Pengaruh Model Pembelajaran Kontekstual terhadap Hasil Belajar Subtema Kebersamaan dalam Keberagaman Kelas IV SD Negeri 091522 Marubun Jaya

Penelitian ini bertujuan (1.untuk mengetahui ada atau tidak Pengaruh Model Pembelajaran Kontekstual Terhadap Hasil Belajar Subtema Kebersaman Dalam Keberagaman Kelas IV SD Negeri 091522 Marubun Jaya.Penelitian ini merupakan penelitian eksperimen, yaitu jenis pre Eksperimental Design. Penelitian ini merupakan penelitian eksperimen yaitu jenis One Group Pretest-Posttest Design. Dengan penelitian ini, hasil perlakuan dapat diketahui lebih akurat, karena dapat membandingkan dengan keadaan sebelum diberi perlakuan (treatment) dan sesudah diberi perlakuan. dengan populasi penelitian adalah siswa kelas IV SD Negeri 091522 Marubun JayaT.A 2021/2022. Insturumen yang digunakan adalah Pretest-Posttest dengan menggunakan model pembelajaran kontekstual dan  Memberikan posttest untuk mengukur variabel terikat setelah perlakuan dilakukan. Data analisis menggunakan rumus regresi sederhana. Hasil penelitian pada taraf signifikan 0,05 menunjukkan bahwa: Terdapat pengaruh yang positif dan signifikan antara Model Pembelajaran Kontekstual Terhadap Hasil Belajar Sub Tema Kebersamaan Dalam Keberagamandengan perolehan koefisien regresi bernilai positif sebesar0,068

PENGARUH STRATEGI PEMBELAJARAN DISCOVERY LEARNING BERBANTUAN MINI-MAGZ TERHADAP HASIL BELAJAR KOGNITIF BIOLOGI SISWA

Penelitian ini dilakukan karena proses pembelajaran yang digunakan guru sebelumnya adalah pembelajaran teacher centre, yang mana hal tersebut membuat siswa merasa bosan, sehingga hasil belajar yang diperoleh rendah. Maka dari itu, peneliti mencoba untuk menggunakan strategi pembelajaran discovery learning berbantuan mini magz untuk melihat hasil belajar siswa. Penelitian ini bertujuan untuk mengetahui pengaruh strategi pembelajaran discovery learning berbantuan mini-magz dalam pembelajaran biologi materi sistem ekskresi pada manusia terhadap hasil belajar kognitif biologi siswa. Desain penelitian ini yaitu non equivalent control group design pretest-posttest. Populasi penelitian ini adalah kelas XI MIA di Pesantren Fajrul Iman, yang mana sampelnya menggunakan 2 kelas dengan metode pengambilan sampel jenuh. Kelas XI MIA A sebagai kelas eksperimen yang menggunakan strategi pembelajaran discovery learning disertai dengan membuat ringkasan berformat mini magz, sedangkan kelas XI MIA B sebagai kelas kontrol menggunakan model pembelajaran konvensional. Teknik pengumpulan datanya yaitu menggunakan tes tertulis, yang terdiri dari pretest yang berjumlah 20 soal dan posttest yang berjumlah 20 soal. Data dianalisis menggunakan analisis statistik inferensial. Berdasarkan hasil penelitian, untuk uji t diperoleh bahwa thitung 3,64 sedangkan ttabel 1,71, itu berarti bahwa thitung > ttabel maka H0 ditolak dan Ha diterima. Kesimpulan dari hasil penelitian ini yaitu terdapat pengaruh strategi pembelajaran discovery learning berbantuan mini magz terhadap hasil belajar kognitif biologi siswa. Saran untuk peneliti lain yaitu apabila peneliti ingin menggunakan strategi pembelajaran discovery learning sebaiknya menyiapkan waktu yang cukup untuk mensosialisasikan strategi ini, supaya hasil yang didapatkan lebih maksimal

Predicting and validating the pathway of Wnt3a-driven suppression of osteoclastogenesis

Wnt signaling plays a major role in bone homeostasis and mechanotransduction, but its role and regulatory mechanism in osteoclast development are not fully understood. Through genome-wide in silico analysis, we examined Wnt3a-driven regulation of osteoclast development. Mouse bone marrow-derived cells were incubated with RANKL in the presence and absence of Wnt3a. Using microarray mRNA expression data, we conducted principal component analysis and predicted transcription factor binding sites (TFBSs) that were potentially involved in the responses to RANKL and Wnt3a. The principal component analysis predicted potential Wnt3a responsive regulators that would reverse osteoclast development, and a TFBS prediction algorithm indicated that the AP1 binding site would be linked to Wnt3a-driven suppression. Since c-Fos was upregulated by RANKL and downregulated by Wnt3a in a dose-dependent manner, we examined its role using RNA interference. The partial silencing of c-Fos suppressed RANKL-driven osteoclastogenesis by downregulating NFATc1, a master transcription factor of osteoclast development. Although the involvement of c-Myc was predicted and partially silencing c-Myc slightly reduced the level of TRAP, c-Myc silencing did not alter the expression of NFATc1. Collectively, the presented systems-biology approach demonstrates that Wnt3a attenuates RANKL-driven osteoclastogenesis by blocking c-Fos expression and suggests that mechanotransduction of bone alters the development of not only osteoblasts but also osteoclasts through Wnt signaling

Suppression of Osteoclastogenesis via Upregulation of Zfyve21 and Ddit4 by Salubrinal and Guanabenz

Salubrinal and guanabenz are two known inhibitors of de-phosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2α), and they suppress osteoclastogenesis through downregulating nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), a master molecule of osteoclastogenesis. The mechanism of NFATc1 suppression is not well understood. Using genome-wide microarray analysis, we investigated molecular regulators of osteoclastogenesis, in particular, in response to salubrinal and guanabenz. We identified two sets of genes: a set of genes that were upregulated by receptor activator of nuclear factor kappa-B ligand (RANKL) and downregulated by salubrinal and guanabenz; and the other set of genes that were downregulated by RANKL and upregulated by salubrinal and guanabenz. The microarray and qPCR result revealed that a zinc finger protein, FYVE domain containing 21 (Zfyve21), as well as DNA-damage-inducible transcript 4 (Ddit4), were suppressed by RANKL and upregulated by salubrinal and guanabenz. A partial silencing of Zfyve21 or Ddit4 attenuated salubrinal- and guanabenz-driven suppression of NFATc1. Collectively, this study demonstrates that Zfyve21 and Ddit4 are two inhibitors of osteoclastogenesis. We expect that they may potentially serve as novel targets for preventing bone loss from skeletal diseases such as osteoporosis

Predicting and validating the pathway of Wnt3a-driven suppression of osteoclastogenesis

20 Wnt signaling plays a major role in bone homeostasis and mechanotransduction, but its role and regulatory 21 mechanism in osteoclast development are not fully understood. Through genome-wide in silico analysis, we 22 examined Wnt3a-driven regulation of osteoclast development. Mouse bone marrow-derived cells were incubated 23 with RANKL in the presence and absence of Wnt3a. Using microarray mRNA expression data, we conducted a 24 principal component analysis and predicted transcription factor binding sites (TFBS) that were potentially 25 involved in the responses to RANKL and Wnt3a. The principal component analysis predicted potential Wnt3a 26 responsive regulators that would reverse osteoclast development, and a TFBS prediction algorithm indicated 27 that the AP1 binding site would be linked to Wnt3a-driven suppression. Since c-Fos was upregulated by RANKL 28 and downregulated by Wnt3a in a dose-dependent manner, we examined its role using RNA interference. The 29 partial silencing of c-Fos suppressed RANKL-driven osteoclastogenesis by downregulating NFATc1, a master 30 transcription factor of osteoclast development. Although the involvement of c-Myc was predicted and partial 31 silencing c-Myc slightly reduced the level of TRAP, c-Myc silencing did not alter the expression of NFATc1. 32 Collectively, the presented systems-biology approach demonstrates that Wnt3a attenuates RANKL-driven 33 osteoclastogenesis by blocking c-Fos expression and suggests that mechanotransduction of bone alters the 34 development of not only osteoblasts but also osteoclasts through Wnt signaling. 3

In Vitro and In Silico Analysis of Osteoclastogenesis in Response to Inhibition of De-phosphorylation of EIF2α by Salubrinal and Guanabenz

An excess of bone resorption over bone formation leads to osteoporosis, resulting in a reduction of bone mass and an increase in the risk of bone fracture. Anabolic and anti-resorptive drugs are currently available for treatment, however, none of these drugs are able to both promote osteoblastogenesis and reduce osteoclastogenesis. This thesis focused on the role of eukaryotic translation initiation factor 2 alpha (eIF2alpha), which regulates efficiency of translational initiation. The elevation of phosphorylated eIF2alpha was reported to stimulate osteoblastogenesis, but its effects on osteoclastogenesis have not been well understood. Using synthetic chemical agents such as salubrinal and guanabenz that are known to inhibit the de-phosphorylation of eIF2alpha, the role of phosphorylation of eIF2alpha in osteoclastogenesis was investigated in this thesis. The questions addressed herein were: Does the elevation of phosphorylated eIF2alpha (p-eIF2alpha) by salubrinal and guanabenz alter osteoclastogenesis? If so, what regulatory mechanism mediates the process? It was hypothesized that p-eIF2alpha could attenuate the development of osteoclast by regulating the transcription factor(s) amd microRNA(s) involved in osteoclastogenesis. To test this hypothesis, we conducted in vitro and in silico analysis of the responses of RAW 264.7 pre-osteoclast cells to salubrinal and guanabenz. First, the in vitro results revealed that the elevated level of phosphorylated eIF2alpha inhibited the proliferation, differentiation, and maturation of RAW264.7 cells and downregulated the expression of NFATc1, a master transcription factor of osteoclastogenesis. Silencing eIF2alpha by RNA interference suppressed the downregulation of NFATc1, suggesting the involvement of eIF2alpha in regulation of NFATc1. Second, the in silico results using genome-wide expression data and custom-made Matlab programs predicted a set of stimulatory and inhibitory regulator genes as well as microRNAs, which were potentially involved in the regulation of NFATc1. RNA interference experiments indicated that the genes such as Zfyve21 and Ddit4 were primary candidates as an inhibitor of NFATc1. In summary, the results showed that the elevation of p-eIF2alpha by salubrinal and guanabenz leads to attenuation of osteoclastogenesis through the downregulation of NFATc1. The regulatory mechanism is mediated by eIF2alpha signaling, but other signaling pathways are likely to be involved. Together with the previous data showing the stimulatory role of p-eIF2alpha in osteoblastogenesis, the results herein suggest that eIF2alpha-mediated signaling could provide a novel therapeutic target for treatment of osteoporosis by promoting bone formation and reducing bone resorption