Stochastic model for nucleosome sliding in the presence of DNA ligands

Heat-induced mobility of nucleosomes along DNA is an experimentally well-studied phenomenon. A recent experiment shows that the repositioning is modified in the presence of minor-groove binding DNA ligands. We present here a stochastic three-state model for the diffusion of a nucleosome along DNA in the presence of such ligands. It allows us to describe the dynamics and the steady state of such a motion analytically. The analytical results are in excellent agreement with numerical simulations of this stochastic process.With this model, we study the response of a nucleosome to an external force and how it is affected by the presence of ligands.Comment: 10 pages, 8 figures, submitted to Eur. Phys. J.

Hand use predicts the structure of representations in sensorimotor cortex.

Fine finger movements are controlled by the population activity of neurons in the hand area of primary motor cortex. Experiments using microstimulation and single-neuron electrophysiology suggest that this area represents coordinated multi-joint, rather than single-finger movements. However, the principle by which these representations are organized remains unclear. We analyzed activity patterns during individuated finger movements using functional magnetic resonance imaging (fMRI). Although the spatial layout of finger-specific activity patterns was variable across participants, the relative similarity between any pair of activity patterns was well preserved. This invariant organization was better explained by the correlation structure of everyday hand movements than by correlated muscle activity. This also generalized to an experiment using complex multi-finger movements. Finally, the organizational structure correlated with patterns of involuntary co-contracted finger movements for high-force presses. Together, our results suggest that hand use shapes the relative arrangement of finger-specific activity patterns in sensory-motor cortex

The combination effects of trivalent gold ions and gold nanoparticles with different antibiotics against resistant Pseudomonas aeruginosa

Despite much success in drug design and development, Pseudomonas aeruginosa is still considered as one of the most problematic bacteria due to its ability to develop mutational resistance against a variety of antibiotics. In search for new strategies to enhance antibacterial activity of antibiotics, in this work, the combination effect of gold materials including trivalent gold ions (Au ) and gold nanoparticles (Au NPs) with 14 different antibiotics was investigated against the clinical isolates of P. aeruginosa, Staphylococcus aureus and Escherichia coli. Disk diffusion assay was carried out, and test strains were treated with the sub-inhibitory contents of gold nanomaterial. Results showed that Au NPs did not increase the antibacterial effect of antibiotics at tested concentration (40 μg/disc). However, the susceptibility of resistant P. aeruginosa increased in the presence of Au and methicillin, erythromycin, vancomycin, penicillin G, clindamycin and nalidixic acid, up to 147 %. As an individual experiment, the same group of antibiotics was tested for their activity against clinical isolates of S. aureus, E. coli and a different resistant strain of P. aeruginosa in the presence of sub-inhibitory contents of Au , where Au increased the susceptibility of test strains to methicillin, erythromycin, vancomycin, penicillin G, clindamycin and nalidixic acid. Our finding suggested that using the combination of sub-inhibitory concentrations of Au and methicillin, erythromycin, nalidixic acid or vancomycin may be a promising new strategy for the treatment of highly resistant P. aeruginosa infections

Prediction of second neurological attack in patients with clinically isolated syndrome using support vector machines

The aim of this study is to predict the conversion from clinically isolated syndrome to clinically definite multiple sclerosis using support vector machines. The two groups of converters and non-converters are classified using features that were calculated from baseline data of 73 patients. The data consists of standard magnetic resonance images, binary lesion masks, and clinical and demographic information. 15 features were calculated and all combinations of them were iteratively tested for their predictive capacity using polynomial kernels and radial basis functions with leave-one-out cross-validation. The accuracy of this prediction is up to 86.4% with a sensitivity and specificity in the same range indicating that this is a feasible approach for the prediction of a second clinical attack in patients with clinically isolated syndromes, and that the chosen features are appropriate. The two features gender and location of onset lesions have been used in all feature combinations leading to a high accuracy suggesting that they are highly predictive. However, it is necessary to add supporting features to maximise the accuracy. © 2013 IEEE

The effect of statin therapy on endoplasmic reticulum stress

The endoplasmic reticulum (ER) is critical in protein processing and particularly in ensuring that proteins undergo their correct folding to exert their functionality. What is becoming increasingly clear is that the ER may undergo increasing stress brought about by nutrient deprivation, hypoxia, oxidized lipids, point mutations in secreted proteins, cellular differentiation or significant deviation from metabolic set points, and loss of Ca2+ homeostasis, with detrimental effects on ER-resident calcium-dependent chaperones, alone or in combination. This results in the unfolded protein response (UPR) that is a repair mechanism to limit the formation of newly damaged proteins until ER homeostasis is restored, though may result in increased cell death. ER stress has been shown to be implicated in a variety of diseases. Statins are well-known cholesterol-lowering drugs and have been extensively reported to possess beneficial cholesterol-independent effects in a variety of human diseases. This review focuses on the concept of ER stress, the underlying molecular mechanisms and their relationship to the pathophysiology and, finally, the role of statins in moderating ER stress and UPR

Effects of statins on brain tumors: a review.

Evidence from preclinical studies suggests that the competitive HMG-CoA reductase (HMGCR) inhibitors universally known as 'statins,' in addition to being powerful drugs that reduce cholesterol and improve cardiovascular risk, also have promising antitumor properties. Statins appear to enhance the treatment outcome of various cancers before and concurrent with other cancer treatment interventions. Glioblastoma multiforme (GBM), a particularly invasive cerebral tumor associated with high mortality, holds a poor median overall survival (OS) of around one year after surgical resection followed by concurrent radiation and chemotherapy. Recently, statins have increasingly appeared as potential adjuvant drugs for the treatment of GBM because of their potential to suppress cell growth, survival, migration, metastasis, inflammation, angiogenesis, and promote apoptosis during both in vitro and in vivo studies. However, the clinical outcomes of statins on the survival of patients with GBM are still controversial. This study aims to review and address some of the documented effects of statin drugs when focusing entirely on cancer treatment, especially GBM, including concurrent statin therapy with chemotherapeutic agents

Immune modulation by curcumin: The role of interleukin-10.

Cytokines are small secreted proteins released by different types of cells with specific effects on cellular signaling and communication via binding to their receptors on the cell surface. IL-10 is known to be a pleiotropic and potent anti-inflammatory and immunosuppressive cytokine that is produced by both innate and adaptive immunity cells including dendritic cells, macrophages, mast cells, natural killer cells, eosinophils, neutrophils, B cells, CD8+ T cells, and TH1, TH2, and TH17 and regulatory T cells. Both direct and indirect activation of the stress axis promotes IL-10 secretion. IL-10 deregulation plays a role in the development of a large number of inflammatory diseases such as neuropathic pain, Parkinson's disease, Alzheimer's disease, osteoarthritis, rheumatoid arthritis, psoriasis, systemic lupus erythematosus, type 1 diabetes, inflammatory bowel disease, and allergy. Curcumin is a natural anti-inflammatory compound able to induce the expression and production of IL-10 and enhancing its action on a large number of tissues. In vitro and in pre-clinical models curcumin is able to modulate the disease pathophysiology of conditions such as pain and neurodegenerative diseases, bowel inflammation, and allergy, but also of infections and cancer through its effect on IL-10 secretion. In humans, at least one part of the positive effects of curcumin on health could be related to its ability to enhance IL-10 -mediated effects