bluuebunny/crossref_metadata_2025 huggingface dataset:
Stoning Law and Human Rights
Authors: Abdullah  , Muntasir  , Safrizal
Published: September 2021

The law contained in Islam can provide values and an essential sense of justice for all Muslim and non-Muslim human beings. One of the laws in Islam is stoning. Adultery is an act that has been forbidden by Allah and is included in a big and very heinous sin. The application of the law of stoning was first applied in Islam before the conquest of Mecca (fathul Mecca), and before the revelation of Surah An-Nur verse 2 regarding vols (whips), Most scholars agree that for adulterers who are muhsan the punishment is death by being stoned with stones or the like. However, there is no reference that states that the type of stoning law violates human rights or does not violate human rights, but the highlight here is the stoning (death) punishment. Whether the death penalty violates human rights or not, this becomes a controversy between one party and another who has a different perspective, the concept of human rights in Islam is different from the concept of human rights in the perspective of western countries.
Kaf'ah Ignore Factors in Marriage (Case Study in Bale Busu Village, Mutiara Subdistrict, Pidie Regency)
Authors: Afrizal
Published: September 2021

Kafa'ahis an alternative for people who want to do marriage in choosing their partner. It is prescribedkafā'ahis to form a sakian household, mawaddah and rahmah. In general, people's understanding of the meaning ofkafā'ahalready understand, but many people ignore it due to certain things. This research is a field research with a qualitative approach. The data sources are primary data sources and secondary data sources using two data collection techniques, namely interview and observation data collection techniques. The results of his research show thatfactors that influence people to ignore kafaah are: (1) prefer a partner who has religious knowledge (2) kafā'ah is not a legal requirement for marriage; (3) Economic Factors (4)their own intentions and arranged marriages by their parents are the causes of non-sequential marriages; (5) choose their own partner and love each other. So the conclusion is that the people of Bale Busu Village actually really understand the meaning of kafā'ah but the practice is very little from the community because it is influenced by certain factors.
Synthesis of New Boron Derived Compounds; Anticancer, Antioxidant and Antimicrobial Effect in Vitro Glioblastoma Tumor Model
Authors: Koldemir-Gündüz Meliha , Aydin Hasan Emre , Berikten Derya , Kaymak Güllü , Köse Dursun Ali , Arslantaş Ali
Published: September 2021

Objective : The aim of our study is to investigate the cytotoxic, antioxidant, and antimicrobial effects of newly synthesized boron compounds in U87MG glioblastoma cell treatment.Methods : We synthesized boron glycine monoester (BGM) and boron glycine diester (BGD) structures containing boron atoms and determined their cytotoxic activities on glioblastoma by the MTT method. The inhibitory concentration 50 (IC50) value was calculated with GraphPad Prism 5.0 program. The IC50 values were administered 48 hours on U87MG glioblastoma cell. Catalase (CAT), acid phosphatase (ACP) and alkaline phosphatase (ALP) enzyme activity, malondialdehyde (MDA), total glutathione (GSH), and total protein levels were detected using spectrophotometric methods. We determined the antimicrobial activities of BGM and BGD with the disc diffusion method.Results : After 48 hours of BGM and BGD application to U87MG glioblastoma cells, we found the IC50 value as 6.6 mM and 26 mM, respectively. CAT and ACP enzyme activities were decreased in BGM and BGD groups. MDA which is a metabolite of lipid peroxidation was increased in both boron compounds groups. GSH level was reduced especially in BGD group. BGM and BGD have been found to be antimicrobial effects.Conclusion : Boron compounds, especially the BGM, can provide a new therapeutic approach for the treatment of glioblastoma with their anticancer, antioxidant, and antimicrobial effects.
ПОСТІЙНО ДІЮЧИЙ СЕМІНАР «ІНФОРМАЦІЙНО-КОМУНІКАЦІЙНІ ТЕХНОЛОГІЇ В ОСВІТНЬОМУ ПРОЦЕСІ ЗАКЛАДІВ ВИЩОЇ ОСВІТИ» ЯК ФОРМА ПІДВИЩЕННЯ КВАЛІФІКАЦІЇ ВИКЛАДАЧІВ
Authors: Саяпіна Світлана Анатоліївна , Коркішко Олена Геннадіївна , Коркішко Артем Володимирович
Published: September 2021

Статтю присвячено актуальній проблемі сучасної вищої школи – формуванню у викладачів уміння застосовувати інформаційно-комунікаційні технології в освітньому процесі закладу вищої освіти. Запропоновано досвід упровадження постійно діючого семінару «Інформаційно-комунікаційні технології в освітньому процесі закладів вищої освіти», створеного для викладачів, його структуру й змістове наповнення, завдання курсу, особливості реалізації, навчальні методи і прийоми, навчальні матеріали, додаткові форми роботи та очікувані результати навчання. З урахуванням наукового доробку сучасних дослідників зазначено, що однією з умов успішної реалізації завдань освіти є розв’язання проблеми підготовки викладачів до використання інформаційно-комунікаційних технологій у своїй професійній діяльності, формування в них професійної та загальної інформаційної культури, цифрової компетентності, що сприятиме всебічному розвитку педагогів, бажанню вчитися впродовж усього життя, розумінню інформаційно-комунікаційних процесів, удосконаленню професійної майстерності та забезпечить підвищення якості освіти. Підкреслено, що засвоєння предметного змісту постійно діючого семінару викладачами допомагає формуванню та вдосконаленню загальних (володіння комп’ютерною та інформаційною культурою, усвідомлення цінності суб’єктивної позиції в інформаційному просторі тощо), загальнопрофесійних (знання та використання раціональних методів пошуку й зберігання інформації в сучасних інформаційних масивах; володіння навичками роботи з різноманітними видами комп’ютерної техніки; уміння передавати інформацію в Інтернеті; володіння навичками організації та проведення занять за допомогою комп’ютерних та інтернет-технологій; уміння організовувати самостійну роботу студентів, використовуючи ІКТ; володіння навичками використання комп’ютерних інтернет-технологій для викладання навчальних дисциплін), спеціальних (здатність обґрунтовано обирати й ефективно використовувати ІКТ з метою забезпечення особистісного та професійного розвитку тощо) компетентностей. Представлено роботу постійно діючого семінару на прикладі теми «Ментальні карти як спосіб організації інформації».
Uluslararası İlişkiler Disiplini ve Niteliksel Yöntem: Türkiye’de Göç Çalışmaları Örneği
Authors: GÖÇER Derya , ŞENYUVA Özgehan
Published: September 2021

Bu çalışma Türkiye’de Uluslararası İlişkiler (Uİ) Disiplini’nin niteliksel yöntemle kurduğu ilişkiyi göç

alanında Türkiye’deki Suriyelilerle ilgili yürütülen çalışmalar örneği bağlamında irdelemektedir. Türkiye’de

Suriyelilerin sayısının dört milyona yakın olması ve ülkenin hemen her yerinde bulunmaları nedeniyle Uİ

disiplininde pek kolay görülmeyen yöntemsel çeşitliliğe zemin hazırlayan bir durum ortaya çıkmıştır. Konunun

önemi ve popülerliği nedeniyle her gün artan sayıda makale, rapor, analiz ile yüksek lisans ve doktora tezleri

yayınlanmaktadır. Bu makalede, 2011 yılından itibaren Uİ alanında bu konuda yayınlanan tezler ve makalelerin

taranması ve bu konudaki uzman akademisyenlerle yapılan derinlemesine görüşmelerle yöntemsel tercih ve

yönelimler incelenmiştir. Bu çerçevede, 1) Uİ disiplini ile Türkiye’de son dönemde göç alanında kurulan özel

ilişki, 2) yöntem seçimini belirleyen faktörler, 3) niteliksel yöntemin bu ilişkiye getirdiği artılar ve eksiler, 4)

araştırma etiğiyle ilgili beliren konular ele alınmaktadır.
What is Matter in Aristotle's Hylomorphism?
Authors: Pfeiffer Christian
Published: September 2021

Aristotle's notion of matter has been seen either as unintelligible, it being some mysterious potential entity that is nothing in its own right, or as simply the notion of an everyday object. The latter is the common assumption in contemporary approaches to hylomorphism, but as has been pointed out, especially by scholars with a background in ancient philosophy, if we conceive of matter as an object itself we cannot account for the unity of hylomorphic substances. Thus, they assume that a hylomorphic substance is an essential unity and matter not a constituent at all. This solution to the problem of unity, however, brings us back to the mysterious notion of matter. For these reasons, I will revisit Aristotle's conception of matter in this paper. I will argue that an understanding of form as a cause of being requires that matter be an independent constituent of the individual substance. However, I agree that the conception of matter as an individual object with an essence makes it impossible to solve the problem of unity. We therefore need to take seriously Aristotle's assertion that matter is nothing in its own right and not an individual. By denying that matter is an individual, Aristotle does not introduce a mysterious entity, nor does he deny that it can be identified independently of the whole; instead, matter for Aristotle is an irreducible plurality, and this explains why it is not an individual and has no essence. I will conclude with some observations on how this gives rise to two competing versions of hylomorphic constitution.
An Unbiased Mineral Compositional Analysis Technique for Circumstellar Disks
Authors: Kipreos Yung , Song Inseok
Published: September 2021

A circumstellar disk that surrounds a star is composed of gas, dust, and rocky objects that are in orbit around it. Around infant stars, this disk can act as a source of material that can be used to form planetesimals, which can then accrete more material and form into planets. Studying the mineral composition of these disks can provide insight into the processes that created our solar system. The purpose of this paper is to analyze the mineral composition of these disks by using a newly created python package, Min-CaLM. This package determines the relative mineral abundance within a disk by using a linear regression technique called non-negative least square minimization. The circumstellar disks that are capable of undergoing compositional analysis must have a spectrum with both a detectable mid-infrared excess and prominent silicate features. From our sample, there are only eight debris disks that qualify to be candidates for the Min-CaLM program. The mineral compositions calculated by Min-CaLM are then compared to the Tholen asteroid classification scheme. HD 23514, HD 105234, HD 15407A, BD+20 307, HD 69830, and HD 172555 are found to have a compositions similar to that expected for C-type asteroids, TYC 9410-532-1 resembles the composition of S-type asteroids, and HD 100546 resembles D-type asteroids. Min-CaLM also calculates the mineral compositions of the comets Tempel 1 and Hale-Bopp, and they are used as a comparison between the material in our early solar system and the debris disk compositions. KEYWORDS: Debris disk; Mineral; Composition; Analysis; Asteroid; Circumstellar; Spectroscopy; Python
PENGETAHUAN TERHADAP KEPATUHAN MENGKONSUMSI TABLET FE PADA IBU HAMIL TRIMESTER III
Authors: Septiyaningsih Rochany , Frisca Dewi Yunadi  , Indratmoko Septiana
Published: September 2021

Anemia dalam kehamilan dapat mempengaruhi nilai kesejahteraan sosial ekonomimasyarakat dan kualitas sumber daya manusia, serta berpotensi membahayakan ibu dananak. Oleh karena itu, anemia dalam kehamilan perlu mendapatkan perhatian yang seriusdari semua pihak yang terkait dalam memberikan pelayanan kesehatan. World HealthOrganization menyatakan prevalensi anemia dalam kehamilan di seluruh dunia adalah41,8% pada tahun 2010. Prevalensi anemia dalam kehamilan di Indonesia mengalamipeningkatan yaitu pada tahun 2013 sebesar 37,1% dan meningkat pada tahun 2018 sebesar48,9%. Upaya Pemerintah yang sudah dilakukan adalah dengan program pemberiansuplementasi tablet besi pada ibu hamil. Pengetahuan yang dimiliki ibu hamil tentanganemia sangat penting, karena akan mempengaruhi perilaku kesehatan yang dilakukansehingga dapat menurunkan risiko anemia selama kehamilan. Penelitian ini penelitiankuantitatif dengan pendekatan cross-sectional. Sampel menggunakan sampel minimalyaitu 30 ibu hamil trimester III, dengan teknik accidental sampling. Analisis dalampenelitian ini adalah Chi-Square. Hasil uji Chi-Square menunjukkan bahwa ada hubungantingkat pengetahuan dengan kepatuhan mengkonsumsi tablet Fe pada ibu hamil trimesterIII di Puskesmas Cilacap Selatan I (p-value=0,000). Ada hubungan pengetahuan dengankepatuhan mengkonsumsi tablet Fe pada ibu hamil trimester III di Puskesmas CilacapSelatan I.
HEALTH LITERACY DAN PERILAKU CERDIK PENDERITA HIPERTENSI DIMASA PANDEMI COVID-19
Authors: Ida Marthilda , Fatmawati Baiq Ruli , Prihatin Kurniati , Arifin Zainal , Albayani Melati Inayati
Published: September 2021

Pandemi secara global yang disebabkan Coronavirus Disease 2019 (Covid-19) telahmewabah dan menyebar dengan cepat, dan terjadi secara bersamaan di seluruh dunia.Peningkatan angka kesakitan dan kematian akibat Covid-19 disebabkan oleh adanyapenyakit penyerta (comorbid). Hipertensi merupakan salah satu comorbid paling banyakditemukan pada Covid-19 sehingga penderita hipertensi diharapkan mampu memodifikasigaya hidup dan mengubah perilaku kesehatan dengan mengoptimalkan health literacydalam pengelolaan kesehatan. Penelitian ini bertujuan untuk mengetahui hubungan healthliteracy dan perilaku CERDIK penderita hipertensi di masa pandemi Covid-19. Metodepenelitian yang digunakan adalah deskriptif analitik dengan Pendekataan Cross Sectional.Jumlah responden sebanyak 138 orang dengan teknik pengambilan sampel accidentalsampling. Data dianalisis dengan chi square dengan hasil penelitian menunjukkan bahwaada hubungan antara health literacy dengan perilaku CERDIK penderita hipertensidi masa pandemi Covid-19 (p-value: 0,000). Kemampuan penderita hipertensi dalammencari health literacy yang baik dapat mengubah gaya hidup dan dapat meningkatkanperubahan perilaku CERDIK sehingga derajat kesehatan meningkat secara optimal dimasa pandemi Covid-19. Penderita hipertensi diharapkan untuk meningkatkan danmengembangkan health literacy guna mengoptimalkan derajat kesehatan yang lebih baikdi masa pandemi Covid-19
Epsilon-poly-L-lysine: Recent Advances in Biomanufacturing and Applications
Authors: Wang Liang , Zhang Chongyang , Zhang Jianhua , Rao Zhiming , Xu Xueming , Mao Zhonggui , Chen Xusheng
Published: September 2021

ε-poly-L-lysine (ε-PL) is a naturally occurring poly(amino acid) of varying polymerization degree, which possesses excellent antimicrobial activity and has been widely used in food and pharmaceutical industries. To provide new perspectives from recent advances, this review compares several conventional and advanced strategies for the discovery of wild strains and development of high-producing strains, including isolation and culture-based traditional methods as well as genome mining and directed evolution. We also summarize process engineering approaches for improving production, including optimization of environmental conditions and utilization of industrial waste. Then, efficient downstream purification methods are described, including their drawbacks, followed by the brief introductions of proposed antimicrobial mechanisms of ε-PL and its recent applications. Finally, we discuss persistent challenges and future perspectives for the commercialization of ε-PL.
Defining Supply Chain Visibility for Industrial Construction Projects
Authors: Dharmapalan Vineeth , O’Brien William J. , Morrice Douglas J.
Published: September 2021

Good Supply Chain Visibility (SCV) is vital for on-time delivery and installation of materials on industrial construction projects. SCV is possible via the exchange of information about materials in the supply chain. Prior academic research has highlighted the importance of SCV. However, the literature lacks the detailed definition of visibility that can be easily applied to projects. This research reviewed prior studies on SCV and adopted an appropriate definition that supports relevant decision-making on industrial construction projects. From this definition, the research objective is to develop detailed operational definitions of information needed to support supply chain decisions on industrial construction projects. The study employed mixed methods that consisted of interviews, review of mini-cases of industrial projects, procurement and material tracking tool assessment, and group discussions in structured workshops with a panel of subject matter experts. The research developed 79 detailed information needs and associated definitions that support ten key supply chain decision areas across detailed design, procurement, and construction phases of industrial construction projects. These definitions were evaluated by multiple means including an external team and a case study of an industrial construction project. The definitions developed by this research will enable both researchers and practitioners to invest in better measurements of visibility and support development of new tools and techniques.
Seeking Health Information and Social Support in the Diabetes Online Community
Authors: Hughes Allyson , Heydarian Nazanin , Gerardo Diana , Solis Isabela , Morera Osvaldo
Published: September 2021

Purpose

People with type 1 diabetes (T1D) search for health information online in the Diabetes Online Community (DOC), where individuals with diabetes, researchers and caregivers post and respond to health questions. The aims of this study were 1) to understand how people with T1D are seeking health information and engaging in health behaviors in the DOC, and 2) develop a measure of online health information seeking in adults with T1D.

Research Method

Ninety-five adults with T1D completed qualitative prompts online.

Results

Themes that emerged in this study included sense of community, and multiple types of social support that are necessary in disease management.

Conclusions

This study used qualitative methods to develop a valid scale tailored for adults with T1D. Future research should seek to collect additional data to bolster validity and reliability.
Roles and Mechanisms of Irisin in Attenuating Pathological Features of Osteoarthritis
Authors: Li Xiangfen , Zhu Xiaofang , Wu Hongle , Van Dyke Thomas E. , Xu Xiaoyang , Morgan Elise F. , Fu Wenyu , Liu Chuanju , Tu Qisheng , Huang Dingming , Chen Jake
Published: September 2021

To investigate the effects and mechanisms of irisin, a newly discovered myokine, in cartilage development, osteoarthritis (OA) pathophysiology and its therapeutic potential for treating OA we applied the following five strategical analyses using (1) murine joint tissues at different developmental stages; (2) human normal and OA pathological tissue samples; (3) experimental OA mouse model; (4) irisin gene knockout (KO) and knock in (KI) mouse lines and their cartilage cells; (5) in vitro mechanistic experiments. We found that Irisin was involved in all stages of cartilage development. Both human and mouse OA tissues showed a decreased expression of irisin. Intra-articular injection of irisin attenuated ACLT-induced OA progression. Irisin knockout mice developed severe OA while irisin overexpression in both irisin KI mice and intraarticular injection of irisin protein attenuated OA progression. Irisin inhibited inflammation and promoted anabolism in chondrogenic ADTC5 cells. Proliferative potential of primary chondrocytes from KI mice was found to be enhanced, while KO mice showed an inhibition under normal or inflammatory conditions. The primary chondrocytes from irisin KI mice showed reduced expression of inflammatory factors and the chondrocytes isolated from KO mice showed an opposite pattern. In conclusion, it is the first time to show that irisin is involved in cartilage development and OA pathogenesis. Irisin has the potential to ameliorate OA progression by decreasing cartilage degradation and inhibiting inflammation, which could lead to the development of a novel therapeutic target for treating bone and cartilage disorders including osteoarthritis.
Mitochondrial Breast Cancer Resistant Protein Sustains the Proliferation and Survival of Drug-Resistant Breast Cancer Cells by Regulating Intracellular Reactive Oxygen Species
Authors: Zhang He , Han Xingxing , Wang Zhaosong , Wang Zhiyong , Cui Yanfen , Tian Ran , Zhu Yuying , Han Baoai , Liu Hui , Zuo Xiaoyan , Ren Sixin , Tian Jianfei , Niu Ruifang , Zhang Fei
Published: September 2021

ATP-binding cassette (ABC) transporter family are major contributors to the drug resistance establishment of breast cancer cells. Breast cancer resistant protein (BCRP), one of the ABC transporters, has long been recognized as a pump that effluxes the therapeutic drugs against the concentration gradient. However, recent studies suggest that the biological function of BCRP is not limited in its drug pump activity. Herein, the role of BCRP in the proliferation and survival of drug-resistant breast cancer cells was investigated. We found that BCRP is not the major drug pump to efflux epirubicin in the resistant cells that express multiple ABC transporters. Silencing of BCRP significantly impairs cell proliferation and induces apoptosis of the resistant cells in vitro and in vivo. RNA-sequencing and high-throughput proteomics suggest that BCRP is an inhibitory factor of oxidative phosphorylation (OXPHOS). Further research suggests that BCRP is localized in the mitochondria of the resistant cells. Knockdown of BCRP elevated the intracellular reactive oxygen species level and eventually promotes the cell to undergo apoptosis. This study demonstrated that BCRP exerts important onco-promoting functions in the drug-resistant breast cancer cells independent of its well-recognized drug efflux activity, which shed new light on understanding the complex functional role of ABC transporters in drug-resistant cells.
Direct Current Stimulation Disrupts Endothelial Glycocalyx and Tight Junctions of the Blood-Brain Barrier in vitro
Authors: Xia Yifan , Li Yunfei , Khalid Wasem , Bikson Marom , Fu Bingmei M.
Published: September 2021

Transcranial direct current stimulation (tDCS) is a non-invasive physical therapy to treat many psychiatric disorders and to enhance memory and cognition in healthy individuals. Our recent studies showed that tDCS with the proper dosage and duration can transiently enhance the permeability (P) of the blood-brain barrier (BBB) in rat brain to various sized solutes. Based on the in vivo permeability data, a transport model for the paracellular pathway of the BBB also predicted that tDCS can transiently disrupt the endothelial glycocalyx (EG) and the tight junction between endothelial cells. To confirm these predictions and to investigate the structural mechanisms by which tDCS modulates P of the BBB, we directly quantified the EG and tight junctions of in vitro BBB models after DCS treatment. Human cerebral microvascular endothelial cells (hCMECs) and mouse brain microvascular endothelial cells (bEnd3) were cultured on the Transwell filter with 3 μm pores to generate in vitro BBBs. After confluence, 0.1–1 mA/cm2 DCS was applied for 5 and 10 min. TEER and P to dextran-70k of the in vitro BBB were measured, HS (heparan sulfate) and hyaluronic acid (HA) of EG was immuno-stained and quantified, as well as the tight junction ZO-1. We found disrupted EG and ZO-1 when P to dextran-70k was increased and TEER was decreased by the DCS. To further investigate the cellular signaling mechanism of DCS on the BBB permeability, we pretreated the in vitro BBB with a nitric oxide synthase (NOS) inhibitor, L-NMMA. L-NMMA diminished the effect of DCS on the BBB permeability by protecting the EG and reinforcing tight junctions. These in vitro results conform to the in vivo observations and confirm the model prediction that DCS can disrupt the EG and tight junction of the BBB. Nevertheless, the in vivo effects of DCS are transient which backup its safety in the clinical application. In conclusion, our current study directly elucidates the structural and signaling mechanisms by which DCS modulates the BBB permeability.
The Role of Osteokines in Sarcopenia: Therapeutic Directions and Application Prospects
Authors: Lu Wenhao , Xiao Wenfeng , Xie Wenqing , Fu Xin , Pan Linyuan , Jin Hongfu , Yu Yongle , Zhang Yi , Li Yusheng
Published: September 2021

Sarcopenia is an age-related disease in which muscle mass, strength and function may decline with age or can be secondary to cachexia or malnutrition and can lead to weakness, falls and even death. With the increase in life expectancy, sarcopenia has become a major threat to the health of the elderly. Currently, our understanding of bone-muscle interactions is not limited to their mechanical coupling. Bone and muscle have been identified as secretory endocrine organs, and their interaction may affect the function of each. Both muscle-derived factors and osteokines can play a role in regulating muscle and bone metabolism via autocrine, paracrine and endocrine mechanisms. Herein, we comprehensively summarize the latest research progress on the effects of the osteokines FGF-23, IGF-1, RANKL and osteocalcin on muscle to explore whether these cytokines can be utilized to treat and prevent sarcopenia.
Calcium Binding Protein S100A16 Expedites Proliferation, Invasion and Epithelial-Mesenchymal Transition Process in Gastric Cancer
Authors: You Xiaoying , Li Min , Cai Hongwei , Zhang Wenwen , Hong Ye , Gao Wenjie , Liu Yun , Liang Xiubin , Wu Tijun , Chen Fang , Su Dongming
Published: September 2021

Gastric cancer (GC) is one of the most common malignant tumors of the digestive system, listed as the second cause of cancer-related deaths worldwide. S100 Calcium Binding Protein A16 (S100A16) is an acidic calcium-binding protein associated with several types of tumor progression. However, the function of S100A16 in GC is still not very clear. In this study, we analyzed S100A16 expression with the GEPIA database and the UALCAN cancer database. Meanwhile, 100 clinical GC samples were used for the evaluation of its role in the prognostic analysis. We found that S100A16 is significantly upregulated in GC tissues and closely correlated with poor prognosis in GC patients. Functional studies reveal that S100A16 overexpression triggers GC cell proliferation and migration both in vivo and in vitro; by contrast, S100A16 knockdown restricts the speed of GC cell growth and mobility. Proteomic analysis results reveal a large S100A16 interactome, which includes ZO-2 (Zonula Occludens-2), a master regulator of cell-to-cell tight junctions. Mechanistic assay results indicate that excessive S100A16 instigates GC cell invasion, migration, and epithelial-mesenchymal transition (EMT) via ZO-2 inhibition, which arose from S100A16-mediated ZO-2 ubiquitination and degradation. Our results not only reveal that S100A16 is a promising candidate biomarker in GC early diagnosis and prediction of metastasis, but also establish the therapeutic importance of targeting S100A16 to prevent ZO-2 loss and suppress GC metastasis and progression.
NR2F1-AS1 Promotes Pancreatic Ductal Adenocarcinoma Progression Through Competing Endogenous RNA Regulatory Network Constructed by Sponging miRNA-146a-5p/miRNA-877-5p
Authors: Luo Dong , Liu Yunfei , Li Zhiqiang , Zhu Hongwei , Yu Xiao
Published: September 2021

The role of NR2F1-AS1 in pancreatic ductal adenocarcinoma (PDAC) remains unknown. Therefore, we aimed to investigate the biological mechanism of NR2F1-AS1 in PDAC. The expression of NR2F1-AS1 was measured by using microarray data and real-time PCR. The effects of NR2F1-AS1 knockdown on proliferation, cell cycle progression, invasion in vitro and tumorigenesis in vivo were investigated. The mechanism of competitive endogenous RNAs was determined from bioinformatics analyses and validated by a dual-luciferase reporter gene assay. Potential target mRNAs from TargetScan 7.2 were selected for subsequent bioinformatics analysis. Key target mRNAs were further identified by screening hub genes and coexpressed protein-coding genes (CEGs) of NR2F1-AS1. NR2F1-AS1 was highly expressed in PDAC, and the overexpression of NR2F1-AS1 was associated with overall survival and disease-free survival. The knockdown of NR2F1-AS1 impaired PDAC cell proliferation, migration, invasion and tumorigenesis. NR2F1-AS1 competitively sponged miR-146a-5p and miR-877-5p, and low expression of the two miRNAs was associated with a poor prognosis. An integrative expression and survival analysis of the hub genes and CEGs demonstrated that the NR2F1-AS1–miR-146a-5p/miR-877-5p–GALNT10/ZNF532/SLC39A1/PGK1/LCO3A1/NRP2/LPCAT2/PSMA4 and CLTC ceRNA networks were linked to the prognosis of PDAC. In conclusion, NR2F1-AS1 overexpression was significantly associated with poor prognosis. NR2F1-AS1 functions as an endogenous RNA to construct a novel ceRNA network by competitively binding to miR-146a-5p/miR-877-5p, which may contribute to PDAC pathogenesis and could represent a promising diagnostic biomarker or potential novel therapeutic target in PDAC.
Mechanisms of Functional Pleiotropy of p73 in Cancer and Beyond
Authors: Logotheti Stella , Richter Christin , Murr Nico , Spitschak Alf , Marquardt Stephan , Pützer Brigitte M.
Published: September 2021

The transcription factor p73 is a structural and functional homolog of TP53, the most famous and frequently mutated tumor-suppressor gene. The TP73 gene can synthesize an overwhelming number of isoforms via splicing events in 5′ and 3′ ends and alternative promoter usage. Although it originally came into the spotlight due to the potential of several of these isoforms to mimic p53 functions, it is now clear that TP73 has its own unique identity as a master regulator of multifaceted processes in embryonic development, tissue homeostasis, and cancer. This remarkable functional pleiotropy is supported by a high degree of mechanistic heterogeneity, which extends far-beyond the typical mode of action by transactivation and largely relies on the ability of p73 isoforms to form protein–protein interactions (PPIs) with a variety of nuclear and cytoplasmic proteins. Importantly, each p73 isoform carries a unique combination of functional domains and residues that facilitates the establishment of PPIs in a highly selective manner. Herein, we summarize the expanding functional repertoire of TP73 in physiological and oncogenic processes. We emphasize how TP73’s ability to control neurodevelopment and neurodifferentiation is co-opted in cancer cells toward neoneurogenesis, an emerging cancer hallmark, whereby tumors promote their own innervation. By further exploring the canonical and non-canonical mechanistic patterns of p73, we apprehend its functional diversity as the result of a sophisticated and coordinated interplay of: (a) the type of p73 isoforms (b) the presence of p73 interaction partners in the cell milieu, and (c) the architecture of target gene promoters. We suppose that dysregulation of one or more of these parameters in tumors may lead to cancer initiation and progression by reactivating p73 isoforms and/or p73-regulated differentiation programs thereof in a spatiotemporally inappropriate manner. A thorough understanding of the mechanisms supporting p73 functional diversity is of paramount importance for the efficient and precise p73 targeting not only in cancer, but also in other pathological conditions where TP73 dysregulation is causally involved.
Using Video to Give More Effective and Engaging Science Talks
Authors: Brennan Eric B.
Published: September 2021

Science presentations at conferences are an important way that scientists share exciting research discoveries. Some presentations are informative and engaging, but unfortunately many are not. This article describes a novel method (Video Let’s Talk, VLT) for more engaging and effective science presentations, where the presenter 1. makes a video that fills half of the presentation time, 2. shows the video in lieu of a live presentation, and 3. spends the remaining time engaging with the audience. The benefits and challenges of the VLT method are described along with tips on how to do the VLT well. These insights are based on the author’s experience giving numerous VLT presentations to scientists, farmers and other groups over the past seven years. The VLT method is timely considering how the COVID pandemic has forced scientists to learn new skills in do it yourself (DIY) video making in order to participate in virtual conferences.
De novo Drug Delivery Modalities for Treating Damaged Hearts: Current Challenges and Emerging Solutions
Authors: Alvi Syed Baseeruddin , Ahmed Salmman , Sridharan Divya , Naseer Zahra , Pracha Nooruddin , Wang Henry , Boudoulas Konstantinos Dean , Zhu Wuqiang , Sayed Nazish , Khan Mahmood
Published: September 2021

Cardiovascular disease (CVD) is the leading cause of mortality, resulting in approximately one-third of deaths worldwide. Among CVD, acute myocardial infarctions (MI) is the leading cause of death. Current treatment modalities for treating CVD have improved over the years, but the demand for new and innovative therapies has been on the rise. The field of nanomedicine and nanotechnology has opened a new paradigm for treating damaged hearts by providing improved drug delivery methods, specifically targeting injured areas of the myocardium. With the advent of innovative biomaterials, newer therapeutics such as growth factors, stem cells, and exosomes have been successfully delivered to the injured myocardial tissue, promoting improvement in cardiac function. This review focuses on three major drug delivery modalities: nanoparticles, microspheres, and hydrogels, and their potential for treating damaged hearts following an MI.
Comparison of Cumulative Live Birth Rate Between Aged PCOS Women and Controls in IVF/ICSI Cycles
Authors: Mai Zhuoyao , Liu Manlin , Pan Ping , Li Lin , Huang Jia , Chen Xiaoli , Yang Dongzi
Published: September 2021

The present study aimed to assess whether women with polycystic ovarian syndrome (PCOS) ≥35 years age undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles experienced a higher cumulative live birth rate (CLBR) over a two-year period compared with age- and body mass index (BMI)-matched patients with tubal factor infertility. Through propensity score matching (PSM) approach, the authors retrospectively analyzed the IVF/ICSI outcomes of 263 PCOS patients (35-46 years of age [mean, 37 years]) and 526 age- and BMI-matched tubal factor controls two years after oocyte retrieval. Multivariate regression analysis was performed to explore factors influencing cumulative live birth. Women with PCOS exhibited better ovarian reserve and response, and higher CLBR in two years compared with age- and BMI-matched controls (CLBR: 55.51% in PCOS vs. 38.02% in control, p<0.001). Multivariate logistic regression analysis revealed that the number of transferable embryos and antral follicle counts were both significant independent factors predicting cumulative live birth after adjusting for female age, female body mass index, percentage of transferred blastocysts, number of embryos transferred per embryo-transfer cycle, diagnosis of PCOS and freeze-all cycles (p<0.001, p=0.045). Women with PCOS ≥ 35 years of age demonstrated a higher CLBR over two years compared with age- and BMI-matched controls. This could be explained by favorable oocyte reserve and more available embryos compared with controls, which overcome the compromised oocyte quality in aged PCOS patients.
Muscle-Bone Crosstalk in Chronic Obstructive Pulmonary Disease
Authors: Zhang Lijiao , Sun Yongchang
Published: September 2021

Sarcopenia and osteoporosis are common musculoskeletal comorbidities of chronic obstructive pulmonary disease (COPD) that seriously affect the quality of life and prognosis of the patient. In addition to spatially mechanical interactions, muscle and bone can also serve as endocrine organs by producing myokines and osteokines to regulate muscle and bone functions, respectively. As positive and negative regulators of skeletal muscles, the myokines irisin and myostatin not only promote/inhibit the differentiation and growth of skeletal muscles, but also regulate bone metabolism. Both irisin and myostatin have been shown to be dysregulated and associated with exercise and skeletal muscle dysfunction in COPD. During exercise, skeletal muscles produce a large amount of IL-6 which acts as a myokine, exerting at least two different conflicting functions depending on physiological or pathological conditions. Remarkably, IL-6 is highly expressed in COPD, and considered to be a biomarker of systemic inflammation, which is associated with both sarcopenia and bone loss. For osteokines, receptor activator of nuclear factor kappa-B ligand (RANKL), a classical regulator of bone metabolism, was recently found to play a critical role in skeletal muscle atrophy induced by chronic cigarette smoke (CS) exposure. In this focused review, we described evidence for myokines and osteokines in the pathogenesis of skeletal muscle dysfunction/sarcopenia and osteoporosis in COPD, and proposed muscle-bone crosstalk as an important mechanism underlying the coexistence of muscle and bone diseases in COPD.
Modelling Human-Fire Interactions: Combining Alternative Perspectives and Approaches
Authors: Ford Adriana E. S. , Harrison Sandy P. , Kountouris Yiannis , Millington James D. A. , Mistry Jayalaxshmi , Perkins Oliver , Rabin Sam S. , Rein Guillermo , Schreckenberg Kate , Smith Cathy , Smith Thomas E. L. , Yadav Kapil
Published: September 2021

Although it has long been recognised that human activities affect fire regimes, the interactions between humans and fire are complex, imperfectly understood, constantly evolving, and lacking any kind of integrative global framework. Many different approaches are used to study human-fire interactions, but in general they have arisen in different disciplinary contexts to address highly specific questions. Models of human-fire interactions range from conceptual local models to numerical global models. However, given that each type of model is highly selective about which aspects of human-fire interactions to include, the insights gained from these models are often limited and contradictory, which can make them a poor basis for developing fire-related policy and management practices. Here, we first review different approaches to modelling human-fire interactions and then discuss ways in which these different approaches could be synthesised to provide a more holistic approach to understanding human-fire interactions. We argue that the theory underpinning many types of models was developed using only limited amounts of data and that, in an increasingly data-rich world, it is important to re-examine model assumptions in a more systematic way. All of the models are designed to have practical outcomes but are necessarily simplifications of reality and as a result of differences in focus, scale and complexity, frequently yield radically different assessments of what might happen. We argue that it should be possible to combine the strengths and benefits of different types of model through enchaining the different models, for example from global down to local scales or vice versa. There are also opportunities for explicit coupling of different kinds of model, for example including agent-based representation of human actions in a global fire model. Finally, we stress the need for co-production of models to ensure that the resulting products serve the widest possible community.
Haploinsufficiency of the Attention-Deficit/Hyperactivity Disorder Risk Gene St3gal3 in Mice Causes Alterations in Cognition and Expression of Genes Involved in Myelination and Sialylation
Authors: Rivero Olga , Alhama-Riba Judit , Ku Hsing-Ping , Fischer Matthias , Ortega Gabriela , Álmos Péter , Diouf David , van den Hove Daniel , Lesch Klaus-Peter
Published: September 2021

Genome wide association meta-analysis identified ST3GAL3, a gene encoding the beta-galactosidase-alpha-2,3-sialyltransferase-III, as a risk gene for attention-deficit/hyperactivity disorder (ADHD). Although loss-of-function mutations in ST3GAL3 are implicated in non-syndromic autosomal recessive intellectual disability (NSARID) and West syndrome, the impact of ST3GAL3 haploinsufficiency on brain function and the pathophysiology of neurodevelopmental disorders (NDDs), such as ADHD, is unknown. Since St3gal3 null mutant mice display severe developmental delay and neurological deficits, we investigated the effects of partial inactivation of St3gal3 in heterozygous (HET) knockout (St3gal3±) mice on behavior as well as expression of markers linked to myelination processes and sialylation pathways. Our results reveal that male St3gal3 HET mice display cognitive deficits, while female HET animals show increased activity, as well as increased cognitive control, compared to their wildtype littermates. In addition, we observed subtle alterations in the expression of several markers implicated in oligodendrogenesis, myelin formation, and protein sialylation as well as cell adhesion/synaptic target glycoproteins of ST3GAL3 in a brain region- and/or sex-specific manner. Taken together, our findings indicate that haploinsufficiency of ST3GAL3 results in a sex-dependent alteration of cognition, behavior and markers of brain plasticity.
Identification and Validation of Potential Candidate Genes of Colorectal Cancer in Response to Fusobacterium nucleatum Infection
Authors: Zhang Jiangguo , Wang Zhimo , Lv Hong , Li Guojun
Published: September 2021

Objective: Recent investigations revealed the relationship between Fusobacterium nucleatum (Fn) infection and colorectal cancer (CRC). However, how the host genes changes contribute to CRC in response to Fn infection remains largely unknown.

Materials and methods: In the present study, we aimed to comprehensively analyze microarray data obtained from a Caco-2 infection cell model using integrated bioinformatics analysis and further identify and validate potential candidate genes in Fn-infected Caco-2 cells and CRC specimens.

Results: We identified 10 hub genes potentially involved in Fn induced tumor initiation and progression. Furthermore, we demonstrated that the expression of centrosomal protein of 55 kDa (CEP55) is significantly higher in Fn-infected Caco-2 cells. Knocking down of CEP55 could arrest the cell cycle progression and induce apoptosis in Fn-infected Caco-2 cells. The expression of CEP55 was positively correlated with the Fn amount in Fn-infected CRC patients, and these patients with high CEP55expression had an obviously poorer differentiation, worse metastasis and decreased cumulative survival rate.

Conclusion: CEP55 plays an important role in Fn-infected colon cancer cell growth and cell cycle progression and could be used as a new diagnostic and prognostic biomarker for Fn-infected CRC.
Cis-Regulatory Logic Produces Gene-Expression Noise Describing Phenotypic Heterogeneity in Bacteria
Authors: Chowdhury Debajyoti , Wang Chao , Lu Aiping , Zhu Hailong
Published: September 2021

Gene transcriptional process is random. It occurs in bursts and follows single-molecular kinetics. Intermittent bursts are measured based on their frequency and size. They influence temporal fluctuations in the abundance of total mRNA and proteins by generating distinct transcriptional variations referred to as “noise”. Noisy expression induces uncertainty because the association between transcriptional variation and the extent of gene expression fluctuation is ambiguous. The promoter architecture and remote interference of differentcis-regulatory elements are the crucial determinants of noise, which is reflected in phenotypic heterogeneity. An alternative perspective considers that cellular parameters dictating genome-wide transcriptional kinetics follow a universal pattern. Research on noise and systematic perturbations of promoter sequences reinforces that both gene-specific and genome-wide regulation occur across species ranging from bacteria and yeast to animal cells. Thus, deciphering gene-expression noise is essential across different genomics applications. Amidst the mounting conflict, it is imperative to reconsider the scope, progression, and rational construction of diversified viewpoints underlying the origin of the noise. Here, we have established an indication connecting noise, gene expression variations, and bacterial phenotypic variability. This review will enhance the understanding of gene-expression noise in various scientific contexts and applications.
Evaluations of Genomic Prediction and Identification of New Loci for Resistance to Stripe Rust Disease in Wheat (Triticum aestivum L.)
Authors: Tomar Vipin , Dhillon Guriqbal Singh , Singh Daljit , Singh Ravi Prakash , Poland Jesse , Chaudhary Anis Ahmad , Bhati Pradeep Kumar , Joshi Arun Kumar , Kumar Uttam
Published: September 2021

Stripe rust is one of the most destructive diseases of wheat (Triticum aestivum L.), caused by Puccinia striiformis f. sp. tritici (Pst), and responsible for significant yield losses worldwide. Single-nucleotide polymorphism (SNP) diagnostic markers were used to identify new sources of resistance at adult plant stage to wheat stripe rust (YR) in 141 CIMMYT advanced bread wheat lines over 3 years in replicated trials at Borlaug Institute for South Asia (BISA), Ludhiana. We performed a genome-wide association study and genomic prediction to aid the genetic gain by accumulating disease resistance alleles. The responses to YR in 141 advanced wheat breeding lines at adult plant stage were used to generate G × E (genotype × environment)-dependent rust scores for prediction and genome-wide association study (GWAS), eliminating variation due to climate and disease pressure changes. The lowest mean prediction accuracies were 0.59 for genomic best linear unbiased prediction (GBLUP) and ridge-regression BLUP (RRBLUP), while the highest mean was 0.63 for extended GBLUP (EGBLUP) and random forest (RF), using 14,563 SNPs and the G × E rust score results. RF and EGBLUP predicted higher accuracies (∼3%) than did GBLUP and RRBLUP. Promising genomic prediction demonstrates the viability and efficacy of improving quantitative rust tolerance. The resistance to YR in these lines was attributed to eight quantitative trait loci (QTLs) using the FarmCPU algorithm. Four (Q.Yr.bisa-2A.1, Q.Yr.bisa-2D, Q.Yr.bisa-5B.2, and Q.Yr.bisa-7A) of eight QTLs linked to the diagnostic markers were mapped at unique loci (previously unidentified for Pst resistance) and possibly new loci. The statistical evidence of effectiveness and distribution of the new diagnostic markers for the resistance loci would help to develop new stripe rust resistance sources. These diagnostic markers along with previously established markers would be used to create novel DNA biosensor-based microarrays for rapid detection of the resistance loci on large panels upon functional validation of the candidate genes identified in the present study to aid in rapid genetic gain in the future breeding programs.