bluuebunny/crossref_metadata_2025 huggingface dataset:
Istraživanje odnosa upravljačkih struktura i eksterne revizije u korporativnom upravljanju
Authors: Filipović Mario
Published: July 2021

Kvalitetna
komunikacija eksternih revizora s upravljačkim strukturama od iznimne je
važnosti za učinkovito poslovanje kreditnih institucija. Stoga se nameće
pitanje može li se oblikovanjem modela odnosa eksternih revizora i upravljačkih
struktura kreditne institucije unaprijediti rad eksterne revizije, s jedne
strane te upravljačkih struktura kreditne institucije, s druge strane. Doprinos
ovog istraživanja su: analiza kvalitete komuniciranja eksternih revizora s
upravljačkim strukturama kreditne institucije i utjecaj kvalitete tih odnosa na
učinkovitost eksterne revizije i upravljačkih struktura; analiza kvalitete
komuniciranja eksternih revizora s revizijskim odborom kreditne institucije i
utjecaj kvalitete tih odnosa na učinkovitost eksterne revizije i upravljačkih
struktura, posebice nadzornog odbora; identificiranje je li neučinkovitost
eksterne revizije povezana s otvaranjem stečajeva nad kreditnim institucijama i
utvrđivanje pridonosi li predloženi model odnosa eksternih revizora i
upravljačkih struktura kreditne institucije boljem radu eksterne revizije kao i
boljem radu upravljačkih struktura kreditne institucije. U istraživanju,
provedenom u Republici Hrvatskoj, sudjelovali su eksterni revizori koji obavljaju ili su obavljali
reviziju godišnjih financijskih izvještaja kreditnih institucija, članovi
uprave i nadzornih odbora kreditnih institucija te stečajni upravitelji i
stručno osoblje kreditnih institucija u stečaju. Rezultati empirijskog istraživanja potvrđuju kako
testirani komunikacijski model pridonosi
učinkovitijem radu eksterne revizije i
upravljačkih struktura kreditne institucije.
PEACE PEDAGOGY OR/AND EDUCATION FOR PEACE: SOME ACTUALITIES
Authors: Lamanauskas Vincentas
Published: July 2021

It seems, that education questions and problems are analysed rather intensively. Educational researches of various sizes and on various subjects are constantly carried out - both at national, regional and international levels. There wouldn’t probably be a country on this planet, in which such theme researches in one way or another wouldn’t be carried out. Education is not only interdisciplinary, but a very diverse sphere. Where the man is in action, education is inevitable. If one could have a look at the publications of the education field, one could see that diversity is enormous. Leaders are brought up, career preparation is going on, creativity is encouraged, modern media and ICT are taught to be used, so - called 21st century skills are sought to be educated and so on. To tell the truth, hardly anyone could tell what these 21st century skills are, because hardly anyone could bring oneself to tell what skills will be necessary, let’s say, in 2050. However, education is such a sphere, that very often various insights, opinions, positions etc. are spread. This is profoundly called pluralism, there are continual activities. However, if we tried to clarify this a little, we would find plenty of information noise here.
PROSPECTIVE TEACHERS’ CREATIVITY FOSTERING BEHAVIORS, PERCEPTIONS ON THEIR TECHNOLOGY SKILLS AND SUCCESS IN PROJECT BASED MATERIAL DEVELOPMENT
Authors: Özyalçin Oskay Özge
Published: July 2021

In this study it was determined how pre-service chemistry teachers’ creativity fostering behaviours and their perceptions of their technology skills predict their success in Project Based Educational Technology and Material Development course. A sample of the study consists of 45 pre-service teachers attending Department of Chemistry Education at Hacettepe University. After the applications which took 10 weeks, pre-service teachers presented their materials and evaluated their peers and themselves. In order to determine pre-service teachers’ creativity fostering behaviours, “Creativity Fostering Teacher Index Scale” which was developed by Soh (2000) and adapted into Turkish by Dikici (2013) was used. In order to determine pre-service chemistry teachers’ perceptions on their technology skills, “Application Based Educational Technology and Material Development Skills Scale” consisting 46 items and developed by Akgül (2010) was used. Descriptive Statistics of “Creativity Fostering Teacher Index Scale” and “Application Based Educational Technology and Material Development Skills Scale” show that prospective teachers have behaviours supporting creativity and their perceptions about their technology skills is over the average. And multiple regression analysis shows that pre-service teachers’ creativity fostering behaviours and their perceptions on their technology skills together predict their success in project based material development course.
Key words: creativity fostering behaviours, perceptions on technology skills, pre-service chemistry teachers, project based educational technology and material development.
QUINTAIS AGROFLORESTAIS: ESTRUTURA, COMPOSIÇÃO E ORGANIZAÇÃO SOCIOPRODUTIVA
Authors: DE OLIVEIRA MOURA RAIMUNDA ROSIMERE , DE OLIVEIRA MOURA NATALINO , ROCHA MARTINS WALMER BRUNO , DE SOUSA OLIVEIRA CARLOS DOUGLAS
Published: July 2021

Os quintais agroflorestais são representações de sistemas diversificados, fundamentados em conhecimentos tradicionais, sendo o manejo pautado em saberes agroecológicos, que abrangem o modo de vida do agricultor. Desse modo, o objetivo foi avaliar a estrutura, composição e a organização socioprodutiva de quintais agroflorestais em comunidades rurais do município de Igarapé Açu, Pará. O estudo foi realizado em dez quintais agroflorestais, localizados nas comunidades do Triângulo, São Jorge do Jabuti, Limão e Dezesseis, localizadas no município de Igarapé-Açu. A metodologia baseou-se em formulários, entrevistas semiestruturadas, técnica turnê guiada, bola de neve e observação direta. Constatou-se que os quintais agroflorestais eram compostos, principalmente, por espécies agrícolas, medicinais e florestais, com expressiva diversidade e distribuição desuniforme. O componente animal mais frequente foram as aves, mantidas com o intuito de assegurar a soberania e segurança alimentar das famílias.
QUALIDADE DE OVOS DE PRODUÇÃO ORGÂNICA AO LONGO DE CINQUENTA SEMANAS DE POSTURA
Authors: Poletti Bruna , Vieira Maitê de Moraes , Pinto Andrea Troller , Ferreira Jeruza Indiara , Do Nascimento Vladimir Pinheiro
Published: July 2021

Atualmente, a produção de ovos em sistemas alternativos vem crescendo, porém não há informações relativas aos seus critérios de qualidade. Com o objetivo de analisar características físico-químicas de ovos orgânicos, associadas ao avanço da idade de postura das aves, avaliou-se peso do ovo, altura de albúmen, espessura da casca, índice e porcentagem de gema, porcentagem de albúmen e de casca e unidade Haugh (UH). Quinzenalmente, seis ovos frescos foram avaliados, durante a 28ª e 80ª semana de postura. A qualidade externa e interna dos ovos foi afetada pela idade. Peso do ovo e espessura da casca resultaram em efeito cúbico e quadrático (P<0,001), respectivamente. Avaliação da UH e da porcentagem de gema e albúmen resultaram em comportamento cúbico (P<0,05). Índice de gema teve comportamento linear decrescente. O aumento da idade das aves ocasionou diminuição de indicadores de qualidade interna. Apesar da redução na qualidade, ovos de sistema orgânico mantiveram os padrões adequados para consumo, ao longo do ciclo produtivo. Com o avanço da idade, os ovos ficaram mais pesados, porém com redução da espessura de casca,  da unidade Haugh e do índice e porcentagem de gema.
AGRICULTURA FAMILIAR E POLÍTICAS PÚBLICAS: ESTUDO DE CASO NA COMUNIDADE VILA RESSACA DA PEDREIRA, MACAPÁ, AMAPÁ, BRASIL
Authors: Saraiva Olivan Do Nascimento , Borges Wardsson Lustrino
Published: July 2021

A análise da adoção de políticas públicas para agricultura familiar em diferentes contextos socioeconômicos releva resultados relevantes para compreensão do desenvolvimento rural. Objetivou-se neste trabalho avaliar o nível de adoção, por parte dos agricultores familiares da comunidade Vila Ressaca da Pedreira, Macapá – AP, de políticas públicas voltadas para promoção do desenvolvimento da agricultura familiar. Nós adotamos a aplicação de formulários semiestruturado, com questões relativas às principais políticas públicas implementadas no estado para um público total de 32 famílias de agricultores. Observou-se que 87,5%, 67,7% e 38,7% foram atendidas pelo serviço oficial de extensão rural e assistência técnica, programa de aquisição de alimentos e o programa nacional de alimentação escolar, respectivamente. Por outro lado, o programa nacional de fortalecimento da agricultura familiar, que é a principal política pública para a agricultura familiar, foi acessado por apenas 6,25% das famílias entrevistadas.
MANEJO DE AGROFLORESTAS NA AMAZÔNIA TOCANTINA: PERCEPÇÕES PARA A EDUCAÇÃO AGROFLORESTAL
Authors: Pompeu Gisele do Socorro dos Santos , Santos Verônica de Paula da Silva , Pinto Erveton da Silva , Rodrigues Renato dos Prazeres
Published: July 2021

Os sistemas de agrofloresta produzem alimentos, geram renda e promovem a valorização dos saberes tradicionais e práticas agroecológicas pelos sujeitos campesinos. O objetivo da pesquisa foi analisar as percepções das famílias camponesas sobre o manejo dos sistemas de agrofloresta, em áreas de várzea, no município de Cametá, Pará, na perspectiva da educação agroflorestal. Entrevistou-se 30 famílias, utilizando roteiro de entrevista semiestruturado, e resultados analisados com apoio da estatística descritiva. As relações construídas no manejo dos sistemas estão relacionadas às percepções sobre o caráter econômico da produção, mas com forte perspectiva sociocultural e ambiental. O manejo intensivo propicia mudanças negativas na paisagem e na vida das famílias, com percepções de alternativas de manejo baseadas na diversidade agroflorestal. O envolvimento de sujeitos formadores ocorre pela valorização dos saberes e troca de experiências, e a sensibilização ancorada na educação agroflorestal.
MANEJO ECOLÓGICO DE SOLO
Authors: Trindade-Santos Matheus Eduardo , Castro Marina Siqueira
Published: July 2021

A agricultura convencional vem contribuindo para a degradação dos ecossistemas naturais e dos agroecossistemas, resultando em perda da biodiversidade e dos serviços ecossistêmicos. Epistemologicamente a agroecologia se expande para além das estruturas do agrícola, auxiliando na mudança ética do ser humano. Assim, o manejo ecológico que caracteriza o solo como um ser vivo e funcional, passa a ser visto como uma ferramenta para a transição agroecológica. Esta pesquisa investiga o papel do manejo ecológico do solo e sua relação com a transição agroecológica, o reestabelecimento dos serviços ecossistêmicos e da agrobiodiversidade edáfica. Trata-se de um estudo qualitativo, utilizando como procedimento metodológico a revisão narrativa do conhecimento presente na literatura científica. Os resultados sugerem que o manejo do solo está conectado de forma indireta/direta aos serviços ecossistêmicos, bem como sua possibilidade de reestabelecer a agrobiodiversidade. Conclui-se que o manejo ecológico de solo reestabelece o papel do solo como autorregulador dos processos ecológicos e fundamental para a transição agroecológica.
POLÍTICAS PÚBLICAS NA PRODUÇÃO DE ALIMENTOS ORGÂNICOS: DESAFIOS E PERSPECTIVAS
Authors: Dos Anjos Cristiane Souza , Carvalho Perelló Luís Fernando
Published: July 2021

A busca por alimentos livres de contaminantes produzidos a partir da agricultura orgânica e agroecológica tem ganhado cada vez mais espaço no mercado consumidor em todo o mundo. A área cultivada passou de 11 milhões de hectares, em 1999, para 50,9 milhões de hectares em 2015, representando crescimento de mais de 460%. Em 2014, o número de produtores orgânicos no mundo era de 2,3 milhões. O Brasil entrou mais recentemente nesse mercado e, apesar de ter implantado um Plano Nacional, em 2013, enfrenta dificuldades para expandir o segmento. Esse trabalho teve como objetivo identificar a evolução de políticas públicas voltadas para a produção de base agroecológica e orgânica de alimentos no Brasil e no Rio Grande do Sul. A revisão pretendeu mostrar o comportamento do crédito rural destinado ao setor. O trabalho foi realizado a partir de revisão bibliográfica e consulta à base de dados nacionais e de organismos internacionais, governamentais e privados. Assim como a burocracia, a fraca ou inexistente assistência técnica na elaboração dos projetos de base ecológica e preços considerados elevados cobrados do agricultor em troca de certificação auditada que são fatores que, entre outros, estão interferindo negativamente no acesso ao crédito, dificultando o emprego de recursos que estão disponíveis no sistema bancário estatal.
CARACTERIZAÇÃO DE PROGÊNIES DE ALFACE OBTIDAS POR MEIO DO MELHORAMENTO GENÉTICO PARTICIPATIVO
Authors: Silva Sylmara , Souza Douglas Correa de , Rosado Renato Domiciano Silva , Gomes Luiz Antônio Augusto
Published: July 2021

O melhoramento genético participativo é uma alternativa para a obtenção de novas cultivares para a agricultura orgânica, uma vez que possibilita maior envolvimento de agricultores, pesquisadores e consumidores. Objetivou-se com este trabalho caracterizar progênies superiores de alface F2:4, oriundas do cruzamento entre as cultivares Salinas 88 e Colorado, previamente selecionadas por meio do melhoramento genético participativo, visando identificar genótipos promissores para a obtenção de novas cultivares para a agricultura orgânica. As características comerciais avaliadas foram coloração, tipo de borda, tipo de limbo, classificação comercial, massa fresca, tolerância ao florescimento precoce e a produção de sementes. Verificou-se que existe grande variabilidade genética para características agronômicas em progênies F2:4 de alface do cruzamento entre Salinas 88 e Colorado, sendo necessário avançar mais gerações, para se identificar material com características comerciais desejáveis.
ICT in Sanità: vecchi problemi e nuove sfide
Authors: Quintaliani G. , Torpia R. , Giovannelli M. , Orecchini A. , De Angelis L.
Published: July 2021

Abstract non disponibile (Clinical_Management)
Budget Impact analysis of ponatinib for the management of patients with chronic myeloid leukemia
Authors: Basile Michele , Rumi Filippo , Cicchetti Americo
Published: July 2021

Background: The current clinical practice for patients affected by chronic myeloid leukemia (CML) is based on the evaluation of second generation alternatives following therapeutic failure that leads to a lengthening of patients’ management times and a consequent negative impact in terms of quality of life.

Objective: To determine the economic absorption of resources associated to the management of patients with CML in a scenario in which an early recourse to ponatinib is considered as compared with a scenario based on the current Italian clinical practice characterized by a cyclical recourse to the available therapies.

Methods: A Budget Impact model was developed to compare the resources absorbed in the scenarios under assessment considering a 3-year time horizon and the perspective of the Italian National Health Service. Results are expressed in terms of differential resources absorbed in the alternative scenarios.

Results: The increase in the recourse to ponatinib allowed a saving of resources for the Italian NHS over the 3-year time horizon of –€ 1,979,322 (€ 825,104,350 vs € 823,125,028). The parameter affecting the most of the results achieved in the base-case is the monthly cost of bosutinib used as a third-line treatment.

Conclusions: The increase in the recourse to ponatinib in patients affected by CML that failed to respond to a previous pharmacological therapy resulted to be associated to a lower level of resources’ absorption in the Italian NHS allowing to re-allocate health founds to other fields of the care sector ensuring greater sustainability of the system.
An Analysis of Student Difficulties in Mathematics Learning in terms of Student Mathematical Connection Ability on Pythagoras Theorem
Authors: Sholeha Viona Aida , Risnawati Risnawati , Habibullah Habibullah
Published: July 2021

This research aimed to describe student difficulties in mathematics learning in terms of student mathematical connection ability on Pythagoras theorem. This research was a qualitative descriptive research with case study design. The research subjects were 18 the IX grade students, then reduced to 5 students and purposive sampling technique was used in this research. Triangulation data such as mathematical connection ability and difficulties of mathematic learning tests and interview were used for collecting the data.  The data were analyzed by Miles and Hubermen techniques including three stages: reduction, presentation, and conclusion/verification. The findings of this research showed that, each respondent has different difficulties at each mathematical connection ability level; (1) The subject (very high) mathematical connection ability level did not have problem with all indicators of difficulties in mathematics learning; (2) The subject (high) mathematical connection ability level had associations or visual-motor combination; (3) The subject (medium) mathematical connection ability level had associations or visual-motor combination and difficulties in recognizing and using symbols; (4) The subject (low) mathematical connection ability level had little spatial disruption, association or visual-motor combination, and little difficulties in recognizing and using symbols; (5) The subject (very low) mathematical connection ability level had spatial disruption, association or visual-motor combination, and difficulties in recognizing and using symbols
Secondary Amenorrhea Due to Unusual Cause (Hematometrocolpos)
Authors: Hamza Elmahaishi , Alia Zwawa , Wael M Elmahaishi , MS Elmahaishi
Published: July 2021

Hematometrocolpos usually caused by obstruction of lower genital tract, somewhere in the vagina such as Imperforated hymen. In our case there is no obstruction in the vagina, but started at the cervix in a form of membrane. This membrane extended in the vagina forming intavaginal cyst which filled with blood and by time gave the complete picture of hematometrocolpos. This case aged 53 years old, para7 and presenting to our clinic complaining of urinary retention burning of micturition and secondary amenorrhea for 9 months.
A structural constraint on neural correlates of consciousness
Authors: Fink Sascha Benjamin , Kob Lukas , Lyre Holger
Published: July 2021

Researchers on the neural correlates of consciousness (NCC) need to distinguish mere statisticalNCCs from NCCs proper. Some neural events may be co-occurrent, probabilistically coupled,or coincidental with a type of conscious experience but lack any deeper connection to it, whilein other cases, the relation between neural states and a type of experience hints at a strongmetaphysical relation, which distinguishes such NCCs proper from mere statistical NCCs. In orderto address this issue of how to distinguish NCCs proper from mere statistical NCCs, we proposea position we call neurophenomenal structuralism. The position hinges on the uncontroversialidea that phenomenal experiences relate to each other in degrees of similarity and difference.These complex structures are used to identify and individuate experiences in the methods ofneuroscience, psychophysics, and phenomenology. Such individuation by structure leads to phenomenalholism, which has implications for how to investigate consciousness neuroscientificallyand generates a constraint by which we can distinguish NCCs proper from mere statistical NCCs:the structural similarity constraint. Neural activation must preserve the structure governing thedomain of experiences it is associated with in order to count as that domain’s NCC proper. Anyactivation that fails to preserve phenomenal structure fails to be an NCC proper. We illustratehow this constraint works with a study by Brouwer & Heeger (2009) as an example.
The neural correlates of consciousness under the free energy principle: From computational correlates to computational explanation
Authors: Wiese Wanja , Friston Karl J.
Published: July 2021

How can the free energy principle contribute to research on neural correlates of consciousness, and to the scientific study of consciousness more generally? Under the free energy principle, neural correlates should be defined in terms of neural dynamics, not neural states, and should be complemented by research on computational correlates of consciousness – defined in terms of probabilities encoded by neural states.

We argue that these restrictions brighten the prospects of a computational explanation of consciousness, by addressing two central problems. The first is to account for consciousness in the absence of sensory stimulation and behaviour. The second is to allow for the possibility of systems that implement computations associated with consciousness, without being conscious, which requires differentiating between computational systems that merely simulate conscious beings and computational systems that are conscious in and of themselves.

Given the notion of computation entailed by the free energy principle, we derive constraints on the ascription of consciousness in controversial cases (e.g., in the absence of sensory stimulation and behaviour). We show that this also has implications for what it means to be, as opposed to merely simulate a conscious system.
In Vivo Foot and Ankle Kinematics During Activities Measured by Using a Dual Fluoroscopic Imaging System: A Narrative Review
Authors: Ye Dongqiang , Sun Xiaole , Zhang Cui , Zhang Shen , Zhang Xini , Wang Shaobai , Fu Weijie
Published: July 2021

Foot and ankle joints are complicated anatomical structures that combine the tibiotalar and subtalar joints. They play an extremely important role in walking, running, jumping and other dynamic activities of the human body. The in vivo kinematic analysis of the foot and ankle helps deeply understand the movement characteristics of these structures, as well as identify abnormal joint movements and treat related diseases. However, the technical deficiencies of traditional medical imaging methods limit studies on in vivo foot and ankle biomechanics. During the last decade, the dual fluoroscopic imaging system (DFIS) has enabled the accurate and noninvasive measurements of the dynamic and static activities in the joints of the body. Thus, this method can be utilised to quantify the movement in the single bones of the foot and ankle and analyse different morphological joints and complex bone positions and movement patterns within these organs. Moreover, it has been widely used in the field of image diagnosis and clinical biomechanics evaluation. The integration of existing single DFIS studies has great methodological reference value for future research on the foot and ankle. Therefore, this review evaluated existing studies that applied DFIS to measure the in vivo kinematics of the foot and ankle during various activities in healthy and pathologic populations. The difference between DFIS and traditional biomechanical measurement methods was shown. The advantages and shortcomings of DFIS in practical application were further elucidated, and effective theoretical support and constructive research direction for future studies on the human foot and ankle were provided.
Membrane Binding of α-Synuclein Stimulates Expansion of SNARE-Dependent Fusion Pore
Authors: Khounlo Ryan , Hawk Brenden J. D. , Khu Tung-Mei , Yoo Gyeongji , Lee Nam Ki , Pierson Josh , Shin Yeon-Kyun
Published: July 2021

SNARE-dependent membrane fusion is essential for neurotransmitter release at the synapse. Recently, α-synuclein has emerged as an important regulator for membrane fusion. Misfolded α-synuclein oligomers are potent fusion inhibitors. However, the function of normal α-synuclein has been elusive. Here, we use the single vesicle-to-supported bilayer fusion assay to dissect the role of α-synuclein in membrane fusion. The assay employs 10 kD Rhodamine B-dextran as the content probe that can detect fusion pores larger than ∼6 nm. We find that the SNARE complex alone is inefficient at dilating fusion pores. However, α-synuclein dramatically increases the probability as well as the duration of large pores. When the SNARE-interacting C-terminal region of α-synuclein was truncated, the mutant behaves the same as the wild-type. However, the double proline mutants compromising membrane-binding show significantly reduced effects on fusion pore expansion. Thus, our results suggest that α-synuclein stimulates fusion pore expansion specifically through its membrane binding.
Light-Controllable PROTACs for Temporospatial Control of Protein Degradation
Authors: Liu Jing , Peng Yunhua , Wei Wenyi
Published: July 2021

PROteolysis-TArgeting Chimeras (PROTACs) is an emerging and promising approach to target intracellular proteins for ubiquitination-mediated degradation, including those so-called undruggable protein targets, such as transcriptional factors and scaffold proteins. To date, plenty of PROTACs have been developed to degrade various disease-relevant proteins, such as estrogen receptor (ER), androgen receptor (AR), RTK, and CDKs. However, the on-target off-tissue and off-target effect is one of the major limitation that prevents the usage of PROTACs in clinic. To this end, we and several other groups have recently developed light-controllable PROTACs, as the representative for the third generation controllable PROTACs, by using either photo-caging or photo-switch approaches. In this review, we summarize the emerging light-controllable PROTACs and the prospective for other potential ways to achieve temporospatial control of PROTACs.
Effect of ISM1 on the Immune Microenvironment and Epithelial-Mesenchymal Transition in Colorectal Cancer
Authors: Wu Yuhui , Liang Xiaojing , Ni Junjie , Zhao Rongjie , Shao Shengpeng , Lu Si , Han Weidong , Yu Liangliang
Published: July 2021

Background: An increasing number of studies have shown that Isthmin 1 (ISM1), a secreted protein, is important in tumorigenesis and invasion, including in colorectal cancer (CRC). However, the mechanisms are still unclear. This study aims to explore the function and prognosis capacity of ISM1 in CRC.

Methods: We investigated the expression of ISM1 in 18 CRC tissues vs. adjacent normal tissues from GSE50760, 473 CRC tissues vs. 41 normal tissues from The Cancer Genome Atlas (TCGA), and across gastrointestinal cancer types. Differences were further confirmed in CRC tissues via quantitative real-time polymerase chain reaction (qRT-PCR). Then, we analyzed correlations between clinicopathologic features and ISM1 expression, including prognostic prediction value, using the Kaplan–Meier method and multivariate Cox regression. Gene set enrichment analysis (GSEA) was performed to identify ISM1-related pathways. In vitro experiments were performed to verify the role of ISM1 in epithelial-mesenchymal transition (EMT) and CRC progression.

Results: Multiple datasets showed that ISM1 is upregulated in CRC tissues, which was validated. Patients with higher ISM1 expression had shorter overall survival (OS), and ISM1 expression served as an independent prognostic factor. Enrichment analysis showed that ISM1 upregulation was positively correlated with cancer-related pathways, such as EMT, hypoxia, and the Notch and KRAS signaling pathways. We were exclusively interested in the connection between ISM1 and EMT because 71% of genes in this pathway were significantly positively co-expressed with ISM1, which may account for why patients with higher ISM1 expression are prone to regional lymph node involvement and progression to advanced stages. In addition, we found that ISM1 was positively correlated with multiple immunosuppressive pathways such as IL2/STAT5, TNF-α/NF-κB, and TGF-β, and immune checkpoints, including PD-L1, PD-1, CTLA-4, and LAG3, which may account for upregulation of ISM1 in immunotherapy-resistant patients. Notably, through in vitro experiments, we found that ISM1 promoted EMT and colon cancer cell migration and proliferation.

Conclusion: ISM1 is critical for CRC development and progression, which enhances our understanding of the low response rate of CRC to immunotherapy via immunosuppressive signaling pathways.
Characterization of Five Transmembrane Proteins: With Focus on the Tweety, Sideroflexin, and YIP1 Domain Families
Authors: Attwood Misty M. , Schiöth Helgi B.
Published: July 2021

Transmembrane proteins are involved in many essential cell processes such as signal transduction, transport, and protein trafficking, and hence many are implicated in different disease pathways. Further, as the structure and function of proteins are correlated, investigating a group of proteins with the same tertiary structure, i.e., the same number of transmembrane regions, may give understanding about their functional roles and potential as therapeutic targets. This analysis investigates the previously unstudied group of proteins with five transmembrane-spanning regions (5TM). More than half of the 58 proteins identified with the 5TM architecture belong to 12 families with two or more members. Interestingly, more than half the proteins in the dataset function in localization activities through movement or tethering of cell components and more than one-third are involved in transport activities, particularly in the mitochondria. Surprisingly, no receptor activity was identified within this dataset in large contrast with other TM groups. The three major 5TM families, which comprise nearly 30% of the dataset, include the tweety family, the sideroflexin family and the Yip1 domain (YIPF) family. We also analyzed the evolutionary origin of these three families. The YIPF family appears to be the most ancient with presence in bacteria and archaea, while the tweety and sideroflexin families are first found in eukaryotes. We found no evidence of common decent for these three families. About 30% of the 5TM proteins have prominent expression in the brain, liver, or testis. Importantly, 60% of these proteins are identified as cancer prognostic markers, where they are associated with clinical outcomes of various tumor types. Nearly 10% of the 5TMs are still not fully characterized and further investigation of their functional activities and expression is warranted. This study provides the first comprehensive analysis of proteins with the 5TM architecture, providing details of their unique characteristics.
Intestinal Metabolites Influence Macrophage Phagocytosis and Clearance of Bacterial Infection
Authors: O’Callaghan Amy A. , Dempsey Elaine , Iyer Namrata , Stiegeler Sarah , Mercurio Kevin , Corr Sinéad C.
Published: July 2021

The metabolite-rich environment that is the intestinal lumen contains metabolic by-products deriving from microbial fermentation and host cell metabolism, with resident macrophages being constantly exposed to this metabolic flux. Succinate, lactate and itaconate are three metabolites secreted by primed macrophages due to a fragmented tri-carboxylic acid (TCA) cycle. Additionally, succinate and lactate are known by-products of microbial fermentation. How these metabolites impact biological functioning of resident macrophages particularly in response to bacterial infection remains poorly understood. We have investigated the potential influence of these metabolites on macrophage phagocytosis and clearance of Escherichia coli (E. coli) infection. Treatment of murine bone-marrow-derived macrophages (BMDMs) with succinate reduced numbers of intracellular E. coli early during infection, while lactate-treated BMDMs displayed no difference throughout the course of infection. Treatment of BMDMs with itaconate lead to higher levels of intracellular E. coli early in the infection with bacterial burden subsequently reduced at later time-points compared to untreated macrophages, indicative of enhanced engulfment and killing capabilities of macrophages in response to itaconate. Expression of engulfment mediators MARCKS, RhoB, and CDC42 were reduced or unchanged following succinate or lactate treatment and increased in itaconate-treated macrophages following E. coli infection. Nitric oxide (NO) levels varied while pro- and anti-inflammatory cytokines differed in secretory levels in all metabolite-treated macrophages post-infection with E. coli or in response to lipopolysaccharide (LPS) stimulation. Finally, the basal phenotypic profile of metabolite-treated macrophages was altered according to marker gene expression, describing how fluid macrophage phenotype can be in response to the microenvironment. Collectively, our data suggests that microbe- and host-derived metabolites can drive distinct macrophage functional phenotypes in response to infection, whereby succinate and itaconate regulate phagocytosis and bactericidal mechanisms, limiting the intracellular bacterial niche and impeding the pathogenesis of infection.
Statin Treatment Induced a Lipogenic Expression Hierarchical Network Centered by SREBF2 in the Liver
Authors: Song Shiyu , Niu Mengyuan , Liang Qiao , Wang Lei , Min Haiyan , Peng Yuming , Wang Hongwei , Gao Qian
Published: July 2021

Statin treatment is a major prevention treatment for hypercholesterolemia and the management of patients with increased risk of cardiovascular disease (CVD) due to its protective effects. However, its long-term safety was questioned regarding its potential role in new-onset type 2 diabetes mellitus, and its effect on gene regulation in the liver is not yet fully understood. By reanalyzing the transcriptome of the livers of patients with obesity and hypercholesterolemia, this study shows a multiple module organization that is related to various clinical metabolic parameters and identified an expression hierarchical network involving cholesterol and fatty acid syntheses in the liver of statin-treated patients. The key genes of the network were validated by QPCR in the hepatocytes upon statin treatment. The upregulation of the key enzymes involving the synthesis of Acetyl-CoA and the induction of gentle global acetylation of pan-protein and histone H4 in hepatocytes were observed. The study provides an overall view of the statin effect on transcriptional and post-transcriptional regulation of genes in the liver.
Numerical Simulation of Transient Characteristics of Start-Up Transition Process of Large Vertical Siphon Axial Flow Pump Station
Authors: Zhang Xiaowen , Tang Fangping , Liu Chao , Shi Lijian , Liu Haiyu , Sun Zhuangzhuang , Hu Wenzhu
Published: July 2021

In order to explore the transient characteristics of the large-scale vertical siphon axial flow pumping station during the start-up and exhaust process, numerical simulations were carried out on the start-up process of the axial flow pumping station under the two starting modes of pre-opening the vacuum breaking valve and keeping the vacuum breaking valve closed. The calculation results show that during the start-up phase of the unit, the flow separation phenomenon of the impeller channel of the pump device with the vacuum breaking valve closed is serious, the large-scale vortex in the guide vane blocks the flow channel, and the instantaneous impact on the blade surface is strong. The flow field of the pump device with pre-open vacuum failure valve is obviously less affected by the instantaneous impact characteristics during the start-up of the pump. The range of high entropy production area in the impeller channel is reduced, the duration of high entropy production area is significantly shortened, and the instantaneous impact on the blade surface is weak. Under the two starting modes, the internal flow field of the pump device is similar in the evolutionary law. The unstable flow phenomenon of the pump device is most prominent in the weir flow stage. The maximum instantaneous impact on the blade surface also mainly occurs in the weir flow stage. A very small part of the remaining gas in the siphon formation stage is difficult to discharge and takes a long time. After the pump device is exhausted and enters a stable operation state, the external characteristic parameters are in good agreement with the test results. Compared with the starting method in which the vacuum breaking valve is kept closed, the method of pre-opening the vacuum breaking valve reduces the maximum starting head by 20% and the exhaust time by 43%. The pre-open vacuum breaking valve effectively avoids the system instability caused by the start-up and exhaust of the pump device.
Effects of Streamside Buffers on Stream Temperatures Associated With Forest Management and Harvesting Using DHSVM-RBM; South Fork Caspar Creek, California
Authors: Ridgeway Julia B. , Surfleet Christopher G.
Published: July 2021

Forest harvesting has been shown to effect water quantity and water quality parameters, highlighting the need for comprehensive forest practice rules. Being able to understand and predict these impacts on stream temperature is especially critical where federally threatened or endangered fish species are located. The goal of this research was to predict responses in stream temperature to potential riparian and forest harvest treatments in a maritime, mountainous environment. The Distributed Hydrology Soil Vegetation Model (DHSVM) and River Basin Model (RBM) were calibrated to measured streamflow and stream temperatures in the South Fork of the Caspar Creek Experimental Watersheds during critical summer periods when temperatures are highest and flows are low for hydrologic years 2010–2016. The modeling scenarios evaluated were (1) varying percentages of stream buffer canopy cover, (2) a harvest plan involving incrementally reduced stand densities in gauged sub-watersheds, and (3) an experimental design converting dominant riparian vegetation along set reaches. The model predicted a noticeable rise in stream temperatures beginning when stream buffer canopy cover was reduced to 25 and 0% retention levels. Larger increases in Maximum Weekly Maximum Temperatures (MWMT), compared to Maximum Weekly Average Temperatures (MWAT), occurred across all scenarios. There was essentially no difference in MWAT or MWMT between altering buffers along only fish bearing (Class I) watercourses and altering buffers along all watercourses. For the scenario with stream buffers at 0% retention, MWMTs consistently rose above recommended thermal limits for coho salmon(Oncorhynchus kisutch). Predictions when clearcutting the entire watershed showed less of an effect than simulations with 0% buffer retention, suggesting groundwater inflows mitigate stream temperature rises in the South Fork. The harvest simulation showed a small but consistent increase in MWATs (avg. 0.11°C), and more varied increases in MWMTs (avg. 0.32°C). Sensitivity analyses suggest potentially unrealistic tracking of downstream temperatures, making the vegetation conversion simulations inconclusive. Additional sensitivity analyses suggest tree height and monthly extinction coefficient (a function of leaf area index) were most influential on temperatures in the South Fork, which was consistent with other modeling studies suggesting management focus on tall, dense buffers compared to wider buffer widths.
Genome Divergence and Dynamics in the Thin-Tailed Desert Sheep From Sudan
Authors: Abied Adam , Ahbara Abulgasim M. , Berihulay Haile , Xu Lingyang , Islam Rabiul , El-Hag Faisal M. , Rekik Mourad , Haile Aynalem , Han Jian-Lin , Ma Yuehui , Zhao Qianjun , Mwacharo Joram M.
Published: July 2021

With climate change bound to affect food and feed production, emphasis will shift to resilient and adapted indigenous livestock to sustain animal production. However, indigenous livestock comprise several varieties, strains and ecotypes whose genomes are poorly characterized. Here, we investigated genomic variation in an African thin-tailed Desert Sheep sampled in Sudan, using 600K genotype data generated from 92 individuals representing five ecotypes. We included data from 18 fat-tailed and 45 thin-tailed sheep from China, to investigate shared ancestry and perform comparative genomic analysis. We observed a clear genomic differentiation between the African thin-tailed Desert Sheep and the Chinese thin-tailed and fat-tailed sheep, suggesting a broad genetic structure between the fat-tailed and thin-tailed sheep in general, and that at least two autosomal gene pools comprise the genome profile of the thin-tailed sheep. Further analysis detected two distinct genetic clusters in both the African thin-tailed Desert Sheep and the Chinese thin-tailed sheep, suggesting a fine-scale and complex genome architecture in thin-tailed sheep. Selection signature analysis suggested differences in adaptation, production, reproduction and morphology likely underly the fine-scale genetic structure in the African thin-tailed Desert Sheep. This may need to be considered in designing breeding programs and genome-wide association studies.
Esophageal Cancer Associated Immune Genes as Biomarkers for Predicting Outcome in Upper Gastrointestinal Tumors
Authors: Zhu Chuanhui , Xia Qianqian , Gu Bin , Cui Mengjing , Zhang Xing , Yan Wenjing , Meng Dan , Shen Siyuan , Xie Shuqian , Li Xueliang , Jin Hua , Wang Shizhi
Published: July 2021

Esophageal cancer (EC) is the seventh most common tumor in the world, ranking the sixth leading cause of cancer death, with a 5-year survival rate of 15-25%. Therefore, reliable prognostic biomarkers are needed to effectively predict the prognosis of EC. In this study, the gene profile information of the EC cohort served as a training set, which was derived from TCGA and Immport databases. GO and KEGG enrichment analysis was performed on the differential genes in normal and tumor groups of EC. The immune genes in differentially expressed genes (DEGs) were further obtained for univariate and multivariate Cox and Lasso regression analysis, and 6 independent immune genes (S100A3, STC2, HSPA6, CCL25, GPER1, and OSM) associated with prognosis were obtained to establish an immune risk score signature (IRSS). The signature was validated using head and neck cancers (HNSC) and gastric cancer (GC)in upper gastrointestinal malignancies as validation sets. The Kaplan-Meier results showed that the prognosis of the high-risk group was significantly favorable than that of the low-risk group in both the training set (P < 0.001; HR = 3.68, 95% CI = 2.14−6.35) and the validation set (P = 0.010; HR = 1.43, 95% CI = 1.09−1.88). A nomogram combining multiple clinical information and IRSS was more effective than a single independent prognostic factor in predicting outcome. This study explored the potential link between immunity and EC, and established and validated prognostic biomarkers that can effectively predict the prognosis of EC, HNSC and GC based on six immune genes.
AeMOPE-1, a Novel Salivary Peptide From Aedes aegypti, Selectively Modulates Activation of Murine Macrophages and Ameliorates Experimental Colitis
Authors: Lara Priscila G. , Esteves Eliane , Sales-Campos Helioswilton , Assis Josiane B. , Henrique Maressa O. , Barros Michele S. , Neto Leila S. , Silva Pedro I. , Martins Joilson O. , Cardoso Cristina R. B. , Ribeiro José M. C. , Sá-Nunes Anderson
Published: July 2021

The sialotranscriptomes of Aedes aegypti revealed a transcript overexpressed in female salivary glands that codes a mature 7.8 kDa peptide. The peptide, specific to the Aedes genus, has a unique sequence, presents a putative secretory nature and its function is unknown. Here, we confirmed that the peptide is highly expressed in the salivary glands of female mosquitoes when compared to the salivary glands of males, and its secretion in mosquito saliva is able to sensitize the vertebrate host by inducing the production of specific antibodies. The synthetic version of the peptide downmodulated nitric oxide production by activated peritoneal murine macrophages. The fractionation of a Ae. aegypti salivary preparation revealed that the fractions containing the naturally secreted peptide reproduced the nitric oxide downmodulation. The synthetic peptide also selectively interfered with cytokine production by murine macrophages, inhibiting the production of IL-6, IL-12p40 and CCL2 without affecting TNF-α or IL-10 production. Likewise, intracellular proteins associated with macrophage activation were also distinctively modulated: while iNOS and NF-κB p65 expression were diminished, IκBα and p38 MAPK expression did not change in the presence of the peptide. The anti-inflammatory properties of the synthetic peptide were tested in vivo on a dextran sulfate sodium-induced colitis model. The therapeutic administration of the Ae. aegypti peptide reduced the leukocytosis, macrophage activity and nitric oxide levels in the gut, as well as the expression of cytokines associated with the disease, resulting in amelioration of its clinical signs. Given its biological properties in vitro and in vivo, the molecule was termed Aedes-specific MOdulatory PEptide (AeMOPE-1). Thus, AeMOPE-1 is a novel mosquito-derived immunobiologic with potential to treat immune-mediated disorders.
Arctigenin Exerts Neuroprotective Effect by Ameliorating Cortical Activities in Experimental Autoimmune Encephalomyelitis In Vivo
Authors: Wei Liangpeng , Xue Zhenyi , Lan Baihui , Yuan Shiyang , Li Yuanyuan , Guo Cunle , Zhang Rongxin , Ding Ran , Shen Hui
Published: July 2021

Multiple sclerosis (MS) is a chronic disease in the central nervous system (CNS), characterized by inflammatory cells that invade into the brain and the spinal cord. Among a bulk of different MS models, the most widely used and best understood rodent model is experimental autoimmune encephalomyelitis (EAE). Arctigenin, a botanical extract from Arctium lappa, is reported to exhibit pharmacological properties, including anti-inflammation and neuroprotection. However, the effects of arctigenin on neural activity attacked by inflammation in MS are still unclear. Here, we use two-photon calcium imaging to observe the activity of somatosensory cortex neurons in awake EAE mice in vivo and found added hyperactive cells, calcium influx, network connectivity, and synchronization, mainly at preclinical stage of EAE model. Besides, more silent cells and decreased calcium influx and reduced network synchronization accompanied by a compensatory rise in functional connectivity are found at the remission stage. Arctigenin treatment not only restricts inordinate individually neural spiking, calcium influx, and network activity at preclinical stage but also restores neuronal activity and communication at remission stage. In addition, we confirm that the frequency of AMPA receptor-mediated spontaneous excitatory postsynaptic current (sEPSC) is also increased at preclinical stage and can be blunted by arctigenin. These findings suggest that excitotoxicity characterized by calcium influx is involved in EAE at preclinical stage. What is more, arctigenin exerts neuroprotective effect by limiting hyperactivity at preclinical stage and ameliorates EAE symptoms, indicating that arctigenin could be a potential therapeutic drug for neuroprotection in MS-related neuropsychological disorders.
B7-H3/CD276: An Emerging Cancer Immunotherapy
Authors: Zhou Wu-Tong , Jin Wei-Lin
Published: July 2021

Immunotherapy aiming at suppressing tumor development by relying on modifying or strengthening the immune system prevails among cancer treatments and points out a new direction for cancer therapy. B7 homolog 3 protein (B7-H3, also known as CD276), a newly identified immunoregulatory protein member of the B7 family, is an attractive and promising target for cancer immunotherapy because it is overexpressed in tumor tissues while showing limited expression in normal tissues and participating in tumor microenvironment (TME) shaping and development. Thus far, numerous B7-H3-based immunotherapy strategies have demonstrated potent antitumor activity and acceptable safety profiles in preclinical models. Herein, we present the expression and biological function of B7-H3 in distinct cancer and normal cells, as well as B7-H3-mediated signal pathways in cancer cells and B7-H3-based tumor immunotherapy strategies. This review provides a comprehensive overview that encompasses B7-H3’s role in TME to its potential as a target in cancer immunotherapy.