Showing papers by "Martin Luther University of Halle-Wittenberg published in 2012"

Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma

Abstract: Glioblastoma multiforme (GBM) is a lethal brain tumour in adults and children. However, DNA copy number and gene expression signatures indicate differences between adult and paediatric cases. To explore the genetic events underlying this distinction, we sequenced the exomes of 48 paediatric GBM samples. Somatic mutations in the H3.3-ATRX-DAXX chromatin remodelling pathway were identified in 44% of tumours (21/48). Recurrent mutations in H3F3A, which encodes the replication-independent histone 3 variant H3.3, were observed in 31% of tumours, and led to amino acid substitutions at two critical positions within the histone tail (K27M, G34R/G34V) involved in key regulatory post-translational modifications. Mutations in ATRX (α-thalassaemia/mental retardation syndrome X-linked) and DAXX (death-domain associated protein), encoding two subunits of a chromatin remodelling complex required for H3.3 incorporation at pericentric heterochromatin and telomeres, were identified in 31% of samples overall, and in 100% of tumours harbouring a G34R or G34V H3.3 mutation. Somatic TP53 mutations were identified in 54% of all cases, and in 86% of samples with H3F3A and/or ATRX mutations. Screening of a large cohort of gliomas of various grades and histologies (n = 784) showed H3F3A mutations to be specific to GBM and highly prevalent in children and young adults. Furthermore, the presence of H3F3A/ATRX-DAXX/TP53 mutations was strongly associated with alternative lengthening of telomeres and specific gene expression profiles. This is, to our knowledge, the first report to highlight recurrent mutations in a regulatory histone in humans, and our data suggest that defects of the chromatin architecture underlie paediatric and young adult GBM pathogenesis.

Vandetanib in Patients With Locally Advanced or Metastatic Medullary Thyroid Cancer: A Randomized, Double-Blind Phase III Trial

Abstract: Purpose There is no effective therapy for patients with advanced medullary thyroid carcinoma (MTC). Vandetanib, a once-daily oral inhibitor of RET kinase, vascular endothelial growth factor receptor, and epidermal growth factor receptor signaling, has previously shown antitumor activity in a phase II study of patients with advanced hereditary MTC.

Clinical practice guidelines for multiple endocrine neoplasia type 1 (MEN1)

Abstract: Objective: The aim was to provide guidelines for evaluation, treatment, and genetic testing for multiple endocrine neoplasia type 1 (MEN1). Participants: The group, which comprised 10 experts, including physicians, surgeons, and geneticists from international centers, received no corporate funding or remuneration. Process: Guidelines were developed by reviews of peer-reviewed publications; a draft was prepared, reviewed, and rigorously revised at several stages; and agreed-upon revisions were incorporated. Conclusions: MEN1 is an autosomal dominant disorder that is due to mutations in the tumor suppressor gene MEN1, which encodes a 610-amino acid protein, menin. Thus, the finding of MEN1 in a patient has important implications for family members because first-degree relatives have a 50% risk of developing the disease and can often be identified by MEN1 mutational analysis. MEN1 is characterized by the occurrence of parathyroid, pancreatic islet, and anterior pituitary tumors. Some patients may also develo...

Rewilding Abandoned Landscapes in Europe

Abstract: For millennia, mankind has shaped landscapes, particularly through agriculture. In Europe, the age-old interaction between humans and ecosystems strongly influenced the cultural heritage. Yet European farmland is now being abandoned, especially in remote areas. The loss of the traditional agricultural landscapes and its consequences for biodiversity and ecosystem services is generating concerns in both the scientific community and the public. Here we ask to what extent farmland abandonment can be considered as an opportunity for rewilding ecosystems. We analyze the perceptions of traditional agriculture in Europe and their influence in land management policies. We argue that, contrary to the common perception, traditional agriculture practices were not environmentally friendly and that the standards of living of rural populations were low. We suggest that current policies to maintain extensive farming landscapes underestimate the human labor needed to sustain these landscapes and the recent and future dynamics of the socio-economic drivers behind abandonment. We examine the potential benefits for ecosystems and people from rewilding. We identify species that could benefit from land abandonment and forest regeneration and the ecosystem services that could be provided such as carbon sequestration and recreation. Finally, we discuss the challenges associated with rewilding, including the need to maintain open areas, the fire risks, and the conflicts between people and wildlife. Despite these challenges, we argue that rewilding should be recognized by policy-makers as one of the possible land management options in Europe, particularly on marginal areas.

Cycling downwards – dissolved organic matter in soils

Abstract: Dissolved organic matter has been recognized as mobile, thus crucial to translocation of metals, pollutants but also of nutrients in soil. We present a conceptual model of the vertical movement of dissolved organic matter with soil water, which deviates from the view of a chromatographic stripping along the flow path. It assumes temporal immobilization (sorptive or by co-precipitation), followed by microbial processing, and re-release (by desorption or dissolution) into soil water of altered compounds. The proposed scheme explains well depth trends in age and composition of dissolved organic matter as well as of solid-phase organic matter in soil. It resolves the paradox of soil organic matter being oldest in the youngest part of the soil profile – the deep mineral subsoil.

Network physiology reveals relations between network topology and physiological function

Abstract: �Received 8 nov 2011 | Accepted 24 Jan 2012 | Published 28 Feb 2012 DOI: 10.1038/ncomms1705 The human organism is an integrated network where complex physiological systems, each with its own regulatory mechanisms, continuously interact, and where failure of one system can trigger a breakdown of the entire network. Identifying and quantifying dynamical networks of diverse systems with different types of interactions is a challenge. Here we develop a framework to probe interactions among diverse systems, and we identify a physiological network. We find that each physiological state is characterized by a specific network structure, demonstrating a robust interplay between network topology and function. Across physiological states, the network undergoes topological transitions associated with fast reorganization of physiological interactions on time scales of a few minutes, indicating high network flexibility in response to perturbations. The proposed system-wide integrative approach may facilitate the development of a new field, network Physiology.

Functional microRNA targets in protein coding sequences

Abstract: Motivation: Experimental evidence has accumulated showing that microRNA (miRNA) binding sites within protein coding sequences (CDSs) are functional in controlling gene expression. Results: Here we report a computational analysis of such miRNA target sites, based on features extracted from existing mammalian high-throughput immunoprecipitation and sequencing data. The analysis is performed independently for the CDS and the 3′-untranslated regions (3′-UTRs) and reveals different sets of features and models for the two regions. The two models are combined into a novel computational model for miRNA target genes, DIANA-microT-CDS, which achieves higher sensitivity compared with other popular programs and the model that uses only the 3′-UTR target sites. Further analysis indicates that genes with shorter 3′-UTRs are preferentially targeted in the CDS, suggesting that evolutionary selection might favor additional sites on the CDS in cases where there is restricted space on the 3′-UTR. Availability: The results of DIANA-microT-CDS are available at www.microrna.gr/microT-CDS Contact:hatzigeorgiou@fleming.gr; reczko@fleming.gr Supplementary information:Supplementary data are available at Bioinformatics online.

Effects of biochar compared to organic and inorganic fertilizers on soil quality and plant growth in a greenhouse experiment

Abstract: Our contemporary society is struggling with soil degradation due to overuse and climate change. Pre-Columbian people left behind sustainably fertile soils rich in organic matter and nutrients well known as terra preta (de Indio) by adding charred residues (biochar) together with organic and inorganic wastes such as excrements and household garbage being a model for sustainable agriculture today. This is the reason why new studies on biochar effects on ecosystem services rapidly emerge. Beneficial effects of biochar amendment on plant growth, soil nutrient content, and C storage were repeatedly observed although a number of negative effects were reported, too. In addition, there is no consensus on benefits of biochar when combined with fertilizers. Therefore, the objective of this study was to test whether biochar effects on soil quality and plant growth could be improved by addition of mineral and organic fertilizers. For this purpose, two growth periods of oat (Avena sativa L.) were studied under tropical conditions (26°C and 2600 mm annual rainfall) on an infertile sandy soil in the greenhouse in fivefold replication. Treatments comprised control (only water), mineral fertilizer (111.5 kg N ha–1, 111.5 kg P ha–1, and 82.9 kg K ha–1), compost (5% by weight), biochar (5% by weight), and combinations of biochar (5% by weight) plus mineral fertilizer (111.5 kg N ha–1, 111.5 kg P ha–1, and 82.9 kg K ha–1), and biochar (2.5% by weight) plus compost (2.5% by weight). Pure compost application showed highest yield during the two growth periods, followed by the biochar + compost mixture. biochar addition to mineral fertilizer significantly increased plant growth compared to mineral fertilizer alone. During the second growth period, plant yields were significantly smaller compared to the first growth period. biochar and compost additions significantly increased total organic C content during the two growth periods. Cation-exchange capacity (CEC) could not be increased upon biochar addition while base saturation (BS) was significantly increased due to ash addition with biochar. On the other hand, compost addition significantly increased CEC. Biochar addition significantly increased soil pH but pH value was generally lower during the second growth period probably due to leaching of base cations. Biochar addition did not reduce ammonium, nitrate, and phosphate leaching during the experiment but it reduced nitrification. The overall plant growth and soil fertility decreased in the order compost > biochar + compost > mineral fertilizer + biochar > mineral fertilizer > control. Further experiments should optimize biochar–organic fertilizer systems.

Functional Mockup Interface 2.0: The Standard for Tool independent Exchange of Simulation Models

Abstract: The Functional Mockup Interface (FMI) is a tool independent standard for the exchange of dynamic models and for co simulation. The first version, FMI 1.0, was published in 2010. Already more than 30 tools support FMI 1.0. In this paper an overview about the recently published version 2.0 of FMI is given that combines the formerly separated interfaces for Model Exchange and Co-Simulation in one standard. Based on the experience on using FMI 1.0, many small details have been improved and new features ease the usability and increase the performance especially for larger models. Additionally, a free FMI compliance checker will become soon available and FMI models from different tools are made available on the web to simplify testing.

Symbionts as major modulators of insect health: lactic Acid bacteria and honeybees.

Abstract: Lactic acid bacteria (LAB) are well recognized beneficial host-associated members of the microbiota of humans and animals. Yet LAB-associations of invertebrates have been poorly characterized and their functions remain obscure. Here we show that honeybees possess an abundant, diverse and ancient LAB microbiota in their honey crop with beneficial effects for bee health, defending them against microbial threats. Our studies of LAB in all extant honeybee species plus related apid bees reveal one of the largest collections of novel species from the genera Lactobacillus and Bifidobacterium ever discovered within a single insect and suggest a long (>80 mya) history of association. Bee associated microbiotas highlight Lactobacillus kunkeei as the dominant LAB member. Those showing potent antimicrobial properties are acquired by callow honey bee workers from nestmates and maintained within the crop in biofilms, though beekeeping management practices can negatively impact this microbiota. Prophylactic practices that enhance LAB, or supplementary feeding of LAB, may serve in integrated approaches to sustainable pollinator service provision. We anticipate this microbiota will become central to studies on honeybee health, including colony collapse disorder, and act as an exemplar case of insect-microbe symbiosis.

Association between Albuminuria, Kidney Function, and Inflammatory Biomarker Profile in CKD in CRIC

Abstract: Summary Background and objectives Increased risk of mortality in patients with CKD has been attributed to inflammation. However, the association between kidney function, albuminuria, and biomarkers of inflammation has not been examined in a large cohort of CKD patients. Design, setting, participants, & measurements This study measured the plasma levels of IL-1β, IL-1 receptor antagonist (IL-1RA), IL-6, TNF-α, TGF-β, high-sensitivity C-reactive protein (hs-CRP), fibrinogen, and serum albumin in 3939 participants enrolled in the Chronic Renal Insufficiency Cohort study between June 2003 and September 2008. An inflammation score was established based on plasma levels of IL-1β, IL-6, TNF-α, hs-CRP, and fibrinogen. Estimated GFR (eGFR) and serum cystatin C were used as measures of kidney function. Albuminuria was quantitated by urine albumin to creatinine ratio (UACR). Results Plasma levels of IL-1β, IL-1RA, IL-6, TNF-α, hs-CRP, and fibrinogen were higher among participants with lower levels of eGFR. Inflammation score was higher among those with lower eGFR and higher UACR. In regression analysis adjusted for multiple covariates, eGFR, cystatin C, and UACR were strongly associated with fibrinogen, serum albumin, IL-6, and TNF-α. Each unit increase in eGFR, cystatin C, and UACR was associated with a −1.2% (95% confidence interval, −1.4, −1), 64.9% (56.8, 73.3) and 0.6% (0.4, 0.8) change in IL-6, respectively (P Conclusions Biomarkers of inflammation were inversely associated with measures of kidney function and positively with albuminuria.

Cyanophora paradoxa Genome Elucidates Origin of Photosynthesis in Algae and Plants

Abstract: The primary endosymbiotic origin of the plastid in eukaryotes more than 1 billion years ago led to the evolution of algae and plants. We analyzed draft genome and transcriptome data from the basally diverging alga Cyanophora paradoxa and provide evidence for a single origin of the primary plastid in the eukaryote supergroup Plantae. C. paradoxa retains ancestral features of starch biosynthesis, fermentation, and plastid protein translocation common to plants and algae but lacks typical eukaryotic light-harvesting complex proteins. Traces of an ancient link to parasites such as Chlamydiae were found in the genomes of C. paradoxa and other Plantae. Apparently, Chlamydia-like bacteria donated genes that allow export of photosynthate from the plastid and its polymerization into storage polysaccharide in the cytosol.

Protein Export According to Schedule: Architecture, Assembly, and Regulation of Type III Secretion Systems from Plant- and Animal-Pathogenic Bacteria

Abstract: Flagellar and translocation-associated type III secretion (T3S) systems are present in most gram-negative plant- and animal-pathogenic bacteria and are often essential for bacterial motility or pathogenicity. The architectures of the complex membrane-spanning secretion apparatuses of both systems are similar, but they are associated with different extracellular appendages, including the flagellar hook and filament or the needle/pilus structures of translocation-associated T3S systems. The needle/pilus is connected to a bacterial translocon that is inserted into the host plasma membrane and mediates the transkingdom transport of bacterial effector proteins into eukaryotic cells. During the last 3 to 5 years, significant progress has been made in the characterization of membrane-associated core components and extracellular structures of T3S systems. Furthermore, transcriptional and posttranscriptional regulators that control T3S gene expression and substrate specificity have been described. Given the architecture of the T3S system, it is assumed that extracellular components of the secretion apparatus are secreted prior to effector proteins, suggesting that there is a hierarchy in T3S. The aim of this review is to summarize our current knowledge of T3S system components and associated control proteins from both plant- and animal-pathogenic bacteria.

Comb-shaped polymers to enhance hydroxide transport in anion exchange membranes

Abstract: Comb-shaped poly(2,6-dimethyl-1,4-phenylene oxide) (PPO) polymers with quaternary ammonium (QA) groups have been synthesized organizing into well-defined micro-morphology for efficient anion (hydroxide) transport. These molecular comb structures show a dramatic enhancement in conductivity and water resistance compared with non-comb-shaped PPOs.

TAL effector RVD specificities and efficiencies

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Short‐term effect of biochar and compost on soil fertility and water status of a Dystric Cambisol in NE Germany under field conditions

Abstract: Crop growth in sandy soils is usually limited by plant-available nutrients and water contents. This study was conducted to determine whether these limiting factors could be improved through applications of compost and biochar. For this purpose, a maize (Zea mays L.) field trial was established at 1 ha area of a Dystric Cambisol in Brandenburg, NE Germany. Five treatments (control, compost, and three biochar-compost mixtures with constant compost amount (32.5 Mg ha–1) and increasing biochar amount, ranging from 5–20 Mg ha–1) were compared. Analyses comprised total organic C (TOC), total N (TN), plant-available nutrients, and volumetric soil water content for 4 months under field conditions during the growing season 2009. In addition, soil water-retention characteristics were analyzed on undisturbed soil columns in the laboratory. Total organic-C content could be increased by a factor of 2.5 from 0.8 to 2% (p < 0.01) at the highest biochar-compost level compared with control while TN content only slightly increased. Plant-available Ca, K, P, and Na contents increased by a factor of 2.2, 2.5, 1.2, and 2.8, respectively. With compost addition, the soil pH value significantly increased by up to 0.6 (p < 0.05) and plant-available soil water retention increased by a factor of 2. Our results clearly demonstrated a synergistic positive effect of compost and biochar mixtures on soil organic-matter content, nutrients levels, and water-storage capacity of a sandy soil under field conditions.

Mirror therapy for improving motor function after stroke

Abstract: Background Mirror therapy is used to improve motor function after stroke. During mirror therapy, a mirror is placed in the person's midsagittal plane, thus reflecting movements of the non-paretic side as if it were the affected side. Objectives To summarise the effectiveness of mirror therapy compared with no treatment, placebo or sham therapy, or other treatments for improving motor function and motor impairment after stroke. We also aimed to assess the effects of mirror therapy on activities of daily living, pain, and visuospatial neglect. Search methods We searched the Cochrane Stroke Group's Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL, AMED, PsycINFO and PEDro (last searched 16 August 2017). We also handsearched relevant conference proceedings, trials and research registers, checked reference lists, and contacted trialists, researchers and experts in our field of study. Selection criteria We included randomised controlled trials (RCTs) and randomised cross-over trials comparing mirror therapy with any control intervention for people after stroke. Data collection and analysis Two review authors independently selected trials based on the inclusion criteria, documented the methodological quality, assessed risks of bias in the included studies, and extracted data. We assessed the quality of the evidence using the GRADE approach. We analysed the results as standardised mean differences (SMDs) or mean differences (MDs) for continuous variables, and as odds ratios (ORs) for dichotomous variables. Main results We included 62 studies with a total of 1982 participants that compared mirror therapy with other interventions. Of these, 57 were randomised controlled trials and five randomised cross-over trials. Participants had a mean age of 59 years (30 to 73 years). Mirror therapy was provided three to seven times a week, between 15 and 60 minutes for each session for two to eight weeks (on average five times a week, 30 minutes a session for four weeks).When compared with all other interventions, we found moderate-quality evidence that mirror therapy has a significant positive effect on motor function (SMD 0.47, 95% CI 0.27 to 0.67; 1173 participants; 36 studies) and motor impairment (SMD 0.49, 95% CI 0.32 to 0.66; 1292 participants; 39 studies). However, effects on motor function are influenced by the type of control intervention. Additionally, based on moderate-quality evidence, mirror therapy may improve activities of daily living (SMD 0.48, 95% CI 0.30 to 0.65; 622 participants; 19 studies). We found low-quality evidence for a significant positive effect on pain (SMD −0.89, 95% CI −1.67 to −0.11; 248 participants; 6 studies) and no clear effect for improving visuospatial neglect (SMD 1.06, 95% CI −0.10 to 2.23; 175 participants; 5 studies). No adverse effects were reported. Authors' conclusions The results indicate evidence for the effectiveness of mirror therapy for improving upper extremity motor function, motor impairment, activities of daily living, and pain, at least as an adjunct to conventional rehabilitation for people after stroke. Major limitations are small sample sizes and lack of reporting of methodological details, resulting in uncertain evidence quality.