bluuebunny/crossref_metadata_2025 huggingface dataset:
PERAN BADAN PENELITIAN DAN PENGEMBANGAN KEMENTERIAN DALAM NEGERI DALAM MENGIMPLEMENTASIKAN INOVASI DAERAH SESUAI DENGAN PERATURAN PEMERINTAH NOMOR 38 TAHUN 2017 TENTANG INOVASI DAERAH
Authors: Simanungkalit David Julianto , Prasojo Eko
Published: January 2022

Penelitian ini bertujuan untuk melihat dan menganalisis bagaimana kebijakan inovasi diimplementasikan oleh Badan Penelitian dan Pengembangan Kementerian Dalam Negeri. Penelitian ini menggunakan paradigma post-positivisme dengan metode penelitian kualitatif. Wawancara mendalam serta studi dokumen dilakukan untuk memperoleh data dan informasi yang diperlukan. Implementasi yang dilaksanakan mulai dari tingkat pimpinan hingga bawahan dan berkolaborasi dengan berbagai aktor diharapkan dapat menjadi tonggak utama pelaksanaan inovasi daerah sehingga berdayaguna untuk meningkatkan kesejahteraan rakyat dan kemandirian daerah. Namun untuk meningkatkan kualitas pelaksanaan program inovasi daerah tersebut masih dibutuhkan penguatan peran BPP Kemendagri meliputi aspek sumber daya manusia, program, dan anggaran.

Kata Kunci: implementasi, inovasi daerah.
PENGELOLAAN KONFLIK POLITIK DI DESA ARANG LIMBUNG KECAMATAN SUNGAI RAYA KABUPATEN KUBU RAYA
Authors: S.stp Hendayana
Published: January 2022

Penelitian ini dilatarbelakangi pada Pengelolaan Konflik Politik Di Desa Arang limbung Kecamatan Sungai Raya Kabupaten Kubu Raya, dimana konflik yang terjadi akibat adanya kelompok yang pro dan kontra atas perubahan status desa Arang Limbung untuk menjadi kecamatan. Tujuan dari penelitian tersebut untuk mengidentifikasikan dan menemukan pemecahan permasalahan yang dihadapi, khususnya yang terkait konflik politik yang terjadi di desa Arang Limbung. Penelitian ini menggunakan metode deskriptif dan analisis data yang digunakan adalah analisis kualitatif yang merupakan proses penyederhanaan data ke dalam bentuk yang lebih mudah dibaca dan diinterpretasikan. Kesimpulan dari pengamatan ini adalah masih ditemukan permasalahan konflik politik di Desa Arang Limbung dari berbagai kepentingan sekelompok orang yang pro dan kontra untuk perubahan status desa Arang Limbung menjadi Kelurahan. Dengan adanya penelitian ini diharapkan dapat menyelesaikan segala konflik politik yang ada di desa Arang Limbung dengan mencari solusi yang terbaik agar dapat menciptakan kondisi yang kondusif, aman, dan tentram di Desa Arang Limbung
IMPLEMENTASI PERATURAN DAERAH NOMOR 13 TAHUN 2018 TENTANG PENEMPATAN TENAGA KERJA LOKAL DI KOTA PEKANBARU PROVINSI RIAU
Authors: Praja Selvia Junita , Auzola Faiq
Published: January 2022

Permasalahan kompleks yang hingga saat ini belum dapat dituntaskan oleh Pemerintah Kota Pekanbaru adalah permasalahan pembangunan ekonomi, khususnya angka pengangguran yang tinggi. Kota Pekanbaru sebagai salah satu kota yang memiliki IHK (indeks harga konsumen) tertinggi di Indonesia mengeluarkan Peraturan Daerah untuk meningkatkan kesejahteraan masyarakat Kota Pekanbaru dengan cara memprioritaskan dan memberdayakan para tenaga kerja lokal. Penelitian ini menggunakan teori Implementasi Edward III. Dalam penelitian ini metode yang digunakan adalah kualitatif dengan pendekatan deskriptif, sedangkan untuk pengumpulan data di lapangan menggunakan teknik dokumentasi, wawancara serta observasi. Berdasarkan hasil penelitian ini menunjukkan bahwa Peraturan Daerah ini belum terlaksana dengan baik. Hal tersebut dapat dilihat dari beberapa faktor yang mempengaruhi gagalnya pencapaian target tersebut yaitu dimensi komunikasi kurangya pemahaman masyarakat, dimensi sumber daya terdapat sarana prasarana yang tidak mendukung, minimnya dana yang dianggarkan, serta kurangnya kuantitas sumber daya manusia di Dinas Tenaga Kerja Lokal Kota Pekanbaru. Dimensi disposisi pemerintah belum mematuhi terkait penyerapan tenaga kerja lokal sebesar 75%, terdapat oknum perusahaan yang tidak transparan dalam pelaporan ketersediaan lowongan pekerjaan, sedangkan dimensi struktur birokrasi sudah baik, dilihat dari adanya standar operasional prosedur. DISNAKER Kota Pekanbaru telah melakukan upaya untuk menyikapi hal tersebut dengan cara melakukan sosialisasi Perda kepada masyarakat, pengawasan dan pembinaan terhadap pihak perusahaan serta mengajukan penambahan jumlah pegawai, dana dan peningkatan sarana prasarana.

Kata Kunci: Implementasi, Peraturan, Tenaga Kerja Lokal.
DINAMIKA EKONOMI POLITIK GLOBAL DAN PEMBAGIAN KERJA INTERNASIONAL
Authors: Arwanto Arwanto , Anggraini Wike
Published: January 2022

Penelitian ini bertujuan untuk mengetahui dinamika dan perspektif ekonomi politik global dengan menggunakan metode kajian literatur. Kaum nasionalis ekonomi menempatkan negara sebagai aktor utama. Sedangkan, liberalis ekonomi berpendapat bahwa negara harus berkolaborasi dengan aktor lain. Ada dua dinamika yang membentuk ekonomi politik global, yaitu perdagangan internasional dan produksi transnasional. Kedua dinamika tersebut berimplikasi pada pembagian kerja secara global. Perdagangan internasional dengan konsep 'keunggulan komparatif' mempengaruhi spesialisasi tenaga kerja, sedangkan produksi transnasional berimplikasi dalam mendorong pembagian kerja di seluruh dunia. Namun, ada skeptisisme terhadap kedua dinamika tersebut. Misalnya, mereka diyakini berperan dalam ketimpangan upah, terutama antara tenaga kerja yang kurang terampil dan tenaga kerja yang lebih terampil, khususnya pada negara-negara berkembang.
Pengaruh Kompetensi dan Disiplin Terhadap Kinerja dengan Etos Kerja sebagai Variabel Mediasi di Kecamatan Lubuk Sikaping
Authors: Afandi Arif
Published: January 2022

Penelitian ini bertujuan untuk mengetahui pengaruh kompetensi dan disiplin kerja terhadap kinerja pegawai kantor Kecamatan Lubuk Sikaping Kabupaten Pasaman dengan etos kerja sebagai variabel mediasi. Penelitian ini dilatarbelakangi oleh kompetensi yang masih rendah, disiplin kerja yang masih perlu ditingkatkan, etos kerja yang masih belum stabil, sehingga mengakibatkan rendahnya kinerja pegawai pada kantor Kecamatan Lubuk Sikaping Kabupaten Pasaman. Jenis penelitian menggunakan pendekatan kuantitatif dengan menggunakan pendekatan Partial Least Square (PLS) dengan model persamaan Structural Equation Modeling (SEM). Teknik pengumpulan data dengan kuesioner, observasi dan wawancara. Responden penelitian ini adalah 40 orang pegawai kantor Kecamatan Lubuk Sikaping Kabupaten Pasaman. Metode penarikan sampel mengunakan metode total sampling dimana seluruh populasi dalam penelitian ini dijadikan sampel penelitian. Pengujian hipotesis dihitung dengan program Smart Partial Least Square (PLS) 3. Dari hasil penelitian ini ditemukan bahwa kompetensi tidak berpengaruh terhadap etos kerja, disiplin kerja tidak berpengaruh terhadap etos kerja, etos kerja berpengaruh terhadap kinerja, kompetensi berpengaruh terhadap kinerja, disiplin kerja tidak berpengaruh terhadap kinerja, etos kerja sebagai variabel mediasi berpengaruh antara kompetensi dan kinerja, serta etos kerja sebagai variabel mediasi berpengaruh antara disiplin kerja dan kinerja pegawai kantor Kecamatan Lubuk Sikaping Kabupaten Pasaman Provinsi Sumatera Barat.
Digitalisasi Pemerintahan Melalui Implementasi SIMRAL dalam Mendukung Keberlanjutan Pembangunan Daerah
Authors: Amanuha Galih , Hasanah Budi , Sururi Ahmad , Sukendar Sukendar
Published: January 2022

Implementasi Sistem Informasi Manajemen Perencanaan, Penganggaran, dan Pelaporan (SIMRAL) di Kabupaten Serang menunjukan adanya kendala dan hambatan khususnya pada kantor-kantor kecamatan. Penelitian ini bertujuan untuk mendiskusikan bagaimana digitalisasi pemerintahan melalui implementasi simral dalam mendukung keberlanjutan pembangunan daerah penerapan aplikasi Sistem Informasi Manajemen Perencanaan, Penganggaran dan Pelaporan (SIMRAL) dalam mendukung pembangunan daerah di Kabupaten Serang dengan menggunakan pendekatan content development, competency building, connectivity, cyber laws, citizen interfaces dan capital. Metode penelitian menggunakan pendekatan kualitatif melalui teknik pengumpulan data wawancara, observasi dan studi dokumentasi. Analisis data menggunakan teknik reduksi data, penyajian data, kesimpulan. Hasil penelitian menunjukkan bahwa implementasi SIMRAL di lingkup Kabupaten Serang pada beberapa indikator menunjukan hasil yang cukup baik, meliputi content development, cyber laws dan capital. Adapun 3 indikator lainnya menunjukan hasil yang kurang baik yaitu competency building, connectivity dan citizen interfaces.
ANALISIS SAHABAT SENSUS PADA SENSUS PENDUDUK ONLINE 2020 DI WILAYAH KALIMANTAN BARAT
Authors: Debataraja Naomi , Sulastri Fitri , Valensia Ellen
Published: January 2022

Implementation of 2020 census of Indonesian Population is the government’s first step in realizing One Indonesian Population Data. The online census of Indonesian population is one of the stages of the 2020 census of Indonesian Population where residents can enter their information independently through the website. In order to increase public participation in 2020 online census of Indonesian population, BPS Collaborates with universities throughout Indonesia, one of which is the Mathematics Department of Tanjungpura University Pontianak as a census friend. This study aims to provide an overview of the publicity of the online census and its responses as well as the obstacles experienced by census friends, to determine the factors that affect the constraints of census friends, and to examine the effect of gender variables on the constraints of census friends. The results of the analysis show that the social media used in the publication of the 2020 online census are Instagram, WhatsApp, Facebook, Telegram, Twitter, and Sestyc. The obstacles experienced by census friends amounted to twelve obstacles. The constraint factor which is formed from the factoring process produces two factors. Besides, it was found that there was no influence between the sexes on the constraints of census friends.

 

Pelaksanaan Sensus Penduduk Indonesia Tahun 2020 merupakan langkah awal pemerintah dalam mewujudkan Satu Data Kependudukan Indonesia. Sensus Penduduk Indonesia secara online merupakan salah satu tahapan dari Sensus Penduduk Indonesia Tahun 2020 dimana penduduk dapat memasukkan informasinya secara mandiri melalui website yang telah disediakan. Dalam rangka meningkatkan partisipasi masyarakat dalam pencacahan penduduk Indonesia secara online tahun 2020, BPS bekerja sama dengan 43 perguruan tinggi di seluruh Indonesia, salah satunya Jurusan Matematika Universitas Tanjungpura Pontianak sebagai sahabat sensus. Penelitian ini bertujuan untuk memberikan gambaran tentang publisitas sensus online beserta tanggapannya serta kendala yang dialami oleh sahabat sensus, menentukan faktor-faktor yang mempengaruhi kendala teman sensus, dan untuk menentukan pengaruh variabel jenis kelamin terhadap kendala tersebut. Hasil analisis menunjukkan bahwa media sosial yang digunakan dalam publikasi sensus online 2020 adalah Instagram, WhatsApp, Facebook, Telegram, Twitter, dan Sestyc. Hambatan yang dialami teman sensus berjumlah dua belas kendala. Faktor kendala yang terbentuk dari proses faktorial menghasilkan dua faktor. Selain itu, tidak ditemukan adanya pengaruh antar jenis kelamin terhadap kendala sahabat sensus.
Supplementation With Chinese Medicinal Plant Extracts From Lonicera hypoglauca and Scutellaria baicalensis Mitigates Colonic Inflammation by Regulating Oxidative Stress and Gut Microbiota in a Colitis Mouse Model
Authors: Wan Fan , Wang Mengyu , Zhong Ruqing , Chen Liang , Han Hui , Liu Lei , Zhao Yong , Lv Huiyuan , Hou Fujiang , Yi Bao , Zhang Hongfu
Published: January 2022

Colitis, a chronic inflammatory bowel disease, is characterized by bloody diarrhea and inflammation in the colon. Lonicera hypoglauca (“Shanyinhua” in Chinese) and Scutellaria baicalensis (“Huangqin” in Chinese) are two traditional Chinese medicinal plants rich in polyphenols, such as chlorogenic acid (CGA) and baicalin (BA), with the effects of anti-inflammation and antioxidation. However, it remains unknown whether extracts from L. hypoglauca and S. baicalensis (LSEs) could mitigate colonic inflammation. In the present study, ICR mice (22.23 ± 1.65 g) were allocated to three groups treated with chow diet without (CON) or with dextran sulfate sodium (DSS) (CON+DSS) in water or LSE supplementation in diet with DSS (LSE+DSS), and then inflammatory and oxidative parameters and colonic microbiota were detected. The results showed that LSE (500 mg/kg) treatment mitigated DSS-induced colitis symptoms and restored the shortened colon length, the increased disease activity index (DAI), and the damaged intestinal barrier. In serum, LSE supplementation significantly decreased levels of pro-inflammatory cytokines including interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and lipopolysaccharide (LPS) and increased IL-10 level. Meanwhile, superoxide dismutase (SOD) and catalase (CAT) were increased, and malondialdehyde (MDA) and reactive oxygen species (ROS) levels were decreased. In the colon tissue, qPCR results showed that LSE supplementation dramatically downregulated the transcriptional expression of IL-1β, IL-6, TNF-α, and MDA and upregulated the expression of SOD1, CAT, and IL-10. Additionally, the damaged gut barriers occludin and zonula occludens-1 (ZO-1) in the CON+DSS group were enhanced with LSE supplementation. Furthermore, LSE treatment regulated the gut microbial communities with higher relative abundance of Dubosiella and Ruminococcus torques group and lower relative abundance of Bacteroides and Turicibacter. Moreover, the contents of short-chain fatty acids (SCFAs) as products of gut microbiota were also increased. Correlation analysis showed that the mRNA expression of SOD1 was negatively correlated with TNF-α (r = -0.900, P < 0.05); the mRNA expression of IL-6 (r = -0.779, P < 0.05) and TNF-α (r = -0.703, P < 0.05) had a dramatically negative correlation with Dubosiella. In conclusion, LSE supplementation could effectively ameliorate inflammation by modulating oxidative stress and gut microbiota in a colitis mouse model.
Phages in the Gut Ecosystem
Authors: Zuppi Michele , Hendrickson Heather L. , O’Sullivan Justin M. , Vatanen Tommi
Published: January 2022

Phages, short for bacteriophages, are viruses that specifically infect bacteria and are the most abundant biological entities on earth found in every explored environment, from the deep sea to the Sahara Desert. Phages are abundant within the human biome and are gaining increasing recognition as potential modulators of the gut ecosystem. For example, they have been connected to gastrointestinal diseases and the treatment efficacy of Fecal Microbiota Transplant. The ability of phages to modulate the human gut microbiome has been attributed to the predation of bacteria or the promotion of bacterial survival by the transfer of genes that enhance bacterial fitness upon infection. In addition, phages have been shown to interact with the human immune system with variable outcomes. Despite the increasing evidence supporting the importance of phages in the gut ecosystem, the extent of their influence on the shape of the gut ecosystem is yet to be fully understood. Here, we discuss evidence for phage modulation of the gut microbiome, postulating that phages are pivotal contributors to the gut ecosystem dynamics. We therefore propose novel research questions to further elucidate the role(s) that they have within the human ecosystem and its impact on our health and well-being.
Automatic Segmentation of Kidneys and Kidney Tumors: The KiTS19 International Challenge
Authors: Sathianathen Niranjan J. , Heller Nicholas , Tejpaul Resha , Stai Bethany , Kalapara Arveen , Rickman Jack , Dean Joshua , Oestreich Makinna , Blake Paul , Kaluzniak Heather , Raza Shaneabbas , Rosenberg Joel , Moore Keenan , Walczak Edward , Rengel Zachary , Edgerton Zach , Vasdev Ranveer , Peterson Matthew , McSweeney Sean , Peterson Sarah , Papanikolopoulos Nikolaos , Weight Christopher
Published: January 2022

Purpose: Clinicians rely on imaging features to calculate complexity of renal masses based on validated scoring systems. These scoring methods are labor-intensive and are subjected to interobserver variability. Artificial intelligence has been increasingly utilized by the medical community to solve such issues. However, developing reliable algorithms is usually time-consuming and costly. We created an international community-driven competition (KiTS19) to develop and identify the best system for automatic segmentation of kidneys and kidney tumors in contrast CT and report the results.

Methods: A training and test set of CT scans that was manually annotated by trained individuals were generated from consecutive patients undergoing renal surgery for whom demographic, clinical and outcome data were available. The KiTS19 Challenge was a machine learning competition hosted on grand-challenge.org in conjunction with an international conference. Teams were given 3 months to develop their algorithm using a full-annotated training set of images and an unannotated test set was released for 2 weeks from which average Sørensen-Dice coefficient between kidney and tumor regions were calculated across all 90 test cases.

Results: There were 100 valid submissions that were based on deep neural networks but there were differences in pre-processing strategies, architectural details, and training procedures. The winning team scored a 0.974 kidney Dice and a 0.851 tumor Dice resulting in 0.912 composite score. Automatic segmentation of the kidney by the participating teams performed comparably to expert manual segmentation but was less reliable when segmenting the tumor.

Conclusion: Rapid advancement in automated semantic segmentation of kidney lesions is possible with relatively high accuracy when the data is released publicly, and participation is incentivized. We hope that our findings will encourage further research that would enable the potential of adopting AI into the medical field.
Texture Analysis Using CT and Chemical Shift Encoding-Based Water-Fat MRI Can Improve Differentiation Between Patients With and Without Osteoporotic Vertebral Fractures
Authors: Sollmann Nico , Becherucci Edoardo A. , Boehm Christof , Husseini Malek El , Ruschke Stefan , Burian Egon , Kirschke Jan S. , Link Thomas M. , Subburaj Karupppasamy , Karampinos Dimitrios C. , Krug Roland , Baum Thomas , Dieckmeyer Michael
Published: January 2022

Purpose

Osteoporosis is a highly prevalent skeletal disease that frequently entails vertebral fractures. Areal bone mineral density (BMD) derived from dual-energy X-ray absorptiometry (DXA) is the reference standard, but has well-known limitations. Texture analysis can provide surrogate markers of tissue microstructure based on computed tomography (CT) or magnetic resonance imaging (MRI) data of the spine, thus potentially improving fracture risk estimation beyond areal BMD. However, it is largely unknown whether MRI-derived texture analysis can predict volumetric BMD (vBMD), or whether a model incorporating texture analysis based on CT and MRI may be capable of differentiating between patients with and without osteoporotic vertebral fractures.

Materials and Methods

Twenty-six patients (15 females, median age: 73 years, 11 patients showing at least one osteoporotic vertebral fracture) who had CT and 3-Tesla chemical shift encoding-based water-fat MRI (CSE-MRI) available were analyzed. In total, 171 vertebral bodies of the thoracolumbar spine were segmented using an automatic convolutional neural network (CNN)-based framework, followed by extraction of integral and trabecular vBMD using CT data. For CSE-MRI, manual segmentation of vertebral bodies and consecutive extraction of the mean proton density fat fraction (PDFF) and T2* was performed. First-order, second-order, and higher-order texture features were derived from texture analysis using CT and CSE-MRI data. Stepwise multivariate linear regression models were computed using integral vBMD and fracture status as dependent variables.

Results

Patients with osteoporotic vertebral fractures showed significantly lower integral and trabecular vBMD when compared to patients without fractures (p<0.001). For the model with integral vBMD as the dependent variable, T2* combined with three PDFF-based texture features explained 40% of the variance (adjusted R2[Ra2] = 0.40; p<0.001). Furthermore, regarding the differentiation between patients with and without osteoporotic vertebral fractures, a model including texture features from CT and CSE-MRI data showed better performance than a model based on integral vBMD and PDFF only (Ra2 = 0.47 vs. Ra2 = 0.81; included texture features in the final model: integral vBMD, CT_Short-run_emphasis, CT_Varianceglobal, and PDFF_Variance).

Conclusion

Using texture analysis for spine CT and CSE-MRI can facilitate the differentiation between patients with and without osteoporotic vertebral fractures, implicating that future fracture prediction in osteoporosis may be improved.
Sellar Region Lesions and Intracranial Aneurysms in the Era of Endoscopic Endonasal Approach
Authors: Yan Siyu , Liu Yifan , Liu Chang , Yang Li , Qin Yun , Liu Ran , Wang Shan , Li Xue , Yang Wenjie , Ma Lu , You Chao , Zhou Liangxue , Tian Rui
Published: January 2022

In the clinical practice of neurosurgery, the endoscopic endonasal approach (EEA) has been the mainstream approach in the management of sellar region diseases. However, clinicians have come to realize that EEA procedure is associated with intraoperative hemorrhage. Due to the limited surgical field and poor proximal control under endoscope, massive hemorrhage always leads to severe complication or even perioperative death. Previously, intraoperative hemorrhage used to be attributed to endoscopic intervention of cavernous sinus or internal carotid artery, but our recent understanding of EEA indicated that preoperatively complicated intracranial aneurysms (IAs) may play a role. In this article, we retrospectively reviewed the baseline characteristics, treatment strategy, pathology, intraoperative findings, as well as radiological profiles of sellar region lesions complicated with IAs. With the focus put on the high comorbidity rate of sellar region lesions and IAs, we did further statistical analysis to sketch the outline of this coexisting circumstance and to emphasize the importance of computed tomography angiography (CTA) as routine EEA preoperative examination. Thorough patient-surgeon communication should be proceeded before the formulation of an individualized treatment strategy.
Liraglutide Activates Type 2 Deiodinase and Enhances β3-Adrenergic-Induced Thermogenesis in Mouse Adipose Tissue
Authors: Oliveira Fernanda C. B. , Bauer Eduarda J. , Ribeiro Carolina M. , Pereira Sidney A. , Beserra Bruna T. S. , Wajner Simone M. , Maia Ana L. , Neves Francisco A. R. , Coelho Michella S. , Amato Angelica A.
Published: January 2022

Aims

Liraglutide is a long-acting glucagon-like peptide 1 (GLP-1) receptor agonist used as an anti-hyperglycemic agent in type 2 diabetes treatment and recently approved for obesity management. Weight loss is attributed to appetite suppression, but therapy may also increase energy expenditure. To further investigate the effect of GLP-1 signaling in thermogenic fat, we assessed adipose tissue oxygen consumption and type 2 deiodinase (D2) activity in mice treated with liraglutide, both basally and after β3-adrenergic treatment.

Methods

Male C57BL/6J mice were randomly assigned to receive liraglutide (400 μg/kg, n=12) or vehicle (n=12). After 16 days, mice in each group were co-treated with the selective β3-adrenergic agonist CL316,243 (1 mg/kg, n=6) or vehicle (n=6) for 5 days. Adipose tissue depots were assessed for gene and protein expression, oxygen consumption, and D2 activity.

Results

Liraglutide increased interscapular brown adipose tissue (iBAT) oxygen consumption and enhanced β3-adrenergic-induced oxygen consumption in iBAT and inguinal white adipose tissue (ingWAT). These effects were accompanied by upregulation of UCP-1 protein levels in iBAT and ingWAT. Notably, liraglutide increased D2 activity without significantly upregulating its mRNA levels in iBAT and exhibited additive effects to β3-adrenergic stimulation in inducing D2 activity in ingWAT.

Conclusions

Liraglutide exhibits additive effects to those of β3-adrenergic stimulation in thermogenic fat and increases D2 activity in BAT, implying that it may activate this adipose tissue depot by increasing intracellular thyroid activation, adding to the currently known mechanisms of GLP-1A-induced weight loss.
Secondary Seed Ingestion in Snakes: Germination Frequency and Rate, Seedling Viability, and Implications for Dispersal in Nature
Authors: Schuett Gordon W. , Reiserer Randall S. , Salywon Andrew M. , Blackwell Steven , Hodgson Wendy C. , Foster C. Drew , Hall James , Zach Ryan , Davis Mark A. , Greene Harry W.
Published: January 2022

The importance of vertebrate animals as seed dispersers (zoochory) has received increasing attention from researchers over the past 20 years, yet one category in particular, diploendozoochory, remains understudied. As the term implies, this is a two-phase seed dispersal system whereby a secondary seed predator (carnivorous vertebrate) consumes a primary seed predator or granivore (rodent and bird) with undamaged seeds in their digestive tract (mouth, cheek pouch, crop, stomach, or other organ), which are subsequently eliminated with feces. Surprisingly, although snakes are among the most abundant predators of granivorous vertebrates, they are the least studied group insofar as our knowledge of seed rescue and secondary dispersal in a diploendozoochorous system. Here, using live snake subjects of the Sonoran Desert (one viperid and two colubrid species) and seeds of the Foothill Palo Verde (Parkinsonia microphylla), a dominant tree of the same region, we experimentally tested germination frequency and rate, and seedling viability. Specifically, to mimic rodents with seed-laden cheek pouches, we tested whether wild-collected P. microphylla seeds placed in the abdomen of thawed laboratory mice and ingested by the snakes would retain their germination viability. Second, we examined whether seeds exposed to gut transit germinated at a greater frequency and rate than the controls. While we found strong statistical support for our first hypothesis, both aspects of the second one were not significant. Accordingly, we provide an explanation for these results based on specific life-history traits (dormant and non-dormant seeds) of P. microphylla. Our study provides support for the role of snakes as important agents of seed rescue and dispersal in nature, their potential as ecosystem engineers, and crucial evidence for the investment of field-based studies on diploendozoochorous systems in deserts and other ecosystems.
Genome Wide Association Study of Beef Traits in Local Alpine Breed Reveals the Diversity of the Pathways Involved and the Role of Time Stratification
Authors: Mancin Enrico , Tuliozi Beniamino , Pegolo Sara , Sartori Cristina , Mantovani Roberto
Published: January 2022

Knowledge of the genetic architecture of key growth and beef traits in livestock species has greatly improved worldwide thanks to genome-wide association studies (GWAS), which allow to link target phenotypes to Single Nucleotide Polymorphisms (SNPs) across the genome. Local dual-purpose breeds have rarely been the focus of such studies; recently, however, their value as a possible alternative to intensively farmed breeds has become clear, especially for their greater adaptability to environmental change and potential for survival in less productive areas. We performed single-step GWAS and post-GWAS analysis for body weight (BW), average daily gain (ADG), carcass fleshiness (CF) and dressing percentage (DP) in 1,690 individuals of local alpine cattle breed, Rendena. This breed is typical of alpine pastures, with a marked dual-purpose attitude and good genetic diversity. Moreover, we considered two of the target phenotypes (BW and ADG) at different times in the individuals’ life, a potentially important aspect in the study of the traits’ genetic architecture. We identified 8 significant and 47 suggestively associated SNPs, located in 14 autosomal chromosomes (BTA). Among the strongest signals, 3 significant and 16 suggestive SNPs were associated with ADG and were located on BTA10 (50–60 Mb), while the hotspot associated with CF and DP was on BTA18 (55–62 MB). Among the significant SNPs some were mapped within genes, such as SLC12A1, CGNL1, PRTG (ADG), LOC513941 (CF), NLRP2 (CF and DP), CDC155 (DP). Pathway analysis showed great diversity in the biological pathways linked to the different traits; several were associated with neurogenesis and synaptic transmission, but actin-related and transmembrane transport pathways were also represented. Time-stratification highlighted how the genetic architectures of the same traits were markedly different between different ages. The results from our GWAS of beef traits in Rendena led to the detection of a variety of genes both well-known and novel. We argue that our results show that expanding genomic research to local breeds can reveal hitherto undetected genetic architectures in livestock worldwide. This could greatly help efforts to map genomic complexity of the traits of interest and to make appropriate breeding decisions.
Residue–Residue Contact Can Be a Potential Feature for the Prediction of Lysine Crotonylation Sites
Authors: Wang Rulan , Wang Zhuo , Li Zhongyan , Lee Tzong-Yi
Published: January 2022

Lysine crotonylation (Kcr) is involved in plenty of activities in the human body. Various technologies have been developed for Kcr prediction. Sequence-based features are typically adopted in existing methods, in which only linearly neighboring amino acid composition was considered. However, modified Kcr sites are neighbored by not only the linear-neighboring amino acid but also those spatially surrounding residues around the target site. In this paper, we have used residue–residue contact as a new feature for Kcr prediction, in which features encoded with not only linearly surrounding residues but also those spatially nearby the target site. Then, the spatial-surrounding residue was used as a new scheme for feature encoding for the first time, named residue–residue composition (RRC) and residue–residue pair composition (RRPC), which were used in supervised learning classification for Kcr prediction. As the result suggests, RRC and RRPC have achieved the best performance of RRC at an accuracy of 0.77 and an area under curve (AUC) value of 0.78, RRPC at an accuracy of 0.74, and an AUC value of 0.80. In order to show that the spatial feature is of a competitively high significance as other sequence-based features, feature selection was carried on those sequence-based features together with feature RRPC. In addition, different ranges of the surrounding amino acid compositions’ radii were used for comparison of the performance. After result assessment, RRC and RRPC features have shown competitively outstanding performance as others or in some cases even around 0.20 higher in accuracy or 0.3 higher in AUC values compared with sequence-based features.
A High-Density Genetic Map Enables Genome Synteny and QTL Mapping of Vegetative Growth and Leaf Traits in Gardenia
Authors: Cui Yang , Fan Baolian , Xu Xu , Sheng Shasha , Xu Yuhui , Wang Xiaoyun
Published: January 2022

The gardenia is a traditional medicinal horticultural plant in China, but its molecular genetic research has been largely hysteretic. Here, we constructed an F1 population with 200 true hybrid individuals. Using the genotyping-by-sequencing method, a high-density sex-average genetic map was generated that contained 4,249 SNPs with a total length of 1956.28 cM and an average genetic distance of 0.46 cM. We developed 17 SNP-based Kompetitive Allele-Specific PCR markers and found that 15 SNPs were successfully genotyped, of which 13 single-nucleotide polymorphism genotypings of 96 F1 individuals showed genotypes consistent with GBS-mined genotypes. A genomic collinearity analysis between gardenia and the Rubiaceae species Coffea arabica, Coffea canephora and Ophiorrhiza pumila showed the relativity strong conservation of LG11 with NC_039,919.1, HG974438.1 and Bliw01000011.1, respectively. Lastly, a quantitative trait loci analysis at three phenotyping time points (2019, 2020, and 2021) yielded 18 QTLs for growth-related traits and 31 QTLs for leaf-related traits, of which qBSBN7-1, qCD8 and qLNP2-1 could be repeatably detected. Five QTL regions (qCD8 and qSBD8, qBSBN7 and qSI7, qCD4-1 and qLLLS4, qLNP10 and qSLWS10-2, qSBD10 and qLLLS10) with potential pleiotropic effects were also observed. This study provides novel insight into molecular genetic research and could be helpful for further gene cloning and marker-assisted selection for early growth and development traits in the gardenia.
Endogenous Retroviruses Provide Protection Against Vaginal HSV-2 Disease
Authors: Jayewickreme Radeesha , Mao Tianyang , Philbrick William , Kong Yong , Treger Rebecca S. , Lu Peiwen , Rakib Tasfia , Dong Huiping , Dang-Lawson May , Guild W. Austin , Lau Tatiana J. , Iwasaki Akiko , Tokuyama Maria
Published: January 2022

Endogenous retroviruses (ERVs) are genomic sequences that originated from retroviruses and are present in most eukaryotic genomes. Both beneficial and detrimental functions are attributed to ERVs, but whether ERVs contribute to antiviral immunity is not well understood. Here, we used herpes simplex virus type 2 (HSV-2) infection as a model and found that Toll-like receptor 7 (Tlr7-/-) deficient mice that have high systemic levels of infectious ERVs are protected from intravaginal HSV-2 infection and disease, compared to wildtype C57BL/6 mice. We deleted the endogenous ecotropic murine leukemia virus (Emv2) locus on the Tlr7-/- background (Emv2-/-Tlr7-/-) and found that Emv2-/-Tlr7-/- mice lose protection against HSV-2 infection. Intravaginal application of purified ERVs from Tlr7-/- mice prior to HSV-2 infection delays disease in both wildtype and highly susceptible interferon-alpha receptor-deficient (Ifnar1-/-) mice. However, intravaginal ERV treatment did not protect Emv2-/-Tlr7-/- mice from HSV-2 disease, suggesting that the protective mechanism mediated by exogenous ERV treatment may differ from that of constitutively and systemically expressed ERVs in Tlr7-/- mice. We did not observe enhanced type I interferon (IFN-I) signaling in the vaginal tissues from Tlr7-/- mice, and instead found enrichment in genes associated with extracellular matrix organization. Together, our results revealed that constitutive and/or systemic expression of ERVs protect mice against vaginal HSV-2 infection and delay disease.
Prevalence of Inflammatory Pathways Over Immuno-Tolerance in Peripheral Blood Mononuclear Cells of Recent-Onset Type 1 Diabetes
Authors: Santos Aritania Sousa , Cunha-Neto Edécio , Gonfinetti Nelson Vinicius , Bertonha Fernanda Bernardi , Brochet Pauline , Bergon Aurelie , Moreira-Filho Carlos Alberto , Chevillard Christophe , Silva Maria Elizabeth Rossi da
Published: January 2022

Background

Changes in innate and adaptive immunity occurring in/around pancreatic islets had been observed in peripheral blood mononuclear cells (PBMC) of Caucasian T1D patients by some, but not all researchers. The aim of our study was to investigate whether gene expression patterns of PBMC of the highly admixed Brazilian population could add knowledge about T1D pathogenic mechanisms.

Methods

We assessed global gene expression in PBMC from two groups matched for age, sex and BMI: 20 patients with recent-onset T1D (≤ 6 months from diagnosis, in a time when the autoimmune process is still highly active), testing positive for one or more islet autoantibodies and 20 islet autoantibody-negative healthy controls.

Results

We identified 474 differentially expressed genes between groups. The most expressed genes in T1D group favored host defense, inflammatory and anti-bacterial/antiviral effects (LFT, DEFA4, DEFA1, CTSG, KCNMA1) and cell cycle progression. Several of the downregulated genes in T1D target cellular repair, control of inflammation and immune tolerance. They were related to T helper 2 pathway, induction of FOXP3 expression (AREG) and immune tolerance (SMAD6). SMAD6 expression correlated negatively with islet ZnT8 antibody. The expression of PDE12, that offers resistance to viral pathogens was decreased and negatively related to ZnT8A and GADA levels. The increased expression of long non coding RNAs MALAT1 and NEAT1, related to inflammatory mediators, autoimmune diseases and innate immune response against viral infections reinforced these data

Conclusions

Our analysis suggested the activation of cell development, anti-infectious and inflammatory pathways, indicating immune activation, whereas immune-regulatory pathways were downregulated in PBMC from recent-onset T1D patients with a differential genetic profile.
An Insight Into Systemic Immune Response in Leishmania donovani Mediated Atypical Cutaneous Leishmaniasis in the New Endemic State of Himachal Pradesh, India
Authors: Thakur Lovlesh , Madaan Priyanka , Jain Aklank , Shankar Vinay , Negi Ajeet , Chauhan Shashi Bhushan , Sundar Shyam , Singh Om Prakash , Jain Manju
Published: January 2022

Leishmaniasis continues to afflict known and newer endemic sites despite global efforts towards its control and elimination. In this regard, the emergence of newer endemic sites with unusual disease formats is recognized wherein Leishmania donovani complex classically known to cause visceral disease is demonstrated to cause cutaneous manifestation. In this context, atypical cutaneous leishmaniasis (CL) cases caused by L. donovani genetic variants from the newer endemic state of Himachal Pradesh (HP) in India are beginning to be understood in terms of parasite determinants. The atypical CL manifestation further needs to be explored to define host immune correlates with a possible role in driving the unusual disease progression. In the given study, we performed comprehensive systemic-immune profiling of the atypical CL patients from the study area in HP, India, in comparison with the classical visceral leishmaniasis (VL) patients from the northeast region of India. The systemic immune response was studied using ELISA-based assessment of Th1, Th2, Th17, Treg, and Th22 specific plasma cytokine expression pattern and parasite-specific total serum IgG/IgG subclasses. The specified immune correlates are known to exhibit heterogeneous association with the different infecting parasite species, infection load, and co-lateral host immunopathology in classical CL and VL. In the atypical CL patient group, altered expression of IL-10 emerged as the key finding that could potentially fine-tune the Th1/Th17/Th22 effector cytokine axis towards a localized cutaneous manifestation. A reduced expression of IL-10 along with a high IFN-γ/IL-10 ratio as a readout of effective parasite killing defined atypical cutaneous outcome. In contrast, high circulatory IL-10 levels and a depressed IFN-γ/IL-10 ratio were seen in classical VL patients in line with an ineffective parasite-killing cytokine response. Overall, the study highlights new knowledge on host immune correlates in terms of cytokine expression pattern and IgG subclasses that underline atypical disease manifestation such that L. donovani, a generally visceralizing parasite species cause skin localized cutaneous lesions.
Diagnostic Biomarkers and Immune Infiltration in Patients With T Cell-Mediated Rejection After Kidney Transplantation
Authors: Zhou Hai , Lu Hongcheng , Sun Li , Wang Zijie , Zheng Ming , Hang Zhou , Zhang Dongliang , Tan Ruoyun , Gu Min
Published: January 2022

T cell-mediated rejection (TCMR) is an important rejection type in kidney transplantation, characterized by T cells and macrophages infiltration. The application of bioinformatic analysis in genomic research has been widely used. In the present study, Microarray data was analyzed to identify the potential diagnostic markers of TCMR in kidney transplantation. Cell-type identification by estimating relative subsets of RNA transcript (CIBERSORT) was performed to determine the distribution of immune cell infiltration in the pathology. Totally 129 upregulated differently expressed genes (DEGs) and 378 downregulated DEGs were identified. The GO and KEGG results demonstrated that DEGs were mainly associated with pathways and diseases involved in immune response. The intersection of the two algorithms (PPI network and LASSO) contains three overlapping genes (CXCR6, CXCL13 and FCGR1A). After verification in GSE69677, only CXCR6 and CXCL13 were selected. Immune cells Infiltration analysis demonstrated that CXCR6 and CXCL13 were positively correlated with gamma delta T cells (p < 0.001), CD4+ memory activated T cells (p < 0.001), CD8+ T cells (p < 0.001) and M1 macrophages (p = 0.006), and negatively correlated with M2 macrophages (p < 0.001) and regulatory T cells (p < 0.001). Immunohistochemical staining and image analysis confirmed the overexpression of CXCR6 and CXCL13 in human allograft TCMR samples. CXCR6 and CXCL13 could be diagnostic biomarkers of TCMR and potential targets for immunotherapy in patients with TCMR.
The Route of Vaccine Administration Determines Whether Blood Neutrophils Undergo Long-Term Phenotypic Modifications
Authors: Feraoun Yanis , Palgen Jean-Louis , Joly Candie , Tchitchek Nicolas , Marcos-Lopez Ernesto , Dereuddre-Bosquet Nathalie , Gallouet Anne-Sophie , Contreras Vanessa , Lévy Yves , Martinon Frédéric , Le Grand Roger , Beignon Anne-Sophie
Published: January 2022

Innate immunity modulates adaptive immunity and defines the magnitude, quality, and longevity of antigen-specific T- and B- cell immune memory. Various vaccine and administration factors influence the immune response to vaccination, including the route of vaccine delivery. We studied the dynamics of innate cell responses in blood using a preclinical model of non-human primates immunized with a live attenuated vaccinia virus, a recombinant Modified vaccinia virus Ankara (MVA) expressing a gag-pol-nef fusion of HIV-1, and mass cytometry. We previously showed that it induces a strong, early, and transient innate response, but also late phenotypic modifications of blood myeloid cells after two months when injected subcutaneously. Here, we show that the early innate effector cell responses and plasma inflammatory cytokine profiles differ between subcutaneous and intradermal vaccine injection. Additionally, we show that the intradermal administration fails to induce more highly activated/mature neutrophils long after immunization, in contrast to subcutaneous administration. Different batches of antibodies, staining protocols and generations of mass cytometers were used to generate the two datasets. Mass cytometry data were analyzed in parallel using the same analytical pipeline based on three successive clustering steps, including SPADE, and categorical heatmaps were compared using the Manhattan distance to measure the similarity between cell cluster phenotypes. Overall, we show that the vaccine per se is not sufficient for the late phenotypic modifications of innate myeloid cells, which are evocative of innate immune training. Its route of administration is also crucial, likely by influencing the early innate response, and systemic inflammation, and vaccine biodistribution.
Interleukin 27 Signaling in Rheumatoid Arthritis Patients: Good or Evil?
Authors: Han Liang , Chen Zhe , Yu Kun , Yan Jiahui , Li Tingting , Ba Xin , Lin Weiji , Huang Yao , Shen Pan , Huang Ying , Qin Kai , Geng Yinhong , Liu Yafei , Wang Yu , Tu Shenghao
Published: January 2022

The occurrence and development of rheumatoid arthritis (RA) is regulated by numerous cytokines. Interleukin 27 (IL-27) is a soluble cytokine that exerts biological effects by regulating the Janus tyrosine kinase (JAK)/signal transducer and activator of the transcription (STAT) signaling pathwayviathe IL-27 receptor. IL-27 is known for its pleiotropic roles in modulating inflammatory responses. Previous studies found that IL-27 levels are elevated in RA blood, synovial fluid, and rheumatoid nodules. Cellular and animal experiments indicated that IL-27 exerts multiple regulatory functions in RA patientsviadifferent mechanisms. IL-27 inhibits ectopic-like structure (ELS) formation and CD4+T helper type 2 (Th2) cell, CD4+T helper type 17 (Th17) cell, and osteoclast differentiation in RA, contributing to alleviating RA. However, IL-27 promotes Th1 cell differentiation, which may exacerbate RA synovitis. Moreover, IL-27 also acts on RA synovial fibroblasts (RA-FLSs) and regulatory T cells (Tregs), but some of its functions are unclear. There is currently insufficient evidence to determine whether IL-27 promotes or relieves RA. Targeting IL-27 signaling in RA treatment should be deliberate based on current knowledge.
CD33 Delineates Two Functionally Distinct NK Cell Populations Divergent in Cytokine Production and Antibody-Mediated Cellular Cytotoxicity
Authors: Hejazi Maryam , Zhang Congcong , Bennstein Sabrina B. , Balz Vera , Reusing Sarah B. , Quadflieg Melissa , Hoerster Keven , Heinrichs Stefan , Hanenberg Helmut , Oberbeck Sebastian , Nitsche Marcus , Cramer Sophie , Pfeifer Rita , Oberoi Pranav , Rühl Heiko , Oldenburg Johannes , Brossart Peter , Horn Peter A. , Babor Florian , Wels Winfried S. , Fischer Johannes C. , Möker Nina , Uhrberg Markus
Published: January 2022

The generation and expansion of functionally competent NK cells in vitro is of great interest for their application in immunotherapy of cancer. Since CD33 constitutes a promising target for immunotherapy of myeloid malignancies, NK cells expressing a CD33-specific chimeric antigen receptor (CAR) were generated. Unexpectedly, we noted that CD33-CAR NK cells could not be efficiently expanded in vitro due to a fratricide-like process in which CD33-CAR NK cells killed other CD33-CAR NK cells that had upregulated CD33 in culture. This upregulation was dependent on the stimulation protocol and encompassed up to 50% of NK cells including CD56dim NK cells that do generally not express CD33 in vivo. RNAseq analysis revealed that upregulation of CD33+ NK cells was accompanied by a unique transcriptional signature combining features of canonical CD56bright (CD117high, CD16low) and CD56dim NK cells (high expression of granzyme B and perforin). CD33+ NK cells exhibited significantly higher mobilization of cytotoxic granula and comparable levels of cytotoxicity against different leukemic target cells compared to the CD33− subset. Moreover, CD33+ NK cells showed superior production of IFNγ and TNFα, whereas CD33− NK cells exerted increased antibody-dependent cellular cytotoxicity (ADCC). In summary, the study delineates a novel functional divergence between NK cell subsets upon in vitro stimulation that is marked by CD33 expression. By choosing suitable stimulation protocols, it is possible to preferentially generate CD33+ NK cells combining efficient target cell killing and cytokine production, or alternatively CD33− NK cells, which produce less cytokines but are more efficient in antibody-dependent applications.