The frequency of CD127low expressing CD4+CD25high T regulatory cells is inversely correlated with human T lymphotrophic virus type-1 (HTLV-1) proviral load in HTLV-1-infection and HTLV-1-associated myelopathy/tropical spastic paraparesis

<p>Abstract</p> <p>Background</p> <p>CD4⁺CD25^highregulatory T (T_Reg) cells modulate antigen-specific T cell responses, and can suppress anti-viral immunity. In HTLV-1 infection, a selective decrease in the function of T_Regcell mediated HTLV-1-tax inhibition of FOXP3 expression has been described. The purpose of this study was to assess the frequency and phenotype of T_Regcells in HTLV-1 asymptomatic carriers and in HTLV-1-associated neurological disease (HAM/TSP) patients, and to correlate with measures of T cell activation.</p> <p>Results</p> <p>We were able to confirm that HTLV-I drives activation, spontaneous IFNγ production, and proliferation of CD4+ T cells. We also observed a significantly lower proportion of CTLA-4⁺T_Regcells (CD4⁺CD25^highT cells) in subjects with HAM/TSP patients compared to healthy controls. Ki-67 expression was negatively correlated to the frequency of CTLA-4⁺T_Regcells in HAM/TSP only, although Ki-67 expression was inversely correlated with the percentage of CD127^lowT_Regcells in healthy control subjects. Finally, the proportion of CD127^lowT_Regcells correlated inversely with HTLV-1 proviral load.</p> <p>Conclusion</p> <p>Taken together, the results suggest that T_Regcells may be subverted in HAM/TSP patients, which could explain the marked cellular activation, spontaneous cytokine production, and proliferation of CD4⁺T cells, in particular those expressing the CD25^highCD127^lowphenotype. T_Regcells represent a potential target for therapeutic intervention for patients with HTLV-1-related neurological diseases.</p

Effects of Transcranial Direct Current Stimulation (tDCS) Over the Frontal Polar Area on Motor and Executive Functions in Parkinson’s Disease; A Pilot Study

Parkinson’s disease (PD) is a neurodegenerative disorder with motor and non-motor symptoms due to degeneration of dopaminergic neurons. The current pharmacological treatments induce complications associated with long-term use. However, current stimulation techniques for PD treatment, such as deep brain stimulation (DBS), are too invasive. In this context, non-invasive brain stimulation including transcranial direct current stimulation (tDCS) may be a safe and effective alternative treatment for PD. We previously reported that anodal tDCS over the frontal polar area (FPA) improved motor functions in heathy subjects. Therefore, in the present study, effects of tDCS over the FPA on motor and cognitive functions of PD patients were analyzed. Nine PD patients (3 men and 6 women) participated in this cross over study with three tDCS protocols; anodal, cathodal or sham tDCS over the FPA. Each tDCS protocol was applied for 1 week (5 times/week). Before and after each protocol, motor and cognitive functions of the patients were assessed using Unified PD Rating Scale [UPDRS (part III: motor examination)], Fugl Meyer Assessment set (FMA), Simple Test for Evaluating hand Function (STEF) and Trail Making Test A (TMT-A). The results indicated that anodal stimulation significantly decreased scores of motor disability in UPDRS-III compared with sham and cathodal stimulation, and significantly increased scores of motor functions in FMA compared with sham stimulation. Furthermore, anodal stimulation significantly decreased time to complete a motor task requiring high dexterity in STEF compared with those requiring low and medium levels of dexterity. In addition, anodal stimulation significantly decreased time to complete the TMT-A task, which requires executive functions, compared with sham stimulation. To the best of our knowledge, this is the first clinical research reporting that tDCS over the FPA successfully improved the motor and non-motor functions in PD patients. These findings suggest that tDCS over the FPA might be a useful alternative for the treatment of PD patients

A Model for the Development of the Rhizobial and Arbuscular Mycorrhizal Symbioses in Legumes and Its Use to Understand the Roles of Ethylene in the Establishment of these two Symbioses

We propose a model depicting the development of nodulation and arbuscular mycorrhizae. Both processes are dissected into many steps, using Pisum sativum L. nodulation mutants as a guideline. For nodulation, we distinguish two main developmental programs, one epidermal and one cortical. Whereas Nod factors alone affect the cortical program, bacteria are required to trigger the epidermal events. We propose that the two programs of the rhizobial symbiosis evolved separately and that, over time, they came to function together. The distinction between these two programs does not exist for arbuscular mycorrhizae development despite events occurring in both root tissues. Mutations that affect both symbioses are restricted to the epidermal program. We propose here sites of action and potential roles for ethylene during the formation of the two symbioses with a specific hypothesis for nodule organogenesis. Assuming the epidermis does not make ethylene, the microsymbionts probably first encounter a regulatory level of ethylene at the epidermis–outermost cortical cell layer interface. Depending on the hormone concentrations there, infection will either progress or be blocked. In the former case, ethylene affects the cortex cytoskeleton, allowing reorganization that facilitates infection; in the latter case, ethylene acts on several enzymes that interfere with infection thread growth, causing it to abort. Throughout this review, the difficulty of generalizing the roles of ethylene is emphasized and numerous examples are given to demonstrate the diversity that exists in plants

Silicic volcanism on Mars evidenced by tridymite in high-SiO2 sedimentary rock at Gale crater

Tridymite, a SiO2 mineral that crystallizes at low pressures and high temperatures (>870 °C) from high-SiO2 materials, was detected at high concentrations in a sedimentary mudstone in Gale crater, Mars. Mineralogy and abundance were determined by X-ray diffraction using the Chemistry and Mineralogy instrument on the Mars Science Laboratory rover Curiosity. Terrestrial tridymite is commonly associated with silicic volcanism where high temperatures and high-silica magmas prevail, so this occurrence is the first in situ mineralogical evidence for martian silicic volcanism. Multistep processes, including high-temperature alteration of silica-rich residues of acid sulfate leaching, are alternate formation pathways for martian tridymite but are less likely. The unexpected discovery of tridymite is further evidence of the complexity of igneous petrogenesis on Mars, with igneous evolution to high-SiO2 compositions

Early pregnancy peripheral blood gene expression and risk of preterm delivery: a nested case control study

<p>Abstract</p> <p>Background</p> <p>Preterm delivery (PTD) is a significant public health problem associated with greater risk of mortality and morbidity in infants and mothers. Pathophysiologic processes that may lead to PTD start early in pregnancy. We investigated early pregnancy peripheral blood global gene expression and PTD risk.</p> <p>Methods</p> <p>As part of a prospective study, ribonucleic acid was extracted from blood samples (collected at 16 weeks gestational age) from 14 women who had PTD (cases) and 16 women who delivered at term (controls). Gene expressions were measured using the GeneChip^®Human Genome U133 Plus 2.0 Array. Student's T-test and fold change analysis were used to identify differentially expressed genes. We used hierarchical clustering and principle components analysis to characterize signature gene expression patterns among cases and controls. Pathway and promoter sequence analyses were used to investigate functions and functional relationships as well as regulatory regions of differentially expressed genes.</p> <p>Results</p> <p>A total of 209 genes, including potential candidate genes (e.g. PTGDS, prostaglandin D2 synthase 21 kDa), were differentially expressed. A set of these genes achieved accurate pre-diagnostic separation of cases and controls. These genes participate in functions related to immune system and inflammation, organ development, metabolism (lipid, carbohydrate and amino acid) and cell signaling. Binding sites of putative transcription factors such as EGR1 (early growth response 1), TFAP2A (transcription factor AP2A), Sp1 (specificity protein 1) and Sp3 (specificity protein 3) were over represented in promoter regions of differentially expressed genes. Real-time PCR confirmed microarray expression measurements of selected genes.</p> <p>Conclusions</p> <p>PTD is associated with maternal early pregnancy peripheral blood gene expression changes. Maternal early pregnancy peripheral blood gene expression patterns may be useful for better understanding of PTD pathophysiology and PTD risk prediction.</p

A Sex-Specific Association between a 15q25 Variant and Upper Aerodigestive Tract Cancers

Sequence variants located at 15q25 have been associated with lung cancer and propensity to smoke. We recently reported an association between rs16969968 and risk of upper aerodigestive tract (UADT) cancers (oral cavity, oropharynx, hypopharynx, larynx and esophagus) in women (odds ratio (OR) =1.24, P=0.003) with little effect in men (OR=1.04, P=0.35)