Pengembangan Model Pembelajaran Kooperatif Handep Untuk Pembelajaran Matematika

Penelitian ini bertujuan untuk mengembangkan Model Pembelajaran Kooperatif berbasis mekanisme gotong royong Handep. Handep adalah bentuk gotong royong suku Dayak Kalimantan Tengah. Model pembelajaran diberi nama Model Pembelajaran Kooperatif (MPK) Handep. Pengembangan MPKHandep dilakukan dengan menyusun buku ajar tentang MPK Handep. Hasil pengembangan divalidasi melalui uji ahli Teknolog Pembelajaran dalam tiga tahapan, dan disimpulkan bahwa preskripsi komponen-komponen MPK Handep telah layak dijadikan sebagai model pembelajaran. Validasi kelompok kecil menunjukkan, MPK Handep telah memenuhi prinsip-prinsip pembelajaran efektif (95,59%), elemen-elemen pembelajaran kooperatif (98,68%), dan kaidah-kaidah Quantum Teaching(75%). Ketercapaian penguasaan kemampuan pemecahan masalah kajian himpunan sebagai dampak instruksional (92%) dan penguasaan keterampilan sosial (91,7%) sebagai dampak pengiring implementasi MPK Handep. The purpose of research developed cooperative learning model based on mechanism of mutual cooperation handep. Handep is the form of collaboration in Dayak Ngaju tribe (Central Kalimantan). The models of teaching and learning namely Handep Cooperative Learning. The model was developed by designing theoretical model of MPK Handep and then validation that model. Cooperative Learning Handep validated by expert in Instructional Technology in three phases and field research in small group of students. The result from the expert validation, that Cooperative Learing Handep prescriptions was sufficiently as a model of learning. The result from field research, that Cooperative Learning Handep were sufficiently for the principles of learning effective (95,59%), the elements of cooperative learning (98,68%), and principles of the Quantum Teaching (75%). Problem solving ability as instructional effect was achieved (92%) and social skill as nurturant effect (91,70%)

Pengaruh Pendekatan Pengajaran Dan Tipe Masalah Terhadap Kemampuan Pemecahan Masalah Tipe ILL Dan WELL-DEFINED

This study focuses on examining the effects of teaching approaches (problem-based learning v.s. regular) and types of problem (ill defined v.s. well defined) on Matematical problem solving abilities. This quasi-experimental study involved 107 elementary school students, who had been randomly selected from 635 clustered students. MANCOVA analysis of pretest and posttest result indicates that there is an interactional effect of teaching approaches and types of problem on problem solving abilities. PBL and ill defined were found to be effective in developing problem solving abilities

Juvenile stress facilitates safety learning in male and female high alcohol preferring mice

Adversities during juvenility increase the risk for stress-related disorders, such as post-traumatic stress disorder (PTSD) and alcohol use disorder. However, stress can also induce coping mechanisms beneficial for later stressful experiences. We reported previously that mice selectively bred for high alcohol preference (HAP) exposed to stress during adolescence (but not during adulthood) showed enhanced fear-conditioned responses in adulthood, as measured by fear-potentiated startle (FPS). However, HAP mice also showed enhanced responding to safety cues predicting the absence of foot shocks in adulthood. Here, we pursue these findings in HAP mice by investigating in further detail how juvenile stress impacts the acquisition of safety and fear learning. HAP mice were subjected to three days of juvenile stress (postnatal days 25, 27, 28) and discriminative safety/fear conditioning in adulthood. FPS was used to assess safety versus fear cue discrimination, fear learning, and fear inhibition by the safety cue. Both stressed and unstressed HAP mice were able to discriminate between both cues as well as learn the fear cue-shock association. Interestingly, it was only the previously stressed mice that were able to inhibit their fear response when the fear cue was co-presented with the safety cue, thus demonstrating safety learning. We also report an incidental finding of alopecia in the juvenile stress groups, a phenotype seen in stress-related disorders. These results in HAP mice may be relevant to understanding the influence of juvenile trauma for individual risk and resilience toward developing PTSD and how individuals might benefit from safety cues in behavioral psychotherapy

<i>PIK3CA</i> missense mutations promote glioblastoma pathogenesis, but do not enhance targeted PI3K inhibition

<div><p>Background</p><p>Glioblastoma (GBM) is the most common adult primary brain tumor. Multimodal treatment is empiric and prognosis remains poor. Recurrent <i>PIK3CA</i> missense mutations (<i>PIK3CA</i>^<i>mut</i>) in GBM are restricted to three functional domains: adaptor binding (ABD), helical, and kinase. Defining how these mutations influence gliomagenesis and response to kinase inhibitors may aid in the clinical development of novel targeted therapies in biomarker-stratified patients.</p><p>Methods</p><p>We used normal human astrocytes immortalized via expression of hTERT, E6, and E7 (NHA). We selected two <i>PIK3CA</i>^<i>mut</i> from each of 3 mutated domains and induced their expression in NHA with (NHA^RAS) and without mutant <i>RAS</i> using lentiviral vectors. We then examined the role of <i>PIK3CA</i>^<i>mut</i> in gliomagenesis <i>in vitro</i> and in mice, as well as response to targeted PI3K (PI3Ki) and MEK (MEKi) inhibitors <i>in vitro</i>.</p><p>Results</p><p><i>PIK3CA</i>^<i>mut</i>, particularly helical and kinase domain mutations, potentiated proximal PI3K signaling and migration of NHA and NHA^RAS<i>in vitro</i>. Only kinase domain mutations promoted NHA colony formation, but both helical and kinase domain mutations promoted NHA^RAS tumorigenesis <i>in vivo</i>. <i>PIK3CA</i>^<i>mut</i> status had minimal effects on PI3Ki and MEKi efficacy. However, PI3Ki/MEKi synergism was pronounced in NHA and NHA^RAS harboring ABD or helical mutations.</p><p>Conclusion</p><p><i>PIK3CA</i>^<i>mut</i> promoted differential gliomagenesis based on the mutated domain. While <i>PIK3CA</i>^<i>mut</i> did not influence sensitivity to single agent PI3Ki, they did alter PI3Ki/MEKi synergism. Taken together, our results demonstrate that a subset of <i>PIK3CA</i>^<i>mut</i> promote tumorigenesis and suggest that patients with helical domain mutations may be most sensitive to dual PI3Ki/MEKi treatment.</p></div

PI3Ki/MEKi synergism <i>in vitro</i> is influenced by <i>PIK3CA</i>^<i>mut</i> and mutant <i>RAS</i>.

<p>Buparlisib and selumetinib inhibited growth and were synergistic in control and PIK3CA^mut NHA (<b>A</b>) and NHA^RAS (<b>B</b>). BLISS showed that synergy was most pronounced with high nanomolar buparlisib and low micromolar/high nanomolar selumetinib in NHA lines. In contrast, synergistic concentrations in NHA^RAS lines were generally most pronounced at both low micromolar buparlisib and selumetinib.</p

MEKi inhibits growth and ablates MAPK regardless of <i>PIK3CA</i>^<i>mut</i> status.

<p>Selumetinib IC₅₀ were similar regardless of <i>PIK3CA</i>^<i>mut</i> status in NHA (<b>A</b>), but slightly higher in most <i>PIK3CA</i>^<i>mut</i> NHA^RAS compared to parental cells (*, P≤0.03) (<b>B</b>) (<b><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0200014#pone.0200014.s011" target="_blank">S11 Fig</a></b>). Fold changes in IC₅₀ relative to parental and <i>PIK3CA</i>^<i>WT</i> lines are shown as heatmaps. Representative immunoblots of control and <i>PIK3CA</i>^<i>mut</i> NHA (<b>C</b>) and NHA^RAS (<b>F</b>) treated with selumetinib for 24 h. Immunoblot quantification (<b>DEGH</b>) demonstrated dose-dependent decreases in MAPK in NHA (<b>D</b>) and NHA^RAS (<b>G</b>) lines. Although proximal PI3K was induced in control and <i>PIK3CA</i>^<i>mut</i> NHA (<b>E</b>), it was only potentiated in GFP and parental NHA^RAS (<b>H</b>) (<b><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0200014#pone.0200014.s012" target="_blank">S12 Fig</a></b>). Western blots were performed either 1 or 2 times per experiment (Mean = 1.8).</p

Helical and kinase <i>PIK3CA</i>^<i>mut</i> potentiate cellular transformation and tumorigenesis.

<p>Only H1047R increased colony formation compared to parental (*, P = 0.03) and <i>PIKCA</i>^<i>WT</i> (ǂ, P = 0.04) NHA (<b>A</b>). H1047R did not affect colony formation of NHA^RAS (P = 0.5). Orthotopic xenografts of GFP, <i>PIK3CA</i>^<i>WT</i>, and <i>PIK3CA</i>^<i>mut</i> NHA^RAS (<b>BC</b>). Median survival of mice with R88Q, E542K, or H1047R <i>PIK3CA</i>^<i>mut</i> NHA^RAS was decreased compared to GFP control tumors (*, P≤0.003). E542K and H1047R <i>PIK3CA</i>^<i>mut</i> also decreased survival compared to <i>PIK3CA</i>^<i>WT</i> (ǂ, P≤0.002) and R88Q <i>PIK3CA</i>^<i>mut</i> (P<0.0001). Fold changes in median survival relative to GFP and <i>PIK3CA</i>^<i>WT</i> NHA^RAS are shown as heatmaps.</p

<i>PIK3CA</i>^<i>mut</i> potentiate proliferation and migration <i>in vitro</i>.

<p>MTS assays showed that <i>PIK3CA</i>^<i>WT</i> and all <i>PIK3CA</i>^<i>mut</i> decreased doubling times of NHA (<b>A</b>), but not NHA^RAS (<b>B</b>) (*, P≤0.02 vs parental, <b><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0200014#pone.0200014.s005" target="_blank">S5A and S5B Fig</a></b>). <i>PIK3CA</i>^<i>mut</i>, except C90Y, decreased doubling times compared to <i>PIK3CA</i>^<i>WT</i> NHA (^ǂ, P≤0.03). Growth rates were analyzed by comparing k values. Error bars are 95% confidence intervals. <i>PIK3CA</i>^<i>WT</i> and <i>PIK3CA</i>^<i>mut</i>, except C90Y, increased migration of both NHA (<b>C</b>) and NHA^RAS (<b>D</b>) (*, P≤0.04, <b><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0200014#pone.0200014.s005" target="_blank">S5C and S5D Fig</a></b>). E542K and H1047R also potentiated migration compared to <i>PIK3CA</i>^<i>WT</i> NHA and NHA^RAS (^ǂ, P≤0.005). Fold changes in doubling times and migration rates relative to parental and <i>PIK3CA</i>^<i>WT</i> lines are shown as heatmaps.</p