Identification of Extracellular Segments by Mass Spectrometry Improves Topology Prediction of Transmembrane Proteins

Transmembrane proteins play crucial role in signaling, ion transport, nutrient uptake, as well as in maintaining the dynamic equilibrium between the internal and external environment of cells. Despite their important biological functions and abundance, less than 2% of all determined structures are transmembrane proteins. Given the persisting technical difficulties associated with high resolution structure determination of transmembrane proteins, additional methods, including computational and experimental techniques remain vital in promoting our understanding of their topologies, 3D structures, functions and interactions. Here we report a method for the high-throughput determination of extracellular segments of transmembrane proteins based on the identification of surface labeled and biotin captured peptide fragments by LC/MS/MS. We show that reliable identification of extracellular protein segments increases the accuracy and reliability of existing topology prediction algorithms. Using the experimental topology data as constraints, our improved prediction tool provides accurate and reliable topology models for hundreds of human transmembrane proteins

Signaling pathways in breast cancer metastasis - novel insights from functional genomics

The advent of genomic profiling technology has brought about revolutionary changes in our understanding of breast cancer metastasis. Gene expression analyses of primary tumors have been used to predict metastatic propensity with high accuracy. Animal models of metastasis additionally offer a platform to experimentally dissect components of the metastasis genetic program. Recent integrated studies have synergized clinical bioinformatic analyses with advanced experimental methodology and begun to uncover the identities and dynamics of signaling programs driving breast cancer metastasis. Such functional genomics studies hold great promise for understanding the genetic basis of metastasis and improving therapeutics for advanced diseases

Effect of angiotensin II receptor blocker on TGF-β1, MMP-1, and collagen type I and type III concentration in New Zealand rabbit urethral stricture model

Safendra Siregar, Reni Farenia, Suwandi Sugandi, Rully M Roesli Urology Division, Department of Surgery, Hasan Sadikin Hospital Bandung, Faculty of Medicine Padjadjaran University, Bandung, Indonesia Introduction: Urethral stricture is a disease with a high recurrence rate. Angiotensin II via AT1 receptor increases collagen formation through its effects on TGF-β1 and inhibition of collagenase activity. In this study, we evaluated the antifibrotic effect of angiotensin II receptor blocker on urethral stricture formation by creating a urethral stricture model in a male rabbit.Material and methods: Thirty three male adult rabbits were separated into 3 groups (control, treatment, and sham). Group I consisted of 15 rabbits with urethral stricture that did not undergo any treatment, group II consisted of 15 rabbits with urethral stricture that were treated with a daily dose of 15 mg/kg losartan, given orally. Group III consisted of 3 rabbits with normal urethra and without any treatment. After 1, 2, and 4 weeks, the urethral tissues were collected, processed, and examined for TGF-β1, MMP-1, collagen type I, and collagen type III using enzyme-linked immunosorbent assay. Data were analyzed using 2-way analysis of variance using SPSS version 20.0.Results: Urethral TGF-β1 concentration in the treatment group was significantly lower during the 2nd and 4th week of observation (p<0.0001), MMP-1 was significantly higher in the 1st, 2nd, and 4th week of observation (p<0.0001), collagen type I was significantly lower during the 2nd (p=0.001) and 4th week (p<0.0001), and collagen type III concentration was significantly lower in the 2nd and 4th week of observation (p<0.0001).Conclusion: Angiotensin II receptor blocker could limit the progression of urethral stricture. The mechanism may be related to the AT1 blockage that leads to a decrease in TGF-β1 concentration, eventually resulting in lower collagen concentration due to increased MMP-1 activity. Keywords: angiotensin receptor blocker, collagen, MMP-1, TGF-β1, urethral strictur

Microalbuminuria in non-insulin dependent diabetes mellitus: an Indonesian experience

[no abstract available

May measurement month 2018: an analysis of blood pressure screening results from Indonesia.

Elevated blood pressure (BP) is a significant burden worldwide, leading to high cardio-cerebro-reno-vascular morbidity and mortality. For the second year of the May Measurement Month (MMM) campaign in Indonesia in 2018, we recruited 174 sites in 31 out of 34 provinces in Indonesia and screened through convenience sampling in public areas and rural primary health centres. Hypertension was defined as systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg, or both, or on the basis of receiving antihypertensive medication. Blood pressure was measured three times followed the standard global MMM protocol, multiple imputation was used to estimate the mean of the 2nd and 3rd BP readings if these were not recorded. A total of 91 222 individuals were screened, and after multiple imputations, 27 331 (30.0%) had hypertension. Of individuals not receiving antihypertensive medication, 14 367 (18.4%) were hypertensive. Among the 47.4% of hypertensive individuals on antihypertensive medication, 10 106 (78.0%) had uncontrolled BP. MMM17 and MMM18 were still the most extensive standardized screening campaigns for BP measurement in Indonesia. Compared to the previous study, the proportion with uncontrolled BP on medication was significantly higher and provided the substantial challenges in managing hypertension in the rural community

Early childhood education and development services in Indonesia

by Hafid Alatas, Sally Brinkman, Mae Chu Chang, Titie Hadiyati, Djoko Hartono, Amer Hasan, Marilou Hyson, Haeil Jung, Angela Kinnell, Menno Pradhan, Rosfita Roesl