bluuebunny/crossref_metadata_2025 huggingface dataset:
Efektivitas Model Pembelajaran TGT (Team Games Tournament) dalam Penulisan Puisi di Kelas II SDN Kedunggalar
Authors: Ulfa Nur’afifah Uci
Published: April 2024

This research was motivated by the low poetry writing performance of students in the Indonesian language subject, particularly in the poetry section, in the second grade of SDN Kedunggalar. One proposed solution to address this issue was to implement the Team Games Tournament (TGT) teaching model. The aim of this research was to describe the improvement in poetry writing skills in the Indonesian language, specifically in the poetry section, among second-grade students at SDN Kedunggalar through the application of the TGT teaching model. The research employed a quantitative methodology, conducted through a series of phases including planning, implementation, observation, reflection, and data collection. The study was carried out in January 2022, involving 32 second-grade students, consisting of 15 males and 17 females. Data collection methods included documentation, observation, and testing. The results of the research indicated that the poetry writing skills of the students in the Indonesian language, poetry section, in the second grade at SDN Kedunggalar were significantly improved. This was reflected in the post-test results of the experimental group, which had an average score of 94.44 and a median score of 95.0. This represented an 80% improvement after the intervention. In conclusion, it can be inferred that the utilization of the TGT teaching model effectively enhanced the learning effectiveness of poetry writing skills among second-grade students in the Indonesian language subject, specifically in the poetry section, at SDN Kedunggalar.
Pengembangan Media E - Komik dalam Pembelajaran PAI Berbasis Kontekstual Materi Kisah Sahabat Rasulullah SAW Kelas 5 SDN Plumbungan Sukodono Sidoarjo
Authors: Mariana Dielfi
Published: April 2024

E-Comics are a learning tool that can facilitate student learning due to the lack of learning media used by educators due to limited ability to create interesting learning media. The absence of e-comic media regarding the story of the Prophet's companions at Plumbungan Elementary School has motivated researchers to develop e-comic media in contextual-based PAI learning so that the desired learning objectives are achieved. This study carries out a form of research (Borg & Gall), researchers practice and modify, this research and development stage can be simpler and easier to understand. The types of data used are qualitative and quantitative data. From the score data obtained, it is a very interesting criterion. The results obtained from the practicality test of Koma products were obtained from teacher response questionnaires ('94.82%) and student responses (84.61%). These data show that the results of the criteria are very practical. Comic book products obtained effective criteria results and there was also an increase in teacher learning activities and student activities before and when using e-comic media, namely student activity before 46.75% to 89.28% while teacher activity before using the product was 74.43%. to '90.27% so it can be concluded that e-comic media in contextual, PAI-based learning is very effective in increasing teacher and student activity in the learning process. Based on these results, e-comic media in contextual-based PAI learning for Grade 5 elementary schools has met the requirements for use in learning because it has met the criteria of valid, interesting, effective and practical.
Pengembangan Media Pembelajaran Matematika Berbasis Android pada Materi Matriks
Authors: Epran Epran , Muhammad Ilham
Published: April 2024

The use of media in learning can help educators' limitations in conveying information and limited teaching hours in class. One of the ICT-assisted learning media that can be used is learning media that is operated on smartphone devices with the Android operating system. The aim of this research is to determine the validity and practicality of Android-based mathematics learning media on matrix material. The model used follows the ADDIE development model (analysis, design, development, implementation evaluation). The data collection technique used is a non-test technique with data collection instruments, namely validation sheets and practicality sheets. The research results show that Android-based mathematics learning media on matrix material is valid and reliable. The results of the student questionnaire assessment show that this application is not only effective in supporting online and offline learning, but is also able to increase students' interest in learning and deepen their understanding of mathematical concepts. The success of this application creates opportunities to increase learning efficiency, provide relevant learning solutions in the digital era, and motivate students to learn independently.
Perencanaan Pendidik dan Tenaga Kependidikan dalam Mentoring Adab di SDITA El Ma’mur Bogor
Authors: Suryati Suryati , Tamam Abas Mansur , Supraha Wido
Published: April 2024

The law of SISDIKNAS No.20 of 2003 article 52 paragraph 1 states that, “the management of Pre-school, Primary School, and Secondary School is carried out based on minimum standard service with the principle of school or madrasah based management.” The aims of this research is to analyze the management of educational staff and educators in Ma’mur Manaf As Salamah Foundation SDITA eL Ma’mur Bogor.  The method that the researcher used is library research by taking references from books, journals, papers, articles, and newspapers that is relevant to this research. Data collection was carry out by in-depth interview, observation, and documentation studies. The result of this research found out that there are several steps in the management of human resources in this case educational staff and educators such as, (1) analyzing the condition and the availability of educational staff and educators, (2) designing and arranging the process of educational staff and educators recruitments’ program, (3) conduct observation and selection for the candidate of educational staff and educators, (4) the placement of human resources based on the requirement, (5) the coaching of human resource according to the qualification of each duty, (6) promotion and mutation, (7) dismissal, (8) compensation, and (9) the evaluation of the staff (reward and punishment (Arianto et al., 2019).
Pentingnya Penggunaan Teknologi Informasi dan Komunikasi dalam Menunjang Pembelajaran Sekolah Dasar
Authors: Jamun Yohannes Marryono , Ntelok Zephisius Rudiyanto Eso , Ngalu Rudolof
Published: April 2024

Information and Communication Technology (ICT) plays a crucial role in the current educational context, and it must be introduced by teachers to their students. Teachers in this 4.0 era of Education need to adapt to this rapidly. The use of ICT in teaching helps explain challenging and abstract materials in a more tangible and contextual way. Additionally, it aims to overcome communication barriers between educators and learners. The objective of this research is to explore a deep understanding of the importance of ICT in the context of elementary school education. The research method used is a literature review based on the analysis and synthesis of information sources available in the literature or references that are relevant to this research topic. The research results explain that use of ICT as a learning tool in elementary schools has a positive impact on students' learning achievements and can stimulate their interest in learning. The use of ICT also enables more flexible and effective learning in improving the quality of education. However, there are challenges, including the lack of infrastructure and teacher readiness. Nevertheless, the use of ICT at the elementary school level holds great potential for enhancing the quality of education. Therefore, efforts are needed to improve access to the use of ICT in education.
Hubungan Bimbingan Orang Tua Dengan Motivasi Belajar Pendidikan Agama Islam Siswa SDIT Rabbani Rajeg Kabupaten Tangerang
Authors: Zubairi Zubairi , Nurdin Nurdin , Halida Tiara Zain
Published: April 2024

This study aims to investigate the relationship between parental guidance and the motivation to study Islamic Religious Education of students at SDIT Rabbani Rajeg, Tangerang Regency. The research method used is a quantitative research method using a questionnaire as a data collection instrument. The research sample consisted of students at SDIT Rabbani who were selected by simple random sampling. In this study there is a positive and meaningful relationship between parental guidance and student learning motivation (specifically in Islamic Religion subjects), the contribution of x to y is shown by a correlation coefficient of 0.951 with a coefficient of determination of 90%. This means that parents contribute 90% of the learning motivation of SDIT Rabbani students. The sample in this research, the authors determined 40 students out of a total of 153 students. Based on research from Suharsimi Arikunto, namely: "If the subject is less than 100, it is better to take all of them, if the subject is large it can be taken between 10 - 15%, or 20 - 25% or more. 5 The author took a sample of 40 students from 153 students at SDIT Rabbani. The sample technique chosen is random sample or simple random sample. Thus it can be concluded that parental guidance can significantly determine student learning motivation. The results showed that there was a significant relationship between parental guidance and the motivation to study Islamic Religious Education for SDIT Rabbani students. Data analysis revealed that the level of guidance given by parents was positively related to the level of students' learning motivation in dealing with Islamic Religious Education subjects. This research makes an important contribution to the understanding of the role of parents in increasing students' motivation to study Islamic Religious Education. The results of this study indicate that the support, guidance, and attention given by parents can influence students' motivation in learning Islam. Therefore, it takes an active and involved role from parents in providing proper guidance in learning Islam to their children.
Representasi Aktor pada Kasus Penembakan Brigadir Joshua dalam Perspektif Analisis Wacana Theo Van Leeweun
Authors: Fatimah Siti Nur , Yulianto Bambang , Subandiyah Heny
Published: April 2024

This study aims to (1) describe the exclusion process in the shooting of Brigadier Joshua, (2) describe the inclusion process in the shooting of Brigadier Joshua. Criminal news is used as an object of research in the field of language, especially discourse analysis. Theo Van Leeweun's discourse analysis model introduces the way a person (actor) is marginalized in a discourse. This research is limited to Deddy Corbuzier's Youtube podcast video discussing the shooting case of Brigadier Joshua. The results of this study found two exclusion processes, namely passivation and nominalization, while the five inclusion processes include differentiation-differentiation, objectivation-abstraction, nomination-categorization, nomination-identification, and determination-indetermination. So it can be concluded that in this video podcast, the actor is marginalized by exclusion because of the actor's relationship involved in the Brigadier Joshua shooting case. While inclusionary marginalization is carried out to maintain the good name of government agencies that are known to be clean and care for the community.
Penerapan Metode Simpleks untuk Menentukan Keuntungan Maksimum Penjualan Jamu Beras Kencur pada Kelompok Usaha Jamu “Jahe Sribu”
Authors: Untari Erny , Astuti Indra Puji , Susanto Doni
Published: April 2024

In the world of trading, optimization problems include maximizing profits (maximization) or minimizing costs (minimization), both of which can be solved using the simplex method. The aim of this research is to maximize the production profits of the Ginger Sribu herbal business group whose address is Bulu Village, Sukomoro District, Magetan Regency using the simplex method. This research was conducted at the Jahe Sribu herbal medicine house (Nur Rohmiati's mother's house) as a production site for Ginger Sribu herbal medicine. The analysis carried out in this research used the simplex method with the Microsoft Excel solver function. The instruments used were observation and interviews. The results of the research show that there is an optimum production amount for each product (small bottle of kencur rice 250ml, medium 500ml, large 600ml) in the production of the Ginger Sribu herbal medicine business group so as to obtain maximum profits.
Design Thinking Sebagai Metode Inovatif dalam Perancangan Aplikasi M-Physics
Authors: Nurussaniah Nurussaniah , Batita Maurish Sofie Rahmi , Ulfa Saida , Praherdhiono Henry , Sari Ira Nofita
Published: April 2024

In the ever-evolving digital era, learning applications have become indispensable tools in the educational process. This research delves into the utilization of Design Thinking as an innovative methodology for crafting M-Physics applications. The study delineates the steps involved in Design Thinking, which encompass empathy, definition, ideation, and prototyping. The findings demonstrate that Design Thinking aids researchers in gaining a deeper understanding of user needs, articulating problems more precisely, generating creative ideas, and ultimately, devising more innovative solutions. The foundation of the M-Physics prototype design lies in presenting material in a manner that is both succinct and detailed, aligning with the principles of generative learning. M-Physics aims to assist learners, particularly students, in comprehending physics material. Future research should endeavor to complete the Design Thinking process through to the testing stage, ensuring the production of a comprehensive product that truly meets user needs. The insights gleaned from this research are anticipated to be of value to other educational application developers seeking to incorporate a Design Thinking approach into their design processes.
Linguistic Landscape as a Pedagogy of Reading for English Learning: A Case Study of Shop Names in Sidoarjo City
Authors: Hasanah Nurul Uswatun , Munir Ahmad , Setiawan Slamet
Published: April 2024

Learning English does not only occur in the four corners of the classroom, but is possible even within the immediate community of learners. Learning English can be improved through a variety of sources such as the linguistic landscape available. Based on Cenoz and Gorter, LL is particularly on major shopping streets and in commercial areas, which is sometimes the text has only one language, however often has two or more languages (2017). Mainly, in ths research is focused on LL in English language learning as pedagogical resource for young learners. In this case, focusing on senior high school level in Sidoarjo city’s who Javanese as a mother language is. The methodology of this research tha use mix method. Those are qualitative and quantitative method. For the result, the LL in the shop names that written in English is the highest language. Many shop names English language usage as the follows (34%) of the precentage. And the second grade that written in Indonesian languages (30%) score. However, there is no one shop names that written in Javanese. It will be giving a bilingual and trilingual language that used in the shop names written when Javanese language conducted of that. It is a good things that LL can be applied in English language material for learning. Based on the senior high school students’ in Sidoarjo area, there are highest desires can be imply LL in the material of the schools program?
The International Students’ Experiences of Their Intercultural Communication Competence in Indonesia
Authors: Anfas Muhammad Taufiqurrohman , Retnaningdyah Pratiwi , Munir Ahmad
Published: April 2024

The study examined how, in the age of globalization, education had advanced to a new level where the sharing of information had transcended national boundaries and examined intercultural communication competency based on the experiences of foreign students in Indonesia. But educational establishments weren't completely equipped to meet these contemporary demands. Even though intercultural communication research is not new, concerns about emerging cultural diversity have only recently gained a lot of attention. As a result, intercultural communication competency (ICC) in educational sectors is still quite low and needs further investigation. The study used a descriptive qualitative methodology in conjunction with a case and phenomenological investigation strategy. Semi-structured interviews were used to collect the data, along with research material. Through the analysis of the interactive multicultural building model—which is bolstered by the ideas of intercultural communication and the internationalization of higher education—the research findings demonstrate the persistence of disparities and opinions, as well as an evaluation of the three-perspective model that serves as the main focus of the study. It consists of three processes: behavioral (intercultural adeptness), cognitive (intercultural awareness), and emotional (intercultural sensitivity). In addition, there are other difficulties that need to be overcome.
Integrating Social Media Marketing and Brand Gestalt: An Empirical Analysis in Educational Institutions
Authors: Pasuhuk Lefrand S. , Mandagi Deske W
Published: April 2024

This study endeavors to assess the effectiveness of Social Media Marketing (SMM) on the brand gestalt of educational institutions, with a specific focus on universities. In particular, the research aims to examine the impact of SMM on 4S dimensions of brand gestalt: story, sensescape, servicescape, and stakeholders. The research design employed is descriptive causal, utilizing primary data collected through a survey of 209 samples consisting of private university students in North Sulawesi, Indonesia. Data analysis was carried out using Structural Equation Modeling (SEM), supported by the SmartPLS statistical program. The results of the analysis reveal a positive and significant influence of SMM on all four dimensions of brand gestalt: story, sensescape, servicescape, and stakeholders. These findings shed light on the crucial role of social media in shaping robust brand perceptions.
Dampak Pembelajaran Lintas Jurusan pada Program PMM-MBKM
Authors: Jufri Amar , Harfiani Rizka
Published: April 2024

This study aims to analyze the negative and positive impacts of cross-department learning (LINJUR) in the Independent Student Exchange Program 3 (PMM3) at the University of Muhammadiyah Malang (UMM). Through a qualitative approach, this study highlights the challenges faced by PAI students who take part in the program, such as information discrepancies, difficulties in academic adaptation, language and cultural barriers, and difficulties in building relationships. However, there are also positive impacts, such as broadening of horizons and knowledge, development of communication and interpersonal skills, personal growth and adaptation skills, building networks and career opportunities, and increased confidence and initiative. Implications of these findings include the need to provide more accurate information on available courses, better support in the adaptation process, and further exploration of strategies that can maximize the benefits of cross-departmental student exchange programs. This research provides a deep understanding of students' experiences in facing challenges and taking advantage of opportunities in the context of cross-department learning, as well as providing a basis for further development in the implementation of PMM programs.
TRAUMETS TID – ET EKSISTENSPSYKOLOGISK OG KROPSFÆNOMENOLOGISK PERSPEKTIV PÅ DISSOCIATION
Authors: Manon Kristensen Mkandawire  , Anders Essom-Stenz
Published: April 2024

I følgende artikel undersøger vi ved hjælp af eksistenspsykologisk og kropsfænomenologisk teori, hvordan traumatisk dissociation kan forstås på baggrund af tidsbevidsthed og meningsdannelse. Vi gør et forsøg på at beskrive og forstå traumeramtes oplevelse af at befinde sig uden for sig selv, tiden og verden. Vi analyserer kropslig tidsbevidsthed, både i den oprindelige traumatiske situation og i efterfølgende genlevelser. Vores analyse viser, at peritraumatisk- og traumatisk dissociation kan forstås som et kollaps i tidsbevidsthedens intentionelle netværk, hvorved bevidsthedens evne til at strække sig mod fortid og fremtid forringes. Uden en fornemmelse for fortiden og fremtiden udfordres den traumeramtes meningsskabelse i det daglige liv, da en fornemmelse for tidslig kontinuitet er afgørende for oplevelsen af mening. Meningsdannelse sker i intersubjektive relationer og i relation til verden, og disse er betinget af en sammenhængende tidsforståelse. Dissociation influerer således de fleste aspekter i den traumeramtes livsverden.
Følelsernes fylogenese
Authors: Karpatschof Benny
Published: April 2024

Litteraturen om følelseslivet er præget af en betydelig forvirring. Til begrebet følelse er der knyttet en hel række af tilsyneladende uoverstigelige metafysiske spaltninger, og disse spaltninger viser sig også i den uenighed mht terminologi og definitioner inden for udforskningen af følelserne. Artiklen forsøger at manøvrere uden om disse kaotiske tilstande ved at angribe følelseslivet fylogenetisk, idet den hegelianske idé om sammenhængen mellem begrebs- og udviklingslogik søges fastholdt. Udgangspunktet er Leontjews virksomhedsbegreb og hans stadieteori for udviklingen af det psykiske. Herigennem bliver begreberne behov og motivation adskilt fra følelse, og begrebet følelse bliver dels bestemt som en generel evaluering af relationen mellemindivid og omverden, dels underopdelt i tre niveauer, affekt, emotion og værdi.
Substances dangerous to public health according to the Criminal Code of 1922 and 1926: comparative legal analysis and criminal law regulation
Authors: Kukharuk Vladimir Vasilevich
Published: April 2024

The subject of the study is the legislation on illegal actions with narcotic drugs and other substances with generally dangerous properties under the criminal codes of 1922 and 1926 in the context of normative continuity with the Code of Criminal and Correctional Punishments of 1845. A comparative legal analysis of the concepts of poisonous, potent and intoxicating substances as subjects of the relevant crimes of the first Soviet criminal codes and the relevant norms of the current criminal law is carried out. For the first time, archival official documents of the highest state bodies were used to substantiate the high degree of public danger of illegal trafficking of potent and poisonous substances. According to the results of the study, legal science and medicine in the studied period had a developed arsenal of conceptual means of describing illegal trafficking and the consequences of the use of substances that pose a danger to public health. The first Soviet legislator took into account unlimited possibilities in the field of chemical synthesis and therefore considered the list of intoxicating substances to be open, referring to any substances whose qualitative features and actual use corresponded to the literal meaning of their names. The concept of potent substances was generic in relation to the concepts of narcotic drugs and other substances, the defining property of which was the intensity of their effects on the body. The continued use of pre-revolutionary conceptual constructions in modern criminal legislation serves as a normative obstacle to the development of the criminal law institute for the protection of public health based on the norms of international law.
International legal approach to liability and prosecution for concluding and participating in anti-competitive agreements
Authors: Troyanov Yaroslav Olegovich
Published: April 2024

Economic development is one of the main goals of states, state entities and unions. An important place in the development of the economy is to maintain and ensure competition. The legal order and forms of maintaining competition in state entities are different. At the same time, they are all aware of the high public danger of anti-competitive agreements. In this connection, the legislation of most countries and unions (organizations) provides for the prohibition of anti-competitive agreements and serious measures of prosecution for their conclusion. The aim of the work is the author's analysis of the international legal approach to the regulation of liability and prosecution of persons (both legal and physical) for the conclusion and participation in anti-competitive agreements. In this work, the methods of logical and analytical analysis of the legislation of countries, international organizations and unions were used.   According to the results of the study, it can be concluded that the importance (and hence the danger of cartels) of combating anti-competitive agreements is understood in most countries with leading economies. This danger is recognized both at the level of the state itself and at the level of state unions and organizations. The international community pays great attention to the issue of competition. The competition law of developed countries and international organizations in which they are composed is a developed system of effective regulation. In order to optimize the interaction of law enforcement agencies and agencies involved in the fight against cartels, it is necessary to create common information bases, regulate the exchange of documents and information. In our opinion, it seems necessary to develop and implement the institute of joint activities by foreign agencies.
Exploring carp scales (Cyprinus carpio L.) as a novel source of collagen for dental use: Extraction and characterization
Authors: Carolina Dyah Nindita , Satari Mieke Hemiawati , Priosoeryanto Bambang Pontjo , Susanto Agus , Sukotjo Cortino , Kartasasmita Rahmana Emran
Published: April 2024

Previous studies have shown that using bovine and pork collagen in dentistry is associated with various limitations, such as bovine spongiform encephalopathy, transmissible spongiform encephalopathy, and foot and mouth disease. This study aims to examine the extraction and characterization of collagen from common carp (Cyprinus carpio L.) scales, as an alternative source in dentistry. The samples used in this study consisted of common carp (C. carpio L.) scales. In the first step, common carp scales were acid-extracted and spray-dried to isolate collagen. After the collagen had been isolated, it was tested for moisture content, ash, acidity, and functional groups, with Indonesian National Standard (SNI) 8076:2014 as the reference standard. The characterization parameters of the common carp scale collagen powder revealed an 11% yield, 3.66% moisture content, 0.32% ash content, and a pH of 7.38. Furthermore, fourier transform infrared spectroscopy spectra confirmed the presence of a triple helix structure. The extraction of collagen from common carp scales using the acetic acid method and spray drying technique successfully adhered to the composition standards specified by the SNI 8076:2014. Based on these findings, common carp scales could be considered a viable collagen replacement source for applications in dentistry.
Quantum interference and spin transport in M-OPE molecular devices controlled by N or B atom substitution
Authors: Peng Shu-Ping , Deng Shu-Ling , Liu Qian , Dong Cheng-Qi , Fan Zhi-Qiang ,   School of Physics and Electronic Science, Changsha University of Science and Technology, Changsha 410114, China,   College of Environmental Science and Engineering, Nanjing University of Technology, Nanjing 211816, China
Published: April 2024

In this paper, the first-principles method based on density functional theory and non-equilibrium Green’s function is used to investigate the modulation of quantum interference and spin transport in N and B atom substituted meta-phenylene (M-OPE) molecular devices. The zero bias spin transmission spectrum of M-OPE molecular device shows that highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) are located at higher energy positions on both sides of the Fermi level, and there is a clear transmission spectrum valley (anti resonance peak) on the right side of the Fermi level. This indicates that M-OPE molecules are typical destructive quantum interference molecular systems. Research has found that N and B atoms replace carbon atoms at positions 1, 2, and 3 on the central ring of the molecule, which suppress the original destructive quantum interference of M-OPE molecular device to different extents. The substitution of N and B atoms at position 1 has no effect on the original destructive quantum interference of M-OPE molecular device, while the substitution of N and B atoms at positions 2 and 3 significantly suppresses the original destructive quantum interference of M-OPE molecular device. Therefore, there is a significant difference in the electrical conductivity of devices with N and B atoms at different positions, with the order of electrical conductivity values being N2 > N3 > N1 and B2 > B3 > B1. In this study, it is also found that the spin current value of device with B atom substitution is significantly higher than that of device with N atom substitution. After the substitution of B atom at position 2, the spin current value of the device under negative bias is significantly greater than that under positive bias, exhibiting a significant spin rectification effect. Based on the extended curled arrow rule proposed by O’Driscoll et al. to predict the behavior of quantum interference effects, we explain the physical mechanism by which N and B protons at different positions have different effects on the suppression of quantum interference in M-OPE molecular device. The results of the quantum interference and spin transport regulation of molecular systems by the substitution of B and N atoms can provide theoretical guidance for realizing the further application of heterocyclic aromatic hydrocarbons in molecular electronics.
A concerted increase in readthrough and intron retention drives transposon expression during aging and senescence
Authors: Pabis Kamil , Barardo Diogo , Sirbu Olga , Selvarajoo Kumar , Gruber Jan , Kennedy Brian K
Published: April 2024

Aging and senescence are characterized by pervasive transcriptional dysfunction, including increased expression of transposons and introns. Our aim was to elucidate mechanisms behind this increased expression. Most transposons are found within genes and introns, with a large minority being close to genes. This raises the possibility that transcriptional readthrough and intron retention are responsible for age-related changes in transposon expression rather than expression of autonomous transposons. To test this, we compiled public RNA-seq datasets from aged human fibroblasts, replicative and drug-induced senescence in human cells, and RNA-seq from aging mice and senescent mouse cells. Indeed, our reanalysis revealed a correlation between transposons expression, intron retention, and transcriptional readthrough across samples and within samples. Both intron retention and readthrough increased with aging or cellular senescence and these transcriptional defects were more pronounced in human samples as compared to those of mice. In support of a causal connection between readthrough and transposon expression, analysis of models showing induced transcriptional readthrough confirmed that they also show elevated transposon expression. Taken together, our data suggest that elevated transposon reads during aging seen in various RNA-seq dataset are concomitant with multiple transcriptional defects. Intron retention and transcriptional readthrough are the most likely explanation for the expression of transposable elements that lack a functional promoter.
Ligand bias underlies differential signaling of multiple FGFs via FGFR1
Authors: Karl Kelly , Del Piccolo Nuala , Light Taylor , Roy Tanaya , Dudeja Pooja , Ursachi Vlad-Constantin , Fafilek Bohumil , Krejci Pavel , Hristova Kalina
Published: April 2024

The differential signaling of multiple FGF ligands through a single fibroblast growth factor (FGF) receptor (FGFR) plays an important role in embryonic development. Here, we use quantitative biophysical tools to uncover the mechanism behind differences in FGFR1c signaling in response to FGF4, FGF8, and FGF9, a process which is relevant for limb bud outgrowth. We find that FGF8 preferentially induces FRS2 phosphorylation and extracellular matrix loss, while FGF4 and FGF9 preferentially induce FGFR1c phosphorylation and cell growth arrest. Thus, we demonstrate that FGF8 is a biased FGFR1c ligand, as compared to FGF4 and FGF9. Förster resonance energy transfer experiments reveal a correlation between biased signaling and the conformation of the FGFR1c transmembrane domain dimer. Our findings expand the mechanistic understanding of FGF signaling during development and bring the poorly understood concept of receptor tyrosine kinase ligand bias into the spotlight.
Yeast cell responses and survival during periodic osmotic stress are controlled by glucose availability
Authors: Duveau Fabien , Cordier Céline , Chiron Lionel , Le Bec Matthias , Pouzet Sylvain , Séguin Julie , Llamosi Artémis , Sorre Benoit , Di Meglio Jean-Marc , Hersen Pascal
Published: April 2024

Natural environments of living organisms are often dynamic and multifactorial, with multiple parameters fluctuating over time. To better understand how cells respond to dynamically interacting factors, we quantified the effects of dual fluctuations of osmotic stress and glucose deprivation on yeast cells using microfluidics and time-lapse microscopy. Strikingly, we observed that cell proliferation, survival, and signaling depend on the phasing of the two periodic stresses. Cells divided faster, survived longer, and showed decreased transcriptional response when fluctuations of hyperosmotic stress and glucose deprivation occurred in phase than when the two stresses occurred alternatively. Therefore, glucose availability regulates yeast responses to dynamic osmotic stress, showcasing the key role of metabolic fluctuations in cellular responses to dynamic stress. We also found that mutants with impaired osmotic stress response were better adapted to alternating stresses than wild-type cells, showing that genetic mechanisms of adaptation to a persistent stress factor can be detrimental under dynamically interacting conditions.
Warming and altered precipitation independently and interactively suppress alpine soil microbial growth in a decadal-long experiment
Authors: Ruan Yang , Ling Ning , Jiang Shengjing , Jing Xin , He Jin-Sheng , Shen Qirong , Nan Zhibiao
Published: April 2024

Warming and precipitation anomalies affect terrestrial carbon balance partly through altering microbial eco-physiological processes (e.g., growth and death) in soil. However, little is known about how such processes responds to simultaneous regime shifts in temperature and precipitation. We used the
18
O-water quantitative stable isotope probing approach to estimate bacterial growth in alpine meadow soils of the Tibetan Plateau after a decade of warming and altered precipitation manipulation. Our results showed that the growth of major taxa was suppressed by the single and combined effects of temperature and precipitation, eliciting 40-90% of growth reduction of whole community. The antagonistic interactions of warming and altered precipitation on population growth were common (~70% taxa), represented by the weak antagonistic interactions of warming and drought, and the neutralizing effects of warming and wet. The members in
Solirubrobacter
and
Pseudonocardia
genera had high growth rates under changed climate regimes. These results are important to understand and predict the soil microbial dynamics in alpine meadow ecosystems suffering from multiple climate change factors.
Integrative analysis of DNA replication origins and ORC-/MCM-binding sites in human cells reveals a lack of overlap
Authors: Tian Mengxue , Wang Zhenjia , Su Zhangli , Shibata Etsuko , Shibata Yoshiyuki , Dutta Anindya , Zang Chongzhi
Published: April 2024

Based on experimentally determined average inter-origin distances of ~100 kb, DNA replication initiates from ~50,000 origins on human chromosomes in each cell cycle. The origins are believed to be specified by binding of factors like the origin recognition complex (ORC) or CTCF or other features like G-quadruplexes. We have performed an integrative analysis of 113 genome-wide human origin profiles (from five different techniques) and five ORC-binding profiles to critically evaluate whether the most reproducible origins are specified by these features. Out of ~7.5 million union origins identified by all datasets, only 0.27% (20,250 shared origins) were reproducibly obtained in at least 20 independent SNS-seq datasets and contained in initiation zones identified by each of three other techniques, suggesting extensive variability in origin usage and identification. Also, 21% of the shared origins overlap with transcriptional promoters, posing a conundrum. Although the shared origins overlap more than union origins with constitutive CTCF-binding sites, G-quadruplex sites, and activating histone marks, these overlaps are comparable or less than that of known transcription start sites, so that these features could be enriched in origins because of the overlap of origins with epigenetically open, promoter-like sequences. Only 6.4% of the 20,250 shared origins were within 1 kb from any of the ~13,000 reproducible ORC-binding sites in human cancer cells, and only 4.5% were within 1 kb of the ~11,000 union MCM2-7-binding sites in contrast to the nearly 100% overlap in the two comparisons in the yeast, Saccharomyces cerevisiae. Thus, in human cancer cell lines, replication origins appear to be specified by highly variable stochastic events dependent on the high epigenetic accessibility around promoters, without extensive overlap between the most reproducible origins and currently known ORC- or MCM-binding sites.
The embryonic role of juvenile hormone in the firebrat, Thermobia domestica, reveals its function before its involvement in metamorphosis
Authors: Truman James W , Riddiford Lynn M , Konopova Barbora , Nouzova Marcela , Noriega Fernando G , Herko Michelle
Published: April 2024

To gain insights into how juvenile hormone (JH) came to regulate insect metamorphosis, we studied its function in the ametabolous firebrat, Thermobia domestica. Highest levels of JH occur during late embryogenesis, with only low levels thereafter. Loss-of-function and gain-of-function experiments show that JH acts on embryonic tissues to suppress morphogenesis and cell determination and to promote their terminal differentiation. Similar embryonic actions of JH on hemimetabolous insects with short germ band embryos indicate that JH’s embryonic role preceded its derived function as the postembryonic regulator of metamorphosis. The postembryonic expansion of JH function likely followed the evolution of flight. Archaic flying insects were considered to lack metamorphosis because tiny, movable wings were evident on the thoraces of young juveniles and their positive allometric growth eventually allowed them to support flight in late juveniles. Like in Thermobia, we assume that these juveniles lacked JH. However, a postembryonic reappearance of JH during wing morphogenesis in the young juvenile likely redirected wing development to make a wing pad rather than a wing. Maintenance of JH then allowed wing pad growth and its disappearance in the mature juvenile then allowed wing differentiation. Subsequent modification of JH action for hemi- and holometabolous lifestyles are discussed.
Ocular dominance-dependent binocular combination of monocular neuronal responses in macaque V1
Authors: Zhang Sheng-Hui , Zhao Xing-Nan , Jiang Dan-Qing , Tang Shi-Ming , Yu Cong
Published: April 2024

Primates rely on two eyes to perceive depth, while maintaining stable vision when either one eye or both eyes are open. Although psychophysical and modeling studies have investigated how monocular signals are combined to form binocular vision, the underlying neuronal mechanisms, particularly in V1 where most neurons exhibit binocularity with varying eye preferences, remain poorly understood. Here, we used two-photon calcium imaging to compare the monocular and binocular responses of thousands of simultaneously recorded V1 superficial-layer neurons in three awake macaques. During monocular stimulation, neurons preferring the stimulated eye exhibited significantly stronger responses compared to those preferring both eyes. However, during binocular stimulation, the responses of neurons preferring either eye were suppressed on the average, while those preferring both eyes were enhanced, resulting in similar neuronal responses irrespective of their eye preferences, and an overall response level similar to that with monocular viewing. A neuronally realistic model of binocular combination, which incorporates ocular dominance-dependent divisive interocular inhibition and binocular summation, is proposed to account for these findings.
Expanding the Drosophila toolkit for dual control of gene expression
Authors: Zirin Jonathan , Jusiak Barbara , Lopes Raphael , Ewen-Campen Benjamin , Bosch Justin A , Risbeck Alexandria , Forman Corey , Villalta Christians , Hu Yanhui , Perrimon Norbert
Published: April 2024

The ability to independently control gene expression in two different tissues in the same animal is emerging as a major need, especially in the context of inter-organ communication studies. This type of study is made possible by technologies combining the GAL4/UAS and a second binary expression system such as the LexA system or QF system. Here, we describe a resource of reagents that facilitate combined use of the GAL4/UAS and a second binary system in various Drosophila tissues. Focusing on genes with well-characterized GAL4 expression patterns, we generated a set of more than 40 LexA-GAD and QF2 insertions by CRISPR knock-in and verified their tissue specificity in larvae. We also built constructs that encode QF2 and LexA-GAD transcription factors in a single vector. Following successful integration of this construct into the fly genome, FLP/FRT recombination is used to isolate fly lines that express only QF2 or LexA-GAD. Finally, using new compatible shRNA vectors, we evaluated both LexA and QF systems for in vivo gene knockdown and are generating a library of such RNAi fly lines as a community resource. Together, these LexA and QF system vectors and fly lines will provide a new set of tools for researchers who need to activate or repress two different genes in an orthogonal manner in the same animal.
A metabolic modeling-based framework for predicting trophic dependencies in native rhizobiomes of crop plants
Authors: Ginatt Alon Avraham , Berihu Maria , Castel Einam , Medina Shlomit , Carmi Gon , Faigenboim-Doron Adi , Sharon Itai , Tal Ofir , Droby Samir , Somera Tracey , Mazzola Mark , Eizenberg Hanan , Freilich Shiri
Published: April 2024

The exchange of metabolites (i.e., metabolic interactions) between bacteria in the rhizosphere determines various plant-associated functions. Systematically understanding the metabolic interactions in the rhizosphere, as well as in other types of microbial communities, would open the door to the optimization of specific predefined functions of interest, and therefore to the harnessing of the functionality of various types of microbiomes. However, mechanistic knowledge regarding the gathering and interpretation of these interactions is limited. Here, we present a framework utilizing genomics and constraint-based modeling approaches, aiming to interpret the hierarchical trophic interactions in the soil environment. 243 genome scale metabolic models of bacteria associated with a specific disease-suppressive vs disease-conducive apple rhizospheres were drafted based on genome-resolved metagenomes, comprising an in silico native microbial community. Iteratively simulating microbial community members’ growth in a metabolomics-based apple root-like environment produced novel data on potential trophic successions, used to form a network of communal trophic dependencies. Network-based analyses have characterized interactions associated with beneficial vs non-beneficial microbiome functioning, pinpointing specific compounds and microbial species as potential disease supporting and suppressing agents. This framework provides a means for capturing trophic interactions and formulating a range of testable hypotheses regarding the metabolic capabilities of microbial communities within their natural environment. Essentially, it can be applied to different environments and biological landscapes, elucidating the conditions for the targeted manipulation of various microbiomes, and the execution of countless predefined functions.
The E3 ubiquitin ligase RNF220 maintains hindbrain Hox expression patterns through regulation of WDR5 stability
Authors: Wang Huishan , Liu Xingyan , Liu Yamin , Yang Chencheng , Ye Yaxin , Yu Xiaomei , Sheng Nengyin , Zhang Shihua , Mao Bingyu , Ma Pengcheng
Published: April 2024

The spatial and temporal linear expression of Hox genes establishes a regional Hox code, which is crucial for the antero-posterior (A-P) patterning, segmentation, and neuronal circuit development of the hindbrain. RNF220, an E3 ubiquitin ligase, is widely involved in neural development via targeting of multiple substrates. Here, we found that the expression of Hox genes in the pons was markedly up-regulated at the late developmental stage (post-embryonic day E15.5) in Rnf220-/- and Rnf220+/- mouse embryos. Single-nucleus RNA sequencing (RNA-seq) analysis revealed different Hox de-repression profiles in different groups of neurons, including the pontine nuclei (PN). The Hox pattern was disrupted and the neural circuits were affected in the PN of Rnf220+/- mice. We showed that this phenomenon was mediated by WDR5, a key component of the TrxG complex, which can be polyubiquitinated and degraded by RNF220. Intrauterine injection of WDR5 inhibitor (WDR5-IN-4) and genetic ablation of Wdr5 in Rnf220+/- mice largely recovered the de-repressed Hox expression pattern in the hindbrain. In P19 embryonal carcinoma cells, the retinoic acid-induced Hox expression was further stimulated by Rnf220 knockdown, which can also be rescued by Wdr5 knockdown. In short, our data suggest a new role of RNF220/WDR5 in Hox pattern maintenance and pons development in mice.
Single-cell RNA sequencing of iPSC-derived brain organoids reveals Treponema pallidum infection inhibiting neurodevelopment
Authors: Xu Qiu-Yan , Wang Yong-Jing , He Yun , Zheng Xin-Qi , Tong Man-Li , Lin Yu , Yang Tian-Ci
Published: April 2024

Congenital syphilis is a vertically transmitted bacterial infection caused by Treponema pallidum , often causing multidomain neurodevelopmental disabilities. However, little is known about the pathogenesis of this disease. Brain organoids platform derived from the induced pluripotent stem cell (iPSC) is employed and exposed to T. pallidum infection for modelling congenital neurodevelopmental impairment. Single-cell RNA sequencing is used for identifying the subpopulations of differentially expressed genes and cellular heterogeneity and reconstructing differentiation trajectories following T. pallidum infection. The results reveal that T. pallidum infection influences the formation of neural rosette structures, reduces the cell number of the neural progenitor cell subcluster 1B (subNPC1B) and hindbrain neurons, and affects the neurodevelopment of the brain organoid. Moreover, it is speculated that T. pallidum inhibit the hindbrain neuron cell number through the suppression of subNPC1B subgroup in the organoids and inhibits transcription factor 3 activity in the subNPC1B-hindbrain neuronal axis. This is the first report on the inhibited effects of T. pallidum on the neurodevelopment of the iPSC-derived brain organoid model. It is concluded that T. pallidum could inhibit the differentiation of subNPC1B in brain organoids, thereby reducing the differentiation from subNPC1B to hindbrain neurons, and ultimately affecting the development and maturation of hindbrain neurons.