Interhemispheric Inhibition during Mental Actions of Different Complexity

Several investigations suggest that actual and mental actions trigger similar neural substrates. Yet, neurophysiological evidences on the nature of interhemispheric interactions during mental movements are still meagre. Here, we asked whether the content of mental images, investigated by task complexity, is finely represented in the inhibitory interactions between the two primary motor cortices (M1s). Subjects’ left M1 was stimulated by means of transcranial magnetic stimulation (TMS) while they were performing actual or mental movements of increasing complexity with their right hand and exerting a maximum isometric force with their left thumb and index. Thus, we simultaneously assessed the corticospinal excitability in the right opponent pollicis muscle (OP) and the ipsilateral silent period (iSP) in the left OP during actual and mental movements. Corticospinal excitability in right OP increased during actual and mental movements, but task complexity-dependent changes were only observed during actual movements. Interhemispheric motor inhibition in the left OP was similarly modulated by task complexity in both mental and actual movements. Precisely, the duration and the area of the iSP increased with task complexity in both movement conditions. Our findings suggest that mental and actual movements share similar inhibitory neural circuits between the two homologous primary motor cortex areas.     

Quantitative Renal Perfusion Measurements in a Rat Model of Acute Kidney Injury at 3T: Testing Inter- and Intramethodical Significance of ASL and DCE-MRI

Objectives

To establish arterial spin labelling (ASL) for quantitative renal perfusion measurements in a rat model at 3 Tesla and to test the diagnostic significance of ASL and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in a model of acute kidney injury (AKI).

Material and Methods

ASL and DCE-MRI were consecutively employed on six Lewis rats, five of which had a unilateral ischaemic AKI. All measurements in this study were performed on a 3 Tesla MR scanner using a FAIR True-FISP approach and a TWIST sequence for ASL and DCE-MRI, respectively. Perfusion maps were calculated for both methods and the cortical perfusion of healthy and diseased kidneys was inter- and intramethodically compared using a region-of-interest based analysis.

Results/Significance

Both methods produce significantly different values for the healthy and the diseased kidneys (P<0.01). The mean difference was 147±47 ml/100 g/min and 141±46 ml/100 g/min for ASL and DCE-MRI, respectively. ASL measurements yielded a mean cortical perfusion of 416±124 ml/100 g/min for the healthy and 316±102 ml/100 g/min for the diseased kidneys. The DCE-MRI values were systematically higher and the mean cortical renal blood flow (RBF) was found to be 542±85 ml/100 g/min (healthy) and 407±119 ml/100 g/min (AKI).

Conclusion

Both methods are equally able to detect abnormal perfusion in diseased (AKI) kidneys. This shows that ASL is a capable alternative to DCE-MRI regarding the detection of abnormal renal blood flow. Regarding absolute perfusion values, nontrivial differences and variations remain when comparing the two methods.     

Bayesian clustering analyses for genetic assignment and study of hybridization in oaks: effects of asymmetric phylogenies and asymmetric sampling schemes

Bayesian clustering methods have been widely used for studying species delimitation and genetic introgression. In order to test the effect of phylogenetic relationships and sampling scheme on the inferred clustering solution and on the performance of Bayesian clustering analysis, I simulated genotypes of the interfertile oak species Quercus robur, Quercus petraea, and Quercus pubescens and I run analyses using two popular software programs, STRUCTURE and BAPS. First, based on purebred simulations, I compared clustering solutions resulting from different sample size configurations. While clustering solution generally reflected the taxonomic relationships when equal samples of each species were included, spurious partition was inferred by STRUCTURE when some species were represented by larger and others by smaller samples. In very unbalanced configurations, STRUCTURE failed to identify the three species, even if three subpopulations were assumed. By contrast, BAPS could properly identify the three species under any sampling scheme. Second, based on simulations of purebreds and hybrids, I tested the performance of individual assignments with variable number of loci. This analysis showed that STRUCTURE can detect introgressed individuals more efficiently than BAPS. However, BAPS could assign purebreds more efficiently with a lower number of loci. Method performance also depended on phylogenetic relationships. In the case of Q. petraea, Q. pubescens, and their hybrids, method performance was lower due to their phylogenetic affinity. Inclusion of three instead of two species into the analysis led to reduction of performance, and to misclassification of hybrids, which often reflected the phylogenetic affinity between Q. petraea and Q. pubescens.     

A Novel MVA Vectored Chikungunya Virus Vaccine Elicits Protective Immunity in Mice

Background

Chikungunya virus (CHIKV) is a re-emerging arbovirus associated with febrile illness often accompanied by rash and arthralgia that may persist for several years. Outbreaks are associated with high morbidity and create a public health challenge for countries affected. Recent outbreaks have occurred in both Europe and the Americas, suggesting CHIKV may continue to spread. Despite the sustained threat of the virus, there is no approved vaccine or antiviral therapy against CHIKV. Therefore, it is critical to develop a vaccine that is both well tolerated and highly protective.

Methodology/Principal Findings

In this study, we describe the construction and characterization of a modified Vaccinia virus Ankara (MVA) virus expressing CHIKV E3 and E2 proteins (MVA-CHIK) that protected several mouse models from challenge with CHIKV. In particular, BALB/c mice were completely protected against viremia upon challenge with CHIKV after two doses of MVA-CHIK. Additionally, A129 mice (deficient in IFNα/β) were protected from viremia, footpad swelling, and mortality. While high anti-virus antibodies were elicited, low or undetectable levels of neutralizing antibodies were produced in both mouse models. However, passive transfer of MVA-CHIK immune serum to naïve mice did not protect against mortality, suggesting that antibodies may not be the main effectors of protection afforded by MVA-CHIK. Furthermore, depletion of CD4⁺, but not CD8⁺ T-cells from vaccinated mice resulted in 100% mortality, implicating the indispensable role of CD4⁺ T-cells in the protection afforded by MVA-CHIK.

Conclusions/Significance

The results presented herein demonstrate the potential of MVA to effectively express CHIKV E3-E2 proteins and generate protective immune responses. Our findings challenge the assumption that only neutralizing antibodies are effective in providing protection against CHIKV, and provides a framework for the development of novel, more effective vaccine strategies to combat CHIKV.     

Role of protein kinase C delta in curcumin-induced antioxidant response element-mediated gene expression in human monocytes

The Nrf2/antioxidant response element (ARE) signaling pathway plays a key role in activating cellular antioxidants, including heme oxygenase-1 (HO-1), NADPH quinone oxidoreductase-1 (NQO1), and glutathione. Protein kinase C (PKC) may also regulate these antioxidants, as PKC phosphorylates Nrf2 in vitro. This study examined the role of PKC in ARE-mediated gene regulation in human monocytes by curcumin, a potent inducer of the Nrf2/ARE pathway. Curcumin increased HO-1 and glutamyl cysteine ligase modulator (GCLM) expression and stimulated Nrf2 binding to the ARE. Curcumin also rapidly stimulated PKC phosphorylation and Ro-31-8220, a pan-PKC inhibitor, decreased curcumin-induced GCLM and HO-1 mRNA expression and ARE binding. Rottlerin (a PKC delta inhibitor) and PKC delta antisense oligonucleotides significantly inhibited curcumin-induced GCLM and HO-1 mRNA expression and ARE binding. Furthermore, a p38 MAP kinase inhibitor reduced GCLM and HO-1 expression and rottlerin inhibited curcumin-induced p38 phosphorylation. In summary, curcumin activates ARE-mediated gene expression in human monocytes via PKC delta, upstream of p38 and Nrf2.     

Simple sleep questions can predict 12-year mortality in a rural population

Sleep and Biological Rhythms - There is apt evidence in favor of a significant association between sleep and mortality. So far, most studies examine sleep problems using comprehensive,...     

Synthesis of tetrazole analogs of gamma- and delta-amino acids.

N-benzyloxycarbonyl-protected alpha- or beta-amino alcohols, easily prepared from alpha- and beta-amino acids, were converted into aldehydes and directly reacted with (triphenyl phosphoranylidene) acetonitrile, leading to unsaturated nitriles. Treatment of nitriles with NaN(3) and ZnBr(2) produced unsaturated gamma- and delta-amino tetrazoles, which were deprotected and converted to the corresponding saturated compounds by catalytic hydrogenation. For the case of delta-amino tetrazole, the methylation of the acidic moiety occurred after treatment with CH(2)N(2), leading to the N(1)- and N(2)-methylated constitutional isomers, which were separated by column chromatography and hydrogenated.     

Structural characterisation of oligosaccharides obtained by Fenton-type radical depolymerisation of dermatan sulfate

The contamination of heparin in 2008 brought to the attention of health authorities an urgent need for structural characterisation of low molecular weight heparins and other glycosaminoglycans (GAGs) intended for clinical applications. Potentially harmful compounds can be introduced into these preparations as contaminants of the original material or as by-products of the depolymerisation process. Radical depolymerisation is one of the methods used for fractionations of GAGs. We report here on the results of the Fenton-type radical depolymerisation of dermatan sulfate (DS) by hydrogen peroxide in the presence of Cu²⁺ cations. A low molecular fraction of the reaction mixture was investigated by a combination of 2D ¹H,¹³C HSQC, 2D HSQC-TOCSY and 2D HMBC experiments at 800 MHz. The analysis of the spectra revealed the formation of oligosaccharides with structures corresponding to the native DS sequence and containing almost exclusively GalNAc4S as the reducing end monosaccharide. In addition, oligosaccharides containing a C-4 sulfated N-acetylgalactosaminic acid in place of the reducing end GalNAc4S were identified. This open chain monosaccharide represents a non-native DS structure.