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Reduction of adipose tissue mass by the angiogenesis inhibitor ALS-L1023
Get PDFObjective: Angiogenesis has been demonstrated to modulate adipogenesis and obesity. This study was undertaken to determine whether the botanical drug ALS-L1023 (ALS), which exhibits antiangiogenic activity, can regulate adipose tissue growth in high-fat-diet-induced obese mice.Materials and Methods: The effects of ALS on angiogenesis and extracellular matrix remodeling were measured using in vitro assays. The effects of ALS on adipose tissue growth was investigated in nutritionally obese mice. Results: ALS inhibited angiogenesis in a concentration-dependent manner in the tube formation assay and the VEGF-induced proliferation assay using human umbilical vein endothelial cells. ALS also suppressed matrix metalloproteinase (MMP) activity in vitro. ALS administration to high-fat-diet-induced obese mice significantly reduced body weight gain, adipose tissue mass, and adipocyte size compared with the findings in the controls. ALS treatment decreased blood vessel density and MMP activity in adipose tissues. ALS reduced the mRNA levels of angiogenic factors (VEGFs and FGF-2) and MMPs (MMP-2 and MMP-9), whereas it increased the mRNA levels of angiogenic inhibitors (TSP-1 and TIMPs) in adipose tissues. Conclusion: These results suggest that in vivo and in vitro treatment with ALS, which has antiangiogenic and MMP inhibitory activities, reduces adipose tissue mass in nutritionally induced obese mice, providing evidence that adipose tissue growth can be regulated by angiogenesis inhibitors
Comparison of Efficiency of Photodynamic Diagnostics with Topical Use of the 3% and 15% Aminolevulinic Acid in the Detection of Vulvar Lesions
No full textThe objective of the study was evaluating the efficiency of the photodynamic method PDD (photodynamic diagnosis) in the detection of vulvar lesions when two concentrations of the photosensitizer were used ( 3%- and 15%-aminolevulinic acid ), as well as evaluating the efficiency of this method when compared to the efficiency of vulvoscopy, against the result of histological examination. Two concentrations of the 5-ALA cream ( aminolevulinic acid ) - 3% and 15% - were used in the PDD testing. The study group was divided into two subgroups A and B. In subgroup A the 15% eucerine - based cream was used. In subgroup B the 3% ALA gel with addition of 2% DMSO was used. The photosensitizer was applied to the vulva four to six hours before the examination. In order to obtain fluorescence, energy in the form of light whose wavelength was approximately 405 nm, and whose source was a SLED diode, was transmitted to vulvar tissue. The positive result of the exam was obtaining tissue fluorescence. All patients underwent vulvoscopy and a histological examination of tissue samples was performed in all cases. The efficiency of the photodynamic testing in subgroups A and B was compared with the efficiency of vulvoscopy, against the result of histological examination. Sensitivity, specificity, as well as positive and negative predictive values of the PDD examination and vulvoscopy in both subgroups, were evaluated. When the 15% ALA was used in detecting vulvar lesions, the photodynamic diagnostics was characterized by sensitivity of 100%, specificity of 92%, positive predictive value of 80%, negative predictive value of 100%, and correlation with the histopathological examination of 93.9%. When the 3% ALA was used, we observed: sensitivity of 100%, specificity of 91.4%, positive predictive value of 78.5%, negative predictive value of 100%, and correlation with the histopathological examination of 93.4%. Differences in the two subgroups were not statistically significant
Soil extracellular enzyme activities from a forest harvest and climate manipulation experiment in central Pennsylvania
No full textWe have previously shown that warming and wetting a post-harvest forest soil increased C and N mineralization rates. A series of interacting processes may lead to these observed patterns including shifts in microbial allocation among extracellular enzymes. We monitored soil extracellular enzyme activity (EEA) for 2.5 years in a post-harvest, climate manipulated field experiment. A 2 ha forest in Central Pennsylvania was whole-tree harvested in 2007 and climate manipulations of +2 °C (warmed), and +20% mean monthly historical precipitation (wetted) were added to plots and in combination in a factorial design. The following enzymes were quantified: β-1,4-glucosidase (BG), cellobiohydrolase (CBH), leucine aminopeptidase (LA), N-acetyglucosaminidase (NAG), peroxidase (PER), and polyphenol oxidase (PPO). 
Soil hydrolase enzymes (BG, CBH, LA, and NAG) all showed greater mean activities than those reported from other studies, including study sites with similar climatic and edaphic characteristics. This is indicative of high overall soil microbial activity after forest harvest. Only BG and NAG showed significant treatment effects with a two-factor interaction (warming+wetting) on BG (p = 0.029) and warmed effect on NAG (p = 0.007). Warming decreased BG relative to ambient and NAG relative to wetted plots. There was substantial variability in the season and time since harvest, but water-extractable organic C (WEOC), C:N, and total N best explained the variability of EEAs over the experiment (p’s < 0.05). Two exoenzyme ratios previously used in the literature, BG:(LA+NAG) and BG:PPO, did not vary among treatments. However, the ratio of nitrogen acquiring enzymes (LA+NAG) to the sum of all other enzymes was higher in single-factor treatments compared to the ambient treatment (p = 0.007). Extracellular enzyme activity in a post-harvest forest soil was affected more by increased temperature than by increased precipitation, warming decreasing BG and NAG. Warming has been shown to decrease EEA in other ecosystem warming studies, but this usually is accompanied by a decrease in soil C and N fluxes (also called “attenuation to heating”). Surprisingly the warming treatment had the opposite effect on soil C and N fluxes, increasing fluxes compared to ambient. This inconsistency indicates a physiological change, including a possible shift towards alternate C and N acquiring enzymes, and that disturbed soil EEAs may not respond to climate change in the same way as undisturbed systems
Endothelin-Induced Sarcoplasmic Reticulum Calcium Depletion Waves in Vascular Smooth Muscle Cells
Get PDFAgonist-stimulated waves of elevated cytoplasmic Ca2+ concentration ([Ca2+]i ) regulate blood vessel tone and vasomotion in vascular smooth muscle. Previous studies employing cytoplasmic Ca2+ indicators revealed that these Ca2+ waves were generated by a combination of inositol 1,4,5-trisphosphate (IP3) and Ca2+ induced Ca2+ release (CICR) from the sarcoplasmic reticulum (SR); although, some of the mechanistic details remain uncertain. However, these findings were derived indirectly from observing agonist-induced [Ca2+]i fluctuations in the cytoplasm.
Here, for the first time, we have recorded Endothelin-1 (ET-1) induced waves of Ca2+ depletion from the SR lumen in vascular smooth muscle cells (VSMCs) using a calsequestrin-targeted Ca2+ indicator. Our findings show that these waves: (1) are due to regenerative CICR by the receptors for IP3 (IP3R), (2) have a marked latency period, (3) are characterized by a transient increase in SR Ca2+ ([Ca2+]SR ) both at the point of origin and at the wave front, (4) proceed with diminishing velocity, and (5) are arrested by the nuclear envelope. Our quantitative model indicates that the gradual decrease in the velocity of the SR depletion wave, in the absence of external Ca2+, results from continuity of the SR luminal network
Atomic and molecular structures of positronium, dipositronium and positronium hydride
Get PDFThe three positron based chemical entities, analogous to hydrogen atom, hydrogen molecule and hydride, are drawing increasing attention in the literature. While a lot is known about the binding energies, not much is known about the radii of the atoms and ions and bond lengths and structures of these exotic entities. This article brings for the first time exact values of these structural properties which are comparable with known data. It is hoped that the results will be of help for a better understanding and further development of the chemistry and physics of these exotic compounds and of their possible role as intermediates in chemical and interfacial processes
A Systems Biology Approach to the Evolution of Codon Use Pattern
Get PDFThe genetic code is redundant as amino acids are encoded by synonymous codons that are unequally used.This codon usage bias (CUB) affects gene expression and cellular functions yet the underlying mechanisms have not been elucidated. We used a sequence-specific, stoichiometric model of metabolism and macromolecular synthesis for Escherichia coli K12 MG1655 to test the effect of randomly changed CUB on growth maximization under various environmental conditions. Amongst CUB mutant strains, we identified reduced growth phenotypes, which were caused by tRNA supply shortage. We propose, supported by computations and bibliomic data, that expansion of tRNA gene content or tRNA reading is a mechanism to respond to changes in CUB. Our systems biology modelling framework suggests that in order to maximize growth and to adapt to new environmental niches, CUB and tRNA content must co-evolve and provides further evidence for the mutation-selection-drift balance theory of CUB
ExO: An Ontology for Exposure Science
Get PDFAn ontology is a formal representation of knowledge within a domain and typically consists of classes, the properties of those classes, and the relationships between them. Ontologies are critically important for specifying data of interest in a consistent manner, thereby enabling data aggregation, analysis and exchange. An exposure ontology, consistent with those being used in toxicology and other health sciences, is required to formally represent exposure concepts, the relationships between these concepts and most important, the relationships between exposure, susceptibility, and toxicology information. A successful exposure ontology must facilitate the semantic retrieval of exposure data in the context of environmental health science, medical surveillance, disease control, health tracking, risk assessment, and other public health and environmental science endeavors. To address this need, an Exposure Ontology, ExO, was designed and a prototype developed to provide the foundation for exposure data centralization and integration. The root classes forming the basis for the ontology are 'exposure event’ ‘exposure stressor', 'exposure receptor', and 'exposure outcome'. Although the initial development of ExO was focused on human exposure to chemicals, the ultimate intent is to provide domains that can be extended to address exposures to the full suite of environmental stressors
Neurodegeneration: Potential Causes, Prevention, and Future Treatment Options
Get PDFHere I advance a hypothesis that neurodegeneration is a natural process associated with aging due to the loss of genetic redundancy following a mathematical model R(t) = R0(1-αe(βC+γI+δEt)t), where the calorie intake (C) and immune response (I) play critical roles. The early onset of neurodegenerative diseases such as Alzheimer’s disease is due to metabolic imbalance or chronic immune reactions to various infections. Therefore, the potential treatment options for neurodegenerative diseases are to modulate metabolism and immune response
Managing Bio-Models: Model Storage, Retrieval, Ranking and Versioning
Get PDFIn this poster, we present our experience with techniques for the management of bio-models (i.e. XML-encoded computational models of biological systems) in repositories. These techniques support users to find, access, adapt and then re-submit models - tasks which are essential for the reuse of models in systems biology. Here, we focus on model retrieval, the ranking of search results and concepts to track the history of a model through version control. These concepts have so far not been sufficiently addressed in existing systems.
To validate our techniques, we have been implemented a framework called Sombi. The underlying database called mDB is tailored towards a fine-grained storage of the model and its annotations. The design is applicable to different representation formats but, to begin with, has been tested with SBML models (Köhn et al., 2009).
We furthermore present a retrieval algorithm for bio-model repositories (Henkel et al., 2010). The algorithm has been implemented and validated with mDB and the BioModels Database (www.ebi.ac.uk/biomodels-main/). The ranked retrieval enhances the result set by incorporating expert knowledge in the annotations. In contrast to existing systems, our approach provides a ranked result which is justified and explains the ordering of retrieved models to the users. The mDB design furthermore enables the application of structured queries on the stored model data.
Finally, the poster proposes a solution to model version control. We introduce a library called BiVeS for tracking a model’s history in a diff tree; i.e. a tree-like storage of changes between model versions. These changes are additionally classified into modifications to XML structure, biology and mathematics. This information helps to understand existing models.
All approaches are independent of the SBML format and can therefore be applied to other XML based exchange formats. All code is freely available on Sourceforge from http://bives.sourceforge.net/ and http://sombi.sourceforge.net/
Conceptual model of E. coli transcriptional machinery
Get PDFAt the moment one type of analysis of transcription regulatory networks (TRNs) in prokaryotes is topological analysis of graph structure of possible regulatory interaction links (see for example [1]). That type of analysis takes into account possibility links that designate the fact that one gene product in some conditions can modulate transcription of the other. The benefit of such approach is that it is allow analyzing TRN at the whole cell level. At the same type it is known that at least some responses are regulated by abundance of elements of transcription machinery [2-3]. We have developed conceptual model of whole cell E. coli TRN with SBGN ER, SBGN PD and SBGN AF languages [4]. That model is the first step towards incorporation of some quantitative information into whole cell TRN modeling.

1.	Freyre-González et al. Functional architecture of Escherichia coli: new insights provided by a natural decomposition approach. Genome Biol (2008) vol. 9 (10) pp. R154
2.	Klumpp and Hwa. Growth-rate-dependent partitioning of RNA polymerases in bacteria. Proc Natl Acad Sci USA (2008) vol. 105 (51) pp. 20245-50
3.	Barker et al. Mechanism of regulation of transcription initiation by ppGpp. II. Models for positive control based on properties of RNAP mutants and competition for RNAP. J Mol Biol (2001) vol. 305 (4) pp. 689-702
4.	Le Novère et al. The systems biology graphical notation. Nature biotechnology (2009) vol. 27 (8) pp. 735-41