bluuebunny/crossref_metadata_2025 huggingface dataset:
Pengaruh Profitabilitas, Risiko Finansial dan Harga Saham Terhadap Nilai Perusahaan Bank Syariah Indonesia (BSI) Di BEI Periode Tahun 2014 - 2021
Authors: Hartini Hartini , Marhandrie Dessy
Published: July 2024

ROA (Return On Assets) having for positive signifikan to assess firm. This matter that if ROA ascends therefore followed by its rise assesses firm. DER (Debt to Equity Ratio) having for positive and signifikan to assess firm. This matter if DER ascends therefore firm point will come on rise. Positive influential stock price and signifikan to assess firm. This matter if stock price ascends therefore firm point will come on rise. ROA, DER and ala stock price simultan (jointly) having for positive and signifikan to assess firm. For investor: one that wants to get investment on Syariah's Bank stock Indonesian to notice fundamental factor as DER and basal ROA judgment gets investment on sectorallies it, since in height DER can make firm point also increases. So even with ROA, in height ROA therefore firm point also tall. For firm: that more notices, keep and increases DER and ROA, since DER and ROA has influence that signifikan to assess firm. So corporate point thus gets increasingly.
Entrepreneurial Readiness of Inmates at The Women's Penitentiary Through Entrepreneurship Education And Self-Efficacy
Authors: Aspiannor Akhmad
Published: July 2024

This research aims to examine the influence of entrepreneurship education and self-efficacy on the entrepreneurial readiness of inmates at the Martapura Class IIA Women's Penitentiary. The sample consists of 86 individuals who have undergone entrepreneurship education or training at the Martapura Class IIA Women's Penitentiary. The first hypothesis states that entrepreneurship education has a significant influence on entrepreneurial readiness, with a t-value of 5.319 > 1.666 at a significance level of 0.000 < 0.05. The second hypothesis states that self-efficacy has a significant influence on entrepreneurial readiness, with a t-value of 4.564 > 1.666 at a significance level of 0.000 < 0.05. The third hypothesis states that entrepreneurship education and self-efficacy together have a significant influence on entrepreneurial readiness, with an F-value of 41.444 > F-table 3.09 at a significance level of 0.000 < 0.05. This research indicates that entrepreneurship education and self-efficacy have a positive and significant impact on the entrepreneurial readiness of inmates at the Martapura Class IIA Women's Penitentiary
Analysis Of The Effect Of Organizational Culture On Performance Of Employees (Case Study Of The Kominfo Office Of Pariaman City)
Authors: Mulia Rizki Afri , Putri Rianda Prima , Saputra Nika
Published: July 2024

This study aims to analyze, Influence Organizational Culture Against Employee Performance At the Office of Communications and Information Technology of Pariaman. This research is a quantitative research that shows a causal relationship. The sample in this study were 47 employees. Data collection techniques used were observation, questionnaire and documentation. Data analysis techniques used are descriptive statistical analysis using percentages, averages, and standard deviations and for inferential statistical analysis using data normality tests, simple linear regression analysis, and product moment correlation analysis. The results of the study show that the organizational culture is in a very good category in terms of indicators, namely: Innovation and Courage to take risks; Attention to detail; Results oriented; Human oriented; Team oriented; Aggressive; and stable. Employee performance is in a very good category in terms of indicators of discipline of service personnel, responsibility of service personnel, ability of service personnel, politeness and friendliness of officers, based on simple linear regression analysis shows that there is an influence of organizational culture on employee performance at the Pariaman City Communication and Information Agency Pariaman City. From the results of product moment correlation analysis obtained a significant level of relationship between the influence of organizational culture on the performance of employees at the Office of Communication and Information Office of , Pariaman City with the Strong category.
Implementasi Prinsip-Prinsip Good Governance Dalam Pelayanan Pembuatan E-KTP Pada Dinas Kependudukan dan Pencatatan Sipil (DUKCAPIL) Kabupaten Kerinci
Authors: Andayani Meri , Lanin Dasman
Published: July 2024

Implementasi Prinsip-Prinsip Good Governance Dalam Pelayanan Pembuatan e-KTP Pada Dinas Kependudukan Dan Pencatatan Sipil  (DUKCAPIL) Kabupaten Kerinci. Adapun tujuan dari penelitian ini adalah untuk mengetahui implementasi prinsip-prinsip good governance dalam pelayanan Pembuatan e-KTP  Pada Dinas Kependudukan Dan Pencatatan Sipil  (DUKCAPIL) Kabupaten Kerinci. Metode penelitian yang dipakai adalah metode pendekatan kualitatif. Informan dalam penelitian ini berasal dari Kepala Dinas, Sekretaris  dan Pegawai pada Pada Dinas Kependudukan Dan Pencatatan Sipil  (DUKCAPIL) Kabupaten Kerinci. Instrumen penelitian adalah peneliti sendiri dan pengumpulan data melalui wawancara dan observasi lapangan. Implementasi Prinsip-Prinsip Good Governance Dalam Pelayanan Pembuatan e-KTP Pada Dinas Kependudukan Dan Pencatatan Sipil (DUKCAPIL) Kabupaten Kerinci  ini mencakup prinsip-prinsip good governance dalam pelayanan e-KTP. Berdasarkan hasil wawancara dan observasi langsung ke Kantor (DUKCAPIL) Kabupaten Kerinci tentang pelayanan pembuatan e-KTP pada (DUKCAPIL) Kabupaten  Kerinci dari semua indikator sudah hampir mendekati baik. namun masih ada juga ditemukan berbagai kekurangan dan kelemahan dalam pelaksanaannya.
Upaya Keberatan Atas Putusan Badan Penyelesaian Sengketa Konsumen Dalam Kasus Penarikan Unit Kendaraan Bermotor
Authors: Sembiring Susanti , Pratama Bisma Putra
Published: July 2024

Badan Penyelesaian Sengketa Konsumen merupakan lembaga penunjang dalam bidang quasi peradilan. Oleh karenanya, putusan BPSK mestinya harus dipandang sebagai putusan yang mempunyai kekuatan hukum yang tetap. Namun, apabila dibandingkan prinsip (res judicata pro vitatate habetur) tersebut dengan Pasal 56 Ayat (2) UUPK, ternyata para pihak masih bias mengajukan keberatan ke Pengadilan Negeri. Kejadian tersebut disebabkan karena lemahnya kedudukan dan kewenangan yang diberikan oleh UUPK terhadap BPSK terutama menyangkut putusan yang bersifat final dan mengikat.. Permasalahan yang diangkat dalam penelitian ini adalah bagaimanakah mekanisme upaya keberatan atas putusan Badan Penyelesaian Sengketa Konsumen (BPSK) di Pengadilan Negeri Kelas IA Padang. Spesifikasi penelitian ini adalah merupakan penelitian yang bersifat deskriptif analitis. Metode pendekatan yang digunakan adalah yuridis normatif sebagai pendekatan utama dan didukung pendekatan yuridis empiris. Data yang digunakan adalah data sekunder dan data primer. Data yang didapat dianalisis secara kualitatif dan disajikan secara deskriptif analitis. Berdasarkan penelitian dan pembahasan dapat diketahui bahwa mekanisme upaya keberatan atas putusan BPSK di PN Kelas IA Padang dapat dilakukan apabila terdapat salah satu pihak yang beperkara menganggap bahwa putusan BPSK tidak berhasil sehingga dapat mengajukan keberatan ke PN Kelas IA Padang dengan catatan setelah terpenuhinya persyaratan pemohon keberatan dapat mengajukan keberatan dan pengajuan keberatan masih dalam tenggang waktu yang ditentukan yakni 14 hari sejak putusan BPSK diumumkan dan jika PN menerima pengajuan keberatan maka dalam waktu paling lama 21 hari akan diberikan putusan, sehingga mekanisme dari upaya hukum keberatan itu sendiri berjalan lebih cepat jika dibandingkan dengan gugatan baru maupun banding yang memerlukan waktu yang lebih lama.
Management of the Smart Indonesia Program of the Ministry of Education and Culture for Junior High School Students
Authors: Fadhlan Fadhlan
Published: July 2024

This research aims to determine the management of the Smart Indonesia Program in junior high schools throughout Sawahlunto City. This type of research is qualitative. The data sources in this research are data on the implementation of the Smart Indonesia Program (PIP) in junior high schools as well as direct field observations. The research informants were 21 (twenty-one) people, consisting of the Head of the Education Department, the Head of the Basic Education Division, the Head of Curriculum and Student Section, the Education Service Operator, the Principal, the School Operator, and the Community. The researcher's main data collection techniques were observation, interviews, and document study. The results of the research conclude that it is not yet optimal. Judging from the results of the research regarding the proposal, determination, distribution, and collection of funds, there are still obstacles when implementing the management of the Smart Indonesia Program in junior high schools. Because there are still many obstacles that occur in the implementation of the Smart Indonesia Program, management needs to be improved so that management of the Smart Indonesia Program is more effective and better.
Implementasi Kebijakan Smart City Dalam Era Revolusi Industri 4.0 di Masa Pandemi Covid-19
Authors: Simanjorang Yuniara , Sukmawati Nur
Published: July 2024

Smart city adalah kota pintar yang dirancang untuk membantu berbagai aktivitas masyarakat dan memberikan kemudahan akses informasi bagi masyarakat di Indonesia. Seiring berjalannya waktu, perkembangan zaman dan teknologi dapat menghadirkan informasi kepada masyarakat melalui sebuah aplikasi. Revolusi Industri 4.0 memberikan peluang penguasaan teknologi sebagai kunci penentu daya saing bangsa. Pendekatan pembangunan yang memaknai kerangka smart city semakin menemukan relevansinya selama pandemi Covid-19. Ketika protokol kesehatan harus diterapkan dan membatasi tatap muka, terjadi perubahan gaya hidup yang luar biasa. Implementasi kebijakan smart city bertujuan untuk memandu kabupaten/kota dalam menyusun masterplan Smart City untuk memaksimalkan pemanfaatan teknologi, baik dalam meningkatkan pelayanan publik maupun mengakselerasi potensi yang ada di masing-masing daerah. Metode penelitian yang digunakan dalam penelitian ini adalah deskriptif dengan pendekatan literature review. Informasi diperoleh dari situs resmi Berita, artikel akademik dan sumber lain yang dianggap relevan. Maka dapat disimpulkan dari hasil penelitian Smart City ini yang menekankan pada tiga konsep, yang pertama penerapan sistem pemerintahan daerah dalam mengelola masyarakat perkotaan, kedua memerlukan pengelolaan wilayah atas seluruh sumber daya secara efektif dan efisien dan ketiga smart city diharapkan mampu menjalankan fungsi penyediaan informasi secara tepat kepada masyarakat dan mampu mengantisipasi kejadian. yang tak terduga selama pandemi Covid-19.
Systematic Literature Review: Implementasi Prinsip-prinsip Administrasi Keuangan di Indonesia
Authors: Erbara Acil , Takdir Muhammad
Published: July 2024

Sebuah tinjauan sistematis dari literatur administrasi publik tentang implementasi prinsip-prinsip administrasi keuangan publik di Indonesia dilakukan dengan maksud untuk mengklasifikasikan, meiringkas, dan mengungkapkan efektivitas pengendalian anggaran, pengaruh penerapan anggaran berbasis kinerja, kualitas sumber daya manusia, aspek akuntabilitas publik, pencapaian kinerja anggaran dan transparansi dalam mencapai tujuan anggaran secara efetif dan efisien di sektor publik. Metode yang digunakan dalam penelitian ini adalah Metode Systematic Literature Review (SLR). Metode SLR digunakan untuk mengidentifikasi, mengkaji, mengevaluasi, dan menafsirkan semua penelitian yang tersedia dengan bidang topik fenomena yang menarik, dengan pertanyaan penelitian tertentu yang relevan. Dengan penggunaan Metode SLR dapat dilakukan review dan identifikasi jurnal secara sistematis, yang pada setiap prosesnya mengikuti langkah-langkah atau protokol yang telah ditetapkan. Adapun Jumlah artikel yang ditemukan sebanyak 56 artikel dengan karakteristik sesuai target penelitian, kemudian melalui proses screening diambil 30 artikel, setelah itu tahapan selanjutnya kriteria inklusi eksklusi sehingga ditemukan 25 artikel untuk selanjutnya dilakukan review. Hasil penelitian menunjukkan bahwa platform yang dominan digunakan dalam pengembangan sistem informasi adalah berbasis website sedangkan metode dominan digunakan dalam menyelesaikan pengembangan sistem informasi adalah metode terstruktur.
Implementasi Program Usaha Peningkatan Pendapatan Keluarga Sejahtera (UPPKS) Untuk Pemberdayaan Masayarakat Miskin di Kota Padang Panjang
Authors: Mardhatillah Muntaha
Published: July 2024

This study aims to determine how the process of implementing a business program to increase the income of a prosperous family in the city of Padang Panjang, identify the obstacles encountered and determine the efforts taken to overcome the obstacles in implementing the program. This research is motivated by not all people from the poor who are included, efforts are not carried out collectively, the lack of participation from the III plus prosperous family group to want to act as a foster father, the amount of capital provided by the government is insufficient in carrying out UPPKS activities and frequent capital. in the wrong use for consumptive purposes. The method used in the research is qualitative using descriptive methods because the research provides a description of the situation as it should be. The selection of informants was carried out by purposive sampling. The types of data are primary data and secondary data which are collected through observation, interview and documentation study. The validity test was carried out through source triangulation. Then the data analysis techniques used can be grouped into 3 stages, namely data reduction, presentation and drawing conclusions. The findings of the study indicate that the implementation of the UPPKS program is in accordance with existing procedures but has not been fully able to improve the welfare of its members and has not been optimal. This can be seen from the fact that constraints are still found in implementation, the obstacles faced in implementing the UPPKS program in the City of Padang Panjang can be categorized into two forms, namely internal constraints and external constraints. Internal constraints include weak supervision of the program, lack of capital sourced from the government, uneven coaching. And external obstacles include the use of aid funds that have not been maximized, the lack of creativity and innovation of several groups in finding and utilizing sources of funds, delays in repaying loans. To overcome obstacles in the process of implementing the UPPKS program, efforts were made, including prosperous families III as foster fathers in groups, providing guidance, and obstacles originating from program participants, such as guidance regarding the real goals of the UPPKS program, implementing a ball pick-up system. against members who are stuck in payment.
Perlindungan Terhadap Konsumen Kosmetik Ilegal Yang Mengandung Zat Berbahaya
Authors: Sembiring Susanti , Pratama Bisma Putra
Published: July 2024

Saat ini banyak pelaku usaha yang tidak bertanggungjawab untuk meraih keuntungan lebih dengan memproduksi atau memperdagangkan kosmetik yang tidak memenuhi persyaratan untuk diedarkan. Kosmetik impor ilegal yang mengandung zat aditif tentu menjadi salah satu ancaman bagi konsumen para pengguna kosmetik, terlebih kosmetik saat ini sudah menjadi kebutuhan pokok bagi manusia. Saat ini banyak beredar kosmetik yang mengandung bahan berbahaya khususnya kosmetik impor. Adapun tujuan dari penelitian ini adalah untuk mengetahui bentuk perlindungan hukum konsumen kosmetik impor ilegal yang mengandung zat aditif ditinjau dari Undang-Undang Nomor 8 Tahun 1999 tentang perlindungan konsumen. Penelitian ini menggunakan metode penelitian normatif dengan pendekatan perundang-undangan yang bersifat deskriptif. Sumber data penelitian ini menggunakan data primer berupa peraturan perundang-undangan dan data sekunder dari bahan kepustakaan. Data di uraikan dalam bentuk teks naratif secara sistematis. Metode analisis data yang digunakan adalah metode kualitatif. Hasil penelitian menunjukkan faktor-faktor yang membuat peredaran kosmetik impor ilegal yang mengandung zat aditif terus berkembang hingga saat ini adalah pertama kecenderungan masyarakat membeli produk kosmetik secara online hal ini dapat menjadi celah bagi para pelaku usaha kosmetik impor ilegal untuk selalu bisa memasarkan produknya, kedua, pola pikir masyarakat pada hasil instan, ini bisa menjadi salah satu pemicu maraknya peredaran produk kosmetik yang mengandung zat berbahaya atau bahan berbahaya karena pihak produsen akan selalu mengikuti kemauan pasar jika pasar menginginkan sebuah produk dengan hasil instan maka zat berbahaya akan menjadi pilihan para produsen demi mengikuti arus pasar.
Implementation of the Silungkang Songket Development Program with Natural Dyeing by the Koperindag Department in Sawahlunto City
Authors: Nazirwan Nazirwan , Tovalini Krismena , Andini Surya
Published: July 2024

The aim of the research is to find out an overview of the implementation of the Silungkang songket development program with natural dyeing by the Koperindag Department in Sawahlunto City. The importance of implementation is to understand the implementation of the Silungkang songket development program policy with natural dyeing by the Cooperative Industry and Trade Service in Sawahlunto City, namely the synergy between UKM actors and the Sawahlunto City Government, which acts as a regulator and facilitator in empowering songket craftsmen so that they are able to increase the ability of Silungkang songket craftsmen with natural dyeing. The research method uses a qualitative-descriptive approach, with the type of data collection carried out through interviews with the Head of the Sawahlunto City Cooperative Industry and Trade Service, the Head of the Sawahlunto City Bappeda, the Sawahlunto City Cooperative Industry and Trade Head, Sawahlunto City IKM TPL, Silungkang songket craftsmen with natural dyeing, and the community around the central area. The research results show why the implementation of the Silungkang Songket Development Program with Natural Dyeing by the Koperindag Department in Sawahlunto City has not been optimal due to the lack of clarity in the SOP, limited human resources, inadequate supporting facilities and infrastructure, access to capital sources that is still limited, the absence of UPT and third parties for business development, and socialization and coordination that are not yet massive.
Analysis of the Village Head Replacement Mechanism Based on Law Number 6 of 2014 concerning Villages and Derivative Regulations
Authors: Suryaningsih Suryaningsih , Krisnawansyah Yahya , Zamhasari Zamhasari , Gafar Tengku Fahrul , Octavia Santi
Published: July 2024

Law no. 6 of 2014 concerning villages regulates the appointment and dismissal of village heads. In carrying out the mandate for 6 years, it cannot be denied that along the way the village head will die, resign or be dismissed for one reason or another. Law no. 6/2014 does not regulate in detail the mechanism for replacing the village head. The replacement mechanism is regulated in derivative regulations, such as government regulations (PP) and several Minister of Home Affairs regulations. This article will analyze the mechanism for replacing village heads as regulated in the village law and its derivatives. The results of the research show that Law no. 6 of 2014 and its derivative regulations stipulate that if the village head dies, resigns from his position, and fulfills one of the conditions for being dismissed, the BPD reports to the regent via the sub-district head. The regent/mayor will make a decision to permanently dismiss the village head. The replacement of the village head then looks at 2 things, firstly, if the remaining term of office of the dismissed village head is less than 1 year, then leadership in the village will be held by the acting village head until the village head election. However, if the remaining term of office of the village head is more than 1 year, then leadership in the village is held by the acting village head until the village head is elected at the village meeting.
O efeito de variáveis macrossociais e macroeconómicas sobre a criminalidade: o caso português
Authors: Ferreira Eduardo Viegas
Published: July 2024

Este estudo analisou o efeito da variação do rendimento, da desigualdade na distribuição do mesmo, da privação relativa e severa, das qualificações académicas, do emprego por profissões, da concentração da população em regiões urbanas, do envelhecimento da população, da incidência do uso de drogas e da imigração sobre a variação verificada, em Portugal, em onze grupos de crimes. Os resultados obtidos apontam para efeitos das qualificações académicas sobre os crimes registados contra a propriedade, contra a vida e integridade física e de condução, bem como para efeitos do produto interno bruto por residente, da idade média da população, das profissões, da urbanização, da desigualdade na distribuição do rendimento e da imigração.
Canónicos, anticanónicos, e nenhum cânone em absoluto: ir “para além do cânone” ou escrutinar as opções anticanónicas?
Authors: Oliveira Nuno
Published: July 2024

Respaldando-me na reflexão que um caso concreto suscitou, neste artigo pretendo refutar algumas das reivindicações dos críticos do cânone sociológico, salientando três vícios lógicos no seu raciocínio que designo por facilitismos. Em contrapartida, sugiro três critérios de acesso ao cânone que podem ser utilizados como parâmetros de admissibilidade dos autores sugeridos como alternativos. Para tal, revisito a polémica entre canónicos e anticanónicos retraçando os seus principais argumentos e proponho escrutinar algumas obras emblemáticas do movimento “para além do cânone”. Finalmente, sugiro que a discussão deve ser deslocada da retórica do empoderamento para o valor teórico das alternativas apresentadas pelos críticos do cânone.
MotorNet: a Python toolbox for controlling differentiable biomechanical effectors with artificial neural networks
Authors: Codol Olivier , Michaels Jonathan A , Kashefi Mehrdad , Pruszynski J Andrew , Gribble Paul L
Published: July 2024

Artificial neural networks (ANNs) are a powerful class of computational models for unravelling neural mechanisms of brain function. However, for neural control of movement, they currently must be integrated with software simulating biomechanical effectors, leading to limiting impracticalities: (1) researchers must rely on two different platforms and (2) biomechanical effectors are not generally differentiable, constraining researchers to reinforcement learning algorithms despite the existence and potential biological relevance of faster training methods. To address these limitations, we developed MotorNet, an open-source Python toolbox for creating arbitrarily complex, differentiable, and biomechanically realistic effectors that can be trained on user-defined motor tasks using ANNs. MotorNet is designed to meet several goals: ease of installation, ease of use, a high-level user-friendly API, and a modular architecture to allow for flexibility in model building. MotorNet requires no dependencies outside Python, making it easy to get started with. For instance, it allows training ANNs on typically used motor control models such as a two joint, six muscle, planar arm within minutes on a typical desktop computer. MotorNet is built on PyTorch and therefore can implement any network architecture that is possible using the PyTorch framework. Consequently, it will immediately benefit from advances in artificial intelligence through PyTorch updates. Finally, it is open source, enabling users to create and share their own improvements, such as new effector and network architectures or custom task designs. MotorNet’s focus on higher order model and task design will alleviate overhead cost to initiate computational projects for new researchers by providing a standalone, ready-to-go framework, and speed up efforts of established computational teams by enabling a focus on concepts and ideas over implementation.
Associations of proton pump inhibitors with susceptibility to influenza, pneumonia, and COVID-19: Evidence from a large population-based cohort study
Authors: Zeng Ruijie , Ma Yuying , Zhang Lijun , Luo Dongling , Jiang Rui , Wu Huihuan , Zhuo Zewei , Yang Qi , Li Jingwei , Leung Felix W , Duan Chongyang , Sha Weihong , Chen Hao
Published: July 2024

Background:

Adverse effects of proton pump inhibitors (PPIs) have raised wide concerns. The association of PPIs with influenza is unexplored, while that with pneumonia or COVID-19 remains controversial. Our study aims to evaluate whether PPI use increases the risks of these respiratory infections.

Methods:

The current study included 160,923 eligible participants at baseline who completed questionnaires on medication use, which included PPI or histamine-2 receptor antagonist (H2RA), from the UK Biobank. Cox proportional hazards regression and propensity score-matching analyses were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs).

Results:

Comparisons with H2RA users were tested. PPI use was associated with increased risks of developing influenza (HR 1.32, 95% CI 1.12–1.56) and pneumonia (hazard ratio [HR] 1.42, 95% confidence interval [CI] 1.26–1.59). In contrast, the risk of COVID-19 infection was not significant with regular PPI use (HR 1.08, 95% CI 0.99–1.17), while the risks of severe COVID-19 (HR 1.19. 95% CI 1.11–1.27) and mortality (HR 1.37. 95% CI 1.29–1.46) were increased. However, when compared with H2RA users, PPI users were associated with a higher risk of influenza (HR 1.74, 95% CI 1.19–2.54), but the risks with pneumonia or COVID-19-related outcomes were not evident.

Conclusions:

PPI users are associated with increased risks of influenza, pneumonia, as well as COVID-19 severity and mortality compared to non-users, while the effects on pneumonia or COVID-19-related outcomes under PPI use were attenuated when compared to the use of H2RAs. Appropriate use of PPIs based on comprehensive evaluation is required.

Funding:

This work is supported by the National Natural Science Foundation of China (82171698, 82170561, 81300279, 81741067, 82100238), the Program for High-level Foreign Expert Introduction of China (G2022030047L), the Natural Science Foundation for Distinguished Young Scholars of Guangdong Province (2021B1515020003), the Guangdong Basic and Applied Basic Research Foundation (2022A1515012081), the Foreign Distinguished Teacher Program of Guangdong Science and Technology Department (KD0120220129), the Climbing Program of Introduced Talents and High-level Hospital Construction Project of Guangdong Provincial People’s Hospital (DFJH201923, DFJH201803, KJ012019099, KJ012021143, KY012021183), and in part by VA Clinical Merit and ASGE clinical research funds (FWL).
Differential functions of the dorsal and intermediate regions of the hippocampus for optimal goal-directed navigation in VR space
Authors: Hwang Hyeri , Jin Seung-Woo , Lee Inah
Published: July 2024

Goal-directed navigation requires the hippocampus to process spatial information in a value-dependent manner, but its underlying mechanism needs to be better understood. Here, we investigated whether the dorsal (dHP) and intermediate (iHP) regions of the hippocampus differentially function in processing place and its associated value information. Rats were trained in a place-preference task involving reward zones with different values in a visually rich virtual reality environment where two-dimensional navigation was possible. Rats learned to use distal visual scenes effectively to navigate to the reward zone associated with a higher reward. Inactivation of both dHP and iHP with muscimol altered the efficiency and precision of wayfinding behavior, but iHP inactivation induced more severe damage, including impaired place preference. Our findings suggest that the iHP is more critical for value-dependent navigation toward higher-value goal locations.
Dimer-monomer transition defines a hyper-thermostable peptidoglycan hydrolase mined from bacterial proteome by lysin-derived antimicrobial peptide-primed screening
Authors: Zhang Li , Hu Fen , Zhao Zirong , Li Xinfeng , Zhong Mingyue , He Jiajun , Yao Fangfang , Zhang Xiaomei , Mao Yuxuan , Wei Hongping , He Jin , Yang Hang
Published: July 2024

Phage-derived peptidoglycan hydrolases (i.e. lysins) are considered promising alternatives to conventional antibiotics due to their direct peptidoglycan degradation activity and low risk of resistance development. The discovery of these enzymes is often hampered by the limited availability of phage genomes. Herein, we report a new strategy to mine active peptidoglycan hydrolases from bacterial proteomes by lysin-derived antimicrobial peptide-primed screening. As a proof-of-concept, five peptidoglycan hydrolases from the Acinetobacter baumannii proteome (PHAb7-PHAb11) were identified using PlyF307 lysin-derived peptide as a template. Among them, PHAb10 and PHAb11 showed potent bactericidal activity against multiple pathogens even after treatment at 100°C for 1 hr, while the other three were thermosensitive. We solved the crystal structures of PHAb8, PHAb10, and PHAb11 and unveiled that hyper-thermostable PHAb10 underwent a unique folding-refolding thermodynamic scheme mediated by a dimer-monomer transition, while thermosensitive PHAb8 formed a monomer. Two mouse models of bacterial infection further demonstrated the safety and efficacy of PHAb10. In conclusion, our antimicrobial peptide-primed strategy provides new clues for the discovery of promising antimicrobial drugs.
Interleukin-1 prevents SARS-CoV-2-induced membrane fusion to restrict viral transmission via induction of actin bundles
Authors: Zheng Xu , Yu Shi , Zhou Yanqiu , Yu Kuai , Gao Yuhui , Chen Mengdan , Duan Dong , Li Yunyi , Cui Xiaoxian , Mou Jiabin , Yang Yuying , Wang Xun , Chen Min , Jiu Yaming , Zhao Jincun , Meng Guangxun
Published: July 2024

Innate immune responses triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection play pivotal roles in the pathogenesis of COVID-19, while host factors including pro-inflammatory cytokines are critical for viral containment. By utilizing quantitative and qualitative models, we discovered that soluble factors secreted by human monocytes potently inhibit SARS-CoV-2-induced cell-cell fusion in viral-infected cells. Through cytokine screening, we identified that interleukin-1β (IL-1β), a key mediator of inflammation, inhibits syncytia formation mediated by various SARS-CoV-2 strains. Mechanistically, IL-1β activates RhoA/ROCK signaling through a non-canonical IL-1 receptor-dependent pathway, which drives the enrichment of actin bundles at the cell-cell junctions that prevents syncytia formation. Notably,
in vivo
infection experiment in mice confirms that IL-1β significantly restricted SARS-CoV-2 spreading in the lung epithelia. Together, by revealing the function and underlying mechanism of IL-1β on SARS-CoV-2-induced cell-cell fusion, our study highlights an unprecedented antiviral function for cytokines during viral infection.
Beyond A and B Compartments: how major nuclear locales define nuclear genome organization and function
Authors: Gholamalamdari Omid , van Schaik Tom , Wang Yuchuan , Kumar Pradeep , Zhang Liguo , Zhang Yang , Hernandez Gonzalez Gabriela A , Vouzas Athanasios E , Zhao Peiyao A , Gilbert David M , Ma Jian , van Steensel Bas , Belmont Andrew S
Published: July 2024

Models of nuclear genome organization often propose a binary division into active versus inactive compartments, yet they overlook nuclear bodies. Here we integrated analysis of sequencing and image-based data to compare genome organization in four human cell types relative to three different nuclear locales: the nuclear lamina, nuclear speckles, and nucleoli. Whereas gene expression correlates mostly with nuclear speckle proximity, DNA replication timing correlates with proximity to multiple nuclear locales. Speckle attachment regions emerge as DNA replication initiation zones whose replication timing and gene composition vary with their attachment frequency. Most facultative LADs retain a partially repressed state as iLADs, despite their positioning in the nuclear interior. Knock out of two lamina proteins, Lamin A and LBR, causes a shift of H3K9me3-enriched LADs from lamina to nucleolus, and a reciprocal relocation of H3K27me3-enriched partially repressed iLADs from nucleolus to lamina. Thus, these partially repressed iLADs appear to compete with LADs for nuclear lamina attachment with consequences for replication timing. The nuclear organization in adherent cells is polarized with nuclear bodies and genomic regions segregating both radially and relative to the equatorial plane. Together, our results underscore the importance of considering genome organization relative to nuclear locales for a more complete understanding of the spatial and functional organization of the human genome.
PRR adjuvants restrain high stability peptides presentation on APCs
Authors: Li Bin , Zhang Jin , He Taojun , Yuan Hanmei , Wu Hui , Wang Peng , Wu Chao
Published: July 2024

Adjuvants can affect the function of APCs and boost the adaptive immune responses post vaccination. However, whether adjuvants modulate the specificity of immune responses, especially the specificity of immunodominant epitope responses, and the mechanisms of adjuvants regulating antigen processing and presentation remain poorly defined. Here, using overlapping synthetic peptides, we screened the dominant epitopes of Th1 responses in mice post vaccination with different adjuvants and found that adjuvants altered antigen-specific CD4
+
T cell immunodominant epitope hierarchy. MHC-II immunopeptidome demonstrates that peptide repertoires presented by APCs are altered by adjuvants significantly. Unexpectedly, no novel peptide presentation was detected post adjuvants treatment, on the contrary, peptides with high binding stability for MHC-II presented in the control group were missing post adjuvant stimulation, especially in the MPLA and CpG group. The low stability peptide presented in adjuvant groups elicited robust T cell responses effectively and formed immune memory. Taken together, our results suggest that adjuvants (MPLA and CpG) restrain high stability peptides presentation instead of revealing cryptic epitopes, which may alter the specificity of the CD4
+
T-cell dominant epitope responses. This capacity of adjuvants to modify pMHC stability and antigen-specific T cell immunodominant epitope responses has fundamental implications for the selection of suitable adjuvants in the vaccine design process and the development of epitope vaccines.
A lytic transglycosylase connects bacterial focal adhesion complexes to the peptidoglycan cell wall
Authors: Ramirez Carbo Carlos A , Faromiki Olalekan G , Nan Beiyan
Published: July 2024

The Gram-negative bacterium Myxococcus xanthus glides on solid surfaces. Dynamic bacterial focal adhesion complexes (bFACs) convert proton motive force from the inner membrane into mechanical propulsion on the cell surface. It is unclear how the mechanical force transmits across the rigid peptidoglycan (PG) cell wall. Here, we show that AgmT, a highly abundant lytic PG transglycosylase homologous to Escherichia coli MltG, couples bFACs to PG. Coprecipitation assay and single-particle microscopy reveal that the gliding motors fail to connect to PG and thus are unable to assemble into bFACs in the absence of an active AgmT. Heterologous expression of E. coli MltG restores the connection between PG and bFACs and thus rescues gliding motility in the M. xanthus cells that lack AgmT. Our results indicate that bFACs anchor to AgmT-modified PG to transmit mechanical force across the PG cell wall.
Atomistic Tuning of the GeoCas9 Recognition Lobe Modulates Allosteric Motions and Guide RNA Interactions
Authors: Belato Helen B , Knight Alexa L , D’Ordine Alexandra M , Fan Zhiqiang , Luo Jinping , Jogl Gerwald , Lisi George P
Published: July 2024

The intuitive manipulation of specific amino acids to alter the activity or specificity of CRISPR-Cas9 has been a topic of great interest. As a large multi-domain RNA-guided endonuclease, the intricate molecular crosstalk within the Cas9 protein hinges on its conformational dynamics, but a comprehensive understanding of the extent and timescale of the motions that drive its allosteric function and association with nucleic acids remains elusive. Here, we investigated the structure and multi-timescale molecular motions of the recognition (Rec) lobe of
Geo
Cas9, a thermophilic Cas9 from
Geobacillus stearothermophilus.
Our results provide new atomic details about the
Geo
Rec subdomains (
Geo
Rec1,
Geo
Rec2) and the full-length domain in solution. Two single-point mutants, K267E and R332A, enhanced and redistributed micro-millisecond flexibility throughout
Geo
Rec, and NMR studies of the interaction between
Geo
Rec and its guide RNA showed that mutations reduced this affinity and the stability of the ribonucleoprotein complex. Despite measured biophysical differences due to the mutations, DNA cleavage assays reveal only modest functional differences in on-target activity, and similar specificity. These data highlight how guide RNA interactions can be tuned in the absence of major functional losses, but also raise questions about the underlying mechanism of
Geo
Cas9, since analogous single-point mutations have significantly impacted on- and off-target DNA editing in mesophilic
S. pyogenes
Cas9. A K267E/R332A double mutant did modestly enhance
Geo
Cas9 specificity, highlighting the robust evolutionary tolerance of Cas9 and species-dependent complexity. Ultimately, this work provides an avenue by which to modulate the structure, motion, and nucleic acid interactions at the level of the Rec lobe of
Geo
Cas9, setting the stage for future studies of
Geo
Cas9 variants and their effect on its allosteric mechanism.
Intestinal microbiome dysbiosis increases Mycobacteria pulmonary colonization in mice by regulating the Nos2-associated pathways
Authors: Han MeiQing , Wang Xia , Su Lin , Pan Shiqi , Liu Ningning , Li Duan , Liu Liang , Cui JunWei , Zhao Huajie , Yang Fan
Published: July 2024

Increasing researches reveal gut microbiota was associated with the development of tuberculosis (TB). How to prevent or reduce Mycobacterium tuberculosis colonization in the lungs is a key measure to prevent TB. However, the data on gut microbiota preventing Mycobacterium colonization in the lungs were scarce. Here, we established the clindamycin-inducing intestinal microbiome dysbiosis and fecal microbial transplantation models in mice to identify gut microbiota’s effect on Mycobacterium’s colonization in the mouse lungs and explore its potential mechanisms. The results showed that clindamycin treatment altered the diversity and composition of the intestinal bacterial and fungal microbiome, weakened the trans-kingdom network interactions between bacteria and fungi, and induced gut microbiome dysbiosis in the mice. Gut microbiota dysbiosis increases intestinal permeability and enhances the susceptibility of Mycobacterium colonization in the lungs of mice. The potential mechanisms were gut microbiota dysbiosis altered the lung transcriptome and increased Nos2 expression through the ‘gut–lung axis’. Nos2 high expression disrupts the intracellular antimicrobial and anti-inflammatory environment by increasing the concentration of nitric oxide, decreasing the levels of reactive oxygen species and Defb1 in the cells, and promoting Mycobacteria colonization in the lungs of mice. The present study raises a potential strategy for reducing the risks of Mycobacteria infections and transmission by regulating the gut microbiome balance.
Old Shrines, New Worshipers: Cultural Practices for Connection with Nature
Authors: Troeva Evgenia ,   Institute  of  Ethnology  and  Folklore  Studies  with  Ethnographic Museum, Bulgarian Academy of Sciences, Sofia, Bulgaria
Published: July 2024

There are many ancient cultural sites in Bulgaria that not only attract tourists but are also believed to facilitate a person’s connection with deities and natural forces. Today, cultural practices performed at these sacred places from the period of antiquity and the early Middle Ages are often associated with neopaganism and the New Age movement, while also incorporating elements of Bulgarian traditional culture. Through ‘mysterious’ rituals, the participants seek to connect with a higher spirituality, which they feel is missing in their everyday lives. Interest in ancient paganism is also one of the manifestations of contemporary nationalism. The feasts, reenactments and rituals presented serve to ‘re-establish’ man’s relationship with nature, with the aim of achieving health, well-being, and spiritual growth in an uncertain world. These practices often interweave esoteric and environmentalist ideas with strategies for the development of cultural tourism.
Constructing Sacred Sites as a Form of Collective Memory: The Sacrificial Stone on Toomemägi Hill in Tartu
Authors: Heinapuu Ott ,   Centre for Environmental History, Tallinn University, Estonia
Published: July 2024

Sacred natural sites retained their relevance in Estonian culture during and after the shift from mainly oral to mainly literary culture. However, the framework for conceptualising sacred natural sites has changed. Premodern sites have acquired new meanings and functions (notably those associated with national identity) and new sites have been taken into use. The article will present a typology describing the different ways of conceptualising the sacred natural sites that is current in Estonian culture and will offer a case study of a sacred site with a pivotal role in Estonian national identity, the sacrificial stone on Toomemägi hill in the city of Tartu.
Plants and migration
Authors: Zhekova Mariyanka Borisova ,   Institute  of  Ethnology  and  Folklore  Studies  with  Ethnographic Museum, Bulgarian Academy of Sciences, Sofia, Bulgaria
Published: July 2024

The article focuses on the ethnobotany, analysing the migration of plants that accompany Bulgarians to new destinations. The functions and meanings of these plants are outlined. Plants ‘in migration’ in this way are considered in the light of the relationship between culture and place. Some plants perceived as traditionally Bulgarian are rediscovered and transferred to the receiving country and are present in the stories, cultural practices, and everyday lives of migrants. These plants can be examined through the lens of sensory anthropology, as bearers of knowledge and emotion through perception in the form of vision, smell, touch, taste. Plants can be seen as a synecdoche of the homeland. According to the interviews, Bulgarians abroad perceive some plants as emblematic of Bulgaria. Plants transported abroad are recognised by migrants as Bulgarian cultural heritage, through which cultural values and symbols are maintained. Bulgarians take abroad plants that give them aesthetic pleasure and remind them of Bulgaria, of home, of family, of childhood. An emotional connection with the homeland is also provided by the plants, the cultivation of which in the new place is an experiment with no guarantee of success. ‘Bulgarian’ plants taken and grown abroad (flowers, fruits, vegetables, spices, herbs) offer a wealth of sensory perception and have an aroma and/or taste often defined by respondents as the “aroma and taste of Bulgaria”. Plants in migration develop versatile functionality, facilitate adaptation, and concentrate narratives.
The Nature of Culture: Rites of Interaction Between Ukrainian Refugees and Latvian Society (2022)
Authors: Kiope Māra ,   Institute of Philosophy and Sociology, University of Latvia
Published: July 2024

The article deals with the challenge in migration studies to find a solution to the problem of how to analyse the rapidly emerging and increasing immigration of Ukraine war refugees, which started in 2022 in Latvia as well as in other European Union countries. This topic is important in migration studies to provide national and municipal decision-makers with a scientific perspective and rationale for informed decisions. In Latvia, the humanities, including philosophy, have not yet been used to understand migration processes, although they do supply a wider context, which is necessary to understand the culture, attitudes, values, and peculiarities of an immigration group. The task of integrating and including the immigrant group presupposes knowledge and recognition of its uniqueness, which is best researched with the methods of the humanities, and significantly complements the approaches of economics, sociology and human geography. Thus, the research presented in this article uses a wide range of social science research findings, ritual phenomenology, topological hermeneutics, and solutions from micro-group sociology as data sources to complement the understanding of migration as an object with a perspective that also includes human experience and the intersubjective space in which people meet to create community. The objective of the study is to explore the research hypothesis, based on previous studies and daily observations, that a new social reality is emerging that can be called the newly emerged community of Ukraine in Latvia. This means that communication and reciprocity between most of Latvian society and refugees from the Ukrainian war has been, and is being, established. The article analyses to what extent Latvian society was ready for the reception and inclusion of refugees from the Ukrainian war; how the inclusion of the concept of place can help to address the issue of the formation of new communities; how rituals reveal a new step towards the creation of communion on both sides of the newly formed community; and how rituals and interactivity interact in rituals involving micro-groups and micro-group forming rituals. Thus, factors affecting the genesis of the Ukraine in Latvia community were discovered in the analysis of the interactive rituals that confirm the existence of a social reality aimed at integration and inclusion. Thus, the study reveals the perspectives on the use of resources rooted in culture at the national and municipal levels.
Epidemics in the Vilayet Of Kosovo (1877–1912)
Authors: Rizani Marigonë ,   UBT College, Prishtina, Kosovo, Shabani Zekirja ,   Istanbul University, Türkiye,   Institute of Albanology. Prishtina, Kosovo
Published: July 2024

With the increase in activities and interaction between societies, the rate of spread of epidemics has also increased. Given that the physical structure and location of the Vilayet of Kosovo during the Ottoman period was in the middle of the Balkan Peninsula, connecting the land routes with the Central Europe, it had become a destination where epidemics spread easily. The main purpose of this paper is to analyse and evaluate epidemiological diseases in the Vilayet of Kosovo such as cholera, smallpox, dysentery, rubella. The main objective of this work is to cover the years 1877–1912. This paper, which deals with the epidemic in the Vilayet of Kosovo, investigates the historical background of the conduct of the central and local authorities as far as health policies and public health were concerned in the face of deadly infectious diseases. At this point, administrative and sanitary measures taken by the relevant institutions in the Vilayet of Kosovo had been identified, such as the employment of health personnel, the distribution of vaccines, border blockage, the restriction of the movement of people and putting them in quarantine. In addition, attention has been paid to the assessment and analysis of health services and hospital infrastructure in the Zekirja Shabani, Marigonë Rizani Vilayet of Kosovo. This study, which contributes to the knowledge of the history of epidemiology and public health in the Vilayet of Kosovo, is mainly supported by documents from the Ottoman Archives of the Presidency in Istanbul. In addition, studies, theses and research papers on epidemiology and public health in the Ottoman Empire were used.