Fungal rDNA signatures in coronary atherosclerotic plaques

Bacterial DNA has been found in coronary plaques and it has therefore been concluded that bacteria may play a role as trigger factors in the chronic inflammatory process underlying coronary atherosclerosis. However, the microbial spectrum is complex and it is not known whether microorganisms other than bacteria are involved in coronary disease. Fungal 18S rDNA signatures were systematically investigated in atherosclerotic tissue obtained through catheter-based atherectomy of 38 patients and controls (unaffected coronary arteries) using clone libraries, denaturating gradient gel analysis (DGGE), in situ hybridization and fluorescence in situ hybridization (FISH). Fungal DNA was found in 35 of 38 (92.11%) coronary heart disease patients by either polymerase chain reaction (PCR) with universal primers or in situ hybridization analysis (n = 5), but not in any control sample. In a clone library with more than 350 sequenced clones from pooled patient DNA, an overall richness of 19 different fungal phylotypes could be observed. Fungal profiles of coronary heart disease patients obtained by DGGE analysis showed a median richness of fungal species of 5 (range from 2 to 9) with a high interindividual variability (mean similarity 18.83%). For the first time, the presence of fungal components in atherosclerotic plaques has been demonstrated. Coronary atheromatous plaques harbour diverse and variable fungal communities suggesting a polymicrobial contribution to the chronic inflammatory aetiology.     

Role of Organic Amendments to Mitigate Cd Toxicity and Its Assimilation in <i>Triticum aestivum</i> L.

In soil biota, higher and enduring concentration of heavy metals like cadmium (Cd) is hazardous and associated with great loss in growth, yield, and quality parameters of most of the crop plants. Recently, in-situ applications of eco-friendly stabilizing agents in the form of organic modifications have been utilized to mitigate the adverse effects of Cd-toxicity. This controlled experiment was laid down to appraise the imprints of various applied organic amendments namely poultry manure (PM), farmyard manure (FYM), and sugarcane press mud (PS) to immobilize Cd in polluted soil. Moreover, phytoavailability of Cd in wheat was also accessed under an alkaline environment. Results revealed that the addition of FYM (5–10 ton ha^-1 ) in Cd-contaminated soil significantly increased germination rate, leaf chlorophyll content, plant height, spike length, biological and grain yield amongst all applied organic amendments. Moreover, the addition of FYM (5–10 ton ha^-1 ) also reduced the phytoavailability of Cd by 73–85% in the roots, 57–83% in the shoots, and 81–90% in grains of wheat crop. Thus, it is affirmed that incorporation of FYM (5–10 ton ha^-1 ) performed better to enhance wheat growth and yield by remediating Cd. Thus, the application of FYM (5–10 ton ha^-1 ) reduced the toxicity induced by Cd to plants by declining its uptake and translocation as compared to all other applied organic amendments to immobilize Cd under sandy alkaline polluted soil.     

Upregulation of CD271 transcriptome in breast cancer promotes cell survival via NFκB pathway

Molecular Biology Reports - Biological treatment of many cancers currently targets membrane bound receptors located on a cell surface. We are in a great to need identify novel membrane proteins...     

Hybridization and pre-zygotic reproductive barriers in Plasmodium

Sexual reproduction is an obligate step in the life cycle of many parasites, including the causative agents of malaria (Plasmodium). Mixed-species infections are common in nature and consequently, interactions between heterospecific gametes occur. Given the importance of managing gene flow across parasite populations, remarkably little is understood about how reproductive isolation between species is maintained. We use the rodent malaria parasites P. berghei and P. yoelii to investigate the ecology of mixed-species mating groups, identify proteins involved in pre-zygotic barriers, and examine their evolution. Specifically, we show that (i) hybridization occurs, but at low frequency; (ii) hybridization reaches high levels when female gametes lack the surface proteins P230 or P48/45, demonstrating that these proteins are key for pre-zygotic reproductive isolation; (iii) asymmetric reproductive interference occurs, where the fertility of P. berghei gametes is reduced in the presence of P. yoelii and (iv) as expected for gamete recognition proteins, strong positive selection acts on a region of P230 and P47 (P48/45 paralogue). P230 and P48/45 are leading candidates for interventions to block malaria transmission. Our results suggest that depending on the viability of hybrids, applying such interventions to populations where mixed-species infections occur could either facilitate or hinder malaria control.     

Comprehensive Annotation of Physcomitrella patens Small RNA Loci Reveals That the Heterochromatic Short Interfering RNA Pathway Is Largely Conserved in Land Plants

Many plant small RNAs are sequence-specific negative regulators of target mRNAs and/or chromatin. In angiosperms, the two most abundant endogenous small RNA populations are usually 21-nucleotide microRNAs (miRNAs) and 24-nucleotide heterochromatic short interfering RNAs (siRNAs). Heterochromatic siRNAs are derived from repetitive regions and reinforce DNA methylation at targeted loci. The existence and extent of heterochromatic siRNAs in other land plant lineages has been unclear. Using small RNA-sequencing (RNA-seq) of the moss Physcomitrella patens, we identified 1090 loci that produce mostly 23- to 24-nucleotide siRNAs. These loci are mostly in intergenic regions with dense DNA methylation. Accumulation of siRNAs from these loci depends upon P. patens homologs of DICER-LIKE3 (DCL3), RNA-DEPENDENT RNA POLYMERASE2, and the largest subunit of DNA-DEPENDENT RNA POLYMERASE IV, with the largest subunit of a Pol V homolog contributing to expression at a smaller subset of the loci. A MINIMAL DICER-LIKE (mDCL) gene, which lacks the N-terminal helicase domain typical of DCL proteins, is specifically required for 23-nucleotide siRNA accumulation. We conclude that heterochromatic siRNAs, and their biogenesis pathways, are largely identical between angiosperms and P. patens, with the notable exception of the P. patens-specific use of mDCL to produce 23-nucleotide siRNAs.     

Cost-effectiveness of second-line antihyperglycemic therapy in patients with type 2 diabetes mellitus inadequately controlled on metformin

Background:

Metformin is widely accepted as first-line pharmacotherapy for patients with type 2 diabetes mellitus when glycemic control cannot be achieved by lifestyle interventions alone. However, uncertainty exists regarding the optimal second-line therapy for patients whose diabetes is inadequately controlled by metformin monotherapy. Increased use of newer, more costly agents, along with the rising incidence of type 2 diabetes, carries significant budgetary implications for health care systems. We conducted this analysis to determine the relative costs, benefits and cost-effectiveness of options for second-line treatment of type 2 diabetes.

Methods:

We used the United Kingdom Prospective Diabetes Study Outcomes Model to forecast diabetes-related complications, quality-adjusted life-years and costs of alternative second-line therapies available in Canada for adults with type 2 diabetes inadequately controlled by metformin. We obtained clinical data from a systematic review and mixed treatment comparison meta-analysis, and we obtained information on costs and utilities from published sources. We performed extensive sensitivity analyses to test the robustness of results to variation in inputs and assumptions.

Results:

Sulphonylureas, when added to metformin, were associated with the most favourable cost-effectiveness estimate, with an incremental cost of $12 757 per quality-adjusted life-year gained, relative to continued metformin monotherapy. Treatment with other agents, including thiazolidinediones and dipeptidyl peptidase-4 inhibitors, had unfavourable cost-effectiveness estimates compared with sulphonylureas. These results were robust to extensive sensitivity analyses.

Interpretation:

For most patients with type 2 diabetes that is inadequately controlled with metformin monotherapy, the addition of a sulphonylurea represents the most cost-effective second-line therapy.Type 2 diabetes mellitus is a progressive disease typically treated in a stepwise fashion, beginning with lifestyle modification, followed by the addition of one or more oral antihyperglycemic drugs and, finally, administration of exogenous insulin. Metformin monotherapy is widely recommended as first-line pharmacotherapy,^1,2 given its favourable effects in controlling blood glucose and body weight, low risk of hypoglycemia, low cost and association with mortality benefit.³ Multiple second-line treatment strategies are available for patients in whom glycemic control has become inadequate. These approaches are typically used in addition to continued metformin therapy.^4,5 Numerous second-line agents are available in Canada, including older oral agents, such as sulphonylureas, and more recently introduced agents, such as thiazolidinediones and dipeptidyl peptidase-4 inhibitors.The large number of choices for second-line therapy has increased uncertainty regarding the optimal treatment pathway. Recent clinical practice guidelines, including those produced by the Canadian Diabetes Association¹ and by the American Diabetes Association and the European Association for the Study of Diabetes,² have suggested selecting from among several agents on the basis of their respective advantages and disadvantages. There has been a considerable increase in the use of newer, more costly oral antihyperglycemic agents, which has resulted in substantial increases in associated costs to patients and both public and private drug plans in Canada.⁴ In light of current therapeutic uncertainty, the large proportion of patients requiring second-line therapy over time^3,6 and the increasing prevalence of type 2 diabetes,⁷ the utilization and cost of second-line therapy are likely to continue to grow.Informed decisions regarding optimal prescribing and reimbursement of second-line agents by public and private health care payers requires information about clinical benefits, costs and cost-effectiveness.⁸ As part of a larger initiative to determine optimal prescribing of antihyperglycemic agents, we sought to determine the incremental cost-effectiveness of treatment with alternative second-line agents added to metformin in patients with type 2 diabetes no longer adequately controlled by metformin monotherapy.     

Dupuytren's: a systems biology disease

Dupuytren's disease (DD) is an ill-defined fibroproliferative disorder of the palm of the hands leading to digital contracture. DD commonly occurs in individuals of northern European extraction. Cellular components and processes associated with DD pathogenesis include altered gene and protein expression of cytokines, growth factors, adhesion molecules, and extracellular matrix components. Histology has shown increased but varying levels of particular types of collagen, myofibroblasts and myoglobin proteins in DD tissue. Free radicals and localised ischaemia have been suggested to trigger the proliferation of DD tissue. Although the existing available biological information on DD may contain potentially valuable (though largely uninterpreted) information, the precise aetiology of DD remains unknown. Systems biology combines mechanistic modelling with quantitative experimentation in studies of networks and better understanding of the interaction of multiple components in disease processes. Adopting systems biology may be the ideal approach for future research in order to improve understanding of complex diseases of multifactorial origin. In this review, we propose that DD is a disease of several networks rather than of a single gene, and show that this accounts for the experimental observations obtained to date from a variety of sources. We outline how DD may be investigated more effectively by employing a systems biology approach that considers the disease network as a whole rather than focusing on any specific single molecule.     

Removal of chromium on Polyalthia longifolia leaves biomass

Adsorption is an environmental friendly process for removal and/or recovery of heavy metals from wastewater. In recent years, it has been substantiated as a popular technique to treat industrial waste effluents, with significant advantages. In this work, batchwise removal of chromium (III) ions from water by Polyalthia longifolia leaves was studied as a function of adsorbent dose, pH, contact time, and agitation speed. Surface characteristics of the leaves were evaluated by recording IR spectra. The Langmuir, Freundlich, and Temkin adsorption isotherms were employed to explain the sorption process. It was found that one gram of leaves can remove 1.87 mg of trivalent chromium when working at pH 3.0. It has been concluded that Polyalthia longifolia leaves can be used as cost-effective and benign adsorbents for removal of Cr(III) ions from wastewater.