bluuebunny/crossref_metadata_2025 huggingface dataset:
A Review of the Comprehensive Application of Big Data, Artificial Intelligence, and Internet of Things Technologies in Smart Cities
Authors: Yao Yao
Published: June 2024

As global populations rise and urbanization intensifies, cities face significant challenges in sustainable development. Leveraging next-generation information technologies, particularly Artificial Intelligence (AI), machine learning, Big Data, and the Internet of Things (IoT), is essential to enhance urban operational efficiency and livability. This paper provides an in-depth analysis of the current applications and future trends of these technologies in smart cities, covering urban planning, intelligent transportation, environmental protection, and energy management. By integrating these technologies, smart cities can manage urban resources more effectively, improve residents' quality of life, and promote sustainability. Key issues and challenges are also discussed, providing a roadmap for future research and development.
Deep Learning-Based Multifunctional End-to-End Model for Optical Character Classification and Denoising
Authors: Xiong Shuguang , Chen Xiaoyang , Zhang Huitao
Published: June 2024

Optical Character Recognition (OCR) has revolutionized document processing by converting scanned documents, PDFs, and images captured by cameras into editable and searchable text. This technology is crucial for digitizing historical documents, streamlining data entry processes, and improving accessibility for the visually impaired through text-to-speech technologies. Despite its widespread application, OCR faces significant challenges, especially in accurately recognizing text in noisy or degraded images. Traditionally, OCR systems have treated noise reduction and character classification as separate stages, which can compromise the overall effectiveness of text recognition. Our research introduces a groundbreaking Multifunctional End-to-End Model for Optical Character Classification and Denoising, which integrates these functions within a unified framework. By employing a dual-output autoencoder, our model concurrently denoises images and recognizes characters, thereby enhancing both the efficiency and accuracy of OCR. This paper outlines the model's development and implementation, explores the interplay between denoising and classification, and presents compelling experimental results that demonstrate marked improvements over conventional OCR methods.
An Assessment of the Trainers' Competence in Implementing Online Teaching and Learning in TVET
Authors: Kipkoech Frank , Kerre Bonaventure
Published: June 2024

Due to the ever-changing technological environment and digitization of education, Trainers need to use new technologies for content delivery to the trainees. The acceptance and willingness of trainers to use online learning is the key to success and is faced with various challenges. Trainers must use communication technology skills to fit successfully in a knowledge-based society. Moreover, regardless of the availability of technology, trainers need ICT skills for online teaching and learning. The study sought to assess the trainers' competence in implementing e-Learning in technical institutions. A descriptive research design was used in the study; structured questionnaires, both open-ended and closed, were issued to a sample size of n=77 trainer participants in the six selected technical training institutes in Nandi County. The study revealed that 81.8 % (n=63) of the respondents received prior technical training in e-learning. Trainers also reported difficulty in using the e-Learning platform. Technological expertise is essential to ensure the success of e-learning. Inadequate computer literacy hindered many trainers from content delivery using e-Learning, especially during Covid-19 lockdown times. It was evident that most trainers struggled with the online platforms, accessibility of learning equipment such as whiteboards, projectors, low internet connectivity, and inadequate training skills attributed to slow implementation. The study revealed that trainers had difficulty using the e-Learning platform issued. This is due to the inadequate training that they had received and the complex system used. The study found that trainers preferred other platforms which were user-friendly for e-Learning. Additionally, the institutions' LAN network is limited to the laboratories and institution library only; hence, some offices at a distance from the administration cannot access the LAN internet. Implementing online learning requires the stakeholders to come together to make online learning successful.
An Evaluation of the Effect of Domestic Debt and External Debt on Economic Growth in Kenya
Authors: Ptengwe Cheworei Peter , Okelo Odwori Paul , Winrose Chepng'eno
Published: June 2024

During the period 1963 to 2008, Kenya’s economy went through cyclical booms and depressions. As a result, the Kenyan government turned to external and domestic borrowing to finance the budget deficits. However, this has negatively affected the country - leading to high dependency ratio as compared to the previous years. Therefore, this study assessed the effects of domestic borrowing and external borrowing on economic growth in Kenya for the period between 1988 and 2019. The study was anchored on the Keynesian theory of economic growth and the dynamic theory of public spending. Autoregressive Distributed Lag (ARDL) model was used to analyze data, with the aid of SPSS and STATA. The findings of the study show that 1% increase in domestic debt causes a 1.25 % decline in Kenya's economic growth while a 1% increase in external debt causes a 1.10 % decline in Kenya's economic growth. Results also revealed that there exists a significant inverse short-term relationship between economic growth and domestic debt. These results imply that both domestic debt stock and external debt stock are significantly correlated with Kenya's economic growth. It is recommended that proper debt management need to be done to contain increases in debt level in order to ensure a steady economic growth in Kenya.
Research on the development and application process of Living Lab project to improve convergent thinking ability: Focusing on students of the liberal arts high school convergence club
Authors: Jang Seo-yoon , Paik Seoung-Hey
Published: June 2024

In this study, it is assumed that 'knowledge information processing competency' and 'creative thinking competency' directly or indirectly affect students' convergent thinking ability, and can be applied to improve students' convergent thinking ability in the educational field. Based on Beane's collaborative design model, 'D.A.P. A convergence class model was developed, and an activity sheet to which design thinking was applied was designed and used to effectively guide students' activities. In addition, since convergence thinking ability is not a competency that can be formed in a short period of time, the 'Living Lab Project', which recognizes problem situations in learners' lives and solves them, was incorporated to observe the change process of students in the course of long-term activities. In the course of the research, I tried to induce students' leading participation, and through the process of solving social problems, I was able to derive the educational value that students should cultivate as democratic citizens and preliminary members of society. In the course of the Living Lab Project activity, students of the convergence club can observe changes in the definitional aspect, such as changes in communication in cooperative dialogue, growth in a sense of responsibility as a leader, and formation of an attitude of respect for the other party that students of the convergence club conduct group activities. could As a result, it was concluded that the 'Living Lab Project' activity had a positive effect on the improvement of students' convergence thinking ability in the overall aspect.
PKM PENGEMBANGAN SISTEM INFORMASI UNTUK PENATAAN ADMINISTRASI MANAJEMEN GEREJA DI JEMAAT GPM LILIBOOI
Authors: Tamtelahitu Trientje Marlein , Makatita Josephus Albert
Published: June 2024

Jemaat Gereja Protestan Maluku (GPM) Lilibooi terletak di desa Lilibooi yang berjarak 31,6 Km dari Universitas Kristen Indonesia Maluku (UKIM) dengan jarak tempuh darat 50 menit. Jemaat GPM Lilibooi mengalami pertumbuhan jumlah jemaat dari tahun ke tahun sehingga jumlah data yang ada pada Jemaat GPM Lilibooi semakin banyak.Invetarisasi data jemaat perlu diperhatikan agar pelayanan dan program gereja dapat berjalan dengan baik. Mencermati masalah pertumbuhan jemaat dari tahun ke tahun yang ada pada Jemaat GPM Lilibooi maka tim Program pengembangan kepada masyarakat (PkM) Universitas Kristen Indonesia Maluku (UKIM) Ambon berinisiatif mendekati Jemaat GPM Lilibooi untuk mendiskusikan masalah-masalah terkait yang dihadapi, seperti : (1) Masih banyak informasi jemaat GPM Lilibooi yang tersimpan dalam bentuk hardcopy (arsip fisik atau dokumen tercetak) termasuk catatan atau riwayat masing-masing jemaat sehingga membutuhkan waktu yang lama dalam proses pencarian.; (2) Pihak gereja seringkali mengalami kesulitan dalam melakukan inventarisasi jemaat.; (3) Pengolahan data masih terbatas pada penggunaan MS office word dan MS office excel yang belum terintegrasi secara sistem sehingga bila gereja atau jemaat membutuhkan suatu informasi maka setiap file yang ada harus diperiksa satu persatu, memperlambat proses penyediaan data.Berdasarkan masalah dan rencana solusi yang telah didiskusikan sebelumnya dengan mitra, maka iptek yang telah diimplementasikan pada mitra jemaat GPM Lilibooi adalah : (1) Pemanfaataan teknologi informasi yang membantu proses pelayanan Jemaat GPM Lilibooidengan meminimalkan penyimpanan dalam bentuk hardcopy(arsip fisik atau dokumen tercetak); (2) Mitra telah diberikan pengetahuan dan ketrampilan menggunakan sistem informasi jemaat yang membantu mitra dalam menjawab kesulitan inventarisasi jemaat.; (3) Mitra juga telah dilatih cara mencari informasi jemaat yang tetap yang disesuaikan dengan kebutuhan pihak gereja atau jemaat; (4) Mitra juga telah dilatih cara membuat laporan dan penyajian data yang dinamis yang mudah dan informatif.Luaran kegiatan ini telah dipublikasi pada media massa elektronik Mimbar Rakyat News(http://mimbarrakyatnews.com/?s=pkm+ukim+ambon+gelar+pelatihan+aplikasi+sistem+informasi),video kegiatan telah di upload pada chanel YouTube (https://youtu.be/zrmqWNxqQXI).
PERILAKU HIDUP BERSIH DAN SEHAT PADA SISWA SISWI DAN GURU DI SD NEGERI 5 SULI, KECAMATAN SALAHUTU, KABUPATEN MALUKU TENGAH
Authors: Mamuly Wilma Fransisca , Siahaya Griennasty Clawdya
Published: June 2024

SD Negeri 5 Suli, merupakan salah satu SD yang berada di Desa Suli, Kecamatan Salahatu, Kabupaten Maluku Tengah, dengan jumlah tenaga guru 20 orang dan 242 jumlah siswa-siswi. Setelah dilakukan observasi awal dan dari hasil wawancara antara Tim PKM dengan mitra disepakati bersama ada beberapa masalah yang menjadi prioritas diantaranya Minimnya pengetahuan mitra tentang pentingnya PHBS, dikhususkan buat sampah dan cuci tangan pakai sabun, Kurangnya fasilitas tempat sampah dan juga wadah untuk mencuci tangan pada SD Negeri 5 Suli ( Mitra ), Kurangnya kesadaran mitra tentang bahaya merokok, bagi diri sendiri dan lingkungan, UKS (Usaha Kesehatan Sekolah) yang sudah tidak berfungsi, Tidak ada poster â€“ poster kesehatan.Solusi yang ditawarkan dari permasalahan mitra adalah penyuluhan tentang sampah dan langkah-langkah mencuci tangan, serta pelatihan 7 langkah mencuci tangan, Pengadaan tempat sampah dan wadah untuk mencuci tangan. Penyuluhan tentang bahaya merokok ( terkhusus bagi para Guru ). Kegiatan PKM telah dilakukan oleh tim selama kurang lebih 1 bulan, kegiatan yang dilakukan antara lain, sosialisasi PHBS di Sekolah, Pemberdayaan UKS, penyediaan fasilitas-fasilitas yang menunjang program PHBS di Sekolah di antaranya Timbangan, Kotak P3K, Tempat Sampah, Wadah untuk mencuci tangan, Tempat tidur untuk ruangan UKS dan juga poster â€“poster kesehatan, dari hasil pembagian pre test dan post test terjadi peningkatan pengetahuan 90% dari mitra. Target luaran yang telah dicapai, publikasi pada jurnal LPM UKIM, Publikasi media massa online Maluku News https://.malukunews.co/berita/kiriman-pengunjung/zse14trc0rk5aq7/budayakan-phbs-di-sekolah dan video kegiatan dapat diakses melalui https://youtu.be/X10wIRG5vls.
REVITALISASI JALAN LINGKUNGAN PADA RT 003/RW 04 KELURAHAN RIJALI KOTA AMBON
Authors: Lewaherilla Nusye Mozes Yohannes , Tiwery Charles Johandersson
Published: June 2024

Pembangunan jalan lingkungan merupakan bagian dari pembangunan infrastruktur desa berbasis masyarakat. Tujuan pembangunan infrastruktur desa/kecamatan berbasis masyarakat adalah untuk meningkatkan kesejahteraan masyarakat desa melalui peningkatan peran serta masyarakat desa dalam pembangunan serta menumbuhkan kesadaran dan kemandirian masyarakat dalam mengatasi permasalahan dan penyediaan infrastruktur perdesaan. RT 003/RW04 merupakan daerah yang terletak di pusat kota Ambon tepatnya di Keluarahan Rijali depan Kantor DPRD Kota Ambon, secara khusus jalan lingkungan ini menjadi sesuatu yang prioritas bagi warga setempat karena merupakan jalur akses ke pusat pendidikan, pemerintahan maupun pusat peribadatan yang ada disekitar. Perbaikan jalan lingkungan RT003/RW04 ini disebabkan oleh konstruksi jalan yang sudah mengalami keretakan atau hancur serta sering tergenang air pada saat musim hujan Berdasarkan penjelasan diatas, maka tujuan yag ingin dicapai adalah memperbaiki atau merevitalisasi jalan lingkungan RT 003/RW04 untuk layak pakai sesuai standar mutu SNI dan layak untuk digunakan, serta merasa aman dan nyaman bagi warga dan pergerakan arus lalu lintas. Dari hasil sosialisasi dengan warga diketahui beberapa masalah antara lain : (1) Jalan setapak beton yang dilalui warga selama ini sudah cukup rusak dan tidak aman dilewati apalagi saat hujan turun; (2) Saluran Drainase sudah banyak yang mengalami rusak sehingga limbah rumah tangga merembes masuk ke dalam tanah dan juga memberi dampak bau yang tidak sedap bagi lingkungan. Berdasarkan masalah diatas maka iptek yang telah diimplementasikan pada mitra RT003/RW04 adalah (1) Masyarakat mengenal lebih dekat pengetahuan tentang apa itu beton normal atau beton non struktural secara teknis; (2) Mitra juga mengetahui tentang proporsi campuran beton normal sesuai SNI; (3) Mitra di belajarkan tentang pengaruh prosentase kandungan air dalam campuran beton terhadap kualitas atau mutu beton. Luaran kegiatan ini telah dipublikasikan pada media massa elektronik Harian Spektrum dan media massa online Maluku terkini (https://www.malukuterkini.com/2019/12/16/pkm-ukim-revitalisasi-jalan-lingkungan-kelurahan-rijali/) dan Video kegiatan ini telah di upload pada chanel YouTube (https://www.youtube.com/watch?v=YyKBYD8OKe4t=7s)
BUDIDAYA TANAMAN SEHAT DENGAN METODE HYDROPONIK
Authors: Wakanno Grace Jeny , Souisa Gracia Victoria , Molle Lucky
Published: June 2024

Mitra Program Kemitraan Masyarakat (PkM) yang dipilih oleh tim pelaksana adalah para guru SMP Negeri 12 Desa Halong Atas, Kecamatan Baguala, Kota Ambon. Hal ini dilakukan berdasarkan persoalan yang dihadapi mitra yaitu masih kurangnya pengetahuan dan kesadaran mitra tentang cara mendapatkan sayur organik bebas pestisida, dengan metode hydroponik, kurangnya informasi terkait akibat atau dampak negatif yang disebabkan oleh mengkonsumsi sayuran yang mengandung pestisida (Pembasmi hama dan penyakit) dalam jangka waktu tertentu, belum adanya simulasi terkait cara bercocok tanam organik (bebas pestisida) dengan menggunakan sistem hidroponik. Tujuan Program Kemitraan Masyarakat adalah meningkatkan pengetahuan dan pemahaman mitra tentang cara bercocok tanam organik bebas pestisida dengan metode hidroponik. Metode yang digunakan untuk mencapai tujuan diatas adalah penyuluhan/sosialisasi, simulasi, pemutaran video. Hasil yang didapatkan adalah setelah dilakukan penyuluhan, pengetahuan mitra mengalami peningkatan yaitu untuk nilai baik (70) dari 4 orang (14,29 % pretest) menjadi 28 orang (100% post test). Sedangkan nilai mean dan median meningkat dari 45 menjadi 90. Hal ini menunjukkan adanya peningkatan pengetahuan mitra setelah diberikan penyuluhan dan simulasi. Kesimpulan dari kegiatan ini adalah terjadi peningkatan pengetahuan para guru melalui metode penyuluhan dan simulasi tanaman organik (bebas pestisida) dengan cara hidroponik.
PHBS DAN SOSIALISASI PERGAULAN BEBAS, BERPERILAKU ETIS DALAM MENGELOLA KEUANGAN NEGERI/JEMAAT GPM AMAHUSU
Authors: Wattimena Demsy , Silooy Marissa
Published: June 2024

Negeri Amahusu, adalah Desa di Kecematan Nusaniwe, Kota Ambon,Provinsi Maluku, yang merupakan desa yang dekat dengan pusat kota ambon waktu tempuh dari pusat kota ambon ke Negeri Amahusu hanya dapat ditempuh dengan waktu 15-20 menit perjalan.. Negeri Amahusu sebagai salah satu desa berkembang, yang mungkin hampir sejajar dengan kota ambon. Amahusu sebagai salah satu negeri (Desa) yang tiap tahunnya selalu dipercayakan sebagai tuan rumah Yacht Race Darwin-Ambon, membawa Negeri Amahusu tak menutup diri dari pengaruh luar yang tentuhnya dapat membawah dampak positif. Diantara keindahan, kemegahan dan kemasyuran negeri Amahusu. Dibalik pesona Negeri Amahusu yang sangat luar biasa, ternyata masih ada hal-hal yang belum disadari benar oleh masyarakat setempat. Hal pertama dari sisi kesehatan dapat dilihat bahwa sebagian masyarakat negeri Amahusu sudah berlaku hidup sehat tetapi sebagian besar masyarakat belum menyadari pentingnya hidup bersih dan sehat. dari sisi pergaulan bebas masyarakat lebih di khususkan kepada remaja pada negeri amahusu tidak diragukan lagi dalam melakukan pertemanan atau peggaulan tetapi ada sebagian kecil remaja yang belum memahami tentang petemanan atau pergaulan yang baik dan benar. dari sisi pengelolaan keuangan dalam berorganisasi kata “uang” adalah hal yang paling sensitif. Tingkat sensitifitasnya akan lebih tinggi ketika dalam pengelolaan keuangan ditemukan adanya penyimpangan-penyimpangan. Dalam kajian manajemen keuangan, penyimpanganpenyimpangan yang terjadi disebabkan karena perilaku (behavior) seseorang dalam mengelola keuangan. Uang dapat membuat seseorang termotivasi dan mempengaruhi pengambilan keputusan keuangan karena seorang individu sudah tidak hanya menghubungkan uang dengan nilai, kegunaan dan kekayaa, persoalan mendasar yang terjadi di mitra antara lain : (1) Kurangnya pemahaman/pengetahuan tentang PHBS (Perilaku Hidup Bersih dan Sehat), (2) Kurangnya pengetahuan tentang pergaulan bebas. (3) Kurangnya pengetahuan tentang Perilaku Etis dalam Mengelola Keuangan. (4) Tidak ada buku panduan tentang PHBS (Perilaku Hidup Bersih dan Sehat)
VII Almanzora Comparte: cuando el aprendizaje es el mejor de los viajes
Authors: Sanz Martos Sandra
Published: June 2024

La comarca del Almanzora debe su nombre al río que la atraviesa a lo largo del valle. Prácticamente en paralelo, discurre también la antigua vía del ferrocarril que unía Lorca con Granada; el granaíno lo llamaban. Lamentablemente, ya no circula ningún tren por esos raíles desde hace casi 40 años. Pero el legado de aquella época próspera va más allá de los restos de hierro y madera de los caminos: los edificios de viajeros, los andenes, muelles de carga, depósitos de agua, casetas de guardagujas y de guardavías, cocherones, etc.
A microRNA that controls the emergence of embryonic movement
Authors: Menzies Jonathan AC , Maia Chagas André , Baden Tom , Alonso Claudio R
Published: June 2024

Movement is a key feature of animal systems, yet its embryonic origins are not fully understood. Here, we investigate the genetic basis underlying the embryonic onset of movement in Drosophila focusing on the role played by small non-coding RNAs (microRNAs, miRNAs). To this end, we first develop a quantitative behavioural pipeline capable of tracking embryonic movement in large populations of fly embryos, and using this system, discover that the Drosophila miRNA miR-2b-1 plays a role in the emergence of movement. Through the combination of spectral analysis of embryonic motor patterns, cell sorting and RNA in situs, genetic reconstitution tests, and neural optical imaging we define that miR-2b-1 influences the emergence of embryonic movement by exerting actions in the developing nervous system. Furthermore, through the combination of bioinformatics coupled to genetic manipulation of miRNA expression and phenocopy tests we identify a previously uncharacterised (but evolutionarily conserved) chloride channel encoding gene – which we term Movement Modulator (Motor) – as a genetic target that mechanistically links miR-2b-1 to the onset of movement. Cell-specific genetic reconstitution of miR-2b-1 expression in a null miRNA mutant background, followed by behavioural assays and target gene analyses, suggest that miR-2b-1 affects the emergence of movement through effects in sensory elements of the embryonic circuitry, rather than in the motor domain. Our work thus reports the first miRNA system capable of regulating embryonic movement, suggesting that other miRNAs are likely to play a role in this key developmental process in Drosophila as well as in other species.
ElectroPhysiomeGAN: Generation of Biophysical Neuron Model Parameters from Recorded Electrophysiological Responses
Authors: Kim Jimin , Liu Qiang , Shlizerman Eli
Published: June 2024

Recent advances in connectomics, biophysics, and neuronal electrophysiology warrant modeling of neurons with further details in both network interaction and cellular dynamics. Such models may be referred to as ElectroPhysiome, as they incorporate the connectome and individual neuron electrophysiology to simulate neuronal activities. The nervous system of
C. elegans
is considered a viable framework for such ElectroPhysiome studies due to advances in connectomics of its somatic nervous system and electrophysiological recordings of neuron responses. In order to achieve a simulated ElectroPhysiome, the set of parameters involved in modeling individual neurons need to be estimated from electrophysiological recordings. Here, we address this challenge by developing a novel deep generative method called ElectroPhysiomeGAN (EP-GAN), which once trained, can instantly generate parameters associated with the Hodgkin-Huxley neuron model (HH-model) for neurons with graded potential response. The method combines Generative Adversarial Network (GAN) architecture with Recurrent Neural Network (RNN) Encoder and can generate an extensive number of parameters (>170) given the neuron’s membrane potential responses and steady-state current profiles. We validate our method by estimating HH-model parameters for 200 synthetic neurons with graded membrane potential followed by 9 experimentally recorded neurons (where 6 of them newly recorded) in the nervous system of
C. elegans
. Compared to other methods, EP-GAN is advantageous in both accuracy of generated parameters and inference speed. In addition, EP-GAN preserves performance when provided with incomplete membrane potential responses up to 25% and steady-state current profiles up to 75%. EP-GAN is designed to leverage the generative capability of GAN to align with the dynamical structure of HH-model, and thus able to achieve such performance.
Selective recruitment: Evidence for task-dependent gating of inputs to the cerebellum
Authors: Shahshahani Ladan , King Maedbh , Nettekoven Caroline , Ivry Richard , Diedrichsen Jörn
Published: June 2024

fMRI studies have documented cerebellar activity across a wide array of tasks. However, the functional contribution of the cerebellum within these task domains remains unclear because cerebellar activity is often studied in isolation. This is problematic, as cerebellar fMRI activity may simply reflect the transmission of neocortical activity through fixed connections. Here we present a new approach that addresses this problem. Rather than focus on task-dependent activity changes in the cerebellum alone, we ask if neocortical inputs to the cerebellum are gated in a task-dependent manner. We hypothesize that input is upregulated when the cerebellum functionally contributes to a task. We first validated this approach using a finger movement task, where the integrity of the cerebellum has been shown to be essential for the coordination of rapid alternating movements but not for force generation. While both neocortical and cerebellar activity increased with increasing speed and force, the speed-related changes in the cerebellum were larger than predicted by an optimized cortico-cerebellar connectivity model. We then applied the same approach in a cognitive domain, assessing how the cerebellum supports working memory. Enhanced gating was associated with the encoding of items in working memory, but not with the manipulation or retrieval of the items. Focusing on task-dependent gating of neocortical inputs to the cerebellum offers a promising approach for using fMRI to understand the specific contributions of the cerebellum to cognitive function.
Modeling Hereditary Diffuse Leukoencephalopathy with Axonal Spheroids using microglia-sufficient brain organoids
Authors: Wong Wei Jie , Zhu Yi Wen , Wang Hai Ting , Qian Jia Wen , Li Ziyi , Li Song , Liu Zhao Yuan , Guo Wei , Zhang Shuang Yan , Su Bing , He Fang Ping , Wang Kang , Ginhoux Florent
Published: June 2024

Hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) is a rare, fatal, adult-onset neurodegenerative disease that is most often caused by mutations affecting the Colony Stimulating factor-1 Receptor (CSF-1R). To understand how CSF-1R-mutation affects human microglia – the specialized brain-resident macrophages of the central nervous system – and the downstream consequences for neuronal cells, we used a macrophage and forebrain organoid co-culture system based on induced pluripotent stem cells generated from two patients with HDLS, with
CSF-1R
gene-corrected isogenic organoids as controls. Macrophages derived from iPSC (iMacs) of patients exhibited a metabolic shift towards the glycolytic pathway and reduced CSF-1 sensitivity, which was associated with higher levels of IL-1β production and an activated inflammatory phenotype. Single-cell RNA sequencing revealed that iMacs adopt a reactive state that leads to impaired regulation of neuronal cell populations in organoid cultures, thereby identifying microglial dysregulation and specifically IL-1β production as key contributors to the degenerative neuro-environment in HDLS.
The common Sting1 HAQ, AQ alleles rescue CD4 T cellpenia, restore T-regs, and prevent SAVI (N153S) inflammatory disease in mice
Authors: Aybar-Torres Alexandra a , Saldarriaga Lennon A , Pham Ann T , Emtiazjoo Amir M , Sharma Ashish K , Bryant Andrew j , Jin Lei
Published: June 2024

The significance of STING1 gene in tissue inflammation and cancer immunotherapy has been increasingly recognized. Intriguingly, common human STING1 alleles R71H-G230A-R293Q (HAQ) and G230A-R293Q (AQ) are carried by ~60% of East Asians and ~40% of Africans, respectively. Here, we examine the modulatory effects of HAQ, AQ alleles on STING-associated vasculopathy with onset in infancy (SAVI), an autosomal dominant, fatal inflammatory disease caused by gain-of-function human STING1 mutations. CD4 T cellpenia is evident in SAVI patients and mouse models. Using Sting1 knock-in mice expressing common human STING1 alleles HAQ, AQ, and Q293, we found that HAQ, AQ, and Q293 splenocytes resist STING1-mediated cell death ex vivo, establishing a critical role of STING1 residue 293 in cell death. The HAQ/SAVI(N153S) and AQ/SAVI(N153S) mice did not have CD4 T cellpenia. The HAQ/SAVI(N153S), AQ/SAVI(N153S) mice have more (~10-fold, ~20-fold, respectively) T-regs than WT/SAVI(N153S) mice. Remarkably, while they have comparable TBK1, IRF3, and NFκB activation as the WT/SAVI, the AQ/SAVI mice have no tissue inflammation, regular body weight, and normal lifespan. We propose that STING1 activation promotes tissue inflammation by depleting T-regs cells in vivo. Billions of modern humans have the dominant HAQ, AQ alleles. STING1 research and STING1-targeting immunotherapy should consider STING1 heterogeneity in humans.
The common TMEM173 HAQ, AQ alleles rescue CD4 T cellpenia, restore T-regs, and prevent SAVI (N153S) inflammatory disease in mice
Authors: Aybar-Torres Alexandra , Saldarriaga Lennon A , Pham Ann T. , Emtiazjoo Amir M. , Sharma Ashish K , Bryant Andrew J. , Jin Lei
Published: June 2024

The significance of STING (encoded by the
TMEM173
gene), in tissue inflammation and cancer immunotherapy has been increasingly recognized. Intriguingly, common human
STING
alleles R71H-G230A-R293Q (
HAQ)
and G230A-R293Q (
AQ
) are carried by ∼60% of East Asians and ∼40% of Africans, respectively. Here, we examine the modulatory effects of
HAQ, AQ
alleles on STING-associated vasculopathy with onset in infancy (SAVI), an autosomal dominant, fatal inflammatory disease caused by gain-of-function human
STING
mutations. CD4 T cellpenia is evident in SAVI patients and mouse models. Using STING knock-in mice expressing common human
STING
alleles
HAQ
,
AQ
, and
Q293
, we found that
HAQ, AQ
, and
Q293
splenocytes resist STING-mediated cell death
ex vivo,
establishing a critical role of STING residue 293 in cell death. The
HAQ/SAVI(N153S)
and
AQ/SAVI(N153S)
mice did not have CD4 T cellpenia. The
HAQ/SAVI(N153S), AQ/SAVI(N153S)
mice have more (∼10-fold, ∼20-fold, respectively) T-regs than
WT/SAVI(N153S)
mice. Remarkably, while they have comparable TBK1, IRF3, and NFκB activation as the
WT/SAVI
, the
AQ/SAVI
mice have no tissue inflammation, regular body weight, and normal lifespan. We propose that STING activation promotes tissue inflammation by depleting T-regs cells
in vivo
. Billions of modern humans have the dominant
HAQ, AQ
alleles. STING research and STING-targeting immunotherapy should consider
TMEM173
heterogeneity in humans.
Teaser:
One copy of the common human
HAQ
or
AQ TMEM173
gene prevents the gain-of-function
TMEM173
mutant-caused SAVI disease in mice.
Development of a Marmoset Apparatus for Automated Pulling to study cooperative behaviors
Authors: Meisner Olivia C , Shi Weikang , Fagan Nicholas A , Greenwood Joel , Jadi Monika P , Nandy Anirvan S , Chang Steve WC
Published: June 2024

In recent years, the field of neuroscience has increasingly recognized the importance of studying animal behaviors in naturalistic environments to gain deeper insights into ethologically relevant behavioral processes and neural mechanisms. The common marmoset (Callithrix jacchus), due to its small size, prosocial nature, and genetic proximity to humans, has emerged as a pivotal model toward this effort. However, traditional research methodologies often fail to fully capture the nuances of marmoset social interactions and cooperative behaviors. To address this critical gap, we developed the Marmoset Apparatus for Automated Pulling (MarmoAAP), a novel behavioral apparatus designed for studying cooperative behaviors in common marmosets. MarmoAAP addresses the limitations of traditional behavioral research methods by enabling high-throughput, detailed behavior outputs that can be integrated with video and audio recordings, allowing for more nuanced and comprehensive analyses even in a naturalistic setting. We also highlight the flexibility of MarmoAAP in task parameter manipulation which accommodates a wide range of behaviors and individual animal capabilities. Furthermore, MarmoAAP provides a platform to perform investigations of neural activity underlying naturalistic social behaviors. MarmoAAP is a versatile and robust tool for advancing our understanding of primate behavior and related cognitive processes. This new apparatus bridges the gap between ethologically relevant animal behavior studies and neural investigations, paving the way for future research in cognitive and social neuroscience using marmosets as a model organism.
Patch-walking: Coordinated multi-pipette patch clamp for efficiently finding synaptic connections
Authors: Yip Mighten C. , Gonzalez Mercedes M. , Lewallen Colby F. , Landry Corey R. , Kolb Ilya , Yang Bo , Stoy William M. , Fong Ming-fai , Rowan Matthew J.M. , Boyden Edward S. , Forest Craig R.
Published: June 2024

Significant technical challenges exist when measuring synaptic connections between neurons in living brain tissue. The patch clamping technique, when used to probe for synaptic connections, is manually laborious and time-consuming. To improve its efficiency, we pursued another approach: instead of retracting all patch clamping electrodes after each recording attempt, we cleaned just one of them and reused it to obtain another recording while maintaining the others. With one new patch clamp recording attempt, many new connections can be probed. By placing one pipette in front of the others in this way, one can “walk” across the tissue, termed “patch-walking.” We performed 136 patch clamp attempts for two pipettes, achieving 71 successful whole cell recordings (52.2%). Of these, we probed 29 pairs (i.e., 58 bidirectional probed connections) averaging 91
µ
m intersomatic distance, finding 3 connections. Patch-walking yields 80-92% more probed connections, for experiments with 10-100 cells than the traditional synaptic connection searching method.
The subthalamic nucleus contributes causally to perceptual decision-making in monkeys
Authors: Branam Kathryn , Gold Joshua I , Ding Long
Published: June 2024

The subthalamic nucleus (STN) plays critical roles in the motor and cognitive function of the basal ganglia (BG), but the exact nature of these roles is not fully understood, especially in the context of decision-making based on uncertain evidence. Guided by theoretical predictions of specific STN contributions, we used single-unit recording and electrical microstimulation in the STN of healthy monkeys to assess its causal, computational roles in visual-saccadic decisions based on noisy evidence. The recordings identified subpopulations of STN neurons with distinct task-related activity patterns that related to different theoretically predicted functions. Microstimulation caused changes in behavioral choices and response times that reflected multiple contributions to an ‘accumulate-to-bound’-like decision process, including modulation of decision bounds and evidence accumulation, and to non-perceptual processes. These results provide new insights into the multiple ways that the STN can support higher brain function.
Learning enhances behaviorally relevant representations in apical dendrites
Authors: Benezra Sam E , Patel Kripa B , Perez Campos Citlali , Hillman Elizabeth MC , Bruno Randy M
Published: June 2024

Learning alters cortical representations and improves perception. Apical tuft dendrites in cortical layer 1, which are unique in their connectivity and biophysical properties, may be a key site of learning-induced plasticity. We used both two-photon and SCAPE microscopy to longitudinally track tuft-wide calcium spikes in apical dendrites of layer 5 pyramidal neurons in barrel cortex as mice learned a tactile behavior. Mice were trained to discriminate two orthogonal directions of whisker stimulation. Reinforcement learning, but not repeated stimulus exposure, enhanced tuft selectivity for both directions equally, even though only one was associated with reward. Selective tufts emerged from initially unresponsive or low-selectivity populations. Animal movement and choice did not account for changes in stimulus selectivity. Enhanced selectivity persisted even after rewards were removed and animals ceased performing the task. We conclude that learning produces long-lasting realignment of apical dendrite tuft responses to behaviorally relevant dimensions of a task.
Learning enhances behaviorally relevant representations in apical dendrites
Authors: Benezra Sam E. , Patel Kripa B. , Campos Citlali Pérez , Hillman Elizabeth M.C. , Bruno Randy M.
Published: June 2024

Learning alters cortical representations and improves perception. Apical tuft dendrites in Layer 1, which are unique in their connectivity and biophysical properties, may be a key site of learning-induced plasticity. We used both two-photon and SCAPE microscopy to longitudinally track tuft-wide calcium spikes in apical dendrites of Layer 5 pyramidal neurons as mice learned a tactile behavior. Mice were trained to discriminate two orthogonal directions of whisker stimulation. Reinforcement learning, but not repeated stimulus exposure, enhanced tuft selectivity for both directions equally, even though only one was associated with reward. Selective tufts emerged from initially unresponsive or low-selectivity populations. Animal movement and choice did not account for changes in stimulus selectivity. Enhanced selectivity persisted even after rewards were removed and animals ceased performing the task. We conclude that learning produces long-lasting realignment of apical dendrite tuft responses to behaviorally relevant dimensions of a task.
Opposing actions of co-released GABA and neurotensin on the activity of preoptic neurons and on body temperature
Authors: Tabarean Iustin V
Published: June 2024

Neurotensin (Nts) is a neuropeptide acting as a neuromodulator in the brain. Pharmacological studies have identified Nts as a potent hypothermic agent. The medial preoptic area, a region that plays an important role in the control of thermoregulation, contains a high density of neurotensinergic neurons and Nts receptors. The conditions in which neurotensinergic neurons play a role in thermoregulation are not known. In this study, optogenetic stimulation of preoptic Nts neurons induced a small hyperthermia. In vitro, optogenetic stimulation of preoptic Nts neurons resulted in synaptic release of GABA and net inhibition of the preoptic pituitary adenylate cyclase-activating polypeptide (Adcyap1) neurons firing activity. GABA-A receptor antagonist or genetic deletion of Slc32a1 (VGAT) in Nts neurons unmasked also an excitatory effect that was blocked by a Nts receptor 1 antagonist. Stimulation of preoptic Nts neurons lacking Slc32a1 resulted in excitation of Adcyap1 neurons and hypothermia. Mice lacking Slc32a1 expression in Nts neurons presented changes in the fever response and in the responses to heat or cold exposure as well as an altered circadian rhythm of body temperature. Chemogenetic activation of all Nts neurons in the brain induced a 4–5°C hypothermia, which could be blocked by Nts receptor antagonists in the preoptic area. Chemogenetic activation of preoptic neurotensinergic projections resulted in robust excitation of preoptic Adcyap1 neurons. Taken together, our data demonstrate that endogenously released Nts can induce potent hypothermia and that excitation of preoptic Adcyap1 neurons is the cellular mechanism that triggers this response.
Using linear measurements to diagnose the ecological habitat of Spinosaurus
Authors: Smart Sean , Sakamoto Manabu
Published: June 2024

Much of the ecological discourse surrounding the polarising theropod Spinosaurus has centred on qualitative discussions. Using a quantitative multivariate data analytical approach on size-adjusted linear measurements of the skull, we examine patterns in skull shape across a range of sauropsid clades and three ecological realms (terrestrial, semi-aquatic, and aquatic). We utilise cluster analyses to identify emergent properties of the data which associate properties of skull shape with ecological realm occupancy. Results revealed terrestrial ecologies to be significantly distinct from both semi- and fully aquatic ecologies, the latter two were not significantly different. Spinosaurids (including Spinosaurus) plotted away from theropods in morphospace and close to both marine taxa and wading birds. The position of nares and the degree of rostral elongation had the greatest effect on categorisation. Comparisons of supervised (k-means) and unsupervised clustering demonstrated categorising taxa into three groups (ecological realms) was inappropriate and suggested instead that cluster division is based on morphological adaptations to feeding on aquatic versus terrestrial food items. The relative position of the nares in longirostrine taxa is associated with which skull bones are elongated. Rostral elongation is observed by either elongating the maxilla and the premaxilla or by elongating the maxilla only. This results in the nares positioned towards the orbits or towards the anterior end of the rostrum respectively, with implications on available feeding methods. Spinosaurids, especially Spinosaurus, show elongation in the maxilla-premaxilla complex, achieving similar functional outcomes to elongation of the premaxilla seen in birds, particularly large-bodied piscivorous taxa. Such a skull construction would bolster “stand-and-wait” predation of aquatic prey to a greater extent than serving other proposed feeding methods.
In Vitro Transcription and Immobilized Template Analysis of Preinitiation Complexes
Authors: Lin Justin J. , Carey Michael
Published: January 2012

In the study of gene regulation, it is often necessary to employ functional assays that investigate the action or mechanism of specific promoters or enhancer‐binding factors and their role in transcription by RNA polymerase II. Although many assays measure the transcription of a gene under the control of an endogenous or model activator in vivo, it is often useful to recreate transcription in vitro in order to study specific regulatory mechanisms. In this unit, protocols are presented that will allow the investigator to perform in vitro transcription using preinitiation complexes assembled from cellular extracts on either naked DNA or chromatin templates. Curr. Protoc. Mol. Biol. 97:12.14.1‐12.14.19. © 2012 by John Wiley & Sons, Inc.
Protein Databases on the Internet
Authors: Xu Dong
Published: January 2012

Protein databases have become a crucial part of modern biology. Huge amounts of data for protein structures, functions, and particularly sequences are being generated. Searching databases is often the first step in the study of a new protein. Comparison between proteins or between protein families provides information about the relationship between proteins within a genome or across different species, and hence offers much more information than can be obtained by studying only an isolated protein. In addition, secondary databases derived from experimental databases are also widely available. These databases reorganize and annotate the data or provide predictions. The use of multiple databases often helps researchers understand the structure and function of a protein. Although some protein databases are widely known, they are far from being fully utilized in the protein science community. This unit provides a starting point for readers to explore the potential of protein databases on the Internet. Curr. Protoc. Mol. Biol. 97:19.4.1‐19.4.17. © 2012 by John Wiley & Sons, Inc.
Hexylthiophene‐Featured D–A–π–A Structural Indoline Chromophores for Coadsorbent‐Free and Panchromatic Dye‐Sensitized Solar Cells
Authors: Wu Yongzhen , Zhang Xi , Li Wenqin , Wang Zhong‐Sheng , Tian He , Zhu Weihong
Published: January 2012

For a sensitizer with a strong π‐conjugation system, a coadsorbent is needed to hinder dye aggregation. However, coadsorption always brings a decrease in dye coverage on the TiO2 surface. Organic ‘‘D–A–π–A’’ dyes, WS‐6 and WS‐11, are designed and synthesized based on the known WS‐2 material for coadsorbent‐free, dye‐sensitized solar cells (DSSCs). Compared with the traditional D–π–A structure, these D–A–π–A indoline dyes, with the additional incorporated acceptor unit of benzothiadiazole in the π‐conjugation, exhibit a broad photoresponse, high redox stability, and convenient energy‐level tuning. The attached n‐hexyl chains in both dyes are effective to suppress charge recombination, resulting in a decreased dark current and enhanced open‐circuit voltage. Electrochemical impedance spectroscopy studies indicate that both the resistance for charge recombination and the electron lifetime are increased after the introduction of alkyl chains to the dye molecules. Without deoxycholic acid coadsorption, the power‐conversion efficiency of WS‐6 (7.76%) on a 16 μm‐thick TiO2 film device is 45% higher than that of WS‐2 (5.31%) under the same conditions. The additional n‐hexylthiophene in WS‐11 extends the photoresponse to a panchromatic spectrum but causes a low incident photon‐to‐current conversion efficiency.
Mantle cell lymphoma displays a homogenous methylation profile: A comparative analysis with chronic lymphocytic leukemia
Authors: Halldórsdóttir Anna Margrét , Kanduri Meena , Marincevic Millaray , Mansouri Larry , Isaksson Anders , Göransson Hanna , Axelsson Tomas , Agarwal Prasoon , Jernberg‐Wiklund Helena , Stamatopoulos Kostas , Sander Birgitta , Ehrencrona Hans , Rosenquist Richard
Published: January 2012

Mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL) are mature CD5+ B‐cell malignancies with different biological/clinical characteristics. We recently reported an association between different prognostic subgroups of CLL (i.e., IGHV mutated and unmutated) and genomic methylation pattern. However, the relationship between DNA methylation and prognostic markers, such as the proliferation gene expression signature, has not been investigated in MCL. We applied high‐resolution methylation microarrays (27,578 CpG sites) to assess the global DNA methylation profiles in 20 MCL (10 each with high/low proliferation signature) and 30 CLL (15 poor‐prognostic IGHV unmutated subset #1 and 15 good‐prognostic IGHV mutated subset #4) samples. Notably, MCL and each CLL subset displayed distinct genomic methylation profiles. After unsupervised hierarchical clustering, 17/20 MCL cases formed a cluster separate from CLL, while CLL subsets #1 and #4 formed subclusters. Surprisingly, few differentially methylated genes (n = 6) were identified between high vs. low proliferation MCL. In contrast, distinct methylation profiles were demonstrated for MCL and CLL. Importantly, certain functional classes of genes were preferentially methylated in either disease. For instance, developmental genes, in particular homeobox transcription factor genes (e.g., HLXB9, HOXA13), were more highly methylated in MCL, whereas apoptosis‐related genes were enriched among targets methylated in CLL (e.g., CYFIP2, NR4A1). Results were validated using pyrosequencing, RQ‐PCR and reexpression of specific genes. In summary, the methylation profile of MCL was homogeneous and no correlation with the proliferation signature was observed. Compared to CLL, however, marked differences were discovered such as the preferential methylation of homeobox genes in MCL. Am. J. Hematol., 2012. © 2012 Wiley Periodicals, Inc.
Lung cancer risk among construction workers in California, 1988–2007
Authors: Calvert Geoffrey M. , Luckhaupt Sara , Lee Soo‐Jeong , Cress Rosemary , Schumacher Pam , Shen Rui , Tak SangWoo , Deapen Dennis
Published: January 2012

Background

Although lung cancer risks can vary by race/ethnicity and by construction occupation, these risks have not been examined extensively.

Methods

This study analyzed 110,937 lung cancer cases identified from the California Cancer Registry between 1988 and 2007. Mean age at diagnosis, proportion diagnosed at an advanced stage, and proportion with 3‐year survival were calculated for lung cancer cases employed in the construction industry. Case–control methodology was also used to assess the risk of lung cancer. Morbidity odds ratios (MORs) were estimated by conditional logistic regression.

Results

Construction workers were found to have a significantly elevated risk for all lung cancer combined (MOR = 1.57) and for each lung cancer histologic subtype examined. All construction occupations, except managers/engineers and supervisors, had a significantly elevated risk for all lung cancer combined. Roofers and welders had the highest risks for total lung cancer and for each of the histologic subtypes. Construction workers in each of the four race/ethnicity groups also had significantly increased lung cancer risks. Compared to non‐construction workers, construction workers were diagnosed at an earlier age, at a more advanced stage, and had significantly lower 3‐year survival, though differences were modest.

Conclusion

These findings justify additional reductions in carcinogenic exposures in construction, and increased support for smoking cessation programs at construction sites. Am. J. Ind. Med. 55:412–422, 2012. © 2012 Wiley Periodicals, Inc.