bluuebunny/crossref_metadata_2025 huggingface dataset:
Why Police Violate the Human Rights: Bangladesh Chapter
Authors:   Lecturer of Philosophy, Feni South East Degree College, Adil Md. Sharifur Rahman , Lasker Shamima Parvin ,   Professor of Anatomy & Secretary General, Bangladesh Bioethics Society
Published: April 2024

The police are one of the important law enforcement agency in Bangladesh. Police are the best agency to protect human rights. Indeed, the police have a special responsibility to protect people. In addition, to their duty, they also serve in people's social and moral call, especially during COVID-19 situations they imprint many examples of humanity. People experience many good deeds of police during a national disaster as well. However, allegation against the police for violations of human rights is not uncommon. Cases of torture, death in police custody, involvement in the drug trade and robberies, entrapment with drug, helping in land grabbing, etc. are being published in newspapers. Nevertheless, to protect human rights or to take care of human rights is the prime function of the police. This research efforts to find out the answer to why police violate human rights. This research may help police professionals or administrators in taking policy initiatives to erase the negative image of the police.
PENGEMBANGAN MASYARAKATLAPORAN HASIL OBSERVASI DAN WAWANCARADESA PULAU BETUNG KECAMATAN PEMAYUNG
Authors: Budiarti Ani Muntama , Agnesa Elka Fadhia , Puspita Eva , Dewi Firli Amalia , Sianipar Naomi , Amanda Serlina , Erdita Vivi Maisa
Published: April 2024

Community development is a process undertaken by individuals, groups, or institutions to improve the quality of life and welfare of the community as a whole. In this research, observation can be done in various contexts, such as: Daily Activities, Observations of the daily activities of villagers, such as agricultural activities, work in the fields, trading in the local market, and household activities.Social Interactions, Observing interactions between villagers, such as communication in public places, community meetings, traditional ceremonies, and other social events. Economic Life - Observations of the economic patterns of the village community, including the dominant types of work, trading methods, and survival strategies. Culture and Tradition, Looking at local cultural practices, such as religious rituals, traditional ceremonies, arts, and traditional crafts that exist in the village.Social Structure, Understanding the social structure in rural communities, including value systems, social hierarchies, gender roles, and kinship systems. Through observations of villagers, researchers can gain deep insights into life and social dynamics in the village, which can be the basis for designing development programs, public policies, or further research on rural communities. The purpose of an interview is to gain deeper information, understanding, or perspective on a particular topic, subject, or phenomenon. Interviews can be conducted in a variety of contexts, be it in scientific research, journalism, job selection, surveys, or in counseling.
PENELUSURAN MAKNA, PERKEMBANGAN, DAN SUMBER PENAFSIRAN AL-QURAN DITINJAU DARI SUDUT PANDANG TEORITIS
Authors: Huda Ali Anhar Syi'bul , Abdussalam Aam , Husniah Lu’lu , Salsabila Shavira , Nurhuda Abid
Published: April 2024

The Qu’ran as a guide to human life contains global norms and rules so a study is needed to detail what is contained in it. Along with the development of the era, the study of the Koran has reached various scientific fields, including the field of study of Al-Quran interpretation itself. This research aims to explain the search for the meaning of interpretation, development, and sources of interpretation of the Al-Quran from a theoretical point of view. The method used is descriptive qualitative with a literature study approach technique. The research results show that tafsir is an effort to understand the holy verses of the Koran through several methodologies and has been started since the time of the Prophet, where he was the initial interpreter in explaining the contents contained in the word of Allah to his people. Then after he died, the interpretation of Al-Quran verses continued to develop and the relay of studying these verses continued to the companions, continued back to the tabi'in, and continued exponentially until the modern and digital era. The sources for interpreting the Koran include verses from the Koran, hadiths of the Prophet, or the atsars of friends, then it can also be done with the ability of human reason, and finally with selective Islamic stories
CONFLICT CONCERNS EXPLORED IN THE FILM "THE BATMAN" 2022 DIRECTED BY MATT REEVES
Authors: Poppy Dwi Nurasil
Published: April 2024

This dissertation explores the theme of conflict depicted in the 2022 film "The Batman". The movie centers around a character known as The Riddler, who has murdered several officials in Gotham City and exposes their hidden, darker sides, leading to conflicts with various factions. Conflict, defined as disagreement stemming from differing viewpoints, is the focal point of this analysis. The objective of this study is to delineate the types of conflicts portrayed by the antagonists and to elucidate the resultant impacts. To achieve this, a sociological approach was adopted, supplemented by two theoretical frameworks: Nina Genneby and Ruben Markosyan's theory, and Kun Maryati and Juju Suryawati's theory. Additionally, a descriptive qualitative research methodology was employed to dissect the film. The findings reveal two primary types of conflict: interpersonal and inter-group conflict. Furthermore, seven positive consequences are identified, including enhanced internal solidarity, the fostering of intriguing inter-group dynamics, mobilization of previously passive citizens, the emergence of resilient individuals, stimulation of innovation, facilitation of evaluation, and the formulation of new compromises. Conversely, four negative repercussions are observed, such as the rupture of personal relationships and group cohesion, property damage and loss of life, alterations in individual behavior, and the potential for domination by the victorious faction.
ANALISIS PENGARUH CORPORATE GOVERNANCE, PROFITABILITAS, DAN CAPITAL INTENSITY TERHADAP PENGHINDARAN PAJAK (TAX AVOIDANCE)(Studi Empiris Pada Perusahaan Sektor Pertambangan Yang Terdaftar Di Bursa Efek Indonesia Periode 2012-2016)
Authors: Siyamsih Dwi
Published: April 2024

The aim of this research is to determine the influence of corporate governance, profitability and capital intensity both partially and simultaneously on tax avoidance. This type of research is quantitative research, and the research object is mining sector companies listed on the Indonesia Stock Exchange for the 2012-2016 period. The sample in this research consisted of 11 companies by testing the hypothesis through the classical assumption test, t test, and f test. The results of this research state that corporate governance, which is proxied by the audit committee and audit quality and capital intensity, partially has no effect on tax avoidance, while partial profitability has a significant effect on tax avoidance. Corporate governance as proxied by the audit committee and audit quality, profitability and capital intensity simultaneously have a significant effect on tax avoidance.
Pengaruh Kepemimpinan Transformasional Terhadap Kinerja Karyawan Melalui Keterikatan Karyawan Sebagai Variabel Mediasi Pada Pt. Duren Mandiri Fortuna Jambi
Authors: Hayati Cucu
Published: April 2024

This study aims to determine the effect of transformational leadership on employee performance with employee engagement as a mediating variable. Research conducted using quantitative methods by distributing questionnaires to respondents. The population and sample for this study were employees of PT Duren Mandiri Fortuna with a total sampling of 72 people. The data analysis method used is descriptive statistical analysis with SEM-PLS techniques in the SmartPLS program (v.3.2.9). The results of this study reveal that there is a positive and significant relationship from transformational leadership to employee performance, transformational leadership has a positive and significant effect on employee engagement, employee engagement has a positive and significant effect on employee performance and employee engagement is able to mediate between transformational leadership and employee performance at PT Duren Mandiri Fortuna Jambi. Therefore, it is recommended that the leader of PT Duren Mandiri Fortuna Jambi be able to create comfort during discussions with employees and provide inspiration so that employees are more creative, keep monitoring employee work progress so that time management is well created, and show enthusiastic support for employees so that employees feel their role has contributed to the progress of PT Duren Mandiri Fortuna Jambi.
ANALISIS KESALAHAN BERBAHASA PERCAKAPAN GRUP WHATSAPP MAHASISWA KELAS B LINGUISTIK TERAPAN UNJ ANGKATAN 2023
Authors: Hamid B La Ode Muhammad Idrus , Anwar Miftahulkhairah
Published: April 2024

This study aims to analyze language errors that occur in student WhatsApp group conversations in order to improve understanding and use of language more effectively in the academic environment. This study uses descriptive qualitative method and data collection technique, which is sourced from language errors in WhatsApp grub of Applied Linguistics Doctoral Program UNJ Batch 2023 class B students. The results of this study show that there are a number of language errors that appear in the WhatsApp group conversations of Applied Linguistics Doctoral Program UNJ class 2023 students. The errors include aspects of spelling, capitalization, and improper writing. In various contexts and domains, these language errors occur because the Applied Linguistics Doctoral Program students of Batch 2023 class B use informal language when communicating in the WhatsApp group, which is a non-formal situation among their peers. These language errors can be attributed to the relaxed situation in which the doctoral students express their opinions by using more relaxed and informal language in their daily interactions in the group.
JOURNEY THROUGH THE PAGES: EXPLORING THE RICH TAPESTRY OF ENGLISH LITERATURE
Authors: Rahmat Purnomo
Published: April 2024

This article explores the wealth of English literature, offering diverse narratives spanning centuries. From epic poetry to modern novels, we understand the evolution of English literature and its impact on global culture. The article delves into themes, styles, and voices enriching the landscape of English literature, as well as its role in reflecting and shaping society. The research method employed is qualitative, utilizing literature review and historical research. With this approach, the researcher analyzes literary texts alongside their historical and cultural contexts. The discussion underscores the importance of English literature in capturing human experiences and prompting readers for personal reflection and deeper understanding of the world. The conclusion asserts that journeying through the pages of English literature is a rich and profound experience, enriching our understanding of humanity and the world around us.
THE EFFECT OF ORGANIZATIONAL JUSTICE ON EMPLOYEE PERFORMANCE JOB SATISFACTION AS AN INTERVENING VARIABLE AT PT DURENMANDIRI FORTUNA JAMBI
Authors: Faizah Naela Mikyalul
Published: April 2024

The study aims to determine the effect of organizational justice on employee performance on job satisfaction as an intervening variable. The target of this research is the employees of PT Duren Mandiri Fortuna Jambi. The population and sample for this study were employees of PT. Duren Mandiri Fortuna Jambi, totaling 300 employees with a sample size of 75 employees. This research is quantitative research, the data used in this study were obtained through a questionnaire method. The data analysis method of this research is descriptive statistical analysis using Structural Equation (SEM) techniques, with Partia lLeastSquare (PLS) as a processing tool using the SmartPLS program (v.3.2.9). The results of this study prove that organizational justice has a positive and significant effect on employee performance, organizational justice has a positive and significant effect on job satisfaction, job satisfaction has a positive and significant effect on employee performance, organizational justice has a positive and significant effect on employee performance, job satisfaction as an intervening variable at PT. Duren MandiriFortuna Jambi. So it can be concluded from the research results that HR policies to improve cooperation among coworkers, communication between leaders and subordinates must be well established to provide understanding to employees and job satisfaction in providing promotion opportunities are recommended to be given fairly and in accordance with the requirements for all employees.
Instructional Strategies for TEFL Online Learning
Authors: Novpitri Aas , Juliardi
Published: April 2024

The impact of the COVID-19 outbreak has led to the closure of educational institutions around the world, prompting the exploration of instructional strategies for online teaching in higher education. This case study develops effective online teaching methods without compromising the quality of student learning. Ideas for online education in developing countries, including maintaining the voice of the instructor, practicing vocal functions, and sharing resources before class, are considered. These strategies support improved student learning, with suggestions for collaboration between the Higher Education Commission and the telecommunications industry to address internet issues. Factors such as student feedback, flexible teaching and grading policies, and support from teaching assistants, play an important role in improving distance learning. TEFL certification is becoming an important component in job applications for teaching English abroad, offering the ability to teach English as a foreign language in various countries.
ANALISIS VARIASI BENTUK MATA PISAU TERHADAP KAPASITAS DAN EFISIENSI PERAJANGAN UBI PADA MESIN GRUBI
Authors: Yuni Nur Diana  , Pramono Catur , Hastuti Sri
Published: April 2024

Grubi adalah salah satu makanan oleh-oleh dari Jawa Tengah yang terbuat dari ubi jalar yang dirajang menyerupai bentuk lidi. Proses perajangan ubi jalar masih dilakukan secara manual menggunakan peralatan konvensional melalui dua tahap pengerjaan dengan kapasitas perajangan 5 kg/jam. Peralatan konvensional dinilai kurang efektif dan efisien untuk melakukan proses perajangan ubi jalar sehingga belum mampu memenuhi kebutuhan Usaha Mikro Kecil dan Menengah (UMKM) grubi. Oleh karena itu diperlukan teknologi mesin otomatis yang mampu melakukan perajangan ubi jalar dalam satu kali tahap pengerjaan dengan kapasitas produksi dan efisiensi perajangan yang tinggi. Salah satu faktor yang mempengaruhi hasil perajangan adalah bentuk mata pisau perajang, sehingga perlu dilakukan penelitian tentang analisis variasi bentuk mata pisau terhadap kapasitas produksi dan efisiensi perajangan. Tujuan dari penelitian ini yaitu untuk menganalisis pengaruh masing-masing bentuk mata pisau terhadap kapasitas produksi grubi dan efisiensi perajangan yang dihasilkan. Penelitian ini menggunakan metode eksperimen menggunakan tiga variasi bentuk mata pisau, yaitu bentuk cakram, tabung, dan horizontal dengan prinsip pengulangan sebanyak 5 kali pengulangan sehingga diperoleh 15 hasil percobaan. Teknik analisis data yang digunakan yaitu analisis statistik deskriptif dengan parameter dan perhitungan berdasarkan BSN SNI 0838:2008. Hasil penelitian menunjukkan bahwa variasi bentuk mata pisau horizontal menunjukkan hasil paling optimal dengan kapasitas perajangan mencapai 52,03 kg/jam dengan efisiensi perajangan sebesar 89,71%. Kapasitas perajangan yang dihasilkan pada bentuk mata pisau tabung mencapai 37,51 kg/jam dengan nilai efisiensi perajangan sebesar 78,15%. Kapasitas perajangan paling rendah terdapat pada pengujian dengan bentuk mata pisau cakram yaitu sebesar 35,69 kg/jam dengan nilai efisiensi perajangan sebesar 68,63%.
Kata kunci: efisiensi, grubi, kapasitas, mata pisau, perajangan
Problems Faced by Students in Teaching Learning Process At Secondary School Level In District Nowshehra
Authors: Ali Niaz , Gul Sana
Published: April 2024

The researcher's area of interest was "Problems faced by students in the teaching-learning process at secondary schools level in district Nowshera". The study set out to investigate the issues that male students in district Nowshehra's government high schools faced, as well as the issues that male students in the district's private high schools faced. 200 (100+100) students were chosen at random from the accessible population to gather data from the entire population. District Nowshera provided the data for the study, which was conducted via a questionnaire. Researchers draw the conclusion that students in the public and private sectors encountered distinct types of issues based on their findings. Compared to private schools, the majority of secondary school students in the public system experienced financial difficulties. In contrast to private sector institutions, the majority of students felt that public sector institutions lack enough guidance. Numerous pupils concurred that the examination system does not take into account the students' mental abilities. Compared to pupils in the private sector, transportation is an insurmountable issue for those in the public sector. Students' academics are impacted by load shedding, particularly in public schools. In the public sector, as opposed to the private sector, teacher insincerity also makes it more difficult for them to accomplish their objectives.
Perceptions of Female Students Regarding Male Student Attitudes at Higher Educational Institutions
Authors: Gul Nabi , Samina Samina
Published: April 2024

The study examines female students' perceptions of male student attitudes at the University of Swabi, focusing on gender bias, academic sexism, stereotype threat, and classroom climate, aiming to promote gender equality. The problem statement highlights the need for a comprehensive investigation into female students' perceptions of male student attitudes at the University of Swabi. The objectives of the study are to examine female students' perceptions, identify gender-based biases, and explore the impact of male student attitudes. The research questions are framed to investigate these aspects in detail. The significance of this study lies in its potential to contribute to gender equality in education, enhance student well-being, improve academic performance, nurture healthier social dynamics, promote respect and diversity, inform policy formulation, and ultimately create a more inclusive and supportive educational environment. The findings from the study reveal important patterns in female students' perceptions and experiences at the University of Swabi. In conclusion, this research provides valuable insights into the perceptions and experiences of female students regarding gender-related issues at the University of Swabi. It offers recommendations to further improve the gender-related climate on campus, ultimately contributing to a more equitable and inclusive educational environment.
Effectiveness of Flipped Classrooms in Promoting Student Learning at the Tertiary Level
Authors: Ullah Kifayat , Jinah Sana
Published: April 2024

The study sought to explore the Effectiveness of Flipped Classrooms in Promoting Student Learning at the Tertiary Level. The objectives of the study were to explore the perceptions of students regarding the flipped classroom approach and to find out the effectiveness of flipped classrooms in enhancing students’ learning. All the female students studying in the affiliated colleges of the University of Swabi comprise the population of the study. The number of female students was 273. Out of the total population, 100 female students were randomly selected from the sample institutions. A close-ended questionnaire containing 12 items on the Likert scale was used as a tool for gathering information. Based on the findings, it was concluded that the majority of the participants agreed that the flipped classroom approach can easily be implemented in classrooms. Most of the participants agreed that the video the lecturer provided to us as a home assignment was easily understandable. All of the participants were student agreed that the topic became easy after watching its videos or lecture notes. All participants agreed that the technological facilities available at school and home are necessary for implementing Flipped Classroom. All the participants agreed that the institution may arrange training workshops for teachers and students to enhance the implementation process of flipped classrooms.
Relation of Organization and Critical Thinking Learning Strategy with Students’ Academic Performance at the University of Loralai, Balochistan, Pakistan
Authors: Kamran Muhammad , Habib Shazmina
Published: April 2024

The current study intends to investigate the relationship between students' academic performance in the Department of Education at the University of Loralai, Balochistan, and the organization and critical thinking learning strategy. This quantitative study used a sample of 300 randomly selected students from the University of Lorelai's Department of Education in Balochistan. Using a legitimate and standardized MSLQ questionnaire as a data collection method, the study employed a correlation research design. Two sections of the questionnaire were distributed: one for the study and the other for the demographics. The study portion examined the relationship between students' academic performance and the organization and critical thinking learning strategies. The demographic section contained information about the students at the aforementioned university. Gender, marital status, location, age in years, number of students in class, study program, academic year, university name, department name, and GPA were among the demographic data that were measured. The current researchers employed correlational analysis to look at the relationship between students' academic performance and organization and critical thinking learning style. The current study's findings demonstrated that both organization and critical thinking learning methodologies have the least favorable impact on University of Loralai students' academic performance. This study concludes that students' academic performance at Loralai University was somewhat improved by both organization and critical thinking learning methodologies. The discussion included implications and suggestions for additional research.
National first-class course: International Settlement
Authors:   Guangdong University of Foreign Studies, Guangzhou, Guangdong Province, LIN Chen
Published: April 2024

Guangdong University of Foreign Studies is a teaching and research university with distinctive international characteristics. The major of International Economics and trade is the characteristic specialty of the Ministry of Education and a national first-class major. The course of International Settlement is a required course for international economy and trade, international business, international finance and other majors. It has the characteristics of complex theoretical knowledge, wide range of involvement and strong practical operation. Through a variety of ways and methods to acquire knowledge in the information age, we deeply integrate the Internet and information technology into university education in teaching. At the same time, we also introduce online simulation experiments, Moocs and rain classroom and other information-based teaching methods, expand and extend the learning space and content, form various high-quality teaching resources, build a golden course teaching team, lead the reform of International Settlement courses, and promote high-quality teaching resources for higher education institutions. Through the co-construction and sharing of modern information technology means, we can improve the training quality of international trade professionals and serve the construction of a learning society in the new era. This paper discusses seven aspects: basic course information, teaching professors (teaching team), course objectives, course construction and application, course features and innovations, course construction plan, and a list of supplementary materials. It elaborately presents the core content of the application in strict accordance with the requirements of the second batch of national first-class undergraduate course application (Mixed online and offline courses), offering a reference for the application of the third batch of national first-class undergraduate courses.
Quick-quick-slow: the foxtrot migration and dynamic non-breeding range
Authors: Pokrovsky Ivan , Curk Teja , Dietz Andreas , Fufachev Ivan , Kulikova Olga , Rößler Sebastian , Wikelski Martin
Published: April 2024

Advancements in tracking technologies have revolutionized our understanding of bird migrations, revealing a diverse array of migratory behaviors. We propose a new pattern of migratory behavior termed ‘foxtrot migration,’ characterized by alternating quick and slow phases during the non-breeding period. This behavior involves directional and continuous movements, distinct from traditional seasonal itinerancy or forage-on-fly migration. Using the Rough-legged buzzard as a model species, we confirmed the presence of foxtrot migration and ‘dynamic non-breeding ranges’, driven by environmental factors such as snow cover dynamics. We advocate for accurate representation of dynamic ranges on maps and emphasize the need to consider range dynamics when assessing species conservation status. Our findings underscore the importance of understanding complex migratory behaviors in the face of environmental change, facilitated by advancements in tracking technologies. This knowledge is crucial for effective conservation strategies amid ongoing global environmental challenges.
Asymmetric distribution of color-opponent response types across mouse visual cortex supports superior color vision in the sky
Authors: Franke Katrin , Cai Chenchen , Ponder Kayla , Fu Jiakun , Sokoloski Sacha , Berens Philipp , Tolias Andreas S.
Published: April 2024

Color is an important visual feature that informs behavior, and the retinal basis for color vision has been studied across various vertebrate species. While we know how color information is processed in visual brain areas of primates, we have limited understanding of how it is organized beyond the retina in other species, including most dichromatic mammals. In this study, we systematically characterized how color is represented in the primary visual cortex (V1) of mice. Using large-scale neuronal recordings and a luminance and color noise stimulus, we found that more than a third of neurons in mouse V1 are color-opponent in their receptive field center, while the receptive field surround predominantly captures luminance contrast. Furthermore, we found that color-opponency is especially pronounced in posterior V1 that encodes the sky, matching the statistics of natural scenes experienced by mice. Using unsupervised clustering, we demonstrate that the asymmetry in color representations across cortex can be explained by an uneven distribution of green-On/UV-Off color-opponent response types that are represented in the upper visual field. This type of color-opponency in the receptive field center of V1 neurons was not present in the receptive field center of retinal ganglion cells and, therefore, is likely computed by integrating center and surround information down-stream of the retina. Finally, a simple model with natural scene-inspired parametric stimuli shows that green-On/UV-Off color-opponent response types may enhance the detection of “predatory”-like dark UV-objects in noisy day-light scenes. The results from this study highlight the relevance of color processing in the mouse visual system and contribute to our understanding of how color information is organized in the visual hierarchy across species. More broadly, they support the hypothesis that the visual cortex combines upstream information towards computing neuronal selectivity to behaviorally-relevant sensory features.
PKR activation-induced mitochondrial dysfunction in HIV-transgenic mice with nephropathy
Authors: Yoshida Teruhiko , Latt Khun Zaw , Rosenberg Avi Z. , Santo Briana A. , Myakala Komuraiah , Ishimoto Yu , Zhao Yongmei , Shrivastav Shashi , Jones Bryce A. , Yang Xiaoping , Wang Xiaoxin X. , Tutino Vincent M. , Sarder Pinaki , Levi Moshe , Okamoto Koji , Winkler Cheryl A. , Kopp Jeffrey B.
Published: April 2024

HIV disease remains prevalent in the USA and chronic kidney disease remains a major cause of morbidity in HIV-1-positive patients. Host double-stranded RNA (dsRNA)-activated protein kinase (PKR) is a sensor for viral dsRNA, including HIV-1. We show that PKR inhibition by compound C16 ameliorates the HIV-associated nephropathy (HIVAN) kidney phenotype in the Tg26 transgenic mouse model, with reversal of mitochondrial dysfunction. Combined analysis of single-nucleus RNA-seq and bulk RNA-seq data revealed that oxidative phosphorylation was one of the most downregulated pathways and identified signal transducer and activator of transcription (STAT3) as a potential mediating factor. We identified in Tg26 mice a novel proximal tubular cell cluster enriched in mitochondrial transcripts. Podocytes showed high levels of HIV-1 gene expression and dysregulation of cytoskeleton-related genes; and these cells dedifferentiated. In injured proximal tubules, cell-cell interaction analysis indicated activation of the profibrogenic PKR-STAT3-platelet derived growth factor (PDGF)-D pathway. These findings suggest that PKR inhibition and mitochondrial rescue are potential novel therapeutic approaches for HIVAN.
Omissions of Threat Trigger Subjective Relief and Prediction Error-Like Signaling in the Human Reward and Salience Systems
Authors: Willems Anne L. , Oudenhove Lukas Van , Vervliet Bram
Published: April 2024

The unexpected absence of danger constitutes a pleasurable event that is critical for the learning of safety. Accumulating evidence points to similarities between the processing of absent threat and the well-established reward prediction error (PE). However, clear-cut evidence for this analogy in humans is scarce. In line with recent animal data, we showed that the unexpected omission of (painful) electrical stimulation triggers activations within key regions of the reward and salience pathways and that these activations correlate with the pleasantness of the reported relief. Furthermore, by parametrically violating participants’ probability and intensity related expectations of the upcoming stimulation, we showed for the first time in humans that omission-related activations in the VTA/SN were stronger following omissions of more probable and intense stimulations, like a positive reward PE signal. Together, our findings provide additional support for an overlap in the neural processing of absent danger and rewards in humans.
The delayed kinetics of Myddosome formation explains why Aβ aggregates trigger TLR4 less efficiently than LPS
Authors: Li Bing , Suresh Prasanna , Brelstaff Jack , Kedia Shekhar , Bryant Clare , Klenerman David
Published: April 2024

The Myddosome is a key innate immune signalling platform. It forms at the cell surface and contains MyD88 and IRAK proteins which ultimately coordinate the production of pro-inflammatory cytokines. Toll-like receptor 4 signals via the Myddosome when triggered by Lipopolysaccharide (LPS) or Amyloid-Beta (Aβ) aggregates but the magnitude and time duration of the response are very different for reasons that are unclear. Here we followed the formation of Myddosomes in live macrophages using local delivery of TLR4 agonist to the cell surface and visualisation with 3D rapid light sheet imaging. This was complemented by super-resolution imaging of Myddosomes in fixed macrophages to determine the size of the signalling complex at different times after triggering. Myddosomes formed more rapidly after LPS than in response to sonicated Aβ 1-42 fibrils (80 seconds vs 372 seconds). The mean lifetimes of the Myddosomes was also shorter when triggered by LPS compared to sonicated Aβ fibrils (170 and 220 s) respectively. In both cases a range of Myddosome of different sizes (50-500 nm) were formed. In particular, small round Myddosomes around 100 nm in size formed at early time points, then reduced in proportion over time. Collectively our data suggests that compared to LPS the multivalency of Aβ fibrils leads to the formation of larger Myddosomes which form more slowly and, due to their size, take longer to disassemble. This explains why sonicated Aβ fibrils results in less efficient triggering of TLR4 signalling and may be a general property of protein aggregates.
A mitochondrial carrier transports glycolytic intermediates to link cytosolic and mitochondrial glycolysis in the human gut parasite Blastocystis
Authors: Pyrihová Eva , King Martin S. , King Alannah C. , Toleco M. Rey , van der Giezen Mark , Kunji Edmund R.S.
Published: April 2024

Stramenopiles form a clade of diverse eukaryotic organisms, including multicellular algae, the fish and plant pathogenic oomycetes, such as the potato blight
Phytophthora,
and the human intestinal protozoan
Blastocystis
. In most eukaryotes, glycolysis is a strictly cytosolic metabolic pathway that converts glucose to pyruvate, resulting in the production of NADH and ATP. In contrast, stramenopiles have a branched glycolysis in which the enzymes of the pay-off phase are located in both the cytosol and the mitochondrial matrix. Here, we identify a mitochondrial carrier in
Blastocystis
that can transport glycolytic intermediates, such as dihydroxyacetone phosphate and glyceraldehyde-3-phosphate, across the mitochondrial inner membrane, linking the cytosolic and mitochondrial branches of glycolysis. Comparative analyses with the phylogenetically-related human mitochondrial oxoglutarate carrier (SLC25A11) and dicarboxylate carrier (SLC25A10) show that the glycolytic intermediate carrier has lost its ability to transport the canonical substrates malate and oxoglutarate.
Blastocystis
lacks several key components of oxidative phosphorylation required for the generation of mitochondrial ATP, such as complexes III and IV, ATP synthase and ADP/ATP carriers. The presence of the glycolytic pay-off phase in the mitochondrial matrix generates ATP, which powers energy-requiring processes, such as macromolecular synthesis, as well as NADH, used by mitochondrial complex I to generate a proton motive force to drive the import of proteins and molecules. Given its unique substrate specificity and central role in carbon and energy metabolism, the carrier for glycolytic intermediates identified here represents a specific drug and pesticide target against stramenopile pathogens, which are of great economic importance.
Decoding contextual influences on auditory perception from primary auditory cortex
Authors: Englitz B. , Akram S. , Elhilali M. , Shamma S.
Published: April 2024

Perception can be highly dependent on stimulus context, but whether and how sensory areas encode the context remains uncertain. We used an ambiguous auditory stimulus - a tritone pair - to investigate the neural activity associated with a preceding contextual stimulus that strongly influenced the tritone pair’s perception: either as an ascending or a descending step in pitch.We recorded single-unit responses from a population of auditory cortical cells in awake ferrets listening to the tritone pairs preceded by the contextual stimulus. We find that the responses adapt locally to the contextual stimulus, consistent with human MEG recordings from the auditory cortex under the same conditions. Decoding the population responses demonstrates that pitch-change selective cells are able to predict well the context-sensitive percept of the tritone pairs. Conversely, decoding the
distances
between the pitch representations predicts the
opposite
of the percept. The various percepts can be readily captured and explained by a neural model of cortical activity based on populations of adapting, pitch and pitch-direction selective cells, aligned with the neurophysiological responses.Together, these decoding and model results suggest that contextual influences on perception may well be already encoded at the level of the primary sensory cortices, reflecting basic neural response properties commonly found in these areas.
Structural insights into the GTP-driven monomerization and activation of a bacterial LRRK2 homolog using allosteric nanobodies
Authors: Galicia Christian , Guaitoli Giambattista , Fislage Marcus , Gloeckner Christian Johannes , Versées Wim
Published: April 2024

Roco proteins entered the limelight after mutations in human LRRK2 were identified as a major cause of familial Parkinson’s disease. LRRK2 is a large and complex protein combining a GTPase and protein kinase activity, and disease mutations increase the kinase activity, while presumably decreasing the GTPase activity. Although a cross-communication between both catalytic activities has been suggested, the underlying mechanisms and the regulatory role of the GTPase domain remain unknown. Several structures of LRRK2 have been reported, but structures of Roco proteins in their activated GTP-bound state are lacking. Here, we use single-particle cryo-electron microscopy to solve the structure of a bacterial Roco protein (CtRoco) in its GTP-bound state, aided by two conformation-specific nanobodies: NbRoco1 and NbRoco2. This structure presents CtRoco in an active monomeric state, featuring a very large GTP-induced conformational change using the LRR-Roc linker as a hinge. Furthermore, this structure shows how NbRoco1 and NbRoco2 collaborate to activate CtRoco in an allosteric way. Altogether, our data provide important new insights into the activation mechanism of Roco proteins, with relevance to LRRK2 regulation, and suggest new routes for the allosteric modulation of their GTPase activity.
Short-term social isolation acts on hypothalamic neurons to promote social behavior in a sex- and context-dependent manner
Authors: Zhao Xin , Chae Yurim , Smith Destiny , Chen Valerie , DeFelipe Dylan , Sokol Joshua W , Sadangi Archana , Tschida Katherine
Published: April 2024

Social animals, including both humans and mice, are highly motivated to engage in social interactions. Short-term social isolation promotes social behavior, but the neural circuits through which it does so remain incompletely understood. Here, we sought to identify neurons that promote social behavior in single-housed female mice, which exhibit increased rates of social investigation, social ultrasonic vocalizations (USVs), and mounting during same-sex interactions that follow a period of short-term (3-day) isolation. We first used immunostaining for the immediate early gene Fos to identify a population of neurons in the preoptic hypothalamus (POA) that increase their activity in single-housed females following same-sex interactions (POA
social
neurons) but not in single-housed females that did not engage in social interactions. TRAP2-mediated chemogenetic silencing of POA
social
neurons in single-housed females significantly attenuates the effects of short-term isolation on social investigation, USV production, and mounting. In contrast, caspase-mediated ablation of POA
social
neurons in single-housed females robustly attenuates mounting but does not decrease social investigation or USV production. Optogenetic activation of POA
social
neurons in group-housed females promotes social investigation and USV production but does not recapitulate the effects of short-term isolation on mounting. To understand whether a similar population of POA
social
neurons promotes social behavior in single-housed males, we performed Fos immunostaining in single-housed males following either same-sex or opposite-sex social interactions. These experiments revealed a population of POA neurons that increase Fos expression in single-housed males following opposite-sex, but not same-sex, interactions. Chemogenetic silencing of POA
social
neurons in single-housed males during interactions with females reduces mounting but does not affect social investigation or USV production. These experiments identify a population of hypothalamic neurons that promote social behavior following short-term isolation in a sex- and social context-dependent manner.
Short-term social isolation acts on hypothalamic neurons to promote social behavior in a sex- and context-dependent manner
Authors: Zhao Xin , Chae Yurim , Smith Destiny , Chen Valerie , DeFelipe Dylan , Sokol Joshua W , Sadangi Archana , Tschida Katherine
Published: April 2024

Social animals, including both humans and mice, are highly motivated to engage in social interactions. Short-term social isolation increases social motivation and promotes social behavior, but the neural circuits through which it does so remain incompletely understood. Here, we sought to identify neurons that promote social behavior in single-housed female mice, which exhibit increased rates of social investigation, social ultrasonic vocalizations (USVs), and mounting during same-sex interactions that follow a period of short-term (3-day) isolation. We first used immunostaining for the immediate early gene Fos to identify a population of neurons in the preoptic hypothalamus (POA) that increase their activity in single-housed females following same-sex interactions (POA
iso
neurons). TRAP2-mediated chemogenetic silencing of POA
iso
neurons in single-housed females significantly attenuates the effects of short-term isolation on social investigation and USV production and also tends to reduce mounting. In contrast, caspase-mediated ablation of POA
iso
neurons in single-housed females robustly attenuates mounting but has no effect on social investigation or USV production. Optogenetic activation of POA
iso
neurons in group-housed females promotes USV production but does not recapitulate the effects of short-term isolation on social investigation and mounting. To understand whether a similar population of POA
iso
neurons promotes social behavior in single-housed males, we performed Fos immunostaining in single-housed males following either same-sex or opposite-sex social interactions. These experiments revealed a population of POA neurons that increase Fos expression in single-housed males following opposite-sex, but not same-sex, interactions.Chemogenetic silencing of POA
iso
neurons in single-housed males during interactions with females tends to reduce mounting but does not decrease social investigation or USV production. These experiments identify a population of hypothalamic neurons that promote social behavior following short-term isolation in a sex- and social context-dependent manner.
Modelling collective behavior in groups of mice housed under semi-naturalistic conditions
Authors: Chen Xiaowen , Winiarski Maciej , Puścian Alicja , Knapska Ewelina , Mora Thierry , Walczak Aleksandra M.
Published: April 2024

Social interactions are a crucial aspect of behavior in mice. Nonetheless, it is often difficult to distinguish the effects of interactions, from independent animal behavior. Distinguishing interactions from individual preferences is important to describe how information is transmitted in a horde and to predict behavioral patterns of a whole group. We combine high-throughput data collected in mice housed and location-tracked over multiple days in an ecologically-relevant environment (Eco-HAB system) with statistical inference models to learn the rules controlling the collective dynamics of groups of 10 to 15 individuals. We reproduce the distribution for the co-localization patterns, show they are stable over time, and find that the distribution of the inferred interaction strength captures the social structure among the animals. By separating interactions from individual preferences, we show that affecting neuronal plasticity in the prelimbic cortex - a brain structure crucial for processing social information and interacting with others - does not eliminate social interactions, yet make it harder to transmit information between mice.
High-throughput expansion microscopy enables scalable super-resolution imaging
Authors: Day John H , Della Santina Catherine M , Maretich Pema , Auld Alexander L , Schnieder Kirsten K , Shin Tay , Boyden Edward S , Boyer Laurie A
Published: April 2024

Expansion microscopy (ExM) enables nanoscale imaging using a standard confocal microscope through the physical, isotropic expansion of fixed immunolabeled specimens. ExM is widely employed to image proteins, nucleic acids, and lipid membranes in single cells; however, current methods limit the number of samples that can be processed simultaneously. We developed High-throughput Expansion Microscopy (HiExM), a robust platform that enables expansion microscopy of cells cultured in a standard 96-well plate. Our method enables ~4.2 x expansion of cells within individual wells, across multiple wells, and between plates. We also demonstrate that HiExM can be combined with high-throughput confocal imaging platforms to greatly improve the ease and scalability of image acquisition. As an example, we analyzed the effects of doxorubicin, a known cardiotoxic agent, on human cardiomyocytes (CMs) as measured by the Hoechst signal across the nucleus. We show a dose-dependent effect on nuclear DNA that is not observed in unexpanded CMs, suggesting that HiExM improves the detection of cellular phenotypes in response to drug treatment. Our method broadens the application of ExM as a tool for scalable super-resolution imaging in biological research applications.
A shade-responsive microProtein in the Arabidopsis ATHB2 gene regulates elongation growth and root development
Authors: Edwards Ashleigh , Chiurazzi Maurizio Junior , Blaakmeer Anko , Vittozzi Ylenia , Sharma Ashish , Matton Sanne , Kruusvee Valdeko , Straub Daniel , Sessa Giovanna , Carabelli Monica , Morelli Giorgio , Wenkel Stephan
Published: April 2024

The ability of plants to thrive under suboptimal light conditions, such as shade, is crucial for their overall survival and reproductive success. Here, we show that Arabidopsis seedlings produce a large number of alternative transcripts when exposed to shade. Notably, one of the identified transcript candidates, which was upregulated in shade conditions, was found to be an alternative transcript of the
ATHB2
gene. ATHB2 belongs to the HD-ZIPII class of transcription factors and is a well-established regulator of the shade avoidance response. The function of the alternative transcript and the small leucine zipper protein encoded by it, ATHB2miP, was investigated. We found that ATHB2miP is primarily expressed in the shoot meristem and interacts with full-length ATHB2 protein to inhibit its activity through a negative feedback mechanism. Deletion of the genomic region encoding the leucine zipper domain of the
ATHB2
gene using CRISPR, resulted in plants exhibiting altered shade avoidance responses and root development. We show that the leucine zipper domain is required for dimerising and localising to nuclear photobodies. There is a significant overlap in deregulated genes between plants ectopically expressing ATHB2miP and
athb2
mutant plants. The analysis of gene ontology and clustering revealed that the most affected processes are auxin synthesis and signaling, root development, and iron homeostasis. Shade growth experiments at different iron concentrations revealed a role for
ATHB2
in regulating iron uptake and showed that iron availability affects shade growth in an
ATHB2
-dependent manner. This study identifies ATHB2miP as a novel regulator of shade avoidance responses in Arabidopsis, highlighting the intricate transcriptional regulation underlying these processes.