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11.
12.
Substance use disorders (SUDs) are highly prevalent and exact a large toll on individuals’ health, well-being, and social functioning. Long-lasting changes in brain networks involved in reward, executive function, stress reactivity, mood, and self-awareness underlie the intense drive to consume substances and the inability to control this urge in a person who suffers from addiction (moderate or severe SUD). Biological (including genetics and developmental life stages) and social (including adverse childhood experiences) determinants of health are recognized factors that contribute to vulnerability for or resilience against developing a SUD. Consequently, prevention strategies that target social risk factors can improve outcomes and, when deployed in childhood and adolescence, can decrease the risk for these disorders. SUDs are treatable, and evidence of clinically significant benefit exists for medications (in opioid, nicotine and alcohol use disorders), behavioral therapies (in all SUDs), and neuromodulation (in nicotine use disorder). Treatment of SUDs should be considered within the context of a Chronic Care Model, with the intensity of intervention adjusted to the severity of the disorder and with the concomitant treatment of comorbid psychiatric and physical conditions. Involvement of health care providers in detection and management of SUDs, including referral of severe cases to specialized care, offers sustainable models of care that can be further expanded with the use of telehealth. Despite advances in our understanding and management of SUDs, individuals with these conditions continue to be stigmatized and, in some countries, incarcerated, highlighting the need to dismantle policies that perpetuate their criminalization and instead develop policies to ensure support and access to prevention and treatment. 相似文献
13.
Tanja Albrecht Sophie Haebel Anke Koch Ulrike Krause Nora Eckermann Martin Steup 《European journal of biochemistry》2004,271(20):3978-3989
Saccharomyces cerevisiae possesses two glycogenin isoforms (designated as Glg1p and Glg2p) that both contain a conserved tyrosine residue, Tyr232. However, Glg2p possesses an additional tyrosine residue, Tyr230 and therefore two potential autoglucosylation sites. Glucosylation of Glg2p was studied using both matrix-assisted laser desorption ionization and electrospray quadrupole time of flight mass spectrometry. Glg2p, carrying a C-terminal (His6) tag, was produced in Escherichia coli and purified. By tryptic digestion and reversed phase chromatography a peptide (residues 219-246 of the complete Glg2p sequence) was isolated that contained 4-25 glucosyl residues. Following incubation of Glg2p with UDPglucose, more than 36 glucosyl residues were covalently bound to this peptide. Using a combination of cyanogen bromide cleavage of the protein backbone, enzymatic hydrolysis of glycosidic bonds and reversed phase chromatography, mono- and diglucosylated peptides having the sequence PNYGYQSSPAM were generated. MS/MS spectra revealed that glucosyl residues were attached to both Tyr232 and Tyr230 within the same peptide. The formation of the highly glucosylated eukaryotic Glg2p did not favour the bacterial glycogen accumulation. Under various experimental conditions Glg2p-producing cells accumulated approximately 30% less glycogen than a control transformed with a Glg2p lacking plasmid. The size distribution of the glycogen and extractable activities of several glycogen-related enzymes were essentially unchanged. As revealed by high performance anion exchange chromatography, the intracellular maltooligosaccharide pattern of the bacterial cells expressing the functional eukaryotic transgene was significantly altered. Thus, the eukaryotic glycogenin appears to be incompatible with the bacterial initiation of glycogen biosynthesis. 相似文献
14.
15.
Edgar Vázquez-Contreras Nora Vázquez-Laslop Georges Dreyfus 《Journal of bioenergetics and biomembranes》1995,27(1):109-116
A functional F0F1 ATP synthase that contains the endogenous inhibitor protein (F0F1I) was isolated by the use of two combined techniques [Adolfsen, R., McClung, J.A., and Moudrianakis, E. N. (1975).Biochemistry
14, 1727–1735; Dreyfus, G., Celis, H., and Ramirez, J. (1984).Anal. Biochem.
142, 215–220]. The preparation is composed of 18 subunits as judged by SDS-PAGE. A steady-state kinetic analysis of the latent ATP synthase complex at various concentrations of ATP showed aV
max of 1.28mol min–1 mg–1, whereas theV
max of the complex without the inhibitor was 8.3mol min–1 mg–1. In contrast, theK
m
for Mg-ATP of F0F1 I was 148M, comparable to theK
m
value of 142M of the F0F1 complex devoid of IF1. The hydrolytic activity of the F0F1I increased severalfold by incubation at 60C at pH 6.8, reaching a maximal ATPase activity of 9.5mol min–1 mg–1; at pH 9.0 a rapid increase in the specific activity of hydrolysis was followed by a sharp drop in activity. The latent ATP synthase was reconstituted into liposomes by means of a column filtration method. The proteoliposomes showed ATP-Pi exchange activity which responded to phosphate concentration and was sensitive to energy transfer inhibitors like oligomycin and the uncouplerp-trifluoromethoxyphenylhydrazone. 相似文献
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Ecological surveys were carried out to investigate the distribution and characterization of remaining mangrove stands in Hong
Kong. The field studies indicate that 43 mangrove stands, excluding Mai Po Nature Reserve, still remained along the coastline
of Hong Kong despite tremendous reclamation and development which occurred in the past 40 years. Most mangrove stands were
found in Deep Bay (western part)and Sai Kung District (eastern coasts). The total areas occupied by these mangrove stands
were 178 ha,varying from a very small stand (with 1–2 mangrove shrubs) to fairly extensive mangroves in Deep Bay (> 10 ha).
It appeared that mangrove stands located in Deep Bay area were larger than those in the eastern coasts. Twenty plant species
were identified from these stands, with 13 being exclusive or associate mangrove species. The major constituent species were
Kandelia candel, Aegiceras corniculatum, Excoecaria agallocha and Avicennia marina. Rare species such as Heritiera littoralis
were only found in a few mangrove stands. Out of the 43remaining mangrove stands, 23 were more worthwhile for conservation
and their plant community structures were further investigated by transect and quadrat analyses. The importance values (sum
of relative abundance,frequency and dominance) show that K. candel was the most dominant species. Species richness and Simpson's
indices together with tree height, tree density and canopy area fluctuated significantly between mangrove stands. These values
were used to prioritize the conservation potential of the remaining mangrove stands in Hong Kong.
This revised version was published online in August 2006 with corrections to the Cover Date. 相似文献
18.
Nora M. Bello Juan P. Steibel Robert J. Tempelman 《Biometrical journal. Biometrische Zeitschrift》2010,52(3):297-313
Bivariate mixed effects models are often used to jointly infer upon covariance matrices for both random effects ( u ) and residuals ( e ) between two different phenotypes in order to investigate the architecture of their relationship. However, these (co)variances themselves may additionally depend upon covariates as well as additional sets of exchangeable random effects that facilitate borrowing of strength across a large number of clusters. We propose a hierarchical Bayesian extension of the classical bivariate mixed effects model by embedding additional levels of mixed effects modeling of reparameterizations of u‐ level and e ‐level (co)variances between two traits. These parameters are based upon a recently popularized square‐root‐free Cholesky decomposition and are readily interpretable, each conveniently facilitating a generalized linear model characterization. Using Markov Chain Monte Carlo methods, we validate our model based on a simulation study and apply it to a joint analysis of milk yield and calving interval phenotypes in Michigan dairy cows. This analysis indicates that the e ‐level relationship between the two traits is highly heterogeneous across herds and depends upon systematic herd management factors. 相似文献
19.
Akchheta Karki Joachim Vollbrecht Alexander J. Gillett Philipp Selter Jaewon Lee Zhengxing Peng Nora Schopp Alana L. Dixon Max Schrock Vojtech Ndady Franz Schauer Harald Ade Bradley F. Chmelka Guillermo C. Bazan Richard H. Friend Thuc‐Quyen Nguyen 《Liver Transplantation》2020,10(29)
Even though significant breakthroughs with over 18% power conversion efficiencies (PCEs) in polymer:non‐fullerene acceptor (NFA) bulk heterojunction organic solar cells (OSCs) have been achieved, not many studies have focused on acquiring a comprehensive understanding of the underlying mechanisms governing these systems. This is because it can be challenging to delineate device photophysics in polymer:NFA blends comprehensively, and even more complicated to trace the origins of the differences in device photophysics to the subtle differences in energetics and morphology. Here, a systematic study of a series of polymer:NFA blends is conducted to unify and correlate the cumulative effects of i) voltage losses, ii) charge generation efficiencies, iii) non‐geminate recombination and extraction dynamics, and iv) nuanced morphological differences with device performances. Most importantly, a deconvolution of the major loss processes in polymer:NFA blends and their connections to the complex BHJ morphology and energetics are established. An extension to advanced morphological techniques, such as solid‐state NMR (for atomic level insights on the local ordering and donor:acceptor π? π interactions) and resonant soft X‐ray scattering (for donor and acceptor interfacial area and domain spacings), provide detailed insights on how efficient charge generation, transport, and extraction processes can outweigh increased voltage losses to yield high PCEs. 相似文献
20.