Elevated myc expression and c-myc amplification in spontaneously occurring B lymphoid cell lines

Recently, a minor subpopulation of murine B lymphocytes, Ly-1+ B cells, has been distinguished by its unique ontogeny, tissue distribution, and prominence in certain autoimmune and neoplastic B cell diseases. We have previously described a simple murine spleen culture system that results in the spontaneous and exclusive outgrowth of long-term Ly-1+ B cell lines (B Ly-1 cells). Here, we report that the immortal growth property of B Ly-1 cells correlates with a 10-45-fold elevation of steady-state myc RNA and 2-10-fold amplification of the c-myc locus. While c-myc amplification has been observed in malignant cell lines derived from several tissues of origin, its occurrence in lymphoid cells has not been previously reported. The consistent c-myc amplification in B Ly-1 cells may reflect a unique state of this locus in the Ly-1+ B lymphocyte lineage, and contribute to the spontaneous immortalization of this B cell population in vitro, and its apparent predilection for malignant transformation in vivo

Sustained epidermal growth factor receptor levels and activation by tethered ligand binding enhances osteogenic differentiation of multi-potent marrow stromal cells

Author Manuscript 2011 April 29.Epidermal growth factor receptor (EGFR)-mediated signaling helps regulate bone development and healing through its effects on osteogenic cells. Here, we show how EGFR activity and osteogenic differentiation responses in primary human bone marrow-derived multipotent stromal cells (MSCs) are influenced by presenting covalently tethered epidermal growth factor (tEGF) on the culture substratum, a presentation mode that reduces EGFR internalization and restricts signaling to the cell surface. In both absence and presence of tEGF, MSCs increase expression levels of EGFR and its heterodimerization partner HER2 during the course of osteogenic differentiation. tEGF substrata increased levels of phosphorylated EGFR and phosphorylated extracellular regulated kinase (ERK) compared to control substrata, and these elevations were associated with a twofold enhancement of MSC alkaline phosphatase activity at day 7 and matrix mineralization at day 21. Surprisingly, addition of soluble EGF (sEGF) to cells cultured on tEGF substrata reduces osteogenic differentiation, even though EGFR signaling is more strongly activated in acute, short-term manner by sEGF treatment than by tEGF treatment. A striking concomitant result of the sEGF effects is near-complete downregulation of EGFR and HER2, demonstrating that the tEGF/EGFR interaction is dynamically reversible even though temporally sustained. Taken together, our results show that enhanced MSC osteogenic differentiation corresponds to a sustained combination of receptor expression and ligand presentation, both of which are maintained by tEGF.National Institutes of Health (U.S.) (Grant R01-GM059870-07)National Institutes of Health (U.S.) (Grant R01-DE 019523-10)National Institutes of Health (U.S.) (Grant P40RR017447)United Negro College Fund (Merck Postdoctoral Fellowship)Georgia Institute of Technology (FACES Fellowship)National Center for Research Resources (U.S.) (Grant P40RR017447

Computational and Mathematical Modelling of the EGF Receptor System

This chapter gives an overview of computational and mathematical modelling of the EGF receptor system. It begins with a survey of motivations for producing such models, then describes the main approaches that are taken to carrying out such modelling, viz. differential equations and individual-based modelling. Finally, a number of projects that applying modelling and simulation techniques to various aspects of the EGF receptor system are described

Speeding up systems biology simulations of biochemical pathways using condor

This is the accepted version of the following article: Speeding up Systems Biology Simulations of Biochemical Pathways using Condor". Concurrency and Computation: Practice and Experience Volume 26, Issue 17, pages 2727–2742, 10 December 2014 which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1002/cpe.3161/abstractSystems biology is a scientific field that uses computational modelling to study biological and biochemical systems. The simulation and analysis of models of these systems typically explore behaviour over a wide range of parameter values; as such, they are usually characterised by the need for nontrivial amounts of computing power. Grid computing provides access to such computational resources. In previous research, we created the grid-enabled biochemical networks simulation environment to attempt to speed up system biology simulations over a grid (the UK National Grid Service and ScotGrid). Following on from this work, we have created the simulation modelling of the epidermal growth factor receptor microtubule-associated protein kinase pathway utility, a standalone simulation tool dedicated to the modelling and analysis of the epidermal growth factor receptor microtubule-associated protein kinase pathway. This builds on experiences from biochemical networks simulation environment by decoupling the simulation modelling elements from the Grid middleware. This new utility enables us to interface with different grid technologies. This paper therefore describes the new SIMAP utility and an empirical investigation of its performance when deployed over a desktop grid based on the high throughput computing middleware Condor. We present our results based on a case study with a model of the mammalian ErbB signalling pathway, a pathway strongly linked to cance

KEBIASAAN MINUM BERALKOHOL IMPOR (STUDI ETNOGRAFI KELOMPOK MAHASISWI BERJILBAB CAP DI BANDUNG)

ABSTRAK Penelitian ini membahas tentang bagaimana para mahasiswi berjilbab memiliki kegemaran minum minuman beralkohol impor yang tergabung pada kelompok CAP di Bandung, serta mengungkapkan bagaimana pengetahuan kelompok mahasiswi berjilbab CAP mengenai minuman beralkohol impor dan makna minum bagi mereka. Metode penelitian yang digunakan yakni metode penelitian kualitatif dengan pendekatan etnosains James Spradley yang berupa etnografi dan narasi personal, data yang dikumpulkan melalui studi pustaka, observasi partisipatif, wawancara mendalam, dan dokumentasi serta validasi data yang dilakukan dengan cara mereduksi data dan pengorganisasian data. Hasil penelitian menunjukkan bahwa minuman beralkohol impor bagi kelompok CAP dapat menaikan prestise, dan merasa mendapatkan kepercayaan diri. Kemudian, kelompok CAP memiliki pengetahuan mengenai minuman beralkohol impor yaitu pengetahuan tentang mencampuri minuman beralkohol impor dengan minuman jenis lain, pengetahuan khas yang hanya berlaku di kelompok CAP, serta mereka memaknai minuman beralkohol impor sebagai jembatan dan pengerat tali kasih pertemanan mereka dalam kelompok CAP. Kata kunci: kelompok CAP, kebiasaan, minuman beralkohol impor, etnosains   ABSTRACT This study discusses how the veiled female students have a penchant for drinking imported alcoholic beverages who are members of the CAP group in Bandung, and reveals how the knowledge of the CAP veiled female student group about imported alcoholic beverages and the meaning of drinking for them. The research method used is a qualitative research method with James Spradley\u27s ethnoscience approach in the form of ethnography and personal narrative, data collected through literature study, participatory observation, in-depth interviews, and documentation and data validation by reducing data and organizing data. The results show that imported alcoholic beverages for the CAP group can increase prestige, and feel confident. Then, the CAP group has knowledge about imported alcoholic beverages, namely knowledge about mixing imported alcoholic beverages with other types of drinks, special knowledge that only applies to the CAP group, and they interpret imported alcoholic beverages as a bridge and strengthen their friendship in the CAP group. Keywords: CAP group, habits, imported alcoholic beverages, ethnoscienc

Tailoring Chimeric Ligands for Studying and Biasing ErbB Receptor Family Interactions

Described is the development and application of a versatile semisynthetic strategy, based on a combination of sortase-mediated coupling and tetrazine ligation chemistry, which can be exploited for the efficient incorporation of tunable functionality into chimeric recombinant proteins. To demonstrate the scope of the method, the assembly of a set of bivalent ligands, which integrate members of the epidermal growth factor (EGF) ligand family, is described. By using a series of bivalent EGFs with variable intraligand spacing, the differences in structure were correlated with the ability to bias signaling in the ErbB receptor family in a cell motility assay. Biasing away from EGFR-HER2 dimerization with a bivalent EGF was observed to reduce cell motility in an intraligand distance-dependent fashion, thus demonstrating the utility of the approach for acutely perturbing receptor-mediated cell signaling pathways.National Cancer Institute (U.S.). Integrative Cancer Biology Program (Grant U54-CA112967)National Institutes of Health (U.S.) (R01DE019523-13)Massachusetts Institute of Technology. Computational and Systems Biology Program. MIT-Merck Postdoctoral FellowshipSwiss National Science Foundation (Postdoctoral Fellowship)National Institute of Environmental Health Sciences (Training Grant in Environmental Toxicology 5-T32-ES007020

Multi-pathway Kinase Signatures of Multipotent Stromal Cells are Predictive for Osteogenic Differentiation

Bone marrow-derived multipotent stromal cells (MSCs) offer great promise for regenerating tissue. Although certain transcription factors have been identified in association with tendency toward particular MSC differentiation phenotypes, the regulatory network of key receptor-mediated signaling pathways activated by extracellular ligands that induce various differentiation responses remains poorly understood. Attempts to predict differentiation fate tendencies from individual pathways in isolation are problematic due to the complex pathway interactions inherent in signaling networks. Accordingly, we have undertaken a multivariate systems approach integrating experimental measurement of multiple kinase pathway activities and osteogenic differentiation in MSCs, together with computational analysis to elucidate quantitative combinations of kinase signals predictive of cell behavior across diverse contexts. In particular, for culture on polymeric biomaterial surfaces presenting tethered epidermal growth factor, type I collagen, neither, or both, we have found that a partial least-squares regression model yields successful prediction of phenotypic behavior on the basis of two principal components comprising the weighted sums of eight intracellular phosphoproteins: phospho-epidermal growth factor receptor, phospho-Akt, phospho-extracellular signal-related kinase 1/2, phospho-heat shock protein 27, phospho-c-Jun, phospho-glycogen synthase kinase 3α/β, phospho-p38, and phospho-signal transducer and activator of transcription 3. This combination provides the strongest predictive capability for 21-day differentiated phenotype status when calculated from day-7 signal measurements; day-4 and day-14 signal measurements are also significantly predictive, indicating a broad time frame during MSC osteogenesis wherein multiple pathways and states of the kinase signaling network are quantitatively integrated to regulate gene expression, cell processes, and ultimately, cell fate. STEM CELLS 2009;27:2804–2814National Institutes of Health (U.S.) (Grant NIH R01-GM059870-07)National Institutes of Health (U.S.) (Grant R01 DE019523- 10)United Negro College Fund ((UNCF)/Merck Postdoctoral Fellowship)Georgia Institute of Technology (Facilitating Academic Careers in Engineering and Sciences Fellowship

KEPATUHAN MINUM OBAT PADA PASIEN DIABETES MELITUS TIPE 2 DISERTAI HIPERTENSI DENGAN MENGGUNAKAN METODE MMAS-8

KEPATUHAN MINUM OBAT PADA PASIEN DIABETES MELITUS TIPE 2 DISERTAI HIPERTENSI DENGAN MENGGUNAKAN METODE MMAS-8Citri Mokolomban1), Weny I. Wiyono1), Deby A. Mpila1)1)Program Studi Farmasi FMIPA Unsrat Manado, 95115ABSTRACTType 2 diabetes mellitus (DM) is caused by insulin target cells failing or unable to respond normally to insulin. Disruption of insulin production and function results in an increase in blood sugar levels above normal (hyperglycemia) which will eventually increase blood pressure (hypertension). Type 2 diabetes mellitus patients with hypertension should take their medication properly in order to maintain the patient's blood sugar levels and blood pressure within normal limits. This study aims to determine the adherence to medication consumption of type 2 DM patients with hypertension at the Manado Imanuel Clinic using the MMAS-8 method with prospective data collection of 45 patients. The results of the study showed that adherent patients were 37.78%, and non-adherent were 62.22%. The level of adherence to medication based on the characteristics of the patient, namely the majority of obedient male sex is 38.89%, aged 18-65 years is 22.22%, the last education is high school / equivalent is 42.86%, the patient is not working at 44, 44%, and patients who consumed ≥5 drugs were 60%.Keywords: Type 2 DM hypertension, adherence to taking medication.ABSTRAKDiabetes Melitus (DM) tipe 2 disebabkan karena sel-sel sasaran insulin gagal atau tak mampu merespon insulin secara normal. Gangguan produksi dan fungsi insulin mengakibatkan terjadinya peningkatan kadar gula darah diatas normal (hiperglikemia) yang akhirnya akan meningkatkan tekanan darah (hipertensi). Pasien DM tipe 2 disertai hipertensi harus meminum obatnya dengan benar agar dapat menjaga kadar gula darah dan tekanan darah pasien tetap dalam batas normal. Penelitian ini bertujuan untuk mengetahui kepatuhan minum obat pasien DM tipe 2 disertai hipertensi di Klinik Imanuel Manado menggunakan metode MMAS-8 dengan pengambilan data secara prospektif terhadap 45 pasien. Hasil penelitian menunjukan pasien yang patuh sebesar 37,78%, dan tidak patuh sebesar 62,22%. Tingkat kepatuhan minum obat berdasarkan karakteristik pasien, yaitu mayoritas patuh berjenis kelamin laki-laki sebesar 38,89%, berusia 18-65 tahun sebesar 22,22%, pendidikan terkahir SMA/Sederajat sebesar 42,86%, pasien tidak bekerja sebesar 44,44%, dan pasien yang mengonsumsi ≥5 jenis obat sebesar 60%.Kata Kunci : DM tipe 2 disertai hipertensi, Kepatuhan minum obat

HUBUNGAN ANTARA PERSEPSI TERHADAP GAYA HIDUP CLUBBING DENGAN RELIGIUSITAS PADA REMAJA DI SMA NEGERI 5 SURAKARTA

Individu yang ideal adalah individu yang dapat berhubungan secara harmonis dengan dirinya sendiri, dan secara horizontal harmonis dengan orang lain atau masyarakat, serta secara vertikal berhubungan secara harmonis dengan Tuhannya. Seseorang yang mempunyai religiusitas yang tinggi akan selalu berusaha berbuat baik dan tidak terjerumus dalam kehidupan yang negatif. Salah satu fenomena paling besar yang merupakan bagian dari gaya hidup hedonis dikalangan anak muda perkotaan adalah gaya hidup clubbing. Gaya hidup clubbing dipersepsikan secara berbeda oleh masing-masing individu. Ada yang mempersepsikan gaya hidup secara positif dan negatif. Penelitian ini bertujuan untuk mengetahui: (1) Hubungan antara persepsi terhadap gaya hidup clubbing dengan religiusitas pada remaja di SMA Negeri 5 Surakarta. (2) Tingkat persepsi terhadap gaya hidup clubbing dan religiusitas pada remaja di SMA Negeri 5 Surakarta. (3) Peran persepsi terhadap gaya hidup clubbing terhadap religiusitas pada remaja di SMA Negeri 5 Surakarta. Hipotesis yang diajukan yaitu ada hubungan negatif antara persepsi terhadap gaya hidup clubbing dengan religiusitas pada remaja di SMA Negeri 5 Surakarta. Artinya, subjek yang memiliki religiusitas tinggi, maka persepsi terhadap gaya hidup clubbing semakin rendah atau negatif. Sebaliknya, semakin rendah religiusitas subjek maka persepsi terhadap gaya hidup clubbing akan tinggi atau positif. Populasi dalam penelitian ini yaitu seluruh siswa di SMA Negeri 5 Surakarta berjumlah 1.059 siswa. Sampel dalam penelitian ini adalah siswa kelas XI A1, A2, dan A3 berjumlah 78 siswa, dengan alasan dipilihnya kelas tersebut karena berdasarkan observasi dan wawancara penelitian dapat diketahui bahwa ketiga kelas tersebut termasuk kelas yang siswanya cenderung banyak melakukan kesalahan dibandingkan dengan kelas XI lainnya. Teknik pengambilan sampel yang digunakan adalah teknik purposive sampling. Alat pengumpulan data menggunakan dua skala psikologis, yaitu skala Persepsi terhadap gaya hidup clubbing dan skala religiusitas. Analisis data menggunakan korelasi product moment. Berdasarkan perhitungan yang dilakukan dengan menggunakan analisis korelasi product momen diperoleh hasil r = -0,876 dengan p = 0,000 (p ≤ 0,01) yang berarti ada hubungan negatif yang sangat signifikan antara persepsi terhadap gaya hidup clubbing dengan religiusitas pada remaja di SMA Negeri 5 Surakarta. Artinya, subjek yang memiliki religiusitas tinggi, maka persepsi terhadap gaya hidup clubbing semakin rendah atau negatif. Sebaliknya, semakin rendah religiusitas subjek maka persepsi terhadap gaya hidup clubbing akan tinggi atau positif. Kesimpulan hasil penelitian ini yaitu: (1) Ada hubungan negatif yang sangat signifikan antara persepsi terhadap gaya hidup clubbing dengan religiusitas pada remaja di SMA Negeri 5 Surakarta. (2) Hasil kategori persepsi terhadap gaya hidup clubbing tergolong rendah dengan rerata empirik (ME) = 64,231dan rerata hipotetik (MH) = 85. Hasil kategori religisitas tergolong tinggi dengan rerata empirik (ME) = 115,962 dan rerata hipotetik (MH) = 90. (3) Sumbangan persepsi terhadap gaya hidup clubbing terhadap religiusitas sebesar 0,768 atau 76,8%. Hal ini berarti masih terdapat 23,2%beberapa variabel lain yang mempengaruhi religiusitas