bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic Modelling of Biomethane Production from Waste: Application of Extreme Gradient Boosting
Authors: Pham Thi Yen , Nguyen Lan Huong
Published: May 2024

The escalating fossil fuel prices and greenhouse gases need urgent attention for a sustainable solution. The present study explores as modern machine learning approaches can be employed to prognosticate the complex biomethane generation process from organic wastes, like biowaste or food waste. The research investigates the use of organic sludges and how intelligent approaches can be employed to comprehend the complex nonlinear processes involved in biomethane production. Linear regression and Extreme gradient boosting (XGBoost) based prediction-models were developed and assessed employing a diverse set of statistical parameters, including R, R2, Mean Squared Error (MSE), Mean Absolute Error (MAE), and Kling-Gupta Efficiency (KGE). The results show that the XGBoost model beat the classical Linear Regression (LR) model in both the training and testing phases. During training, the XGBoost had an impressive R2 value of 0.99994, indicating a perfect fit to the data. In contrast, LR achieved an R2 value of 0.65464. Similarly, during the test period, XGBoost outperformed LR with R2 values ​​of 0.9553 to 0.9902. Furthermore, XGBoost reduced prediction errors, with significantly lower MSE and MAE values ​​than LR. Taylor’s graph better illustrates the excellent performance of the XGBoost over LR in both training and testing. These data demonstrate the ability of XGBoost to predict biomethane production, as well as its ability to improve the biomethane production process.
农村职业教育教师幸福感现状研究
Authors: Wang Qiuge , Zhang Bo
Published: May 2024

研究在参考公开发表文献的基础上，自制《农村职业教育教师幸福感量表》，通过电子“问卷星”对1362名农村职业教育教师进行调查。结果显示，性别、年龄、任职、职称、收入存在客观差异，配偶、子女职业范围不同，均能导致教师在心理、能力、健康、人际、经济和环境六个维度上的幸福感存在显著差异。最后，提出改变农村职业教育教师幸福感现状的教育建议。
Choosing Honey Over Vinegar: Using Facebook as Intervention Platform to Save Bully Student from Dropping Out
Authors:   The Rizal Memorial Colleges, Inc., Gamao Wilson
Published: May 2024

With the purpose to save a bully student from dropping out, the study primarily used Facebook as engagement platform to initiate the ground for communication. The researcher consistently interacted with the learner's Facebook posts, offering positive and inspiring comments to foster a supportive online community. Celebrating achievements and offering empathy during setbacks, the researcher aimed to boost the learner's confidence and encourage continued engagement. With these dynamics, the study intends to yield data on these specific objectives: 1) To yield the frequency of the researcher's engagement with the student on Facebook in terms of Like, Chat, and Comment; 2) To identify other ways and resources extended to save the student from dropping out; and, 3) To determine the personal advices extended by the researcher to save the student from dropping out. The results indicate that chatting on Messenger accounted for the highest frequency, totaling 3,686 times. Following this, the researcher liked the student's Facebook posts 1,746 times, while commenting on them occurred 2,037 times. Additionally, the researcher provided financial support, spending Php1,552.00 on transportation allowance and Php 873.00 on snacks for the student. The researcher continuously worked to boost the student's self-esteem and motivation, ensuring that he felt valued and encouraged to continue posting in the future. Additionally, the researcher closely monitored the student's activities and achievements, offering congratulations on successes and expressing sympathy during difficult times. The continuous interaction nurtured a profound connection between the researcher and the student, surpassing the conventional boundaries of the teacher-student dynamic. This deep bond led to the emergence of valuable life insights for the student, instilling a renewed determination to persevere and successfully complete senior high school. As a result, the student gained clarity of purpose and a strengthened resolve to overcome challenges and achieve academic success. Moreover, the study suggests that the Department of Education and school administrators should encourage supportive online communities to boost teacher-student social media use. Facebook should be used by teachers to motivate kids. Social media relationships with teachers can foster learning and personal growth.
Urgensi Pendidikan Seksual Anak: Perspektif Al-Qur’an dan Eksplorasi Preventif
Authors: Nur Ibad Taqwa , Sari Rita , Wahidah Finadatul
Published: May 2024

This research highlights the urgency of sexual education from the perspective of the Qur'an and the preventive exploration by the community towards sexual problems in children. The purpose of this study is to analyze the views of the Qur'an and preventive efforts from the community toward sexual education for children. The research method used is a phenomenological study. The results of the study reveal that sexual education is important to be delivered to children, with material that is appropriate to their age and stage of development. This education must not deviate from the guidance of the Qur'an and must be in harmony with human values and lifelines. The Qur'an teaches sex education through certain verses that emphasize ethical, moral, and moral aspects of sexual behavior
Chemical Footprint of Open Dumping Sites due to Electronic and Battery Waste
Authors:   School of Earth and Environmental Sciences, Central University of Himachal Pradesh, Dharamshala, Kangra, Himachal Pradesh-176215, Singh Umang , Kumar Anil , Pant Deepak ,   Forest Ecology and Climate Change Division, Himalayan Forest Research Institute, Shimla, India
Published: May 2024

Leachate from open dumping sites is found to be a major threat towards carcinogenic chemical footprint. The present study was conducted to evaluate the supply of various chemicals from electronic and battery (E&B) waste in dumping sites. Various types of E&B waste from household sources are regularly mixed with municipal solid waste (MSW). This study reports the presence of various types of primary and secondary pollutants in MSW from E&B waste. The major organic compounds found in the leachate were various phthalates, pyrrolidone and succinimidederivatives which may be due to the presence of e-toys and battery waste in the landfill. Intrusion of leachate containing these toxic compounds into river and groundwater systems leads to health implications like reproductive and developmental disorders, endocrine disruption and even cancer. It is concluded that a proper E&B waste management is necessary to ensure human and ecological health.
Tác động của chất lượng giấc ngủ đến tỷ suất sinh lời của nhà đầu tư cá nhân trên thị trường chứng khoán Việt Nam
Authors: Trần Tuấn Vinh  , Lưu Thu Quang
Published: May 2024

Nghiên cứu này phân tích tác động của chất lượng giấc ngủ (CLGN) đến tỷ suất sinh lời (TSSL) của nhà đầu tư cá nhân trên thị trường chứng khoán (TTCK) Việt Nam dựa trên dữ liệu từ 405 nhà đầu tư. CLGN được đánh giá thông qua các yếu tố như thời gian ngủ, thời lượng, số lần thức giấc trong đêm và thói quen ngủ trưa. Kết quả chỉ ra rằng CLGN không có sự ảnh hưởng rõ ràng đến TSSL của các nhà đầu tư nói chung và nhà đầu tư chủ động (là các nhà đầu tư có tần suất giao dịch cao) nói riêng. Tuy nhiên, nhóm tác giả cũng tìm thấy bằng chứng cho rằng CLGN tốt sẽ ảnh hưởng tích cực đến TSSL của các nhà đầu tư thụ động (là các nhà đầu tư có tần suất giao dịch thấp). Kết quả nghiên cứu được đảm bảo tính vững bằng việc sử dụng nhiều mô hình khác nhau bao gồm OLS, PCA, PLSR và GMM. Nhóm tác giả khuyến nghị các nhà đầu tư thụ động nên nâng cao CLGN để duy trì cảm xúc tích cực và nhận thức tốt, điều này sẽ giúp gia tăng TSSL của bản thân.
Tác động của tài chính toàn diện đến ổn định ngân hàng: Nghiên cứu thực nghiệm trường hợp tại ASEAN-5
Authors: Trần Thị Thanh Nga  , Cao Dương Khánh Linh  , Đoàn Tạ Trúc Linh  , Đỗ Lê Hoài Trâm  , Phan Thị Bảo Trân  , Nguyễn Thị Anh Thư
Published: May 2024

Nghiên cứu sử dụng kỹ thuật ước lượng SGMM trong giai đoạn 2007–2021 của 53 ngân hàng để kiểm tra vai trò của tài chính toàn diện (financial inclusion – FI) đến ổn định ngân hàng (Bank stability – BS) (OĐNH) tại các quốc gia ASEAN-5. Kết quả đều cho thấy tài chính toàn diện có tác động đáng kể đến OĐNH ở các quốc gia trong khu vực ASEAN-5 nhưng tuỳ thuộc vào từng biến số đo lường tài chính toàn diện. Các biến số đại diện toàn diện tài chính thể hiện khả năng tiếp cận (số lượng máy rút tiền tự động (ATM) trên 100.000 người lớn; giá trị của các giao dịch tiền qua internet) và biến số sử dụng (số lượng tài khoản tiền gửi tại NHTM trên 1.000 người trưởng thành) có tác động tích cực đến OĐNH. Biến số toàn diện tài chính thể hiện khả năng tiếp cận (với số chi nhánh ngân hàng trên 100.000 người lớn) có tác động tiêu cực đến OĐNH (Z-score); điều này hàm ý rằng, khi số lượng chi nhánh ngân hàng tăng lên sẽ chứa đựng nhiều yếu tố rủi ro vì vậy các nhà quản lý ngân hàng cần phải hết sức thận trọng khi điều chỉnh chính sách. Nghiên cứu này có ý nghĩa quan trọng về quản lý trong ngành ngân hàng ở tại các quốc gia ASEAN-5, đặc biệt là ở các nước mới nổi và đang phát triển, từ đó định hướng nền kinh tế của các quốc gia trong khu vực.
Pelatihan Kewirausahaan Handcrafting Untuk Meningkatkan Pendapatan Bagi Ibu Rumah Tangga Di Kelurahan Pakunden Kota Kediri
Authors: Himmati Risdiana
Published: May 2024

Penyebaran virus Corona telah mengubah banyak aspek kehidupan di Indonesia, termasuk perekonomian dan kehidupan sosial. Dampaknya meliputi peningkatan angka pengangguran dan kemiskinan, serta pergeseran peran tradisional, khususnya bagi ibu rumah tangga. Untuk meningkatkan kesejahteraan keluarga, dilakukan pelatihan rajutan tangan. Tujuannya adalah meningkatkan pengetahuan dan ketrampilan ibu rumah tangga untuk memproduksi karya rajutan yang dapat dijual. Program ini menyasar pengembangan luaran yang terukur dan aplikatif, serta menerapkan hasil pelatihan pasca pandemi Covid-19. Melalui metode perencanaan, pelaksanaan, monitoring, dan evaluasi, program ini bertujuan untuk memberikan dampak positif terhadap ekonomi keluarga di Indonesia, sambil juga memperkuat hubungan antara perguruan tinggi dan masyarakat.
Leading the New Generation: Understanding the Leadership Styles of a Millennial School Head
Authors: Mandap Angelica
Published: May 2024

As the older generation of school heads approaches retirement and exits the workforce, millennial school heads are quickly taking over. While existing studies attribute particular leadership styles to the older generational cohorts presently engaged in the workforce, there is a dearth of prior studies identifying the leadership styles employed by millennial school leaders. This qualitative and descriptive single-case study bridges that gap by exploring and analyzing the leadership styles of a millennial school head. The study employs in-depth interviews with a semi-structured guide to unravel the essential leadership styles crucial for tackling the challenges of school management. The purposively selected participant, a millennial school head currently managing a school, holding the position of Principal, and aged between 26 and 41 years old, becomes the focal point of analysis. The findings reveal four significant themes: transformational leadership style, servant leadership style, instructional leadership style, and authoritative leadership style. In conclusion, millennial school leaders intentionally adopted these leadership styles to tackle the challenges they encounter in overseeing educational institutions. The paper emphasizes implications for pedagogy and educational management while proposing potential avenues for future research.
Extinguishing the Fire: Occupational Stress-Coping Mechanisms of High School Teachers
Authors: Viloria Jolina May
Published: May 2024

The challenging reality that teachers and school personnel face is emerging and demands acknowledgment. High occupational stress exacerbates teacher burnout, loss of engagement, job dissatisfaction, poor performance, and even one of the worst turnover rates in human history, impacting teacher health and well-being. Teachers must address stress promptly to prevent its adverse effects on their work. This illustrative retrospective single-case study design explored and understood the occupational stress-coping mechanisms of private high school teachers. The researcher employed a semi-structured interview guide to collect data about five private high school teachers who teach at a PAASCU Accredited School. The result revealed three themes: Problem-Focused, Self-recreation, and Social-Support Mechanism. Teachers who handle occupational stress well can perform better, creating a positive learning environment for students due to the interconnectedness of stress mechanisms. This study concludes on the premise that being stressed at work affects the overall performance of teachers. Therefore, the ability to cope with occupational stress contributes to teachers, and teachers who feel equipped to handle the demands of their jobs are more likely to find fulfillment in their careers.
Pengaruh Pendidikan Sekolah Minggu Buddhis (SMB) terhadap Perkembangan Fisik-Motorik Peserta Didik di SMB Sariputta Buddhist Studies Pekanbaru
Authors: Wijoyo Hadion , Girivirya Sulaiman
Published: May 2024

Buddhist Sunday School Education (SMB) is very closely related to the physical-motor development of SMB students who have a very broad understanding. SMB education has been provided with a good curriculum, shown with real evidence (with practice and has a purpose), service educators who are responsible by using the heart, and have responsive students. In addition, the use of teaching aids that are appropriate to the development of the situation, delivery methods that are on target, adequate environmental conditions, and material that is easily digested by students in accordance with the times, so that all can be conveyed properly in accordance with the physical-motor development of the participants SMB students by providing optimal results in the form of changes in student behavior. Therefore education must be able to understand changes in student behavior and provide results with the quality of students as expected by parents. SMB education that has vision, mission and quality in the eyes of parents is very important in attracting SMB students to continue learning and help the process of learning and harmony between students and educators so that there will be changes in student behavior. Thus SMB education is expected to have a positive effect on the physical-motor development of SMB students.
Hubungan antara Komitmen Organisasi dengan Kinerja Guru SD Metta Maitreya Pekanbaru
Authors: Sutikno Yadi , Hosan Hosan , Irawati Irawati
Published: May 2024

This research is motivated by the performance of the teachers at SD Metta Maitreya which are still not professional, there are still scores of students under the KKM, and a lack of organizational commitment to school teachers, and there are still teachers who lack teacher responsibility at work. Therefore, this study aims to determine the relationship between organizational commitment and organizational culture with the performance of teachers at SD Metta Maitreya Pekanbaru. The research method used is a survey method with correlational techniques. The study population was 24 teachers of SD Metta Maitreya Pekanbaru, so the sample was 24 people. The data collection instrument was in the form of a questionnaire or questionnaire. The validity and reliability of the questionnaire on performance, organizational commitment, and organizational culture have been tested. The data normality test was carried out by the Kolmogorov Smirnov test. The data analysis used was multiple correlation analysis using a level of α = 0.05. The results of   data   analysis   show   that   there   is   a   significant   relationship   between Organizational Commitment (X1) and Organizational Culture (X2) and Teacher Performance (Y) together with the regression equation Y  = 81.388 + 0.295X1 + 0.466X2, the correlation coefficient is 0.570. The results of this study are expected to be useful for improving the performance, organizational commitment and organizational culture of SD Metta Maitreya Pekanbaru. The conclusion of this study shows that performance can be increased through increasing organizational commitment and organizational culture simultaneously.
Lanthanide Oxide Nanoparticles for Environmental Remediation: A Review
Authors:   Department of Chemistry, Manipal University, Jaipur, Rajasthan 303007, India, Sushil Kumar , Ganga Ram Chaudhary ,   Department of Chemistry, Panjab University, Chandigarh 160014, India, Savita Chaudhary ,   Department of Chemistry, Panjab University, Chandigarh 160014, India, Ahmad Umar ,   Department of Chemistry, Faculty of Science and Arts and Promising Centre for Sensors and Electronic Devices (PCSED), Najran University, Najran-11001, Kingdom of Saudi Arabia. Department of Materials Science and Engineering, The Ohio State University, Columbus 43210, OH, USA
Published: May 2024

The lanthanide oxide nanoparticles were used for the removal of pollutants towards environmental remediation. The enhanced properties and effectiveness of nanotechnology based materials makes them particularly suitable contender in detection of pollutants. The used particles synthesized by facile and easy method with additional standard modification. The origin of pollutants, their toxicity and influential effect of respective pollutants on the environment, humans and ecological system studied in details. The prepared nanoparticles as highly efficient probes, with novel methodology utilized for detection and removal of pollutants. The easy, cost effective and efficient technologies were performed for sensing of these pollutants. This article deals with mainly detection of pollutants present in water, air and soil by using nanomaterial. Further, these nanoparticle is utilized in degradation of various types of pollutants present in the environment.
Teachers’ practices, challenges, and opportunities in developing science literacyamonghigh school students
Authors: Señara Ignacio Jr
Published: May 2024

This research aimed to explore the experiences of high school science teachers, focusing ontheir perceived practices, challenges, and opportunities in fostering science literacy among students in the Talon- Talon District, Division of Zamboanga City. A mixed-methods approach was employed, integrating both qualitative and quantitative research designs. The quantitative component involved administering a structured survey to a broad sample of science teachers, while the qualitative component involved conducting in-depth key informant interviews. The data was analyzed using descriptive statistics and thematic analysis. The findings revealed that teachers perceive their practices in developing science teaching literacy as a complex process that involves a deep understanding of science content, the use of effective pedagogical strategies, and the promotion of actual and post-literacy skills. They face challenges in addressing diverse student needs and fostering creativity and critical thinking. However, opportunities exist in continuous professional development, innovative teaching methods, and promoting higher-order thinking skills. The study provides valuable insights into scienceteachers’ experiences in fostering scientific literacy. The findings could assist in overcoming the challengesfaced in teaching and developing science literacy, thereby aiding in the successful integration of science literacyin the curriculum and teaching. Based on the findings of the study, several recommendations can be made for science teachers, students, school administrators, the Department of Education, and future researchers. These recommendations aim to enhance the teaching and development of science literacy, improve teaching methods, guide the formulation of policies and guidelines related to science literacy, and serve as a basis for future studies.
Protests and use of rubber bullets in South Africa: Unspoken pain and trauma of eye injuries
Authors: Langa Malose , Bruce David , Kirsten Adele , Madi Palesa
Published: May 2024

Introduction: The article examines the experiences of protesters and bystanders who have sustained eye injuries from rubber bullets fired by the police. Use of rubber bullets by police officers during public protests is officially regulated, but there is insufficient documentation about the nature of fatal and non-fatal injuries linked to rubber bullet use during protests in South Africa. Methods: This article presented three case studies based on data gathered from student protests, community protests, and media reports. Through the analysis of these sources, the article presents the personal stories of individuals who have experienced eye injuries, detailing how the incidents occurred and the subsequent impact on their lives. It also examines the accessibility of medical, psychological, and legal services available to victims in addressing the consequences of these injuries. Results: The cases studies illustrate that rubber bullets were used frequently and often without due caution by police officers during the events examined. The use of rubber bullets was linked to numerous eye injuries, resulting in lasting psychological and physical consequences for those affected. Discussion: The article concludes that rubber bullet-related eye injuries during protests are disturbingly common in South Africa. Consequently, there is an urgent need to provide essential services and support to those who suffer from these life-altering incidents
Health impact of electric discharge weapons: a review of case studies
Authors: Brasholt Marie , Aon Maha , Michaelsen Lisa , Modvig Jens
Published: May 2024

Introduction
Electrical discharge weapons (EDWs) are increasingly used by law enforcement around the globe as a less lethal option to firearms. Concerns have been raised about their use, inter alia from the UN Committee Against Torture (UNCAT).
The purpose of this manuscript is to provide an overview of case studies to assess the health consequences of EDW exposure. 
Methods
Medline and Pubmed were searched for case studies on EDWs without restriction on language or date. Screening was first at abstract level and then at full article level. Articles were excluded if they were not case studies, concerned children under 15 years old or were off topic. A PRISMA flow diagram was created.
Results
A total of 71 studies were included, and they demonstrate a wide range of health consequences from minor injuries to lethal conditions. The injuries can be classified as direct and indirect, i.e., related to the use itself (e.g., penetration by darts) and related to falls and burns following neuromuscular incapacitation and ignition of flammable fluids. Cardiac incidents – some being fatal - were the health consequences found most reported, but the relation to the EDW is contested. In other cases, a very plausible association is established between EDW exposure and the health consequences. Description of pain and mental suffering related to EDW exposure was lacking in the reviewed case studies.
Discussion
EDWs may lead to physical and most likely mental suffering. When assessing patients and when documenting cases where persons may have been exposed to EDWs, including torture and ill-treatment cases, it is important to be aware of the different types of health consequences.
The Value of Media Ecology for Enabling Human Rights Defenders to Advocate for the Protection of the Right to Mental Health in the Context of Deploying Artificial Intelligence Technology as part of the Decision-making Process
Authors: Krupiy Tetyana (Tanya)
Published: May 2024

Traditionally, human rights activists gathered evidence about violations of particular individuals' human rights to demand that states change their conduct and adopt measures to prevent further violations. Deploying artificial intelligence as part of the decision-making process creates challenges for activists to detect all sources of harm and demand that states take action to address the harms. Abeba Birhane points out that employing artificial intelligence technology can generate harmful impacts that are either difficult to detect or invisible. If harms remain invisible, then it is difficult for human rights defenders to document them. Equally, it becomes challenging to articulate why the harms in question constitute international human rights law violations. As a result, it is harder for human rights defenders to call on states to take action to safeguard fundamental rights. This article puts forward that individuals can make harms arising from the deployment of artificial intelligence as part of the decision-making process more visible by using the theoretical framework of media ecology. It demonstrates that media ecology can provide an additional tool for human rights activists to detect how using artificial intelligence as part of the decision-making process can undermine the enjoyment of a human right. The article uses the right to mental health as a case study to develop this argument. In order to contextualise the analysis, the article focuses on the employment of artificial intelligence to screen candidates for employment as a case study.
Propagation of the Organization of Works of Art
Authors: Logan Robert K.
Published: May 2024

Our aim in this article is to discuss the propagating organization of artistic sensibility and the works of art that arise from that sensibility which we claim parallels the propagating organization of living organisms. We first examine what distinguishes a work of art from other forms of human artifacts such as tools, technology shelters, toys, games and ornaments. We show that this propagation of art and artistic sensibilities parallels the propagation of the organization of living systems. By doing so we explore the hypothesis that works of art and the artistic sensibility that give rise to them are metaphorically like a living organism in that they propagate their organization and that artistic expression evolvesmuch like the way that living organisms propagate their organization and also evolve.
How the Electric Toothbrush, Search Engine, Smartphone, Social Media and Artificial Intelligence Decision-Making Processes Amplify the Exercise of Power at State and Global Levels: A Media Ecology Analysis
Authors: Krupiy Tetyana (Tanya)
Published: May 2024

Scholars disagree over whether the employment of artificial intelligence technologies entails an inevitable exercise of power over people or whether such technologies can be configured in such a way as to allow a plurality of possible ways to engage in governance. This article uses the media ecology approach to analysis to demonstrate that the concern that artificial intelligence technologies that appear to be mundane are in fact involved in the exercise of power over people is valid. It contributes to the existing literature by showing that numerous applications of artificial intelligence that people use on an everyday basis interact to amplify one another’s effects. These technologies are the electric toothbrush, internet search engine, smartphone, social media and the use of artificial intelligence as part of the decision-making process. These effects occur at the levels of the individual, city, state and inter-state. These effects are cascading and interconnected rather than occurring on distinct planes. The exercise of power over the individual by the state and the corporations becomes difficult to disentangle. Therefore, states need to cooperate regarding governing artificial intelligence and technology companies if they are to meaningfully protect people from harmful effects.
OMEN EST NOMEN ИЛИ НАУКА О КЊИЗИ КОД СРБА
Authors: Шмуља Вања Р.
Published: May 2024

У овом раду бавићемо се приступом проучавању књиге. Приказаћемо научне дисциплине које се тиме баве (библиологију, библиографију и библиотекарство) и указати на неопходност увођења парадигме полиморфне науке о књизи будући да су ове области не само испреплетене него потпуно срасле и да је приступ са само једне позиције у про- учавању књиге недовољан. Библиографски и каталошки опис, управљање збиркама, нарочито фондовима старе и ри- јетке књиге: набавка, одређивање ријеткости, вриједности, посебно чување, каталогизација, одређивање припадајућег издања и тачан опис примјерка – немогући су са позиција само једне области. Стога је неопходно увођење концепта науке о књизи као медију који нуди одговоре на сва питања, без обзира на то да ли књизи приступамо као артефакту или као информацији.
Involvement of TRPV4 in temperature-dependent perspiration in mice
Authors: Kashio Makiko , Derouiche Sandra , Yoshimoto Reiko U. , Sano Kenji , Lei Jing , Kido Mizuho A. , Tominaga Makoto
Published: May 2024

Reports indicate that an interaction between TRPV4 and anoctamin 1 could be widely involved in water efflux of exocrine glands, suggesting that the interaction could play a role in perspiration. In secretory cells of sweat glands present in mouse foot pads, TRPV4 clearly colocalized with cytokeratin 8, anoctamin 1 (ANO1) and aquaporin-5 (AQP5). Mouse sweat glands showed TRPV4-dependent cytosolic Ca
2+
increases that was inhibited by menthol. Acetylcholine-stimulated sweating in foot pads was temperature-dependent in wild-type, but not in TRPV4-deficient mice, and was inhibited by menthol both in wild-type and TRPM8KO mice. The basal sweating without acetylcholine stimulation was inhibited by an ANO1 inhibitor. Sweating could be important for maintaining friction forces in mouse foot pads, and this possibility is supported by the finding that wild-type mice climbed up a slippery slope more easily than TRPV4-deleted mice. Furthermore, TRPV4 expression was significantly higher in controls and normohidrotic skin from patients with AIGA (acquired idiopathic generalized anhidrosis) compared to anhidrotic skin from patients with AIGA. Collectively, TRPV4 is likely involved in temperature-dependent perspiration via interactions with ANO1, and TRPV4 itself or the TRPV4/ANO 1 complex would be targets to develop agents that regulate perspiration.
Reactivation strength during cued recall is modulated by graph distance within cognitive maps
Authors: Kern Simon , Nagel Juliane , Gerchen Martin F , Gürsoy Çağatay , Meyer-Lindenberg Andreas , Kirsch Peter , Dolan Raymond J , Gais Steffen , Feld Gordon B
Published: May 2024

Declarative memory retrieval is thought to involve reinstatement of neuronal activity patterns elicited and encoded during a prior learning episode. Furthermore, it is suggested that two mechanisms operate during reinstatement, dependent on task demands: individual memory items can be reactivated simultaneously as a clustered occurrence or, alternatively, replayed sequentially as temporally separate instances. In the current study, participants learned associations between images that were embedded in a directed graph network and retained this information over a brief 8 min consolidation period. During a subsequent cued recall session, participants retrieved the learned information while undergoing magnetoencephalographic recording. Using a trained stimulus decoder, we found evidence for clustered reactivation of learned material. Reactivation strength of individual items during clustered reactivation decreased as a function of increasing graph distance, an ordering present solely for successful retrieval but not for retrieval failure. In line with previous research, we found evidence that sequential replay was dependent on retrieval performance and was most evident in low performers. The results provide evidence for distinct performance-dependent retrieval mechanisms, with graded clustered reactivation emerging as a plausible mechanism to search within abstract cognitive maps.
Dual engagement of the nucleosomal acidic patches is essential for deposition of histone H2A.Z by SWR1C
Authors: Baier Alexander S , Gioacchini Nathan , Eek Priit , Leith Erik M , Tan Song , Peterson Craig L
Published: May 2024

The yeast SWR1C chromatin remodeling enzyme catalyzes the ATP-dependent exchange of nucleosomal histone H2A for the histone variant H2A.Z, a key variant involved in a multitude of nuclear functions. How the 14-subunit SWR1C engages the nucleosomal substrate remains largely unknown. Studies on the ISWI, CHD1, and SWI/SNF families of chromatin remodeling enzymes have demonstrated key roles for the nucleosomal acidic patch for remodeling activity, however a role for this nucleosomal epitope in nucleosome editing by SWR1C has not been tested. Here, we employ a variety of biochemical assays to demonstrate an essential role for the acidic patch in the H2A.Z exchange reaction. Utilizing asymmetrically assembled nucleosomes, we demonstrate that the acidic patches on each face of the nucleosome are required for SWR1C-mediated dimer exchange, suggesting SWR1C engages the nucleosome in a ‘pincer-like’ conformation, engaging both patches simultaneously. Loss of a single acidic patch results in loss of high affinity nucleosome binding and nucleosomal stimulation of ATPase activity. We identify a conserved arginine-rich motif within the Swc5 subunit that binds the acidic patch and is key for dimer exchange activity. In addition, our cryoEM structure of a Swc5–nucleosome complex suggests that promoter proximal, histone H2B ubiquitylation may regulate H2A.Z deposition. Together these findings provide new insights into how SWR1C engages its nucleosomal substrate to promote efficient H2A.Z deposition.
An arms race between 5’ppp-RNA virus and its alternative recognition receptor MDA5 in RIG-I-lost teleost fish
Authors: Geng Shang , Lv Xing , Zheng Weiwei , Xu Tianjun
Published: May 2024

The incessant arms race between viruses and hosts has led to numerous evolutionary innovations that shape life’s evolution. During this process, the interactions between viral receptors and viruses have garnered significant interest since viral receptors are cell surface proteins exploited by viruses to initiate infection. Our study sheds light on the arms race between the MDA5 receptor and 5’ppp-RNA virus in a lower vertebrate fish,
M. miiuy
. Firstly, the frequent and independent loss events of RIG-I in vertebrates prompted us to search for alternative immune substitutes, with homology-dependent genetic compensation response (HDGCR) being the main pathway. Our further analysis suggested that MDA5 of
M. miiuy and G. gallus
, the homolog of RIG-I, can replace RIG-I in recognizing 5’ppp-RNA virus, which may lead to redundancy of RIG-I and loss from the species genome during evolution. Secondly, as an adversarial strategy, 5’ppp-RNA SCRV can utilize the m
6
A methylation mechanism to degrade MDA5 and weaken its antiviral immune ability, thus promoting its own replication and immune evasion. In summary, our study provides a snapshot into the interaction and coevolution between vertebrate and virus, offering valuable perspectives on the ecological and evolutionary factors that contribute to the diversity of the immune system.
ASAR lncRNAs control DNA replication timing through interactions with multiple hnRNP/RNA binding proteins
Authors: Thayer Mathew J. , Heskett Michael B. , Smith Leslie G. , Spellman Paul T. , Yates Phillip A.
Published: May 2024

ASARs are a family of very-long noncoding RNAs that control replication timing on individual human autosomes, and are essential for chromosome stability. The eight known ASAR lncRNAs remain closely associated with their parent chromosomes. Analysis of RNA-protein interaction data (from ENCODE) revealed numerous RBPs with significant interactions with multiple ASAR lncRNAs, with several hnRNPs as abundant interactors. An ∼7kb domain within the ASAR6-141 lncRNA shows a striking density of RBP interaction sites. Genetic deletion and ectopic integration assays indicate that this ∼7kb RNA binding protein domain contains functional sequences for controlling replication timing of entire chromosomes in
cis
. shRNA-mediated depletion of 10 different RNA binding proteins, including HNRNPA1, HNRNPC, HNRNPL, HNRNPM, HNRNPU, or HNRNPUL1, results in dissociation of ASAR lncRNAs from their chromosome territories, and disrupts the synchronous replication that occurs on all autosome pairs, recapitulating the effect of individual ASAR knockouts on a genome-wide scale. Our results further demonstrate the role that ASARs play during the temporal order of genome-wide replication, and we propose that ASARs function as essential RNA scaffolds for the assembly of hnRNP complexes that help maintain the structural integrity of each mammalian chromosome.
Neurons enhance blood-brain barrier function via upregulating claudin-5 and VE-cadherin expression due to GDNF secretion
Authors: Yang Lu , Lin Zijin , Mu Ruijing , Wu Wenhan , Zhi Hao , Liu Xiaodong , Yang Hanyu , Liu Li
Published: May 2024

Blood-brain barrier (BBB) prevents neurotoxins from entering central nervous system. We aimed to establish and characterize an
in vitro
triple co-culture BBB model consisting of brain endothelial cells hCMEC/D3, astrocytoma U251 cells, and neuroblastoma SH-SY5Y cells. Co-culture of SH-SY5Y and U251 cells markedly enhanced claudin-5 and VE-cadherin expression in hCMEC/D3 cells, accompanied by increased transendothelial electrical resistance and decreased permeability. Conditioned medium (CM) from SH-SY5Y cells (S-CM), U251 cells (U-CM), and co-culture of SH-SY5Y and U251 cells (US-CM) also promoted claudin-5 and VE-cadherin expression. Glial cell line-derived neurotrophic factor (GDNF) levels in S-CM and US-CM were significantly higher than CMs from hCMEC/D3 and U-CM. Both GDNF and US-CM upregulated claudin-5 and VE-cadherin expression, which were attenuated by anti-GDNF antibody and GDNF signaling inhibitors. GDNF increased claudin-5 expression via the PI3K/AKT/FOXO1 and MAPK/ERK pathways. Meanwhile, GDNF promoted VE-cadherin expression by activating PI3K/AKT/ETS1 and MAPK/ERK/ETS1 signaling. The roles of GDNF in BBB integrity were validated using brain-specific
Gdnf
silencing mice. The developed triple co-culture BBB model was successfully applied to predict BBB permeability. In conclusion, neurons enhance BBB integrity by upregulating claudin-5 and VE-cadherin expression through GDNF secretion and established triple co-culture BBB model may be used to predict drugs’ BBB permeability.
The protective roles of Eugenol on type 1 diabetes mellitus through NRF2 mediated oxidative stress pathway
Authors: Jiang Yalan , He Pingping , Sheng Ke , Peng Yongmiao , Wu Huilan , Qian Songwei , Ji Weiping , Guo Xiaoling , Shan Xiaoou
Published: May 2024

Type 1 diabetes mellitus (T1DM), known as insulin-dependent diabetes mellitus, is characterized by persistent hyperglycemia caused by damage to the pancreatic β cells and an absolute insulin deficiency, which will affect multiple organs and has a poor prognosis. Oxidative stress and apoptosis play a major role in the progression of T1DM. Eugenol (EUG) is a natural compound with anti-inflammatory, anti-oxidant, and anti-apoptosis activities. However, the potential effects of EUG on T1DM had not been investigated. In this study, we established the streptozotocin (STZ)-induced T1DM mouse model in vivo and STZ-induced pancreatic β cell MIN6 cell model in vitro to explore the protective effects of EUG on T1DM, and tried to illuminate the potential mechanism. Our results showed that EUG intervention could activate the expression of nuclear factor E2-related factor 2 (NRF2), increase the expressions of downstream proteins NQO-1 and HO-1 regulated by NRF2, alleviate pancreatic β cell damage in T1DM, elevate insulin secretion, and reduce the expression levels of apoptosis and oxidative stress related markers. Furthermore, these effects of EUG could be significantly reversed by ML385, an inhibitor of NRF2. The present study suggested that EUG exerted protective effects on pancreatic β cells in T1DM by mitigating apoptosis and oxidative stress through activating the NRF2 signaling pathway. Consequently, EUG holds great promise as a potential therapeutic candidate for T1DM.
Behavioural pharmacology predicts disrupted signalling pathways and candidate therapeutics from zebrafish mutants of Alzheimer’s disease risk genes
Authors: Kroll François , Donnelly Joshua , Özcan Güliz Gürel , Mackay Eirinn , Rihel Jason
Published: May 2024

By exposing genes associated with disease, genomic studies provide hundreds of starting points that should lead to druggable processes. However, our ability to systematically translate these genomic findings into biological pathways remains limited. Here, we combine rapid loss-of-function mutagenesis of Alzheimer’s risk genes and behavioural pharmacology in zebrafish to predict disrupted processes and candidate therapeutics. FramebyFrame, our expanded package for the analysis of larval behaviours, revealed that decreased night-time sleep was common to F0 knockouts of all four late-onset Alzheimer’s risk genes tested. We developed an online tool, ZOLTAR, which compares any behavioural fingerprint to a library of fingerprints from larvae treated with 3677 compounds. ZOLTAR successfully predicted that sorl1 mutants have disrupted serotonin signalling and identified betamethasone as a drug which normalises the excessive day-time sleep of presenilin-2 knockout larvae with minimal side effects. Predictive behavioural pharmacology offers a general framework to rapidly link disease-associated genes to druggable pathways.
Behavioural pharmacology predicts disrupted signalling pathways and candidate therapeutics from zebrafish mutants of Alzheimer’s disease risk genes
Authors: Kroll François , Donnelly Joshua , Özcan Güliz Gürel , Mackay Eirinn , Rihel Jason
Published: May 2024

By exposing genes associated with disease, genomic studies provide hundreds of starting points that should lead to druggable processes. However, our ability to systematically translate these genomic findings into biological pathways remains limited. Here, we combine rapid loss-of-function mutagenesis of Alzheimer’s risk genes and behavioural pharmacology in zebrafish to predict disrupted processes and candidate therapeutics. FramebyFrame, our expanded package for the analysis of larval behaviours, revealed that decreased night-time sleep was common to F0 knockouts of all four late-onset Alzheimer’s risk genes tested. We developed an online tool, ZOLTAR, which compares any behavioural fingerprint to a library of fingerprints from larvae treated with 3,674 compounds. ZOLTAR successfully predicted that sorl1 mutants have disrupted serotonin signalling and identified betamethasone as a drug which normalises the excessive day-time sleep of presenilin-2 knockout larvae with minimal side effects. Predictive behavioural pharmacology offers a general framework to rapidly link disease-associated genes to druggable pathways.
Heterogeneity of Sonic Hedgehog response dynamics and fate specification in single neural progenitors
Authors: Xiong Fengzhu , Tentner Andrea R. , Nandagopal Sandy , Hiscock Tom W. , Huang Peng , Megason Sean G.
Published: May 2024

During neural tube patterning, a gradient of Sonic hedgehog (Shh) signaling specifies ventral progenitor fates. The cellular response to Shh is processed through a genetic regulatory network (GRN) to specify distinct fate decisions. This process integrates Shh response level, duration and other inputs and is affected by noise in signaling and cell position. How reliably Shh response profile predicts the fate choice of a single cell is unclear. Here we use live imaging to track neural progenitors in developing zebrafish and quantify both Shh and fate reporters in single cells over time. We found that there is significant heterogeneity between Shh response and fate choice in single cells. We quantitatively modeled reporter intensities to obtain single cell response levels over time and systematically evaluated their correlation with cell fate specification. Motor neuron progenitors (pMN) exhibit a high degree of variability in their Shh responses, which is particularly prominent in the posterior neural tube where the Shh response dynamics are similar to those of the more ventrally fated lateral floor plate cells (LFPs). Our results highlight the precision limit of morphogen-interpretation GRNs in small and dynamic target cell fields.
Circular RNA HMGCS1 sponges MIR4521 to aggravate type 2 diabetes-induced vascular endothelial dysfunction
Authors: Zhang Ming , Du Guangyi , Xie Lianghua , Xu Yang , Chen Wei
Published: May 2024

Noncoding RNA plays a pivotal role as novel regulators of endothelial cell function. Type 2 diabetes, acknowledged as a primary contributor to cardiovascular diseases, plays a vital role in vascular endothelial cell dysfunction due to induced abnormalities of glucolipid metabolism and oxidative stress. In this study, aberrant expression levels of circHMGCS1 and MIR4521 were observed in diabetes-induced human umbilical vein endothelial cell dysfunction. Persistent inhibition of MIR4521 accelerated development and exacerbated vascular endothelial dysfunction in diabetic mice. Mechanistically, circHMGCS1 upregulated arginase 1 by sponging MIR4521, leading to decrease in vascular nitric oxide secretion and inhibition of endothelial nitric oxide synthase activity, and an increase in the expression of adhesion molecules and generation of cellular reactive oxygen species, reduced vasodilation and accelerated the impairment of vascular endothelial function. Collectively, these findings illuminate the physiological role and interacting mechanisms of circHMGCS1 and MIR4521 in diabetes-induced cardiovascular diseases, suggesting that modulating the expression of circHMGCS1 and MIR4521 could serve as a potential strategy to prevent diabetes-associated cardiovascular diseases. Furthermore, our findings provide a novel technical avenue for unraveling ncRNAs regulatory roles of ncRNAs in diabetes and its associated complications.
Molecular determinants of Neu5Ac binding to a tripartite ATP independent periplasmic (TRAP) transporter
Authors: Goyal Parveen , Dhanabalan KanagaVijayan , Scalise Mariafrancesca , Friemann Rosmarie , Indiveri Cesare , Dobson Renwick CJ , Vinothkumar Kutti R , Ramaswamy Subramanian
Published: May 2024

N -Acetylneuraminic acid (Neu5Ac) is a negatively charged nine-carbon amino sugar that is often the peripheral sugar in human cell-surface glycoconjugates. Some bacteria scavenge, import, and metabolize Neu5Ac or redeploy it on their cell surfaces for immune evasion. The import of Neu5Ac by many bacteria is mediated by tripartite ATP-independent periplasmic (TRAP) transporters. We have previously reported the structures of SiaQM, a membrane-embedded component of the Haemophilus influenzae TRAP transport system, (Currie et al., 2024). However, none of the published structures contain Neu5Ac bound to SiaQM. This information is critical for defining the transport mechanism and for further structure-activity relationship studies. Here, we report the structures of Fusobacterium nucleatum SiaQM with and without Neu5Ac. Both structures are in an inward (cytoplasmic side) facing conformation. The Neu5Ac-bound structure reveals the interactions of Neu5Ac with the transporter and its relationship with the Na+ binding sites. Two of the Na+-binding sites are similar to those described previously. We identify a third metal-binding site that is further away and buried in the elevator domain. Ser300 and Ser345 interact with the C1-carboxylate group of Neu5Ac. Proteoliposome-based transport assays showed that Ser300-Neu5Ac interaction is critical for transport, whereas Ser345 is dispensable. Neu5Ac primarily interacts with residues in the elevator domain of the protein, thereby supporting the elevator with an operator mechanism. The residues interacting with Neu5Ac are conserved, providing fundamental information required to design inhibitors against this class of proteins.