PENGEMBANGAN MULTIMEDIA INTERAKTIF PADA PEMBELAJARAN PENGEMBANGAN KOMUNIKASI PERSEPSI BUNYI DAN IRAMA KELAS TKLB DI SLB PANGUDI LUHUR JAKARTA BARAT

Penelitian ini menghasilkan sebuah produk digital berupa Multimedia Interaktif untuk guru di Sekolah Luar Biasa Pangudi Luhur, khususnya pada pembelajaran Pengembangan Komunikasi Persepsi Bunyi dan Irama, dan pada materi Identifikasi Bunyi. Dalam mengembangkan multimedia ini, peneliti menggunakan model pengembangan Baker & Schutz. Model ini terdiri dari tujuh tahapan, yaitu perumusan produk, spesifikasi langkah, uji coba soal, pengembangan produk, uji coba produk, revisi produk, dan analisis untuk pemanfaatan. Evaluasi pada penelitian ini melibatkan 1 ahli materi, 1 ahli media dan 1 pengguna. Hasil uji coba ahli menyatakan produk multimedia interaktif sudah cukup layak dan dikemas secara sederhana. Hasil uji coba pengguna menyatakan produk multimedia interaktif dari segi materi sudah cukup baik dan mewakili isi dari pembelajaran PKPBI. This research produces a digital product in the form of Interactive Multimedia for teachers at the Pangudi Luhur Special School, especially in the learning of Sound and Rhythm Perception Communication Development, and on Sound Identification material. In developing this multimedia, researchers used the Baker & Schutz development model. This model consists of seven stages, namely product formulation, step specification, test questions, product development, product testing, product revision, and analysis for utilization. The evaluation in this study involved 1 material expert, 1 media expert and 1 user. The expert test results stated that interactive multimedia products were quite feasible and packaged in a simple way. The results of the user trial stated that the interactive multimedia product in terms of material was quite good and represented the content of PKPBI learning

PENGEMBANGAN MULTIMEDIA INTERAKTIF PADA PEMBELAJARAN “PENGEMBANGAN KOMUNIKASI PERSEPSI BUNYI DAN IRAMA” KELAS TKLB DI SLB PANGUDI LUHUR JAKARTA BARAT

Penelitian ini menghasilkan sebuah produk digital berupa Multimedia Interaktif untuk guru di Sekolah Luar Biasa Pangudi Luhur, khususnya pada pembelajaran Pengembangan Komunikasi Persepsi Bunyi dan Irama, dan pada materi Identifikasi Bunyi. Dalam mengembangkan multimedia ini, peneliti menggunakan model pengembangan Baker & Schutz. Model ini terdiri dari tujuh tahapan, yaitu perumusan produk, spesifikasi langkah, uji coba soal, pengembangan produk, uji coba produk, revisi produk, dan analisis untuk pemanfaatan. Evaluasi pada penelitian ini melibatkan 1 ahli materi, 1 ahli media dan 1 pengguna. Hasil uji coba ahli menyatakan produk multimedia interaktif sudah cukup layak dan dikemas secara sederhana. Hasil uji coba pengguna menyatakan produk multimedia interaktif dari segi materi sudah cukup baik dan mewakili isi dari pembelajaran PKPBI. This research produces a digital product in the form of Interactive Multimedia for teachers at the Pangudi Luhur Special School, especially in the learning of Sound and Rhythm Perception Communication Development, and on Sound Identification material. In developing this multimedia, researchers used the Baker & Schutz development model. This model consists of seven stages, namely product formulation, step specification, test questions, product development, product testing, product revision, and analysis for utilization. The evaluation in this study involved 1 material expert, 1 media expert and 1 user. The expert test results stated that interactive multimedia products were quite feasible and packaged in a simple way. The results of the user trial stated that the interactive multimedia product in terms of material was quite good and represented the content of PKPBI learning

Parental protein malnutrition programmes of offspring growth and vasculature to increase risk of cardiovascular, pancreatic, and metabolic disease: lessons learned from animal studies

It is well known that consumption of a balanced diet throughout adulthood is key toward maintenance of optimal body weight and cardiovascular health. Research using animal models can provide insights into the programming of short and long-term health by parental diet and potential mechanisms by which, for example, protein intake may influence fetal development, adolescent health, and adult morbidity/mortality. Malnutrition, whether consumption of too many or too few individual nutrients or energy, is detrimental to health. For example, in Westernised societies, one of the principal factors contributing towards the global epidemic of obesity is over-consumption of calories, relative to the expenditure of calories through physical activity. A large body of evidence now suggests that many chronic diseases of adulthood, such as obesity and diabetes, are linked to the nutritional environment experienced by the fetus in utero. Maternal consumption of a poor-quality, nutritionally unbalanced diet can programme offspring to become obese, develop high blood pressure and diabetes, and to experience premature morbidity and mortality. More recently, paternal diet has also been shown to influence offspring health through effects carried via the sperm that affect post-fertilisation development. Mechanisms underpinning such developmental programming effects remain elusive, although early development of the microvasculature in the heart and pancreas, particularly after exposure of the mother (or father) to a protein restricted diet, has been proposed as one mechanism linking early diet to perturbed adult function. In this brief review, we explore the longer-term consequences of maternal and paternal protein intakes on the progeny. Using evidence from relevant animal models, we illustrate how protein malnutrition may ‘programme’ lifelong health and disease outcomes, especially in relation to pancreatic function and insulin resistance, and cardiac abnormalities

Dysregulation of complement and coagulation pathways: emerging mechanisms in the development of psychosis

Early identification and treatment significantly improve clinical outcomes of psychotic disorders. Recent studies identified protein components of the complement and coagulation systems as key pathways implicated in psychosis. These specific protein alterations are integral to the inflammatory response and can begin years before the onset of clinical symptoms of psychotic disorder. Critically, they have recently been shown to predict the transition from clinical high risk to first-episode psychosis, enabling stratification of individuals who are most likely to transition to psychotic disorder from those who are not. This reinforces the concept that the psychosis spectrum is likely a central nervous system manifestation of systemic changes and highlights the need to investigate plasma proteins as diagnostic or prognostic biomarkers and pathophysiological mediators. In this review, we integrate evidence of alterations in proteins belonging to the complement and coagulation protein systems, including the coagulation, anticoagulation, and fibrinolytic pathways and their dysregulation in psychosis, into a consolidated mechanism that could be integral to the progression and manifestation of psychosis. We consolidate the findings of altered blood proteins relevant for progression to psychotic disorders, using data from longitudinal studies of the general population in addition to clinical high-risk (CHR) individuals transitioning to psychotic disorder. These are compared to markers identified from first-episode psychosis and schizophrenia as well as other psychosis spectrum disorders. We propose the novel hypothesis that altered complement and coagulation plasma levels enhance their pathways’ activating capacities, while low levels observed in key regulatory components contribute to excessive activation observed in patients. This hypothesis will require future testing through a range of experimental paradigms, and if upheld, complement and coagulation pathways or specific proteins could be useful diagnostic or prognostic tools and targets for early intervention and preventive strategies

Plasma polyunsaturated fatty acids and mental disorders in adolescence and early adulthood: cross-sectional and longitudinal associations in a general population cohort

Polyunsaturated fatty acids (PUFAs) may be pertinent to the development of mental disorders, for example via modulation of inflammation and synaptogenesis. We wished to examine cross-sectional and longitudinal associations between PUFAs and mental disorders in a large cohort of young people. Participants in the Avon Longitudinal Study of Parents and Children were interviewed and provided blood samples at two sampling periods when approximately 17 and 24 years old. Plasma PUFA measures (total omega-6 [n-6], total omega-3 [n-3], n-6:n-3 ratio and docosahexaenoic acid [DHA] percentage of total fatty acids) were assessed using nuclear magnetic resonance spectroscopy. Cross-sectional and longitudinal associations between standardised PUFA measures and three mental disorders (psychotic disorder, moderate/severe depressive disorder and generalised anxiety disorder [GAD]) were measured by logistic regression, adjusting for age, sex, body mass index and cigarette smoking. There was little evidence of cross-sectional associations between PUFA measures and mental disorders at age 17. At age 24, the n-6:n-3 ratio was positively associated with psychotic disorder, depressive disorder and GAD, while DHA was inversely associated with psychotic disorder. In longitudinal analyses, there was evidence of an inverse association between DHA at age 17 and incident psychotic disorder at age 24 (adjusted odds ratio 0.44, 95% confidence interval 0.22–0.87) with little such evidence for depressive disorder or GAD. There was little evidence for associations between change in PUFA measures from 17 to 24 years and incident mental disorders at 24 years. These findings provide support for associations between PUFAs and mental disorders in early adulthood, and in particular, for DHA in adolescence in relation to prevention of psychosis

Role of NADH Dehydrogenase (Ubiquinone) 1 alpha subcomplex 4-like 2 in clear cell renal cell carcinoma

PURPOSE We delineated the functions of the HIF1α target NADH Dehydrogenase (Ubiquinone) 1 alpha subcomplex 4-like 2 (NDUFA4L2) in ccRCC and characterized NDUFA4L2 as a novel molecular target for ccRCC treatment. EXPERIMENTAL DESIGN We evaluated normal kidney and ccRCC patient microarray and RNAseq data from Oncomine and The Cancer Genome Atlas (TCGA) for NDUFA4L2 mRNA levels and the clinical implications of high NDUFA4L2 expression. Additionally, we examined normal kidney and ccRCC patient tissue samples, human ccRCC cell lines, and murine models of ccRCC for NDUFA4L2 mRNA and protein expression. Utilizing shRNA, we performed NDUFA4L2 knockdown experiments and analyzed the proliferation, clonogenicity, metabolite levels, cell structure, and autophagy in ccRCC cell lines in culture. RESULTS We found that NDUFA4L2 mRNA and protein are highly expressed in ccRCC samples but undetectable in normal kidney tissue samples, and that NDUFA4L2 mRNA expression correlates with tumor stage and lower overall survival. Additionally, we demonstrated that NDUFA4L2 is a HIF1α target in ccRCC and that NDUFA4L2 knockdown has a profound anti-proliferative effect, alters metabolic pathways, and causes major stress in cultured RCC cells. CONCLUSIONS Collectively, our data show that NDUFA4L2 is a novel molecular target for ccRCC treatment

Regulation of vascular endothelial growth factor in prostate cancer

Prostate cancer (PCa) is the most common malignancy affecting men in the western world. Although radical prostatectomy and radiation therapy can successfully treat PCa in the majority of patients, up to ∼30% will experience local recurrence or metastatic disease. Prostate carcinogenesis and progression is typically an androgen-dependent process. For this reason, therapies for recurrent PCa target androgen biosynthesis and androgen receptor function. Such androgen deprivation therapies (ADT) are effective initially, but the duration of response is typically ≤24 months. Although ADT and taxane-based chemotherapy have delivered survival benefits, metastatic PCa remains incurable. Therefore, it is essential to establish the cellular and molecular mechanisms that enable localized PCas to invade and disseminate. It has long been accepted that metastases require angiogenesis. In the present review, we examine the essential role for angiogenesis in PCa metastases, and we focus in particular on the current understanding of the regulation of vascular endothelial growth factor (VEGF) in localized and metastatic PCa. We highlight recent advances in understanding the role of VEGF in regulating the interaction of cancer cells with tumor-associated immune cells during the metastatic process of PCa. We summarize the established mechanisms of transcriptional and post-transcriptional regulation of VEGF in PCa cells and outline the molecular insights obtained from preclinical animal models of PCa. Finally, we summarize the current state of anti-angiogenesis therapies for PCa and consider how existing therapies impact VEGF signaling

MIR137 is an androgen regulated repressor of an extended network of transcriptional coregulators

Androgens and the androgen receptor (AR) play crucial roles in male development and the pathogenesis and progression of prostate cancer (PCa). The AR functions as a ligand dependent transcription factor which recruits multiple enzymatically distinct epigenetic coregulators to facilitate transcriptional regulation in response to androgens. Over-expression of AR coregulators is implicated in cancer. We have shown that over-expression of KDM1A, an AR coregulator, contributes to PCa recurrence by promoting VEGFA expression. However the mechanism(s) whereby AR coregulators are increased in PCa remain poorly understood. In this study we show that the microRNA hsa-miR-137 (miR137) tumor suppressor regulates expression of an extended network of transcriptional coregulators including KDM1A/LSD1/AOF1, KDM2A/JHDM1A/FBXL11, KDM4A/JMJD2A, KDM5B JARID1B/PLU1, KDM7A/JHDM1D/PHF8, MED1/TRAP220/DRIP205 and NCoA2/SRC2/TIF2. We show that expression of miR137 is increased by androgen in LnCaP androgen PCa responsive cells and that the miR137 locus is epigenetically silenced in androgen LnCaP:C4-2 and PC3 independent PCa cells. In addition, we found that restoration of miR137 expression down-regulates expression of VEGFA, an AR target gene, which suggests a role of miR137 loss also in cancer angiogenesis. Finally we show functional inhibition of mIR137 function enhanced androgen induction of PSA/KLK3 expression. Our data indicate that miR137 functions as an androgen regulated suppressor of androgen signaling by modulating expression of an extended network of transcriptional coregulators. Therefore, we propose that epigenetic silencing of miR137 is an important event in promoting androgen signaling during prostate carcinogenesis and progression