a systemic disorder affecting entire UT microbiota. There are relatively few studies monitoring changes and dynamics of UT microbiota in cystitis patients, making this field of research still an unknown. In this study variations to the UT microbiota of cystitis patients were identified and microbial dynamics has been modeled. The microbial genetic profile of urine samples from 28 patients was analyzed by 16S rDNA Illumina sequencing and bioinformatics analysis. One patient with bacterial cystitis symptoms was prescribed therapy based on national guideline recommendations on antibacterial treatment of urinary tract infections (UTI) and UT microbiota change was monitored by 16S rDNA sequencing on 24 h basis during the entire therapy duration. The results of sequencing implied that a particular class of bacteria is associated with majority of cystitis cases in this study. The contributing role of this class of bacteria – Gammaproteobacteria, was further predicted by generalized Lotka-Volterra modeling (gLVM). Longitudinal microbiota insight obtained from a single patient under prescribed antimicrobial therapy revealed rapid and extensive changes in microbial composition and emphasized the need for current guidelines revision in regards to therapy duration. Models based on gLVM indicated protective role of two taxonomic classes of bacteria, Actinobacteria and Bacteroidia class, which appear to actively suppress pathogen overgrowth.
Chitosan-Based Nanoparticles Against Viral Infections
Authors: Boroumand Homa , Badie Fereshteh , Mazaheri Samaneh , Seyedi Zeynab Sadat , Nahand Javid Sadri , Nejati Majid , Baghi Hossein Bannazadeh , Abbasi-Kolli Mohammad , Badehnoosh Bita , Ghandali Maryam , Hamblin Michael R. , Mirzaei Hamed
Published: March 2021

Viral infections, in addition to damaging host cells, can compromise the host immune system, leading to frequent relapse or long-term persistence. Viruses have the capacity to destroy the host cell while liberating their own RNA or DNA in order to replicate within additional host cells. The viral life cycle makes it challenging to develop anti-viral drugs. Nanotechnology-based approaches have been suggested to deal effectively with viral diseases, and overcome some limitations of anti-viral drugs. Nanotechnology has enabled scientists to overcome the challenges of solubility and toxicity of anti-viral drugs, and can enhance their selectivity towards viruses and virally infected cells, while preserving healthy host cells. Chitosan is a naturally occurring polymer that has been used to construct nanoparticles (NPs), which are biocompatible, biodegradable, less toxic, easy to prepare, and can function as effective drug delivery systems (DDSs). Furthermore, chitosan is Generally Recognized as Safe (GRAS) by the US Food and Drug Administration (U.S. FDA). Chitosan NPs have been used in drug delivery by the oral, ocular, pulmonary, nasal, mucosal, buccal, or vaginal routes. They have also been studied for gene delivery, vaccine delivery, and advanced cancer therapy. Multiple lines of evidence suggest that chitosan NPs could be used as new therapeutic tools against viral infections. In this review we summarize reports concerning the therapeutic potential of chitosan NPs against various viral infections.
The Expandables: Cracking the Staphylococcal Cell Wall for Expansion Microscopy
Authors: Kunz Tobias C. , Rühling Marcel , Moldovan Adriana , Paprotka Kerstin , Kozjak-Pavlovic Vera , Rudel Thomas , Fraunholz Martin
Published: March 2021

Expansion Microscopy (ExM) is a novel tool improving the resolution of fluorescence microscopy by linking the sample into a hydrogel that gets physically expanded in water. Previously, we have used ExM to visualize the intracellular Gram-negative pathogens Chlamydia trachomatis, Simkania negevensis, and Neisseria gonorrhoeae. Gram-positive bacteria have a rigid and thick cell wall that impedes classic expansion strategies. Here we developed an approach, which included a series of enzymatic treatments resulting in isotropic 4× expansion of the Gram-positive pathogen Staphylococcus aureus. We further demonstrate the suitability of the technique for imaging of planktonic bacteria as well as endocytosed, intracellular bacteria at a spatial resolution of approximately 60 nm with conventional confocal laser scanning microscopy.
Multiscale Risk Factors of Cardiovascular Disease: CLSA Analysis of Genetic and Psychosocial Factors
Authors: Menniti Gabriella , Paquet Catherine , Han Hannah Yang , Dube Laurette , Nielsen Daiva E.
Published: March 2021

Background: Cardiovascular disease (CVD) is a complex disease resulting from multiscale risk factors including genetics, age, and psychosocial factors (PSFs) such as depression and social isolation. However, previous research has lacked in operationalizing multiscale risk factors to determine individual and interactive associations over the life course. Therefore, this study aimed to evaluate individual and interactive associations of multiscale risk factors for CVD outcomes including genetics and PSFs at middle and older-aged stages of the life course.

Methods: Baseline data from the Canadian Longitudinal Study on Aging (CLSA; n = 9,892 with genome-wide genotyping data) was used for this investigation. A 39 single nucleotide polymorphism polygenic risk score (PRS) for CVD was constructed. PSFs consisted of: (1) Depressive symptoms categorized into: “none” (Group 1, reference), “current” (Group 2), “clinical depression with no current symptoms” (Group 3), and “potential, recurrent depression” (Group 4); and (2) Social isolation index as a binary variable comprised of marital status, living arrangements, retirement status, contacts, and social participation. Heart-related disorders (HRD: myocardial infarction, angina and heart disease) was the primary outcome of interest and peripheral/vascular-related disorders (PVRD: stroke, peripheral vascular disease and hypertension) was the secondary outcome. Multivariable logistic regression models adjusted for socio-demographic factors were conducted stratified by age group (middle-aged: 45–69 years, older-aged: ≥70 years).

Results: PRS was associated with HRD among middle- and older-aged participants [OR (95% confidence interval)] [1.06 (1.03–1.08), 1.06 (1.03–1.08), respectively]. Most depressive symptoms groups compared to the reference associated with HRD and PVRD, but only Group 4 associated with PVRD among older-aged [1.69 (1.08–2.64)]. Social isolation was associated with only PVRD among middle-aged [1.84 (1.04–3.26)]; however, socially isolated CLSA participants were underrepresented in the genotyped cohort (1.2%). No significant PRS*PSFs interactions were observed.

Conclusions: Genetics and PSFs are independently associated with CVD. Varying observations across age groups underscores the need to advance research on multiscale risk factors operating both at a given point in time and over the life course. Future cohort studies may benefit from use of mobile assessment units to enable better reach to socially isolated participants for collection of biospecimens.
Genetic and Cellular Interaction During Cardiovascular Development Implicated in Congenital Heart Diseases
Authors: Kodo Kazuki , Uchida Keiko , Yamagishi Hiroyuki
Published: March 2021

Congenital heart disease (CHD) is the most common life-threatening congenital anomaly. CHD occurs due to defects in cardiovascular development, and the majority of CHDs are caused by a multifactorial inheritance mechanism, which refers to the interaction between genetic and environmental factors. During embryogenesis, the cardiovascular system is derived from at least four distinct cell lineages: the first heart field, second heart field, cardiac neural crest, and proepicardial organ. Understanding the genes involved in each lineage is essential to uncover the genomic architecture of CHD. Therefore, we provide an overview of recent research progress using animal models and mutation analyses to better understand the molecular mechanisms and pathways linking cardiovascular development and CHD. For example, we highlight our recent work on genes encoding three isoforms of inositol 1,4,5-trisphosphate receptors (IP3R1, 2, and 3) that regulate various vital and developmental processes, which have genetic redundancy during cardiovascular development. Specifically, IP3R1 and 2 have redundant roles in the atrioventricular cushion derived from the first heart field lineage, whereas IP3R1 and 3 exhibit redundancy in the right ventricle and the outflow tract derived from the second heart field lineage, respectively. Moreover, 22q11.2 deletion syndrome (22q11DS) is highly associated with CHD involving the outflow tract, characterized by defects of the cardiac neural crest lineage. However, our studies have shown thatTBX1, a major genetic determinant of 22q11DS, was not expressed in the cardiac neural crest but rather in the second heart field, suggesting the importance of the cellular interaction between the cardiac neural crest and the second heart field. Comprehensive genetic analysis using the Japanese genome bank of CHD and mouse models revealed that a molecular regulatory network involving GATA6, FOXC1/2, TBX1, SEMA3C, and FGF8 was essential for reciprocal signaling between the cardiac neural crest and the second heart field during cardiovascular development. Elucidation of the genomic architecture of CHD using induced pluripotent stem cells and next-generation sequencing technology, in addition to genetically modified animal models and human mutation analyses, would facilitate the development of regenerative medicine and/or preventive medicine for CHD in the near future.
Tablet-Based Automatic Assessment for Early Detection of Alzheimer's Disease Using Speech Responses to Daily Life Questions
Authors: Yamada Yasunori , Shinkawa Kaoru , Kobayashi Masatomo , Nishimura Masafumi , Nemoto Miyuki , Tsukada Eriko , Ota Miho , Nemoto Kiyotaka , Arai Tetsuaki
Published: March 2021

Health-monitoring technologies for automatically detecting the early signs of Alzheimer's disease (AD) have become increasingly important. Speech responses to neuropsychological tasks have been used for quantifying changes resulting from AD and differentiating AD and mild cognitive impairment (MCI) from cognitively normal (CN). However, whether and how other types of speech tasks with less burden on older adults could be used for detecting early signs of AD remains unexplored. In this study, we developed a tablet-based application and compared speech responses to daily life questions with those to neuropsychological tasks in terms of differentiating MCI from CN. We found that in daily life questions, around 80% of speech features showing significant differences between CN and MCI overlapped those showing significant differences in both our study and other studies using neuropsychological tasks, but the number of significantly different features as well as their effect sizes from life questions decreased compared with those from neuropsychological tasks. On the other hand, the results of classification models for detecting MCI by using the speech features showed that daily life questions could achieve high accuracy, i.e., 86.4%, comparable to neuropsychological tasks by using eight questions against all five neuropsychological tasks. Our results indicate that, while daily life questions may elicit weaker but statistically discernable differences in speech responses resulting from MCI than neuropsychological tasks, combining them could be useful for detecting MCI with comparable performance to using neuropsychological tasks, which could help develop health-monitoring technologies for early detection of AD in a less burdensome manner.
Locating Thunder Source Using a Large-Aperture Micro-Barometer Array
Authors: Rusz Jan , Chum Jaroslav , Baše Jiří
Published: March 2021

Lightning generates sound waves across a wide range of frequencies, including infrasonic waves below 20 Hz. Source mechanism for these low frequency pulses is still area for debate. Infrasound pulses detected after rapid changes of electrostatic field during the thunderstorm activity were analyzed. The measurements were done by large aperture array of absolute microbarometers located in the Western part of the Czech Republic. Distances between four measuring sites are in the range of 4–10 km. The infrasound source position was calculated from time delays between the rapid change of electrostatic field and infrasound signal arrival to the individual microbarometers assuming propagation of spherical waves from the source. Only cases with a sufficient signal-to-noise ratio on all four microbarometers were analyzed. The variation of sound speed with height due to temperature height profile was taken into account. For most of the analyzed cases, the calculated infrasound source position corresponds to the lightning location determined by European lightning detection network (EUCLID). The calculated height of infrasound source is most often 3–5 km.
ESL Teacher Certification Policy: Current Trends and Best Practices
Authors: Gras Christopher , Kitson Christina
Published: March 2021

Utilizing aspects of the Standards for Initial TESOL Pre-K-12 Teacher Preparation Programs (2018), this study seeks to review and critique current trends in ESL teacher certification policy nationwide. Data collection involved triangulating state policies found online with a brief questionnaire sent to teacher certification boards nationwide (51 in total). The researchers focused on whether or not state policies: (1) offer initial and/or add-on ESL certification; (2) have a test-out option for add-on ESL certification; (3) require a certain number of credits for add-on ESL certification; (4) align their coursework topic requirements with guidelines set forth by TESOL. Data analysis highlighted changes in policy from a previous survey conducted during the NCLB era (Reeves, 2010), and compared requirements in each state’s policy to the Standards for Initial TESOL Pre-K-12 Teacher Preparation Programs (2018). Findings reveal an alarming trend toward less rigorous add-on certification (i.e., endorsement) pathways as well as a number of states either no longer offering initial certification or providing options for testing-out of coursework altogether. Additionally, many state policies outline required coursework, but few follow ESL teacher preparation guidelines set by TESOL International Association (TESOL) (2019). This has led to a notable rift between current ESL teacher education policy and evidence-based best practices such as coursework on the linguistic and cultural aspects of second language learning.
Case Report: Pheochromocytoma and Synchronous Neuroblastoma in a Family With Hereditary Pheochromocytoma Associated With a MAX Deleterious Variant
Authors: Duarte Diana Borges , Ferreira Lia , Santos Ana P. , Costa Cláudia , Lima Jorge , Santos Catarina , Afonso Mariana , Teixeira Manuel R. , Carvalho Rui , Cardoso Maria Helena
Published: March 2021

Introduction

Pheochromocytomas are rare catecholamine-producing neuroendocrine tumours arising from chromaffin cells of the adrenal medulla or extra-adrenal sympathetic paraganglia. Recent studies have indicated that up to 40% of pheochromocytomas could be attributable to an inherited germline variant in an increasing list of susceptibility genes. Germline variants of the MYC-associated factor (MAX) gene have been associated with familial pheochromocytomas and paragangliomas with an autosomal dominant pattern of inheritance, a median age at onset of 33 years and an overall frequency estimated at 1.9%. We describe a deleterious MAX variant associated with hereditary pheochromocytoma in a family with four affected individuals.

Case presentation

The first patient presented with bilateral pheochromocytoma in 1995; genetic testing was proposed to his oldest son, when he was diagnosed with a bilateral pheochromocytoma with a synchronous neuroblastoma. Upon the identification of the MAX variant c.97C>T, p.(Arg33Ter), in the latter individual, his two siblings and their father were tested and the same variant was identified in all of them. Both siblings were subsequently diagnosed with pheochromocytoma (one of them bilateral) and choose to remain on active surveillance before they were submitted to adrenalectomy. All the tumours secreted predominantly norepinephrine, accordingly to the typical biochemical phenotype ascribed to variants in the MAX gene.

Conclusion

This case series is, to our knowledge, the one with the largest number of individuals with hereditary pheochromocytoma with a deleterious MAX variant in the same family. It is also the first case with a synchronous pheochromocytoma and neuroblastoma in carriers of a MAX deleterious variant. This report draws attention to some ill-defined features of pheochromocytoma and other malignancies associated with a MAX variant and highlights the importance of understanding the genotype-phenotype correlation in hereditary pheochromocytoma and the impact of oriented genetic testing to detect, survey and treat patients and kindreds at risk.
Transcription Factor TonEBP Stimulates Hyperosmolality-Dependent Arginine Vasopressin Gene Expression in the Mouse Hypothalamus
Authors: Kim Dong Hee , Kim Kwang Kon , Lee Tae Hwan , Eom Hyejin , Kim Jin Woo , Park Jeong Woo , Jeong Jin Kwon , Lee Byung Ju
Published: March 2021

The hypothalamic neuroendocrine system is strongly implicated in body energy homeostasis. In particular, the degree of production and release of arginine vasopressin (AVP) in the hypothalamus is affected by plasma osmolality, and that hypothalamic AVP is responsible for thirst and osmolality-dependent water and metabolic balance. However, the osmolality-responsive intracellular mechanism within AVP cells that regulates AVP synthesis is not clearly understood. Here, we report a role for tonicity-responsive enhancer binding protein (TonEBP), a transcription factor sensitive to cellular tonicity, in regulating osmosensitive hypothalamic AVP gene transcription. Our immunohistochemical work shows that hypothalamic AVP cellular activity, as recognized by c-fos, was enhanced in parallel with an elevation in TonEBP expression within AVP cells following water deprivation. Interestingly, our in vitro investigations found a synchronized pattern of TonEBP and AVP gene expression in response to osmotic stress. Those results indicate a positive correlation between hypothalamic TonEBP and AVP production during dehydration. Promoter and chromatin immunoprecipitation assays confirmed that TonEBP can bind directly to conserved binding motifs in the 5’-flanking promoter regions of the AVP gene. Furthermore, dehydration- and TonEBP-mediated hypothalamic AVP gene activation was reduced in TonEBP haploinsufficiency mice, compared with wild TonEBP homozygote animals. Therefore, our result support the idea that TonEBP is directly necessary, at least in part, for the elevation of AVP transcription in dehydration conditions. Additionally, dehydration-induced reductions in body weight were rescued in TonEBP haploinsufficiency mice. Altogether, our results demonstrate an intracellular machinery within hypothalamic AVP cells that is responsible for dehydration-induced AVP synthesis.
Pasireotide in the Personalized Treatment of Acromegaly
Authors: Puig-Domingo Manel , Bernabéu Ignacio , Picó Antonio , Biagetti Betina , Gil Joan , Alvarez-Escolá Cristina , Jordà Mireia , Marques-Pamies Montserrat , Soldevila Berta , Gálvez María-Angeles , Cámara Rosa , Aller Javier , Lamas Cristina , Marazuela Mónica
Published: March 2021

The delay in controlling the disease in patients who do not respond to first-line treatment with first generation somatostatin receptor ligands (first-generation SRLs) can be quantified in years, as every modification in the medical therapy requires some months to be fully evaluated. Considering this, acromegaly treatment should benefit from personalized medicine therapeutic approach by using biomarkers identifying drug response. Pasireotide has been positioned mostly as a compound to be used in first-generation SRLs resistant patients and after surgical failure, but sufficient data are now available to indicate it is a first line therapy for patients with certain characteristics. Pasireotide has been proved to be useful in patients in which hyperintensity T2 MRI signal is shown and in those depicting low SST2 and high expression of SST5, low or mutated AIP condition and sparsely granulated immunohistochemical pattern. This combination of clinical and pathological characteristics is unique for certain patients and seems to cluster in the same cases, strongly suggesting an etiopathogenic link. Thus, in this paper we propose to include this clinico-pathologic phenotype in the therapeutic algorithm, which would allow us to use as first line medical treatment those compounds with the highest potential for achieving the fastest control of GH hypersecretion as well as a positive effect upon tumor shrinkage, therefore accelerating the implementation of precision medicine for acromegaly. Moreover, we suggest the development, validation and clinical use of a pasireotide acute test, able to identify patients responsive to pasireotide LAR as the acute octreotide test is able to do for SRLs.
Case Report: Irreversible Watery Diarrhea, Severe Metabolic Acidosis, Hypokalemia and Achloridria Syndrome Related to Vasoactive Intestinal Peptide Secreting Malignant Pheochromocytoma
Authors: Negro Aurelio , Verzicco Ignazio , Tedeschi Stefano , Campanini Nicoletta , Zanelli Magda , Negri Emanuele , Farnetti Enrico , Nicoli Davide , Palladini Barbara , Santi Rosaria , Cunzi Davide , Calvi Anna , Coghi Pietro , Gerra Luigi , Volpi Riccardo , Graiani Gallia , Cabassi Aderville
Published: March 2021

Background

Pheochromocytoma (PHEO) clinical manifestations generally mirror excessive catecholamines secretion; rarely the clinical picture may reflect secretion of other hormones. Watery diarrhea, hypokalemia and achlorhydria (WDHA) is a rare syndrome related to excessive secretion of vasoactive intestinal peptide (VIP).

Clinical Case

A 73-year-old hypotensive man affected by adrenal PHEO presented with weight loss and watery diarrhea associated with hypokalemia, hyperchloremic metabolic acidosis (anion gap 15 mmol/l) and a negative urinary anion gap. Abdominal computed tomography scan showed a right adrenal PHEO, 8.1 cm in maximum diameter, with tracer uptake on 68GaDOTA-octreotate positron emission tomography. Metastasis in lumbar region and lung were present. Both chromogranin A and VIP levels were high (more than10 times the normal value) with slightly elevated urine normetanephrine and metanephrine excretion. Right adrenalectomy was performed and a somatostatin analogue therapy with lanreotide started. Immunostaining showed chromogranin A and VIP co-expression, with weak somatostatin-receptor-2A positivity. In two months, patient clinical conditions deteriorated with severe WDHA and multiple liver and lung metastasis. Metabolic acidosis and hypokalemia worsened, leading to hemodynamic shock and exitus.

Conclusions

A rare case of WDHA syndrome caused by malignant VIP-secreting PHEO was diagnosed. High levels of circulating VIP were responsible of the rapidly evolving clinical picture with massive dehydration and weight loss along with severe hyperchloremic metabolic acidosis and hypokalemia due to the profuse untreatable diarrhea. The rescue treatment with lanreotide was unsuccessful because of the paucity of somatostatin-receptor-2A on VIP-secreting PHEO chromaffin cells.