Differential DNA methylation associated with allergy might provide novel insights into the shared or unique etiology of asthma, rhinitis, and eczema.
We sought to identify DNA ...methylation profiles associated with childhood allergy.
Within the European Mechanisms of the Development of Allergy (MeDALL) consortium, we performed an epigenome-wide association study of whole blood DNA methylation by using a cross-sectional design. Allergy was defined as having symptoms from at least 1 allergic disease (asthma, rhinitis, or eczema) and positive serum-specific IgE to common aeroallergens. The discovery study included 219 case patients and 417 controls at age 4 years and 228 case patients and 593 controls at age 8 years from 3 birth cohorts, with replication analyses in 325 case patients and 1111 controls. We performed additional analyses on 21 replicated sites in 785 case patients and 2124 controls by allergic symptoms only from 8 cohorts, 3 of which were not previously included in analyses.
We identified 80 differentially methylated CpG sites that showed a 1% to 3% methylation difference in the discovery phase, of which 21 (including 5 novel CpG sites) passed genome-wide significance after meta-analysis. All 21 CpG sites were also significantly differentially methylated with allergic symptoms and shared between asthma, rhinitis, and eczema. The 21 CpG sites mapped to relevant genes, including ACOT7, LMAN3, and CLDN23. All 21 CpG sties were differently methylated in asthma in isolated eosinophils, and 10 were replicated in respiratory epithelium.
Reduced whole blood DNA methylation at 21 CpG sites was significantly associated with childhood allergy. The findings provide novel insights into the shared molecular mechanisms underlying asthma, rhinitis, and eczema.
CD99 (MIC2; single-chain type-1 glycoprotein) is a heavily O-glycosylated transmembrane protein (32 kDa) present on leukocytes and activated endothelium. Expression of CD99 on endothelium is ...important in lymphocyte diapedesis. CD99 is a diagnostic marker for Ewing's Sarcoma (EWS), as it is highly expressed by these tumors. It has been reported that CD99 can affect the migration, invasion and metastasis of tumor cells. Our results show that CD99 is also highly expressed in the tumor vasculature of most solid tumors. Furthermore, we found that
CD99 expression in cultured endothelial cells is induced by starvation. Targeting of murine CD99 by a conjugate vaccine, which induced antibodies against CD99 in mice, resulted in inhibition of tumor growth in both a tumor model with high CD99 (Os-P0109 osteosarcoma) and low CD99 (CT26 colon carcinoma) expression. We demonstrated that vaccination against CD99 is safe, since no toxicity was observed in mice with high antibody titers against CD99 in their sera during a period of almost 11 months. Targeting of CD99 in humans is more complicated due to the fact that the human and mouse CD99 protein are not identical. We are the first to show that growth factor activated endothelial cells express a distinct human CD99 isoform. We conclude that our observations provide an opportunity for specific targeting of CD99 isoforms in human tumor vasculature.
Recent developments in Geant4 Allison, J.; Amako, K.; Apostolakis, J. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
11/2016, Letnik:
835, Številka:
C
Journal Article
Recenzirano
Odprti dostop
Geant4 is a software toolkit for the simulation of the passage of particles through matter. It is used by a large number of experiments and projects in a variety of application domains, including ...high energy physics, astrophysics and space science, medical physics and radiation protection. Over the past several years, major changes have been made to the toolkit in order to accommodate the needs of these user communities, and to efficiently exploit the growth of computing power made available by advances in technology. The adaptation of Geant4 to multithreading, advances in physics, detector modeling and visualization, extensions to the toolkit, including biasing and reverse Monte Carlo, and tools for physics and release validation are discussed here.
•Multithreading resulted in a smaller memory footprint and nearly linear speed-up.•Scoring options, faster geometry primitives, more versatile visualization were added.•Improved electromagnetic and hadronic models and cross sections were developed.•Reverse Monte Carlo and general biasing methods were added.•Physics validation efforts were expanded and new validation tools were added.
•Both DS tested were useful to carry out an OMBR process for treating wastewater.•COD removal efficiencies were always higher than 80%.•Salt reverse flux was higher when the industrial wastewater was ...used as DS.•Industrial waste water as DS had less membrane fouling and higher water flux.•Industrial waste water was a DS very attractive for the OMBR operation.
Osmotic membrane bioreactor (OMBR) is an emerging membrane process which has gained interest in the recent years because of the low energy consumption and the high effluent quality. The osmotic membrane bioreactor combines a forward osmosis (FO) membrane and a biological treatment. However, salt reverse flux is the main problem because of the negative effect of the salt concentration increase in the reactor on the microbial activity. This is the reason why the study of a suitable draw solution (DS) is very important in the overall performance of the reactor. This study compares the process performance using two draw solutions: a 53gL−1 NaCl solution and a real waste water solution (waste water from an absorption column consisting mainly of SO42− and NH4-N with concentrations of 153gL−1 and 19gL−1, respectively). The comparison is focused on the salt reverse flux during the reactor operation, the mixed liquor characteristics, the membrane fouling and the overall performance. The results indicated that the industrial wastewater showed a higher salt reverse flux, but also a less severe fouling and a higher the osmotic pressure difference in comparison with the NaCl solution. In terms of chemical oxygen demand (COD) removal efficiencies, both draw solutions attained values higher than 80%, though the efficiency was slightly lower when the industrial effluent was used as DS. This was related to the higher conductivity reached in the bioreactor when the industrial effluent was used as draw solution. In spite of it, the use of this industrial effluent as draw solution is strongly recommended because of the high permeate fluxes yielded, the low membrane fouling and the lack of necessity of regenerating the draw solution.
To validate new mitochondrial myopathy serum biomarkers for diagnostic use.
We analyzed serum FGF21 (S-FGF21) and GDF15 from patients with (1) mitochondrial diseases and (2) nonmitochondrial ...disorders partially overlapping with mitochondrial disorder phenotypes. We (3) did a meta-analysis of S-FGF21 in mitochondrial disease and (4) analyzed S-Fgf21 and skeletal muscle Fgf21 expression in 6 mouse models with different muscle-manifesting mitochondrial dysfunctions.
We report that S-FGF21 consistently increases in primary mitochondrial myopathy, especially in patients with mitochondrial translation defects or mitochondrial DNA (mtDNA) deletions (675 and 347 pg/mL, respectively; controls: 66 pg/mL, p < 0.0001 for both). This is corroborated in mice (mtDNA deletions 1,163 vs 379 pg/mL, p < 0.0001). However, patients and mice with structural respiratory chain subunit or assembly factor defects showed low induction (human 335 pg/mL, p < 0.05; mice 335 pg/mL, not significant). Overall specificities of FGF21 and GDF15 to find patients with mitochondrial myopathy were 89.3% vs 86.4%, and sensitivities 67.3% and 76.0%, respectively. However, GDF15 was increased also in a wide range of nonmitochondrial conditions.
S-FGF21 is a specific biomarker for muscle-manifesting defects of mitochondrial translation, including mitochondrial transfer-RNA mutations and primary and secondary mtDNA deletions, the most common causes of mitochondrial disease. However, normal S-FGF21 does not exclude structural respiratory chain complex or assembly factor defects, important to acknowledge in diagnostics.
This study provides Class III evidence that elevated S-FGF21 accurately distinguishes patients with mitochondrial myopathies from patients with other conditions, and FGF21 and GDF15 mitochondrial myopathy from other myopathies.
Oculopharyngeal muscular dystrophy (OPMD) is a genetic disorder caused by an abnormal expansion of GCN triplets within the
gene. Previous descriptions have focused on lower limb muscles in small ...cohorts of patients with OPMD, but larger imaging studies have not been performed. Previous imaging studies have been too small to be able to correlate imaging findings to genetic and clinical data.
We present cross-sectional, T1-weighted muscle MRI and CT-scan data from 168 patients with genetically confirmed OPMD. We have analysed the pattern of muscle involvement in the disease using hierarchical analysis and presented it as heatmaps. Results of the scans were correlated with genetic and clinical data.
Fatty replacement was identified in 96.7% of all symptomatic patients. The tongue, the
and the
were the most commonly affected muscles. Muscle pathology on MRI correlated positively with disease duration and functional impairment.
We have described a pattern that can be considered characteristic of OPMD. An early combination of fat replacement in the tongue,
and
can be helpful for differential diagnosis. The findings suggest the natural history of the disease from a radiological point of view. The information generated by this study is of high diagnostic value and important for clinical trial development.
Assuring the safety of muscle foods and seafood is based on prerequisites and specific measures targeted against defined hazards. This concept is augmented by 'interventions', which are chemical or ...physical treatments, not genuinely part of the production process, but rather implemented in the framework of a safety assurance system. The present paper focuses on 'Cold Atmospheric pressure Plasma' (CAP) as an emerging non-thermal intervention for microbial decontamination. Over the past decade, a vast number of studies have explored the antimicrobial potential of different CAP systems against a plethora of different foodborne microorganisms. This contribution aims at providing a comprehensive reference and appraisal of the latest literature in the area, with a specific focus on the use of CAP for the treatment of fresh meat, fish and associated products to inactivate microbial pathogens and extend shelf life. Aspects such as changes to organoleptic and nutritional value alongside other matrix effects are considered, so as to provide the reader with a clear insight into the advantages and disadvantages of CAP-based decontamination strategies.
Calorie-rich diets induce hyperphagia and promote obesity, although the underlying mechanisms remain poorly defined. We find that short-term high-fat-diet (HFD) feeding of mice activates ...prepronociceptin (PNOC)-expressing neurons in the arcuate nucleus of the hypothalamus (ARC). PNOC
neurons represent a previously unrecognized GABAergic population of ARC neurons distinct from well-defined feeding regulatory AgRP or POMC neurons. PNOC
neurons arborize densely in the ARC and provide inhibitory synaptic input to nearby anorexigenic POMC neurons. Optogenetic activation of PNOC
neurons in the ARC and their projections to the bed nucleus of the stria terminalis promotes feeding. Selective ablation of these cells promotes the activation of POMC neurons upon HFD exposure, reduces feeding, and protects from obesity, but it does not affect food intake or body weight under normal chow consumption. We characterize PNOC
neurons as a novel ARC neuron population activated upon palatable food consumption to promote hyperphagia.
•COD removal efficiencies were around 80% until the 50-th day of operation.•The DS used offered enough driving force for the OMBR operation.•Salinity build-up in the bioreactor increased the SMP but ...did not affect eEPS.•Nitrification did not occur at a high extent.•Denitrification occurred and was proved by the absence of nitrites and nitrates.
The performance of an osmotic membrane bioreactor (OMBR) for treating tannery wastewater at laboratory scale has been evaluated in this study. The forward osmosis (FO) membrane tested was CTA-NW from HTI. As draw solution, actual waste water from an absorption column for ammonia separation, which consists mainly of ammonium sulphate was used. The study was focused on the salt reverse flux during the OMBR operation, membrane water flux, biomass characteristics and membrane fouling. Regarding membrane water flux change with the time, the measured values diminished from 3.44 to 0.72 LMH due to the membrane fouling and the salt accumulation in the biological reactor. The stable mixed liquor conductivity value at the end of the experiment was 29.8mS·cm−1. The chemical oxygen demand (COD) removal efficiencies were maintained near 80% until the first 50 days of operation, considering the soluble COD in the reactor instead of the COD in the membrane permeate for the performance calculation. Thence, COD removal efficiencies decreased progressively due to the accumulation of non degradable COD coming from the tannery wastewater. Concerning to the membrane fouling, FESEM/EDX analysis corroborated that organic fouling was predominant on the membrane active layer.
NASA’s Interface Region Imaging Spectrograph (IRIS) provides high-resolution observations of the solar atmosphere through ultraviolet spectroscopy and imaging. Since the launch of IRIS in June 2013, ...we have conducted systematic observation campaigns in coordination with the Swedish 1 m Solar Telescope (SST) on La Palma. The SST provides complementary high-resolution observations of the photosphere and chromosphere. The SST observations include spectropolarimetric imaging in photospheric Fe
I
lines and spectrally resolved imaging in the chromospheric Ca
II
8542 Å, H
α
, and Ca
II
K lines. We present a database of co-aligned IRIS and SST datasets that is open for analysis to the scientific community. The database covers a variety of targets including active regions, sunspots, plages, the quiet Sun, and coronal holes.
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