Pengaruh penggunaan learning management system dan motivasi berprestasi terhadap hasil belajar siswa program international baccalaureate di Sekolah Pelita Harapan Lippo Cikarang

This study aimed 1) to determine the effect of using Learning Management System (LMS) on student learning outcomes, 2) to determine the effect of achievement motivation on student learning outcomes, 3) to determine the effect of using LMS and achievement motivation simultaneously on student learning outcomes in the International Baccalaureate (IB) program at Sekolah Pelita Harapan Lippo Cikarang. The research method used is quantitative research method. The research sample amounted to 32 people who were the entire population of students in the IB program (saturation sampling). The results showed that 1) The use of LMS (X1) has a positive and significant effect on student learning outcomes (Y) at Sekolah Pelita Harapan (SPH) Lippo Cikarang. This is evidenced by the results of statistical tests where the use of LMS has a significance value of 0.000 <0.05 and the value of t count> t table (4.771> 2.045); 2) Achievement motivation (X2) does not have a positive and significant effect on student learning outcomes at Sekolah Pelita Harapan Lippo. Statistical tests show that the achievement motivation variable has a significance value of 0.309> 0.05 and the t value < t table (-1.037> 2.045); 3) The use of LMS (X1) and Achievement motivation (X2) simultaneously has a positive and significant effect on student learning outcomes (Y) at Sekolah Pelita Harapan Lippo Cikarang. This is evidenced by the statistical test results where the value of Sig. 0.000 <0.05 and the calculated F value is 12.687> 3.32. The test results of the Coefficient of Determination resulted in 0.467 or 46.7%. This means that the variables of LMS usage (X1) and Achievement motivation (X2) have an influence of 46.7% on student learning outcomes (Y), the remaining 53.3% is influenced by other factors

The Influence of the Principal's Leadership and Work Motivation on Teacher Performance at SD Inpres Dimembe District

The purpose of this study was to obtain the results of the analysis and interpretation of the influence of the principal's leadership on the performance of SD Inpres teachers in Dimembe District, the influence of work motivation on the performance of SD Inpres teachers in Dimembe District, the influence of principal leadership and work motivation together on performance. teacher at the Inpres Elementary School in the Dimembe District. The method in this study is to use quantitative research. There are 7 Inpres schools in Dimembe District, North Minahasa Regency. The Inpres Elementary School in Dimembe District is a level of education managed by the government. From the initial monitoring of researchers in these schools there is still a shortage of teaching staff and minimal learning facilities so that teachers have not received challenges in the learning process, there are still teachers who arrive late and leave not on time. A good school can be seen from the performance of the teachers who are in it, for this reason the teacher's performance needs to be considered properly because good teacher performance will determine the success or failure of the school in achieving its goals

F-actin bundles direct the initiation and orientation of lamellipodia through adhesion-based signaling

During cell migration, F-actin bundles/filopodia serve as templates for formation and orientation of lamellipodia and prime their stabilization by adhesion-based PI3K signaling.Mesenchymal cells such as fibroblasts are weakly polarized and reorient directionality by a lamellipodial branching mechanism that is stabilized by phosphoinositide 3-kinase (PI3K) signaling. However, the mechanisms by which new lamellipodia are initiated and directed are unknown. Using total internal reflection fluorescence microscopy to monitor cytoskeletal and signaling dynamics in migrating cells, we show that peripheral F-actin bundles/filopodia containing fascin-1 serve as templates for formation and orientation of lamellipodia. Accordingly, modulation of fascin-1 expression tunes cell shape, quantified as the number of morphological extensions. Ratiometric imaging reveals that F-actin bundles/filopodia play both structural and signaling roles, as they prime the activation of PI3K signaling mediated by integrins and focal adhesion kinase. Depletion of fascin-1 ablated fibroblast haptotaxis on fibronectin but not platelet-derived growth factor chemotaxis. Based on these findings, we conceptualize haptotactic sensing as an exploration, with F-actin bundles directing and lamellipodia propagating the process and with signaling mediated by adhesions playing the role of integrator

Lamellipodia are crucial for haptotactic sensing and response

Haptotaxis is the process by which cells respond to gradients of substrate-bound cues, such as extracellular matrix proteins (ECM); however, the cellular mechanism of this response remains poorly understood and has mainly been studied by comparing cell behavior on uniform ECMs with different concentrations of components. To study haptotaxis in response to gradients, we utilized microfluidic chambers to generate gradients of the ECM protein fibronectin, and imaged the cell migration response. Lamellipodia are fan-shaped protrusions that are common in migrating cells. Here, we define a new function for lamellipodia and the cellular mechanism required for haptotaxis – differential actin and lamellipodial protrusion dynamics lead to biased cell migration. Modest differences in lamellipodial dynamics occurring over time periods of seconds to minutes are summed over hours to produce differential whole cell movement towards higher concentrations of fibronectin. We identify a specific subset of lamellipodia regulators as being crucial for haptotaxis. Numerous studies have linked components of this pathway to cancer metastasis and, consistent with this, we find that expression of the oncogenic Rac1 P29S mutation abrogates haptotaxis. Finally, we show that haptotaxis also operates through this pathway in 3D environments

Mesenchymal Chemotaxis Requires Selective Inactivation of Myosin II at the Leading Edge via a Noncanonical PLCγ/PKCα Pathway

Chemotaxis, migration towards soluble chemical cues, is critical for processes such as wound healing and immune surveillance, and is exhibited by various cell types from rapidly-migrating leukocytes to slow-moving mesenchymal cells. To interrogate the mechanisms involved in mesenchymal chemotaxis, we observed cell migration in microfluidic chambers that generate stable gradients of the chemoattractant PDGF. Surprisingly, we found that pathways implicated in amoeboid chemotaxis, such as PI3K and mTOR signaling, are dispensable for chemotaxis to PDGF. Instead, we find that local inactivation of Myosin IIA, through a non-canonical Ser1/2 phosphorylation of the regulatory light chain, is essential. This site is phosphorylated by PKCα, which is activated by an intracellular gradient of diacylglycerol generated by PLCγ. Using a combination of TIRF imaging and gradients of activators/inhibitors in the microfluidic chambers, we demonstrate that this signaling pathway and subsequent inhibition of Myosin II activity at the leading edge is required for mesenchymal chemotaxis

Myeloid Slc2a1-Deficient Murine Model Revealed Macrophage Activation and Metabolic Phenotype Are Fueled by GLUT1

Macrophages (MΦs) are heterogeneous and metabolically flexible, with metabolism strongly affecting immune activation. A classic response to proinflammatory activation is increased flux through glycolysis with a downregulation of oxidative metabolism, whereas alternative activation is primarily oxidative, which begs the question of whether targeting glucose metabolism is a viable approach to control MΦ activation. We created a murine model of myeloid-specific glucose transporter GLUT1 (Slc2a1) deletion. Bone marrow-derived MΦs (BMDM) from Slc2a1M-/- mice failed to uptake glucose and demonstrated reduced glycolysis and pentose phosphate pathway activity. Activated BMDMs displayed elevated metabolism of oleate and glutamine, yet maximal respiratory capacity was blunted in MΦ lacking GLUT1, demonstrating an incomplete metabolic reprogramming. Slc2a1M-/- BMDMs displayed a mixed inflammatory phenotype with reductions of the classically activated pro- and anti-inflammatory markers, yet less oxidative stress. Slc2a1M-/- BMDMs had reduced proinflammatory metabolites, whereas metabolites indicative of alternative activation-such as ornithine and polyamines-were greatly elevated in the absence of GLUT1. Adipose tissue MΦs of lean Slc2a1M-/- mice had increased alternative M2-like activation marker mannose receptor CD206, yet lack of GLUT1 was not a critical mediator in the development of obesity-associated metabolic dysregulation. However, Ldlr-/- mice lacking myeloid GLUT1 developed unstable atherosclerotic lesions. Defective phagocytic capacity in Slc2a1M-/- BMDMs may have contributed to unstable atheroma formation. Together, our findings suggest that although lack of GLUT1 blunted glycolysis and the pentose phosphate pathway, MΦ were metabolically flexible enough that inflammatory cytokine release was not dramatically regulated, yet phagocytic defects hindered MΦ function in chronic diseases

Diversified actin protrusions promote environmental exploration but are dispensable for locomotion of leukocytes

Most migrating cells extrude their front by the force of actin polymerization. Polymerization requires an initial nucleation step, which is mediated by factors establishing either parallel filaments in the case of filopodia or branched filaments that form the branched lamellipodial network. Branches are considered essential for regular cell motility and are initiated by the Arp2/3 complex, which in turn is activated by nucleation-promoting factors of the WASP and WAVE families. Here we employed rapid amoeboid crawling leukocytes and found that deletion of the WAVE complex eliminated actin branching and thus lamellipodia formation. The cells were left with parallel filaments at the leading edge, which translated, depending on the differentiation status of the cell, into a unipolar pointed cell shape or cells with multiple filopodia. Remarkably, unipolar cells migrated with increased speed and enormous directional persistence, while they were unable to turn towards chemotactic gradients. Cells with multiple filopodia retained chemotactic activity but their migration was progressively impaired with increasing geometrical complexity of the extracellular environment. These findings establish that diversified leading edge protrusions serve as explorative structures while they slow down actual locomotion

Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study

Introduction: The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods: A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results: None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR- 145 correlated with nadir CD4+ T cell count. Discussion: No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection