Diterpenoid quinones from rosemary (Rosmarinus officinalis L.)

Two new abietane-type diterpenoid o-quinones, 7beta-methoxyabieta-8,13-diene-11,12-dione-(20,6beta)-olide (rosmaquinone A) (1) and 7alpha-methoxyabieta-8,13-diene-11,12-dione-(20,6beta)-olide (rosmaquinone B) (2), together with six known compounds were isolated from the aerial parts of Rosmarinus officinalis L. The structures of the new compounds were determined by extensive spectroscopic analysis, including IR, UV, HR-EIMS, 1D and 2D 400 MHz NMR data (1H, 13C NMR, DEPT, 1H-1H COSY, HMQC, HMBC and NOEs).     

Identification of Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as a binding protein for a 68-kDa <Emphasis Type=Italic>Bacillus thuringiensis</Emphasis> parasporal protein cytotoxic against leukaemic cells

Background  

Bacillus thuringiensis (Bt), an ubiquitous gram-positive spore-forming bacterium forms parasporal proteins during the stationary phase of its growth. Recent findings of selective human cancer cell-killing activity in non-insecticidal Bt isolates resulted in a new category of Bt parasporal protein called parasporin. However, little is known about the receptor molecules that bind parasporins and the mechanism of anti-cancer activity. A Malaysian Bt isolate, designated Bt18 produces parasporal protein that exhibit preferential cytotoxic activity for human leukaemic T cells (CEM-SS) but is non-cytotoxic to normal T cells or other cancer cell lines such as human cervical cancer (HeLa), human breast cancer (MCF-7) and colon cancer (HT-29) suggesting properties similar to parasporin. In this study we aim to identify the binding protein for Bt18 in human leukaemic T cells.     

Ranking and compacting binding segments of protein families using aligned pattern clusters

Background

Discovering sequence patterns with variation can unveil functions of a protein family that are important for drug discovery. Exploring protein families using existing methods such as multiple sequence alignment is computationally expensive, thus pattern search, called motif finding in Bioinformatics, is used. However, at present, combinatorial algorithms result in large sets of solutions, and probabilistic models require a richer representation of the amino acid associations. To overcome these shortcomings, we present a method for ranking and compacting these solutions in a new representation referred to as Aligned Pattern Clusters (APCs). To tackle the problem of a large solution set, our method reveals a reduced set of candidate solutions without losing any information. To address the problem of representation, our method captures the amino acid associations and conservations of the aligned patterns. Our algorithm renders a set of APCs in which a set of patterns is discovered, pruned, aligned, and synthesized from the input sequences of a protein family.

Results

Our algorithm identifies the binding or other functional segments and their embedded residues which are important drug targets from the cytochrome c and the ubiquitin protein families taken from Unitprot. The results are independently confirmed by pFam's multiple sequence alignment. For cytochrome c protein the number of resulting patterns with variations are reduced by 76.62% from the number of original patterns without variations. Furthermore, all of the top four candidate APCs correspond to the binding segments with one of each of their conserved amino acid as the binding residue. The discovered proximal APCs agree with pFam and PROSITE results. Surprisingly, the distal binding site discovered by our algorithm is not discovered by pFam nor PROSITE, but confirmed by the three-dimensional cytochrome c structure. When applied to the ubiquitin protein family, our results agree with pFam and reveals six of the seven Lysine binding residues as conserved aligned columns with entropy redundancy measure of 1.0.

Conclusion

The discovery, ranking, reduction, and representation of a set of patterns is important to avert time-consuming and expensive simulations and experimentations during proteomic study and drug discovery.

     

Simulated seasonal marine mining impacts on plankton

A computer simulated model is presented which predicts changes in phytoplankton populations from six-week mining operations conducted at different times of the year. Barely perceptable changes are predicted from the six-week May mining operation, while similar operations at other times of the year were predicted to have variable and sometimes long term impacts on the phytoplankton dynamics.     

Evidence for AMPK-dependent regulation of exocytosis of lipoproteins in a model liver cell line

5′-AMP-activated kinase (AMPK) plays a key role in the regulation of cellular lipid metabolism. The contribution of vesicular exocytosis to this regulation is not known. Accordingly, we studied the effects of AMPK on exocytosis and intracellular lipid content in a model liver cell line. Activation of AMPK by metformin or 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR) increased the rates of constitutive exocytosis by about 2-fold. Stimulation of exocytosis by AMPK occurred within minutes, and persisted after overnight exposure to metformin or AICAR. Activation of AMPK also increased the amount of triacylglycerol (TG) and apolipoprotein B (apoB) secreted from lipid-loaded cells. These effects were accompanied by a decrease in the intracellular lipid content indicating that exocytosis of lipoproteins was involved in these lipid-lowering effects. While AMPK increased the rates of fatty acid oxidation (FAO), the lipid-lowering effects were quantitatively significant even after inhibition of FAO with R-etomoxir. These results suggest that hepatic AMPK stimulates constitutive exocytosis of lipoproteins, which may function in parallel with FAO to regulate intracellular lipid content.     

Inhibitory effects of biochanin A on titanium particle‐induced osteoclast activation and inflammatory bone resorption via NF‐κB and MAPK pathways

Revision operations have become a new issue after successful artificial joint replacements, and periprosthetic osteolysis leading to prosthetic loosening is the main cause of why the overactivation of osteoclasts (OCs) plays an important role. The effect of biochanin A (BCA) has been examined in osteoporosis, but no study on the role of BCA in prosthetic loosening osteolysis has been conducted yet. In this study, we utilised enzyme‐linked immunosorbent assay, computed tomography imaging, and histological analysis. Results showed that BCA downregulated the secretion levels of tumor necrosis factor‐α, interleukin‐1α (IL‐1α), and IL‐1β to suppress inflammatory responses. The secretion levels of receptor‐activated nuclear factor‐κB ligand, CTX‐1, and osteoclast‐associated receptor as well as Ti‐induced osteolysis were also reduced. BCA effectively inhibited osteoclastogenesis and suppressed hydroxyapatite resorption by downregulating OC‐related genes in vitro. Analysis of mechanisms indicated that BCA inhibited the signalling pathways of mitogen‐activated protein kinase (P38, extracellular signal‐regulated kinase, and c‐JUN N‐terminal kinase) and nuclear factor‐κB (inhibitor κB‐α and P65), thereby downregulating the expression of nuclear factor of activated T cell 1 and c‐Fos. In conclusion, BCA may be an alternative choice for the prevention of prosthetic loosening caused by OCs.     

Effect of environmental,economic and health factors on CoVid-19 transmission

The severe acute respiratory syndrome (SARS) is affected by meteorological parameters such as temperature and humidity. It is also observed that people having asthma are at risk for SARS. Therefore, it is of interest to report the effect of environmental, economic, and health factors on the spread of CoVid-19. We used data reporting CoVid-19 cases from 24 cities in eight different countries for this analysis. Data was analyzed using multiple linear regressions between these parameters. Data shows that temperature has effects on CoVid-19. A one-degree rise in temperature causes a -0.19 decrease in CoVid-19 cases per million people (log natural value per million populations). The effect of humidity is not significant at a p value of 0.26. Moreover, one-unit increase in asthma and GDP cases per million people show 0.06 and 0.46 increases in CoVid-19 cases, respectively.     

Stability in a Plankton Model

A technique for analyzing the stability of a phytoplankton-nutrient interaction model is described which may be applicable to a broader range of models. It is shown that periodicity of solutions in a differential equation does not imply the same for the corresponding difference equation model.     

Atypical B cells are part of an alternative lineage of B cells that participates in responses to vaccination and infection in humans

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