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After almost twenty years of intense work on the celebrated LaAlO3/SrTiO3system, the recent discovery of a superconducting two-dimensional electron gas (2-DEG) in (111)-oriented KTaO3-based heterostructures injects new momentum to the field of oxides interface. However, while both interfaces share common properties, experiments also suggest important differences between the two systems. Here, we report gate tunable superconductivity in 2-DEGs generated at the surface of a (111)-oriented KTaO3 crystal by the simple sputtering of a thin Al layer. We extract the superfluid stiffness of the 2-DEGs and show that its temperature dependence is consistent with a node-less superconducting order parameter having a gap value larger than expected within a simple BCS weak-coupling limit model. The superconducting transition follows the Berezinskii-Kosterlitz-Thouless scenario, which was not reported on SrTiO3-based interfaces. Our finding offers innovative perspectives for fundamental science but also for device applications in a variety of fields such as spin-orbitronics and topological electronics. Heterostructures based on (111)-oriented KTaO3crystals are a new platform for studying oxide interfaces. Gate-tunable superconductivity in 2D electron gases at the surface of (111)-oriented KTaO3is now reported, with the superconducting transition being of the Berezinskii-Kosterlitz-Thouless type. [ABSTRACT FROM AUTHOR]

Condensation and faithful separation of the genome are crucial for the cellular life cycle. During chromosome segregation, mechanical forces generated by the mitotic spindle pull apart the sister chromatids. The mechanical nature of this process has motivated a lot of research interest into the mechanical properties of mitotic chromosomes. Although their fundamental mechanical characteristics are known, it still remains unclear how these characteristics emerge from the structure of the mitotic chromosome. Recent advances in genomics, computational and super-resolution microscopy techniques have greatly promoted our understanding of the chromosomal structure and have motivated us to review the mechanical characteristics of chromosomes in light of the current structural insights. In this review, we will first introduce the current understanding of the chromosomal structure, before reviewing characteristic mechanical properties such as the Young's modulus and the bending modulus of mitotic chromosomes. Then we will address the approaches used to relate mechanical properties to the structure of chromosomes and we will also discuss how mechanical characterization can aid in elucidating their structure. Finally, future challenges, recent developments and emergent questions in this research field will be discussed. [ABSTRACT FROM AUTHOR]

Aims: DNA methylation‐based central nervous system (CNS) tumour classification has identified numerous molecularly distinct tumour types, and clinically relevant subgroups among known CNS tumour entities that were previously thought to represent homogeneous diseases. Our study aimed at characterizing a novel, molecularly defined variant of glioneuronal CNS tumour. Patients and methods: DNA methylation profiling was performed using the Infinium MethylationEPIC or 450 k BeadChip arrays (Illumina) and analysed using the 'conumee' package in R computing environment. Additional gene panel sequencing was also performed. Tumour samples were collected at the German Cancer Research Centre (DKFZ) and provided by multinational collaborators. Histological sections were also collected and independently reviewed. Results: Genome‐wide DNA methylation data from >25 000 CNS tumours were screened for clusters separated from established DNA methylation classes, revealing a novel group comprising 31 tumours, mainly found in paediatric patients. This DNA methylation‐defined variant of low‐grade CNS tumours with glioneuronal differentiation displays recurrent monosomy 14, nuclear clusters within a morphology that is otherwise reminiscent of oligodendroglioma and other established entities with clear cell histology, and a lack of genetic alterations commonly observed in other (paediatric) glioneuronal entities. Conclusions: DNA methylation‐based tumour classification is an objective method of assessing tumour origins, which may aid in diagnosis, especially for atypical cases. With increasing sample size, methylation analysis allows for the identification of rare, putative new tumour entities, which are currently not recognized by the WHO classification. Our study revealed the existence of a DNA methylation‐defined class of low‐grade glioneuronal tumours with recurrent monosomy 14, oligodendroglioma‐like features and nuclear clusters. [ABSTRACT FROM AUTHOR]

Ependymomas are common childhood brain tumours that occur throughout the nervous system, but are most common in the paediatric hindbrain. Current standard therapy comprises surgery and radiation, but not cytotoxic chemotherapy as it does not further increase survival. Whole-genome and whole-exome sequencing of 47 hindbrain ependymomas reveals an extremely low mutation rate, and zero significant recurrent somatic single nucleotide variants. Although devoid of recurrent single nucleotide variants and focal copy number aberrations, poor-prognosis hindbrain ependymomas exhibit a CpG island methylator phenotype. Transcriptional silencing driven by CpG methylation converges exclusively on targets of the Polycomb repressive complex 2 which represses expression of differentiation genes through trimethylation of H3K27. CpG island methylator phenotype-positive hindbrain ependymomas are responsive to clinical drugs that target either DNA or H3K27 methylation both in vitro and in vivo. We conclude that epigenetic modifiers are the first rational therapeutic candidates for this deadly malignancy, which is epigenetically deregulated but genetically bland. [ABSTRACT FROM AUTHOR]

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Rheumatoid arthritis (RA) is a chronic, inflammatory joint disease of unknown etiology and pronounced interpatient heterogeneity. To characterize RA at the molecular level and to uncover pathomechanisms, we performed genome-wide gene expression analysis. We identified a set of 1,054 genes significantly deregulated in pair-wise comparisons between RA and osteoarthritis (OA) patients, RA and normal donors (ND), or OA and ND. Correlation analysis revealed gene sets regulated identically in all three groups. As a prominent example secreted phosphoprotein 1 (SPP1) was identified to be significantly upregulated in RA compared with both OA and ND. SPP1 expression was found to correlate with genes expressed during an inflammatory response, T-cell activation and apoptosis, suggesting common underlying regulatory networks. A subclassification of RA patients was achieved on the basis of proteoglycan 4 (PRG4) expression, distinguishing PRG4 high and low expressors and reflecting the heterogeneity of the disease. In addition, we found that low PRG4 expression was associated with a more aggressive disease stage, which is in accordance with PRG4 loss-of-function mutations causing camptodactyly-arthropathy-coxa vara-pericarditis syndrome. Altogether we provide evidence for molecular signatures of RA and RA subclasses, sets of new candidate genes as well as for candidate gene networks, which extend our understanding of disease mechanisms and may lead to an improved diagnosis. [ABSTRACT FROM AUTHOR]

UDP-glucuronosyltransferases (UGT) catalyze the glucuronidation of various compounds and thus inactivate toxic substrates. Genetic variations reducing the activity of UGT1A7 have been associated with various gastrointestinal cancers. Most recently, the UGT1A7*3 allele has been reported as a significant risk factor for pancreatic disorders, but we could not confirm these data. This study focused on the possible causes for the noted discrepancy. UGT1A7 genotypes were assessed in 37 samples, which were previously analyzed for UGT1A7 polymorphisms by others. We determined genotypes by melting curve analysis and by DNA sequencing. Additionally, we produced UGT1A7*1 and *3 constructs with or without a mutation at position − 57 of UGT1A7 and analyzed various combinations of these constructs. In 14/37 samples UGT1A7 genotyping results differed. The discrepancy could be explained by polymerase chain reaction bias owing to an unbalanced allelic amplification which was caused by a −57T>G variant located within the sequence of the chosen primer template in previous studies. Our findings indicate that most of the previously reported genetic associations between UGT1A7 and gastrointestinal cancers are based on primer-dependent genotyping errors.The Pharmacogenomics Journal (2008) 8, 34–41; doi:10.1038/sj.tpj.6500443; published online 27 February 2007 [ABSTRACT FROM AUTHOR]

An efficient immune response against hepatitis C virus (HCV) is necessary to clear infection. As HCV is a single-stranded RNA virus, a role for TLR7 in the immune response against HCV is possible, and early clinical studies have demonstrated an antiviral effect of TLR7 stimulation. We tested the hypothesis that genetic variations of TLR7 are associated with chronic HCV-infection and outcome of therapy. The prevalence of three TLR7 variations was analysed in 978 patients with chronic HCV-infection, 898 patients with chronic liver disease of other aetiologies, and in 203 healthy controls. The prevalence of TLR7 variations was correlated with the response to interferon-α-based treatment in 544 patients with chronic HCV-infection. We analysed TLR7 polymorphisms by melting curve analysis and reconstructed haplotypes. The c.32A>T variation was over-represented in female patients with chronic HCV-infection compared to patients with other chronic liver diseases and to healthy controls ( P < 0.05). In contrast, c.2403 G>A was less prevalent in male patients with chronic HCV-infection ( P < 0.05). No association was observed for the third variant, c.1-120T>G. Haplotype analysis confirmed the differential distribution of TLR7 variants between the groups. Within the group of female patients with chronic HCV-infection, c.32T was predictive of an unfavourable outcome of interferon-α therapy ( P < 0.05). This study reports the association of TLR7 variants with chronic HCV-infection and with the response to interferon-α therapy in patients with chronic HCV-infection. Our results suggest that variations of TLR7 impair the immune response to HCV and imply a gender-specific effect of this X-chromosomal variation. [ABSTRACT FROM AUTHOR]

Background A recent study reported that a non-synonymous single nucleotide polymorphism (rs11209026, p.Arg381Gln) located in the IL23R gene is a protective marker for inflammatory bowel disease. Aim To analyse the frequency of p.Arg381Gln in three independent European inflammatory bowel disease cohorts and to evaluate how this variant influences disease behaviour. Methods We assessed a European cohort of 919 inflammatory bowel disease patients and compared the IL23R p.Arg381Gln genotype frequency with 845 healthy controls. Inflammatory bowel disease patients originated from Germany [Crohn’s disease (CD): n = 318; ulcerative colitis (UC): n = 178], Hungary (CD: n = 148; UC: n = 118) and the Netherlands (CD: n = 157). Ethnically matched controls were included. We performed subtyping analysis in respect to CARD15 alterations and clinical characteristics. Results The frequency of the glutamine allele of p.Arg381Gln was significantly lower in inflammatory bowel disease patients compared with controls in a pooled analysis of all three cohorts ( P < 0.000001) as well as in the individual cohorts (Germany: P = 0.001, Hungary: P = 0.02 and the Netherlands: P = 0.0002). The p.Arg381Gln genotype distribution was similar between CD and UC. We did not observe either statistical interactions between p.Arg381Gln and CARD15 variants or any significant associations between p.Arg381Gln genotype and subphenotypes. Conclusions The p.Arg381Gln IL23R variant confers a protective effect against both CD and UC, but does not determine disease phenotype. [ABSTRACT FROM AUTHOR]

The clinical phenotype of human dilated cardiomyopathy (DCM) encompasses a broad spectrum of etiologically distinct disorders. As targeting of etiology-related pathogenic pathways may be more efficient than current standard heart failure treatment, we obtained the genomic expression profile of a DCM subtype characterized by cardiac inflammation to identify possible new therapeutic targets in humans. In this inflammatory cardiomyopathy (DCMi), a distinctive cardiac expression pattern not described in any previous study of cardiac disorders was observed. Two significantly altered gene networks of particular interest and possible interdependence centered around the cysteine-rich angiogenic inducer 61 (CYR61) and adiponectin (APN) gene. CYR61 overexpression, as in human DCMi hearts in situ, was similarly induced by inflammatory cytokines in vascular endothelial cells in vitro. APN was strongly downregulated in DCMi hearts and completely abolished cytokine-dependent CYR61 induction in vitro. Dysbalance between the CYR61 and APN networks may play a pathogenic role in DCMi and contain novel therapeutic targets. Multiple immune cell-associated genes were also deregulated (e.g., chemokine ligand 14, interleukin-17D, nuclear factors of activated T cells). In contrast to previous investigations in patients with advanced or end-stage DCM where etiology-related pathomechanisms are overwhelmed by unspecific processes, the deregulations detected in this study occurred at a far less severe and most probably fully reversible disease stage. [ABSTRACT FROM AUTHOR]

Recent discoveries of trypsinogen and trypsin inhibitor mutations in patients with chronic pancreatitis (CP) support the hypothesis that an inappropriate activation of pancreatic zymogens to active enzymes within the pancreatic parenchyma starts the inflammatory process. Current data suggest that CP may be inherited dominant, recessive, or complex as a result of mutations in the above mentioned or yet unidentified genes. Evaluation of patients with CP should include genetic testing. Cystic fibrosis (CF) is an autosomal recessive inherited disorder caused by mutations in the CF transmembrane conductance regulator (CFTR) gene and is characterized by pancreatic insufficiency and chronic bronchopulmonary infection. The progression and severity of pulmonary disease differs considerably between people with identical CFTR mutations and does not seem to correlate with the type or class of the CFTR mutation. The identification of further disease modifying genetic factors will increase the pathophysiological understanding and may help to identify new therapeutic targets. [ABSTRACT FROM AUTHOR]

Background: An association between α1-antitrypsin deficiency and chronic pancreatitis (CP) has been reported in several case reports and two systematic studies. However, conflicting results have been shown in other studies of patients with CP. All previous studies were performed by phenotyping or by measurement of serum concentrations of α1-antitrypsin. The aim of this study was to investigate the relationship between α1-antitrypsin deficiency and CP by genetic analysis. Methods: Ninety-six unrelated children and adolescents with idiopathic or hereditary CP and 185 healthy controls were enrolled. DNA was extracted from peripheral blood leukocytes and the exons 5 and 7 of the α1-antitrypsin gene were amplified by polymerase chain reaction using mutagenic forward primers introducing a Taq I restriction site. Genotyping of the S allele and the Z allele was performed by restriction fragment length polymorphism analysis using Taq I. Results: Seven out of 96 patients (7.3%) with CP were heterozygous for an α1-antitrypsin deficiency allele (4 for the S allele and 3 for the Z allele). No patient was homozygous or compound heterozygous for these alleles. Twenty out of 185 control individuals (10.8%) were heterozygous for the S or Z allele (PiS: 12 controls; PiZ: 8 controls). No significant differences were found between the allele frequency in patients and the control individuals (P > 0.1). Conclusions: α1- antitrypsin deficiency is not related to the pathogenesis of idiopathic or hereditary CP. [ABSTRACT FROM AUTHOR]

This study was performed to investigate whether patient exposure and diagnostic quality of the image is significantly influenced by the introduction of digital image acquisition techniques. Evaluation was performed for three different techniques (analogue, analogue fluoro + digital radiography, digital) in examination of the upper gastrointestinal tract. The evaluation was done from data acquired in three different departments. Patient exposure was recorded as KERMA-area product (KAP) and the individual patient readings were normalised to a standard size patient. Image quality was assessed using visual grading with a reference image. The recorded KAP values were significantly higher (22.3 Gycm2) for the fully digital technique compared to the others (analogue 6.8 Gycm2, analogue + digital 3.6 Gycm2). This was due mostly to an increased number of exposures. The diagnostic quality of the image was, however, also regarded to be slightly lower for the technique giving the lowest patient dose with the smallest number of exposures (analogue + digital). The digital examination technique, as used in this study, thus resulted in significantly higher patient dose without any significant gain in diagnostic quality of the image. [ABSTRACT FROM AUTHOR]

The efficacy and safety of 25 mg pyrimethamine plus 500 mg sulfadoxine given twice a week in preventing relapses of AIDS-related toxoplasmic encephalitis was evaluated in an open study. The 56 HIV-infected patients evaluated had responded to intensive treatment with pyrimethamine/clindamycin prior to starting the present prophylactic regimen. Four patients (7 %) experienced relapse while on pyrimethamine/sulfadoxine. The probability of freedom from relapse was >90 % for 12 months and >80 % for 24 months. Side effects comprised mild or moderate allergic reactions which occurred in 23 patients (41 %), leading to discontinuation in four patients (7%). Forty-nine of the 56 patients did not have a history of Pneumocystis carinii pneumonia and did not receive antiparasitic prophylaxis other than pyrimethamine/sulfadoxine; two of them (4 %) developed pneumocystosis. The probability of freedom from pneumocystosis was about 90 % for 24 months. Pyrimethamine/sulfadoxine twice a week appears to be a promising regimen for prevention of toxoplasmic encephalitis, and also appears to provide protection against Pneumocystis carinii pneumonia. Although allergic reactions are usually mild and disappear on continuation, they may limit the value of this regimen. [ABSTRACT FROM AUTHOR]

The reaction sequence between the primary electron acceptor, the oxidized Chlorophyll-a, and the terminal electron donor, the water splitting enzyme system S, is being described in the range from nanoseconds to milliseconds. For the cleavage of water Chlorophyll-a extracts four electrons in four turnovers from the enzyme system S responsible for the water oxidation. For each extraction the electron is moved step by step along the chain that connects the Chlorophyll-a center with that of S. Beginning with the transfer from the immediate donor, D, to Chl-a, the subsequent transfer from D to D ends in the electron transfer from S to D. This final act establishes in S the oxidizing equivalent, probably in the form of oxidized manganese. Coupled with these acts is an intrinsic proton release and a surplus charge formation. After the generation of the 4th oxidizing equivalent in a concerted final action the evolution of O from water takes place. Correlations between the events are described quantitatively. [ABSTRACT FROM AUTHOR]

Oxygen evolution and reduction kinetics of the photooxidized Chl-a have been measured in oxygen-evolving complexes from the thermophilic cyanobacterium Synechococcus sp. [ABSTRACT FROM AUTHOR]

Copyright of Fresenius' Zeitschrift für Analytische Chemie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)