Methylation of histone 3 at lysine 79 (H3K79) and its catalyst, a disrupter of telomeric silencing (DOT1l), have been coupled to multiple forms of stress, such as bioenergetic and ER challenges. ...However, studies on H3K79 methylation and Dot1l in the (aging) brain and neurons are limited. This, together with the increasing evidence of a dynamic neuroepigenome, made us wonder if H3K79 methylation and its activator Dot1l could play important roles in brain aging and associated disorders. In aged humans, we found strong and consistent global hypermethylation of H3K79 in neurons. Specific in dopaminergic neurons, we found a strong increase in H3K79 methylation in lipofucsin positive neurons, which are linked to pathology. In animals, where we conditionally removed Dot1l, we found a rapid loss of H3K79 methylation. As a consequence, we found some decrease in specific dopaminergic genes, and surprisingly, a clear up-regulation of almost all genes belonging to the family of the respiratory chain. These data, in relation to the observed increase in global H3K79 methylation, suggest that there is an inverse relationship between H3K79 methylation and the capacity of energy metabolism in neuronal systems.
In acute ischemic stroke, imaging of the cranio-cervical vessels is essential for intra-arterial treatment selection. Fast, reliable and easy accessible imaging is necessary 24 hours a day, 7 days a ...week. Radiologists in training and non-expert readers often perform initial reviewing. In this pilot study, the potential benefit of adding 4Dimensional-CT Angiography (4D-CTA) to the patient selection protocol for intra-arterial therapy is investigated.
Twenty-five datasets of prospectively recruited patients, eligible for intra-arterial treatment, were enrolled. Four radiologists-in-training consecutively reviewed CTA, CT-Perfusion and 4D-CTA (post-processed from CTP datasets) and scored: occlusion-presence and diagnostic certainty (scale 1-10). Time-to-diagnosis was registered.
Arterial occlusion was present in 8 patients. Accuracy improved from 88-92% after CTA and CTP assessment to 96-100% after 4D-CTA assessment (P-values >0,05). Mean diagnostic certainty improved from 7,2-8,6 to 8,8-9,3 (P-values all < 0,05). Mean time to diagnosis increased from 3, 5, 5 and 4 minutes after CTA to 9, 14, 12, and 10 minutes after 4D-CTA.
4D-CTA as an additive to regular CTA and CT-Perfusion in patients with acute ischemic stroke eligible for intra-arterial treatment shows a tendency to increase diagnostic accuracy and improves diagnostic certainty, when reviewed by radiologist in training, while only mildly prolonging time to diagnosis.
The growing interest in the therapeutic application of bacteriophages leads to a drastic increase in the number of sequenced genomes. Luckily, recent insights in phage taxonomy facilitate the ...classification of phages in a comprehensive and data-driven manner as recently proposed by the International Committee on Taxonomy of Viruses. In this research, we present the taxonomical classification of a novel, narrow host range Xanthomonas phage FoX4, isolated from a Brussels sprouts field in Belgium infested with Xanthomonas campestris pv. campestris. The phage has a limited ability to lyse a bacterial culture, yet adsorbs efficiently to its host. Based on its genome sequence and low similarity to previously described phages, the phage comprises the novel phage genus Foxquatrovirus.
is a member of the NK homeobox family and resembles
both in homology and expression pattern. However, while
is required for development of serotonergic neurons, the role of
in the mid-hindbrain ...region is still ill-defined. We have previously shown that
expression is downregulated upon loss of
during development. Here, we determined whether mdDA neurons require
during their development. We show that
is strongly expressed in the IsO and in the VZ and SVZ of the embryonic midbrain, and the majority of mdDA neurons expressed
during their development. Although the expression of
and
are slightly affected during development, the overall development and cytoarchitecture of TH-expressing neurons is not affected in the adult
-depleted midbrain. Transcriptome analysis at E14.5 indicated that genes involved in mid- and hindbrain development are affected by
-ablation, such as
and
. Although the expression of
extends more rostral into the isthmic area in the
mutants, the establishment of the IsO is not affected. Taken together, these data point to a minor role for
in mid-hindbrain patterning by repressing a hindbrain-specific cell-fate in the IsO and by subtle regulation of mdDA neuronal subset specification.
Antibiotic resistance represents a key challenge of the 21st century. Since the pipeline of new antibiotics in development is limited, the introduction of alternative antimicrobial strategies is ...urgently required. Bacteriophage therapy, the use of bacterial viruses to selectively kill bacterial pathogens, is re-emerging as a potential strategy to tackle difficult-to-treat and multidrug-resistant pathogens. The last decade has seen a surge in scientific investigation into bacteriophage therapy, including targeting orthopaedic-device-related infections (ODRIs) in several successful case studies. However, pharmacological data, knowledge on the interplay with the immune system and, especially in ODRIs, the optimal local application strategy and treatment outcomes remain scarce. The present review reports the state-of-the-art in bacteriophage therapy in ODRIs and addresses the hurdles in establishing bacteriophage therapy under good clinical practice guidelines. These hurdles include a lack of data concerning bacteriophage production, processing, administration and dosing, as well as follow-up clinical monitoring reports. To overcome these challenges, an integrated clinical approach is required, supported by comprehensive legislature to enable expansive and correctly implemented clinical trials.
biovar 1 is a soilborne plant pathogen with the ability to colonize the irrigation system of greenhouses, causing hairy root disease (HRD). Currently, management focuses on using hydrogen peroxide to ...disinfect the nutrient solution, but due to the emergence of resistant strains, its efficacy and sustainability are questioned. Using a relevant collection of pathogenic
biovar 1 strains, OLIVR1 to 6, six phages specific to this pathogen and belonging to three different genera were isolated from
biovar 1-infected greenhouses. All phages were named OLIVR, referring to their location of isolation,
nze-
eve-
ouwe-Waver, and were characterized by whole-genome analysis, confirming their strictly lytic lifestyle. They remained stable under greenhouse-relevant conditions. To assess the efficacy of the phages, their ability to disinfect greenhouse nutrient solution inoculated with agrobacteria was tested. Each of the phages infected their host, but their ability to decrease the bacterial concentration differed. For instance, OLIVR1 reduced the bacterial concentration with 4 log units without phage resistance emerging. While OLIVR4 and OLIVR5 were also infectious in nutrient solution, they did not always decrease the bacterial load below the limit of detection, and phage resistance emerged. Finally, the mutations causing phage resistance by receptor modification were identified. For OLIVR4-resistant
isolates, but not for OLIVR5-resistant isolates, motility decreased. Together, these data show the potential of some of these phages as disinfectant of nutrient solution, and they might be a valuable tool to tackle HRD.
Hairy root disease, caused by rhizogenic
biovar 1 is a rapidly emerging bacterial disease worldwide. It affects tomatoes, cucumbers, eggplant, and bell pepper, causing high yield losses in hydroponic greenhouses. Recent findings suggest that the current management practices, mainly focusing on UV-C and hydrogen peroxide to disinfect contaminated water, have a questionable efficacy. Hence, we investigate the potential of phages as a biological means of preventing this disease. Using a diverse collection of
biovar 1, we isolated three different phage species that together infect 75% of the collection. Since these phages are strictly lytic, while remaining both stable and infectious under greenhouse-relevant conditions, they might be suitable candidates for biological control.
High quality nuclear data is the most fundamental underpinning for all neutron metrology applications. This paper describes the release of version II of the International Reactor Dosimetry and Fusion ...File (IRDFF-II) that contains a consistent set of nuclear data for fission and fusion neutron metrology applications up to 60 MeV neutron energy. The library is intended to support: a) applications in research reactors; b) safety and regulatory applications in the nuclear power generation in commercial fission reactors; and c) material damage studies in support of the research and development of advanced fusion concepts. The paper describes the contents of the library, documents the thorough verification process used in its preparation, and provides an extensive set of validation data gathered from a wide range of neutron benchmark fields. The new IRDFF-II library includes 119 metrology reactions, four cover material reactions to support self-shielding corrections, five metrology metrics used by the dosimetry community, and cumulative fission products yields for seven fission products in three different neutron energy regions. In support of characterizing the measurement of the residual nuclei from the dosimetry reactions and the fission product decay modes, the present document lists the recommended decay data, particle emission energies and probabilities for 68 activation products. It also includes neutron spectral characterization data for 29 neutron benchmark fields for the validation of the library contents. Additional six reference fields were assessed (four from plutonium critical assemblies, two measured fields for thermal-neutron induced fission on 233U and 239Pu targets) but not used for validation due to systematic discrepancies in C/E reaction rate values or lack of reaction-rate experimental data. Another ten analytical functions are included that can be useful for calculating average cross sections, average energy, thermal spectrum average cross sections and resonance integrals. The IRDFF-II library and comprehensive documentation is available online at www-nds.iaea.org/IRDFF/. Evaluated cross sections can be compared with experimental data and other evaluations at www-nds.iaea.org/exfor/endf.htm. The new library is expected to become the international reference in neutron metrology for multiple applications.
Small fission chambers manufactured by Photonis, Reuter-Stokes, CEA, and Centronic are routinely calibrated in standard neutron fields of the BR1 reactor at SCK CEN in Mol, Belgium. Two irradiation ...fields are available: fast spectrum in the MARK3 convertor and thermal spectrum in the Empty Cavity. In this work, for the first time the calibration procedure of larger fission chambers (Photonis CFUL01 and CFUM21 type) with the deposit length exceeding the length of the convertor is presented. Spatial energy correction factors taking into account the neutron flux shape beyond the convertor and radial gradient of the neutron flux were calculated with MCNP and experimentally validated. The combination of calibration (i.e., effective mass measurement) in fast and thermal irradiation fields allows for determination of the purity of 238 U deposit. This is demonstrated on three CFUL01-type fission chambers with purity between 99.8% and 99.998%.
Argumentation as the public exchange of reasons is widely thought to enhance deliberative interactions that generate and justify reasonable public policies. Adopting an argumentation-theoretic ...perspective, we survey the norms that should govern public argumentation and address some of the complexities that scholarly treatments have identified. Our focus is on norms associated with the ideals of
correctness
and
participation
as sources of a politically legitimate deliberative outcome. In principle, both ideals are mutually coherent. If the information needed for a correct deliberative outcome is distributed among agents, then maximising participation increases information diversity. But both ideals can also be in tension. If participants lack competence or are prone to biases, a correct deliberative outcome requires limiting participation. The central question for public argumentation, therefore, is how to strike a balance between both ideals. Rather than advocating a preferred normative framework, our main purpose is to illustrate the complexity of this theme.
The aim of this study was to evaluate the sensitivity and specificity of MR angiography (MRA) in the diagnosis of ruptured and unruptured intracranial aneurysms.
A systematic search was performed on ...4 electronic databases on relevant articles that were published from January 1998 to October 2013. Inclusion criteria were met by 12 studies that compared MRA with digital subtraction angiography as reference standard. Two independent reviewers evaluated the methodological quality of the studies. Data from eligible studies were extracted and used to construct 2×2 contingency tables on a per-aneurysm level. Pooled estimates of sensitivity and specificity were calculated for all studies and subgroups of studies. Heterogeneity was tested, and risk for publication bias was assessed.
Included studies were of high methodological quality. Studies with larger sample size tended to have higher diagnostic performance. Most studies used time-of-flight MRA technique. Among the 960 patients assessed, 772 aneurysms were present. Heterogeneity with reference to sensitivity and specificity was moderate to high. Pooled sensitivity of MRA was 95% (95% confidence interval, 89%-98%), and pooled specificity was 89% (95% confidence interval, 80%-95%). False-negative and false-positive aneurysms detected on MRA were mainly located at the skull base and middle cerebral artery. Freehand 3-dimensional reconstructions performed by the radiologist significantly increased diagnostic performance. Studies performed on 3 Tesla showed a trend toward higher performance (P=0.054).
Studies on diagnostic performance of MRA show high sensitivity with large variation in specificity in the detection of intracranial aneurysms.
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