bluuebunny/crossref_metadata_2025 huggingface dataset:
Meaning Used By Pranatacara in Javanese Wedding Ceremony “Panggih Manten”
Authors: Natsir Muhammad , Tiara Artha Dewi  , Bahagia Saragih
Published: March 2022

This study used the descriptive qualitative method. The qualitative method was a research procedure which results in descriptive data, including written and oral word from the research objectives. The data used in this study were taken from the speech utterances by Pranatacara in "Panggih Manten" wedding ceremony in the Aeksongsongan. The researcher took the data from two Pranatacara and two Panggih Manten which taken from the speech utterances. The researcher used a source of theories about the semantic field by Knowles and Moon to support the thesis. Some steps were undertaken during the data collection: the process of selecting, focusing on the important things, simplifying, abstracting and transforming the data that appear in transcription. The results showed that the data into 23 metaphorical meanings from total  two pranatacara of Javanese Wedding Ceremony or Panggih Manten. The dominant of metaphorical meaning was creative metaphor which had the highest percentage. The other result showed the least of metaphorical meaning was conventional meaning which had the lowest percentage. We took to identify and consider three things : metaphor, meaning, and connection by analysing and discussing metaphors in any depth. The percentage of the sequences Panggih Manten consisted of the opening, balangan gantal, injak telur, sinduran, dulangan, kacar kucur, sungkeman and the closing.
Feminist stylistic analysis and LGBTQA+ representation in Lady Gaga’s born this way
Authors: Rangkuti Rahmadsyah , Hafifah Siti
Published: March 2022

This study is intended to find out the exact meaning of the lyrics at different levels of language, and phonetic devices, as well as to reveal how these stylistic devices work on Lady Gaga’s Born This Way (LGBTQA+). This study employed qualitative content analysis. The source of the data was the song Born This Way by Lady Gaga and the data were the linguistics aspects of the song, which are the words, phrases, clauses and sentences, as well as the discourse unit of the song. It was found that the song aims to speak to as many perspectives as possible, through different races, sexualities, and gender expressions, through the language uses that are represented in the song. By then, this song has completely succeeded to not only raising up feminist voice, but also, most likely, if there was no song with all the impact and events, understanding about gender and equality would not develop as it is today. The song strongly emphasizes the equality notion by accepting who we are as we are all born this way. The choices of word, phrase, clause and sentence as well as the discourse unit credit about self-liberation, and loving every part of oneself, no matter what race, belief, or sexuality one is on. This also proves that this song is not solely an LGBTQA+ community anthem, instead, it is a song for all kind of self-acceptance.
Gestão de pessoas e a liderança na Empresa: o líder diante das mudanças organizacionais
Authors: Lima Jônatas de Sousa
Published: March 2022

O presente estudo tem por objetivo investigar qual o perfil do líder na gestão de pessoas em empresas modernas frente as alterações de uma maneira genérica no mundo e acentuado impacto no mundo empresarial. O desenvolvimento do estudo se justifica pelo fato de poder mostrar para a sociedade que, em tempos globalizados, de processos informatizados e de intensa concorrência, as empresas advieram a precisar ainda mais de sistemas de gestão eficazes e lideranças competentes, para assim poder aproveitar o melhor de suas equipes e competências e proporcionar produtos e serviços com melhor qualidade e rapidez de entrega. Em se tratando da metodologia de pesquisa aplicada, esta trata-se de uma revisão de literatura que possui como objetivo abordar e apresentar os pensamentos dos autores consultados sobre o tema proposto no estudo para em seguida chegar aos objetivos propostos no presente estudo. Concluiu-se que o líder deve ter um perfil motivador, evidenciando uma conduta e entusiasmo individual e assim tornar-se um símbolo da conduta, além de abordar os colaboradores particularmente, com a finalidade de dispersar a empolgação. Portanto, o líder precisa procurar sucesso para criar um sentimento de melhoria em toda a mudança.
Construção civil e as transformações socioambientais: a experiência da centralidade urbana de Kilamba
Authors: Mateus António Paulo , Argueta Lourdes Brazil dos Santos , Longo Orlando Celso , Jorge Pascoal Paulo , Cuhema Salvador Lindo Bernardo
Published: March 2022

O presente artigo é parte de um projeto de pesquisa realizada para identificar os impactos socioambientais, numa perspectiva ampliada dos impactos produzidos pela construção da centralidade do Kilamba, Luanda, Angola. As centralidades são um tipo de construções realizadas em Angola a partir de 2008, visando atender a demanda de habitação por parte da população. Constituem um conjunto de obras que abrangem construção de casas, equipamentos sociais, entre os quais jardins de infância, escolas primárias e secundárias, posto de saúde, parques comunitários, zonas comerciais e áreas de lazer. A metodologia utilizada foi a qualitativa através do estudo de caso. O objetivo foi identificar os impactos das principais etapas da construção: planejamento, execução e operacionalização. O estudo compreendeu o levantamento bibliográfico, revisão bibliográfica, entrevistas, visitas ao local, o qual foi possível identificar os impactos sociais, ambientais, ecológicos e culturais de cada etapa que comprometem a vida e o desenvolvimento da população e as cadeias ecológicas e ambientais, responsáveis pela oferta de serviços ecossistêmicos, importantes para o enfrentamento de problemas ambientais globais, como as alterações climáticas e ocorrência de pandemias.
STRATEGY FOR EMPOWERMENT OF SMALL AND MEDIUM MICRO ENTERPRISES (UMKM) IN CIBUNIAN VILLAGE
Authors: Mursyidah Azizah
Published: March 2022

Abstrak. Usaha Mikro, Kecil dan Menengah (UMKM) menjadi pusat perhatian karena kontribusinya yang besar dalam pertumbuhan ekonomi. Salah satu upaya yang dilakukan oleh Penulis dalam mengatasi permasalahan ini adalah, sosialisasi melalui kepala desa serta tokoh masyarakat dalam pemberdayaan. Contoh Pemberdayaan masyarakat di Desa Cibunian adalah Industri kolang kaling dan krupuk di Kabupaten Bogor. tujuan pengabdian ini untuk mendeskripsikan dan menganalisis strategi pemberdayaan UMKM di Desa Cibunian kabupaten Bogor.  Metode Pelaksanaan kegiatan ini, dimulai dengan metode observasi, dan  Pendekatan Orang Dewasa (POD) yang dilakukan secara partisipatif dengan metode ceramah, diskusi kelompok dan praktik keterampilan sesuai dengan kondisi di lapangan. Praktik keterampilan dilakukan dengan cara praktik mandiri yang telah dipersiapkan bahan produksi pembuatan kerupuk kolang-kaling dan kerupuk. Faktor-faktor pendukung dan penghambat yang ditemui dalam strategi pemberdayaan UMKM di Kabupaten Bogor meliputi (1) membantu akses permodalan, (2) pembinaan SDM, (3) kemitraan (4) Para Stakeholder terkait Usaha Mikro, Kecil dan Menengah (UMKM) perlu melakukan pendampingan serta pemberdayaan  secara terus menerus untuk memfasilitasi UMKM. Kata Kunci: UMKM, Kemitraan, Kolang-kaling
IDENTIFIKASI MODEL PEMBELAJARAN ANAK BERKEBUTUHAN KHUSUS PADA PENDIDIKAN USIA DINI
Authors: Putra Windisyah
Published: March 2022

Pendidikan khusus merujuk kepada Pendidikan untuk peserta didik yang memiliki kecerdasan luar biasa. Ada beberapa model pembelajaran dapat diaplikasikan untuk melihat apakah model pembelajaran tersebut sesuai diaplikasikan pada peserta didik yang memiliki kecerdasan khusus. Artikel ini melaporkan hasil dari penelitian mengguanakan metode kualitatif dan pendekatan deskriptif analisis untuk mengetahui model pembelajaran terhadap minat anak dan menjadi bahan pertimbangan bagi TK Permata Bunda Takengon. Penelitian ini meliputi 3 Anak Berkebutuhan Khusus (ABK) dari kelas B semester genap. Teknik pengumpulan data melalui pengamatan partisipatif, wawancara, dan dokumentasi. Selanjutnya dianalisis dengan reduksi data, penyajian data, pengambilan kesimpulan dan verifikasi data. Hasil penelitian menunjukkan; (1) MY memiliki jenis ketunaan ADD (Attention Deficit Disorder) gangguan tingkah laku atau berkurangnya perhatian terhadap suatu obyek. Kecendrungan kecerdasan spasial visual dan memiliki gaya belajarnya visual (penglihatan) dengan model pembelajaran yang banyak menampilkan gambar dan lukisan; (2) AN memiliki jenis ketunaan slow leaner (lambat belajar), memiliki kecerdasan linguistic (bahasa) dan kecendrungan kedalam gaya belajar auditori (pendengaran) melalui model pembelajaran bercerita dan ceramah; dan (3) AA memiliki jenis ketunaan ADHD (Attention Deficit Hiperaktif Disorder) gangguan tingkah laku hiperaktif, memiliki kecenderungan kecerdasan kenistetik dan spasial visual. Sementara gaya belajarnya tactile/kinestetik (perabaan/gerakan) dan menerapkan model pembelajaran role play dengan mengamati langsung dan merasakan pelajarannya.
THE EFFECT OF PQRST (PREVIEW, QUESTION, READ, SUMMARY, AND TEST) STRATEGY ON READING COMPREHENSION AT FIRST-GRADE STUDENTS OF SMAN 1 SABAK AUH SIAK
Authors: Arbandari Ratna , Azhar Fadly , Erni Erni
Published: March 2022

This paper discusses an experimental research study regarding the effect of PQRST (Preview, Question, Read, Summary, and Test) strategy on reading comprehension of the first-year students at SMAN 1 of Sabak Auh Siak. The study shows that 65% of the students have difficulties in comprehending the reading passage about a descriptive text. Based on the students’ reading indicators, it can be identified that they have difficulties in determining the main idea, locating references, understanding vocabulary, making inferences, and finding detailed information. This study uses a quantitative method on a true experimental design of two groups of first-year students using pre-test and post-test. The study involves 44 students, divided into two classes: the control class with 21 students and the experimental class with 23 students. The instrument is a test that consists of questions with multiple choices and four options (A/B/C/D). In order to analyze the data formula, statistical software namely SPSS version 23 is used to analyze the results of the study. The significant effect of PQRST (Preview, Question, Read, Summary, and Test) strategy on reading comprehension at the first-year students of SMAN 1 Sabak Auh in Kabupaten Siak (2-tailed) is. 000 ˂ .005, which means that the H0 is rejected, while Ha is accepted. Thus, there is a significant effect on first-year students' reading comprehension in descriptive text between the students who are taught by applying the PQRST strategy and those who are not.
Kendala Penerapan Kurikulum 2013 dalam Pembelajaran Fisika Di SMA Kabupaten Kotabaru
Authors: Ali Muhammad
Published: March 2022

The general objective of this research is to describe the constraints of high school teachers in applying the 2013 Curriculum in Physics learning in Kotabaru District and the specific objectives of selecting lesson plans, understanding learning activities and understanding learning principles. This research method is descriptive data analysis with the object of research of high school physics teachers in Kotabaru Regency and this study is a qualitative study. The research data was obtained through observation / interviews and teacher responses questionnaire. The results of the study show: (1) 25.53% Teachers are still constrained by the preparation of lesson plans, especially in various learning sources (open texts, internet, natural and social environment), varied learning media, media that are compatible with learning material, scientific learning approaches, (2) 25.25% Teachers are still constrained in implementing learning activities which include the delivery of competencies to be achieved to students, have not carried out contextual and scientific learning, have not facilitated students to analyze information to make conclusions, have not used varied learning media, ( 3) 36.71% Teachers are constrained to understand the principle of learning mainly related to differences in textual approaches with scientific approaches, differences in partial learning with integrated learning, learning differences that emphasize single answers with learning that requires multi-dimensional answers, and differences in learning of verbalism with learning. applicable learning.

 

Keywords: Teacher Constraints, 2013 Curriculum, Scientific.
Analisis Kontrastif Fonologi Bahasa Banjar dan Bahasa Jawa di Desa Sebelimbingan Kecamatan Pulau Laut Utara Kabupaten Kotabaru
Authors: Suryana Rudy
Published: March 2022

This study aims to identify the similarities, phonological similarities of Banjar languages and Javanese as a basis for language learning models. The field study was carried out in Sebelimbingan Village, Pulau Laut Utara Subdistrict, Kotabaru Regency, where Banjar and Javanese languages are used by the villagers in everyday language. This research uses descriptive qualitative methods, data collected through observation, and listening and analyzed using synchronous contrastive analysis techniques. The subject of this research is the daily conversation of the Javanese that can be recorded and then carried out a phonological analysis of the Banjar and Javanese phonology in the community of Sebelimbing Village, Pulau Laut Utara District, Kotabaru Regency. Linguistic studies are very interesting to study, especially in contrastive studies of analysis comparing several languages in the world. In phonological studies, especially phonetic studies on equality and similarity in two languages, namely Banjar and Javanese. The comparison of the two languages in the similarity of sound has characteristics in similarities and differences. The results of this study indicate that the similarity between the two languages, namely Banjar language and Javanese language lies at the level of vocabulary, language sounds, and their meanings. At the vocabulary level, there are phonological similarities. This research can be used as a consideration for regional language learning models by utilizing the similarities and similarities held by the two languages, both regarding vocabulary, their meaning and the structure of clauses or sentences. At the very least, the similarity and similarity of the linguistic aspects is used at the beginning of the beginning in learning two languages namely Banjar and Javanese so that they do not experience difficulties in learning and mastering the language.

 

Keywords: Analysis, Contrastive, Phonology, Banjar Language and Javanese Language.
PROBLEMATIKA PEMBELAJARAN SASTRA BERBASIS DIGITAL DI MASA PANDEMI DALAM RUANG LINGKUP STKIP PARIS BARANTAI
Authors: Normasunah Normasunah Normasunah
Published: March 2022

Pendidikan jarak jauhberbasis digital menjadi salah satu kebijakan yang dilakukan pemerintah di Indonesia agar pendidikantetap berjalan.Namun, dalam aktualisasi pembelajaran berbasis digital tersebut banyak ditemukankeluhandariberbagaikalangan,terutamadarimahasiswa. Tujuan penelitian ini adalah untuk mendeskripsikan media pembelajaran serta akses jaringan internet yang digunakan sebagai penyambung pembelajaran dimasa pandemi yang menjadi problem dalam proses pembelajaran sastra.

Penelitian ini menggunakan metode deskriptifkualitatif,yaitumendeskripsikan problematika yang dialami mahasiswa ketika mengikuti pembelajaran sastra berbasis digital. Hasil penelitian ini menunjukkan bahwa problematika pembelajaranberbasis digital ditemukan dari berbagai aspek, baik dari dosen, mahasiswa,maupun pada aspekmedia pembelajaran berbasis digital yang digunakan.Uraian problematika pembelajaran berbasisdigital di masa pandemi sebagai hasilpenelitian ini sangat bermanfaat bagi pengembangan kreativitasmengajar.Dapat disimpulkan bahwa berbagai aspek dalam pembelajaran berbasis digital masih perluditingkatkan dan dikembangkan.Dosen harus terus meningkatkan kreativitas mengajar, dan mediapembelajaran masih perlu diperbaharui.

 

 

Kata Kunci: Problematik, Pengajaran Digital, Sastra
A Bioreactor for 3D In Vitro Modeling of the Mechanical Stimulation of Osteocytes
Authors: Aw Yong Koh Meng , Horst Eric , Neale Dylan , Royzenblat Sonya , Lahann Joerg , Greineder Colin , Weivoda Megan , Mehta Geeta , Keller Evan T.
Published: March 2022

The bone is a mechanosensitive organ that is also a common metastatic site for prostate cancer. However, the mechanism by which the tumor interacts with the bone microenvironment to further promote disease progression remains to be fully understood. This is largely due to a lack of physiological yet user-friendly models that limit our ability to perform in-depth mechanistic studies. Here, we report a tunable bioreactor which facilitates the 3D culture of the osteocyte cell line, MLO-Y4, in a hydroxyapatite/tricalcium phosphate (HA/TCP) scaffold under constant fluidic shear stress and tunable hydrostatic pressure within physiological parameters. Increasing hydrostatic pressure was sufficient to induce a change in the expression of several bone remodeling genes such as Dmp1, Rankl, and Runx2. Furthermore, increased hydrostatic pressure induced the osteocytes to promote the differentiation of the murine macrophage cell line RAW264.7 toward osteoclast-like cells. These results demonstrate that the bioreactor recapitulates the mechanotransduction response of osteocytes to pressure including the measurement of their functional ability in a 3D environment. In conclusion, the bioreactor would be useful for exploring the mechanisms of osteocytes in bone health and disease.
Photooxidation and Pentagalloyl Glucose Cross-Linking Improves the Performance of Decellularized Small-Diameter Vascular Xenograft In Vivo
Authors: Liu Yuhong , Chen Chunyang , Xie Xinlong , Yuan Haoyong , Tang Zhenjie , Qian Tao , Liu Yalin , Song Mingzhe , Liu Sixi , Lu Ting , Wu Zhongshi
Published: March 2022

Small-diameter vascular grafts have a significant need in peripheral vascular surgery and procedures of coronary artery bypass graft (CABG); however, autografts are not always available, synthetic grafts perform poorly, and allografts and xenografts dilate, calcify, and induce inflammation after implantation. We hypothesized that cross-linking of decellularized xenogeneic vascular grafts would improve the mechanical properties and biocompatibility and reduce inflammation, degradation, and calcification in vivo. To test this hypothesis, the bovine internal mammary artery (BIMA) was decellularized by detergents and ribozymes with sonication and perfusion. Photooxidation and pentagalloyl glucose (PGG) were used to cross-link the collagen and elastin fibers of decellularized xenografts. Modified grafts’ characteristics and biocompatibility were studied in vitro and in vivo; the grafts were implanted as transposition grafts in the subcutaneous of rats and the abdominal aorta of rabbits. The decellularized grafts were cross-linked by photooxidation and PGG, which improved the grafts’ biomechanical properties and biocompatibility, prevented elastic fibers from early degradation, and reduced inflammation and calcification in vivo. Short-term aortic implants in the rabbits showed collagen regeneration and differentiation of host smooth muscle cells. No occlusion and stenosis occurred due to remodeling and stabilization of the neointima. A good patency rate (100%) was maintained. Notably, implantation of non-treated grafts exhibited marked thrombosis, an inflammatory response, calcification, and elastin degeneration. Thus, photooxidation and PGG cross-linking are potential tools for improving grafts’ biological performance within decellularized small-diameter vascular xenografts.
Transglutaminase-Catalyzed Bottom-Up Synthesis of Polymer Hydrogel
Authors: Lai Enping , Bao Binyu , Zhu Yifei , Lin Haitao
Published: March 2022

Enzyme catalysis has attracted increasing attention for application in the synthesis of polymer hydrogel due to the eco-friendly process and the devisable catalytic reaction. Moreover, bottom-up approaches combining enzyme catalysts and molecular self-assembly have been explored for synthesizing hydrogel with complex architectures. An enzyme widely distributed in nature, transglutaminase (TGase) has been confirmed to catalyze the formation of isopeptide bonds between proteins, which can effectively improve the gelation of proteins. In this mini-review, TGase-catalyzed synthesis of polymer hydrogels, including fibrin hydrogels, polyethylene glycol hydrogels, soy protein hydrogels, collagen hydrogels, gelatin hydrogels and hyaluronan hydrogels, has been reviewed in detail. The catalytic process and gel formation mechanism by TGase have also been considered. Furthermore, future perspectives and challenges in the preparation of polymer hydrogels by TGase are also highlighted.
Regioselective One-Pot Synthesis of Hydroxy-(S)-Equols Using Isoflavonoid Reductases and Monooxygenases and Evaluation of the Hydroxyequol Derivatives as Selective Estrogen Receptor Modulators and Antioxidants
Authors: Song Hanbit , Lee Pyung-Gang , Kim Junyeob , Kim Joonwon , Lee Sang-Hyuk , Kim Hyun , Lee Uk-Jae , Kim Jin Young , Kim Eun-Jung , Kim Byung-Gee
Published: March 2022

Several regiospecific enantiomers of hydroxy-(S)-equol (HE) were enzymatically synthesized from daidzein and genistein using consecutive reduction (four daidzein-to-equol–converting reductases) and oxidation (4-hydroxyphenylacetate 3-monooxygenase, HpaBC). Despite the natural occurrence of several HEs, most of them had not been studied owing to the lack of their preparation methods. Herein, the one-pot synthesis pathway of 6-hydroxyequol (6HE) was developed using HpaBC (EcHpaB) from Escherichia coli and (S)-equol-producing E. coli, previously developed by our group. Based on docking analysis of the substrate or products, a potential active site and several key residues for substrate binding were predicted to interpret the (S)-equol hydroxylation regioselectivity of EcHpaB. Through investigating mutations on the key residues, the T292A variant was verified to display specific mono-ortho-hydroxylation activity at C6 without further 3′-hydroxylation. In the consecutive oxidoreductive bioconversion using T292A, 0.95 mM 6HE could be synthesized from 1 mM daidzein, while 5HE and 3′HE were also prepared from genistein and 3′-hydroxydaidzein (3′HD or 3′-ODI), respectively. In the following efficacy tests, 3′HE and 6HE showed about 30∼200-fold higher EC50 than (S)-equol in both ERα and ERβ, and they did not have significant SERM efficacy except 6HE showing 10% lower β/α ratio response than that of 17β-estradiol. In DPPH radical scavenging assay, 3′HE showed the highest antioxidative activity among the examined isoflavone derivatives: more than 40% higher than the well-known 3′HD. In conclusion, we demonstrated that HEs could be produced efficiently and regioselectively through the one-pot bioconversion platform and evaluated estrogenic and antioxidative activities of each HE regio-isomer for the first time.
Identification of Kic1p and Cdc42p as Novel Targets to Engineer Yeast Acetic Acid Stress Tolerance
Authors: Chen Hong-Qi , Xing Qi , Cheng Cheng , Zhang Ming-Ming , Liu Chen-Guang , Champreda Verawat , Zhao Xin-Qing
Published: March 2022

Robust yeast strains that are tolerant to multiple stress environments are desired for an efficient biorefinery. Our previous studies revealed that zinc sulfate serves as an important nutrient for stress tolerance of budding yeast Saccharomyces cerevisiae. Acetic acid is a common inhibitor in cellulosic hydrolysate, and the development of acetic acid-tolerant strains is beneficial for lignocellulosic biorefineries. In this study, comparative proteomic studies were performed using S. cerevisiae cultured under acetic acid stress with or without zinc sulfate addition, and novel zinc-responsive proteins were identified. Among the differentially expressed proteins, the protein kinase Kic1p and the small rho-like GTPase Cdc42p, which is required for cell integrity and regulation of cell polarity, respectively, were selected for further studies. Overexpression of KIC1 and CDC42 endowed S. cerevisiae with faster growth and ethanol fermentation under the stresses of acetic acid and mixed inhibitors, as well as in corncob hydrolysate. Notably, the engineered yeast strains showed a 12 h shorter lag phase under the three tested conditions, leading to up to 52.99% higher ethanol productivity than that of the control strain. Further studies showed that the transcription of genes related to stress response was significantly upregulated in the engineered strains under the stress condition. Our results in this study provide novel insights in exploring zinc-responsive proteins for applications of synthetic biology in developing a robust industrial yeast.
Vangl2 Promotes Hematopoietic Stem Cell Expansion
Authors: Bouali Sarah , Hétu-Arbour Roxann , Gardet Célia , Heinonen Krista M.
Published: March 2022

Regulation of hematopoietic stem cell (HSC) self-renewal and differentiation is essential for their maintenance, and HSC polarity has been shown to play an important role in this regulation. Vangl2, a key component of the Wnt/polarity pathway, is expressed by fetal and adult HSCs, but its role in hematopoiesis and HSC function is unknown. Here we show the deletion of Vangl2 in mouse hematopoietic cells impairs HSC expansion and hematopoietic recovery post-transplant. Old Vangl2-deficient mice showed increased expansion of myeloid-biased multipotent progenitor cells concomitant with splenomegaly. Moreover, Vangl2-deficient cells were not able to effectively reconstitute the recipient bone marrow in serial transplants, or when coming from slightly older donors, demonstrating impaired self-renewal or expansion. Aged Vangl2-deficient HSCs displayed increased levels of cell cycle inhibitor p16INK4a and active β–catenin, which could contribute to their impaired function. Overall, our findings identify Vangl2 as a new regulator of hematopoiesis.
Modelling the Collective Mechanical Regulation of the Structure and Morphology of Epithelial Cell Layers
Authors: Khataee Hamid , Fraser Madeleine , Neufeld Zoltan
Published: March 2022

The morphology and function of epithelial sheets play an important role in healthy tissue development and cancer progression. The maintenance of structure of closely packed epithelial layers requires the coordination of various mechanical forces due to intracellular activities and interactions with other cells and tissues. However, a general model for the combination of mechanical properties which determine the cell shape and the overall structure of epithelial layers remains elusive. Here, we propose a computational model, based on the Cellular Potts Model, to analyse the interplay between mechanical properties of cells and dynamical transitions in epithelial cell shapes and structures. We map out phase diagrams as functions of cellular properties and the orientation of cell division. Results show that monolayers of squamous, cuboidal, and columnar cells are formed when the axis of cell proliferation is perpendicular to the substrate or along the major axis of the cells. Monolayer-to-multilayer transition is promoted via cell extrusion, depending on the mechanical properties of cells and the orientation of cell division. The results and model predictions are discussed in the context of experimental observations.
ITGAL as a Prognostic Biomarker Correlated With Immune Infiltrates in Gastric Cancer
Authors: Zhang Junchang , Wang Han , Yuan Cheng , Wu Jing , Xu Jiannan , Chen Songyao , Zhang Changhua , He Yulong
Published: March 2022

Integrin alpha L (ITGAL) is a member of the integrin family in which the abnormal expression is linked with carcinogenesis and immune regulation. However, the relation between ITGAL and the prognosis of gastric cancer (GC) and tumor-infiltrating lymphocytes (TILs) are not well understood. The differential expressions of ITGAL in human tumors and the clinical prognosis in GC were systematically analyzed via multiple databases including Gene Expression Profiling Interaction Analysis (GEPIA), UALCAN, Tumor Immune Estimation Resource (TIMER), and Kaplan–Meier (KM) plotter. TIMER, GEPIA, and TISIDB databases were used to comprehensively investigate the correlation between ITGAL and tumor infiltration immune cells. Also, further results were investigated by immunohistochemistry, qRT-PCR, and Western blot. We found that ITGAL expression in GC samples was considerably increased than in peritumor samples. Sample type, subgroup, cancer stage, lymphatic node stage, and worse survival were strongly related to high ITGAL expression. Moreover, upregulated ITGAL expression was strongly connected with immunomodulators, chemokines, and infiltrating levels of CD8+, CD4+ T cell, B cell, monocyte, neutrophil, macrophage, T-cell regulatory, NK cell, and myeloid dendritic cell in stomach adenocarcinoma (STAD). Specifically, immunohistochemistry and bioinformatic analysis showed that ITGAL expression was shown to have strong relationships with various immunological marker sets including PD1 (T-cell exhaustion marker). In conclusion, ITGAL is a prognostic biomarker for GC patients. It might regulate tumor immune microenvironment leading to poor prognosis. Furthermore, studies are essential to explore therapeutic targeting ITGAL.
Robust Acquisition of Spatial Transcriptional Programs in Tissues With Immunofluorescence-Guided Laser Capture Microdissection
Authors: Zhang Xiaodan , Hu Chuansheng , Huang Chen , Wei Ying , Li Xiaowei , Hu Miaomiao , Li Hua , Wu Ji , Czajkowsky Daniel M. , Guo Yan , Shao Zhifeng
Published: March 2022

The functioning of tissues is fundamentally dependent upon not only the phenotypes of the constituent cells but also their spatial organization in the tissue, as local interactions precipitate intra-cellular events that often lead to changes in expression. However, our understanding of these processes in tissues, whether healthy or diseased, is limited at present owing to the difficulty in acquiring comprehensive transcriptional programs of spatially- and phenotypically-defined cells in situ. Here we present a robust method based on immunofluorescence-guided laser capture microdissection (immuno-LCM-RNAseq) to acquire finely resolved transcriptional programs with as few as tens of cells from snap-frozen or RNAlater-treated clinical tissues sufficient to resolve even isoforms. The protocol is optimized to protect the RNA with a small molecule inhibitor, the ribonucleoside vanadyl complex (RVC), which thereby enables the typical time-consuming immunostaining and laser capture steps of this procedure during which RNA is usually severely degraded in existing approaches. The efficacy of this approach is exemplified by the characterization of differentially expressed genes between the mouse small intestine lacteal cells at the tip versus the main capillary body, including those that function in sensing and responding to local environmental cues to stimulate intra-cellular signalling. With the extensive repertoire of specific antibodies that are presently available, our method provides an unprecedented capability for the analysis of transcriptional networks and signalling pathways during development, pathogenesis, and aging of specific cell types within native tissues.
B-A Chromosome Translocations Possessing an A Centromere Partly Overcome the Root-Restricted Process of Chromosome Elimination in Aegilops speltoides
Authors: Li Daiyan , Ruban Alevtina , Fuchs Jörg , Kang Houyang , Houben Andreas
Published: March 2022

Some eukaryotes exhibit dramatic genome size differences between cells of different organs, resulting from the programmed elimination of chromosomes. Aegilops speltoides is an annual diploid species from the Poaceae family, with a maximum number of eight B chromosomes (Bs) in addition to its inherent seven pairs of standard A chromosomes (As). The Bs of this species undergo precise elimination in roots early in embryo development. In areal parts of the plant, the number of Bs is stable. To affect the root restricted process of B chromosome elimination, we employed X-ray mutagenesis, and different types of restructured Bs were identified. Standard Bs were observed in all analyzed shoots of mutagenized plants, while B-A translocations were only observed in 35.7% of F1 plants. In total 40 different B variants inconsistently escaped the elimination process in roots. As a result, mosaicism of B chromosome variants was found in roots. Only a small B chromosome fragment fused to an A chromosome was stably maintained in roots and shoots across F1 to F3 generations. The absence of B-A translocation chromosomes possessing a derived B centromere in root cells implies that the centromere of the B is a key component of the chromosome elimination process.
Direct Full-Length RNA Sequencing Reveals an Important Role of Epigenetics During Sexual Reversal in Chinese Soft-Shelled Turtle
Authors: Zhou Tong , Chen Guobin , Chen Meng , Wang Yubin , Zou Guiwei , Liang Hongwei
Published: March 2022

Sex dimorphism is a key feature of Chinese soft-shelled turtle (Pelodiscus sinensis). The males (M) have higher econosmic value than females (F) due to wider calipash and faster growth. Exogenous hormones like estradiol and methyltestosterone can induce sexual reversal to form new phenotypes (pseudo-female, PF; pseudo-male, PM) without changing the genotype. The possibility of inducing sexual reversal is particularly important in aquaculture breeding, but the underlying biological mechanisms remain unclear. Here we applied a direct RNA sequencing method with ultralong reads using Oxford Nanopore Technologies to study the transcriptome complexity in P. sinensis. Nanopore sequencing of the four gender types (M, F, PF, and PM) showed that the distribution of read length and gene expression was more similar between same-sex phenotypes than same-sex genotypes. Compared to turtles with an M phenotype, alternative splicing was more pronounced in F turtles, especially at alternative 3′ splice sites, alternative 5′ splice sites, and alternative first exons. Furthermore, the two RNA methylation modifications m5C and m6A were differentially distributed across gender phenotypes, with the M type having more modification sites in coding sequence regions, but fewer modification sites in 3′UTR regions. Quantitative analysis of enriched m6A RNAs revealed that the N6-methylated levels of Odf2, Pacs2, and Ak1 were significantly higher in M phenotype individuals, while the N6-methylated levels of Ube2o were reduced after sexual reversal from both M and F phenotypes. Taken together, these findings reveal an important role of epigenetics during sexual reversal in Chinese soft-shelled turtles.
Secretomics—A Key to a Comprehensive Picture of Unconventional Protein Secretion
Authors: Poschmann Gereon , Bahr Jasmin , Schrader Jürgen , Stejerean-Todoran Ioana , Bogeski Ivan , Stühler Kai
Published: March 2022

For a long time, leaderless secreted proteins (LLSP) were neglected as artifacts derived from dying cells. It is now generally accepted that secretion of LLSP–as a part of the collective term unconventional protein secretion (UPS) - is an evolutionarily conserved process and that these LLSP are actively and selectively secreted from living cells bypassing the classical endoplasmic reticulum-Golgi pathway. However, the mechanism of UPS pathways, as well as the number of LLSP and which part of a protein is involved in the selection of LLSPs for secretion, are still enigmatic and await clarification. Secretomics-a proteomics-based approach to identify and quantify all proteins secreted by a cell-is inherently unbiased toward a particular secretion pathway and offers the opportunity to shed light on the UPS. Here, we will evaluate and present recent results of proteomic workflows allowing to obtain high-confident secretome data. Additionally, we address that cell culture conditions largely affect the composition of the secretome. This has to be kept in mind to control cell culture induced artifacts and adaptation stress in serum free conditions. Evaluation of click chemistry for secretome analysis of cells under serum-containing conditions showed a significant change in the cellular proteome with longer incubation time upon treatment with non-canonical amino acid azidohomoalanine. Finally, we showed that the number of LLSP far exceeds the number of secreted proteins annotated in Uniprot and ProteinAtlas. Thus, secretomics in combination with sophisticated microbioanalytical and sample preparation methods is well suited to provide a comprehensive picture of UPS.
A Case Study of the Glycoside Hydrolase Enzyme Mechanism Using an Automated QM-Cluster Model Building Toolkit
Authors: Cheng Qianyi , DeYonker Nathan John
Published: March 2022

Glycoside hydrolase enzymes are important for hydrolyzing the β-1,4 glycosidic bond in polysaccharides for deconstruction of carbohydrates. The two-step retaining reaction mechanism of Glycoside Hydrolase Family 7 (GH7) was explored with different sized QM-cluster models built by the Residue Interaction Network ResidUe Selector (RINRUS) software using both the wild-type protein and its E217Q mutant. The first step is the glycosylation, in which the acidic residue 217 donates a proton to the glycosidic oxygen leading to bond cleavage. In the subsequent deglycosylation step, one water molecule migrates into the active site and attacks the anomeric carbon. Residue interaction-based QM-cluster models lead to reliable structural and energetic results for proposed glycoside hydrolase mechanisms. The free energies of activation for glycosylation in the largest QM-cluster models were predicted to be 19.5 and 31.4 kcal mol−1 for the wild-type protein and its E217Q mutant, which agree with experimental trends that mutation of the acidic residue Glu217 to Gln will slow down the reaction; and are higher in free energy than the deglycosylation transition states (13.8 and 25.5 kcal mol−1 for the wild-type protein and its mutant, respectively). For the mutated protein, glycosylation led to a low-energy product. This thermodynamic sink may correspond to the intermediate state which was isolated in the X-ray crystal structure. Hence, the glycosylation is validated to be the rate-limiting step in both the wild-type and mutated enzyme.
The Synthesis of Picolinamide-Supported Tetracoordinated Organoboron Complexes with Aggregation-Induced Emission Property
Authors: You Gaoqiang , Xu Liang , Wei Yu
Published: March 2022

The picolinamide-supported tetracoordinated organoboron complexes containing diaryl boronyl segments have been synthesized for the first time. Aryl trifluoroborates were utilized as the BAr2 sources to introduce different aryl motifs with diverse functional groups. The optical experiments discovered these five-membered boron-containing complexes were aggregation-induced emission (AIE) active, thus affording a new class of AIE molecules.
Multifunctional Nanomaterials for Ferroptotic Cancer Therapy
Authors: Shi Zhiyuan , Zheng Jianzhong , Tang Wenbin , Bai Yang , Zhang Lei , Xuan Zuodong , Sun Huimin , Shao Chen
Published: March 2022

Patient outcomes from the current clinical cancer therapy remain still far from satisfactory. However, in recent years, several biomedical discoveries and nanotechnological innovations have been made, so there is an impetus to combine these with conventional treatments to improve patient experience and disease prognosis. Ferroptosis, a term first coined in 2012, is an iron-dependent regulated cell death (RCD) based on the production of reactive oxygen species (ROS) and the consequent oxidization of polyunsaturated fatty acids (PUFAs). Many nanomaterials that can induce ferroptosis have been explored for applications in cancer therapy. In this review, we summarize the recent developments in ferroptosis-based nanomaterials for cancer therapy and discuss the future of ferroptosis, nanomedicine, and cancer therapy.
An Unexpected Inactivation of N-Heterocyclic Carbene Organic Catalyst by 1-Methylcyclopropylcarbaldehyde and 2,2,2-Trifluoroacetophenone
Authors: Chen Yanling , Lv Jie , Pan Xuling , Jin Zhichao
Published: March 2022

An unprecedented inactivation process of the indanol-derived NHC catalysts bearing N-C6F5 groups is reported. An unexpected multi-cyclic complex product is obtained from the 3-component reaction with the 1-methylcyclopropyl-carbaldehyde, the 2,2,2-trifluoroacetophenone and the NHC catalyst. The absolute structure of the inactivation product is unambiguously assigned via X-ray analysis on its single crystals. The formation of the structurally complex product is rationalized through a multi-step cascade cyclization process.
Microbiome Characterization of Infected Diabetic Foot Ulcers in Association With Clinical Outcomes: Traditional Cultures Versus Molecular Sequencing Methods
Authors: Mudrik-Zohar Hadar , Carasso Shaqed , Gefen Tal , Zalmanovich Anat , Katzir Michal , Cohen Yael , Paitan Yossi , Geva-Zatorsky Naama , Chowers Michal
Published: March 2022

Background

Infected diabetic foot ulcers (IDFU) are a major complication of diabetes mellitus. These potentially limb-threatening ulcers are challenging to treat due to impaired wound healing characterizing diabetic patients and the complex microbial environment of these ulcers.

Aim

To analyze the microbiome of IDFU in association with clinical outcomes.

Methods

Wound biopsies from IDFU were obtained from hospitalized patients and were analyzed using traditional microbiology cultures, 16S rRNA sequencing and metagenomic sequencing. Patients’ characteristics, culture-based results and sequencing data were analyzed in association with clinical outcomes.

Results

A total of 31 patients were enrolled. Gram-negative bacteria dominated the IDFU samples (79%, 59% and 54% of metagenomics, 16S rRNA and cultures results, respectively, p<0.001). 16S rRNA and metagenomic sequencing detected significantly more anaerobic bacteria, as compared to conventional cultures (59% and 76%, respectively vs. 26% in cultures, p=0.001). Culture-based results showed that Staphylococcus aureus was more prevalent among patients who were treated conservatively (p=0.048). In metagenomic analysis, the Bacteroides genus was more prevalent among patients who underwent amputation (p<0.001). Analysis of metagenomic-based functional data showed that antibiotic resistance genes and genes related to biofilm production and to bacterial virulent factors were more prevalent in IDFU that resulted in amputation (p<0.001).

Conclusion

Sequencing tools uncover the complex biodiversity of IDFU and emphasize the high prevalence of anaerobes and Gram-negative bacteria in these ulcers. Furthermore, sequencing results highlight possible associations among certain genera, species, and bacterial functional genes to clinical outcomes.
Biological Membrane-Penetrating Peptides: Computational Prediction and Applications
Authors: de Oliveira Ewerton Cristhian Lima , da Costa Kauê Santana , Taube Paulo Sérgio , Lima Anderson H. , Junior Claudomiro de Souza de Sales
Published: March 2022

Peptides comprise a versatile class of biomolecules that present a unique chemical space with diverse physicochemical and structural properties. Some classes of peptides are able to naturally cross the biological membranes, such as cell membrane and blood-brain barrier (BBB). Cell-penetrating peptides (CPPs) and blood-brain barrier-penetrating peptides (B3PPs) have been explored by the biotechnological and pharmaceutical industries to develop new therapeutic molecules and carrier systems. The computational prediction of peptides’ penetration into biological membranes has been emerged as an interesting strategy due to their high throughput and low-cost screening of large chemical libraries. Structure- and sequence-based information of peptides, as well as atomistic biophysical models, have been explored in computer-assisted discovery strategies to classify and identify new structures with pharmacokinetic properties related to the translocation through biomembranes. Computational strategies to predict the permeability into biomembranes include cheminformatic filters, molecular dynamics simulations, artificial intelligence algorithms, and statistical models, and the choice of the most adequate method depends on the purposes of the computational investigation. Here, we exhibit and discuss some principles and applications of these computational methods widely used to predict the permeability of peptides into biomembranes, exhibiting some of their pharmaceutical and biotechnological applications.
A Nomogram With Six Variables Is Useful to Predict the Risk of Acquiring Carbapenem-Resistant Microorganism Infection in ICU Patients
Authors: Zhang Jin , Liu Wanjun , Shi Wei , Cui Xuanxuan , Liu Yu , Lu Zongqing , Xiao Wenyan , Hua Tianfeng , Yang Min
Published: March 2022

Background

Carbapenem-resistant microorganism (CRO) transmission in the medical setting confers a global threat to public health. However, there is no established risk prediction model for infection due to CRO in ICU patients. This study aimed to develop a nomogram to predict the risk of acquiring CRO infection in patients with the first ICU admission and to determine the length of ICU stay (ICU-LOS) and 28-day survival.

Methods

Patient data were retrieved from the Medical Information Mart for Intensive Care (MIMIC-IV) database based on predetermined inclusion and exclusion criteria. A CRO was defined as a bacterium isolated from any humoral microbial culture that showed insensitivity or resistance to carbapenems. The characteristics of CRO and non-CRO patients in the first ICU admission were compared. Propensity score matching was applied to balance the differences between the CRO and non-CRO cohorts. Kaplan–Meier curves were constructed to determine the 28-day survival rate and ICU-LOS. Furthermore, after randomization of the CRO cohort into the training and validation sets, a predictive nomogram was constructed based on LASSO regression and Logistic regression analysis, and its performance was verified by internal validation.

Results

Overall, 4531 patients who had first ICU admission as recorded in MIMIC-IV were enrolled, 183 (4.04%) of whom were diagnosed with CRO infection. Moreover, CRO infection was independently associated with 28-day survival and ICU-LOS in ICU patients. Parameters eligible for inclusion in this nomogram were male sex, hemoglobin-min, temperature-max, use of a peripherally inserted central catheter line, dialysis treatment, and use of carbapenems. This nomogram showed a better performance as indicated by the area under the receiver operating characteristic curve values of 0.776 (95% confidence interval [CI] 0.667-0.750) and 0.723 (95% CI 0.556-0.855) in the training and validation sets, respectively, in terms of predicting the risk of acquiring CRO infection.

Conclusions

CRO infection was independently associated with ICU-LOS and 28-day survival in patients with first ICU admission. The nomogram showed the best prediction of the risk of acquiring CRO infection in ICU patients. Based on the nomogram-based scoring, we can management the risk factors and guide individualized prevention and control of CRO.