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Showing papers by "University of Würzburg published in 2014"


24 Apr 2014
TL;DR: In this article, the quantum spin Hall effect was observed in HgTe/(Hg,Cd)Te quantum wells with well width d 6.3 nanometers and the residual conductance was independent of sample width, indicating that it is caused by edge states.
Abstract: Recent theory predicted that the quantum spin Hall effect, a fundamentally new quantum state of matter that exists at zero external magnetic field, may be realized in HgTe/(Hg,Cd)Te quantum wells. We fabricated such sample structures with low density and high mobility in which we could tune, through an external gate voltage, the carrier conduction from n-type to p-type, passing through an insulating regime. For thin quantum wells with well width d 6.3 nanometers), the nominally insulating regime showed a plateau of residual conductance close to 2e(2)/h, where e is the electron charge and h is Planck's constant. The residual conductance was independent of the sample width, indicating that it is caused by edge states. Furthermore, the residual conductance was destroyed by a small external magnetic field. The quantum phase transition at the critical thickness, d = 6.3 nanometers, was also independently determined from the magnetic field-induced insulator-to-metal transition. These observations provide experimental evidence of the quantum spin Hall effect.

2,958 citations


Journal ArticleDOI
TL;DR: Electrocardiographic monitoring with an ICM was superior to conventional follow-up for detecting atrial fibrillation after cryptogenic stroke in patients with cryptogenic Stroke.
Abstract: Background Current guidelines recommend at least 24 hours of electrocardiographic (ECG) monitoring after an ischemic stroke to rule out atrial fibrillation. However, the most effective duration and type of monitoring have not been established, and the cause of ischemic stroke remains uncertain despite a complete diagnostic evaluation in 20 to 40% of cases (cryptogenic stroke). Detection of atrial fibrillation after cryptogenic stroke has therapeutic implications. Methods We conducted a randomized, controlled study of 441 patients to assess whether long-term monitoring with an insertable cardiac monitor (ICM) is more effective than conventional follow-up (control) for detecting atrial fibrillation in patients with cryptogenic stroke. Patients 40 years of age or older with no evidence of atrial fibrillation during at least 24 hours of ECG monitoring underwent randomization within 90 days after the index event. The primary end point was the time to first detection of atrial fibrillation (lasting >30 seconds) within 6 months. Among the secondary end points was the time to first detection of atrial fibrillation within 12 months. Data were analyzed according to the intention-to-treat principle. Results By 6 months, atrial fibrillation had been detected in 8.9% of patients in the ICM group (19 patients) versus 1.4% of patients in the control group (3 patients) (hazard ratio, 6.4; 95% confidence interval [CI], 1.9 to 21.7; P<0.001). By 12 months, atrial fib rillation had been detected in 12.4% of patients in the ICM group (29 patients) versus 2.0% of patients in the control group (4 patients) (hazard ratio, 7.3; 95% CI, 2.6 to 20.8; P<0.001). Conclusions ECG monitoring with an ICM was superior to conventional follow-up for detecting atrial fibrillation after cryptogenic stroke. (Funded by Medtronic; CRYSTAL AF ClinicalTrials.gov number, NCT00924638.)

1,632 citations


Journal ArticleDOI
TL;DR: The present guidelines are the most recent data on postoperative nausea and vomiting (PONV) and an update on the 2 previous sets of guidelines published in 2003 and 2007.
Abstract: The present guidelines are the most recent data on postoperative nausea and vomiting (PONV) and an update on the 2 previous sets of guidelines published in 2003 and 2007. These guidelines were compiled by a multidisciplinary international panel of individuals with interest and expertise in PONV under the auspices of the Society for Ambulatory Anesthesia. The panel members critically and systematically evaluated the current medical literature on PONV to provide an evidence-based reference tool for the management of adults and children who are undergoing surgery and are at increased risk for PONV. These guidelines identify patients at risk for PONV in adults and children; recommend approaches for reducing baseline risks for PONV; identify the most effective antiemetic single therapy and combination therapy regimens for PONV prophylaxis, including nonpharmacologic approaches; recommend strategies for treatment of PONV when it occurs; provide an algorithm for the management of individuals at increased risk for PONV as well as steps to ensure PONV prevention and treatment are implemented in the clinical setting.

1,180 citations


Journal ArticleDOI
TL;DR: The authors compared variation in the replicability of 13 classic and contemporary effects across 36 independent samples totaling 6,344 participants and found that the results of these experiments are more dependent on the effect itself than on the sample and setting used to investigate the effect.
Abstract: Although replication is a central tenet of science, direct replications are rare in psychology. This research tested variation in the replicability of 13 classic and contemporary effects across 36 independent samples totaling 6,344 participants. In the aggregate, 10 effects replicated consistently. One effect – imagined contact reducing prejudice – showed weak support for replicability. And two effects – flag priming influencing conservatism and currency priming influencing system justification – did not replicate. We compared whether the conditions such as lab versus online or US versus international sample predicted effect magnitudes. By and large they did not. The results of this small sample of effects suggest that replicability is more dependent on the effect itself than on the sample and setting used to investigate the effect.

767 citations


Journal ArticleDOI
TL;DR: These European Society for Clinical Microbiology and Infectious Diseases and European Confederation of Medical Mycology Joint Clinical Guidelines focus on the diagnosis and management of mucormycosis and strongly recommend continuing treatment until complete response demonstrated on imaging and permanent reversal of predisposing factors.

725 citations


Journal ArticleDOI
TL;DR: This work used path analysis to determine whether compound indices detected more relationships between diversities of different organisms and traits than more basic indices, and demonstrated that while common diversity indices may appear interchangeable in simple analyses, when considering complex interactions, the choice of index can profoundly alter the interpretation of results.
Abstract: Biodiversity, a multidimensional property of natural systems, is difficult to quantify partly because of the multitude of indices proposed for this purpose. Indices aim to describe general properties of communities that allow us to compare different regions, taxa, and trophic levels. Therefore, they are of fundamental importance for environmental monitoring and conservation, although there is no consensus about which indices are more appropriate and informative. We tested several common diversity indices in a range of simple to complex statistical analyses in order to determine whether some were better suited for certain analyses than others. We used data collected around the focal plant Plantago lanceolata on 60 temperate grassland plots embedded in an agricultural landscape to explore relationships between the common diversity indices of species richness (S), Shannon's diversity (H'), Simpson's diversity (D-1), Simpson's dominance (D-2), Simpson's evenness (E), and Berger-Parker dominance (BP). We calculated each of these indices for herbaceous plants, arbuscular mycorrhizal fungi, aboveground arthropods, belowground insect larvae, and P.lanceolata molecular and chemical diversity. Including these trait-based measures of diversity allowed us to test whether or not they behaved similarly to the better studied species diversity. We used path analysis to determine whether compound indices detected more relationships between diversities of different organisms and traits than more basic indices. In the path models, more paths were significant when using H', even though all models except that with E were equally reliable. This demonstrates that while common diversity indices may appear interchangeable in simple analyses, when considering complex interactions, the choice of index can profoundly alter the interpretation of results. Data mining in order to identify the index producing the most significant results should be avoided, but simultaneously considering analyses using multiple indices can provide greater insight into the interactions in a system.

712 citations


Journal ArticleDOI
TL;DR: Panobinostat is a potent oral pan-deacetylase inhibitor that in preclinical studies has synergistic anti-myeloma activity when combined with bortezomib and dexamethasone and the proportion of patients achieving an overall response did not differ between treatment groups.
Abstract: Summary Background Panobinostat is a potent oral pan-deacetylase inhibitor that in preclinical studies has synergistic anti-myeloma activity when combined with bortezomib and dexamethasone. We aimed to compare panobinostat, bortezomib, and dexamethasone with placebo, bortezomib, and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma. Methods PANORAMA1 is a multicentre, randomised, placebo-controlled, double-blind phase 3 trial of patients with relapsed or relapsed and refractory multiple myeloma who have received between one and three previous treatment regimens. Patients were randomly assigned (1:1) via an interactive web-based and voice response system, stratified by number of previous treatment lines and by previous use of bortezomib, to receive 21 day cycles of placebo or panobinostat (20 mg; on days 1, 3, 5, 8, 10, 12, orally), both in combination with bortezomib (1·3 mg/m 2 on days 1, 4, 8, 11, intravenously) and dexamethasone (20 mg on days 1, 2, 4, 5, 8, 9, 11, 12, orally). Patients, physicians, and the investigators who did the data analysis were masked to treatment allocation; crossover was not permitted. The primary endpoint was progression-free survival (in accordance with modified European Group for Blood and Marrow Transplantation criteria and based on investigators' assessment) and was analysed by intention to treat. The study is ongoing, but no longer recruiting, and is registered at ClinicalTrials.gov, number NCT01023308. Findings 768 patients were enrolled between Jan 21, 2010, and Feb 29, 2012, with 387 randomly assigned to panobinostat, bortezomib, and dexamethasone and 381 to placebo, bortezomib, and dexamethasone. Median follow-up was 6·47 months (IQR 1·81–13·47) in the panobinostat group and 5·59 months (2·14–11·30) in the placebo group. Median progression-free survival was significantly longer in the panobinostat group than in the placebo group (11·99 months [95% CI 10·33–12·94] vs 8·08 months [7·56–9·23]; hazard ratio [HR] 0·63, 95% CI 0·52–0·76; p vs 208 [54·6%, 49·4–59·7] for placebo; p=0·09); however, the proportion of patients with a complete or near complete response was significantly higher in the panobinostat group than in the placebo group (107 [27·6%, 95% CI 23·2–32·4] vs 60 [15·7%, 12·2–19·8]; p=0·00006). Minimal responses were noted in 23 (6%) patients in the panobinostat group and in 42 (11%) in the placebo group. Median duration of response (partial response or better) was 13·14 months (95% CI 11·76–14·92) in the panobinostat group and 10·87 months (9·23–11·76) in the placebo group, and median time to response (partial response or better) was 1·51 months (1·41–1·64) in the panobinostat group and 2·00 months (1·61–2·79) in the placebo group. Serious adverse events were reported in 228 (60%) of 381 patients in the panobinostat group and 157 (42%) of 377 patients in the placebo group. Common grade 3–4 laboratory abnormalities and adverse events (irrespective of association with study drug) included thrombocytopenia (256 [67%] in the panobinostat group vs 118 [31%] in the placebo group), lymphopenia (202 [53%] vs 150 [40%]), diarrhoea (97 [26%] vs 30 [8%]), asthenia or fatigue (91 [24%] vs 45 [12%]), and peripheral neuropathy (67 [18%] vs 55 [15%]). Interpretation Our results suggest that panobinostat could be a useful addition to the treatment armamentarium for patients with relapsed or relapsed and refractory multiple myeloma. Longer follow up will be necessary to determine whether there is any effect on overall survival. Funding Novartis Pharmaceuticals.

685 citations


Journal ArticleDOI
TL;DR: An overview of the biological questions single-cell RNA-seq has been used to address, the major findings obtained from such studies, and current challenges and expected future developments in this booming field are provided.
Abstract: Phenotypically identical cells can dramatically vary with respect to behavior during their lifespan and this variation is reflected in their molecular composition such as the transcriptomic landscape. Single-cell transcriptomics using next-generation transcript sequencing (RNA-seq) is now emerging as a powerful tool to profile cell-to-cell variability on a genomic scale. Its application has already greatly impacted our conceptual understanding of diverse biological processes with broad implications for both basic and clinical research. Different single-cell RNA-seq protocols have been introduced and are reviewed here—each one with its own strengths and current limitations. We further provide an overview of the biological questions single-cell RNA-seq has been used to address, the major findings obtained from such studies, and current challenges and expected future developments in this booming field.

659 citations


Journal ArticleDOI
TL;DR: It is found that massive gene loss occurred in the wake of sex-chromosome 'birth' in Cynoglossus semilaevis, and the sex chromosomes of these fish are derived from the same ancestral vertebrate protochromosome as the avian W and Z chromosomes.
Abstract: Genetic sex determination by W and Z chromosomes has developed independently in different groups of organisms. To better understand the evolution of sex chromosomes and the plasticity of sex-determination mechanisms, we sequenced the whole genomes of a male (ZZ) and a female (ZW) half-smooth tongue sole (Cynoglossus semilaevis). In addition to insights into adaptation to a benthic lifestyle, we find that the sex chromosomes of these fish are derived from the same ancestral vertebrate protochromosome as the avian W and Z chromosomes. Notably, the same gene on the Z chromosome, dmrt1, which is the male-determining gene in birds, showed convergent evolution of features that are compatible with a similar function in tongue sole. Comparison of the relatively young tongue sole sex chromosomes with those of mammals and birds identified events that occurred during the early phase of sex-chromosome evolution. Pertinent to the current debate about heterogametic sex-chromosome decay, we find that massive gene loss occurred in the wake of sex-chromosome 'birth'.

618 citations


Journal ArticleDOI
19 Feb 2014-Neuron
TL;DR: A consortium of neurobiologists studying arthropod brains, the Insect Brain Name Working Group, has established the present hierarchical nomenclature system, using the brain of Drosophila melanogaster as the reference framework, while taking the brains of other taxa into careful consideration for maximum consistency and expandability.

544 citations


Journal ArticleDOI
25 Jun 2014-JAMA
TL;DR: Among patients with early diffuse cutaneous systemic sclerosis, HSCT was associated with increased treatment-related mortality in the first year after treatment, however, HCST conferred a significant long-term event-free survival benefit.
Abstract: Importance High-dose immunosuppressive therapy and autologous hematopoietic stem cell transplantation (HSCT) have shown efficacy in systemic sclerosis in phase 1 and small phase 2 trials. Objective To compare efficacy and safety of HSCT vs 12 successive monthly intravenous pulses of cyclophosphamide. Design, Setting, and Participants The Autologous Stem Cell Transplantation International Scleroderma (ASTIS) trial, a phase 3, multicenter, randomized (1:1), open-label, parallel-group, clinical trial conducted in 10 countries at 29 centers with access to a European Group for Blood and Marrow Transplantation–registered transplant facility. From March 2001 to October 2009, 156 patients with early diffuse cutaneous systemic sclerosis were recruited and followed up until October 31, 2013. Interventions HSCT vs intravenous pulse cyclophosphamide. Main Outcomes and Measures The primary end point was event-free survival, defined as time from randomization until the occurrence of death or persistent major organ failure. Results A total of 156 patients were randomly assigned to receive HSCT (n = 79) or cyclophosphamide (n = 77). During a median follow-up of 5.8 years, 53 events occurred: 22 in the HSCT group (19 deaths and 3 irreversible organ failures) and 31 in the control group (23 deaths and 8 irreversible organ failures). During the first year, there were more events in the HSCT group (13 events [16.5%], including 8 treatment-related deaths) than in the control group (8 events [10.4%], with no treatment-related deaths). At 2 years, 14 events (17.7%) had occurred cumulatively in the HSCT group vs 14 events (18.2%) in the control group; at 4 years, 15 events (19%) had occurred cumulatively in the HSCT group vs 20 events (26%) in the control group. Time-varying hazard ratios (modeled with treatment × time interaction) for event-free survival were 0.35 (95% CI, 0.16-0.74) at 2 years and 0.34 (95% CI, 0.16-0.74) at 4 years. Conclusions and Relevance Among patients with early diffuse cutaneous systemic sclerosis, HSCT was associated with increased treatment-related mortality in the first year after treatment. However, HCST conferred a significant long-term event-free survival benefit. Trial Registration isrctn.org Identifier:ISRCTN54371254

Journal ArticleDOI
TL;DR: Aggressive and indolent ACCs correspond to two distinct molecular entities driven by different oncogenic alterations, which are validated in an independent cohort of 77 ACCs.
Abstract: Adrenocortical carcinomas (ACCs) are aggressive cancers originating in the cortex of the adrenal gland. Despite overall poor prognosis, ACC outcome is heterogeneous. We performed exome sequencing and SNP array analysis of 45 ACCs and identified recurrent alterations in known driver genes (CTNNB1, TP53, CDKN2A, RB1 and MEN1) and in genes not previously reported in ACC (ZNRF3, DAXX, TERT and MED12), which we validated in an independent cohort of 77 ACCs. ZNRF3, encoding a cell surface E3 ubiquitin ligase, was the most frequently altered gene (21%) and is a potential new tumor suppressor gene related to the β-catenin pathway. Our integrated genomic analyses further identified two distinct molecular subgroups with opposite outcome. The C1A group of ACCs with poor outcome displayed numerous mutations and DNA methylation alterations, whereas the C1B group of ACCs with good prognosis displayed specific deregulation of two microRNA clusters. Thus, aggressive and indolent ACCs correspond to two distinct molecular entities driven by different oncogenic alterations.


Journal ArticleDOI
20 Feb 2014-Blood
TL;DR: The Lymphoma/Leukemia Molecular Profiling Project's Lymph2Cx assay is a parsimonious digital gene expression (NanoString)-based test for COO assignment in formalin-fixed paraffin-embedded tissue (FFPET) that is accurate, robust, and robust, with >95% concordance of COO assignments between 2 independent laboratories.

Journal ArticleDOI
TL;DR: The data indicate that Treg cells beneficially influence wound healing after MI by modulating monocyte/macrophage differentiation, and therapeutic activation of TReg cells constitutes a novel approach to improve healing post-MI.
Abstract: Rationale:An exaggerated or persistent inflammatory activation after myocardial infarction (MI) leads to maladaptive healing and subsequent remodeling of the left ventricle. Foxp3+ CD4+ regulatory T cells (Treg cells) contribute to inflammation resolution. Therefore, Treg cells might influence cardiac healing post-MI. Objective:Our aim was to study the functional role of Treg cells in wound healing post-MI in a mouse model of permanent left coronary artery ligation. Methods and Results:Using a model of genetic Treg-cell ablation (Foxp3DTR mice), we depleted the Treg-cell compartment before MI induction, resulting in aggravated cardiac inflammation and deteriorated clinical outcome. Mechanistically, Treg-cell depletion was associated with M1-like macrophage polarization, characterized by decreased expression of inflammation-resolving and healing-promoting factors. The phenotype of exacerbated cardiac inflammation and outcome in Treg-cell–ablated mice could be confirmed in a mouse model of anti-CD25 monoclo...

Journal ArticleDOI
06 Feb 2014-Nature
TL;DR: Two phylotypes of the candidate genus ‘Entotheonella’ with genomes of greater than 9 megabases and multiple, distinct biosynthetic gene clusters co-inhabit the chemically and microbially rich marine sponge Theonella swinhoei.
Abstract: Cultivated bacteria such as actinomycetes are a highly useful source of biomedically important natural products. However, such ‘talented’ producers represent only a minute fraction of the entire, mostly uncultivated, prokaryotic diversity. The uncultured majority is generally perceived as a large, untapped resource of new drug candidates, but so far it is unknown whether taxa containing talented bacteria indeed exist. Here we report the single-cell- and metagenomics-based discovery of such producers. Two phylotypes of the candidate genus ‘Entotheonella’ with genomes of greater than 9 megabases and multiple, distinct biosynthetic gene clusters co-inhabit the chemically and microbially rich marine sponge Theonella swinhoei. Almost all bioactive polyketides and peptides known from this animal were attributed to a single phylotype. ‘Entotheonella’ spp. are widely distributed in sponges and belong to an environmental taxon proposed here as candidate phylum ‘Tectomicrobia’. The pronounced bioactivities and chemical uniqueness of ‘Entotheonella’ compounds provide significant opportunities for ecological studies and drug discovery.

Journal ArticleDOI
TL;DR: The findings provide evidence for the strong need for psycho-oncological interventions in cancer populations using a proportional stratified random sample based on the nationwide cancer incidence in Germany.
Abstract: Purpose To provide the 4-week prevalence estimates of mental disorders in cancer populations. Patients and Methods We enrolled adult patients with cancer from in- and outpatient care facilities, using a proportional stratified random sample based on the nationwide cancer incidence in Germany. Patients who scored 9 or above on the Patient Health Questionnaire (PHQ-9) were administered to the standardized computer-assisted Composite International Diagnostic Interview for mental disorders adapted for cancer patients (CIDI-O). A random sample of those with a PHQ-9 score that was less than 9 were selected for a CIDI-O. Results A total of 5,889 patients were identified, which led to 4,020 participants (a 68.3% response rate); of those, 2,141 patients were interviewed. The 4-week total prevalence for any mental disorder was 31.8% (95% CI, 29.8% to 33.8%); this included any anxiety disorder (11.5%; 95% CI, 10.2% to 12.9%), any adjustment disorder (11.1%; 95% CI, 9.7% to 12.4%), any mood disorder (6.5%; 95% CI, 5....

Journal ArticleDOI
TL;DR: The food-pics image database, a picture database comprising 568 food images and 315 non-food images along with detailed meta-data, is developed with the hope that the set will facilitate standardization and comparability across studies and advance experimental research on the determinants of eating behavior.
Abstract: Our current environment is characterized by the omnipresence of food cues. The sight and smell of real foods, but also graphically depictions of appetizing foods, can guide our eating behavior, for example, by eliciting food craving and influencing food choice. The relevance of visual food cues on human information processing has been demonstrated by a growing body of studies employing food images across the disciplines of psychology, medicine, and neuroscience. However, currently used food image sets vary considerably across laboratories and image characteristics (contrast, brightness, etc.) and food composition (calories, macronutrients, etc.) are often unspecified. These factors might have contributed to some of the inconsistencies of this research. To remedy this, we developed food-pics, a picture database comprising 568 food images and 315 non-food images along with detailed meta-data. A total of N = 1988 individuals with large variance in age and weight from German speaking countries and North America provided normative ratings of valence, arousal, palatability, desire to eat, recognizability and visual complexity. Furthermore, data on macronutrients (g), energy density (kcal), and physical image characteristics (color composition, contrast, brightness, size, complexity) are provided. The food-pics image data base is freely available under the creative commons license with the hope that the set will facilitate standardization and comparability across studies and advance experimental research on the determinants of eating behavior.

Journal ArticleDOI
TL;DR: Proovread as discussed by the authors is a hybrid correction pipeline for SMRT reads, which can be flexibly adapted on existing hardware and infrastructure from a laptop to a high-performance computing cluster.
Abstract: Motivation: Today, the base code of DNA is mostly determined through sequencing by synthesis as provided by the Illumina sequencers. Although highly accurate, resulting reads are short, making their analyses challenging. Recently, a new technology, single molecule real-time (SMRT) sequencing, was developed that could address these challenges, as it generates reads of several thousand bases. But, their broad application has been hampered by a high error rate. Therefore, hybrid approaches that use high-quality short reads to correct erroneous SMRT long reads have been developed. Still, current implementations have great demands on hardware, work only in well-defined computing infrastructures and reject a substantial amount of reads. This limits their usability considerably, especially in the case of large sequencing projects. Results: Here we present proovread, a hybrid correction pipeline for SMRT reads, which can be flexibly adapted on existing hardware and infrastructure from a laptop to a high-performance computing cluster. On genomic and transcriptomic test cases covering Escherichia coli, Arabidopsis thaliana and human, proovread achieved accuracies up to 99.9% and outperformed the existing hybrid correction programs. Furthermore, proovread-corrected sequences were longer and the throughput was higher. Thus, proovread combines the most accurate correction results with an excellent adaptability to the available hardware. It will therefore increase the applicability and value of SMRT sequencing. Availability and implementation: proovread is available at the following URL: http://proovread.bioapps.biozentrum.uni-wuerzburg.de Contact: ed.grubzreuw-inu.murtnezoib@retsreof.knarf Supplementary information: Supplementary data are available at Bioinformatics online.

Journal ArticleDOI
TL;DR: It is proposed that for meaningful replications, attempts at reinstating the original circumstances are not sufficient and replicators must ascertain that conditions are realized that reflect the theoretical variable(s) manipulated (and/or measured) in the original study.
Abstract: There has been increasing criticism of the way psychologists conduct and analyze studies. These critiques as well as failures to replicate several high-profile studies have been used as justification to proclaim a “replication crisis” in psychology. Psychologists are encouraged to conduct more “exact” replications of published studies to assess the reproducibility of psychological research. This article argues that the alleged “crisis of replicability” is primarily due to an epistemological misunderstanding that emphasizes the phenomenon instead of its underlying mechanisms. As a consequence, a replicated phenomenon may not serve as a rigorous test of a theoretical hypothesis because identical operationalizations of variables in studies conducted at different times and with different subject populations might test different theoretical constructs. Therefore, we propose that for meaningful replications, attempts at reinstating the original circumstances are not sufficient. Instead, replicators must ascertain that conditions are realized that reflect the theoretical variable(s) manipulated (and/or measured) in the original study.

Journal ArticleDOI
TL;DR: Recommendation of statin or statin/ezetimibe treatment in adults aged ⩾50 years with estimated glomerular filtration rate (eGFR) but not treated with chronic dialysis or kidney transplantation and follow-up measurement of lipid levels is not recommended.

Journal ArticleDOI
TL;DR: Exome sequencing data provide more evidence supporting the role of aberrant RNA processing in motor neuron degeneration in ALS kindreds and observed MATR3 pathology in ALS-affected spinal cords with and withoutMATR3 mutations.
Abstract: MATR3 is an RNA- and DNA-binding protein that interacts with TDP-43, a disease protein linked to amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. Using exome sequencing, we identified mutations in MATR3 in ALS kindreds. We also observed MATR3 pathology in ALS-affected spinal cords with and without MATR3 mutations. Our data provide more evidence supporting the role of aberrant RNA processing in motor neuron degeneration.

Journal ArticleDOI
TL;DR: Exclusion experiments with strawberries showed bee pollination to improve fruit quality, quantity and market value compared with wind and self-pollination, and bee-pollinated fruits were heavier, had less malformations and reached higher commercial grades.
Abstract: Pollination improves the yield of most crop species and contributes to one-third of global crop production, but comprehensive benefits including crop quality are still unknown. Hence, pollination is underestimated by international policies, which is particularly alarming in times of agricultural intensification and diminishing pollination services. In this study, exclusion experiments with strawberries showed bee pollination to improve fruit quality, quantity and market value compared with wind and self-pollination. Bee-pollinated fruits were heavier, had less malformations and reached higher commercial grades. They had increased redness and reduced sugar–acid–ratios and were firmer, thus improving the commercially important shelf life. Longer shelf life reduced fruit loss by at least 11%. This is accounting for 0.32 billion US$ of the 1.44 billion US$ provided by bee pollination to the total value of 2.90 billion US$ made with strawberry selling in the European Union 2009. The fruit quality and yield effects are driven by the pollination-mediated production of hormonal growth regulators, which occur in several pollination-dependent crops. Thus, our comprehensive findings should be transferable to a wide range of crops and demonstrate bee pollination to be a hitherto underestimated but vital and economically important determinant of fruit quality.

Journal ArticleDOI
TL;DR: This issue of Surgical Endoscopy, the first part of the Guidelines is published including sections on basics, indication for surgery, perioperative management, and key points of technique, and the next part will address complications and comparisons between open and laparoscopic techniques.
Abstract: Guidelines are increasingly determining the decision process in day-to-day clinical work. Guidelines describe the current best possible standard in diagnostics and therapy. They should be developed by an international panel of experts, whereby alongside individual experience, above all, the results of comparative studies are decisive. According to the results of high-ranking scientific studies published in peer-reviewed journals, statements and recommendations are formulated, and these are graded strictly according to the criteria of evidence-based medicine. Guidelines can therefore be valuable in helping particularly the young surgeon in his or her day-to-day work to find the best decision for the patient when confronted with a wide and confusing range of options. However, even experienced surgeons benefit because by virtue of a heavy workload and commitment, they often find it difficult to keep up with the ever-increasing published literature. All guidelines require regular updating, usually every 3 years, in line with progress in the field. The current Guidelines focus on technique and perioperative management of laparoscopic ventral hernia repair and constitute the first comprehensive guidelines on this topic. In this issue of Surgical Endoscopy, the first part of the Guidelines is published including sections on basics, indication for surgery, perioperative management, and key points of technique. The next part (Part 2) of the Guidelines will address complications and comparisons between open and laparoscopic techniques. Part 3 will cover mesh technology, hernia prophylaxis, technique-related issues, new technologic developments, lumbar and other unusual hernias, and training/education.

Journal ArticleDOI
24 Jul 2014-Nature
TL;DR: Changes in MYC levels activate and repress specific sets of direct target genes that are characteristic of MYC-transformed tumour cells that have considerable prognostic value, suggesting that different cellular responses to physiological and oncogenic MyC levels are controlled by promoter affinity.
Abstract: In mammalian cells, the MYC oncoprotein binds to thousands of promoters. During mitogenic stimulation of primary lymphocytes, MYC promotes an increase in the expression of virtually all genes. In contrast, MYC-driven tumour cells differ from normal cells in the expression of specific sets of up- and downregulated genes that have considerable prognostic value. To understand this discrepancy, we studied the consequences of inducible expression and depletion of MYC in human cells and murine tumour models. Changes in MYC levels activate and repress specific sets of direct target genes that are characteristic of MYC-transformed tumour cells. Three factors account for this specificity. First, the magnitude of response parallels the change in occupancy by MYC at each promoter. Functionally distinct classes of target genes differ in the E-box sequence bound by MYC, suggesting that different cellular responses to physiological and oncogenic MYC levels are controlled by promoter affinity. Second, MYC both positively and negatively affects transcription initiation independent of its effect on transcriptional elongation. Third, complex formation with MIZ1 (also known as ZBTB17) mediates repression of multiple target genes by MYC and the ratio of MYC and MIZ1 bound to each promoter correlates with the direction of response.

Journal ArticleDOI
TL;DR: Mycoses summarized in the hyalohyphomycosis group are heterogeneous, defined by the presence of hyaline (non-dematiaceous) hyphae, and management usually consists of surgery and antifungal treatment, depending on the clinical presentation.

Journal ArticleDOI
TL;DR: It is proposed that SGLT2 inhibition can lower GFR independent of reducing BG (consistent with the tubular hypothesis of diabetic glomerular hyperfiltration), while attenuation of albuminuria, kidney growth, and inflammation in the early diabetic kidney may mostly be secondary to lower BG.
Abstract: Our previous work has shown that gene knockout of the sodium-glucose cotransporter SGLT2 modestly lowered blood glucose in streptozotocin-diabetic mice (BG; from 470 to 300 mg/dl) and prevented glomerular hyperfiltration but did not attenuate albuminuria or renal growth and inflammation. Here we determined effects of the SGLT2 inhibitor empagliflozin (300 mg/kg of diet for 15 wk; corresponding to 60–80 mg·kg−1·day−1) in type 1 diabetic Akita mice that, opposite to streptozotocin-diabetes, upregulate renal SGLT2 expression. Akita diabetes, empagliflozin, and Akita + empagliflozin similarly increased renal membrane SGLT2 expression (by 38–56%) and reduced the expression of SGLT1 (by 33–37%) vs. vehicle-treated wild-type controls (WT). The diabetes-induced changes in SGLT2/SGLT1 protein expression are expected to enhance the BG-lowering potential of SGLT2 inhibition, and empagliflozin strongly lowered BG in Akita (means of 187–237 vs. 517–535 mg/dl in vehicle group; 100–140 mg/dl in WT). Empagliflozin modestly reduced GFR in WT (250 vs. 306 μl/min) and completely prevented the diabetes-induced increase in glomerular filtration rate (GFR) (255 vs. 397 μl/min). Empagliflozin attenuated increases in kidney weight and urinary albumin/creatinine ratio in Akita in proportion to hyperglycemia. Empagliflozin did not increase urinary glucose/creatinine ratios in Akita, indicating the reduction in filtered glucose balanced the inhibition of glucose reabsorption. Empagliflozin attenuated/prevented the increase in systolic blood pressure, glomerular size, and molecular markers of kidney growth, inflammation, and gluconeogenesis in Akita. We propose that SGLT2 inhibition can lower GFR independent of reducing BG (consistent with the tubular hypothesis of diabetic glomerular hyperfiltration), while attenuation of albuminuria, kidney growth, and inflammation in the early diabetic kidney may mostly be secondary to lower BG.

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TL;DR: In this paper, a general framework and examples of approaches for enhancing pollinator richness and abundance, quantity and quality of pollen on stigmas, crop yield, and farmers' profit, including some benefits detected only through longterm monitoring.
Abstract: Recent evidence highlights the value of wild-insect species richness and abundance for crop pollination worldwide. Yet, deliberate physical importation of single species (eg European honey bees) into crop fields for pollination remains the mainstream management approach, and implementation of practices to enhance crop yield (production per area) through wild insects is only just beginning. With few exceptions, studies measuring the impacts of pollinator-supporting practices on wild-insect richness and pollination service success – particularly in relation to long-term crop yield and economic profit – are rare. Here, we provide a general framework and examples of approaches for enhancing pollinator richness and abundance, quantity and quality of pollen on stigmas, crop yield, and farmers' profit, including some benefits detected only through long-term monitoring. We argue for integrating the promotion of wild-insect species richness with single-species management to benefit farmers and society.

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TL;DR: It appears that K(+) is not just the essential nutrient required to support optimal plant growth and yield but is also an important signaling agent mediating a wide range of plant adaptive responses to environment.

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Georges Aad1, Brad Abbott2, Jalal Abdallah3, S. Abdel Khalek4  +2871 moreInstitutions (167)
TL;DR: In this article, the authors presented the electron and photon energy calibration achieved with the ATLAS detector using about 25 fb(-1) of LHC proton-proton collision data taken at center-of-mass energies of root s = 7 and 8 TeV.
Abstract: This paper presents the electron and photon energy calibration achieved with the ATLAS detector using about 25 fb(-1) of LHC proton-proton collision data taken at centre-of-mass energies of root s = 7 and 8 TeV. The reconstruction of electron and photon energies is optimised using multivariate algorithms. The response of the calorimeter layers is equalised in data and simulation, and the longitudinal profile of the electromagnetic showers is exploited to estimate the passive material in front of the calorimeter and reoptimise the detector simulation. After all corrections, the Z resonance is used to set the absolute energy scale. For electrons from Z decays, the achieved calibration is typically accurate to 0.05% in most of the detector acceptance, rising to 0.2% in regions with large amounts of passive material. The remaining inaccuracy is less than 0.2-1% for electrons with a transverse energy of 10 GeV, and is on average 0.3% for photons. The detector resolution is determined with a relative inaccuracy of less than 10% for electrons and photons up to 60 GeV transverse energy, rising to 40% for transverse energies above 500 GeV.