1,056 research outputs found
Mechanical Stretching of Proteins: Calmodulin and Titin
Mechanical unfolding of several domains of calmodulin and titin is studied
using a Go-like model with a realistic contact map and Lennard-Jones contact
interactions. It is shown that this simple model captures the experimentally
observed difference between the two proteins: titin is a spring that is tough
and strong whereas calmodulin acts like a weak spring with featureless
force-displacement curves. The difference is related to the dominance of the
alpha secondary structures in the native structure of calmodulin. The tandem
arrangements of calmodulin unwind simultaneously in each domain whereas the
domains in titin unravel in a serial fashion. The sequences of contact events
during unraveling are correlated with the contact order, i.e. with the
separation between contact making amino acids along the backbone in the native
state. Temperature is found to affect stretching in a profound way.Comment: To be published in a special bio-issue of Physica A; 14 figure
Impact of COVID-19 pandemic on chronic pain and opioid use in marginalized populations: A scoping review
IntroductionThe COVID-19 pandemic has had a variable effect on vulnerable populations, including patients with chronic pain who rely on opioid treatment or have comorbid opioid use disorder. Limited access to care due to isolation measures may lead to increased pain severity, worse mental health symptoms, and adverse opioid-related outcomes. This scoping review aimed to understand the impact of the COVID-19 pandemic on the dual epidemics of chronic pain and opioids in marginalized communities worldwide.MethodsSearches of primary databases including PubMed, Web of Science, Scopus, and PsycINFO were performed in March 2022, restricting the publication date to December 1, 2019. The search yielded 685 articles. After title and abstract screening, 526 records were screened by title and abstract, 87 through full-text review, of which 25 articles were included in the final analysis.ResultsOur findings illuminate the differential distribution of pain burden across marginalized groups and how it serves to heighten existing disparities. Service disruptions due to social distancing orders and infrastructural limitations prevented patients from receiving the care they needed, resulting in adverse psychological and physical health outcomes. Efforts to adapt to COVID-19 circumstances included modifications to opioid prescribing regulations and workflows and expanded telemedicine services.ConclusionResults have implications for the prevention and management of chronic pain and opioid use disorder, such as challenges in adopting telemedicine in low-resource settings and opportunities to strengthen public health and social care systems with a multidisciplinary and multidimensional approach
MicroRNA-Mediated Control of Oligodendrocyte Differentiation
SummaryMicroRNAs (miRNAs) regulate various biological processes, but evidence for miRNAs that control the differentiation program of specific neural cell types has been elusive. To determine the role of miRNAs in the formation of myelinating oligodendrocytes, we selectively deleted a miRNA-processing enzyme, Dicer1, in oligodendrocyte lineage cells. Mice lacking Dicer1 display severe myelinating deficits despite an expansion of the oligodendrocyte progenitor pool. To search for miRNAs responsible for the induction of oligodendrocyte maturation, we identified miR-219 and miR-338 as oligodendrocyte-specific miRNAs in spinal cord. Overexpression of these miRNAs is sufficient to promote oligodendrocyte differentiation. Additionally, blockage of these miRNA activities in oligodendrocyte precursor culture and knockdown of miR-219 in zebrafish inhibit oligodendrocyte maturation. miR-219 and miR-338 function in part by directly repressing negative regulators of oligodendrocyte differentiation, including transcription factors Sox6 and Hes5. These findings illustrate that miRNAs are important regulators of oligodendrocyte differentiation, providing new targets for myelin repair
Oxidative Cleavage of Alkene C=C Bonds Using a Manganese Catalyzed Oxidation with H2O2 Combined with Periodate Oxidation
A one-pot multi-step method for the oxidative cleavage of alkenes to aldehydes/ketones under ambient conditions is described as an alternative to ozonolysis. The first step is a highly efficient manganese catalyzed epoxidation/cis-dihydroxylation of alkenes. This step is followed by an Fe(III) assisted ring opening of the epoxide (where necessary) to a 1,2-diol. Carbon-carbon bond cleavage is achieved by treatment of the diol with sodium periodate. The conditions used in each step are not only compatible with the subsequent step(s), but also provide for increased conversion compared to the equivalent reactions carried out on the isolated intermediate compounds. The described procedure allows for carbon-carbon bond cleavage in the presence of other alkenes, oxidation sensitive moieties and other functional groups; the mild conditions (r.t.) used in all three steps make this a viable general alternative to ozonolysis and especially for use under flow or continuous batch conditions
Mechanical Strength of 17 134 Model Proteins and Cysteine Slipknots
A new theoretical survey of proteins' resistance to constant speed stretching
is performed for a set of 17 134 proteins as described by a structure-based
model. The proteins selected have no gaps in their structure determination and
consist of no more than 250 amino acids. Our previous studies have dealt with
7510 proteins of no more than 150 amino acids. The proteins are ranked
according to the strength of the resistance. Most of the predicted top-strength
proteins have not yet been studied experimentally. Architectures and folds
which are likely to yield large forces are identified. New types of potent
force clamps are discovered. They involve disulphide bridges and, in
particular, cysteine slipknots. An effective energy parameter of the model is
estimated by comparing the theoretical data on characteristic forces to the
corresponding experimental values combined with an extrapolation of the
theoretical data to the experimental pulling speeds. These studies provide
guidance for future experiments on single molecule manipulation and should lead
to selection of proteins for applications. A new class of proteins, involving
cystein slipknots, is identified as one that is expected to lead to the
strongest force clamps known. This class is characterized through molecular
dynamics simulations.Comment: 40 pages, 13 PostScript figure
Amino acids as highly efficient modulators for single crystals of zirconium and hafnium metalâorganic frameworks
The synthesis of zirconium and hafnium metalâorganic frameworks (MOFs) often relies on coordination modulation â the addition of competing monotopic modulators to reaction mixtures â to reproducibly generate highly crystalline material. Typically, large excesses of monocarboxylic acids such as formic, acetic and benzoic acid are applied, but access to diffraction quality single crystals, particularly of UiO-66 topology MOFs, remains troublesome. Herein, we show that amino acids, in particular L-proline, are highly efficient modulators of Zr and Hf MOFs of the UiO-66 series, with as little as four equivalents affording access to large, diffraction quality single crystals that are free of defects. Five crystal structures are reported, including MOFs which previously could not be characterised in this manner, with molecular dynamics simulations utilised to understand dynamic disorder. Additionally, a series of MOFs are characterised in depth, allowing a comparison of the thermal stabilities and porosities for Zr and Hf analogues. We also show that the protocol can be extended to microwave synthesis, and that modulating ability varies dramatically across a series of amino acids. Access to single crystals has facilitated our own in depth study of the mechanical properties of these MOFs, and we expect that our protocols will enable the discovery of new Zr and Hf MOFs as well as offer new insights into their materials properties
Comparative transcriptomic analysis reveals the coordinated mechanisms of Populus Ă canadensis âNevaâ leaves in response to cadmium stress
Cadmium (Cd), a heavy metal element has strong toxicity to living organisms. Excessive Cd accumulation directly affects the absorption of mineral elements, inhibits plant tissue development, and even induces mortality. Populus Ă canadensis âNevaâ, the main afforestation variety planted widely in northern China, was a candidate variety for phytoremediation. However, the genes relieving Cd toxicity and increasing Cd tolerance of this species were still unclear. In this study, we employed transcriptome sequencing on two Cd?treated cuttings to identify the key genes involved in Cd stress responses of P. Ă canadensis âNevaâ l induced by 0 (CK), 10 (C10), and 20 (C20) mg/L Cd(NO3)2 4H2O. We discovered a total of 2,656 (1,488 up-regulated and 1,168 downregulated) and 2,816 DEGs (1,470 up-regulated and 1,346 down-regulated) differentially expressed genes (DEGs) between the CK vs C10 and CK vs C20, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses in response to the Cd stress indicated that many DEGs identified were involved in the catalytic activity, the oxidoreductase activity, the transferase activity, and the biosynthesis of secondary metabolites. Based on the enrichment results, potential candidate genes were identified related to the calcium ion signal transduction, transcription factors, the antioxidant defense system, and transporters and showed divergent expression patterns under the Cd stress. We also validated the reliability of transcriptome data with the real-time PCR. Our findings deeper the understanding of the molecular responsive mechanisms of P. Ă canadensis âNevaâ lon Cd tolerance and further provide critical resources for phytoremediation applications
Studies on CuCe0.75Zr0.25Ox preparation using bacterial cellulose and its application in toluene complete oxidation
A series of CuCe0.75Zr0.25Ox catalysts (CCZ) were synthesized based on the environmentalâfriendly bacterial cellulose (BC) by using the solâgel method. The corresponding synthesis mechanism, physicochemical properties of the catalysts and catalytic performances for toluene oxidation were comprehensively studied. In the presence of BC without sugar, the CCZâA synthesized by ethanolâgel exhibits better catalytic activity than the CCZâW synthesized by waterâgel, which may be due to the different roles of BC in different solvents. However, it is worth noting that the graft copolymerization between BC and active metal (Ce4+, Cu2+) is the same process in both waterâgel and ethanolâgel. The activity of CCZâSW synthesized by waterâgel using BC with sugar is obviously higher than that of CCZâW and CCZâA. The temperature of complete degradation of toluene over CCZâSW is 205â°C, which is 35â°C lower than that of CCZâW. The results from BET, Raman and H2âTPR indicate that the larger the specific surface area, the more oxygen vacancies and better lowâtemperature reducibility, that are mainly responsible for the excellent activity of CCZâSW. The existence of sugar in BC could hinder the agglomeration of active metal particles during the calcination process. Combined with the results of inâ
situ DRIFT, the adsorbed toluene on the catalyst surface is oxidized into alkoxide, aldehydic and carboxylic acid species as intermediates before the complete oxidation into CO2 and H2O.
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