SEKOLAH SEPAKBOLA USIA MUDA DI BANDA ACEH

Sepakbola merupakan olahraga yang sangat populer dan digemari di dunia, begitu juga di Indonesia. Tak heran jika hampir semua negara di dunia berlomba-lomba menggalang prestasi membanggakan di cabang olahraga ini. Indonesia belum mampu meraih prestasi yang membanggakan di cabang olahraga sepakbola, bahkan Indonesia sulit bersaing di kancah Internasional. Klub-klub sepakbola Aceh juga tidak dapat berbuat banyak di kompetisi internal, sedangkan Aceh merupakan salah satu provinsi yang banyak memunculkan pemain muda berbakat.Kualitas persepakbolaan di Indonesia yang rendah dan minim prestasi ini dikarenakan kurang pembinaan dan pelatihan pemain mulai dari usia dini untuk didik menjadi pemain profesional. Sarana pelatihan yang ada di Indonesia belum serius ke arah profesional seperti akademi sepakbola di Eropa. Di negara-negara maju dalam sepakbola, prestasi tim nasional pada umumnya dilatarbelakangi oleh sistem dan proses pembinaan klub yang sudah mapan.Sekolah sepakbola usia muda di Banda Aceh merupakan sebuah sarana pelatihan dan pembinaan sepakbola pemain usia dini di Banda Aceh. Pemain tersebut akan dididik, dilatih dan dibina sejak dini sebagai usaha pembibitan pemain sepakbola Aceh yang potensial. Sekolah sepakbola ini berlokasi di Lhong Raya, sesuai dengan rencana pengembangan kawasan pusat olahraga di Banda Aceh. Dengan mengusung tema arsitektur metafora, diharapkan bangunan sekolah sepakbola ini dapat menjadi objek arsitektur yang melekat di masyarakat.Tahap awal dalam proses perancangan Sekolah Sepakbola Usia Muda di Banda Aceh ini adalah studi literatur data dan studi banding. Selanjutnya permasalahan yang ada diidentifikasi dan dianalisis sesuai dengan batasan perancangan. Dalam lingkup batasan tema arsitektur metafora dan kondisi iklim setempat selanjutnya melahirkan konsep perancangan sesuai dengan hasil analisis.Kata kunci: olahraga, sekolah, sepakbolaBanda Ace

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Publisher Copyright: © 2022, The Author(s).Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.Peer reviewe

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Abstract Background Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Funding GMP, PN, and CW are supported by NHLBI R01HL127564. GMP and PN are supported by R01HL142711. AG acknowledge support from the Wellcome Trust (201543/B/16/Z), European Union Seventh Framework Programme FP7/2007–2013 under grant agreement no. HEALTH-F2-2013–601456 (CVGenes@Target) & the TriPartite Immunometabolism Consortium [TrIC]-Novo Nordisk Foundation’s Grant number NNF15CC0018486. JMM is supported by American Diabetes Association Innovative and Clinical Translational Award 1–19-ICTS-068. SR was supported by the Academy of Finland Center of Excellence in Complex Disease Genetics (Grant No 312062), the Finnish Foundation for Cardiovascular Research, the Sigrid Juselius Foundation, and University of Helsinki HiLIFE Fellow and Grand Challenge grants. EW was supported by the Finnish innovation fund Sitra (EW) and Finska Läkaresällskapet. CNS was supported by American Heart Association Postdoctoral Fellowships 15POST24470131 and 17POST33650016. Charles N Rotimi is supported by Z01HG200362. Zhe Wang, Michael H Preuss, and Ruth JF Loos are supported by R01HL142302. NJT is a Wellcome Trust Investigator (202802/Z/16/Z), is the PI of the Avon Longitudinal Study of Parents and Children (MRC & WT 217065/Z/19/Z), is supported by the University of Bristol NIHR Biomedical Research Centre (BRC-1215–2001) and the MRC Integrative Epidemiology Unit (MC_UU_00011), and works within the CRUK Integrative Cancer Epidemiology Programme (C18281/A19169). Ruth E Mitchell is a member of the MRC Integrative Epidemiology Unit at the University of Bristol funded by the MRC (MC_UU_00011/1). Simon Haworth is supported by the UK National Institute for Health Research Academic Clinical Fellowship. Paul S. de Vries was supported by American Heart Association grant number 18CDA34110116. Julia Ramierz acknowledges support by the People Programme of the European Union’s Seventh Framework Programme grant n° 608765 and Marie Sklodowska-Curie grant n° 786833. Maria Sabater-Lleal is supported by a Miguel Servet contract from the ISCIII Spanish Health Institute (CP17/00142) and co-financed by the European Social Fund. Jian Yang is funded by the Westlake Education Foundation. Olga Giannakopoulou has received funding from the British Heart Foundation (BHF) (FS/14/66/3129). CHARGE Consortium cohorts were supported by R01HL105756. Study-specific acknowledgements are available in the Additional file 32: Supplementary Note. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services.Peer reviewedPublisher PD

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Funding Information: GMP, PN, and CW are supported by NHLBI R01HL127564. GMP and PN are supported by R01HL142711. AG acknowledge support from the Wellcome Trust (201543/B/16/Z), European Union Seventh Framework Programme FP7/2007–2013 under grant agreement no. HEALTH-F2-2013–601456 (CVGenes@Target) & the TriPartite Immunometabolism Consortium [TrIC]-Novo Nordisk Foundation’s Grant number NNF15CC0018486. JMM is supported by American Diabetes Association Innovative and Clinical Translational Award 1–19-ICTS-068. SR was supported by the Academy of Finland Center of Excellence in Complex Disease Genetics (Grant No 312062), the Finnish Foundation for Cardiovascular Research, the Sigrid Juselius Foundation, and University of Helsinki HiLIFE Fellow and Grand Challenge grants. EW was supported by the Finnish innovation fund Sitra (EW) and Finska Läkaresällskapet. CNS was supported by American Heart Association Postdoctoral Fellowships 15POST24470131 and 17POST33650016. Charles N Rotimi is supported by Z01HG200362. Zhe Wang, Michael H Preuss, and Ruth JF Loos are supported by R01HL142302. NJT is a Wellcome Trust Investigator (202802/Z/16/Z), is the PI of the Avon Longitudinal Study of Parents and Children (MRC & WT 217065/Z/19/Z), is supported by the University of Bristol NIHR Biomedical Research Centre (BRC-1215–2001) and the MRC Integrative Epidemiology Unit (MC_UU_00011), and works within the CRUK Integrative Cancer Epidemiology Programme (C18281/A19169). Ruth E Mitchell is a member of the MRC Integrative Epidemiology Unit at the University of Bristol funded by the MRC (MC_UU_00011/1). Simon Haworth is supported by the UK National Institute for Health Research Academic Clinical Fellowship. Paul S. de Vries was supported by American Heart Association grant number 18CDA34110116. Julia Ramierz acknowledges support by the People Programme of the European Union’s Seventh Framework Programme grant n° 608765 and Marie Sklodowska-Curie grant n° 786833. Maria Sabater-Lleal is supported by a Miguel Servet contract from the ISCIII Spanish Health Institute (CP17/00142) and co-financed by the European Social Fund. Jian Yang is funded by the Westlake Education Foundation. Olga Giannakopoulou has received funding from the British Heart Foundation (BHF) (FS/14/66/3129). CHARGE Consortium cohorts were supported by R01HL105756. Study-specific acknowledgements are available in the Additional file : Supplementary Note. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services. Publisher Copyright: © 2022, The Author(s).Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.Peer reviewe

Placental Barrier-on-a-Chip: Modeling Placental Inflammatory Responses to Bacterial Infection

Placental inflammation, as a recognized cause of preterm birth and neonatal mortality, displays extensive placental involvement or damage with the presence of organisms. The inflammatory processes are complicated and tightly associated with increased inflammatory cytokine levels and innate immune activation. However, the deep study of the underlying mechanisms was limited by conventional cell and animal models because of great variations in the architecture and function of placenta. Here, we established a micro engineered model of human placental barrier on the chip and investigated the associated inflammatory responses to bacterial infection. The multilayered design of the microdevice mimicked the microscopic structure in the fetal-maternal interfaces of human placenta, and the flow resembled the dynamic environment in the mother's body. Escherichia coli (E. coli), one of the predominant organisms found in fetal organs, were applied to the maternal side, modeling acute placental inflammation. The data demonstrated the complex responses including the increased secretion of inflammatory cytokines by trophoblasts and the adhesion of maternal macrophages following bacterial infection. Particularly, transplacental communication was observed between two placental cells, and implied the potential role of trophoblast in fetal inflammatory response syndrome in clinic. These complex responses are of potential significance to placental dysfunctions, even abnormal fetal development and preterm birth. Collectively, placental barrier-on-a-chip microdevice presents a simple platform to explore the complicated inflammatory responses in human placenta, and might help our understanding of the mechanisms underlying reproductive diseases

Modeling type 2 diabetes-like hyperglycemia in C-elegans on a microdevice

Caenorhabditis elegans (C. elegans) has been widely used as a model organism for biomedical research due to its sufficient homology with mammals at the molecular and genomic levels. In this work, we describe a microfluidic assay to model type 2 diabetes-like hyperglycemia in C. elegans to examine several aspects of this disease on a microdevice. The microdevice is characterized by the integration of long-term worm culture, worm immobilization, and precise chemical stimuli in a single device, thus enabling the multi-parameter analysis of individual worms at a single-animal resolution. With this device, the lifespan, oxidative stress responses, and lipid metabolism of individual worms in response to different glucose concentrations were characterized. It was found that the mean lifespan of worms was significantly reduced by as much as 29.0% and 30.8% in worms that were subjected to 100 mM and 200 mM glucose, respectively. The expression of oxidative stress protein gst-4 was increased, and the expression of hsp-70 (heat shock protein) and skn-1 (redox sensitive transcription factor) genes was down-regulated in worms treated with a high level of glucose. Moreover, fat storage was markedly increased in the bodies of VS29 worms (vha-6p::GFP::dgat-2) that were exposed to the high-glucose condition. The established approach is not only suitable for further elucidation of the mechanism of metabolic disorders involved in diabetes and its complications, but also facilitates the evaluation of anti-diabetic drugs in a high-throughput manner

A 3D human placenta-on-a-chip model to probe nanoparticle exposure at the placental barrier

With the commercialization of nanomaterials, environmental exposure to nanoparticles (NPs) has raised great concerns due to the long-term effects to human body, particularly to pregnant women. Previous studies found that NPs had an adverse impact on placenta in mice, but care must be taken when extrapolating the results to human pregnancy in consideration of the great difference between species. Here, we proposed a micro engineered 3D placental barrier-on-a-chip microdevice and further explored complicated placental responses to NPs exposure in vitro. The microdevice recreated near-physiological 3D microenvironment and dynamic conditions in fetal maternal circulation combined with the extracellular matrix and flow. With the exposure to titanium dioxide nanoparticles (TiO2-NPs), a common nanomaterial, a series of placental responses were investigated, including oxidative stress, cell apoptosis, barrier permeability, and maternal immune cell behavior. By contrast to oxidative stress and cell apoptosis, placental barrier integrity and maternal immune cells were greatly influenced even with low concentrated NPs, suggesting the potential damages triggered by NPs in our daily life. Collectively, this in vitro experimental model of human placenta provides a simple platform to study environmental exposure to NPs, and might be potential for a wide range of applications in biological study, disease treatment and drug assessment

Engineering Brain Organoids to Probe Impaired Neurogenesis Induced by Cadmium

Brain organoids derived from human induced pluripotent stem cells (hiPSCs) are three-dimensional in vitro models with near-physiological cellular composition and structural organization, which is representative of the developing human brain. They provide an ideal experimental system for the investigation of brain development and diseases. Prenatal exposure to the heavy metal cadmium (Cd) poses a serious health threat, particularly to the developing brain due to a long biological half-life of Cd in vivo. Although it is known that prolonged exposure to Cd will cause toxic effects because of its low rate of excretion from the body, the underlying mechanisms of Cd neurotoxicity remain unclear. Herein, we proposed a simple approach to engineer brain organoids on an array chip with octagon-shaped micropillars and explored neural dysfunctions of brain organoids under Cd exposure. hiPSC-derived brain organoids with millimeter-size recapitulated spatial and temporal patterning events in the early developing brain, including gene expression programs and three-dimensional organization. With Cd exposure, brain organoids displayed induced cell apoptosis, skewed neural differentiation, and varied brain regionalization, indicating the presence of impaired neurogenesis in the human fetal brain. This work provides a simple manner to generate brain organoids efficiently and a powerful platform for the investigation of abnormal neurogenesis induced by many different toxic factors in vitro

Bioinspired onion epithelium-like structure promotes the maturation of cardiomyocytes derived from human pluripotent stem cells

Organized cardiomyocyte alignment is critical to maintain the mechanical properties of the heart. In this study, we present a new and simple strategy to fabricate a biomimetic microchip designed with an onion epithelium-like structure and investigate the guided behavior of human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) on the substrate. The hiPSC-CMs were observed to be confined by the three dimensional surficial features morphologically, analogous to the in vivo microenvironment, and exhibited an organized anisotropic alignment on the onion epithelium-like structure with good beating function. The calcium imaging of hiPSC-CMs demonstrated a more mature Ca2+ spark pattern as well. Furthermore, the expression of sarcomere genes (TNNI3, MYH6 and MYH7), potassium channel genes (KCNE1 and KCNH2), and calcium channel genes (RYR2) was significantly up-regulated on the substrate with an onion epithelium-like structure instead of the surface without the structure, indicating a more matured status of cardiomyocytes induced by this structure. It appears that the biomimetic micro-patterned structure, analogous to in vivo cellular organization, is an important factor that might promote the maturation of hiPSC-CMs, providing new biological insights to guide hiPSC-CM maturation by biophysical factors. The established approach may offer an effective in vitro model for investigating cardiomyocyte differentiation, maturation and tissue engineering applications