bluuebunny/crossref_metadata_2025 huggingface dataset:
A influência da percepção do valor da marca no processo de decisão de escolha: uma análise às instituições do ensino superior da Cidade de Maputo
Authors: De Moçambique Universidade Católica
Published: November 2024

A globalização do mercado impulsionada pelos avanços tecnológicos, trouxe uma nova dinâmica na produção e disponibilização de produtos e serviços em todas as categorias de negócio. As estratégias de marketing são uma prioridade para destacarem as marcas num cenário competitivo, sobretudo num contexto em que os consumidores se tornaram mais exigentes e criteriosos no processo de decisão de escolha das marcas. Ora, o propósito deste artigo consiste em analisar a influência da percepção do valor da marca na decisão de escolha de Instituições de Ensino Superior (IES), sob orientação do modelo teórico brand equity ten de Aaker e o modelo de Kotler e Keller. Assumiu- se uma abordagem quantitativa para o apuramento de dados primários. De forma geral, os resultados apontaram para a existência de uma influência positiva da lealdade, notoriedade, associação a marca e qualidade percebida no processo de decisão de escolha. Igualmente, constatou-se que as principais fontes de estímulo para o reconhecimento do problema são os amigos e familiares, e as fontes para a busca de informações para avaliação da escolha são as consultas às IES através das visitas realizadas e dos amigos e familiares. Percebeu-se, ainda, que os principais atributos para a avaliação das alternativas foram a qualidade de ensino, o reconhecimento e o prestígio, as infraestruturas e os docentes qualificados. Concluiu- se, assim, que existe uma satisfação generalizada com as escolhas feitas pela disposição em permanecerem nas IES e indicá-las aos amigos e familiares.
Dasar Dan Peran Sistem Informasi Manajemen
Authors: Widodo  , Syafrizal Fuady
Published: October 2024

Sistem informasi manajemen merupakan hal yang sangat dibutuhkan dalam manajemen. Dan manajemen memiliki peranan yang sangat penting dalam sistem informasi sebagai bahan dalam pengambilan keputusan oleh manajer suatu organisasi. Sistem informasi dalam suatu organisasi dapat dikatakan sebagai suatu sistem yang menyediakan informasi bagi semua tingkatan dalam organisasi tersebut kapan saja diperlukan. Sistem ini menyimpan, mengambil, mengubah, mengolah dan mengkomunikasikan informasi yang diterima dengan menggunakan sistem informasi atau peralatan sistem lainnya. Sistem informasi harus dikembangkan dengan alasan adanya permasalahan berupa adanya ketertinggalan sistem dan pertumbuhan organisasi. Tujuan dari penelitian ini  untuk memaparkan konsep dasar sistem informasi manejemen dan bagaimana peranan manajemen dalam sistem informasi.
lingkungan Sosial Pendidikan Di MA Al-Huda Karang Melati Sebagai Pendukung Pembelajaran Bahasa Arab Siswa
Authors: Anang Silahuddin
Published: October 2024

Guru sebagai satu-satunya sumber belajar  adalah paradikma lama yang menjadikan kegiatan belajar mengajar kurang kondusif dan kurangnya inovasi, pengajar di dalam menyampaikan materi dan juga kurangnya para pengajar dalam menguasai materi dan metode menjadikan Susana belajar menjadi terasa sangat membosankan.Tidak terkecuali pelajaran bahasa Arab, pelajaran bahasa Arab adalah pembelajaran yang sangat membutuhkan media untuk membantu peran guru di dalam mengajar, baik media yang berupa audio, atau visual atau bahkan audio visual. Dalam mempelajari bahasa kedua, masuk kedalam dunia bahasa sasaran adalah langkah paling yang paling efektif bagi para pembelajar bahasa.di Nūrus-Sālām  misalnya, yang membuat program lingkungan berbahasa untuk membiasakan  siswa nya berbahasa Arab.
Manajemen System (DBMS) Basic Concepts
Authors: Widodo
Published: October 2024

Database Management System (DBMS) adalah sebuah perangkat lunak yang mendesain, mengelola, dan memanipulasi basis data. Konsep dasar DBMS meliputi pengorganisasian data, pemeliharaan integritas, dan penyediaan akses yang efisien ke informasi. DBMS mengizinkan pengguna untuk menyimpan, mengambil, dan memanipulasi data dengan cara yang terstruktur dan terpusat. Arsitektur DBMS mencakup komponen-komponen utama seperti model data, mesin penyimpanan, bahasa query, dan pengelola transaksi. Model data seperti model relasional, hierarkis, atau jaringan digunakan untuk mendefinisikan struktur data dalam basis data. Sistem penyimpanan data memungkinkan untuk penyimpanan yang efisien dan pengelolaan ruang penyimpanan yang terstruktur. Bahasa query, seperti SQL (Structured Query Language), memungkinkan pengguna untuk berinteraksi dengan basis data dengan cara yang mudah dimengerti dan terstandarisasi. Pengelola transaksi memastikan keakuratan data dengan mengelola transaksi yang terjadi secara bersamaan, memungkinkan konsistensi dan isolasi data. DBMS juga menawarkan keamanan data dengan sistem izin akses yang terdefinisi dengan baik, membatasi akses ke informasi yang sensitif. Keandalan dan pemulihan data juga menjadi aspek penting, di mana DBMS menyediakan fitur backup dan restore untuk memastikan pemulihan data dalam kasus kegagalan sistem. Penerapan DBMS memiliki dampak besar dalam berbagai bidang seperti bisnis, sains, pendidikan, dan lainnya. Penggunaan yang tepat dari DBMS dapat meningkatkan efisiensi, akurasi, dan keamanan dalam mengelola data, menjadi landasan penting dalam pengembangan teknologi informasi yang terus berkembang.
MageMemo
Authors: Winghart Hunter , Al Zaidy Ahmed
Published: October 2024

This paper presents MageMemo, an innovative productivity tool that integrates gamification and fantasy storytelling to enhance user engagement in task management. Traditional productivity applications often struggle to sustain long-term user interest, decreasing effectiveness over time. MageMemo addresses this challenge by creating a captivating experience where users earn achievements, level up, and uncover an unfolding narrative as they complete real-life tasks. By combining principles of Human-Computer Interaction (HCI) with a compelling fantasy theme, MageMemo offers a novel approach to improving productivity and motivation. Outlined are the design methodology, technical implementation, and evaluation metrics employed in the development of MageMemo, providing insights into its progression and potential to revolutionize how people use task management applications.
Cómo Gestionar una Empresa de Manera Responsable y Ética. Una Revisión de la Literatura
Authors: Mendez Quiroga Jorge Samuel
Published: November 2024

El presente trabajo aborda la importancia de gestionar una empresa de manera responsable y ética. El objetivo de esta investigación es demostrar que la responsabilidad social empresarial (RSE) y la sostenibilidad son factores clave para el éxito a largo plazo de una empresa. Para ello, se revisaron diversos estudios y se analizaron las estrategias más efectivas para implementar una gestión responsable y ética en una empresa. Entre las estrategias identificadas se encuentran la integración de los valores éticos en la cultura corporativa, el establecimiento de metas y objetivos de sostenibilidad, la medición y evaluación periódica de los impactos sociales, ambientales y económicos de la empresa, y el diálogo y compromiso activo con los stakeholders. Los resultados muestran que la gestión responsable y ética puede generar importantes beneficios para la empresa, como el fortalecimiento de la reputación y la marca, la mejora de la satisfacción y fidelización de los clientes, la reducción de costos y riesgos, y el aumento de la motivación y retención de los empleados. Asimismo, se destaca la importancia de que la gestión responsable y ética se integre en la estrategia y operaciones cotidianas de la empresa para lograr un impacto sostenible y duradero. En conclusión, este trabajo demuestra la importancia de una gestión responsable y ética para el éxito sostenible de una empresa. Las estrategias identificadas pueden ser implementadas por cualquier tipo de empresa, independientemente de su tamaño o sector, y pueden generar importantes beneficios tanto para la empresa como para la sociedad y el medio ambiente.
Implementación de Sistemas de Tutoría Inteligente para Mejorar la Enseñanza de Matemáticas en Escuelas Primarias de Caravaca De La Cruz – Murcia - España
Authors: Fernández Sánchez Diego
Published: November 2024

En la búsqueda de métodos innovadores para la enseñanza de matemáticas, este estudio se enfoca en la implementación de sistemas de tutoría inteligente en escuelas primarias de Caravaca de la Cruz, Murcia - España. La investigación aborda cómo estas tecnologías afectan tanto el rendimiento académico en matemáticas como las actitudes de los estudiantes hacia su aprendizaje. A través de un diseño cuasi-experimental, que incluye grupos control y experimental con pre-pruebas y post-pruebas, se examinó el impacto de la tutoría inteligente en un grupo de 100 estudiantes de cuarto grado, seleccionados de dos escuelas con características demográficas y educativas similares. Con el objetivo de encontrar métodos nuevos para la enseñanza de las matemáticas, esta investigación se centra en la incursión de sistemas de tutoría inteligente en algunas escuelas primarias de Caravaca de la Cruz, Murcia – España. Este trabajo encara la afectación de las tecnologías en el rendimiento académico de los alumnos en matemáticas, como así también los factores actitudinales hacia su proceso de aprendizaje. Los hallazgos revelan que el grupo de estudiantes que interactuó con los sistemas de tutoría inteligente mostró mejoras significativas en su rendimiento en matemáticas en comparación con el grupo de control, que continuó con los métodos de enseñanza tradicionales. Además, se observó un aumento notable en la motivación y la confianza hacia el aprendizaje de matemáticas entre los estudiantes del grupo experimental. Estos resultados sugieren que los sistemas de tutoría inteligente ofrecen un medio eficaz y personalizado para abordar los desafíos de la enseñanza de matemáticas, potenciando el aprendizaje individualizado y la participación activa del estudiante. La investigación contribuye a la literatura existente sobre la integración de tecnologías educativas en el currículo escolar, subrayando la importancia de adoptar enfoques innovadores en la educación. Los sistemas de tutoría inteligente emergen como herramientas valiosas para mejorar el rendimiento académico y fomentar una actitud positiva hacia el aprendizaje. Este estudio no solo destaca los beneficios de la tutoría inteligente en la enseñanza de matemáticas, sino que también plantea preguntas para futuras investigaciones sobre su aplicación en otras áreas y niveles educativos.
Evolución de la Industria del Turismo Sostenible en España
Authors: Céspedes Morai Jorge Manuel
Published: November 2024

El turismo sostenible ha emergido como una prioridad clave a nivel global, debido a su potencial para equilibrar el desarrollo económico con la conservación ambiental y el bienestar social. En España, un destino turístico de renombre mundial, la industria turística enfrenta el reto de adoptar prácticas sostenibles para mitigar los impactos negativos del turismo de masas. Este estudio analiza la evolución del turismo sostenible en diversas regiones turísticas de España, evaluando el impacto económico, las prácticas sostenibles adoptadas, la percepción de los turistas y las políticas de apoyo implementadas. Se utilizó un enfoque cuantitativo basado en cuestionarios estructurados, distribuidos a una muestra representativa de turistas, operadores turísticos y residentes locales. Los resultados indican una creciente adopción de prácticas sostenibles, aunque con variaciones significativas entre regiones. Las percepciones de los turistas respecto al turismo sostenible son mayoritariamente positivas, aunque identifican áreas de mejora, particularmente en la comunicación y educación sobre prácticas sostenibles. Las políticas de apoyo, aunque en general efectivas, presentan desafíos en su implementación y seguimiento. Este estudio ofrece valiosas recomendaciones para mejorar la sostenibilidad del turismo en España, destacando la necesidad de políticas más coherentes y una mayor colaboración entre stakeholders. Asimismo, subraya la importancia de la educación y sensibilización de los turistas para fomentar un comportamiento más responsable. Los hallazgos de esta investigación pueden servir como base para futuras políticas y estrategias, contribuyendo al desarrollo sostenible del turismo en España.
Calculation of productive capacity: From theory to practice
Authors: Chavarría Hidalgo Carlos
Published: November 2024

This article suggests and conceptualizes a methodology for calculating capacity in production processes, applicable to both the manufacturing industry and service companies. Its relevance lies in the fact that a correct dimensioning of the productive capacities of a company is a fundamental aspect, not only for its operations department, but also for the rest of the functional areas of the organization. The study begins with a reflection of the main concepts associated with measuring the capacity of production processes; where the main activities of the methodology stand out: description of the process, time study, capacity calculation and planning; in addition to the concepts of bottleneck and profitability. And it ends with the application of the step-by-step methodology on a case raised about a venture about the sale of fresh sugar cane juice on weekends at a farmer market. In short, it is important to mention that the article also aims to serve as a tool to contribute to the development of the Know-How competencies of future industrial engineers given its importance recognized by the employers sector (Ramírez-Mora, 2023). And, that it serves as an instrument to facilitate the study of students during their hours of independent work in their study plans. (Ramírez-Mora, 2023).
Identificando a Inteligência em Crianças: Traços Físicos e Comportamentais
Authors: Agrela Rodrigues Fabiano de Abreu , Moreira da Silveira Francis , Moreira de Lima Murillo Ribeiro , Pinto Uchôa Karliny Sales
Published: November 2024

Este artigo explora a identificação precoce da inteligência em crianças através de traços físicos e comportamentais observáveis. São discutidos indicadores como olhar atento, capacidade de concentração, curiosidade insaciável, raciocínio profundo, habilidades verbais avançadas e alta capacidade de memória. O texto é sustentado por estudos neurocientíficos e genômicos, destacando a complexa interação entre o cérebro, a genética e o comportamento. Exemplos práticos são fornecidos para ilustrar cada traço.
Reproducibility of in vivo electrophysiological measurements in mice
Authors:   International Brain Laboratory, Banga Kush , Benson Julius , Bhagat Jai , Biderman Dan , Birman Daniel , Bonacchi Niccolò , Bruijns Sebastian A , Buchanan Kelly , Campbell Robert AA , Carandini Matteo , Chapuis Gaëlle A , Churchland Anne K , Davatolhagh M Felicia , Lee Hyun Dong , Faulkner Mayo , Gerçek Berk , Hu Fei , Huntenburg Julia , Hurwitz Cole , Khanal Anup , Krasniak Christopher , Langfield Christopher , Meijer Guido T , Miska Nathaniel J , Mohammadi Zeinab , Noel Jean-Paul , Paninski Liam , Pan-Vazquez Alejandro , Roth Noam , Schartner Michael , Socha Karolina , Steinmetz Nicholas A , Svoboda Karel , Taheri Marsa , Urai Anne E , Wells Miles , West Steven J , Whiteway Matthew R , Winter Olivier , Witten Ilana B
Published: October 2024

Understanding brain function relies on the collective work of many labs generating reproducible results. However, reproducibility has not been systematically assessed within the context of electrophysiological recordings during cognitive behaviors. To address this, we formed a multi-lab collaboration using a shared, open-source behavioral task and experimental apparatus. Experimenters in ten laboratories repeatedly targeted Neuropixels probes to the same location (spanning secondary visual areas, hippocampus, and thalamus) in mice making decisions; this generated a total of 121 experimental replicates, a unique dataset for evaluating reproducibility of electrophysiology experiments. Despite standardizing both behavioral and electrophysiological procedures, some experimental outcomes were highly variable. A closer analysis uncovered that variability in electrode targeting hindered reproducibility, as did the limited statistical power of some routinely used electrophysiological analyses, such as single-neuron tests of modulation by task parameters. Reproducibility was enhanced by histological and electrophysiological quality-control criteria. Our observations suggest that data from systems neuroscience is vulnerable to a lack of reproducibility, but that across-lab standardization, including metrics we propose, can serve to mitigate this.
Comparative neuroimaging of the carnivoran brain: Neocortical sulcal anatomy
Authors: Boch Magdalena , Karadachka Katrin , Loh Kep Kee , Benn R Austin , Roumazeilles Lea , Bertelsen Mads F , Manger Paul R , Wriggelsworth Ethan , Spiro Simon , Spocter Muhammad A , Johnson Philippa J , Avelino-de-Souza Kamilla , Patzke Nina , Lamm Claus , Miller Karla L , Sallet Jérôme , Khrapitchev Alexandre A , Tendler Benjamin C , Mars Rogier B
Published: October 2024

Carnivorans are an important study object for comparative neuroscience, as they exhibit a wide range of behaviours, ecological adaptations, and social structures. Previous studies have mainly examined relative brain size, but a comprehensive understanding of brain diversity requires the investigation of other aspects of their neuroanatomy. Here, we obtained primarily post-mortem brain scans from eighteen species of the order Carnivora, reconstructed their cortical surfaces, and examined neocortical sulcal anatomy to establish a framework for systematic inter-species comparisons. We observed distinct regional variations in sulcal anatomy, potentially related to the species’ behaviour and ecology. Arctoidea species with pronounced forepaw dexterity exhibited complex sulcal configurations in the presumed somatosensory cortex but low sulcal complexity in the presumed visual and auditory occipitotemporal cortex. Canidae had the largest number of unique major sulci with a unique sulcus in the occipital cortex and highly social canids featuring an additional frontal cortex sulcus. We also observed differentially complex occipito-temporal sulcal patterns in Felidae and Canidae, indicative of changes in auditory and visual areas that may be related to foraging strategies and social behaviour. In conclusion, this study presents an inventory of the sulcal anatomy of a number of rarely studied carnivoran brains and establishes a framework and novel avenues for further investigations employing a variety of neuroimaging modalities to reveal more about carnivoran brain diversity.
Stochastic cell-intrinsic stem cell decisions control colony growth in planarians
Authors: Frankovits Tamar , Cherian Prakash Varkey , Yesharim Yarden , Dobler Simon , Wurtzel Omri
Published: November 2024

Stem cells contribute to organismal homeostasis by balancing division, self-renewal and differentiation. Elucidating the strategies by which stem cells achieve this balance is critical for understanding homeostasis, and for addressing pathogenesis associated with the disruption of this balance (e.g., cancer). Planarians, highly regenerative flatworms, use pluripotent stem cells called neoblasts to maintain and regrow organs. A single neoblast can rescue an entire animal depleted from stem cells and regenerate all cell lineages. How neoblast differentiation and clonal expansion are governed to produce all the required cell types is unclear. Here, we integrated experimental and computational approaches to develop a quantitative model revealing basic principles of clonal growth of individual neoblasts. By experimentally suppressing differentiation to major lineages, we elucidated the interplay between colony growth and lineage decisions. Our findings suggest that neoblasts select their progenitor lineage based on a cell-intrinsic fate distribution. Arresting differentiation into specific lineages disrupts neoblast proliferative capacity without inducing compensatory expression of other lineages. Our analysis of neoblast colonies is consistent with a cell-intrinsic decision model that can operate without memory or communication between neoblasts. This simple cell fate decision process breaks down in homeostasis, likely because of the activity of feedback mechanisms. Our findings uncover essential principles of stem cell regulation in planarians, which are distinct from those observed in many vertebrate models. These mechanisms enable robust production of diverse cell types and facilitate regeneration of missing tissues.
Comparative analysis of the syncytiotrophoblast in placenta tissue and trophoblast organoids using snRNA sequencing
Authors: Keenen Madeline M , Yang Liheng , Liang Huan , Farmer Veronica J , Singh Rohit , Gladfelter Amy S , Coyne Carolyn B
Published: November 2024

The outer surface of chorionic villi in the human placenta consists of a single multinucleated cell called the syncytiotrophoblast (STB). The unique cellular ultrastructure of the STB presents challenges in deciphering its gene expression signature at the single-cell level, as the STB contains billions of nuclei in a single cell. There are many gaps in understanding the molecular mechanisms and developmental trajectories involved in STB formation and differentiation. To identify the underlying control of the STB, we performed comparative single nucleus (SN) and single cell (SC) RNA sequencing on placental tissue and tissue-derived trophoblast organoids (TOs). We found that SN was essential to capture the STB population from both tissue and TOs. Differential gene expression and pseudotime analysis of TO-derived STB identified three distinct nuclear subtypes reminiscent of those recently identified
in vivo
. These included a juvenile nuclear population that exhibited both CTB and STB marker expression, a population enriched in genes involved in oxygen sensing, and a fully differentiated subtype. Notably, suspension culture conditions of TOs that restore the native orientation of the STB (STB
out
) showed elevated expression of canonical STB markers and pregnancy hormones, along with a greater proportion of the terminally differentiated mature STB subtype, compared to those cultivated with an inverted STB polarity (STB
in
). Gene regulatory analysis identified novel markers of STB differentiation conserved in tissue and TOs, including the chromatin remodeler RYBP, that exhibited STB-specific RNA and protein expression. Finally, we compared STB gene expression signatures amongst first trimester tissue, full-term tissue, and TOs, identifying many commonalities but also notable variability across each sample type. This indicates that STB gene expression is responsive to its environmental context. Our findings emphasize the utility of TOs to accurately model STB differentiation and the distinct nuclear subtypes observed
in vivo
, offering a versatile platform for unraveling the molecular mechanisms governing STB functions in placental biology and disease.
Oviductin sets the species-specificity of the mammalian zona pellucida
Authors: de la Fuente Daniel , Maroto Maria , Cajas Yulia N , Cañón-Beltrán Karina , Fernandez-Gonzalez Raul , Munoz-Maceda Ana , Sanchez-Puig Juana M , Blasco Rafael , Cots Paula , Aviles Manuel , Rizos Dimitrios , Gutiérrez-Adán Alfonso
Published: October 2024

The zona pellucida (ZP) is vital for species-specific fertilization as this barrier mediates sperm-oocyte binding. Here, we determined whether sperm from distant mammalian orders (Carnivora, Primates, and Rodentia) could penetrate bovine oocytes by examining the role of bovine oviductal fluid and species-specific oviductal glycoprotein (OVGP1 or oviductin) from bovine, murine, or human sources in modulating the species specificity of bovine and murine oocytes. Sperm from all the species were found to penetrate intact bovine ovarian oocytes to form hybrid embryos. However, contact with oviductal fluid or bovine, murine, or human OVGP1, conferred the ZP species specificity, allowing only the penetration of the corresponding sperm regardless of the ZP’s origin. Glycolytic and microstructural analyses revealed that OVGP1 covers the pores present in the ZP and that OVGP1 glycosylation determines sperm specificity. This suggests specific fertilization capacity is acquired in the oviduct through the ZP’s incorporation of specific oviductin.
Multi-gradient Permutation Survival Analysis Identifies Mitosis and Immune Signatures Steadily Associated with Cancer Patient Prognosis
Authors: Cai Xinlei , Ye Yi , Liu Xiaoping , Fang Zhaoyuan , Chen Luonan , Li Fei , Ji Hongbin
Published: October 2024

The inconsistency of the association between genes and cancer prognosis is often attributed to many variables that contribute to patient survival. Whether there exist the Genes Steadily Associated with Prognosis (GEARs) and what their functions are remain largely elusive. We have developed a novel method called “Multi-gradient Permutation Survival Analysis” (MEMORY) to screen the GEARs using RNA-seq data from the TCGA database. Then we employed a network construction approach to identify hub genes from GEARs, and utilized them for cancer classification. In the case of LUAD, the GEARs were found to be related to mitosis. Our analysis suggested that LUAD cell lines carrying
PIK3CA
mutations exhibit increased drug resistance. For BRCA, the GEARs were related to immunity. The analysis revealed that
CDH1
mutation might influence immune infiltration through the EMT process in BRCA. We further explored the prognostic relevance of mitosis and immunity through their respective scores. This study offers significant biological insights into GEARs and highlights their potential as robust prognostic indicators across diverse cancer types.
Diverse somatic Transformer and sex chromosome karyotype pathways regulate gene expression in Drosophila gonad development
Authors: Mahadevaraju Sharvani , Pal Soumitra , Bhaskar Pradeep , McDonald Brennan D , Benner Leif , Denti Luca , Cozzi Davide , Bonizzoni Paola , Przytycka Teresa M , Oliver Brian
Published: October 2024

The somatic sex determination gene
transformer
(
tra
) is required for the highly sexually dimorphic development of most somatic cells, including those of the gonads. In addition, somatic
tra
is required for the germline development even though it is not required for sex determination within germ cells. Germ cell autonomous gene expression is also necessary for their sex determination. To understand the interplay between these signals, we compared the phenotype and gene expression of larval wild-type gonads and the sex-transformed
tra
gonads. XX larval ovaries transformed into testes were dramatically smaller than wild-type, with significant reductions in germ cell number, likely due to altered geometry of the stem cell niche. Additionally, there was a defect in progression into spermatocyte stages. XY larval testes transformed into ovaries had excessive germ cells, possibly due to the earlier onset of cell division. We suggest that germ cells are neither fully female nor male following somatic sex transformation, with certain pathways characteristic of each sex expressed in
tra
mutants. We found multiple patterns of somatic and germline gene expression control exclusively due to
tra
, exclusively due to sex chromosome karyotype, but usually due to a combination of these factors showing
tra
and sex chromosome karyotype pathways regulate gene expression during Drosophila gonad development.
RNase III in Salmonella Enteritidis enhances bacterial virulence by reducing host immune responses
Authors: Chan Bill Kwan-wai , Li Yingxue , Ni Hongyuhang , Chan Edward Wai-chi , Deng Xin , Huang Linfeng , Chen Sheng
Published: October 2024

Salmonella
is an important foodborne pathogen which comprises strains that exhibit varied virulence phenotypes and the capability of causing invasive human infection. In this study, the gene expression profile of foodborne and clinical
Salmonella
strains that exhibit high- and low-level virulence was investigated, with results showing that the expression level of a number of genes, including the
rnc
gene which encodes the RNase III ribonuclease, were exceptionally high in the high virulence strains. Investigation of the role of
rnc
in mediating expression of virulence phenotypes in
Salmonella
showed that the product of this gene could enhance expression of the superoxide dismutase SodA, which is an essential determinant of survival fitness of
Salmonella
under the oxidative stress elicited by the host immunity. On the other hand, we also discovered that the double-stranded RNA (dsRNA) released from
Salmonella
could trigger immune response of the host, and that the high-level expression of the
rnc
gene enabled
Salmonella
to evade the host immunity by reducing the amount of dsRNA accumulated in the bacterial cell. These findings provide insightful understanding of the regulation of
Salmonella
virulence and facilitate development of novel antimicrobial treatments through suppression of virulence expression and survival fitness of this important pathogen.
Evidence for a role of human blood-borne factors in mediating age-associated changes in molecular circadian rhythms
Authors: Schwarz Jessica E , Mrčela Antonijo , Lahens Nicholas F , Li Yongjun , Hsu Cynthia , Grant Gregory R , Skarke Carsten , Zhang Shirley L , Sehgal Amita
Published: November 2024

Aging is associated with a number of physiologic changes including perturbed circadian rhythms; however, mechanisms by which rhythms are altered remain unknown. To test the idea that circulating factors mediate age-dependent changes in peripheral rhythms, we compared the ability of human serum from young and old individuals to synchronize circadian rhythms in culture. We collected blood from apparently healthy young (age 25–30) and old (age 70–76) individuals at 14:00 and used the serum to synchronize cultured fibroblasts. We found that young and old sera are equally competent at initiating robust ~24 hr oscillations of a luciferase reporter driven by clock gene promoter. However, cyclic gene expression is affected, such that young and old sera promote cycling of different sets of genes. Genes that lose rhythmicity with old serum entrainment are associated with oxidative phosphorylation and Alzheimer’s Disease as identified by STRING and IPA analyses. Conversely, the expression of cycling genes associated with cholesterol biosynthesis increased in the cells entrained with old serum. Genes involved in the cell cycle and transcription/translation remain rhythmic in both conditions. We did not observe a global difference in the distribution of phase between groups, but found that peak expression of several clock-controlled genes (PER3, NR1D1, NR1D2, CRY1, CRY2, and TEF) lagged in the cells synchronized ex vivo with old serum. Taken together, these findings demonstrate that age-dependent blood-borne factors affect circadian rhythms in peripheral cells and have the potential to impact health and disease via maintaining or disrupting rhythms respectively.
Large-scale characterization of cocaine addiction-like behaviors reveals that escalation of intake, aversion-resistant responding, and breaking-points are highly correlated measures of the same construct
Authors: de Guglielmo Giordano , Carrette Lieselot , Kallupi Marsida , Brennan Molly , Boomhower Brent , Maturin Lisa , Conlisk Dana , Sedighim Sharona , Tieu Lani , Fannon McKenzie J , Martinez Angelica R , Velarde Nathan , Othman Dyar , Sichel Benjamin , Ramborger Jarryd , Lau Justin , Kononoff Jenni , Kimbrough Adam , Simpson Sierra , Smith Lauren C , Shankar Kokila , Bonnet-Zahedi Selene , Sneddon Elizabeth A , Avelar Alicia , Plasil Sonja Lorean , Mosquera Joseph , Crook Caitlin , Chun Lucas , Vang Ashley , Milan Kristel K , Schweitzer Paul , Lin Bonnie , Peng Beverly , Chitre Apurva S , Polesskaya Oksana , Solberg Woods Leah C , Palmer Abraham A , George Olivier
Published: November 2024

Addiction is commonly characterized by escalation of drug intake, compulsive drug seeking, and continued use despite harmful consequences. However, the factors contributing to the transition from moderate drug use to these problematic patterns remain unclear, particularly regarding the role of sex. Many preclinical studies have been limited by small sample sizes, low genetic diversity, and restricted drug access, making it challenging to model significant levels of intoxication or dependence and translate findings to humans. To address these limitations, we characterized addiction-like behaviors in a large sample of >500 outbred heterogeneous stock (HS) rats using an extended cocaine self-administration paradigm (6 hr/daily). We analyzed individual differences in escalation of intake, progressive ratio (PR) responding, continued use despite adverse consequences (contingent foot shocks), and irritability-like behavior during withdrawal. Principal component analysis showed that escalation of intake, progressive ratio responding, and continued use despite adverse consequences loaded onto a single factor that was distinct from irritability-like behaviors. Categorizing rats into resilient, mild, moderate, and severe addiction-like phenotypes showed that females exhibited higher addiction-like behaviors, with a lower proportion of resilient individuals compared to males. These findings suggest that, in genetically diverse rats with extended drug access, escalation of intake, continued use despite adverse consequences, and PR responding are highly correlated measures of a shared underlying construct. Furthermore, our results highlight sex differences in resilience to addiction-like behaviors.
FGF8-mediated gene regulation affects regional identity in human cerebral organoids
Authors: Bertacchi Michele , Maharaux Gwendoline , Loubat Agnès , Jung Matthieu , Studer Michèle
Published: November 2024

The morphogen FGF8 establishes graded positional cues imparting regional cellular responses via modulation of early target genes. The roles of FGF signaling and its effector genes remain poorly characterized in human experimental models mimicking early fetal telencephalic development. We used hiPSC-derived cerebral organoids as an in vitro platform to investigate the effect of FGF8 signaling on neural identity and differentiation. We found that FGF8 treatment increases cellular heterogeneity, leading to distinct telencephalic and mesencephalic-like domains that co-develop in multi-regional organoids. Within telencephalic regions, FGF8 affects the anteroposterior and dorsoventral identity of neural progenitors and the balance between GABAergic and glutamatergic neurons, thus impacting spontaneous neuronal network activity. Moreover, FGF8 efficiently modulates key regulators responsible for several human neurodevelopmental disorders. Overall, our results show that FGF8 signaling is directly involved in both regional patterning and cellular diversity in human cerebral organoids and in modulating genes associated with normal and pathological neural development.
Conservation of the cooling agent binding pocket within the TRPM subfamily
Authors: Huffer Kate , Denley Matthew CS , Oskoui Elisabeth V , Swartz Kenton J
Published: November 2024

Transient receptor potential (TRP) channels are a large and diverse family of tetrameric cation-selective channels that are activated by many different types of stimuli, including noxious heat or cold, organic ligands such as vanilloids or cooling agents, or intracellular Ca2+. Structures available for all subtypes of TRP channels reveal that the transmembrane domains are closely related despite their unique sensitivity to activating stimuli. Here, we use computational and electrophysiological approaches to explore the conservation of the cooling agent binding pocket identified within the S1–S4 domain of the Melastatin subfamily member TRPM8, the mammalian sensor of noxious cold, with other TRPM channel subtypes. We find that a subset of TRPM channels, including TRPM2, TRPM4, and TRPM5, contain pockets very similar to the cooling agent binding pocket in TRPM8. We then show how the cooling agent icilin modulates activation of mouse TRPM4 to intracellular Ca2+, enhancing the sensitivity of the channel to Ca2+ and diminishing outward-rectification to promote opening at negative voltages. Mutations known to promote or diminish activation of TRPM8 by cooling agents similarly alter activation of TRPM4 by icilin, suggesting that icilin binds to the cooling agent binding pocket to promote opening of the channel. These findings demonstrate that TRPM4 and TRPM8 channels share related ligand binding pockets that are allosterically coupled to opening of the pore.
DNA‐encoded chemical libraries – achievements and remaining challenges
Authors: Favalli Nicholas , Bassi Gabriele , Scheuermann Jörg , Neri Dario
Published: April 2018

DNA‐encoded chemical libraries (DECLs) are collections of compounds, individually coupled to DNA tags serving as amplifiable identification barcodes. Since individual compounds can be identified by the associated DNA tag, they can be stored as a mixture, allowing the synthesis and screening of combinatorial libraries of unprecedented size, facilitated by the implementation of split‐and‐pool synthetic procedures or other experimental methodologies. In this review, we briefly present relevant concepts and technologies, which are required for the implementation and interpretation of screening procedures with DNA‐encoded chemical libraries. Moreover, we illustrate some success stories, detailing how novel ligands were discovered from encoded libraries. Finally, we critically review what can realistically be achieved with the technology at the present time, highlighting challenges and opportunities for the future.
The Path From Litter to Soil: Insights Into Soil C Cycling From Long‐Term Input Manipulation and High‐Resolution Mass Spectrometry
Authors: Reynolds Lorien L. , Lajtha Kate , Bowden Richard D. , Tfaily Malak M. , Johnson Bart R. , Bridgham Scott D.
Published: April 2018

The path of carbon (C) from plant litter to soil organic matter (SOM) is key to understanding how soil C stocks and microbial decomposition will respond to climate change and whether soil C sinks can be enhanced. Long‐term ecosystem‐scale litter manipulations and molecular characterization of SOM provide a unique opportunity to explore these issues. We incubated soils from a 20‐year litter input experiment for 525 days and asked how litter quantity and source (i.e., roots versus aboveground litter) affected C cycling, microbial function, and the size and molecular composition of C pools. Input exclusion led to a 30% loss of soil C, attributable largely to the nonmineral‐associated C fraction, and to declines in soil C decomposition. The absence of roots caused a shift in the microbial catabolic profile, though there was little evidence that root litter was preferentially stabilized. Although C pool size did not change with litter additions, Fourier transform ion cyclotron resonance mass spectrometry analysis of the finest mineral fraction revealed dramatic changes to the chemical composition of carbon. Lipid content increased proportionally with input addition and was subsequently mineralized during incubation, indicating that this fraction was metabolically active. Moreover, nonmetric dimensional scaling showed that both litter treatments and incubation caused the molecular composition of SOM to change. We conclude that the path of C from litter to soil may involve labile pools and root‐driven microbial activity associated directly with SOM in the soil mineral matrix otherwise previously hypothesized to be stable.
Gasless Reactive Compositions for Materials Joining: An Overview
Authors: Rogachev Alexander S. , Vadchenko Sergey G. , Nepapushev Andrey A. , Rogachev Sergey A. , Scheck Yury B. , Mukasyan Alexander S.
Published: April 2018

Some results of recent studies on materials joining by using exothermic reactive compositions that burn without notable gas evolution are overviewed. We also considered some possible routes to controlling wave propagation velocity in conditions of strong heat sink, to lowering ignition temperature for exothermic combustion reactions, and to improving the adhesion strength. The use of exothermic powder compositions opens up new horizons for combustion‐aided joining of materials, including refractory and dissimilar ones. Further advance in the field can be reached through mechanical activation (nanostucturing) of green compositions in ball mills and by cold rolling of reactive mixtures to fabricate reactive tapes. The examples of joining carbon materials, metals, and ceramic–metal pairs were presented. To date, the technique of combustion‐assisted joining of materials has become a promising and rapidly developing branch of modern R & D.
Microstructure and Mechanical Properties of B4C/6061Al Nanocomposites Fabricated by Advanced Powder Metallurgy
Authors: Liu Ruifeng , Wang Wenxian , Chen Hongsheng , Tan Minbo , Zhang Yuyang
Published: April 2018

In this study, B4C/6061Al nanocomposites reinforced with various volume fractions of nano‐sized B4C particles (B4C/6061Al NCs) are successfully fabricated by a powder metallurgy route consisting of spark plasma sintering (SPS) and hot extrusion and rolling (HER). The microstructure evolution, phase composition, and mechanical properties of B4C/6061Al NCs are experimentally investigate. The results show that nearly fully dense (maximum ≈99.21%) as‐SPSed NCs can be fabricated, and this can be attributed to joule heating at the particle contacts and tip spark plasma at the gaps. Nanosized B4C particles mainly distributed in the 6061Al particles boundaries and formed inhomogeneous network materials in as‐SPSed NCs, while B4C particles distributed relatively homogeneously in the 6061Al matrix after HER. No new phases are found in the B4C/6061Al NCs over three deformation stages. The pin effect of the nanosized B4C can suppress dynamic recovery and improve the driving force for dynamic recrystallization. The mechanical properties are further improved after HER, and the maximum ultimate tensile strength and yield strength for as‐rolled NCs are 305 and 168 MPa. The strengthening mechanisms mainly included load transfer strengthening, dislocation strengthening, Orowan strengthening, and fine‐grain strengthening.
Exploring the Nickel–Graphene Nanocomposite Coatings for Superior Corrosion Resistance: Manipulating the Effect of Deposition Current Density on its Morphology, Mechanical Properties, and Erosion‐Corrosion Performance
Authors: Yasin Ghulam , Arif Muhammad , Shakeel Muhammad , Dun Yuchao , Zuo Yu , Khan Waheed Qamar , Tang Yuming , Khan Ajmal , Nadeem Muhammad
Published: April 2018

The use of graphene‐based composite as anti‐corrosion and protective coatings for metallic materials is still a provocative topic worthy of debate. Nickel–graphene nanocomposite coatings have been successfully fabricated onto the mild steel by electrochemical co‐deposition technique. This research demonstrates the properties of nickel–graphene composite coatings influenced by different electrodeposition current densities. The effect of deposition current density on the; surface morphologies, composition, microstructures, grain sizes, mechanical, and electrochemical properties of the composite coatings are executed. The coarseness of deposited coatings increases with the increasing of deposition current density. The carbon content in the composite coatings increases first and then decreases by further increasing of current density. The improved mechanical properties and superior anti‐corrosion performance of composite coatings are obtained at the peak value of current density of 9 A dm−2. The incorporation of graphene sheets into nickel metal matrix lead to enhance the micro hardness, surface roughness, and adhesion strength of produced composite coatings. Furthermore, the presence of graphene in composite coating exhibits the reduced grain sizes and the enhanced erosion–corrosion resistance properties.
Expanded Vermiculite: A Promising Natural Encapsulation Material of LiNO3, NaNO3, and KNO3 Phase Change Materials for Medium‐Temperature Thermal Energy Storage
Authors: Deng Yong , Li Jinhong , Nian Hongen
Published: April 2018

In the study, with LiNO3, NaNO3, and KNO3 as medium‐temperature phase change materials (PCMs) and expanded vermiculite (EVM) as the encapsulation material, form‐stable composite PCMs (fs‐CPCMs) are prepared. The experimental value of maximum encapsulation mass fractions of LiNO3‐EVM, NaNO3‐EVM, and KNO3‐EVM is, respectively, 84.6, 85.7, and 87.0 wt%, which is lower than the theoretical value since the pore structures of EVM are not fully filled by PCMs. SEM results indicate that the PCMs are uniformly distributed and embedded into the pores or on the surfaces of EVM. The excellent chemical compatibility of PCMs with EVM is confirmed by XRD and FT‐IR results. DSC tests indicate the phase change temperatures of three fs‐CPCMs are between 243.1 and 325.1 °C and that latent heats are between 83.1 and 295.4 J g−1. After 100 melting/solidification cycles, the decrease in latent heats of fs‐CPCMs are below 1.91%, exhibiting desirable thermal reliability. The thermal conductivity of LiNO3‐EVM, NaNO3‐EVM, and KNO3‐EVM is, respectively, 0.51, 0.44, and 0.33 W/(m K), indicating acceptable thermal energy charging/discharging rate. TGA analysis reveal that fs‐CPCMs show good thermal stability within the designed working temperature range. Therefore, EVM is a promising natural encapsulation material for medium‐temperature heat storage.
One‐Step Fabrication of Pillar and Crater‐Like Structures on Titanium Using Direct Laser Interference Patterning
Authors: Zwahr Christoph , Voisiat Bogdan , Welle Alexander , Günther Denise , Lasagni Andrés Fabián
Published: April 2018

Direct laser interference patterning (DLIP) is used to create periodic crater‐ and pillar‐like patterns on titanium surfaces. A Nd:YAG laser operating at 532 nm wavelength with a pulse duration of 8 ns and the ability to control the polarization of each individual beam is used for the laser patterning process. The generated periodic patterns with spatial periods of 5 and 10 μm are produced with energy densities between 0.3 and 5.1 J cm−2 with a single laser pulse. By varying the polarization of each interfering beam and the energy density, various forms of the occurring topography are observed due to the different shape of the interference intensity pattern and the solidification front of the molten material at the maxima positions. The characterization of the surface chemistry shows that the laser treatment increases the relative content of alumina in the reactive layer from 36% to 51%. The structural analysis of pillar‐like patterned surface shows no changes in microstructure after the laser treatment. Contact angles of 47° ± 7° down to 6° ± 4° are measured on both, crater‐ and pillar‐like surfaces which are significantly lower compared to the untreated reference (79° ± 2°).