Long-Range Superharmonic Josephson Current

We consider a long superconductor-ferromagnet-superconductor junction with one spin-active region. It is shown that an \textit{odd} number of Cooper pairs cannot have a long-range propagation when there is \textit{only one} spin-active region. When temperature is much lower than the Thouless energy, the coherent transport of \textit{two} Cooper pairs becomes dominant process and the \textit{superharmonic} current-phase relation is obtained ($I\propto\sin2\phi$).Comment: 4 pages, 3 figure

Modelling mitochondrial dysfunction in mice

Summary Understanding mitochondrial role in normal physiology and pathological conditions has proven to be of high importance as mitochondrial dysfunction is connected with a number of disorders as well as some of the most common diseases (e.g. diabetes or Parkinson's disease). Modeling mitochondrial dysfunction has been difficult mainly due to unique features of mitochondrial genetics. Here we discuss some of the most important mouse models generated so far and lessons learned from them

Comparative study of the phenolic composition of seeds from grapes cv cardinal and alphonse lavallee during last month of ripening

During the last month of ripening, the phenolic composition of seeds from two widely distributed table grapes, cv Cardinal and Alphonse Lavallee, was determined by HPLC/DAD/ESI/MS. Besides, the concentrations of nutrients in leaf blades of grapevine were measured. Generally, the most abundant phenolic in grape seed was gallic acid, followed by methyl gallate and monomeric flavan-3-ols. In comparison to Alphonse Lavallee, the amounts of phenolics were higher in grape seed of Cardinal, in which gallic acid glucoside was not detected. Among analyzed phenolics, the increase of gallic acid was evidenced in grape seed of Cardinal. The most of phenolics decreased during the last month of grape ripening, and some of them had no significantly different content. Results of bivariate correlations showed that the amounts of some phenolics in grape seed of Cardinal increased with increasing of the content of potassium and phosphorus in leaves

The influence of gibberellic acid and paclobutrazol on induction of somatic embryogenesis in wild type and hairy root cultures of Centaurium erythraea Gillib.

The effects of exogenous gibberellic acid (GA3) and paclobutrazol on induction of somatic embryos in wild type and hairy root culture of Centaurium erythraea Gillib. were investigated. Both compoundswere incorperated into 1/2 MS medium at 6 concentrations (0.01, 0.03, 0.1, 0.3, 1.0 and 3.0 ìM). Wild type root and hairy root explants cultured in the presence of GA3 at all tested concentrations under 16-h photoperiod or in the darkness decreased the number of somatic embryos that were produced. Paclobutrazol (0.3 mM) induced the largest number (19.7, 16.5) of somatic embryos in wild type and hairy root cultures, respectively. Rooting of plants derived from somatic embryos as achieved on ½MSmedium. These results indicate that paclobutrazol is beneficial for somatic embryo induction and formation in wild type and hairy root culture

Comparative study of the phenolic composition of seeds from grapes cv cardinal and alphonse lavallee during last month of ripening

During the last month of ripening, the phenolic composition of seeds from two widely distributed table grapes, cv Cardinal and Alphonse Lavallee, was determined by HPLC/DAD/ESI/MS. Besides, the concentrations of nutrients in leaf blades of grapevine were measured. Generally, the most abundant phenolic in grape seed was gallic acid, followed by methyl gallate and monomeric flavan-3-ols. In comparison to Alphonse Lavallee, the amounts of phenolics were higher in grape seed of Cardinal, in which gallic acid glucoside was not detected. Among analyzed phenolics, the increase of gallic acid was evidenced in grape seed of Cardinal. The most of phenolics decreased during the last month of grape ripening, and some of them had no significantly different content. Results of bivariate correlations showed that the amounts of some phenolics in grape seed of Cardinal increased with increasing of the content of potassium and phosphorus in leaves

DNA methylation and differential gene regulation in photoreceptor cell death

Retinitis pigmentosa (RP) defines a group of inherited degenerative retinal diseases causing progressive loss of photoreceptors. To this day, RP is still untreatable and rational treatment development will require a thorough understanding of the underlying cell death mechanisms. Methylation of the DNA base cytosine by DNA methyltransferases (DNMTs) is an important epigenetic factor regulating gene expression, cell differentiation, cell death, and survival. Previous studies suggested an involvement of epigenetic mechanisms in RP, and in this study, increased cytosine methylation was detected in dying photoreceptors in the rd1, rd2, P23H, and S334ter rodent models for RP. Ultrastructural analysis of photoreceptor nuclear morphology in the rd1 mouse model for RP revealed a severely altered chromatin structure during retinal degeneration that coincided with an increased expression of the DNMT isozyme DNMT3a. To identify disease-specific differentially methylated DNA regions (DMRs) on a genomic level, we immunoprecipitated methylated DNA fragments and subsequently analyzed them with a targeted microarray. Genome-wide comparison of DMRs between rd1 and wild-type retina revealed hypermethylation of genes involved in cell death and survival as well as cell morphology and nervous system development. When correlating DMRs with gene expression data, we found that hypermethylation occurred alongside transcriptional repression. Consistently, motif analysis showed that binding sites of several important transcription factors for retinal physiology were hypermethylated in the mutant model, which also correlated with transcriptional silencing of their respective target genes. Finally, inhibition of DNMTs in rd1 organotypic retinal explants using decitabine resulted in a substantial reduction of photoreceptor cell death, suggesting inhibition of DNA methylation as a potential novel treatment in RP

Is there an optimal strategy for real-time continuous glucose monitoring in pediatrics? A 12-month French multi-center, prospective, controlled randomized trial (Start-In!)

AIM: To compare the efficacy of three strategies for real-time continuous glucose monitoring (RT-CGM) over 12 months in children and adolescents with type 1 diabetes. METHODS: A French multicenter trial (NCT00949221) with a randomized, controlled, prospective, open, and parallel-group design was conducted. After 3 months of RT-CGM, patients were allocated to one of three groups: return to self-monitoring of blood glucose, continuous CGM (80% of the time), or discontinuous CGM (40% of the time). The primary outcome was hemoglobin A1c (HbA1c) levels from 3 to 12 months. The secondary outcomes were acute metabolic events, hypoglycemia, satisfaction with CGM and cost. RESULTS: We included 151 subjects, aged 2 to 17 years, with a mean HbA1c level of 8.5% (SD0.7; 69 mmol/mol). The longitudinal change in HbA1c levels was similar in all three groups, at 3, 6, 9 and 12 months. The medical secondary endpoints did not differ between groups. The rate of severe hypoglycemia was significantly lower than that for the pretreatment year for the entire study population. Subjects reported consistent use and good tolerance of the device, regardless of age or insulin treatment. The use of full-time RT-CGM for 3 months costs the national medical insurance system €2629 per patient. CONCLUSION: None of the three long-term RT-CGM strategies evaluated in pediatric type 1 diabetes was superior to the others in terms of HbA1c levels. CGM-use for 3 months decreased rates of severe hypoglycemia. Our results confirm the feasibility of long-term RT-CGM-use and the need to improve educational support for patients and caregivers

Correction to 'DNA polymerase gamma mutations that impair holoenzyme stability cause catalytic subunit depletion'.

Mutations in POLG, encoding POLγA, the catalytic subunit of the mitochondrial DNA polymerase, cause a spectrum of disorders characterized by mtDNA instability. However, the molecular pathogenesis of POLG-related diseases is poorly understood and efficient treatments are missing. Here, we generate the PolgA449T/A449T mouse model, which reproduces the A467T change, the most common human recessive mutation of POLG. We show that the mouse A449T mutation impairs DNA binding and mtDNA synthesis activities of POLγ, leading to a stalling phenotype. Most importantly, the A449T mutation also strongly impairs interactions with POLγB, the accessory subunit of the POLγ holoenzyme. This allows the free POLγA to become a substrate for LONP1 protease degradation, leading to dramatically reduced levels of POLγA in A449T mouse tissues. Therefore, in addition to its role as a processivity factor, POLγB acts to stabilize POLγA and to prevent LONP1-dependent degradation. Notably, we validated this mechanism for other disease-associated mutations affecting the interaction between the two POLγ subunits. We suggest that targeting POLγA turnover can be exploited as a target for the development of future therapies.publishedVersio