Pattern of 25-hydroxy vitamin D response at short (2 month) and long (1 year) interval after 8 weeks of oral supplementation with cholecalciferol in Asian Indians with chronic hypovitaminosis D

Hypovitaminosis D is common in Asian Indians. Physicians often prescribe 1500 μ g (60 000 IU) cholecalciferol per week for 8 weeks for vitamin D deficiency in India. Its efficacy to increase serum 25-hydroxy vitamin D (25(OH)D) over short (2 months) and long (1 year) term is not known. We supplemented a group of twenty-eight apparently healthy Asian Indians detected to have low serum 25(OH)D (mean 13.5 (sd 3.0) nmol/l) on screening during January-March 2005. Serum parathyroid hormone (PTH) level was supranormal in 30 % of them. Oral supplementation included 1500 μ g cholecalciferol per week and 1g elemental Ca daily for 8 weeks. Serum 25(OH)D, total Ca, inorganic P and intact (i) PTH were reassessed in twenty-three subjects (twelve females and eleven males) who had follow up at both 8 weeks and 1 year. At 8 weeks the mean 25(OH)D levels increased to 82.4 (SD 20.7) nmol/l and serum PTH normalized in all. Twenty-two of the twenty-three subjects had 25(OH)D levels>49.9 nmol/l. At 1 year, though the mean 25(OH)D level of 24.7 (SD 10.9) nmol/l was significantly higher than the baseline, all subjects were 25(OH)D deficient. Five subjects with supranormal iPTH at baseline showed recurrence of biochemical hyperparathyroidism. Thus, with 8 weeks of cholecalciferol supplementation in Asian Indians with chronic hypovitaminosis D, mean serum 25(OH)D levels would be normalized and serum PTH value would be reduced to half. However, such quick supplementation would not maintain their 25(OH)D levels in the sufficient range for 1 year. For sustained improvement in 25(OH)D levels vitamin D supplementation has to be ongoing after the initial cholecalciferol loading

Machine Learning and Rule Mining Techniques in the Study of Gene Inactivation and RNA Interference

RNA interference (RNAi) and gene inactivation are extensively used biological terms in biomedical research. Two categories of small ribonucleic acid (RNA) molecules, viz., microRNA (miRNA) and small interfering RNA (siRNA) are central to the RNAi. There are various kinds of algorithms developed related to RNAi and gene silencing. In this book chapter, we provided a comprehensive review of various machine learning and association rule mining algorithms developed to handle different biological problems such as detection of gene signature, biomarker, gene module, potentially disordered protein, differentially methylated region and many more. We also provided a comparative study of different well-known classifiers along with other used methods. In addition, we demonstrated the brief biological information regarding the immense biological challenges for gene activation as well as their advantages, disadvantages and possible therapeutic strategies. Finally, our study helps the bioinformaticians to understand the overall immense idea in different research dimensions including several learning algorithms for the benevolent of the disease discovery

Pattern of 25-hydroxy vitamin D response at short (2 month) and long (1 year) interval after 8 weeks of oral supplementation with cholecalciferol in Asian Indians with chronic hypovitaminosis

Hypovitaminosis D is common in Asian Indians. Physicians often prescribe 1500 mg (60 000 IU) cholecalciferol per week for 8 weeks for vitamin D deficiency in India. Its efficacy to increase serum 25-hydroxy vitamin D (25(OH)D) over short (2 months) and long (1 year) term is not known. We supplemented a group of twenty-eight apparently healthy Asian Indians detected to have low serum 25(OH)D (mean 13·5 (SD 3·0) nmol/l) on screening during January -March 2005. Serum parathyroid hormone (PTH) level was supranormal in 30 % of them. Oral supplementation included 1500 mg cholecalciferol per week and 1g elemental Ca daily for 8 weeks. Serum 25(OH)D, total Ca, inorganic P and intact (i) PTH were reassessed in twenty-three subjects (twelve females and eleven males) who had follow up at both 8 weeks and 1 year. At 8 weeks the mean 25(OH)D levels increased to 82·4 (SD 20·7) nmol/l and serum PTH normalized in all. Twenty-two of the twenty-three subjects had 25(OH)D levels . 49·9 nmol/l. At 1 year, though the mean 25(OH)D level of 24·7 (SD 10·9) nmol/l was significantly higher than the baseline, all subjects were 25(OH)D deficient. Hypovitaminosis D is common in India despite its sunny environment (1 -3) . More than 90 % of apparently healthy Indians residing in India have subnormal serum 25-hydroxy vitamin D (25(OH)D) levels with values almost undetectable during winter (1 -3

Influence of a Hyperglycemic Microenvironment on a Diabetic Versus Healthy Rat Vascular Endothelium Reveals Distinguishable Mechanistic and Phenotypic Responses

Hyperglycemia is a critical factor in the development of endothelial dysfunction in type 2 diabetes mellitus (T2DM). Whether hyperglycemic states result in a disruption of similar molecular mechanisms in endothelial cells under both diabetic and non-diabetic states, remains largely unknown. This study aimed to address this gap in knowledge through molecular and functional characterization of primary rat cardiac microvascular endothelial cells (RCMVECs) derived from the T2DM Goto-Kakizaki (GK) rat model in comparison to control Wistar-Kyoto (WKY) in response to a normal (NG) and hyperglycemic (HG) microenvironment. GK and WKY RCMVECs were cultured under NG (4.5 mM) and HG (25 mM) conditions for 3 weeks, followed by tandem mass spectrometry (MS/MS), qPCR, tube formation assay, microplate based fluorimetry, and mitochondrial respiration analyses. Following database matching and filtering (false discovery rate ≤ 5%, scan count ≥ 10), we identified a greater percentage of significantly altered proteins in GK (7.1%, HG versus NG), when compared to WKY (3.5%, HG versus NG) RCMVECs. Further stringent filters (log2ratio of > 2 or < –2, p < 0.05) followed by enrichment and pathway analyses of the MS/MS and quantitative PCR datasets (84 total genes screened), resulted in the identification of several molecular targets involved in angiogenic, redox and metabolic functions that were distinctively altered in GK as compared to WKY RCMVECs following HG exposure. While the expression of thirteen inflammatory and apoptotic genes were significantly increased in GK RCMVECs under HG conditions (p < 0.05), only 2 were significantly elevated in WKY RCMVECs under HG conditions. Several glycolytic enzymes were markedly reduced and pyruvate kinase activity was elevated in GK HG RCMVECs, while in mitochondrial respiratory chain activity was altered. Supporting this, TNFα and phorbol ester (PMA)-induced Reactive Oxygen Species (ROS) production were significantly enhanced in GK HG RCMVECs when compared to baseline levels (p < 0.05). Additionally, PMA mediated increase was the greatest in GK HG RCMVECs (p < 0.05). While HG caused reduction in tube formation assay parameters for WKY RCMVECs, GK RCMVECs exhibited impaired phenotypes under baseline conditions regardless of the glycemic microenvironment. We conclude that hyperglycemic microenvironment caused distinctive changes in the bioenergetics and REDOX pathways in the diabetic endothelium as compared to those observed in a healthy endothelium

Toward community standards and software for whole-cell modeling

Whole-cell (WC) modeling is a promising tool for biological research, bioengineering, and medicine. However, substantial work remains to create accurate, comprehensive models of complex cells. Methods: We organized the 2015 Whole-Cell Modeling Summer School to teach WC modeling and evaluate the need for new WC modeling standards and software by recoding a recently published WC model in SBML. Results: Our analysis revealed several challenges to representing WC models using the current standards. Conclusion: We, therefore, propose several new WC modeling standards, software, and databases. Significance:We anticipate that these new standards and software will enable more comprehensive models

A model of an integrated immune system pathway in Homo sapiens and its interaction with superantigen producing expression regulatory pathway in Staphylococcus aureus: comparing behavior of pathogen perturbed and unperturbed pathway.

Response of an immune system to a pathogen attack depends on the balance between the host immune defense and the virulence of the pathogen. Investigation of molecular interactions between the proteins of a host and a pathogen helps in identifying the pathogenic proteins. It is necessary to understand the dynamics of a normally behaved host system to evaluate the capacity of its immune system upon pathogen attack. In this study, we have compared the behavior of an unperturbed and pathogen perturbed host system. Moreover, we have developed a formalism under Flux Balance Analysis (FBA) for the optimization of conflicting objective functions. We have constructed an integrated pathway system, which includes Staphylococcal Superantigen (SAg) expression regulatory pathway and TCR signaling pathway of Homo sapiens. We have implemented the method on this pathway system and observed the behavior of host signaling molecules upon pathogen attack. The entire study has been divided into six different cases, based on the perturbed/unperturbed conditions. In other words, we have investigated unperturbed and pathogen perturbed human TCR signaling pathway, with different combinations of optimization of concentrations of regulatory and signaling molecules. One of these cases has aimed at finding out whether minimization of the toxin production in a pathogen leads to the change in the concentration levels of the proteins coded by TCR signaling pathway genes in the infected host. Based on the computed results, we have hypothesized that the balance between TCR signaling inhibitory and stimulatory molecules can keep TCR signaling system into resting/stimulating state, depending upon the perturbation. The proposed integrated host-pathogen interaction pathway model has accurately reflected the experimental evidences, which we have used for validation purpose. The significance of this kind of investigation lies in revealing the susceptible interaction points that can take back the Staphylococcal Enterotoxin (SE)-challenged system within the range of normal behavior

Graph shows optimization of two conflicting objective functions in an integrated pathway system of SAg expression regulatory pathway of <i>S. aureus</i> and TCR signaling pathway of an infected host (<i>H. sapiens</i>).

<p>Here, is maximized, while is minimized.</p

Displaying the concept behind the construction of integrated pathway system that includes SAg expression regulatory pathway of <i>S. aureus</i> and TCR signaling pathway of an infected host (<i>H. sapiens</i>).

<p>Displaying the concept behind the construction of integrated pathway system that includes SAg expression regulatory pathway of <i>S. aureus</i> and TCR signaling pathway of an infected host (<i>H. sapiens</i>).</p

Comparing -values [0–1] of the molecules present in TCR signaling pathway of <i>H. sapiens</i> in three cases: (1) in an unperturbed TCR signaling pathway, (2) in a perturbed one and (3) after applying conflicting objective function optimization (case 4) on the perturbed TCR signaling pathway.

<p>Comparing -values [0–1] of the molecules present in TCR signaling pathway of <i>H. sapiens</i> in three cases: (1) in an unperturbed TCR signaling pathway, (2) in a perturbed one and (3) after applying conflicting objective function optimization (case 4) on the perturbed TCR signaling pathway.</p

Effects on some of the TCR signaling molecules upon perturbing the concentrations of ZAP70, LCK and FYN for unperturbed and perturbed TCR signaling pathways of <i>H. sapiens</i>.

<p>Effects on some of the TCR signaling molecules upon perturbing the concentrations of ZAP70, LCK and FYN for unperturbed and perturbed TCR signaling pathways of <i>H. sapiens</i>.</p