Delineating human cardiac pathologies and their basic molecular mechanisms relies on research conducted in model organisms. Yet translating findings from preclinical models to humans present a ...significant challenge, in part due to differences in cardiac protein expression between humans and model organisms. Proteins immediately determine cellular function, yet their large-scale investigation in hearts has lagged behind those of genes and transcripts. Here, we set out to bridge this knowledge gap: By analyzing protein profiles in humans and commonly used model organisms across cardiac chambers, we determine their commonalities and regional differences. We analyzed cardiac tissue from each chamber of human, pig, horse, rat, mouse, and zebrafish in biological replicates. Using mass spectrometry-based proteomics workflows, we measured and evaluated the abundance of approximately 7,000 proteins in each species. The resulting knowledgebase of cardiac protein signatures is accessible through an online database: atlas.cardiacproteomics.com. Our combined analysis allows for quantitative evaluation of protein abundances across cardiac chambers, as well as comparisons of cardiac protein profiles across model organisms. Up to a quarter of proteins with differential abundances between atria and ventricles showed opposite chamber-specific enrichment between species; these included numerous proteins implicated in cardiac disease. The generated proteomics resource facilitates translational prospects of cardiac studies from model organisms to humans by comparisons of disease-linked protein networks across species.
The inhibition of transcriptional elongation plays an important role in gene regulation in metazoans, including C. elegans. Here, we combine genomic and biochemical approaches to dissect a role of ...ZFP-1, the C. elegans AF10 homolog, in transcriptional control. We show that ZFP-1 and its interacting partner DOT-1.1 have a global role in negatively modulating the level of polymerase II (Pol II) transcription on essential widely expressed genes. Moreover, the ZFP-1/DOT-1.1 complex contributes to progressive Pol II pausing on essential genes during development and to rapid Pol II pausing during stress response. The slowing down of Pol II transcription by ZFP-1/DOT-1.1 is associated with an increase in H3K79 methylation and a decrease in H2B monoubiquitination, which promotes transcription. We propose a model wherein the recruitment of ZFP-1/DOT-1.1 and deposition of H3K79 methylation at highly expressed genes initiates a negative feedback mechanism for the modulation of their expression.
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•ZFP-1(AF10) and DOT-1.1 slow down Pol II transcription of highly expressed genes•DOT-1.1 opposes H2B ubiquitination for dynamic gene regulation•ZFP-1/DOT-1.1 complex regulates the level of Pol II pausing during development•Recruitment of DOT-1.1 by ZFP-1 during stress promotes Pol II pausing
Perovskite materials host an incredible variety of functionalities. Although the lightest element, hydrogen, is rarely encountered in oxide perovskite lattices, it was recently observed as the ...hydride anion H(-), substituting for the oxide anion in BaTiO3. Here we present a series of 30 new complex hydride perovskite-type materials, based on the non-spherical tetrahydroborate anion BH4(-) and new synthesis protocols involving rare-earth elements. Photophysical, electronic and hydrogen storage properties are discussed, along with counterintuitive trends in structural behaviour. The electronic structure is investigated theoretically with density functional theory solid-state calculations. BH4-specific anion dynamics are introduced to perovskites, mediating mechanisms that freeze lattice instabilities and generate supercells of up to 16 × the unit cell volume in AB(BH4)3. In this view, homopolar hydridic di-hydrogen contacts arise as a potential tool with which to tailor crystal symmetries, thus merging concepts of molecular chemistry with ceramic-like host lattices. Furthermore, anion mixing BH4(-)←X(-) (X(-)=Cl(-), Br(-), I(-)) provides a link to the known ABX3 halides.
Aims:
The aims of this study were to provide Danish population norms for the EQ-5D-5L and to assess the measurement properties of the instrument in a Danish population setting.
Methods:
We used data ...from the Danish 5L valuation study in which a representative sample of the Danish population completed the EQ-5D-5L and answered socio-demographic questions. We generated population norms for the five EQ-5D-5L dimensions, corresponding utility scores and the EQ-5D visual analogue scale (EQ VAS) according to age and sex. Measurement properties of ceiling effects, known-group construct validity and convergent validity were assessed.
Results:
The mean EQ-5D-5L utility score for the 1014 respondents completing the EQ-5D-5L was 0.90 (standard deviation (SD)=0.16). No significant differences emerged across age groups (minimum mean utility score=0.88 (SD=0.19); maximum mean utility score=0.93 (SD=0.11)) or sex (mean utility score for women=0.89 (SD=0.17); mean utility score for men=0.91 (SD=0.15)). Statistical differences were found across educational level, occupational status, income and living situation. Similar patterns were observed for the EQ VAS. Generally, respondents most often reported problems with pain and discomfort, but young women most often reported problems with anxiety/depression. There was a significant strong correlation between EQ-5D-5L utility and the EQ VAS and a significant correlation between overall health and each of the five EQ-5D-5L dimensions. The overall ceiling effect for the EQ-5D-5L was 39% (compared to 56% for the EQ-5D-3L).
Conclusions:
Danish population norms for the EQ-5D-5L are now available. We found fewer ceiling effects for the EQ-5D-5L compared to the EQ-5D-3L, and we provide evidence for convergent and known-group validity of the EQ-5D-5L.
To evaluate parameters related to safety and efficacy of liraglutide in patients with type 2 diabetes and dialysis-dependent end-stage renal disease (ESRD).
Twenty-four patients with type 2 diabetes ...and ESRD and 23 control subjects with type 2 diabetes and normal kidney function were randomly allocated to 12 weeks of double-blind liraglutide (titrated to a maximum dose of 1.8 mg) or placebo treatment (1:1) injected subcutaneously once daily as add on to ongoing antidiabetic treatment. Dose-corrected plasma trough liraglutide concentration was evaluated at the final trial visit as the primary outcome measure using a linear mixed model.
Twenty patients with ESRD (1:1 for liraglutide vs. placebo) and 20 control subjects (1:1) completed the study period. Dose-corrected plasma trough liraglutide concentration at the final visit was increased by 49% (95% CI 6-109, P = 0.02) in the group with ESRD compared with the control group. Initial and temporary nausea and vomiting occurred more frequently among liraglutide-treated patients with ESRD compared with control subjects (P < 0.04). Glycemic control tended to improve during the study period in both liraglutide-treated groups as assessed by daily blood glucose measurements (P < 0.01), and dose of baseline insulin was reduced in parallel (P < 0.04). Body weight was reduced in both liraglutide-treated groups (-2.4 ± 0.8 kg mean ± SE in the group with ESRD, P = 0.22; -2.9 ± 1.0 kg in the control group, P = 0.03).
Plasma liraglutide concentrations increased during treatment in patients with type 2 diabetes and ESRD, who experienced more gastrointestinal side effects. Reduced treatment doses and prolonged titration period may be advisable.
Knowledge of school attendance problems (SAPs) is needed to inform treatments targeting SAPs and protecting youths from negative outcomes associated with SAPs.
This study examined the school absence, ...absence categories (i.e., absence due to illness, excused, non-excused), sociodemographic characteristics, and mental health problems among youths seeking psychological treatment for SAPs.
The study used a cross-sectional design. Sociodemographic and clinical characteristics of 152 help-seeking youths with SAPs (i.e., >10% absenteeism) and their parents were examined. The data were derived from the baseline assessment conducted before treatment start.
Older youths, youths with mental health problems, and youths whose parents had mental health problems exhibited higher levels of absence. Lower levels of non-excused absence were found among youths with highly educated fathers, and youths living with both parents. Many youths had clinical levels of anxiety, depression, or 'emotional and behavioral difficulties'.
The study highlights the need for early intervention, addressing a broad range of mental health problems.
ClinicalTrials.gov: NCT03459677.
Plasma Activated Organic Fertilizer Graves, David B.; Bakken, Lars B.; Jensen, Morten B. ...
Plasma chemistry and plasma processing,
01/2019, Letnik:
39, Številka:
1
Journal Article
Recenzirano
Improved utilization of organic waste for fertilizer has significant worldwide economic and ecological potential and the use of plasma can help unlock this potential. Organic waste that are used as ...fertilizer includes animal waste (manure and urine), human sewage, food waste and biogas digestate. Air plasma treatment of aqueous solutions of organic fertilizer (plasma activated organic fertilizer, or PAOF) has multiple advantages such as reduction or elimination of atmospheric emission of volatile organic carbon (VOC) compounds, CH
4
and NH
3
. Although the emission of N
2
O
from the fertilized soil may be enhanced by PAOF, we surmise that N
2
O
emission at large is reduced because the losses of reactive nitrogen from the agro-ecosystem (which cause N
2
O
emissions elsewhere) are significantly reduced. In addition, PAOF will improve the commercial value of fertilizer that can be made from organic waste. This includes altering both the quantity and chemical form of N contained in the organic fertilizer, as well as odor reduction. PAOF appears to function using chemical reactivity similar to well-studied natural antimicrobial processes, resulting in significant antibacterial effects in treated waste. The commercial viability of PAOF depends on numerous factors, the most important of which are the energy efficiency and capital costs associated with the plasma process and associated processing equipment; the cost of electricity; and the nature and extent of government regulations regarding pollution from organic waste and all types of fertilizer. We estimate that if the total cost of plasma production of reactive nitrogen is below about €2/kg N–€3/kg N, the process will be economically viable in the absence of penalties or subsidies.
Since the 1970s, hydrogen has been considered as a possible energy carrier for the storage of renewable energy. The main focus has been on addressing the ultimate challenge: developing an ...environmentally friendly successor for gasoline. This very ambitious goal has not yet been fully reached, as discussed in this review, but a range of new lightweight hydrogen-containing materials has been discovered with fascinating properties. State-of-the-art and future perspectives for hydrogen-containing solids will be discussed, with a focus on metal borohydrides, which reveal significant structural flexibility and may have a range of new interesting properties combined with very high hydrogen densities.
Multiple reaction mixtures with different composition ratios of MCl3–LiBH4 (M = La, Gd) were studied by mechano-chemical synthesis, yielding two new bimetallic borohydride chlorides, LiM(BH4)3Cl (M = ...La, Gd). The Gd-containing phase was obtained only after annealing the ball-milled mixture. Additionally, a solvent extracted sample of Gd(BH4)3 was studied to gain insight into the transformation from Gd(BH4)3 to LiGd(BH4)3Cl. The novel compounds were investigated using in situ synchrotron radiation powder X-ray diffraction, thermal analysis combined with mass spectroscopy, Sieverts measurements, Fourier transform infrared spectroscopy, and electrochemical impedance spectroscopy. The two new compounds, LiLa(BH4)3Cl and LiGd(BH4)3Cl, have high lithium ion conductivities of 2.3 × 10–4 and 3.5 × 10–4 S·cm–1 (T = 20 °C) and high hydrogen densities of ρm = 5.36 and 4.95 wt % H2, and both compounds crystallize in the cubic crystal system (space group I-43m) with unit cell parameter a = 11.7955(1) and a = 11.5627(1) Å, respectively. The structures contain isolated tetranuclear anionic clusters M4Cl4(BH4)124– with distorted cubane M4Cl4 cores M = La or Gd. Each lanthanide atom coordinates three chloride ions and three borohydride groups, thus completing the coordination environment to an octahedron. The Li+ ions are disordered on 2/3 of the 12d Wyckoff site, which agrees well with the very high lithium ion conductivities. The conductivity is purely ionic, as electronic conductivities were measured to only 1.4 × 10–8 and 9 × 10–8 S·cm–1 at T = 20 °C for LiLa(BH4)3Cl and LiGd(BH4)3Cl, respectively. In situ synchrotron radiation powder X-ray diffraction (SR-PXD) reveals that the decomposition products at 300 °C consist of LaB6/LaH2 or GdB4/GdH2 and LiCl. The size of the rare-earth metal atom is shown to be crucial for the formation and stability of the borohydride phases in MCl3–LiBH4 systems.
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