bluuebunny/crossref_metadata_2025 huggingface dataset:
PERBEDAAN MEMORI JANGKA PENDEK ANTARA SISWI YANG BEROLAHRAGA AEROBIK RUTIN DENGAN TIDAK RUTIN DI SMAN 14 BANDAR LAMPUNG TAHUN 2018
Authors: Alfarisi Ringgo , Nurwidyasari Eka , Lutfianawati Dewi
Published: November 2020

Olahraga aerobik dapat memberikan manfaat meningkatkan aliran darah otak khususnya ke hippocampus dan meningkatkan neoplastisitas otak yang penting agar memori dapat berfungsi dengan baik. Memori  jangka  pendek  merupakan  unsur  inti  dari  perkembangan  kognitif,  sebab  segala bentuk belajar dari individu melibatkan memori. Penelitian ini bertujuan untuk mengetahui perbedaan memori jangka pendek antara siswi yang berolahraga aerobik  rutin  dengan  siswi  yang  tidak  berolahraga  aerobik  rutin  di  SMAN  14  Bandar Lampung Bulan April Tahun 2018.Jenis penelitian ini adalah Survey Analytic dengan pendekatan Cross Sectionlal. Populasi seluruh siswi kelas XI IPA dengan sampel sebanyak 70 siswi di SMAN 14 Bandar Lampung. Penelitian ini menggunakan analisis bivariat dengan menggunakan Uji Mann Whitney. Berdasarkan hasil penelitian ini, didapatkan bahwa nilai rata- rata memori jangka pendek responden dengan olahraga aerobik rutin adalah 117,21 (SD 13,633), dan olahraga aeerobik tidak rutin adalah 90,14 (SD 3,919). Hasil uji komparatif Mann Whitney Test menunjukan adanya perbedaan bermakna dengan nilai p value < 0,001. Kesimpulan penelitian ini adalah terdapat perbedaan memori jangka pendek antara siswi yang berolahraga aerobik  rutin  dengan  siswi  yang  tidak  berolahraga  aerobik  rutin  di  SMAN  14  Bandar Lampung Bulan April Tahun 2018.
HUBUNGAN MUTU PELAYANAN KESEHATAN DENGAN TINGKAT KEPUASAN PASIENRAWAT INAP BPJSDI RUMAH SAKIT PERTAMINA BINTANG AMIN BANDAR LAMPUNG TAHUN 2017
Authors: Farich Achmad , Mandala Zulhafis , Susanti Herlin Mega
Published: November 2020

Mutu pelayanan kesehatan dapat diukur menggunakan lima dimensi mutu yaitu empati (empathy), kehandalan (reliability), bukti nyata (tangible), daya tanggap (responsiveness), dan jaminan (assurance). Mutu pelayanan merupakan salah satu faktor penentu kepuasan pasien. Pada pemberitaan di media online terdapat pemberitaan tentang ketidakpuasan pasien rawat inap di Rumah Sakit Pertamina Bintang Amin. Tujuan penelitian adalah untuk mengetahui Hubungan Mutu Pelayanan Kesehatan dengan Tingkat Kepuasan Pasien Rawat Inap BPJS di Rumah Sakit Pertamina Bintang Amin Bandar Lampung Tahun 2017.Tujuan penelitian ini adalah menjelaskan hubungan mutu pelayanan pasien rawat inap BPJS dengan kepuasan pasien di Rumah Sakit Pertamina Bintang Amin Bandar Lampung. Jenis penelitian analitik dengan pendekatan cross sectional dengan teknik accidental sampling. Sampel penelitian sebanyak 328 responden. Analisis data menggunakan uji Fisher.Hasil penelitian menunjukkan dari 328 responden didapatkan 297  responden (90,5%) merasa puas, 31 responden (9,5%) tidak puas. Empati (empathy) didapatkan 141 responden (43,0%) menyatakan baik, 187 responden (57,0%) kurang baik. Kehandalan (reliability) didapatkan 152 responden (46,3%) menyatakan baik, 176 responden (53,7%) kurang baik. Bukti nyata (tangible) didapatkan 175 responden (53,4%) menyatakan baik, 153 responden (46,6%) kurang baik. Daya tanggap (responsiveness) didapatkan 141 responden (43,0%) menyatakan baik,187 responden (57,0%) kurang baik. Jaminan (assurance) didapatakan 113 responden (34,5%) menyatakan baik, 215 responden (65,5%) kurang baik. Hasil uji Fisher didapatkan empati (p=0,254), kehandalan (p=0,574), bukti nyata (p=0,191), daya tanggap (p=0,254), jaminan (p=0,000). Kesimpulan dari penelitian ini tidak terdapat hubungan yang bermakna antara empati, buktinyata, kehandalan, daya tanggap terhadap kepuasan pasien dan terdapat hubungan yang bermakna antara jaminan terhadap kepuasan pasien.
The Library Workplace Idea Book
Authors: Chandler Martin
Published: November 2020

Book Review
Control of causative agents of fusarium head blight of winter wheat in applying modern fungicides
Authors:   Polissia National University, Tymoshchuk T. , Kotelnytska H. ,   Polissia National University, Gurmanchuk O. ,   Polissia National University, Serba I. ,   Polissia National University, Yurchyk R. ,   Polissia National University, Shchulga O. ,   Polissia National University
Published: November 2020

The mass development of fungal diseases of grain crops leads to a decrease in grain yielding capacity and deterioration of its quality. Crops are particularly threatened by pathogenic agents, including the causative agents of Fusarium head blight, which can contaminate crop supplies with mycotoxins and have a negative impact on human health. The treatment of winter wheat crops with fungicides is considered to be one of the main measures to limit the development of fusariosis. Our research was aimed at studying the effectiveness of modern fungicides applied to control the development of pathogens of Fusarium head blight in the agrophytocenosis of winter wheat. Such species as F. graminearum (68.0 %), F. oxysporum (17.0 %) and F. culmorum (7.0 %) were found to be the most common species of winter wheat mycobiota. The application of fungicides in the phase of BBCH 59–61 of winter wheat promotes to the decrease in the development of Fusarium head blight pathogens by 14.4–18.0 %. The technical efficiency of modern fungicides used for the protection of winter wheat from Fusarium head blight is 70–88 %. A considerable conservation of the grain yield – 0.29–0.55 t/ha compared to the control (water treatment) resulted from the treatment of winter wheat crops with modern fungicides with different chemical composition. The treatment of crops with fungicides Suprim, EW (tebuconazole, 133 g/l + prochloraz, 267 g/l) and Reks Duo, SC (epoxiconazole, 187 g/l + thiophanate-methyl, 310, g/l) ensures the yield preservation up to 0.37– 0.41 t/ha. The highest grain yield (8.19 t/ha) was obtained while treating winter wheat crops with the fungicide Osiris Star, EC (epoxiconazole, 56.25 g + metconazole, 41.25 g/l) with a consumption rate of 1.5 l/ha. Comparing to the treatment of crops with water, the yield preserved is 7.2 %. Further research should be focused on studying the species composition of the microbiota of winter wheat seeds depending on the fungicides applied in the phase of BBCH 59-61.
Formation technologies of the economic mechanism of management decision making
Authors:   Polissia National University, Ovdiuk O.
Published: November 2020

A key place in the formation of the economic mechanism of management decisions is value-oriented management. It is established that the role of the planning function in determining the effectiveness of management system in terms of making sound targeted management decisions within the time horizon is occurring (strategic, operational and current, etc.). This research is based on the use of a dialectical method of cognition of economic processes, scientific developments and publications of both domestic and foreign scientists on the peculiarities of management decision-making at enterprises and organizations. It is proved that the economic component is the basis for the formation of the economic mechanism of management decisions, in terms of a detailed forecast of the development of enterprise potential (planning function) and the function of motivation of management decisions executors. The essence of the “economic mechanism” is defined as a set of organizational and economic approaches to ensure the financial stability of the enterprise, in terms of planning, forecasting and increasing the reserves of the enterprise, taking into account the effects of external and internal factors. It is established that the basis for ensuring the economic component of management decisions is a set of necessary relevant information (both internal and external), which creates the possibility of developing special methodological approaches to planning, evaluation, control and adjustment of the desired financial and economic activities. The formation technology of the economic mechanism of administrative decision is developed. The content and components of the tools for monitoring the management decision-making process (quantitative and qualitative analysis) is also determined.It is established that the formation of the economic mechanism of management decisions at the enterprise consists of a set of certain parameters of the procedure for making and implementing management decisions, the effectiveness of which will give the desired effect and ensure the achievement of the goal. Prospects for further research are the development of organizational and economic mechanism for making and implementing management decisions in the food industry.
The Effect of a Class Visit Supervision Workshop on the Pedagogic Abilities of Basic School Teachers Assessed from Early Pedagogic Ability in Rantau Selatan District, Labuhanbatu District
Authors: Pane Menneria , Sudrajat Ajat , Chandrawati Titin
Published: November 2020

This type of research used in this research is experimental quantitative research. To find out the effect of the classroom visit supervision workshop and teacher certification on the pedagogical ability of elementary school teachers in terms of the initial pedagogical ability in Rantau Selatan District. The population in this study was elementary school teachers in Rantau Selatan District, Labuhanbatu Regency, totalling 377 teachers spread over 23 locations. The sample in this study was 60 teachers. From the research results, it can be concluded that the magnitude of the simultaneous influence of the implementation of the supervisory workshop and the initial ability to the pedagogical ability of teachers is 66.4% while the remaining 33.6% is influenced by other factors outside of the two variables observed in this study.
Obesity and the risk of primary liver cancer: A systematic review and meta-analysis
Authors: Sohn Won , Lee Hyun Woong , Lee Sangheun , Lim Jin Hong , Lee Min Woo , Park Chan Hyuk , Yoon Seung Kew
Published: November 2020

Background/Aims: In this systematic review and meta-analysis, we aimed to clarify the effect of obesity on the occurrence of and mortality from primary liver cancer.Methods: This study was conducted using a systematic literature search of MEDLINE, EMBASE, and the Cochrane Library until November 2018 using the primary keywords “obesity,” “overweight,” “body mass index (BMI),” “body weight,” “liver,” “cancer,” “hepatocellular carcinoma,” “liver cancer,” “risk,” and “mortality.” Studies assessing the relationship between BMI and occurrence of or mortality from primary liver cancer in prospective cohorts and those reporting hazard ratios (HRs) or data that allow HR estimation were included.Results: A total of 28 prospective cohort studies with 8,135,906 subjects were included in the final analysis. These included 22 studies with 6,059,561 subjects for cancer occurrence and seven studies with 2,077,425 subjects for cancerrelated mortality. In the meta-analysis, an increase in BMI was associated with the occurrence of primary liver cancer (HR, 1.69; 95% confidence interval, 1.50–1.90, I2=56%). A BMI-dependent increase in the risk of occurrence of primary liver cancer was reported. HRs were 1.36 (95% CI, 1.02–1.81), 1.77 (95% CI, 1.56–2.01), and 3.08 (95% CI, 1.21–7.86) for BMI >25 kg/m2, >30 kg/m2, and >35 kg/m2, respectively. Furthermore, increased BMI resulted in enhanced liver cancer-related mortality (HR, 1.61; 95% CI, 1.14–2.27, I2=80%).Conclusions: High BMI increases liver cancer mortality and occurrence of primary liver cancer. Obesity is an independent risk factor for the occurrence of and mortality from primary liver cancer.
Key competencies for Korean nurses in prenatal genetic nursing: experiential genetic nursing knowledge, and ethics and law
Authors: Shin Gyeyoung , Jun Myunghee , Kim Hye-Kyung , Wreen Michael , Kubsch Sylvia Mimi
Published: November 2020

Purpose: This study aims at determining the competencies of Korean nurses in prenatal genetic nursing.Methods: First, a 3-round Delphi survey was conducted to establish prenatal genetic nursing competencies. Second, a prenatal genetic nursing education program (PGNEP), incorporating the findings from the Delphi survey, was designed. Third, a single group pre- and post-quasi-experimental study at a PGNEP workshop was conducted to assess the effectiveness of the integration of the competencies into the PGNEP with the measurements of knowledge about prenatal genetic testing and nursing (K-PGTN) and information needs about prenatal genetic testing and nursing (I-PGTN). Finally, the identified competencies were reexamined for their clarity.Results: Based on the Delphi survey 78 competency components were identified. The components were then classified under 10 categories, which were organized under 4 domains. The domain of “experiential genetic nursing knowledge” and the domain of “ethics and law” were ranked as the first and the second in significance. The quasi-experimental study showed that the mean scores in K-PGTN were significantly increased from 8.19±2.67 to 11.25±2.51 (P<0.001). The mean scores of “ethics and law” in I-PGTN decreased significantly (P=0.023). The headings of 4 categories and 2 domains were revised.Conclusion: This study identified competencies for prenatal genetic nursing and nursing education in Korea. There is a need for nursing instructors and researchers to improve the competencies of nurses in the identified areas. Particular emphasis should be placed on experiential nursing knowledge and on ethics and law related to prenatal genetic nursing.
Tuz Gölü (Aksaray)’nde Bazı Katyon ve Anyon Değerlerinin Belirlenmesi
Authors: UZBİLEK Mine , QARANJIKI Abdolsaleh
Published: November 2020

Tuz Gölü’nde Artemia populasyonunun yok olma tehlikesi olduğu dönemde, bazı anyon ve katyonların düzeyinin ortaya konmasının amaçlandığı çalışma, Mart-Temmuz 2014 tarihleri arasında, gölün batısında bir, gölün doğusunda seçilen dört istasyonda yürütülmüştür. Araştırma süresince aylık olarak belirlenen bazı katyon (Sodyum-Na+, Magnezyum-Mg2+, Kalsiyum-Ca2+, Potasyum-K+) ve anyon (Klorür-Cl-, Sülfat-SO42-, Bikarbonat-HCO3-) ortalama değerleri arasındaki farklılıklar aylara ve istasyonlara göre istatistiki olarak önemli bulunmuştur (p<0,05). Tuz Gölü’nde baskın katyon Na+ olup, bunu sırasıyla, Mg2+, Ca2+, K+, anyonlardan ise Cl-baskın olup, sırasıyla, SO42-, HCO3- izlemiştir.
Bu çalışmada gölün anyon ve katyon değerleri, geçmiş yıllarda belirlenen düzeye göre belirgin bir değişim göstermemiştir. Bu bağlamda, göldeki Artemia popülasyonunun kaybolmasında gölün fiziksel, kimyasal ve biyolojik açıdan uzun dönemli izlenmesi önem arz etmektedir.
Musculoskeletal Model Personalization Affects Metabolic Cost Estimates for Walking
Authors: Arones Marleny M. , Shourijeh Mohammad S. , Patten Carolynn , Fregly Benjamin J.
Published: November 2020

Assessment of metabolic cost as a metric for human performance has expanded across various fields within the scientific, clinical, and engineering communities. As an alternative to measuring metabolic cost experimentally, musculoskeletal models incorporating metabolic cost models have been developed. However, to utilize these models for practical applications, the accuracy of their metabolic cost predictions requires improvement. Previous studies have reported the benefits of using personalized musculoskeletal models for various applications, yet no study has evaluated how model personalization affects metabolic cost estimation. This study investigated the effect of musculoskeletal model personalization on estimates of metabolic cost of transport (CoT) during post-stroke walking using three commonly used metabolic cost models. We analyzed walking data previously collected from two male stroke survivors with right-sided hemiparesis. The three metabolic cost models were implemented within three musculoskeletal modeling approaches involving different levels of personalization. The first approach used a scaled generic OpenSim model and found muscle activations via static optimization (SOGen). The second approach used a personalized electromyographic (EMG)-driven musculoskeletal model with personalized functional axes but found muscle activations via static optimization (SOCal). The third approach used the same personalized EMG-driven model but calculated muscle activations directly from EMG data (EMGCal). For each approach, the muscle activation estimates were used to calculate each subject’s CoT at different gait speeds using three metabolic cost models (Umberger et al., 2003;Bhargava et al., 2004;Umberger, 2010). The calculated CoT values were compared with published CoT data as a function of walking speed, step length asymmetry, stance time asymmetry, double support time asymmetry, and severity of motor impairment (i.e., Fugl-Meyer score). Overall, only SOCal and EMGCal with the Bhargava metabolic cost model were able to reproduce accurately published experimental trends between CoT and various clinical measures of walking asymmetry post-stroke. Tuning of the parameters in the different metabolic cost models could potentially resolve the observed CoT magnitude differences between model predictions and experimental measurements. Realistic CoT predictions may allow researchers to predict human performance, surgical outcomes, and rehabilitation outcomes reliably using computational simulations.
Injectable Magnesium-Zinc Alloy Containing Hydrogel Complex for Bone Regeneration
Authors: Wang Wei-Hua , Wang Fei , Zhao Hai-Feng , Yan Ke , Huang Cui-Ling , Yin Yin , Huang Qiang , Chen Zao-Zao , Zhu Wen-Yu
Published: November 2020

Gelatin methacryloyl (GelMA) has been widely used in bone engineering. It can also be filled into the calvarial defects with irregular shape. However, lack of osteoinductive capacity limits its potential as a candidate repair material for calvarial defects. In this study, we developed an injectable magnesium–zinc alloy containing hydrogel complex (Mg-IHC), in which the alloy was fabricated in an atomization process and had small sphere, regular shape, and good fluidity. Mg-IHC can be injected and plastically shaped. After cross-linking, it contents the elastic modulus similar to GelMA, and has inner holes suitable for nutrient transportation. Furthermore, Mg-IHC showed promising biocompatibility according to our evaluations of its cell adhesion, growth status, and proliferating activity. The results of alkaline phosphatase (ALP) activity, ALP staining, alizarin red staining, and real-time polymerase chain reaction (PCR) further indicated that Mg-IHC could significantly promote the osteogenic differentiation of MC3T3-E1 cells and upregulate the genetic expression of collagen I (COL-I), osteocalcin (OCN), and runt-related transcription factor 2 (RUNX2). Finally, after applied to a mouse model of critical-sized calvarial defect, Mg-IHC remarkably enhanced bone formation at the defect site. All of these results suggest that Mg-IHC can promote bone regeneration and can be potentially considered as a candidate for calvarial defect repairing.
Vehicle Connectivity and Automation: A Sibling Relationship
Authors: Ha Paul , Chen Sikai , Du Runjia , Dong Jiqian , Li Yujie , Labi Samuel
Published: November 2020

The evolution of scientific advances has often been characterized by the amalgamation of two or more technologies. With respect to vehicle connectivity and automation, recent literature suggests that these two emerging transportation technologies can and will jointly and profoundly shape the future of transportation. However, it is not certain how the individual and synergistic benefits to be earned from these technologies is related to their prevailing levels of development. As such, it may be considered useful to revisit the primary concepts of automation and connectivity, and to identify any current and expected future synergies between them. Doing this can help generate knowledge that could be used to justify investments related to transportation systems connectivity and automation. In this discussion paper, we attempt to address some of these issues. The paper first reviews the technological concepts of systems automation and systems connectivity, and how they prospectively, from an individual and collective perspective, impact road transportation efficiency and safety. The paper also discusses the separate and common benefits of connectivity and automation, and their possible holistic effects in terms of these benefits where they overlap. The paper suggests that at the current time, the sibling relationship seems to be lopsided: vehicle connectivity has immense potential to enhance vehicle automation. Automation, on the other hand, may not significantly promote vehicle connectivity directly, at least not in the short term but possibly in the long term. The paper argues that future trends regarding market adoption of these two technologies and their relative pace of advancement or regulation, will shape the future synergies between them.
S100A10 Accelerates Aerobic Glycolysis and Malignant Growth by Activating mTOR-Signaling Pathway in Gastric Cancer
Authors: Li Yan , Li Xiao-Yu , Li Li-Xiang , Zhou Ru-Chen , Sikong Yinhe , Gu Xiang , Jin Bi-Ying , Li Bing , Li Yan-Qing , Zuo Xiu-Li
Published: November 2020

S100 calcium-binding protein A10 (S100A10) is crucially involved in the tumorigenesis of multiple malignant tumors. Reprogrammed glucose metabolism is emerging as a hallmark of various human cancers. However, the function of S100A10 in aerobic glycolysis is unclear. The expression of S100A10 was analyzed using the Oncomine database, Gene Expression Profiling Interactive Analysis (GEPIA), The Cancer Genome Atlas (TCGA), and the UALCAN cancer database. Prognostic analysis was performed using the Kaplan–Meier Plotter. The correlation between S100A10 and key glycolytic factors was assessed by GEPIA. The glycolysis level was examined by determining glucose consumption, lactate production, adenosine triphosphate production, cellular oxygen consumption rate, and extracellular acidification rate. Cell apoptosis was investigated by flow cytometry. Colony formation and BrdU assays were performed to detect cell proliferation. A subcutaneous xenograft mouse model was established to evaluate the effects of S100A10in vivo. Gene Set Enrichment Analysis and western blotting were performed to explore the downstream signaling pathway. S100A10 was significantly upregulated in gastric cancer. Its expression was associated with poor survival. S100A10 increased glucose consumption, lactate production, and the switch from oxidative phosphorylation to aerobic glycolysis. S100A10 promoted malignant proliferation and suppressed cell apoptosis in gastric cancer. S100A10 activated the mTOR pathway by interacting with annexin A2 (ANXA2) to accelerate tumor glycolysis, resulting in tumor malignant progression. S100A10 contributed to aerobic glycolysis and accelerated malignant growth by modulating the Src/ANXA2/AKT/mTOR signaling pathway. Thus, S100A10 may have pivotal roles in gastric cancer.
2-[(4-Hydroxybenzyl) Amino] Phenol (HBAP) Restores the Mutated p53 to the Level Similar to That of Wild-Type p53 Protein and Inhibits Breast Cancer Growth in vivo to by Inducing Tumor Cells Apoptosis
Authors: Xu Chenxi , Zhuang Jianjian , Zhang Xiaobo
Published: November 2020

P53 is a transcriptional factor that plays important roles in apoptosis and is mutated in more than 50% of tumor cells. However, the restoration of mutated p53 to the level similar to wild-type p53 by a natural compound has not been explored intensively. In this study, the 2-[(4-hydroxybenzyl) amino] phenol (HBAP) compound, obtained from deep-sea virus-challenged thermophile Geobacillus sp. E263, interacted specifically with the mutated p53 protein. HBAP was able to induce apoptosis of p53-mutated breast cancer cells, but not normal breast cells and p53-unmutated breast cancer cells. HBAP activated the mutant p53 transcriptional activity by restoring the function of mutant p53 to that of wild-type p53. Further analysis indicated that HBAP bound only to the DNA binding domain of mutant p53 and that the interaction was dependent on the HBAP hydroxyl groups. In vivo data demonstrated that HBAP was toxicity-free and could suppress tumor growth by inducing tumor cell apoptosis. Therefore our findings revealed that recovering mutated p53 function to that of wild-type p53 caused by HBAP triggered cancer cell apoptosis and that metabolites from deep-sea virus-challenged thermophiles could be a promising source of anti-tumor drugs.
Cone Photoreceptor Degeneration and Neuroinflammation in the Zebrafish Bardet-Biedl Syndrome 2 (bbs2) Mutant Does Not Lead to Retinal Regeneration
Authors: Song Ping , Fogerty Joseph , Cianciolo Lauren T. , Stupay Rachel , Perkins Brian D.
Published: November 2020

Bardet-Biedl syndrome (BBS) is a heterogeneous and pleiotropic autosomal recessive disorder characterized by obesity, retinal degeneration, polydactyly, renal dysfunction, and mental retardation. BBS results from defects in primary and sensory cilia. Mutations in 21 genes have been linked to BBS and proteins encoded by 8 of these genes form a multiprotein complex termed the BBSome. Mutations inBBS2, a component of the BBSome, result in BBS as well as non-syndromic retinal degeneration in humans and rod degeneration in mice, but the role of BBS2 in cone photoreceptor survival is not clear. We used zebrafishbbs2–/–mutants to better understand how loss ofbbs2leads to photoreceptor degeneration. Zebrafishbbs2–/–mutants exhibited impaired visual function as larvae and adult zebrafish underwent progressive cone photoreceptor degeneration. Cone degeneration was accompanied by increased numbers of activated microglia, indicating an inflammatory response. Zebrafish exhibit a robust ability to regenerate lost photoreceptors following retinal damage, yet cone degeneration and inflammation was insufficient to trigger robust Müller cell proliferation. In contrast, high intensity light damage stimulated Müller cell proliferation and photoreceptor regeneration in both wild-type andbbs2–/–mutants, although thebbs2–/–mutants could only restore cones to pre-damaged densities. In summary, these findings suggest that cone degeneration leads to an inflammatory response in the retina and that BBS2 is necessary for cone survival. The zebrafishbbs2mutant also represents an ideal model to identify mechanisms that will enhance retinal regeneration in degenerating diseases.
Human Fetal Scalp Dermal Papilla Enriched Genes and the Role of R-Spondin-1 in the Restoration of Hair Neogenesis in Adult Mouse Cells
Authors: Weber Erin L. , Lai Yung-Chih , Lei Mingxing , Jiang Ting-Xin , Chuong Cheng-Ming
Published: November 2020

Much remains unknown about the regulatory networks which govern the dermal papilla’s (DP) ability to induce hair follicle neogenesis, a capacity which decreases greatly with age. To further define the core genes which characterize the DP cell and to identify pathways prominent in DP cells with greater hair inductive capacity, comparative transcriptome analyses of human fetal and adult dermal follicular cells were performed. 121 genes were significantly upregulated in fetal DP cells in comparison to both fetal dermal sheath cup (DSC) cells and interfollicular dermal (IFD) populations. Comparison of the set of enriched human fetal DP genes with human adult DP, newborn mouse DP, and embryonic mouse dermal condensation (DC) cells revealed differences in the expression of Wnt/β-catenin, Shh, FGF, BMP, and Notch signaling pathways. We chose R-spondin-1, a Wnt agonist, for functional verification and show that exogenous administration restores hair follicle neogenesis from adult mouse cells in skin reconstitution assays. To explore upstream regulators of fetal DP gene expression, we identified twenty-nine transcription factors which are upregulated in human fetal DP cells compared to adult DP cells. Of these, seven transcription factor binding motifs were significantly enriched in the candidate promoter regions of genes differentially expressed between fetal and adult DP cells, suggesting a potential role in the regulatory network which confers the fetal DP phenotype and a possible relationship to the induction of follicle neogenesis.
mTORC1 Transcriptional Regulation of Ribosome Subunits, Protein Synthesis, and Molecular Transport in Primary Human Trophoblast Cells
Authors: Rosario Fredrick J. , Powell Theresa L. , Gupta Madhulika B. , Cox Laura , Jansson Thomas
Published: November 2020

Mechanistic Target of Rapamycin Complex 1 (mTORC1) serves as positive regulator of placental nutrient transport and mitochondrial respiration. The role of mTORC1 signaling in modulating other placental functions is largely unexplored. We used gene array following silencing of raptor to identify genes regulated by mTORC1 in primary human trophoblast (PHT) cells. Seven hundred and thirty-nine genes were differentially expressed; 487 genes were down-regulated and 252 up-regulated. Bioinformatic analyses demonstrated that inhibition of mTORC1 resulted in decreased expression of genes encoding ribosomal proteins in the 60S and 40S ribosome subunits. Furthermore, down-regulated genes were functionally enriched in genes involved in eIF2, sirtuin and mTOR signaling, mitochondrial function, and glutamine and zinc transport. Stress response genes were enriched among up-regulated genes following mTORC1 inhibition. The protein expression of ribosomal proteins RPL26 (RPL26) and Ribosomal Protein S10 (RPS10) was decreased and positively correlated to mTORC1 signaling and System A amino acid transport in human placentas collected from pregnancies complicated by intrauterine growth restriction (IUGR). In conclusion, mTORC1 signaling regulates the expression of trophoblast genes involved in ribosome and protein synthesis, mitochondrial function, lipid metabolism, nutrient transport, and angiogenesis, representing novel links between mTOR signaling and multiple placental functions critical for normal fetal growth and development.
Role of Cofilin in Alzheimer’s Disease
Authors: Wang Qiang , Yuan Wei , Yang Xiaohang , Wang Yuan , Li Yongfeng , Qiao Haifa
Published: November 2020

Alzheimer’s disease (AD) is a degenerative neurological disease and has an inconspicuous onset and progressive development. Clinically, it is characterized by severe dementia manifestations, including memory impairment, aphasia, apraxia, loss of recognition, impairment of visual-spatial skills, executive dysfunction, and changes in personality and behavior. Its etiology is unknown to date. However, several cellular biological signatures of AD have been identified such as synaptic dysfunction, β-amyloid plaques, hyperphosphorylated tau, cofilin-actin rods, and Hirano bodies which are related to the actin cytoskeleton. Cofilin is one of the most affluent and common actin-binding proteins and plays a role in cell motility, migration, shape, and metabolism. They also play an important role in severing actin filament, nucleating, depolymerizing, and bundling activities. In this review, we summarize the structure of cofilins and their functional and regulating roles, focusing on the synaptic dysfunction, β-amyloid plaques, hyperphosphorylated tau, cofilin-actin rods, and Hirano bodies of AD.
Integrating the Hallmarks of Aging Throughout the Tree of Life: A Focus on Mitochondrial Dysfunction
Authors: van der Rijt Sanne , Molenaars Marte , McIntyre Rebecca L. , Janssens Georges E. , Houtkooper Riekelt H.
Published: November 2020

Since the identification and definition of the hallmarks of aging, these aspects of molecular and cellular decline have been most often described as isolated or distinct mechanisms. However, there is significant evidence demonstrating interplay between most of these hallmarks and that they have the capacity to influence and regulate one another. These interactions are demonstrable across the tree of life, yet not all aspects are conserved. Here, we describe an integrative view on the hallmarks of aging by using the hallmark “mitochondrial dysfunction” as a focus point, and illustrate its capacity to both influence and be influenced by the other hallmarks of aging. We discuss the effects of mitochondrial pathways involved in aging, such as oxidative phosphorylation, mitochondrial dynamics, mitochondrial protein synthesis, mitophagy, reactive oxygen species and mitochondrial DNA damage in relation to each of the primary, antagonistic and integrative hallmarks. We discuss the similarities and differences in these interactions throughout the tree of life, and speculate how speciation may play a role in the variation in these mechanisms. We propose that the hallmarks are critically intertwined, and that mapping the full extent of these interactions would be of significant benefit to the aging research community.
The Dimensions of Primary Mitochondrial Disorders
Authors: Schlieben Lea D. , Prokisch Holger
Published: November 2020

The concept of a mitochondrial disorder was initially described in 1962, in a patient with altered energy metabolism. Over time, mitochondrial energy metabolism has been discovered to be influenced by a vast number of proteins with a multitude of functional roles. Amongst these, defective oxidative phosphorylation arose as the hallmark of mitochondrial disorders. In the premolecular era, the diagnosis of mitochondrial disease was dependent on biochemical criteria, with inherent limitations such as tissue availability and specificity, preanalytical and analytical artifacts, and secondary effects. With the identification of the first mitochondrial disease-causing mutations, the genetic complexity of mitochondrial disorders began to unravel. Mitochondrial dysfunctions can be caused by pathogenic variants in genes encoded by the mitochondrial DNA or the nuclear DNA, and can display heterogenous phenotypic manifestations. The application of next generation sequencing methodologies in diagnostics is proving to be pivotal in finding the molecular diagnosis and has been instrumental in the discovery of a growing list of novel mitochondrial disease genes. In the molecular era, the diagnosis of a mitochondrial disorder, suspected on clinical grounds, is increasingly based on variant detection and associated statistical support, while invasive biopsies and biochemical assays are conducted to an ever-decreasing extent. At present, there is no uniform biochemical or molecular definition for the designation of a disease as a “mitochondrial disorder”. Such designation is currently dependent on the criteria applied, which may encompass clinical, genetic, biochemical, functional, and/or mitochondrial protein localization criteria. Given this variation, numerous gene lists emerge, ranging from 270 to over 400 proposed mitochondrial disease genes. Herein we provide an overview of the mitochondrial disease associated genes and their accompanying challenges.
Discovery of 5,5′-Methylenedi-2,3-Cresotic Acid as a Potent Inhibitor of the Chemotactic Activity of the HMGB1·CXCL12 Heterocomplex Using Virtual Screening and NMR Validation
Authors: De Leo Federica , Quilici Giacomo , De Marchis Francesco , Mantonico Malisa Vittoria , Bianchi Marco Emilio , Musco Giovanna
Published: November 2020

HMGB1 is a key molecule that both triggers and sustains inflammation following infection or injury, and is involved in a large number of pathologies, including cancer. HMGB1 participates in the recruitment of inflammatory cells, forming a heterocomplex with the chemokine CXCL12 (HMGB1·CXCL12), thereby activating the G-protein coupled receptor CXCR4. Thus, identification of molecules that disrupt this heterocomplex can offer novel pharmacological opportunities to treat inflammation-related diseases. To identify new HMGB1·CXCL12 inhibitors we have performed a study on the ligandability of the single HMG boxes of HMGB1 followed by a virtual screening campaign on both HMG boxes using Zbc Drugs and three different docking programs (Glide, AutoDock Vina, and AutoDock 4.2.6). The best poses in terms of scoring functions, visual inspection, and predicted ADME properties were further filtered according to a pharmacophore model based on known HMGB1 binders and clustered according to their structures. Eight compounds representative of the clusters were tested for HMGB1 binding by NMR. We identified 5,5′-methylenedi-2,3-cresotic acid (2a) as a binder of both HMGB1 and CXCL12;2aalso targets the HMGB1·CXCL12 heterocomplex. In cell migration assays2ainhibited the chemotactic activity of HMGB1·CXCL12 with IC50in the subnanomolar range, the best documented up to now. These results pave the way for future structure activity relationship studies to optimize the pharmacological targeting of HMGB1·CXCL12 for anti-inflammatory purposes.
A Systematic Review of Personalized Collaborative Systems
Authors: Neumayr Thomas , Augstein Mirjam
Published: November 2020

Personalization, aiming at supporting users individually, according to their individual needs and prerequisites, has been discussed in a number of domains including learning, search, or information retrieval. In the field of human–computer interaction, personalization also bears high potential as users might exhibit varying and strongly individual preferences and abilities related to interaction. For instance, there is a good amount of work on personalized or adaptive user interfaces (also under the notion of intelligent user interfaces). Personalized human–computer interaction, however, does not only subsume approaches to support the individual user, it also bears high potential if applied to collaborative settings, for example, through supporting the individuals in a group as well as the group itself (considering all of its special dynamics). In collaborative settings (remote or co-located), there generally is a number of additional challenges related to human-to-human collaboration in a group, such as group communication, awareness or territoriality, device or software tool selection, or selection of collaborators. Personalized Collaborative Systems thus attempt to tackle many of these challenges. For instance, there are collaborative systems that recommend tools, content, or team constellations. Such systems have been suggested in different domains and different collaborative settings and contexts. In most cases, these systems explicitly focus on a certain aspect of personalized collaboration support (such as team composition). This article provides a broader, concise overview of existing approaches to Personalized Collaborative Systems based on a systematic literature review considering the ACM Digital Library.
Key Player in Cardiac Hypertrophy, Emphasizing the Role of Toll-Like Receptor 4
Authors: Xiao Zheng , Kong Bin , Yang Hongjie , Dai Chang , Fang Jin , Qin Tianyou , Huang He
Published: November 2020

Toll-like receptor 4 (TLR4), a key pattern recognition receptor, initiates the innate immune response and leads to chronic and acute inflammation. In the past decades, accumulating evidence has implicated TLR4-mediated inflammatory response in regulation of myocardium hypertrophic remodeling, indicating that regulation of the TLR4 signaling pathway may be an effective strategy for managing cardiac hypertrophy's pathophysiology. Given TLR4's significance, it is imperative to review the molecular mechanisms and roles underlying TLR4 signaling in cardiac hypertrophy. Here, we comprehensively review the current knowledge of TLR4-mediated inflammatory response and its interaction ligands and co-receptors, as well as activation of various intracellular signaling. We also describe the associated roles in promoting immune cell infiltration and inflammatory mediator secretion, that ultimately cause cardiac hypertrophy. Finally, we provide examples of some of the most promising drugs and new technologies that have the potential to attenuate TLR4-mediated inflammatory response and prevent or reverse the ominous cardiac hypertrophy outcomes.
Mammals Make Use of Cashew Plantations in a Mixed Forest–Cashew Landscape
Authors: Rege Anushka , Punjabi Girish Arjun , Jathanna Devcharan , Kumar Ajith
Published: November 2020

Heterogeneous landscapes harboring mosaics of natural habitat and agriculture are increasingly gaining conservation focus in the tropics. While research on cash crops such as coffee, rubber, and oil palm has led to an understanding of their role as supplementary habitats, such has remained limited in cashew plantations despite it being a cash crop of global significance. We conducted a study to understand the occurrence of terrestrial mammal species in a mixed forest–cashew landscape in the northern Western Ghats, India. During January to April 2016, we used trail cameras to sample a total area of 25 km2divided into 100 grid cells of 0.25 km2each. We deployed six trail cameras for a 24 h period in each grid cell and obtained photo-captures of 11 species in forests, of which nine were detected in cashew plantations, but most species showed low capture rates. For three of these species—Indian crested porcupine, sambar, and wild pig—we modeled habitat use as a function of site-specific attributes. Wild pig showed a higher probability of use of cashew than forest, while porcupine and sambar did not show any pronounced differences between the two land uses. The probability of habitat use by sambar and porcupine was positively influenced by undergrowth but not for the wild pig. Wild pig habitat use was positively related to increased proximity of human settlements and increasing distance to forests, but the pattern was unreliable for sambar and porcupine. Our preliminary study demonstrates that a subset of terrestrial mammals in the forest makes use of cashew plantations and highlights the need for further research in forest–cashew landscapes to assess conservation opportunities.
Transgenerational Plasticity and Bet-Hedging: A Framework for Reaction Norm Evolution
Authors: Joschinski Jens , Bonte Dries
Published: November 2020

Decision-making under uncertain conditions favors bet-hedging (avoidance of fitness variance), whereas predictable environments favor phenotypic plasticity. However, entirely predictable or entirely unpredictable conditions are rarely found in nature. Intermediate strategies are required when the time lag between information sensing and phenotype induction is large (e.g., transgenerational plasticity) and when cues are only partially predictive of future conditions. Nevertheless, current theory regards plasticity and bet-hedging as distinct entities. We here develop a unifying framework: based on traits with binary outcomes like seed germination or diapause incidence we clarify that diversified bet-hedging (risk-spreading among one’s offspring) and transgenerational plasticity are mutually exclusive strategies, arising from opposing changes in reaction norms (allocating phenotypic variance among or within environments). We further explain the relationship of this continuum with arithmetic mean maximization vs. conservative bet-hedging (a risk-avoidance strategy), and canalization vs. phenotypic variance in a three-dimensional continuum of reaction norm evolution. We discuss under which scenarios costs and limits may constrain the evolution of reaction norm shapes.
Identification of Aedes (Diptera: Culicidae) Species and Arboviruses Circulating in Arauca, Eastern Colombia
Authors: Martínez David , Hernández Carolina , Muñoz Marina , Armesto Yulieth , Cuervo Andres , Ramírez Juan David
Published: November 2020

The identification of vector species and their natural infection with arboviruses results in important data for the control of their transmission. However, for the eastern region of Colombia, this information is limited. Therefore, this study morphologically and molecularly identified species of the genus Aedes and the detection of arboviruses (Dengue, Chikungunya, Zika, and Mayaro) in female mosquitoes (individually) present in three municipalities (Saravena, Arauquita, and Tame) by amplifying the genetic material using RT-PCR (reverse transcriptase polymerase chain reaction) in the department of Arauca, eastern Colombia. Inconsistencies between morphological and molecular identification were detected in 13 individuals with Aedes albopictus initially determined as Aedes aegypti based on morphology (n = 13). Molecular identification showed the simultaneous presence of A. aegypti (n = 111) and A. albopictus (n = 58) in the urban municipalities of Saravena and Arauquita. These individuals were naturally infected with Dengue virus type 1 (DENV-1) and Chikungunya virus (CHIKV). The most frequent arbovirus was DENV-1 with an infection rate of 40.7% (11/27) for A. aegypti and 39.7% (23/58) for A. albopictus, which was followed by CHIKV with an infection rate of 1.8% for A. aegypti (2/111) and 6.9% for A. albopictus (4/58). Additionally, a mixed infection of DENV-1 and CHIKV was obtained in 4.5% of A. aegypti (5/111). Zika virus (ZIKV) and Mayaro virus (MAYV) infections were not detected. This study found that barcoding (fragment gene COI) is a successful method for identifying Aedes species. Additionally, we recommend the individual processing of insects as a more accurate strategy for arboviruses detection since the infection rate is obtained and co-infection between DENV-1 and CHIKV is also possible.
Cytokine Signature in Schnitzler Syndrome: Proinflammatory Cytokine Production Associated to Th Suppression
Authors: Masson Regnault Marie , Frouin Eric , Jéru Isabelle , Delwail Adriana , Charreau Sandrine , Barbarot Sébastien , Néel Antoine , Masseau Agathe , Puéchal Xavier , Kyndt Xavier , Gayet Stephane , Lifermann François , Asli Bouchra , Balguerie Xavier , Blanchard-Delaunay Claire , Aubin François , Rizzi Rita , Rongioletti Franco , Boyé Thierry , Gusdorf Laurence , Bessis Didier , Morel Franck , Hainaut Ewa , Lipsker Dan , Lecron Jean-Claude
Published: November 2020

Background

Schnitzler syndrome (SchS) is a rare autoinflammatory disease characterized by urticarial exanthema, bone and joint alterations, fever and monoclonal IgM gammopathy. Overactivation of the interleukin(IL)-1 system is reported, even though the exact pathophysiological pathways remain unknown.

Objective

To determine ex vivo cytokine profiles of Peripheral Blood Mononuclear Cells (PBMCs) from SchS patients prior to treatment and after initiation of anti-IL-1 therapy (anakinra). The sera cytokine profile was studied in parallel.

Methods

We collected blood samples from thirty-six untreated or treated SchS. PBMCs were cultured with and without LPS or anti-CD3/CD28. Cytokine levels were evaluated in serum and cell culture supernatants using Luminex technology.

Results

Spontaneous TNFα, IL-6, IL-1β, IL-1α, and IL-1RA release by PBMCs of SchS patients were higher than in controls. LPS-stimulation further induced the secretion of these cytokines. In contrast, after T-cell stimulation, TNFα, IL-10, IFNγ, IL-17A, and IL-4 production decreased in SchS patients compared to healthy controls, but less in treated patients. Whereas IL-1β serum level was not detected in most sera, IL-6, IL-10, and TNFα serum levels were higher in patients with SchS and IFNγ and IL-4 levels were lower. Of note, IL-6 decreased after treatment in SchS (p = 0.04).

Conclusion

Our data strengthen the hypothesis of myeloid inflammation in SchS, mediated in particular by IL-1β, TNFα, and IL-6, associated with overproduction of the inhibitors IL-1RA and IL-10. In contrast, we observed a loss of Th1, Th2, and Th17 cell functionalities that tends to be reversed by anakinra.