IMPORTANCE: The benefits of vitamin D, omega-3 fatty acids, and exercise in disease prevention remain unclear. OBJECTIVE: To test whether vitamin D, omega-3s, and a strength-training exercise ...program, alone or in combination, improved 6 health outcomes among older adults. DESIGN, SETTING, AND PARTICIPANTS: Double-blind, placebo-controlled, 2 × 2 × 2 factorial randomized clinical trial among 2157 adults aged 70 years or older who had no major health events in the 5 years prior to enrollment and had sufficient mobility and good cognitive status. Patients were recruited between December 2012 and November 2014, and final follow-up was in November 2017. INTERVENTIONS: Participants were randomized to 3 years of intervention in 1 of the following 8 groups: 2000 IU/d of vitamin D3, 1 g/d of omega-3s, and a strength-training exercise program (n = 264); vitamin D3 and omega-3s (n = 265); vitamin D3 and exercise (n = 275); vitamin D3 alone (n = 272); omega-3s and exercise (n = 275); omega-3s alone (n = 269); exercise alone (n = 267); or placebo (n = 270). MAIN OUTCOMES AND MEASURES: The 6 primary outcomes were change in systolic and diastolic blood pressure (BP), Short Physical Performance Battery (SPPB), Montreal Cognitive Assessment (MoCA), and incidence rates (IRs) of nonvertebral fractures and infections over 3 years. Based on multiple comparisons of 6 primary end points, 99% confidence intervals are presented and P < .01 was required for statistical significance. RESULTS: Among 2157 randomized participants (mean age, 74.9 years; 61.7% women), 1900 (88%) completed the study. Median follow-up was 2.99 years. Overall, there were no statistically significant benefits of any intervention individually or in combination for the 6 end points at 3 years. For instance, the differences in mean change in systolic BP with vitamin D vs no vitamin D and with omega-3s vs no omega-3s were both −0.8 (99% CI, –2.1 to 0.5) mm Hg, with P < .13 and P < .11, respectively; the difference in mean change in diastolic BP with omega-3s vs no omega-3s was –0.5 (99% CI, –1.2 to 0.2) mm Hg; P = .06); and the difference in mean change in IR of infections with omega-3s vs no omega-3s was –0.13 (99% CI, –0.23 to –0.03), with an IR ratio of 0.89 (99% CI, 0.78-1.01; P = .02). No effects were found on the outcomes of SPPB, MoCA, and incidence of nonvertebral fractures). A total of 25 deaths were reported, with similar numbers in all treatment groups. CONCLUSIONS AND RELEVANCE: Among adults without major comorbidities aged 70 years or older, treatment with vitamin D3, omega-3s, or a strength-training exercise program did not result in statistically significant differences in improvement in systolic or diastolic blood pressure, nonvertebral fractures, physical performance, infection rates, or cognitive function. These findings do not support the effectiveness of these 3 interventions for these clinical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01745263
For half a century, the process of economic integration of the Amazon has been based on intensive use of renewable and nonrenewable natural resources, which has brought significant basin-wide ...environmental alterations. The rural development in the Amazonia pushed the agricultural frontier swiftly, resulting in widespread land-cover change, but agriculture in the Amazon has been of low productivity and unsustainable. The loss of biodiversity and continued deforestation will lead to high risks of irreversible change of its tropical forests. It has been established by modeling studies that the Amazon may have two “tipping points,” namely, temperature increase of 4 °C or deforestation exceeding 40% of the forest area. If transgressed, large-scale “savannization” of mostly southern and eastern Amazon may take place. The region has warmed about 1 °C over the last 60 y, and total deforestation is reaching 20% of the forested area. The recent significant reductions in deforestation—80% reduction in the Brazilian Amazon in the last decade—opens up opportunities for a novel sustainable development paradigm for the future of the Amazon. We argue for a new development paradigm—away from only attempting to reconcile maximizing conservation versus intensification of traditional agriculture and expansion of hydropower capacity—in which we research, develop, and scale a high-tech innovation approach that sees the Amazon as a global public good of biological assets that can enable the creation of innovative high-value products, services, and platforms through combining advanced digital, biological, and material technologies of the Fourth Industrial Revolution in progress.
Viruses of the genus
Begomovirus
(family
Geminiviridae
) are emergent pathogens of crops throughout the tropical and subtropical regions of the world. By virtue of having a small DNA genome that is ...easily cloned, and due to the recent innovations in cloning and low-cost sequencing, there has been a dramatic increase in the number of available begomovirus genome sequences. Even so, most of the available sequences have been obtained from cultivated plants and are likely a small and phylogenetically unrepresentative sample of begomovirus diversity, a factor constraining taxonomic decisions such as the establishment of operationally useful species demarcation criteria. In addition, problems in assigning new viruses to established species have highlighted shortcomings in the previously recommended mechanism of species demarcation. Based on the analysis of 3,123 full-length begomovirus genome (or DNA-A component) sequences available in public databases as of December 2012, a set of revised guidelines for the classification and nomenclature of begomoviruses are proposed. The guidelines primarily consider a) genus-level biological characteristics and b) results obtained using a standardized classification tool, Sequence Demarcation Tool, which performs pairwise sequence alignments and identity calculations. These guidelines are consistent with the recently published recommendations for the genera
Mastrevirus
and
Curtovirus
of the family
Geminiviridae
. Genome-wide pairwise identities of 91 % and 94 % are proposed as the demarcation threshold for begomoviruses belonging to different species and strains, respectively. Procedures and guidelines are outlined for resolving conflicts that may arise when assigning species and strains to categories wherever the pairwise identity falls on or very near the demarcation threshold value.
Boron in Prebiological Evolution Franco, Ana; Silva, José Armando L.
Angewandte Chemie (International ed.),
May 3, 2021, Letnik:
60, Številka:
19
Journal Article
Recenzirano
Boron(III), as borate (or boric acid), mediates the synthesis of ribose, ribonucleosides, and ribonucleotides. These reactions are carried out under moderate temperatures (typically 70–95 °C) with ...organic molecules (or their derivatives) detected in interstellar space and inorganic ions found in minerals on Earth (and could occur during early stages of prebiotic evolution). Research in this century suggests that borate was a relevant prebiological reagent, thus reinforcing the RNA world hypothesis as an explanation for the origin of life. Herein, these developments on prebiological chemistry related to boron species are reviewed.
Research suggests that borate could have mediated the prebiotic synthesis of RNA precursors (ribose, ribonucleosides, and ribonucleotides) in reactions relevant for the origin of life. This minireview provides an overview of recent developments in prebiological chemistry related to boron species.
Rising adverse impact of climate change caused by anthropogenic activities is calling for advanced methods to reduce carbon dioxide emissions. Here, we review adsorption technologies for carbon ...dioxide capture with focus on materials, techniques, and processes, additive manufacturing, direct air capture, machine learning, life cycle assessment, commercialization and scale-up.
Fatigue is a common, disabling, and difficult-to-manage problem in rheumatic diseases. Prevalence estimates of fatigue within rheumatic diseases vary considerably. Data on the prevalence of severe ...fatigue across multiple rheumatic diseases using a similar instrument is missing. Our aim was to provide an overview of the prevalence of severe fatigue across a broad range of rheumatic diseases and to examine its association with clinical and demographic variables. Online questionnaires were filled out by an international sample of 6120 patients (88 % female, mean age 47) encompassing 30 different rheumatic diseases. Fatigue was measured with the RAND(SF)-36 Vitality scale. A score of ≤35 was taken as representing severe fatigue (90 % sensitivity and 81 % specificity for chronic fatigue syndrome). Severe fatigue was present in 41 to 57 % of patients with a single inflammatory rheumatic disease such as rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, Sjögren’s syndrome, psoriatic arthritis, and scleroderma. Severe fatigue was least prevalent in patients with osteoarthritis (35 %) and most prevalent in patients with fibromyalgia (82 %). In logistic regression analysis, severe fatigue was associated with having fibromyalgia, having multiple rheumatic diseases without fibromyalgia, younger age, lower education, and language (French: highest prevalence; Dutch: lowest prevalence). In conclusion, one out of every two patients with a rheumatic disease is severely fatigued. As severe fatigue is detrimental to the patient, the near environment, and society at large, unraveling the underlying mechanisms of fatigue and developing optimal treatment should be top priorities in rheumatologic research and practice.
Recent breakthrough experiments revealed the iso-reticular Zr-MOFs, MIL-140B and MIL-140C, as promising sorbents for the separation of C6 isomers. Interestingly while the ultra-small pore MIL-140B ...exhibited hexane isomer sorption hierarchy according to the normal boiling point order (
n
-C6 > 3MP (3-methyl pentane)), an uncommon shift in the elution order was observed in the larger pore MIL-140C. It was only speculated that the flexibility of the MOFs might be the origin of this intriguing behavior. Herein, flexible force field hybrid osmotic Monte Carlo combined with molecular dynamics simulations were carried out to unravel the microscopic mechanism of the adsorption and dynamics of both C6 isomers in MIL140B and MIL140C. Thermodynamically preferred adsorption of
n
-C6 over 3MP was predicted for MIL-140B and to a slightly less extent for MIL-140C. Interestingly while the mobility of
n
-C6 was found to remain higher than that of 3MP in the whole range of loading for MIL-140B, 3MP becomes more mobile than
n
-C6 at saturation in MIL-140C. This suggests that this kinetics order is most probably the origin of the inversion of the elution order observed experimentally for MIL-140C. The translational and rotational dynamics of the two guests in MIL-140B and MIL-140C was further understood in-depth.
Recent breakthrough experiments revealed the iso-reticular Zr-MOFs, MIL-140B and MIL-140C, as promising sorbents for the separation of C6 isomers.
Citrullination is the post-translational conversion of an arginine residue within a protein to the non-coded amino acid citrulline. This modification leads to the loss of a positive charge and ...reduction in hydrogen-bonding ability. It is carried out by a small family of tissue-specific vertebrate enzymes called peptidylarginine deiminases (PADIs) and is associated with the development of diverse pathological states such as autoimmunity, cancer, neurodegenerative disorders, prion diseases and thrombosis. Nevertheless, the physiological functions of citrullination remain ill-defined, although citrullination of core histones has been linked to transcriptional regulation and the DNA damage response. PADI4 (also called PAD4 or PADV), the only PADI with a nuclear localization signal, was previously shown to act in myeloid cells where it mediates profound chromatin decondensation during the innate immune response to infection. Here we show that the expression and enzymatic activity of Padi4 are also induced under conditions of ground-state pluripotency and during reprogramming in mouse. Padi4 is part of the pluripotency transcriptional network, binding to regulatory elements of key stem-cell genes and activating their expression. Its inhibition lowers the percentage of pluripotent cells in the early mouse embryo and significantly reduces reprogramming efficiency. Using an unbiased proteomic approach we identify linker histone H1 variants, which are involved in the generation of compact chromatin, as novel PADI4 substrates. Citrullination of a single arginine residue within the DNA-binding site of H1 results in its displacement from chromatin and global chromatin decondensation. Together, these results uncover a role for citrullination in the regulation of pluripotency and provide new mechanistic insights into how citrullination regulates chromatin compaction.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Adalimumab, etanercept and infliximab are effective TNF inhibitors (TNFis) in the treatment of RA, but no randomized clinical trials have compared the three agents. Prior observational data are not ...consistent. We compared their effectiveness over 1 year in a prospective cohort.
Analyses were performed on subjects' first episode of TNFi use in the Rheumatic Diseases Portuguese Register, Reuma.pt. The primary outcome was the proportion of patients with European League Against Rheumatism good response sustained at two consecutive observations separated by 3 months during the first year of TNFi use. Comparisons were performed using conventional adjusted logistic regression, as well as matching subjects across the three agents using a propensity score. In addition, baseline predictors of treatment response to TNFi were identified.
The study cohort included 617 RA patients, 250 starting etanercept, 206 infliximab and 161 adalimumab. Good response was achieved by 59.6% for adalimumab, 59.2% for etanercept and 51.9% for infliximab (P = 0.21). The modelled probability of good response did not significantly differ across agents (etanercept vs adalimumab OR = 0.97, 95% CI 0.55, 1.71; etanercept vs infliximab OR = 1.25, 95% CI 0.74, 2.12; infliximab vs adalimumab OR = 0.80, 95% CI 0.47, 1.36). Matched propensity score analyses also showed no significant treatment response differences. Greater educational attainment was a predictor of better response, while smoking, presence of ACPA, glucocorticoid use and worse physician assessment of disease activity at baseline each predicted a reduced likelihood of treatment response.
Over 1 year, we found no difference in effectiveness between adalimumab, etanercept and infliximab.
Herein, the effect of the insertion of a thin dielectric HfO2:Al2O3 (HAO) layer at different positions in the Pt/0.5Ba(Zr0.2Ti0.8)O3–0.5(Ba0.7Ca0.3)TiO3 (BCZT)/Au structure on the energy storage ...performance of the capacitors is investigated. A high storage performance is achieved through the insertion of a HAO layer between BCZT and Au layers. The insertion of the dielectric layer causes a depolarization field which results in a high linearity hysteresis loop with low energy dissipation. The Pt/BCZT/HAO/Au capacitors show an impressive energy storage density of 99.8 J cm−3 and efficiency of 71.0%, at an applied electric field of 750 kV cm−1. Further, no significant change in the energy storage properties is observed after passing 108 switching cycles through the capacitor. The presence of resistive switching (RS) in leakage current characteristics confirms the strong charge coupling between ferroelectric and insulator layers. The same trend of the RS ratio and the energy storage performance with the variation of the architecture of the devices suggests that the energy storage properties can be improved through the charge coupling between the layers. By combining ferroelectrics and dielectrics into one single structure, the proposed strategy provides an efficient way for developing highly efficient energy storage capacitors.
It is demonstrated that high‐performance energy storage devices can be achieved through integration of ferroelectric and dielectric thin films and can be further optimized through selection of proper architecture of the device. The Pt/BCZT/HAO/Au capacitors exhibit an energy storage density of 99.8 J cm−3 and efficiency of 71.0%, with no significant change in the energy storage properties observed after passing 108 switching cycles.
PDF
