bluuebunny/crossref_metadata_2025 huggingface dataset:
La enseñanza de la lectura y la escritura mediada por tecnología en la educación superior
Authors: Clerici Carolina
Published: December 2023

La lectura y la escritura son prácticas que atraviesan la vida académica de nivel superior y, en ese contexto, además de su valor como medios para acumular información o para rendir cuentas del conocimiento aprendido, se destacan principalmente como instrumentos poderosos para generar y transformar conocimiento. En tanto prácticas sociales, se inscriben en un contexto histórico que les imprime rasgos específicos.
Enfoques actuales del aprendizaje en línea
Authors: Mena Marta
Published: December 2023

Comentar este libro coordinado por Wolfram Laaser me hahecho retrotraer a muchos años atrás cuando compartimosexperiencias, tanto en su visita a la Facultad de CienciasEconómicas de la Universidad de Buenos Aires como en miestadía en la Fern Universität de Hagen en Alemania.
Challenges and Recommendations for the Implementation of Outcome-Based Education: A Systematic Review
Authors: Piyasena K.G.C.C. , Ali Mohammed Lubna , Dhanapala R.M.
Published: December 2023

Enhancing the quality of education through focusing on the outcomes of the educational process is an increasingly highlighted area in the field of education. Outcome-based education (OBE) has been considered as the best approach to enhance the quality of education, and it is implementing inserted of traditional teacher-centered content-based education approach in most educational reforms. Also, there are research findings about this change in the literature. It is important to explore challenges and recommendations for OBE implementation especially for ‘those who are struggling with the same challenges’ and ‘who are planning for the same reforms.’ The purpose of this study is to discuss challenges and recommendations for OBE implementation in previous literature. The ‘conceptual content analyses’ on phenomenological and case study-based recent research publications were conducted. PRISMA article selection process was employed to identify suitable research papers. Twelve research papers published in the last ten years fulfilled all inclusion criteria. These research papers were selected from ‘Google Scholar’, Emerald Insight’ and ‘SAGE’ databases. Findings in both, challenges and recommendations were compiled under four categories. The first three categories: ‘defining intended learning outcomes’, ‘deciding teaching-learning activities’, and ‘student assessment’ were derived from the theory of constructive alignment. All other challenges and recommendations were discussed in the last category, ‘general’. However, there are more improvements with the OBE. However, it should not be considered as a magic solution for all issues and should be implemented carefully because there are no chances to learn through mistakes in educational reforms.
An Analysis of Persistent Expressions: Examining the Resonance of Words - A Literature Review
Authors: Yong Tao , Yang Liu , Qi Sun
Published: December 2023

In Julian Barnes' novel "The Sense of an Ending," the author effectively employs the literary technique of repetition to depict a wide range of complex human emotions that elude facile categorization. This provides an additional function, namely, to emphasize the inherent subjectivity and fallibility that are intrinsic to the disciplines of history and memory. Notwithstanding the importance of this literary technique, scholars have yet to fully explore it. The present study aims to address this gap by providing a systematic classification of the literary repetitions identified in the novel and elucidating their role in shaping the narrative's central themes. The study delineates and characterizes three fundamental iterations, namely the reoccurrence of indistinguishable circumstances, the manifestation of sceneries with minor alterations, and the replication of identical lines with varying connotations. The text has various instances of these types of repeats. The fundamental objective of this research is to elucidate the way the motifs of obsession, misunderstanding, and consequences reverberate throughout the narrative, so augmenting the reader's grasp of the central topics of the text.
Pengaruh Electronic Word Of Mouth Dan Persepsi Harga Terhadap Keputusan Pembelian Dalam Membeli Seblak Di Daerah Tirtayasa
Authors: Badriyah Badriyah  , Sukiyah Sukiyah  , Siti Mariskah  , Riki Gana Suyatna
Published: December 2023

This study is motivated by the competition of seblak business actors in the Tirtayasa area. This study aims to determine how influential the Electronic Word of Mouth variable is on price perceptions, on purchasing decisions. The population in this study were all buyers who bought Seblak in the Tirtayasa area. The research methodology used quantitative with respondents in this study were the Tirtayasa community, 64 community respondents who had bought Seblak Tirtayasa were obtained. Then the data was obtained using a questionnaire. The results showed that Electronic Word of Mouth (X1) 57.8% has a significant effect on purchasing decisions (Y) 73.4% price perception (X2) 57.8% has a significant effect on purchasing decisions (Y).
Analysis Of Promotion And Service Quality On Customer Loyalty At Pln Tanjung Pura Ulp Mediated By Customer Satisfaction In The Use Of Pln Mobile Application
Authors: Taufik Harijanto  , Toyib Daulay  , Desy Astuti  , Elfitra Desy Surya  , Mesra B
Published: December 2023

This research investigates the impact of promotion, service quality, and emotional bonding on customer loyalty at PLN Tanjung Pura ULP, mediated by customer satisfaction through the PLN Mobile application. Utilizing a quantitative approach with structural equation modeling, the study reveals that promotion and service quality significantly influence customer satisfaction, subsequently affecting customer loyalty. The findings emphasize the importance of effective promotional strategies, high service quality, and emotional connections in enhancing customer satisfaction and loyalty. Recommendations include promoting PLN Mobile adoption through step-by-step guidance, improving service quality through employee training and customer feedback, and fostering emotional bonds with special offers for loyal users. Overall, the study highlights the interconnected dynamics shaping customer loyalty in the context of PLN Mobile usage.
القوة المعيارية في السياسة الخارجية للإتحاد الأوروبي
Authors: أ.م.د. عماد مؤيد جاسم
Published: December 2023

يبدي الإتحاد الأوروبي ومنذ تأسيسه في القرن الماضي إهتماماً شديداً بمجموعة من القيم والمبادئ من قبيل: إحترام حقوق الإنسان، دعم الديمقراطية، تشجيع الحكم الصالح، التركيز على الحقوق والحريات إرساء السلام وحل النزاعات بالطرق السلمية وغيرها. هذه القيم التي أسهمت بشكل كبير في توفير عوامل مشتركة لتأسيس الإتحاد وتوسيعه خلال السنوات الماضية أصبحت جزء من إتجاهات السياسة الخارجية له . ويبدو أن هذه القيم التي كانت عامل توحيد بين أعضاءه ، باتت جزءاً من معضلة بناء قوة عسكرية والإتفاق على السياسيات الأمنية والدفاعية، بحكم أن هذه المعايير والمبادئ وخلال سنوات طويلة ساعدت في بروز ما بات متداولاً على أنه (القوة المدنية) لأوروبا و القوة المعيارية) وهو ما خلق شعوراً طاغياً لدى الأوروبيين أن موازين العالم باتت تتغير بإتجاه قوة الإقتصاد والقيم وليس بإتجاه مظاهر القوة العسكرية التقليدية، ما عزز القناعة لدى البعض بعدم الحاجة للتركيز على بناء ذراع عسكري للإتحاد الأوروبي . وعلى الرغم من أن القوة المعيارية) لأوروبا أسهمت في بناء صورة جذابة عن الإتحاد وحققت بعض غاياته، إلا انها - حسب رأي بعض الخبراء - أضعفت من مركزه في ظل عودة العالم المعاصر إلى سياسات القوة والتنافس المسلح.
الرقابة القضائية على قرارات مجلس الخدمة العامة الاتحادي
Authors: م.د. زينب ماجد محمد علي  , م.د غصون علي عبد الزهرة  , عماد رحيم م.د. كرار
Published: December 2023

يعد مجلس الخدمة العامة الاتحادي هيأة حديثة العهد نسبياً ، عمد دستور جمهورية العراق لسنة ۲۰۰٥ إلى إنشائها للاضطلاع بتنظيم شؤون الوظيفة العامة، فيعد المجلس بمثابة تجربة مؤسساتية دستورية، جاءت منسجمة مع التطورات الإدارية التي طالت الجهاز الإداري في العراق، ونظراً لما يتمتع المجلس به سلطة تقديرية في التعيين وإعادة التعيين والترقية كان لابد من أن يخضع المجلس فيما يقوم به من أعمال لرقابة القضاء الإداري ومن ثم توقيع الجزاء اللازم عند مخالفته لأحكام القانون، فكما هو معلوم أن الرقابة القضائية تعد الضمانة الحقيقية لمبدأ المشروعية فضلاً عن دورها في تحقيق التوازن بين مقتضيات المصلحة العامة ، التي تسعى الإدارة إلى تحقيقها وبين حقوق الأفراد من تعسف الإدارة في حال اعتدائها على هذه الحقوق كونه جهة تتمتع بالحياد والاستقلالية.
ألفاظ الوجوب في القانون المدني العراقي
Authors: م م. ساره کاظم راهي
Published: December 2023

أهمية موضوع البحث عن البعد اللغوي والواقعي لألفاظ الوجوب المستعملة ، وفيما إذا كانت تلك الألفاظ مستوعبة لكافة ما تحمله من معانٍ ، ولما يمكن أن تولده في ذهن من يستعين بها عند التطبيق من أجل إعطاء النص القانوني المعنى الملائم ، الذي قصده المُشرع ، الذي ينطبق على الوقائع المعروضة والأوضاع القانونية الناشئة عنها، ولذلك يترتب على صياغة النص القانوني نتائج هامة إذ أن عدم الدقة في استعمال الفاظ الوجوب سواء لجهة اللفظ المستعمل أم لجهة مكان هذا اللفظ في النص يولد التباسات في التطبيق ، وربما تؤدي إلى إعمال القاعدة القانونية بصورة مخالفة الإرادة المشرع
Behandling af hepatitis C hos børn med direktevirkende antiviral medicin
Authors: Hansen Krestine Rosager , Kjærgaard Jesper , Kvistgaard Helene , Grosen Dorthe , Holm Mette , Gerstoft Jan , Nordly Sannie , Helt Thora Wesenberg , Christensen Vibeke Brix
Published: December 2023

Treatment of hepatitis C in children with direct-acting antiviral drugs The primary purpose of treating chronic hepatitis C (HCV) is to prevent the development of liver fibrosis, cirrhosis, and cancer. In the last decade, direct-acting antiviral medicine (DAA) has been approved to treat children with HCV. This treatment has a higher efficacy, shorter duration, and milder side effects than the previously approved treatment. In this review, it is recommended to track down children who might be infected with HCV to enhance early treatment to prevent transmission of the virus and the possible complications.
AVALIAÇÃO DA ATIVIDADE LARVICIDA E ADULTICIDA DE DERIVADOS SEMISSINTÉTICOS ALFA-METILESTIRENO PARA O CONTROLE DO MOSQUITO Aedes aegypti (DIPTERA: CULICIDAE) EM CONDIÇÕES DE LABORATÓRIO
Authors: DO NASCIMENTO KAMILA LIMA , PINTO ANA CRISTINA DA SILVA , SALES DIANA VIEIRA , ROQUE ROSEMARY APARECIDA , DO VALE EUNICE DA SILVA MEDEIROS
Published: December 2023

O Aedes aegypti é o principal vetor da dengue, febre amarela, Zika e febre chikungunya, desempenhando papel importante em surtos de doenças há mais de um século. O controle químico permanece como o método mais utilizado na prevenção de doenças transmitidas por mosquitos. Porém, há relatos nas literaturas sobre a resistência em populações pelo uso contínuo de inseticidas químicos. Nesse sentido os produtos de origem vegetal, como extratos vegetais, óleos essenciais e derivados de plantas, surgem como uma alternativa promissora. No presente trabalho foi estudado a oleorresina da espécie Protium rubrum, do qual foi isolado o monoterpeno 1-isopropenyl-2,5- dimethoxy-4-methylbenzene (IDMB) e a partir dele foram preparados os derivados semissintéticos DBr, DOBu e DPip. Todas as substâncias foram avaliadas quanto ao seu potencial larvicida e adulticida em A. aegypti. Foi preparada uma solução-mãe de cada substância, solubilizadas em dimetilsulfóxido (DMSO), e a partir destas 50% em sua concentração intermediária, além de apresentar menor concentração letal de CL50 28,05 µg/mL, em comparação às demais substâncias. No bioensaio adulticida observou-se que IDMB causou 50% de mortalidade das fêmeas na concentração de 500 µg/mL, e apresentou menor valor de CL50 28,05 µg/mL, que foram avaliadas para o bioensaio larvicida nas concentrações: 100, 50, 25 e 12,5 e 6,25 µg/mL, e no teste adulticida: 1000, 500, 250 e 125 µg/mL. O resultado do bioensaio larvicida demonstrou que a substância natural IDMB apresentou maior potencial causando mortalidade das larvas comparado aos seus derivados. Este é o primeiro trabalho a demonstrar o efeito larvicida e adulticida da substância majoritária do óleo essencial da espécie P. rubrum em A. aegypti.
Special Issue: 2023 Research Data Access and Preservation (RDAP) Summit
Authors: Cappello Alicia , Hertz Marla , Griffin Tina , Jones Jamaica
Published: December 2023

The 2023 Research Data Access and Preservation (RDAP) Summit, Building on Experience: Centering Communities in Data Creation and Access, focused on engagement with and building communities within data environments, including how data is being made more accessible for a wider range of communities. The 2023 RDAP Summit was a natural extension from the prior year’s theme of Envisioning an Inclusive Data Future, which highlighted the ways data service providers tailor their services to address specific needs. A selection of presentations from this year’s Summit were expanded into articles for this special issue covering topics on developing and maintaining communities that address aspects across the research data life cycle.
Italian Chivalric Literature and Digital Humanities
Authors: Cavallo Jo Ann
Published: December 2023

There is an ever-growing number of Digital Humanities initiatives that explore Italian chivalric literature and its reception in the theatrical and visual arts, from combined digital and print projects that include Italian-language narratives within a panorama of world epics to interactive websites focused on a single epic text. This essay spotlights digital resources that I have found especially fruitful for the study and teaching of Italian chivalric works as well as two websites that I’m in the process of developing and other in-progress digital initiatives that have come to my attention.
La mesa y la magia en los libros de caballerías: algunos motivos sintagmáticos compuestos
Authors: Cuesta Torre María Luzdivina , Soriano Sarahí
Published: December 2023

Los banquetes son motivos habituales en muchos libros de caballerías, pues representan una situación cotidiana que brinda a la escena más realismo (lo que permite al lector identificar la estructura cronológica del relato y asociarla a su experiencia), dentro de la atmósfera de ficción. En este trabajo aplicaremos la metodología de investigación de motivos caballerescos y, en sus fases iniciales, haremos uso de la herramienta digital MeMoRam, con el propósito de estudiar la relación que existe entre este tipo de escenas y la irrupción de acontecimientos mágicos en ellas o en su contexto inmediato. Se analizarán distintas combinaciones del motivo del banquete en palacio y diversos motivos mágicos, con el objetivo de establecer la existencia de motivos singulares compuestos. Finalmente, se propondrán unas conclusiones en torno a la tipología de estas combinaciones.
Una primera aproximación a los géneros literarios de la obra cervantina desde la estilometría y el análisis de redes
Authors: Hernández-Lorenzo Laura
Published: December 2023

Siguiendo la línea de estudios previos que aplican métodos estilométricos para el estudio de cuestiones estilísticas no autoriales, en este trabajo se realiza una primera aproximación a la obra de Miguel de Cervantes. Mediante la combinación de la estilometría y del análisis de redes, se pretende explorar las relaciones entre sus obras y determinar qué papel juegan la periodización de estas, así como los diferentes géneros literarios que abarcan. Los resultados obtenidos, si bien no muestran una señal cronológica clara, ponen de manifiesto que es posible detectar relaciones de género literario de forma automática a través de estas metodologías. Se realizan, además, nuevas aportaciones sobre las características genéricas de obras concretas, que abren novedosas vías de investigación para el futuro.
Caballeros codificados: las ediciones digitales de las obras de Hartmann von Aue (finales del s. XII)
Authors: González Miranda Emilio , Millet Victor
Published: December 2023

Las ediciones digitales de las cuatro obras narrativas de Hartmann von Aue (ca. 1180–1205) aprovechan una potente infraestructura de edición desarrollada por el Servicio de Publicaciones de la Universidad de Heidelberg. Se ofrecen imágenes completas en alta resolución de todos los testimonios, así como transcripciones completas de los mismos, edición de manuscritos selectos, anotación, aparato de variantes y materiales. El artículo presenta el proyecto, plantea sus fortalezas y dificultades, y llama la atención sobre la necesidad de avanzar hacia el tratamiento automatizado de textos en lenguas no estandarizadas.
«Universo de Almourol»: nueva actualización 2023
Authors: Vargas Díaz-Toledo Aurelio
Published: December 2023

Mediante el presente trabajo nos disponemos a ofrecer una nueva actualización de nuestro proyecto de investigación titulado Base de dados da matéria cavaleiresca portuguesa dos séculos XVI-XVIII, que comenzó su andadura en la Universidad de Oporto, dentro del Instituto de Filosofía y gracias a la Fundação para a Ciência e Tecnologia. Este proyecto se materializó en la página Universo de Almourol, que ahora está alojada en el portal de Literatura Medieval Hispánica Parnaseo. De este modo, nos disponemos a mostrar los avances de los contenidos que ha enriquecido este proyecto.
Milla Altabás, María Belén, «El príncipe travestido. Género, transgresión y violencia en la tercera parte del "Florisel de Niquea" de Feliciano de Silva», Madrid, Guillermo Escolar, 2022
Authors: Mérida Jiménez Rafael M.
Published: December 2023

Ressenya de María Belén Milla Altabás, El príncipe travestido. Género, transgresión y violencia en la tercera parte del «Florisel de Niquea» de Feliciano de Silva¸ Madrid, Guillermo Escobar, 2022.
Structural and mechanistic insight into ribosomal ITS2 RNA processing by nuclease-kinase machinery
Authors: Chen Jiyun , Chen Hong , Li Shanshan , Lin Xiaofeng , Hu Rong , Zhang Kaiming , Liu Liang
Published: December 2023

Precursor ribosomal RNA (pre-rRNA) processing is a key step in ribosome biosynthesis and involves numerous RNases. A HEPN nuclease Las1 and a polynucleotide kinase Grc3 assemble into a tetramerase responsible for rRNA maturation. Here, we report the structures of full-length
Saccharomyces cerevisiae
and
Cyberlindnera jadinii
Las1-Grc3 complexes, and
Cyberlindnera jadinii
Las1. The Las1-Grc3 structures show that the central coiled coil domain of Las1 facilitates pre-rRNA binding and cleavage, while the Grc3 C-terminal loop motif directly binds to the HEPN active center of Las1 and regulates pre-rRNA cleavage. Structural comparison between Las1 and Las1-Grc3 complex exhibits that Grc3 binding induces conformational rearrangements of catalytic residues associated with HEPN nuclease activation. Biochemical assays identify that Las1 processes pre-rRNA at the two specific sites (C2 and C2′), which greatly facilitates rRNA maturation. Our structures and specific pre-rRNA cleavage findings provide crucial insights into the mechanism and pathway of pre-rRNA processing in ribosome biosynthesis.
Association of genetic variation in COL11A1 with adolescent idiopathic scoliosis
Authors: Yu Hao , Khanshour Anas M. , Ushiki Aki , Otomo Nao , Koike Yoshinao , Einarsdottir Elisabet , Fan Yanhui , Antunes Lilian , Kidane Yared H. , Cornelia Reuel , Sheng Rory , Zhang Yichi , Pei Jimin , Grishin Nick V. , Evers Bret M. , Cheung Jason Pui Yin , Herring John A. , Terao Chikashi , Song You-Qiang , Gurnett Christina A. , Gerdhem Paul , Ikegawa Shiro , Rios Jonathan J. , Ahituv Nadav , Wise Carol A.
Published: December 2023

Adolescent idiopathic scoliosis (AIS) is a common and progressive spinal deformity in children that exhibits striking sexual dimorphism, with girls at more than five-fold greater risk of severe disease compared to boys. Despite its medical impact, the molecular mechanisms that drive AIS are largely unknown. We previously defined a female-specific AIS genetic risk locus in an enhancer near the
PAX1
gene. Here we sought to define the roles of
PAX1
and newly-identified AIS-associated genes in the developmental mechanism of AIS. In a genetic study of 10,519 individuals with AIS and 93,238 unaffected controls, significant association was identified with a variant in
COL11A1
encoding collagen (α1) XI (rs3753841; NM_080629.2_c.4004C>T; p.(Pro1335Leu); P=7.07e
-11
, OR=1.118). Using CRISPR mutagenesis we generated
Pax1
knockout mice (

Pax1
-/

-
). In postnatal spines we found that PAX1 and collagen (α1) XI protein both localize within the intervertebral disc (IVD)-vertebral junction region encompassing the growth plate, with less collagen (α1) XI detected in

Pax1
-/-

spines compared to wildtype. By genetic targeting we found that wildtype
Col11a1
expression in costal chondrocytes suppresses expression of
Pax1
and of
Mmp3
, encoding the matrix metalloproteinase 3 enzyme implicated in matrix remodeling. However, this suppression was abrogated in the presence of the AIS-associated
COL11A1
P1335L
mutant. Further, we found that either knockdown of the estrogen receptor gene
Esr2
, or tamoxifen treatment, significantly altered
Col11a1
and
Mmp3
expression in chondrocytes. We propose a new molecular model of AIS pathogenesis wherein genetic variation and estrogen signaling increase disease susceptibility by altering a
Pax1
-
Col11a1
-
Mmp3
signaling axis in spinal chondrocytes.
Base editing strategies to convert CAG to CAA diminish the disease-causing mutation in Huntington’s disease
Authors: Choi Doo Eun , Shin Jun Wan , Zeng Sophia , Hong Eun Pyo , Jang Jae-Hyun , Loupe Jacob M , Wheeler Vanessa C , Stutzman Hannah E , Kleinstiver Ben , Lee Jong-Min
Published: December 2023

An expanded CAG repeat in the huntingtin gene (HTT) causes Huntington’s disease (HD). Since the length of uninterrupted CAG repeat, not polyglutamine, determines the age-at-onset in HD, base editing strategies to convert CAG to CAA are anticipated to delay onset by shortening the uninterrupted CAG repeat. Here, we developed base editing strategies to convert CAG in the repeat to CAA and determined their molecular outcomes and effects on relevant disease phenotypes. Base editing strategies employing combinations of cytosine base editors and guide RNAs (gRNAs) efficiently converted CAG to CAA at various sites in the CAG repeat without generating significant indels, off-target edits, or transcriptome alterations, demonstrating their feasibility and specificity. Candidate BE strategies converted CAG to CAA on both expanded and non-expanded CAG repeats without altering HTT mRNA and protein levels. In addition, somatic CAG repeat expansion, which is the major disease driver in HD, was significantly decreased in the liver by a candidate BE strategy treatment in HD knock-in mice carrying canonical CAG repeats. Notably, CAG repeat expansion was abolished entirely in HD knock-in mice carrying CAA-interrupted repeats, supporting the therapeutic potential of CAG-to-CAA conversion strategies in HD and potentially other repeat expansion disorders.
High-risk Escherichia coli clones that cause neonatal meningitis and association with recrudescent infection
Authors: Nhu Nguyen Thi Khanh , Phan Minh-Duy , Hancock Steven J. , Peters Kate M. , Alvarez-Fraga Laura , Forde Brian M. , Andersen Stacey B. , Miliya Thyl , Harris Patrick N.A. , Beatson Scott A. , Schlebusch Sanmarie , Bergh Haakon , Turner Paul , Brauner Annelie , Westerlund-Wikström Benita , Irwin Adam D. , Schembri Mark A.
Published: December 2023

Neonatal meningitis is a devasting disease associated with high mortality and neurological sequelae.
Escherichia coli
is the second most common cause of neonatal meningitis (herein NMEC) and the most common cause of meningitis in preterm neonates. Here we investigated the genomic relatedness of a collection of NMEC strains spanning 1974-2020 and isolated from seven different geographic regions. We show NMEC are comprised of strains from diverse sequence types (STs), with ST95 (34.5%) and ST1193 (15.5%) the most common. No single virulence factor was conserved in all strains; however, genes encoding fimbrial adhesins, iron acquisition systems, the K1 capsule, and O antigen types O18, O75 and O2 were most prevalent. Antibiotic resistance genes occurred infrequently. We also monitored the infection dynamics in three patients that suffered relapsed infection caused by the original infecting strain despite appropriate antibiotic treatment based on antibiogram profile and resistance genotype. These patients exhibited severe gut dysbiosis. In one patient, the causative NMEC isolate was also detected in the fecal flora at the time of the second infection episode and after treatment. Thus, although antibiotics are the standard of care for NMEC treatment, our data suggests that failure to eliminate the causative NMEC that resides intestinally can lead to the existence of a refractory reservoir that may seed recrudescent infection.
BMP signaling maintains auricular chondrocyte identity and prevents microtia development by inhibiting protein kinase A
Authors: Yang Ruichen , Chu Hongshang , Yue Hua , Mishina Yuji , Zhang Zhenlin , Liu Huijuan , Li Baojie
Published: December 2023

Elastic cartilage constitutes a major component of the external ear, which functions to guide sound to the middle and inner ears. Defects in auricle development cause congenital microtia, which affects hearing and appearance in patients. Mutations in several genes have been implicated in microtia development, yet, the pathogenesis of this disorder remains incompletely understood. Here, we show that
Prrx1
genetically marks auricular chondrocytes in adult mice. Interestingly, BMP-Smad1/5/9 signaling in chondrocytes is increasingly activated from the proximal to distal segments of the ear, which is associated with a decrease in chondrocyte regenerative activity. Ablation of
Bmpr1a
in auricular chondrocytes led to chondrocyte atrophy and microtia development at the distal part. Transcriptome analysis revealed that
Bmpr1a
deficiency caused a switch from the chondrogenic program to the osteogenic program, accompanied by enhanced protein kinase A activation, likely through increased expression of
Adcy5/8
. Inhibition of PKA blocked chondrocyte-to-osteoblast transformation and microtia development. Moreover, analysis of single-cell RNA-seq of human microtia samples uncovered enriched gene expression in the PKA pathway and chondrocyte-to-osteoblast transformation process. These findings suggest that auricle cartilage is actively maintained by BMP signaling, which maintains chondrocyte identity by suppressing osteogenic differentiation.
Conditional Chemoconnectomics: A Set of Libraries Targeting All Chemical Transmission Corresponding Genes Efficiently
Authors: Mao Renbo , Yu Jianjun , Deng Bowen , Dai Xihuimin , Du Yuyao , Du Sujie , Zhang Wenxia , Rao Yi
Published: December 2023

Dissection of neural circuitry underlying behaviors is a central theme in neurobiology. Chemical transmission is the predominant model for signaling between neurons. Here we have created lines target all chemical transmission corresponding genes in Drosophila after modifying GFP RNA interference, Flp-out and CRISPR/Cas9 technologies. After thorough validation, all three strategies are demonstrated to be highly effective with the best using chromatin-peptide fused Cas9 variants and scaffold optimized sgRNAs. As a proof of principle, we conduct a comprehensive intersection analysis of chemoconnectome (CCT) genes expression profiles in the clock neurons using chemoconnectomics driver lines, leading to the finding of 45 CCT genes presented in clock neurons. Mutating these genes specifically in clock neurons revealed that loss of the neuropeptide CNMa in two posterior dorsal clock neurons (DN1p) or its receptor (CNMaR) caused advanced morning activity, opposite to the mutants of neuropeptide PDF or its receptor (PDFR). These results demonstrate the effectiveness of conditional chemoconnectomics libraries and indicate an antagonistic relationship between CNMa-CNMaR and PDF-PDFR signaling in regulating morning anticipation.
A parameterized two-domain thermodynamic model explains diverse mutational effects on protein allostery
Authors: Liu Zhuang , Gillis Thomas G , Raman Srivatsan , Cui Qiang
Published: December 2023

New experimental findings continue to challenge our understanding of protein allostery. Recent deep mutational scanning study showed that allosteric hotspots in the tetracycline repressor (TetR) and its homologous transcriptional factors are broadly distributed rather than spanning well-defined structural pathways as often assumed. Moreover, hotspot mutation-induced allostery loss was rescued by distributed additional mutations in a degenerate fashion. Here, we develop a two-domain thermodynamic model for TetR, which readily rationalizes these intriguing observations. The model accurately captures the in vivo activities of various mutants with changes in physically transparent parameters, allowing the data-based quantification of mutational effects using statistical inference. Our analysis reveals the intrinsic connection of intra- and inter-domain properties for allosteric regulation and illustrate epistatic interactions that are consistent with structural features of the protein. The insights gained from this study into the nature of two-domain allostery are expected to have broader implications for other multi-domain allosteric proteins.
Pigmentation level of human iPSC-derived RPE does not indicate a specific gene expression profile
Authors: Nakai-Futatsugi Yoko , Jin Jianshi , Ogawa Taisaku , Sakai Noriko , Maeda Akiko , Hironaka Ken-ichi , Fukuda Masakazu , Danno Hiroki , Tanaka Yuji , Hori Seiji , Shiroguchi Katsuyuki , Takahashi Masayo
Published: December 2023

Retinal pigment epithelium (RPE) cells show heterogeneous levels of pigmentation when cultured in vitro. To know whether their color in appearance is correlated with the function of the RPE, we analyzed the color intensities of human-induced pluripotent stem cell-derived RPE cells (iPSC-RPE) together with the gene expression profile at the single-cell level. For this purpose, we utilized our recent invention, Automated Live imaging and cell Picking System (ALPS), which enabled photographing each cell before RNA-sequencing analysis to profile the gene expression of each cell. While our iPSC-RPE were categorized into four clusters by gene expression, the color intensity of iPSC-RPE did not project any specific gene expression profiles. We reasoned this by less correlation between the actual color and the gene expressions that directly define the level of pigmentation, from which we hypothesized the color of RPE cells may be a temporal condition not strongly indicating the functional characteristics of the RPE.
Autophagosome development and chloroplast segmentation occur synchronously for piecemeal degradation of chloroplasts
Authors: Izumi Masanori , Nakamura Sakuya , Otomo Kohei , Ishida Hiroyuki , Hidema Jun , Nemoto Tomomi , Hagihara Shinya
Published: December 2023

Plants distribute many nutrients to chloroplasts during leaf development and maturation. When leaves senesce or experience sugar starvation, the autophagy machinery degrades chloroplast proteins to facilitate efficient nutrient reuse. Here, we report on the intracellular dynamics of an autophagy pathway responsible for piecemeal degradation of chloroplast components. Through live-cell monitoring of chloroplast morphology, we observed the formation of chloroplast budding structures in sugar-starved leaves. The buds were then released and incorporated into the vacuolar lumen as an autophagic cargo termed a Rubisco-containing body. These budding structures did not accumulate in mutants of core autophagy machinery, suggesting that autophagosome creation is required for forming chloroplast protrusions. Simultaneous tracking of chloroplast morphology and autophagosome development revealed that the isolation membranes of autophagosomes tightly interact with part of the chloroplast surface before forming chloroplast buds. Chloroplasts then protrude at the site associated with the isolation membranes, which divide synchronously with autophagosome maturation. This autophagy-related division does not require DYNAMIN-RELATED PROTEIN 5B (DRP5B), which constitutes the division ring for chloroplast proliferation in growing leaves. An unidentified division machinery may thus fragment chloroplasts for degradation in coordination with the development of the chloroplast-associated isolation membrane.
Expanding the Drosophila toolkit for dual control of gene expression
Authors: Zirin Jonathan , Jusiak Barbara , Lopes Raphael , Ewen-Campen Benjamin , Bosch Justin A , Risbeck Alexandria , Forman Corey , Villalta Christians , Hu Yanhui , Perrimon Norbert
Published: December 2023

The ability to independently control gene expression in two different tissues in the same animal is emerging as a major need, especially in the context of inter-organ communication studies. This type of study is made possible by technologies combining the GAL4/UAS and a second binary expression system such as the LexA system or QF system. Here, we describe a resource of reagents that facilitate combined use of the GAL4/UAS and a second binary system in various Drosophila tissues. Focusing on genes with well-characterized GAL4 expression patterns, we generated a set of more than 40 LexA-GAD and QF2 insertions by CRISPR knock-in and verified their tissue specificity in larvae. We also built constructs that encode QF2 and LexA-GAD transcription factors in a single vector. Following successful integration of this construct into the fly genome, FLP/FRT recombination is used to isolate fly lines that express only QF2 or LexA-GAD. Finally, using new compatible shRNA vectors, we evaluated both LexA and QF systems for in vivo gene knockdown and are generating a library of such RNAi fly lines as a community resource. Together, these LexA and QF system vectors and fly lines will provide a new set of tools for researchers who need to activate or repress two different genes in an orthogonal manner in the same animal.
Research Assessment – Navigating Pitfalls and Promoting Change
Authors: Flores Bueso Yensi , Whitaker Kirstie , Dole Hervé , Winther Jan-Gunnar , Larssen Tanja , Aspaas Per Pippin
Published: December 2023

This is a podcast version of the closing panel discussion at The 18th Munin Conference on Scholarly Publishing (Tromsø, Norway, 8–10 November 2023).
The main theme of the conference was scholarly communication in its myriad of forms. The push for a reform of research assessment argues for precisely the need to recognize and reward a wider set of research activities and competencies, not least in order to ensure that science – and scientics – remain in close contact with society. The demands for change will surely impact how and where research is disseminated and communicated. A key question then is how to evaluate research activities and outputs beyond academic publications.
The panelists reflected on questions such as: how do we measure the impact of citizen science, or document quality in innovative research practices and scholarly outputs? And how to ensure consensus on assessment methods for a wider and more inclusive range of research activities within a diverse academic landscape?
The panel consisted of champions of research assessment reform (Yensi Flores Bueso, University of Washington / University College Cork; Kirstie Whitaker, The Alan Turing Institute) and university leaders (Hervé Dole, vice-president for arts, culture and society at Université Paris-Saclay; Jan-Gunnar Winther, pro-rector for research and development, UiT). Questions were prepared by Tanja Larssen (open science adviser, UiT) in collaboration with Per Pippin Aspaas (head of library research and publishing support, UiT), who chaired the panel on the day.
First published as a podcast: December 19, 2023. A video recording of the same session – with metadata providing more detailed information on each panelist – can be found at https://doi.org/10.7557/5.7276.
Novel approach for quantitative and qualitative authors research profiling using feature fusion and tree-based learning approach
Authors: Umer Muhammad , Aljrees Turki , Ullah Saleem , Bashir Ali Kashif
Published: December 2023

Article citation creates a link between the cited and citing articles and is used as a basis for several parameters like author and journal impact factor, H-index, i10 index, etc., for scientific achievements. Citations also include self-citation which refers to article citation by the author himself. Self-citation is important to evaluate an author’s research profile and has gained popularity recently. Although different criteria are found in the literature regarding appropriate self-citation, self-citation does have a huge impact on a researcher’s scientific profile. This study carries out two cases in this regard. In case 1, the qualitative aspect of the author’s profile is analyzed using hand-crafted feature engineering techniques. The sentiments conveyed through citations are integral in assessing research quality, as they can signify appreciation, critique, or serve as a foundation for further research. Analyzing sentiments within in-text citations remains a formidable challenge, even with the utilization of automated sentiment annotations. For this purpose, this study employs machine learning models using term frequency (TF) and term frequency-inverse document frequency (TF-IDF). Random forest using TF with Synthetic Minority Oversampling Technique (SMOTE) achieved a 0.9727 score of accuracy. Case 2 deals with quantitative analysis and investigates direct and indirect self-citation. In this study, the top 2% of researchers in 2020 is considered as a baseline. For this purpose, the data of the top 25 Pakistani researchers are manually retrieved from this dataset, in addition to the citation information from the Web of Science (WoS). The self-citation is estimated using the proposed model and results are compared with those obtained from WoS. Experimental results show a substantial difference between the two, as the ratio of self-citation from the proposed approach is higher than WoS. It is observed that the citations from the WoS for authors are overstated. For a comprehensive evaluation of the researcher's profile, both direct and indirect self-citation must be included.
Impacts of tilapia aquaculture on native fish diversity at an ecologically important reservoir
Authors: Abd Hamid Muzzalifah , Md Sah Amir Shah Ruddin , Idris Izwandy , Mohd Nor Siti Azizah , Mansor Mashhor
Published: December 2023

Background

The Temengor Reservoir is the second largest reservoir in Peninsular Malaysia. Located in the northwestern state of Perak, it was selected to develop a large-scale tilapia (Oreochromis niloticus) aquaculture facility within the Aquaculture Industrial Zone (AIZ) in 2008 due to its favourable environmental conditions. No record of tilapia has ever been reported in the natural waters prior to this. However, a post-establishment study recorded tilapia sightings in the natural waters of this lake. The cultured tilapia was easily recognizable with the elongated mouth and body, and long caudal fin. It is postulated that these were escapees from the floating cages that had invaded the natural waters and would negatively impact the native fish species. To test our hypothesis, we investigated the impact of the aquaculture facility on native fish diversity through a spatial design.

Methods

The study was focused on assessing the impact of tilapia culture at sites nearer to the AIZ vs more distant sites, the former with a greater likelihood of receiving escapees. Two major sites were chosen; within 5 km (near-cage) and within 5–15 km (far-cage) radii from the AIZ. Fish sampling was conducted using multiple mesh sizes of gill nets (3.7, 5.1, 6.5, 7.6, and 10.2 cm) deployed at the littoral zone of the sampling points. Species diversity, abundance, dietary habits, and habitat preference were investigated.

Results

The CPUE (individual/hour) of native fish species at the far-cage site of the AIZ Reservoir was found to be significantly higher (p < 0.05) than that at the near-cage site. Principal component analysis (PCA) based on diet and habitat preferences showed that the tilapia, O. niloticus had almost overlapping diet resources and habitat with native fish species.

Conclusion

We conclude that there is a correlation between the reduced catches of native species (based on CPUE) and the high presence of tilapia. Thus, appropriate actions must be implemented for strategic and effective planning in terms of native fish conservation.
Age- and sex-related differences in upper-body joint and endpoint kinematics during a drinking task in healthy adults
Authors: Nakatake Jun , Arakawa Hideki , Tajima Takuya , Miyazaki Shigeaki , Chosa Etsuo
Published: December 2023

Background

The objective kinematic assessments of activities of daily living are desired. However, the limited knowledge regarding age- and sex-related differences prevents the adaptation of these measurements to clinical settings and in-home exercises. Therefore, this study aimed to determine the effects of age and sex on joint and endpoint kinematics during a common activity of daily living, specifically, drinking from a glass.

Methods

In total, 32 healthy adults (18 males and 14 females) aged 22–77 years performed a drinking task comprising reaching for a glass, bringing it forward and sipping, returning it, and placing the hand back to the starting position, which was recorded using a three-dimensional motion-capturing system. A two-way analysis of variance was used to statistically compare joint angles at five different time points and endpoint kinematic variables in the four drinking phases between older and younger age groups and sexes.

Results

Wrist radial deviation was greater in older adults than in younger participants at all five different time points (F = 5.16–7.34, p ≤ 0.03, η2 = 0.14–0.21). Moreover, lesser shoulder abduction and greater shoulder internal rotation and forearm pronation when moving and returning the hand to the starting position were observed in the female group than in the male group (F = 4.21–20.03, p ≤ 0.0497, η2 = 0.13–0.41). Trunk flexion was lower in the female group than in the male group at all time points (F = 4.25–7.13, p ≤ 0.0485, η2 = 0.12–0.19). Regarding endpoint kinematics, the performance time in the reaching phase was longer in older adults than in younger individuals (F = 4.96, p = 0.03, η2 = 0.14). Furthermore, a shorter time while returning the hand to the starting position was observed in the female group than in the male group (F = 9.55, p < 0.01, η2 = 0.22).

Conclusions

The joint kinematics of drinking were partially characterized by an age effect, whereas endpoint kinematics were scattered in all drinking phases. Sex-related effects in most upper-body motions and postures may cause rapid motions in females. Therefore, clinicians could use this knowledge for precise assessments and to suggest feasible in-home exercises.
Progress of circRNA/lncRNA-miRNA-mRNA axis in atrial fibrillation
Authors: Wen Jia-le , Ruan Zhong-bao , Wang Fei , Hu Yuhua
Published: December 2023

Atrial fibrillation (AF) is a prevalent arrhythmia that requires effective biomarkers and therapeutic targets for clinical management. In recent years, non-coding RNAs (ncRNAs) have emerged as key players in the pathogenesis of AF, particularly through the ceRNA (competitive endogenous RNA) mechanism. By acting as ceRNAs, ncRNAs can competitively bind to miRNAs and modulate the expression of target mRNAs, thereby influencing the biological behavior of AF. The ceRNA axis has shown promise as a diagnostic and prognostic biomarker for AF. This review provides a comprehensive overview of the roles of ncRNAs in the development and progression of AF, highlighting the intricate crosstalk between different ncRNAs in AF pathophysiology. Furthermore, we discuss the potential implications of targeting the circRNA/lncRNA-miRNA-mRNA axis for the diagnosis, prognosis, and therapeutic intervention of AF.
Unveiling the Hidden Agony: Exploring Neuropathic Pain in the Younger Generation: A Narrative Review
Authors: Raju Nithya , Murugesan Roja , Villavan Samyuktha , Ravi Saranya
Published: December 2023

Pain is described as “an unpleasant sensory and emotional experience associated with, or resembling that associated with actual or potential tissue damage.” Neuropathic Pain (NP), a common condition, is characterised by subjective negative and positive sensations that range from numbness to debilitating agony. The prevalence of chronic pain and nerve pain in young individuals is estimated to be around 30%-50% and 6%-11%, respectively. The exact cause of NP is unknown, but research suggests that factors such as allodynia, external sensitisation, neuronal swelling, free radical damage, activation of microglia, and physiological state play a significant role in its development and progression. While there have been recent suggestions for medications, neurostimulation techniques, and interventional management, comprehensive guidelines covering all these treatments are yet to be released. Both peripheral and Central Nervous System (CNS) mechanisms contribute to the persistence of most NP types. The initial approach to treating NP in young individuals often involves pharmacotherapy. The types of drugs prescribed for general and specific types of NP in young individuals, including antidepressants and anticonvulsants, align with guidelines and consensus statements from various organisations worldwide. However, many individuals may not experience complete relief from their pain despite using these first-line treatments. Neuralgia, affecting 7 to 10% of the general population, is caused by dysfunction in the sensory organs of the body, which comprise A, A, and C fibers, as well as the brainstem and spinal cord.
Biochemical Analysis of Liver Function in Individuals Affected and Unaffected by Dental Fluorosis in Endemic Fluoride Rural Areas of YSR Kadapa District, AP, India: A Cross-sectional Study
Authors: Lavanya Sirigala , Ramani Prathiba
Published: December 2023

Introduction: Fluoride is known to affect the nervous system, kidneys, liver, and gastrointestinal system, in addition to teeth and bones, when consumed in amounts exceeding 1 ppm per day over a prolonged period. YSR Kadapa district has been identified as one of the districts with endemic fluoride areas in Andhra Pradesh, India, by the Central Groundwater Board of India. Aim: To assess the toxic effects of fluoride on liver function in individuals affected and unaffected by dental fluorosis, who consume high levels of fluoride in water, in the endemic fluoride rural areas of YSR Kadapa district. Materials and Methods: A cross-sectional study was conducted in six villages of YSR Kadapa district, where the drinking water has elevated fluoride content. A total of 320 subjects were selected as study participants. The subjects were divided into two groups based on age and dental fluorosis: Group A, aged between 21 and 40 years, and Group B, aged between 41 and 60 years. Subjects of each group were further sub-grouped according to presence or absence of fluorosis. The selected subjects were screened for dental fluorosis, and Groups A and B were further divided into subgroups based on the presence or absence of dental fluorosis. Blood samples were collected from the participants to assess liver function using serum levels of liver function markers such as total bilirubin (direct and indirect), Serum Glutamic Oxaloacetic Transaminase (SGOT), Serum Glutamate Pyruvate Transaminase (SGPT), and Alkaline Phosphatase (ALP). Water and urine samples were also tested for fluoride levels using a fluoride ion meter. Statistical significance was determined using the t-test. Results: The mean fluoride levels in the water samples from the study areas ranged from 1.55±0.30 mg/L to 4.10±0.20 mg/L, and the urinary fluoride levels in the urine samples ranged from 0.54±0.46 mg/L to 2.13±0.845 mg/L. Among the study subjects, 60.6% (194) were affected by dental fluorosis, with 58.66% (88) belonging to Group A and 62.35% (106) belonging to Group B. There was no statistically significant difference in liver function markers in the serum between subjects with dental fluorosis and those without dental fluorosis in both groups (p>0.05), and the levels were within the normal reference range. Conclusion: This study found no impaired or altered liver function in adults affected by dental fluorosis and adults unaffected by dental fluorosis who consumed water with high levels of fluoride in the YSR Kadapa district.