bluuebunny/crossref_metadata_2025 huggingface dataset:
Provas digitais no processo do trabalho
Authors: Lima Andréa Ferreira , Nunes Vanessa Ester Ferreira , Vieira Carolina Mesquita
Published: November 2024

Este artigo tem como objetivo pesquisar a validade do uso da geolocalização como meio de prova digital no Processo do Trabalho, uma vez que esse procedimento possibilita, por meio de uso de dados de localização geográfica, indicar a presença ou não de objetos ou pessoas em determinado local. Em algumas reclamações trabalhistas, as empresas passaram a requerer a expedição de ofícios para aplicativos como Google Takeout, Google Maps, iFood, Uber e para companhias de telefonia, a fim de verificar o local em que o reclamante se encontrava no período informado. Por esse procedimento é possível averiguar, entre outros fatos, a realização de horas extraordinárias ou reconhecimento de vínculo de emprego. No entendimento de alguns tribunais, o acesso a essas informações viola a intimidade e a privacidade do empregado, protegidas pela Constituição Federal, Lei Geral de Proteção de Dados Pessoais e normas internacionais, dessa forma instaura-se um conflito de interesses e direitos. O presente estudo é descritivo e qualitativo, com foco na análise da validade da produção desse meio de prova digital no processo do trabalho, frente aos princípios que norteiam o ordenamento jurídico, a doutrina especializada e o posicionamento jurisprudencial acerca do tema.
Aliyyü’l-Kârî’nin Şerhu Kitabi’l-Fıkhı’l-Ekber’de Kullandığı Hadislerin Kaynakları
Authors: Uğurlu Tuğberk
Published: November 2024

Molla Ali el-Kârî, Temel İslami İlimler sahasının birçok alanında (hadis, fıkıh, akaid, tefsir vb.) saygın eserler kaleme almış ve yaşadığı dönemde muasırı âlimlerce itibar görmüş, ayrıca 11. asrın müceddidi ünvanı bazı entelektüeller tarafından kendisine layık görülmüş bir ilim adamıdır. Hadis sahasındaysa günümüze kadar ulaşabilmiş, içerisinde uydurma hadisleri tespit edip derlediklerinin de bulunduğu 19 eser vererek bu alana da hâkimiyetini ispatlamıştır. Hanefi mezhebine mensup olmakla birlikte Ebû Hanîfe’nin görüşlerine son derece sadık kalmış, birçok alanda bu görüşleri savunmuş ve onun eserlerinden bazılarına da şerh yazmıştır. Bu şerhlerden belki de en meşhuru “el-Fıkhu’l-Ekber” adlı, İslam akaidinin temel konularını ele alan ve Hanefi mezhebinin temel kaynaklarından sayılan, İmam Azam Ebû Hanîfe’nin günümüze ulaşabilmiş küçük risalesine yazdığı şerhtir. Bu şerhte yer yer Kuran ayetlerinden, hadis-i şeriflerden ve meşhur ulemanın görüşlerinden faydalanarak Ebû Hanîfe’nin görüşlerini desteklemekle birlikte, batıl kabul ettiği fırkalarında görüşlerine yer verip onları eleştirmektedir. Biz bu çalışmamızda, hadis sahasında yetkinliğini ispatlamış olan Ali el-Kârî’nin, görüşlerini delillendirmek adına öne sürdüğü hadis rivayetlerinin kaynak değerlerini tespit etmeye çalışarak hem müellifin hadisçiliği hakkında fikir sahibi olmaya, hem de İslam akaidi konusunda üzerinde yapılan tartışmaların aktüel değerini koruduğu meseleler hakkında delil olarak zikredilen hadis rivayetlerinin hangi hadis kitaplarında rivayet edildiğini tespit etmeye, varsa rivayetlerin farklı lafızlarına ve senetlerine dikkat çekmeye çalışacağız.
A champion of perseverance
Authors: Desaulniers Laurie
Published: November 2024

Laurie Desaulniers is a determined 24-year-old living with lymphedema in both legs. Although Laurie’s journey is full of obstacles, she will stop at nothing to realize her dreams and lead a happy life, surrounded by her family and friends. We were particularly touched by Laurie’s positive attitude and strength of character, which will surely inspire our readers. The following transcript is of an interview with Laurie by the Lymphedema Association of Quebec (LAQ).
Perancangan Sistem Informasi Berbasis Web Pendataan Stok Helm di Toko Helm Bogor
Authors: Sudibyo Tommy , Setiawan Aji
Published: November 2024

Toko Helm Bogor merupakan usaha otomotif yang beroperasi di Kabupaten Bogor dan memiliki cabang di Bekasi. Proses pendataan stok barang saat ini masih dilakukan secara manual menggunakan Microsoft Excel, yang mengakibatkan kurangnya efisiensi dan akurasi dalam pengolahan data. Sistem informasi ini dirancang untuk mempermudah pengelolaan keluar masuk barang dan laporan stok secara cepat serta mudah. Aplikasi ini mengatur data masuk dan menampilkan laporan yang lengkap sesuai kebutuhan admin. Studi kasus ini menggunakan MySQL sebagai basis data, dan pengembangan aplikasi mengikuti metode waterfall yang dipilih berdasarkan referensi dari berbagai sumber. Diharapkan, sistem informasi ini dapat meningkatkan efisiensi dan akurasi dalam proses pendataan stok barang di Toko Helm Bogor.
The influence of socio-demographic factors on feelings of attachment, involvement, loyalty attitudes, and environmentally responsible behavior toward a cultural destination
Authors: De Cicco Roberta , Dini Mauro , Curina Ilaria , Francioni Barbara , Cioppi Marco
Published: November 2024

Tourist demand is very diverse and there are many alternatives for segmentation, with even basic demographic factors not only effectively discriminating in some markets but serving as a valuable starting point for creating market segmentation methods. Against this perspective, this study aims to provide a deeper analysis into whether and how socio-demographic factors, in terms of nationality, age, gender, and education explain tourists’ place attachment, in terms of place dependence, place identity, and sense of belonging, both online and onsite activity involvement, recommendation and revisit intentions, and environmentally responsible behavior (ERB) toward a cultural Italian destination. Data were collected from 384 tourists participating in a cultural heritage tourism experience. Descriptive statistics were analyzed and reported, and a series of ANOVAs were performed using SPSS to analyze possible differences among nationality, age, gender, and education, regarding the variables of interest. According to the literature, factors that may affect tourists' perceptions include socio-demographic data. However, current research on cultural tourism lacks an in-depth investigation of the relationships between various socio-demographic factors and tourists’ perceptions and behavior. While studies have looked at how these elements affect marketing in general, more data is still required to forecast cultural visitors’ feelings of attachment, involvement, intention, and environmental behavior toward a cultural destination. Results highlight that tourists of an Italian cultural destination have varying levels of education, age, and gender, and are partly represented by foreign visitors. Findings mainly confirm that the variables of interest can be influenced by the socio-demographic characteristics of tourists, with a major impact coming from nationality, age, and education. Moreover, they showed that the main differences were recorded for place identity, sense of belonging, onsite and online activity involvement, revisit intention, and responsible behavior, with only nationality and age respectively affecting place identity and recommendation intention.n intention.
Evaluating Sustainable Tourism: A Composite Index for European Destinations
Authors: Cesarini Samuele , Terraglia Ivan
Published: November 2024

This paper focuses on the analysis of sustainable tourism indicators for the 27 European Union (EU) countries to address the challenges faced by the tourism sector. The impact of sustainable tourism indicators on destination competitiveness was evaluated using the EU Tourism Dashboard, a scheme funded by the European Commission. The Mazziotta-Pareto Index was used to construct the indicator of sustainability by incorporating the three pillars of indicators: Environmental impact, Digitalisation, and Socio-economic vulnerability. The proposed approach provides greater tractability and flexibility for decision-makers to adjust the number of indicators to meet specific case conditions. The sustainable tourism indicators aim to provide critical information for resource allocation and policymaking in the conservation of tourism sites, as well as improving the welfare and inclusiveness of local communities. The findings of the analysis highlight significant disparities among destinations in terms of the examined indicators, emphasizing variations in sustainability profiles and performance within the tourism sector. These disparities underscore the need for personalized and targeted approaches to address the specific challenges and opportunities faced by each destination in achieving sustainable tourism development. Furthermore, the proposed ranking system, updated at regular intervals, can enhance the image and reputation of European areas as high-quality and sustainable destinations, attracting increased tourism demand. Additionally, the ranking system can foster knowledge sharing and the adoption of benchmarking practices, incentivizing countries to maintain and improve their position in the ranking. This work contributes to addressing the evidence gap in tourism sustainability policymaking and provides a comprehensive framework for the development of sustainable tourism analysis in the EU context.
How opinion leaders and operators communicate the image of the sustainable tourism destination
Authors: Capone Veronica , Touti Magda , Del Core Simona
Published: November 2024

Spiritual and cultural routes represent an example of a sustainable tourist destination, meaning a destination with the goal of generating economic activity while simultaneously safeguarding environmental and cultural heritage. In this regard, the Region of Sardinia, through its cultural and spiritual routes, is trying to counter mass tourism and promote the development of slow and sustainable tourism. In light of the region’s objectives, it is interesting to understand how the image of the sustainable destination of Sardinia’s spiritual and cultural routes is perceived and communicated. Specifically, the aim is to understand the image that emerges from the communication of opinion leaders and operators. To achieve the research objective, a mixed-method QUAL-QUAL approach was used, combining auto-photography with participant observation. Auto-photography was used to analyse destination photographs shared by opinion leaders and operators to understand how the image of the sustainable destination was communicated. In addition, participant observation was conducted to enhance the study’s insights through the engagement and direct observation of participants’ experiences. The integration of these two methodologies allowed us to establish the overall destination image. From the research results, it is evident that the overall image portrays a model of slow, experiential, and sustainable tourism. However, the results demonstrated that it needs to be further developed to fully realize its potential. Participant observation revealed that Sardinia is trying to preserve its authenticity and promote slow and sustainable tourism. Still, several challenges have surfaced including limited development, absence of laws to facilitate tourism activities, the need for new professional roles, and slow bureaucracy. The auto-photography revealed that opinion leaders and operators communicate aspects related to slow tourism through photographs, such as the pleasant, uncomplicated, and unhurried experiences. Nevertheless, the communication remains fairly standard, failing to emphasize the destination image’s sustainability, but focusing on aspects related to the cognitive dimension (e.g., beautiful scenery, a variety of fauna, and religious elements). From a theoretical perspective, the subject of sustainable destination image has been relatively underexplored, particularly within the context of cultural and spiritual routes. From a managerial perspective, this study provides insights into the image communicated and promoted by opinion leaders and operators. This enables organizations to assess whether the intended image aligns with that perceived by visitors and, if necessary, adjust their strategies accordingly.
Measuring Italian art cities tourism: a proposal of indicators
Authors: Avena Giuseppe , Gargano Romana
Published: November 2024

In Italy, art cities have traditionally served as “magnets” for cultural tourism, significantly contributing to the country’s economic vitality. Many historic city centers are not simply “boxes” of artworks but are veritable open-air museums. In recent years, the profile of cultural and experiential visitors has increasingly oriented towards experiences that can be enjoyed individually or with family. While the traditional tourism system continues to offer conventional tourist products, it is also evolving to meet the growing demand for unique and unforgettable experiences. This represents new challenges for destination areas that seek to improve services and create attractions that can meet this emerging new audience. The objective of this work is to propose a composite indicator that measures the tourism potential of these art cities, drawing upon existing tourism indexes in the literature and equitable and sustainable well-being (BES) indicators, such as the domains of “landscape and cultural heritage” and “environment”. The decision to employ these indicators stems from their considerable relevance in a country like Italy, as well as the specific focus of our study. Additionally, we developed a ranking of Italian art cities, enabling us to determine their relative levels of attractiveness. To achieve this, a panel of Italian provincial capitals was selected, each with at least one museum and a UNESCO site. The composite indicator developed, which also considers social and environmental perspectives, represents an alternative quantitative approach to assessing the attractiveness of art cities. The underlying principle is that, in the ever-evolving scene of cultural tourism, beyond the indispensable role played by artistic and cultural heritage, the impact of scenic landscapes on people's quality of life and its connection to individual well-being plays a crucial role. This indicator could provide territorial planning professionals with statistical tools capable of identifying the strengths and weaknesses of the tourism offer of those cities that set themselves the goal of being a privileged place of artistic tourist attraction. The proposed composite indicator should make it possible to comprehend whether and how to develop paths to enhance the entire artistic heritage, while also considering the well-being of visitors.
What skills in 21st-century tourism? Empirical evidence from online job advertisements
Authors: Grassini Laura , Kahlawi Adham , Varra Lucia
Published: November 2024

This paper aims to understand what skills are required in jobs in the tourism sector, looking from a particular perspective: that of online job advertisements, which, although not very present in the sector, constitute a valuable source for making reflections on the current use of the tool among operators, the professional figures required, the transversal skills considered most necessary. Furthermore, the study provides a comparison between online job ad data and some statistical sources concerning occupations and skills in tourism. A descriptive and explorative analysis of online job ads is performed to meet the paper's objectives. The study is carried out on a dataset produced by LightcastTM and reporting information on online job advertisements for Italy in 2022. This contribution represents one of the few works that analyse the tourism job market through online job advertisements, with a critical view of the information content of those data sources compared to frameworks and perspectives adopted in the academic literature. Despite the limitations deriving from the fact that tourism is not well represented in online job ads, the results provide helpful reflections on the skills demanded in the sector and their development. There is confirmation that this could help with corporate management choices, education, the development of the job market, and the competitiveness of destinations. At the same time, for these data to provide information consistent with theories and conceptual frameworks specific to human resources research, it is necessary to trace them back to classifications and taxonomies consolidated in the literature.
Tourism in smart villages as an enhancement of rural areas
Authors: Mozzillo Mirko , Amatucci Fabio Michele
Published: November 2024

The purpose of this work is to verify whether Italian smart villages are attractive on a tourist level. This article has the task of analyzing and highlighting the health status of rural villages and checking which and how many of them have evolved toward a sustainable rural village concept, defined in the literature by the name smart village. The study was conducted through the analysis of the projects applied within the two smart villages under study. The two villages analyzed focus on future-oriented development and identify already integrated urban areas as a test bed, capable of attracting the population, workers, and tourists. Both villages have common objectives such as, for example, the transformation from rural villages into smart villages, overcoming the state of depopulation, making them attractive on a tourist level, and pursuing urban development strategies, guaranteeing territorial sustainability. The urban planning process and energy policies are integrated with the Smart Village policies, whose meeting point and strength are represented by the technology applied to the city. The method brings to both experiences multiple points of advantage dictated by the fact that the methodology allows all interested parties of citizens to actively participate in the political life and not only of the city. The successful application of transformation policies in these cities can be used as a future test bed to enable other cities to develop and evolve from classic rural villages to smart villages.
Impact of New Technology in Increasing Cyber Crime in Rwanda
Authors: UWIHANGANYE Vedaste ,   University of Lay Adventists of Kigali, M. Enan Dr. Nyesheja ,   University of Lay Adventists of Kigali, James Dr. RWIGEMA ,   University of Rwanda
Published: November 2024

The ICT sector in Rwanda has grown rapidly in recent years, with access to information and communication technologies available to the government, private sector, communities, and international organizations. The rate of the population mobile users was 76.6% in March 2018 according to the report published by Rwanda Utilities Regulatory Agency (RURA). Also in March 2018, the number of mobile money transactions was 692.5 billion Rwandan francs. Due to this information provided, above we decided to carry out research of assessing the impact of technology in increasing cybercrime in Rwanda and set measures that can be used to avoid cybercrime.
Kajian Etika Profesi Tentang Mutasi Pendeta di Jemaat GMIBM Bethesda Bangunan Wuwuk Wilayah Modayag
Authors: Sumakul Henny W. B. , Lengkong Syalomita Herlin
Published: November 2024

Membahas tentang profesi Pendeta sudah banyak dilakukan oleh peneliti ataupun para teolog.  Namun membahas tentang etika pendeta dalam rangka penempatan dan mutasinya dalam sebuah sinode masih jarang dijumpai. Artikel ini bertujuan  membahas tentang Mutasi Pendeta dalam hubungannya dengan profesi dan panggilan kependetaannya yang mendapat tugas dari Sinode gereja di GMIBM Bethesda Bangunan Wuwuk.. Persoalannya adalah apakah  pendeta yang telah ditetapkan  juga menaati suatu aturan yang berlaku sebab akan berdampak dalam pelayanan di jemaat. Sehingga dalam masalah ini memiliki dampak yang luar biasa dalam pelayanan dan pembangunan. Penelitian ini menggunakan metode kualitatif untuk menunjang penelitian yaitu observasi, wawancara, dan studi kepustakaan. Hasil penelitian ini memberikan pemahaman yang lebih dalam tentang panggilan kependetaan yang terikat juga dengan aturan dan ketetapan gereja termasuk mutasi pendeta. Tesis saya adalah Pendeta juga terikat dalam suatu peraturan dalam organisasi gereja dalam hal ini sinode dimana segala ketentuan dan aturan yang berlaku haruslah dipatuhi.
Misogyny against climate justice activists
Authors: Van der Heyden Katrien
Published: November 2024

The 2019 climate strikes were led by women with Great Thunberg being the first to start the Fridays for Future schoolstrikes. Anuna followed this example in Belgium. Being in this leading position, both received a huge amount of online harassment. The harassers were mainly young boys. The harassment was mainly sexual. This goes to show how the patriarchal masculinity experienced by the boys is felt to be threatened and needs to be defended by instigating violence against women. The deconstruction of patriarchal masculinity into caring types of masculinities/humanities, is to be prioritised in feminist and climate movements.
Compliance como instrumento de cumprimento proativo da função socioambiental da empresa
Authors: Medeiros Neto Elias Marques de , Brida Nério Andrade de
Published: November 2024

O objetivo do presente artigo é demonstrar que o programa de integridade empresarial, denominado de comliance, pode ser hábil ferramenta de atuação proativa da empresa para cumprimento da função socioambiental da atividade econômica empresarial. Em processo de desenvolvimento empírico dialético, constata-se que a função social da empresa está no agir além das obrigações legais estatuídas, promovendo efetivamente e positivamente programas de desenvolvimento sustentável. Para tanto, discorre-se pelos fundamentos da função social da empresa, suas origens e bases constitucionais, voltadas na proteção do meio ambiente. Seguiu-se para exame do instituto do compliance de finalidade de proteção e preservação ambiental, bases fundamentais, legais e de instrumento de cumprimento da função social da empresa. Conclui-se que o compliance ambiental pode integrar-se na modalidade de eficaz instrumento de proposições de programas proativos de desenvolvimento sustentável, em cumprimento da função socioambiental da empresa.
Aspectos regulatórios do uso de anabolizantes e os efeitos da proibição do Conselho Federal de Medicina no mercado fisiculturista
Authors: Freitas Thaís Onofre Caixeta de , Nohara Irene Patrícia
Published: November 2024

O artigo analisa, do prisma regulatório, os impactos do ato normativo veiculado pela Resolução 2.333/2023 do Conselho Federal de Medicina, que proíbe a prescrição de esteroides e anabolizantes para fins meramente estéticos, de ganho de massa muscular e melhora do desempenho esportivo. Objetiva-se problematizar a irrazoabilidade do afastamento do acompanhamento profissional e os efeitos no mercado fisiculturista e fitness, sendo abordados, a partir do método hipotético-dedutivo, os limites do poder de polícia profissional. Espera-se contribuir para se repensar a proibição, com o fito de que haja uma substituição da vedação por uma liberdade condicionada, apta a afastar a indesejada automedicação, sendo esta última muito menos eficaz à garantia do direito à saúde do que o acompanhamento médico.
Control System of the Continuous Extrusion Line Using PLC and Conventional Regulators
Authors: Kocić Igor B. , Danković Nikola B. , Nikolić Saša S. , Mitić Darko B. , Đekić Petar S.
Published: November 2024

This paper presents the functional characteristics of the line parameters based on the developed control software for speed, tension, regulation of traverse device for proper arrangement of the material on drum and temperature regulation. Speed and tension regulation is performed using the PLC controller S7 1500 series and conventional converters and inverters of the Sinamics DCM and G120 series. A control method was used where one device is the leader and all the others follow its speed with a given ratio and tensile control. Setting the parameters of conventional converters and inverters for controlling multi-motor drives was realized using the StartDrive tool. The temperature control of the extruder zones was done taking into account the mutual influence of the zones. Control and monitoring are implemented with software written in TIA Portal V15.1. software package.
Improving the Teaching of Histology by Using the Manual Whole Slide Imaging Technology
Authors: Ljubojević Miloš , Savić Mihajlo , Ljubojević Vesna , Milinković Bojana , Mijić Danijel
Published: November 2024

The tissue sample analysis based on the visualization of the entire tissue sample represents an important methodology in clinical diagnostics, research, and education. This process that enables visualization of the entire tissue sample is named whole slide imaging. For clinical purposes, professional and very expensive scanners are used for tissue sample digitization and the creation of whole slide images. In education, it is possible to use whole slide images that do not necessarily follow strict medical standards and regulations. Therefore, the important research task is to propose a methodology for the manual creation of whole slide images and its adequate use in medical education. In this paper, the use of manually created whole slide images in histology classes education was analyzed. In the experimental part of this research, the methodology of manual creation and usage of whole slide images (WSI) in histology education is presented in more detail. The subjective assessment of the user's satisfaction with WSI usage in education was also performed. It was shown that the whole slide images were evaluated very positively in the histological analysis and education process. Using WSI can significantly improve histology teaching, especially when distance education principles are implemented. Therefore, in crises like the pandemic situation COVID-19 WSI usage becomes a very important educational tool for teaching microscope-related topics. The results of this research showed that the use of whole slide images in histology classes is in line with the process of digital transformation in education.
Molecular characterization of gustatory second-order neurons reveals integrative mechanisms of gustatory and metabolic information
Authors: Mollá-Albaladejo Rubén , Jiménez-Caballero Manuel , Sánchez-Alcañiz Juan A
Published: November 2024

Animals must balance the urgent need to find food during starvation with the critical necessity to avoid toxic substances to ensure their survival. In
Drosophila
, specialized Gustatory Receptors (GRs) expressed in Gustatory Receptor Neurons (GRNs) are critical for distinguishing between nutritious and potentially toxic food. GRNs project their axons from taste organs to the Subesophageal Zone (SEZ) in the Central Brain (CB) of
Drosophila
, where gustatory information is processed. Although the roles of GRs and GRNs are well- documented, the processing of gustatory information in the SEZ remains unclear. To better understand gustatory sensory processing and feeding decision-making, we molecularly characterized the first layer of gustatory interneurons, referred to as Gustatory Second Order Neurons (G2Ns), which receive direct input from GRNs. Using trans-synaptic tracing with
trans-
Tango, cell sorting, and bulk RNAseq under fed and starved conditions, we discovered that G2Ns vary based on gustatory input and that their molecular profile changes with the fly’s metabolic state. Further data analysis has revealed that a pair of neurons in the SEZ, expressing the neuropeptide Leucokinin (SELK neurons), receive simultaneous input from GRNs sensing bitter (potentially toxic) and sweet (nutritious) information. Additionally, these neurons also receive inputs regarding the starvation levels of the fly. These results highlight a novel mechanism of feeding regulation and metabolic integration.
Endogenous FGFs drive ERK-dependent cell fate patterning in 2D human gastruloids
Authors: Jo Kyoung , Liu Zong-Yuan , Patel Gauri , Yu Zhiyuan , Yao LiAng , Teague Seth , Johnson Craig , Spence Jason , Heemskerk Idse
Published: November 2024

The role of FGF is the least understood of the morphogens driving mammalian gastrulation. Here we investigated the function of FGF in a stem cell model for human gastrulation known as a 2D gastruloid. We found a ring of FGF-dependent ERK activity that closely follows the emergence of primitive streak (PS)-like cells but expands further inward. We showed that this ERK activity pattern is required for PS-like differentiation and that loss of PS-like cells upon FGF receptor inhibition can be rescued by directly activating ERK. We further demonstrated that the ERK-ring depends on localized activation of basally localized FGF receptors (FGFR) by endogenous FGF gradients. We confirm and extend previous studies in analyzing expression of FGF pathway components, showing the main receptor to be FGFR1 and the key ligands FGF2/4/17, similar to the human and monkey embryo but different from the mouse. In situ hybridization and scRNA-seq revealed that
FGF4
and
FGF17
expression colocalize with the PS marker TBXT but only
FGF17
is maintained in nascent mesoderm and endoderm. FGF4 and FGF17 reduction both reduced ERK activity and differentiation to PS-like cells and their derivatives, indicating overlapping function. Thus, we have identified a previously unknown role for FGF-dependent ERK signaling in 2D gastruloids and possibly the human embryo, driven by a mechanism where FGF4 and FGF17 signal through basally localized FGFR1 to induce PS-like cells.
An altered cell-specific subcellular distribution of translesion synthesis DNA polymerase kappa (POLK) in aging neurons
Authors: Abdelmageed Mofida , Palanisamy Premkumar , Vernail Victoria , Silberman Yuval , Paul Shilpi , Paul Anirban
Published: November 2024

Genomic stability is critical for cellular function, however, in the central nervous system highly metabolically active differentiated neurons are challenged to maintain their genome over the organismal lifespan without replication. DNA damage in neurons increases with chronological age and accelerates in neurodegenerative disorders, resulting in cellular and systemic dysregulation. Distinct DNA damage response strategies have evolved with a host of polymerases. The Y-family translesion synthesis (TLS) polymerases are well known for bypassing and repairing damaged DNA in dividing cells. However, their expression, dynamics, and role if any, in enduring postmitotic differentiated neurons of the brain are completely unknown. We show through systematic longitudinal studies for the first time that DNA polymerase kappa (POLK), a member of the Y-family polymerases, is highly expressed in neurons. With chronological age, there is a progressive and significant reduction of nuclear POLK with a concomitant accumulation in the cytoplasm that is predictive of brain tissue age. The reduction of nuclear POLK in old brains is congruent with an increase in DNA damage markers. The nuclear POLK colocalizes with damaged sites and DNA repair proteins. The cytoplasmic POLK accumulates with stress granules and endo/lysosomal markers. Nuclear POLK expression is significantly higher in GABAergic interneurons compared to excitatory pyramidal neurons and lowest in non-neurons, possibly reflective of the inherent biological differences such as firing rates and neuronal activity. Interneurons associated with microglia have significantly higher levels of cytoplasmic POLK in old age. Finally, we show that neuronal activity itself can lead to an increase in nuclear POLK levels and a reduction of the cytoplasmic fraction. Our findings open a new avenue in understanding how different classes of postmitotic neurons deploy TLS polymerase(s) to maintain their genomic integrity over time, which will help design strategies for longevity, healthspan, and prevention of neurodegeneration.
BEHAV3D Tumor Profiler to map heterogeneous cancer cell behavior in the tumor microenvironment
Authors: Rios-Jimenez Emilio , Zomer Anoek , Collot Raphael , Román Mario Barrera , Ariese Hendrikus , van Ineveld Ravian L , Kleinnijenhuis Michiel , Bessler Nils , Johnson Hannah , Rios Anne , Alieva Maria
Published: November 2024

Intravital microscopy (IVM) enables live imaging of animals at single-cell level, offering essential insights into cancer progression. This technique allows for the observation of single-cell behaviors within their natural 3D tissue environments, shedding light on how genetic and microenvironmental changes influence the complex dynamics of tumors. The complexity of data generated by IVM often surpasses the capabilities of conventional analyses accessible to biomedical scientists, thereby neglecting single-cell heterogeneity and limiting the exploration of microenvironmental influences on cellular behavior without bias. To address this challenge, here we introduce BEHAV3D Tumor Profiler (BEHAV3D-TP), a user-friendly computational framework designed for the comprehensive analysis of single tumor cell behaviors and their interactions with the tumor microenvironment (TME). BEHAV3D-TP facilitates unbiased profiling of cancer cell dynamics without requiring advanced computational expertise. Here, we apply BEHAV3D-TP to study diffuse midline glioma (DMG), a highly aggressive pediatric brain tumor characterized by invasive growth. Our analysis reveals that distinct migratory behaviors of DMG cells correlate with specific TME components such as tumor-associated macrophages and vasculature. This approach, initially aimed at uncovering tumor invasive patterns and their interactions with the TME, holds promise for understanding additional cancer cell behaviors like intravasation and metastasis. BEHAV3D-TP represents a significant advancement in democratizing the analysis of heterogeneous cancer cell behaviors and their TME interactions, providing accessible computational insights into tumor dynamics.
An ancient competition for the conserved branchpoint sequence influences physiological and evolutionary outcomes in splicing
Authors: Pereira de Castro Karen Larissa , Abril Jose M , Liao Kuo-Chieh , Hao Haiping , Donohue John Paul , Russell William K , Fagg W Samuel
Published: November 2024

Recognition of the intron branchpoint during spliceosome assembly is a multistep process that defines both mRNA structure and amount. A branchpoint sequence motif UACUAAC is variably conserved in eukaryotic genomes, but in some organisms more than one protein can recognize it. Here we show that SF1 and Quaking (QKI) compete for a subset of intron branchpoints with the sequence ACUAA. SF1 activates exon inclusion through this sequence, but QKI represses the inclusion of alternatively spliced exons with this intron branchpoint sequence. Using mutant reporters derived from a natural intron with two branchpoint-like sequences, we find that when either branchpoint sequence is mutated, the other is used as a branchpoint, but when both are present, neither is used due to high affinity binding and strong splicing repression by QKI. QKI occupancy at the dual branchpoint site directly prevents SF1 binding and subsequent recruitment of spliceosome-associated factors. Finally, the ectopic expression of QKI in budding yeast (which lacks
QKI
) is lethal, due at least in part to widespread splicing repression. In conclusion, QKI can function as a splicing repressor by directly competing with SF1/BBP for a subset of branchpoint sequences that closely mirror its high affinity binding site. This suggests that
QKI
and degenerate branchpoint sequences may have co-evolved as a means through which specific gene expression patterns could be maintained in QKI-expressing or non-expressing cells in metazoans, plants, and animals.
Amoeboid cells undergo durotaxis with soft end polarized NMIIA
Authors: Kang Chenlu , Chen Pengcheng , Yi Xin , Li Dong , Hu Yiping , Yang Yihong , Cai Huaqing , Li Bo , Wu Congying
Published: November 2024

Cell migration towards stiff substrates has been coined as durotaxis and implicated in development, wound healing and cancer, where complex interplays between immune and non-immune cells are present. Compared to the emerging mechanisms underlying the strongly adhesive mesenchymal durotaxis, little is known about whether immune cells - migrating in amoeboid mode - could follow mechanical cues. Here we develop an imaging-based confined migration device with stiffness gradient. By tracking live cell trajectory and analyzing the directionality of T cells and neutrophils, we observe that amoeboid cells can durotax. We further delineate the underlying mechanism to involve non-muscle myosin IIA (NMIIA) polarization towards the soft-matrix-side but may not require differential actin flow up- or down-stiffness gradient. Using the protista
Dictyostelium
, we demonstrate the evolutionary conservation of amoeboid durotaxis. Finally, these experimental phenomena are theoretically captured by an active gel model capable of mechanosensing. Collectively, these results may shed new lights on immune surveillance and recently identified confined migration of cancer cells, within the mechanically inhomogeneous tumor microenvironment or the inflamed fibrotic tissues.
The nanoscale organization of the Nipah virus fusion protein informs new membrane fusion mechanisms
Authors: Wang Qian , Liu Jinxin , Luo Yuhang , Kliemke Vicky , Matta Giuliana Leonarda , Wang Jingjing , Liu Qian
Published: November 2024

Paramyxovirus membrane fusion requires an attachment protein for receptor binding and a fusion protein for membrane fusion triggering. Nipah virus (NiV) attachment protein (G) binds to ephrinB2 or -B3 receptors, and fusion protein (F) mediates membrane fusion. NiV-F is a class I fusion protein and is activated by endosomal cleavage. The crystal structure of a soluble GCN4-decorated NiV-F shows a hexamer-of-trimer assembly. Here, we used single-molecule localization microscopy to quantify the NiV-F distribution and organization on cell and virus-like-particle membranes at a nanometer precision. We found that NiV-F on biological membranes forms distinctive clusters that are independent of endosomal cleavage or expression levels. The sequestration of NiV-F into dense clusters favors membrane fusion triggering. The nano-distribution and organization of NiV-F are susceptible to mutations at the hexamer-of-trimer interface, and the putative oligomerization motif on the transmembrane domain. We also show that NiV-F nanoclusters are maintained by NiV-F-AP-2 interactions and the clathrin coat assembly. We propose that the organization of NiV-F into nanoclusters facilitates membrane fusion triggering by a mixed population of NiV-F molecules with varied degrees of cleavage and opportunities for interacting with the NiV-G/receptor complex. These observations provide insights into the in-situ organization and activation mechanisms of the NiV fusion machinery.
Modeling and Simulation of Neocortical Micro- and Mesocircuitry. Part II: Physiology and Experimentation
Authors: Isbister James B , Ecker András , Pokorny Christoph , Bolaños-Puchet Sirio , Egas Santander Daniela , Arnaudon Alexis , Awile Omar , Barros-Zulaica Natali , Blanco Alonso Jorge , Boci Elvis , Chindemi Giuseppe , Courcol Jean-Denis , Damart Tanguy , Delemontex Thomas , Dietz Alexander , Ficarelli Gianluca , Gevaert Mike , Herttuainen Joni , Ivaska Genrich , Ji Weina , Keller Daniel , King James , Kumbhar Pramod , Lapere Samuel , Litvak Polina , Mandge Darshan , Muller Eilif B , Pereira Fernando , Planas Judit , Ranjan Rajnish , Reva Maria , Romani Armando , Rössert Christian , Schürmann Felix , Sood Vishal , Teska Aleksandra , Tuncel Anil , Van Geit Werner , Wolf Matthias , Markram Henry , Ramaswamy Srikanth , Reimann Michael W
Published: November 2024

Cortical dynamics underlie many cognitive processes and emerge from complex multi-scale interactions, which are challenging to study
in vivo
. Large-scale, biophysically detailed models offer a tool which can complement laboratory approaches. We present a model comprising eight somatosensory cortex subregions, 4.2 million morphological and electrically-detailed neurons, and 13.2 billion local and mid-range synapses.
In silico
tools enabled reproduction and extension of complex laboratory experiments under a single parameterization, providing strong validation. The model reproduced millisecond-precise stimulus-responses, stimulus-encoding under targeted optogenetic activation, and selective propagation of stimulus-evoked activity to downstream areas. The model’s direct correspondence with biology generated predictions about how multiscale organization shapes activity; for example, how cortical activity is shaped by high-dimensional connectivity motifs in local and mid-range connectivity, and spatial targeting rules by inhibitory subpopulations. The latter was facilitated using a rewired connectome which included specific targeting rules observed for different inhibitory neuron types in electron microscopy. The model also predicted the role of inhibitory interneuron types and different layers in stimulus encoding. Simulation tools and a large subvolume of the model are made available to enable further community-driven improvement, validation and investigation.
Student Teachers’ Study Profiles — Longitudinal Perspective to Research-Based Teacher Education
Authors: Lähteenmäki Marko , Mikkilä-Erdmann Mirjamaija , Laakkonen Eero , Warinowski Anu , Clinton Janet
Published: November 2024

This study examined student teachers’ study profiles and achievement levels from selection through to the bachelor’s phase of their teacher education programmes. The latent profile analysis revealed two student teacher study profile subgroups associated with varying study achievement levels from the first three years of the teacher education programme. In a more detailed examination, the results revealed that the main differences occur during the bachelor’s phase of the teacher education programme, wherein student teachers are learning to understand the research-based teaching profession and how to conceptualise theories and more independently learn to write their bachelor’s theses. A gender comparison between subgroups revealed that male student teachers were more likely to be allocated to the less research-oriented subgroup and female students to the highly research-oriented subgroup. These findings are discussed with regard to how teacher education programmes could better support different learners.
Morphological, molecular and 3D synchrotron X-ray tomographic characterizations of Helicascus satunensis sp. nov., a novel mangrove fungus
Authors: Preedanon Sita , Klaysuban Anupong , Suetrong Satinee , Pracharoen Oraphin , Promchoo Waratthaya , Sangtiean Tanuwong , Rojviriya Catleya , Sakayaroj Jariya
Published: November 2024

A new species of Helicascus satunensis sp. nov. was collected on mature dead fruits of the Nypa palm in Satun Province, southern Thailand. Its morphological characteristics are similar to those of the genus Helicascus. Recently, a genus Helicascus with three species from marine habitats worldwide was studied. The morphology of this fungus was investigated and combined with multigene sequence analyzes of small subunit (SSU), large subunit (LSU), internal transcribed spacer (ITS) ribosomal DNA, translation elongation factor 1-alpha (TEF-1α) and RNA polymerase II (RPB2) genes. Morphologically, H. satunensis sp. nov. is characterized by semi-immersed, lenticular ascomata, multilocules, a bitunicate ascus and smooth, obovoid, dark brown ascospores that are one-septate and unequally two-celled. In addition, 3D visualization using synchrotron X-ray tomography was performed to investigate the interaction between fruiting body and substrata. Molecular phylogeny with multigene revealed that H. satunensis sp. nov. belongs to the family Morosphaeriaceae, order Pleosporales, class Dothideomycetes. Furthermore, H. satunensis sp. nov. forms a well-supported clade with Helicascus species described from marine habitats. Based on the unique morphological and molecular evidence, we propose this fungus, H. satunensis sp. nov., as a new species for Helicascus.
Moringa oleifera Leaf Meal: A Sustainable Approach for Poultry Production: A Review
Authors: Lata Manju , Mondal B.C.
Published: November 2024

Poultry production is among the fastest ways to address the shortage of animal protein supply and intake in many nations. With the prohibition of antibiotics as growth promoters in the poultry industry due to rising bacterial resistance and growing public concern over health and food safety, the sector has been prompted to seek safe alternatives. This shift has led to a focus on finding natural antibiotic substitutes and optimizing feed management to enhance chicken health and growth. Consequently, phytogenics have emerged as promising natural alternatives to antibiotics in the poultry sector. Moringa oleifera has attracted significant research interest recently as a natural supplement with numerous health advantages for poultry. Known for its antimicrobial, antioxidant, anti-inflammatory, and cholesterol-lowering properties, Moringa also aids in activating digestive enzymes in the stomach due to its wealth of bioactive compounds. This review emphasizes the potential impact of Moringa oleifera as a natural feed additive on growth performance, nutrient digestibility, blood biochemical profile, antioxidant effects, immune response, and egg production in poultry.
Impact of Parental Deprivation on Academic Success of Children: A Study of Public Primary Schools in Masaba South, Kenya
Authors: Keari Omwenga Michael , Alice Anika A. , W. Mwangi Sara
Published: November 2024

This study investigated the relationship between parental deprivation and academic achievement among children from public primary schools. Using correlation and cross-sectional study designs, data were collected from 10 schools, involving 324 randomly selected children in grades 4 and 5. Results revealed a high prevalence of parental deprivation, with significant deficits in necessities, safety, shelter, educational resources, and parental care. Most children reported problems with clothing (95.1%), food (98.8%), safety (65.9%), shelter (34.7%), education (87.3%), quality time with parents (88.2%), and parental discipline (83.6%). Parental deprivation negatively impacted academic achievement. Grade level (Adjusted β = 0.1, 95% CI [-0.8, 1.0], p = .819) and age (Adjusted β = 0.5, 95% CI [-0.1, 1.0], p = .110) showed no significant associations with absenteeism or grades. However, difficulties affording shelter were a significant negative predictor of grades (aβ = -2.7, 95% CI [-2.8, -2.6], p < .001), while spending quality time with parents positively influenced grades (aβ = 0.4, 95% CI [0.2, 0.6], p < .001). The study demonstrated the need for comprehensive interventions addressing parental deprivation's material and education achievements. Recommendations include strengthening social safety nets, enhancing educational resources, promoting positive parenting practices, and addressing economic inequalities.
Associating the Instructional Practices and Self-efficacy of Teachers in Selected Public Elementary Schools in Antique, Philippines
Authors: Saragena Nonie D. , Maravillas Nonie C. , Bual Joel M. , Ramales Jethro Lemuel M.
Published: November 2024

This study assessed the instructional practices of public elementary teachers in planning, teaching, and assessing relative to sex, age, length of teaching experience, educational attainment, and current teaching position. It also determined their self-efficacy in behavioral management, instruction, motivation, and non-teaching tasks relative to the demographics. Likewise, it correlated their instructional practices and self-efficacy. This employed the descriptive-correlational design where 192 public elementary teachers in a school division in Central Philippines responded to the validated and reliability-tested researcher-made questionnaires. In data analysis, mean, standard deviation and Pearson product-moment correlation coefficient were utilized. Generally, the teachers rated high instructional practice in planning, teaching, and assessing. Their self-efficacy was found high in behavioral management and instruction while very high in motivation and non-teaching tasks. Finally, a significant positive relationship (r=0.807, p<0.001) was found between instructional practices and self-efficacy. These findings imply that enhancing teachers' competence in planning, teaching, and assessing may positively influence their self-efficacy. The study recommends focused interventions in these areas to ensure successful instructional processes and improve educational outcomes.