bluuebunny/crossref_metadata_2025 huggingface dataset:
Pentecostal transformation in Africa: The rise and growth of the Church of Pentecost
Authors: Onyinah O. Onyinah
Published: April 2024

The emergence, growth and development of The Church of Pentecost (CoP), Ghana is a demonstration of a new era of African Christianity. The Church of Pentecost was listed as the largest Protestant Christian denomination in Ghana by the last empirical church survey of the Ghana Evangelism Committee. In 193 7, James and Sophia McKeown were sent by the Apostolic church in the UK to the then Gold Coast (now Ghana) as missionaries. Working in partnership with the indigenous converts and personnel, McKeown worked tirelessly in Ghana to bring the Gospel of Jesus Christ to the country through his emphases on the word of God, the transforming power of the Holy Spirit, and holy living. In 1953 McKeown was compelled to come out of the Apostolic Church of the UK and get along with the indigenous people under the name 'Ghana Apostolic Church' which was renamed 'The Church of Pentecost' in 1962.
Migration and African diaspora mission and the changing Christian landscape of the West
Authors: Asamoah-Gyadu J. K. Asamoah-Gyadu
Published: April 2024

This Essay reflects on the significance of African and African-led Pentecostal/charismatic churches in the modem West. The basic thesis is that through the establishment of African churches (that is churches made of Africans) and by African Christians forming churches in Europe ( that is churches formed by Africans but that have a predominantly white or mixed race membership), a case has been made for the reference to Christianity as a non-Western religion with Africa as one of its major hubs. Kwame Bediako argued that Christianity has now become a non-Western religion with its centers of dominance in Africa, Asia and Latin America (Bediako 1995).
Pentecostalism and the development of theology of the Holy Spirit
Authors: Kim K. Kim
Published: April 2024

A century ago Pentecostalism was a grassroots movement that focused on experience rather than learning and had few resources for theological research. Today, many prominent theologians come from Pentecostal or charismatic backgrounds, and what is more, reflection on the movement has had deep theological impact- not only on Pentecostal theologians but also ecumenically.
A theological reflection using Pentecostal narratives to explore the connection between Pentecostalism and indigenous religions of Malawi
Authors: Kwiyani H. C. Kwiyani
Published: April 2024

This essay uses a theological reflection of Pentecostal narratives from Malawi in southeast Africa where I was born and raised to explore the connection between Pentecostalism and indigenous religions. It has been sparked and undergirded by several key events that I have experienced in my faith life. I am a descendant of a Pentecostal preacher (my father), a Presbyterian minister (my grandfather) who had two brothers, one an indigenous religion priest and spiritual healer and the other a founding apostle of an African Independent Church. Yet, I have taken on an academic journey in theological education with Pentecostal leanings. Chief among the events that sparked my Pentecostal curiosity behind the argument of this essay is the conversion of my grandfather’s brother from an indigenous religion to Christianity and the myriad struggles he faced as he discerned what to do with his longstanding spiritual gifts as a medium for the community. He had refused to convert to Christianity for a long time in spite of—or maybe because of—his Presbyterian brother’s witness. He always said that Christianity (especially that of his Presbyterian brother) did not understand the spirit world with which he had dealt every day all his adult life. He refused to recognize it as a religion because for him, a religion must attend to the spirit-world. If it did not, like the Christianity of my grandfather, it was only fit to be a moral philosophy.
PERBEDAAN TINGKAT PEMAHAMAN AKUNTANSI MAHASISWA BERDASARKAN LULUSAN PADA MAHASISWA SEMESTER II TAHUN ANGKATAN 2017 PRODI AKUNTANSI UNIVERSITAS MUARA BUNGO
Authors: Lulfaizahni Naela Mikya
Published: April 2024

This research hopes to prove whether there are differences in understanding of accounting material from different school backgrounds. Research object at the Faculty of Economics, Muara Bungo University. In this study, the population used as the population in this study were students majoring in Accounting, totaling 62 second semester students at Muara Bungo University (UMB). This research uses quantitative descriptive data analysis outlined in the form of a frequency table. The scoring technique that will be used is a Likert scale to assess respondents' questionnaire answers. The definition of accounting according to the American Accounting Association is a process of identifying, measuring and reporting economic information to enable clear and firm research and decisions for those who use the information. The results of this research show that there is a significant difference in the level of understanding of assets between students from vocational school majoring in accounting, high school majoring in social studies and Madrasah Aliyah General. Assets, There is a significant difference in the level of understanding of obligations between students from the Accounting Department Vocational School, the Social Sciences Department High School and the General Madrasah Aliyah. Obligations, and There is a significant difference in the level of understanding of capital between students from the Accounting Department Vocational School, the Social Sciences Department High School and the General Madrasah Aliyah Equity.
Quantitative Analysis of the Relationship between Income and Welfare of Tuna Fishermen from the Perspective of Sharia Finance
Authors: Ode Santi , Hamizar Arizal
Published: April 2024

This study aims to investigate the correlation between income levels and the welfare of fishermen operating in Waitomu Hamlet, Leihitu Subdistrict, Central Maluku Regency; and the relationship between the application of Sharia financial management principles with the income and welfare of tuna fishermen in that area. The research method applied is associative research, with research participants being actively operating fishermen in Waitomu Hamlet. The research approach involves the use of various techniques, including observation, distribution of questionnaires, and document analysis, with data analysis conducted using moment product correlation calculations. The results of the study revealed two main findings. First, the moment product correlation analysis showed a significant positive correlation between fishermen's income and the level of welfare, indicating that increasing income tends to have a positive impact on their welfare. Second, from a financial perspective, the practice of Sharia financial management applied by tuna fishermen in Waitomu Hamlet is considered successful.
METODE PENDAMPINGAN DARING DAN SEMI DARING: STRATEGI PEMBERDAYAAN MASYARAKAT DI MASA PANDEMI NORMAL BARU
Authors: Rustiati Elly Lestari , Virnarenata Elsa , Priyambodo Priyambodo , Alimudin Salih , Asmi Dwi , Santoso Edi , Yulianti Yanti , Pratiwi Dian Neli , Suroso Erdi
Published: April 2024

Penata layanan masyarakat dapat dilakukan secara langsung.  Interaksi langsung merupakan hal yang umum dilakukan, dihargai, dan memudahkan komunikasi.  Selama pandemi COVID-19, interaksi dan kunjungan langsung hampir tidak mungkin dilakukan karena adanya pembatasan aktivitas dan pembatasan sosial.  Interaksi secara daring dan semi daring dengan mengundang perwakilan komunitas secara terbatas yang dikombinasikan dengan metode daring dapat diterapkan.  Inisiasi komunikasi daring diperkenalkan.  Proyek ini dilakukan melalui pendampingan dan pelatihan di Braja Harjosari dan Labuhan Ratu VII, Lampung Timur.  Setelah pengenalan metode online dan semi online, masyarakat setempat dapat menerapkan dan berbagi pengetahuan dengan paradigma new normal.
Double butterfly theorem on ellips
Authors: Mashadi Mashadi , Dinata Muhammad Farhan
Published: April 2024

The butterfly and the double butterfly theorem are applied to a circle. In this paper, we will modify the double butterfly theorem on an ellipse. The method of proving the double butterfly theorem on an ellipse can be done if Haruki’s lemma can apply to any ellipse. Thus, in this paper will also be given a modified Haruki’s lemma on an ellipse.
PENGARUH VARIASI TEKANAN DAN FRAKSI VOLUME PADA HYBRID COMPOSITE SERAT SABUT KELAPA DAN SERAT BAMBU BERMATRIKS RESIN POLYESTER TERHADAP KEKUATAN TARIK DAN BENDING
Authors: Febryan Utama Putra  , Paundra Fajar , Abdul Muhyi  , Fuad Hakim  , Lukman Triawan  , Abdul Aziz
Published: April 2024

Composite is a material that is formed from a combination of two or more constituent materials with a heterogeneous mixing process, which has different mechanical properties. This study aims to determine the effect of volume fraction and molding pressure of composite materials on tensile and bending strength. The volume fractions used are SK 25% & SB 5%, SK 20% & SB 10%, SK 15% & SB 15%, SK 10% & SB 20%, and SK 5% & SB 25%. Each change in printing pressure is carried out at a pressure of 60 bar, 70 bar and 80 bar. Composite testing was carried out using ASTM D3039 for tensile testing and ASTM D790 for bending testing. The results obtained are the highest tensile strength at E3 with a value of 23.573 MPa and the lowest tensile strength at C1 with a value of 9.199 MPa, then the highest bending strength at E2 with a value of 38.665 MPa and the lowest bending strength at B1 with a value of 30.318 MPa.
Un exceptionnel zircon photochrome de 9,89 carats
Authors:   GGTL Laboratories Switzerland, 4bis route des Jeunes, 1227 Genève, Blumentritt Féodor , Notari Franck ,   GGTL Laboratories Switzerland, 4bis route des Jeunes, 1227 Genève
Published: April 2024

We were fortunate to observe and analyze a remarkable 9.89 ct zircon showing a strong color change from vivid orange to dark brown after longwave ultraviolet illumination (excited state). Its color comes back to vivid orange after being kept in the dark at room temperature for several months, or by heating the stone up to around 100°C for a few seconds. The color shift is reversible. These characteristics are typical of what is called a T-type photochromism phenomenon. Our spectroscopic absorption analyses showed that large bands at 510 and 800 nm are involved in the process, but their assignation is yet to be unraveled. We were fortunate to observe and analyze a remarkable 9.89 ct zircon showing a strong color change from vivid orange to dark brown after longwave ultraviolet illumination (excited state). Its color comes back to vivid orange after being kept in the dark at room temperature for several months, or by heating the stone up to around 100°C for a few seconds. The color shift is reversible. These characteristics are typical of what is called a T-type photochromism phenomenon. Our spectroscopic absorption analyses showed that large bands at 510 and 800 nm are involved in the process, but their assignation is yet to be unraveled.
ТҮСТЕРДІ БЕЛГІЛЕЙТIН АҒЫЛШЫН ЖӘНЕ ҚАЗАҚ ИДИОМАЛАРЫНЫҢ САЛЫСТЫРМАЛЫ ТАЛДАУЫ
Authors: Сәрсембай Сая
Published: April 2024

Мақаланың мақсаты «Түс атаулары» тақырыбы негізінде ағылшын және қазақ тілдерінде кездесетін тұрақты сөз тіркестерді салыстыру, олардың өзара қарым- қатынас сипаты мен аударма ерекшеліктерін анықтау. Әр тілде түр-түс атаулары тек қана дәлме-дәл мағыналарында ғана қабылданбайды, олар символикалық өзгешіліктеріне де ие. Әр этномәдени халық әлемнің түр-түсін өзгеше көріп таниды және осы ерекшелік әлем туралы олардың этникалық ұлттық түсініктері бар екендігін көрсетеді. Түрлі халықтардың осындай түр-түс туралы мәдени түсініктерінің ерекшеліктері әсіресе ассоциацияларда байқалады. Мақалада ағылшын және қазақ тілдері фразеологиясында кездесетін осындай сөз тіркестердің қолдану жиіліктігіне талдау жасалынды, соның негізінде түр-түс компоненттерінің семантикалық коннотациялары талданды және олардың арасындағы айырмашылықтары мен ұқсастықтары анықталды.
Assessing the Impact of Cross-Cultural Interactions on English Language Acquisition in Kazakhstan's Educational System
Authors: Dzhubanova Sholpan
Published: April 2024

This article examines the impact of cross-cultural interactions on English language acquisition within Kazakhstan's educational system. Recognizing the increasing globalization and the role of English as a lingua franca, this study explores how cross-cultural exchanges influence language learning. Using a mixed-methods approach, the research analyzes data from surveys and interviews with teachers and students across various schools in Kazakhstan. The study also incorporates case studies of specific programs promoting cross-cultural understanding. Key findings suggest that exposure to different cultures, whether through exchange programs, digital platforms, or multicultural classrooms, significantly enhances language acquisition. This enhancement is particularly noticeable in aspects of language learning such as vocabulary expansion, pronunciation, and understanding of cultural nuances in language use. The research highlights the importance of incorporating cross-cultural elements into language curricula to foster a more holistic understanding of English. Challenges such as limited resources for exchange programs and the need for teacher training in multicultural education are discussed. The article concludes with recommendations for integrating cross-cultural interactions in language learning and suggestions for future research directions in this area.
Anglicisms in the Works of Scientists of Kazakhstan
Authors: Abdikadyrova Aigerim , Kuzembekova Zhanna
Published: April 2024

The article talks about the culture of language and the culture of speech, and the study of anglicisms in the works of Kazakhstani scientists is considered. Language is a means of communication, a mirror reflecting a person’s way of thinking, cultural status, intelligence, and spiritual wealth. The relevance of linguistic culture has always been taken into account, and not a single nation has avoided this issue. The Kazakh people also attached great importance to the ability to speak, saying that “art is a language.” Currently, the cultural diversity of the language in the country has increased. The future of the language of the Kazakh people lies with modern youth, and in this article we will analyze the current state of language use by these youth. The task of our work is to determine the method of formation and features of the use of introduced words that came into the Kazakh language from the English language. The role of language in culture and the influence of culture on the formation of language are becoming increasingly relevant and are widely considered in modern linguistics and linguoculturology. Among languages with a thousand-year history, there is no doubt that Kazakh-English cultural ties have left their mark on the vocabulary of these languages.
THE IMPACT OF THE USE OF DIGITAL TECHNOLOGIES IN TEACHING MATHEMATICS AT SCHOOL
Authors: Taukebayeva Gulsum , Bakirova Elmira
Published: April 2024

The dependence of students on gadgets and digital technologies poses a significant challenge to the education system, making it imperative to find effective solutions. Interactive games offer a promising approach to addressing this issue, as they not only engage students but also enhance problem-solving skills, facilitate homework checking, and reinforce theoretical concepts. Despite these benefits, interactive games are underutilized in mathematics lessons in Kazakhstan. Therefore, this study aims to experimentally assess the effectiveness of interactive games in enhancing students' cognitive activity during mathematics lessons.The experiment involved 22 10th-grade students from a comprehensive school, divided into a research group and a control group. The research methods included analysis, comparative analysis, synthesis, and generalization of scientific literature, as well as documentary analysis of normative legal acts and educational concepts related to computerization and informatization of education.The experimental intervention lasted one month and consisted of three interactive game-based lessons and one traditional lesson as an exam. The results indicated that students in the research group demonstrated higher levels of engagement and scored approximately 50% higher on the test compared to the control group. These findings suggest that interactive games can effectively enhance cognitive activity and could be implemented in both specialized and general education settings. However, the study's scope was limited to one topic and did not include repetition or other topics, highlighting the need for further research in this area.
Design and Application of Intelligent Transportation Systems Based on Optoelectronic Information Processing and Time-optimal Algorithms
Authors:   Harbin Institute of Technology，Weihai, DING Xiaofeng
Published: April 2024

The project employs photoelectric information acquisition technology and integrates it with an intersection waiting time optimization algorithm to achieve traffic light control at urban intersections through photoelectric acquisition, data analysis, data processing, and module control. Its objective is to efficiently and effectively address the issue of traffic congestion at intersections, providing a solution for the development of intelligent urban transportation.
“L’art és vida.” Ensayo visual de la falla como experiencia de arte efímero en una clase de 3 años
Authors: Monleón Oliva Vicente
Published: April 2024

La fiesta de las Fallas se entiende como un elemento propio de la identidiad y de la cultura valenciana. Debido a ello, la legislación educativa vigente la contempla en sus currículos autonómicos y oficiales como uno de los saberes básicos a tratar desde la etapa de Educación Infantil. En este ensayo visual, como método de investigación de los estudios de corte artístico, se comparte la aplicación y el tratamiento didáctico de los elementos falleros en un aula de 3 años. La propuesta nace a nivel de centro en el CEIP L’Almassil de Mislata bajo el lema “L’art és vida” y se adapta a la etapa de Educación Infantil (segundo ciclo). Concretamente, se analiza visualmente la intervención didáctica en el grupo de 3 años A en el curso 2022-2023. Los elementos abordados son: la falla como monumento, la gastronomía, la banda de música, la mascletà, la comitiva fallera y la cremà.
La comunicación de la identidad territorial desde los carteles institucionales. Análisis aplicado al caso valenciano
Authors: Gómez-Aguilella María José , Ramon Ricard
Published: April 2024

El artículo presenta una propuesta de análisis de los carteles institucionales desde la identidad. Elaboramos esta propuesta teniendo en cuenta una serie de factores en conexión con la proyección identitaria de los carteles. Los aplicamos al estudio de un caso: los carteles institucionales valencianos y su proyección identitaria, cómo influyen todos los factores propuestos en el análisis de la comprensión de la comunicación de una identidad a través de ellos. Concluimos observando las contribuciones del cartel institucional en la comunicación identitaria y validamos los factores de análisis.
Investigar des de les arts sobre la identitat valenciana
Authors: Ramon Ricard
Published: April 2024

Ressenya de la publicació: Identitart. Investigar sobre la identitat valenciana a través de les arts. (2023). Universitat de València.
L’évolution du concept de la protection des droits fondamentaux dans l’ordre juridique communautaire
Authors: Ćeranić Perišić Jelena
Published: April 2024

Les pères fondateurs des Communautés européenne estimaient qu’il n’était pas nécessaire d’inclure dans les traites fondateurs les dispositions sur la protection des droits fondamentaux, principalement en raison de la vocation économique du processus d’intégration européenne. Néanmoins, il est apparu rapidement que même dans le domaine des compétences transférées, pourtant essentiellement économiques, la question de la protection des droits fondamentaux se posait. La protection des droits fondamentaux dans l’ordre juridique communautaire est le résultat de la jurisprudence de la Cour de justice. La Cour a établi un corpus des droits fondamentaux qu’elle garantit en se référant aux principes généraux du droit et aux traités internationaux, comme sources d’inspiration. Cet article suit chronologiquement l’évolution de concept de protection des droits fondamentaux dans l’ordre juridique communautaire, en le présentant en quatre étapes. D’abord, l’article aborde la contribution de la jurisprudence de la Cour de justice au développement du concept de protection des droits fondamentaux dans l’ordre juridique communautaire. Ensuite, il présente la contribution des amendements apportés par les traités de Maastricht, Amsterdam et Nice au protection des droits fondamentaux. L’attention particulière est consacrée à la Charte des droit fondamentaux. L’article aussi analyse les défis de l’adhésion de l’Union européenne à la Convention européenne des droit de l’homme et des liberté fondamentales. Finalement, il présente le system actuel de la protection des droit fondamentaux, établit par le traité de Lisbonne, qui repose sur trois piliers de protection des droits fondamentaux dans l’Union européenne.
The Death Penalty in the XXI Century
Authors: Marić Tamara
Published: April 2024

In relation to imprisonment and fines, which occupy a central place in most modern systems of criminal sanctions, there are still deep cross-sectional opinions of legal theorists and public opinion on the justification of the existence of the death penalty. Although in the last few decades it has been deleted from the punishment system in a large number of countries, at the same time the death penalty still exists in the criminal legislation of countries around the world. What do the latest statistics say about the number of death sentences carried out at the world level, how does the death penalty exist in criminal legislation where it exists and for which crimes it can be imposed, on the basis of which legal mechanisms it was abolished where it no longer exists, what are the arguments legal theorists who are still advocating for the abolition of this punishment and what are the justifications of its advocates, what forms of execution exist today, these are all questions whose answers will be addressed within the topic of this report.
Rats emit aversive 44-kHz ultrasonic vocalizations during prolonged Pavlovian fear conditioning
Authors: Olszyński Krzysztof H. , Polowy Rafał , Wardak Agnieszka D. , Łaska Izabela A. , Grymanowska Aneta W. , Puławski Wojciech , Gawryś Olga , Koliński Michał , Filipkowski Robert K.
Published: April 2024

Rats are believed to communicate their emotional state by emitting two distinct types of ultrasonic vocalizations. The first is long “22-kHz” vocalizations (>300 ms, <32 kHz) with constant frequency, signaling aversive states and the second, is short “50-kHz” calls (<150 ms, >32 kHz), often frequency-modulated, in appetitive situations. Here we are first to describe a new-type of aversive vocalizations emitted at a higher pitch by Wistar and spontaneously hypertensive rats (SHR) in an intensified aversive state – prolonged fear conditioning. These calls, which we named “44-kHz” vocalizations, are long (>150 ms), generally at a constant frequency (usually within 35-50 kHz range) and have an overall spectrographic image similar to 22-kHz calls. Some 44-kHz vocalizations are comprised of both 22-kHz-like and 44-kHz-like elements. Furthermore, two separate clustering methods confirmed that these 44-kHz calls are distinct from other vocalizations. We observed 44-kHz calls to be associated with freezing behavior during fear conditioning, during which they constituted up to 19.4% of all calls. We also show that some of rats’ responses to the playback of 44-kHz calls were more akin to that of aversive calls, e.g., heart rate changes, whereas other responses were at an intermediate level between aversive and appetitive calls. Our results suggest that rats have a wider vocal repertoire than previously believed, and current definitions of major call types may require reevaluation. We hope that future investigations of 44-kHz calls in rat models of human diseases will contribute to expanding our understanding and therapeutic strategies related to human psychiatric conditions.
The Alk receptor tyrosine kinase regulates Sparkly, a novel activity regulating neuropeptide precursor in the Drosophila CNS
Authors: Sukumar Sanjay Kumar , Antonydhason Vimala , Molander Linnea , Sandakly Jawdat , Kleit Malak , Umapathy Ganesh , Mendoza-Garcia Patricia , Masudi Tafheem , Schlossser Andreas , Nässel Dick R. , Wegener Christian , Shirinian Margret , Palmer Ruth H.
Published: April 2024

Numerous roles for the Alk receptor tyrosine kinase have been described in
Drosophila
, including functions in the central nervous system (CNS), however the molecular details are poorly understood. To gain mechanistic insight, we employed Targeted DamID (TaDa) transcriptional profiling to identify targets of Alk signaling in the larval CNS. TaDa was employed in larval CNS tissues, while genetically manipulating Alk signaling output. The resulting TaDa data were analysed together with larval CNS scRNA-seq datasets performed under similar conditions, identifying a role for Alk in the transcriptional regulation of neuroendocrine gene expression. Further integration with bulk/scRNA-seq and protein datasets from larval brains in which Alk signaling was manipulated, identified a previously uncharacterized
Drosophila
neuropeptide precursor encoded by
CG4577
as an Alk signaling transcriptional target.
CG4577
, which we named
Sparkly (Spar),
is expressed in a subset of Alk-positive neuroendocrine cells in the developing larval CNS, including circadian clock neurons. In agreement with our TaDa analysis, overexpression of the
Drosophila
Alk ligand Jeb resulted in increased levels of Spar protein in the larval CNS. We show that Spar protein is expressed in circadian (Clock) neurons, and flies lacking Spar exhibit defects in sleep and circadian activity control. In summary, we report a novel activity regulating neuropeptide precursor gene that is regulated by Alk signaling in the
Drosophila
CNS.
Sex-biased regulatory changes in the placenta of native highlanders contribute to adaptive fetal development
Authors: Yue Tian , Guo Yongbo , Qi Xuebin , Zheng Wangshan , Zhang Hui , Wang Bin , Liu Kai , Zhou Bin , Zeng Xuerui , Ouzhuluobu  , He Yaoxi , Su Bing
Published: April 2024

Compared with lowlander migrants, native Tibetans have a higher reproductive success at high altitude though the underlying mechanism remains unclear. Here, we compared the transcriptome and histology of full-term placentas between native Tibetans and Han migrants. We found that the placental trophoblast shows the largest expression divergence between Tibetans and Han, and Tibetans show decreased immune response and endoplasmic reticulum stress. Remarkably, we detected a sex-biased expression divergence, where the male-infant placentas show a greater between-population difference than the female-infant placentas. The umbilical cord plays a key role in the sex-biased expression divergence, which is associated with the higher birth weight of the male newborns of Tibetans. We also identified adaptive histological changes in the male-infant placentas of Tibetans, including larger umbilical artery wall and umbilical artery intima and media, and fewer syncytial knots. These findings provide valuable insights into the sex-biased adaptation of human populations, with significant implications for medical and genetic studies of human reproduction.
Mecp2 Fine-tunes Quiescence Exit by Targeting Nuclear Receptors
Authors: Yang Jun , Zou Shitian , Qiu Zeyou , Lai Mingqiang , Long Qing , Chen Huan , Lai Pinglin , Zhang Sheng , Rao Zhi , Xie Xiaoling , Gong Yan , Liu Anling , Li Mangmang , Bai Xiaochun
Published: April 2024

Quiescence (G0) maintenance and exit are crucial for tissue homeostasis and regeneration in mammals. Here, we show that methyl-CpG binding protein 2 (Mecp2) expression is cell cycle-dependent and negatively regulates quiescence exit in cultured cells and in an injury-induced liver regeneration mouse model. Specifically, acute reduction of Mecp2 is required for efficient quiescence exit, as deletion of Mecp2 accelerates, while overexpression of Mecp2 delays quiescence exit, and forced expression of Mecp2 after Mecp2 conditional knockout rescues cell cycle reentry. The E3 ligase Nedd4 mediates the ubiquitination and degradation of Mecp2, and thus facilitates quiescence exit. Genome-wide study uncovered the dual role of Mecp2 in preventing quiescence exit by transcriptionally activating metabolic genes while repressing proliferation-associated genes. Particularly, disruption of two nuclear receptors (NRs),
Rara
or
Nr1h3,
accelerates quiescence exit, mimicking the Mecp2 depletion phenotype. Our studies unravel a previously unrecognized role for Mecp2 as an essential regulator of quiescence exit and tissue regeneration.
Strong isolation by distance and evidence of population microstructure reflect ongoing Plasmodium falciparum transmission in Zanzibar
Authors: Connelly Sean V. , Brazeau Nicholas F. , Msellem Mwinyi , Ngasala Billy E. , Aydemir Özkan , Goel Varun , Niaré Karamoko , Giesbrecht David J. , Popkin-Hall Zachary R. , Hennelly Christopher M. , Park Zackary , Moormann Ann M. , Ong’echa John Michael , Verity Robert , Mohammed Safia , Shija Shija J. , Mhamilawa Lwidiko E. , Morris Ulrika , Mårtensson Andreas , Lin Jessica T. , Björkman Anders , Juliano Jonathan J. , Bailey Jeffrey A.
Published: April 2024

The Zanzibar archipelago of Tanzania has become a low-transmission area for
Plasmodium falciparum.
Despite being considered an area of pre-elimination for years, achieving elimination has been difficult, likely due to a combination of imported infections from mainland Tanzania, and continued local transmission. To shed light on these sources of transmission, we applied highly multiplexed genotyping utilizing molecular inversion probes to characterize the genetic relatedness of 282
P. falciparum
isolates collected across Zanzibar and in Bagamoyo District on the coastal mainland from 2016-2018. Overall, parasite populations on the coastal mainland and Zanzibar archipelago remain highly related. However, parasite isolates from Zanzibar exhibit population microstructure due to rapid decay of parasite relatedness over very short distances. This, along with highly related pairs within
shehias
, suggests ongoing low level local transmission. We also identified highly related parasites across
shehias
that reflect human mobility on the main island of Unguja and identified a cluster of highly related parasites, suggestive of an outbreak, in the Micheweni district on Pemba island. Parasites in asymptomatic infections demonstrated higher complexity of infection than those in symptomatic infections, but have similar core genomes. Our data support importation as a main source of genetic diversity and contribution to the parasite population on Zanzibar, but they also show local outbreak clusters where targeted interventions are essential to block local transmission. These results highlight the need for preventive measures against imported malaria and enhanced control measures in areas that remain receptive for malaria reemergence due to susceptible hosts and competent vectors.
SMAD4 promotes somatic-germline contact during murine oocyte growth
Authors: Granados-Aparici Sofia , Yang Qin , Clarke Hugh
Published: April 2024

Development of the mammalian oocyte requires physical contact with the surrounding granulosa cells of the follicle, which provide it with essential nutrients and regulatory signals. This contact is achieved through specialized filopodia, termed transzonal projections (TZPs), that extend from the granulosa cells to the oocyte surface. Transforming growth factor (TGFβ) family ligands produced by the oocyte increase the number of TZPs, but how they do so is unknown. Using an inducible Cre recombinase strategy together with expression of green fluorescent protein to verify Cre activity in individual granulosa cells, we examined the effect of depleting the canonical TGFβ mediator, SMAD4. We observed a 20-50% decrease in the total number of TZPs in SMAD4-depleted granulosa cell-oocyte complexes, and a 50% decrease in the number of newly generated TZPs when the granulosa cells were reaggregated with granulosa cell-free wild-type oocytes. Three-dimensional image analysis revealed that TZPs of SMAD4-depleted cells were also longer than controls and more frequently oriented towards the oocyte. Strikingly, the transmembrane proteins, N-cadherin and Notch2, were reduced by 50% in these cells. SMAD4 may thus modulate a network of cell adhesion proteins that stabilize the attachment of TZPs to the oocyte, thereby amplifying signalling between the two cell types.
Divergent Folding-Mediated Epistasis Among Unstable Membrane Protein Variants
Authors: Chamness Laura M. , Kuntz Charles P. , McKee Andrew G. , Penn Wesley D. , Hemmerich Christopher M. , Rusch Douglas B. , Woods Hope , Dyotima  , Meiler Jens , Schlebach Jonathan P.
Published: April 2024

Many membrane proteins are prone to misfolding, which compromises their functional expression at the plasma membrane. This is particularly true for the mammalian gonadotropin-releasing hormone receptor GPCRs (GnRHR). We recently demonstrated that evolutionary GnRHR modifications appear to have coincided with adaptive changes in cotranslational folding efficiency. Though protein stability is known to shape evolution, it is unclear how cotranslational folding constraints modulate the synergistic, epistatic interactions between mutations. We therefore compared the pairwise interactions formed by mutations that disrupt the membrane topology (V276T) or tertiary structure (W107A) of GnRHR. Using deep mutational scanning, we evaluated how the plasma membrane expression of these variants is modified by hundreds of secondary mutations. An analysis of 251 mutants in three genetic backgrounds reveals that V276T and W107A form distinct epistatic interactions that depend on both the severity and the mechanism of destabilization. V276T forms predominantly negative epistatic interactions with destabilizing mutations in soluble loops. In contrast, W107A forms positive interactions with mutations in both loops and transmembrane domains that reflect the diminishing impacts of the destabilizing mutations in variants that are already unstable. These findings reveal how epistasis is remodeled by conformational defects in membrane proteins and in unstable proteins more generally.
Inhibition of miR-199b-5p reduces pathological alterations in Osteoarthritis by potentially targeting Fzd6 and Gcnt2
Authors: Feng Tong , Zhang Qi , Li Si-Hui , Ping Yan-ling , Tian Mu-qiu , Zhou Shuan-hu , Wang Xin , Wang Jun-Meng , Liang Fan-Rong , Yu Shu-Guang , Wu Qiao-Feng
Published: April 2024

Osteoarthritis (OA) is a degenerative disease with a high prevalence in the elderly population, but our understanding of its mechanisms remains incomplete. Analysis of serum exosomal small RNA sequencing data from clinical patients and gene expression data from OA patient serum and cartilage obtained from the GEO database revealed a common dysregulated miRNA, miRNA-199b-5p. In vitro cell experiments demonstrated that miRNA-199b-5p inhibits chondrocyte vitality and promotes extracellular matrix degradation. Conversely, inhibition of miRNA-199b-5p under inflammatory conditions exhibited protective effects against damage. Local viral injection of miRNA-199b-5p into mice induced a decrease in pain threshold and OA-like changes. In an OA model, inhibition of miRNA-199b-5p alleviated the pathological progression of OA. Furthermore, bioinformatics analysis and experimental validation identified
Gcnt2
and
Fzd6
as potential target genes of miRNA-199b-5p. Thus, these results indicated that miRNA-199b-5p/
Gcnt2
and
Fzd6
axis might be a novel therapeutic target for the treatment of OA.
FMNL2 regulates actin for ER and mitochondria distribution in oocyte meiosis
Authors: Pan Meng-Hao , Pan Zhen-Nan , Sun Ming-Hong , Li Xiao-Han , Ju Jia-Qian , Luo Shi-Ming , Ou Xiang-Hong , Sun Shao-Chen
Published: April 2024

During mammalian oocyte meiosis, spindle migration and asymmetric cytokinesis are unique steps for the successful polar body extrusion. The asymmetry defects of oocytes will lead to the failure of fertilization and embryo implantation. In present study we reported that an actin nucleating factor formin-like 2 (FMNL2) played critical roles in the regulation of spindle migration and organelle distribution. Our results showed that FMNL2 mainly localized at the oocyte cortex and periphery of spindle. Depletion of FMNL2 led to the failure of polar body extrusion and large polar bodies in oocytes. Live-cell imaging revealed that the spindle failed to migrate to the oocyte cortex, which caused polar body formation defects, and this might be due to the decreased polymerization of cytoplasmic actin by FMNL2 depletion. Furthermore, mass spectrometry analysis indicated that FMNL2 was associated with mitochondria and endoplasmic reticulum-related proteins, and FMNL2 depletion disrupted the function and distribution of mitochondria and endoplasmic reticulum, showing with decreased mitochondrial membrane potential and the occurrence of endoplasmic reticulum stress. Microinjecting Fmnl2-EGFP mRNA into FMNL2-depleted oocytes significantly rescued these defects. Thus, our results indicate that FMNL2 is essential for the actin assembly, which further involves into meiotic spindle migration and ER/mitochondria functions in mouse oocytes.
Signatures of transposon-mediated genome inflation, host specialization, and photoentrainment in Entomophthora muscae and allied entomophthoralean fungi
Authors: Stajich Jason E. , Lovett Brian , Lee Emily , Macias Angie M. , Hajek Ann E. , de Bivort Benjamin L. , Kasson Matt T. , De Fine Licht Henrik H. , Elya Carolyn
Published: April 2024

Despite over a century of observations, the obligate insect parasites within the order Entomophthorales remain poorly characterized at the genetic level. This is in part due to their large genome sizes and difficulty in obtaining sequenceable material. In this manuscript, we leveraged a recently-isolated, laboratory-tractable
Entomophthora muscae
isolate and improved long-read sequencing to obtain a largely-complete entomophthoralean genome. Our
E. muscae
assembly is 1.03 Gb, consists of 7,810 contigs and contains 81.3% complete fungal BUSCOs. Using a comparative approach with other available (transcriptomic and genomic) datasets from entomophthoralean fungi, we provide new insight into the biology of these understudied pathogens. We offer a head-to-head comparison of morphological and molecular data for species within the
E. muscae
species complex. Our findings suggest that substantial taxonomic revision is needed to define species within this group and we provide recommendations for differentiating strains and species in the context of the existing body of
E. muscae
scientific literature. We show that giant genomes are the norm within Entomophthoraceae owing to extensive, but not recent, Ty3 retrotransposon activity, despite the presence of machinery to defend against transposable elements(RNAi). In addition, we find that
E. muscae
and its closest allies are enriched for M16A peptidases and possess genes that are likely homologs to the blue-light sensor
white-collar 1
, a
Neurospora crassa
gene that has a well-established role in maintaining circadian rhythms. We find that
E. muscae
has an expanded group of acid-trehalases, consistent with trehalose being the primary sugar component of fly (and insect) hemolymph. We uncover evidence that
E. muscae
diverged from other entomophthoralean fungi by expansion of existing families, rather than loss of particular domains, and possesses a potentially unique suite of secreted catabolic enzymes, consistent with
E. muscae
’s species-specific, biotrophic lifestyle. Altogether, we provide a genetic and molecular foundation that we hope will provide a platform for the continued study of the unique biology of entomophthoralean fungi.
Downregulation of Let-7 miRNA promotes Tc17 differentiation and emphysema via de-repression of RORγt
Authors: Erice Phillip A. , Huang Xinyan , Seasock Matthew J. , Robertson Matthew J. , Tung Hui-Ying , Perez-Negron Melissa A. , Lotlikar Shivani L. , Corry David B , Kheradmand Farrah , Rodriguez Antony
Published: April 2024

Environmental air irritants including nanosized carbon black (nCB) can drive systemic inflammation, promoting chronic obstructive pulmonary disease (COPD) and emphysema development. The
let-7
family of miRNAs is associated with IL-17-driven T cell inflammation, a canonical signature of lung inflammation. Recent evidence suggests the
let-7
family is downregulated in patients with COPD, however, whether this repression conveys a functional consequence on emphysema pathology has not been elucidated. Here we show that overall expression of the
let-7
miRNA clusters,
let-7b/let-7c2
and
let-7a1/let-7f1/let-7d
, are reduced in the lungs and T cells of smokers with emphysema as well as in mice with cigarette smoke (CS)- or nCB-elicited emphysema. We demonstrate that loss of the
let-7b/let-7c2-
cluster in T cells predisposed mice to exaggerated CS- or nCB-elicited emphysema. Furthermore, ablation of the
let-7b/let-7c2-
cluster enhanced CD8
+
IL17a
+
T cells (Tc17) formation in emphysema development in mice. Additionally, transgenic mice overexpressing
let-7
in T cells are resistant to Tc17 and CD4
+
IL17a
+
T cells (Th17) development when exposed to nCB. Mechanistically, our findings reveal the master regulator of Tc17/Th17 differentiation, RAR-related orphan receptor gamma t (RORγt), as a direct target of
let-7
miRNA in T cells. Overall, our findings shed light on the
let-7/
RORγt axis with
let-7
acting as a molecular brake in the generation of Tc17 cells and suggests a novel therapeutic approach for tempering the augmented IL-17-mediated response in emphysema.
Exploring the Spatial Distribution of Persistent SARS-CoV-2 Mutations - Leveraging mobility data for targeted sampling
Authors: Spott Riccardo , Pletz Mathias W. , Fleischmann-Struzek Carolin , Kimmig Aurelia , Hadlich Christiane , Hauert Mathias , Lohde Mara , Jundzill Mateusz , Marquet Mike , Dickmann Petra , Schüchner Ruben , Hölzer Martin , Kühnert Denise , Brandt Christian
Published: April 2024

Given the rapid cross-country spread of SARS-CoV-2 and the resulting difficulty in tracking lineage spread, we investigated the potential of combining mobile service data and fine-granular metadata (such as postal codes and genomic data) to advance integrated genomic surveillance of the pandemic in the federal state of Thuringia, Germany. We sequenced over 6,500 SARS-CoV-2 Alpha genomes (B.1.1.7) across seven months within Thuringia while collecting patients’ isolation dates and postal codes. Our dataset is complemented by over 66,000 publicly available German Alpha genomes and mobile service data for Thuringia. We identified the existence and spread of nine persistent mutation variants within the Alpha lineage, seven of which formed separate phylogenetic clusters with different spreading patterns in Thuringia. The remaining two are sub-clusters. Mobile service data can indicate these clusters’ spread and highlight a potential sampling bias, especially of low-prevalence variants. Thereby, mobile service data can be used either retrospectively to assess surveillance coverage and efficiency from already collected data or to actively guide part of a surveillance sampling process to districts where these variants are expected to emerge. The latter concept proved successful as we introduced a mobility-guided sampling strategy for the surveillance of Omicron sublineage BQ.1.1. The combination of mobile service data and SARS-CoV-2 surveillance by genome sequencing is a valuable tool for more targeted and responsive surveillance.
Protection afforded by post-infection SARS-CoV-2 vaccine doses: A cohort study in Shanghai
Authors: Zheng Bo , Gonçalves Bronner P , Deng Pengfei , Wang Weibing , Tian Jie , Liang Xueyao , Yao Ye , Xue Caoyi
Published: April 2024

Background:

In many settings, a large fraction of the population has both been vaccinated against and infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Hence, quantifying the protection provided by post-infection vaccination has become critical for policy. We aimed to estimate the protective effect against SARS-CoV-2 reinfection of an additional vaccine dose after an initial Omicron variant infection.

Methods:

We report a retrospective, population-based cohort study performed in Shanghai, China, using electronic databases with information on SARS-CoV-2 infections and vaccination history. We compared reinfection incidence by post-infection vaccination status in individuals initially infected during the April–May 2022 Omicron variant surge in Shanghai and who had been vaccinated before that period. Cox models were fit to estimate adjusted hazard ratios (aHRs).

Results:

275,896 individuals were diagnosed with real-time polymerase chain reaction-confirmed SARS-CoV-2 infection in April–May 2022; 199,312/275,896 were included in analyses on the effect of a post-infection vaccine dose. Post-infection vaccination provided protection against reinfection (aHR 0.82; 95% confidence interval 0.79–0.85). For patients who had received one, two, or three vaccine doses before their first infection, hazard ratios for the post-infection vaccination effect were 0.84 (0.76–0.93), 0.87 (0.83–0.90), and 0.96 (0.74–1.23), respectively. Post-infection vaccination within 30 and 90 days before the second Omicron wave provided different degrees of protection (in aHR): 0.51 (0.44–0.58) and 0.67 (0.61–0.74), respectively. Moreover, for all vaccine types, but to different extents, a post-infection dose given to individuals who were fully vaccinated before first infection was protective.

Conclusions:

In previously vaccinated and infected individuals, an additional vaccine dose provided protection against Omicron variant reinfection. These observations will inform future policy decisions on COVID-19 vaccination in China and other countries.

Funding:

This study was funded the Key Discipline Program of Pudong New Area Health System (PWZxk2022-25), the Development and Application of Intelligent Epidemic Surveillance and AI Analysis System (21002411400), the Shanghai Public Health System Construction (GWVI-11.2-XD08), the Shanghai Health Commission Key Disciplines (GWVI-11.1-02), the Shanghai Health Commission Clinical Research Program (20214Y0020), the Shanghai Natural Science Foundation (22ZR1414600), and the Shanghai Young Health Talents Program (2022YQ076).
Secreted antigen A peptidoglycan hydrolase is essential for Enterococcus faecium cell separation and priming of immune checkpoint inhibitor therapy
Authors: Klupt Steven , Fam Kyong Tkhe , Zhang Xing , Chodisetti Pavan Kumar , Mehmood Abeera , Boyd Tumara , Grotjahn Danielle , Park Donghyun , Hang Howard C.
Published: April 2024

Enterococcus faecium
is a microbiota species in humans that can modulate host immunity
1
, but has also acquired antibiotic resistance and is a major cause of hospital-associated infections
2
. Notably, diverse strains of
E. faecium
produce SagA, a highly conserved peptidoglycan hydrolase that is sufficient to promote intestinal immunity
3–5
and immune checkpoint inhibitor antitumor activity
6
. However, the functions of SagA in
E. faecium
were unknown. Here we report that deletion of
sagA
impaired
E. faecium
growth and resulted in bulged and clustered enterococci due to defective peptidoglycan cleavage and cell separation. Moreover, Δ
sagA
showed increased antibiotic sensitivity, yielded lower levels of active muropeptides, displayed reduced activation of the peptidoglycan pattern-recognition receptor NOD2, and failed to promote cancer immunotherapy. Importantly, plasmid-based expression of SagA, but not its catalytically-inactive mutant, restored Δ
sagA
growth, production of active muropeptides and NOD2 activation. SagA is therefore essential for
E. faecium
growth, stress resistance and activation of host immunity.