Single high-dose buprenorphine for opioid craving during withdrawal.

BackgroundOpioid use disorder is one of the most prevalent addiction problems worldwide. Buprenorphine is used as a medication to treat this disorder, but in countries where buprenorphine is unavailable in combination with naloxone, diversion can be a problem if the medication is given outside a hospital setting.ObjectiveThe objective of this research is to evaluate the effect of a single, high dose of buprenorphine on craving in opioid-dependent patients over 5 days of abstinence from use of other opioids. The primary goal was to determine the safety and efficacy of buprenorphine during withdrawal in a hospital setting.MethodsNinety men who used opium, heroin, or prescribed opioids and met DSM-5 criteria for opioid use disorder (severe form) were randomized to three groups (n = 30 per group) to receive a single, sublingual dose of buprenorphine (32, 64, or 96 mg). The study was conducted in an inpatient psychiatric ward, with appropriate precautions and monitoring of respiratory and cardiovascular measures. Buprenorphine was administered when the patients were in moderate opiate withdrawal, as indicated by the presence of four to five symptoms. A structured clinical interview was conducted, and urine toxicology testing was performed at baseline. Self-reports of craving were obtained at baseline and on each of the 5 days after buprenorphine administration.FindingsCraving decreased from baseline in each of the three groups (p < 0.0001), with a significant interaction between group and time (p < 0.038), indicating that groups with higher doses of buprenorphine had greater reduction.ConclusionsA single, high dose of buprenorphine can reduce craving during opioid withdrawal; additional studies with follow-up are warranted to evaluate safety

Application of nanocellulose composites in the environmental engineering: A review

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The Role of YAP and TAZ in Angiogenesis and Vascular Mimicry

Angiogenesis, the formation of new blood vessels from pre-existing vasculature, is a physiological process that begins in utero and continues throughout life in both good health and disease. Understanding the underlying mechanism in angiogenesis could uncover a new therapeutic approach in pathological angiogenesis. Since its discovery, the Hippo signaling pathway has emerged as a key player in controlling organ size and tissue homeostasis. Recently, new studies have discovered that Hippo and two of its main effectors, Yes-associated protein (YAP) and its paralog transcription activator with PDZ binding motif (TAZ), play critical roles during angiogenesis. In this review, we summarize the mechanisms by which YAP/TAZ regulate endothelial cell shape, behavior, and function in angiogenesis. We further discuss how YAP/TAZ function as part of developmental and pathological angiogenesis. Finally, we review the role of YAP/TAZ in tumor vascular mimicry and propose directions for future work

Extraction and Characterization of Extracellular Proteins and Their Post-Translational Modifications from Arabidopsis thaliana Suspension Cell Cultures and Seedlings: A Critical Review

Proteins secreted by plant cells into the extracellular space, consisting of the cell wall, apoplastic fluid, and rhizosphere, play crucial roles during development, nutrient acquisition, and stress acclimation. However, isolating the full range of secreted proteins has proven difficult, and new strategies are constantly evolving to increase the number of proteins that can be detected and identified. In addition, the dynamic nature of the extracellular proteome presents the further challenge of identifying and characterizing the post-translational modifications (PTMs) of secreted proteins, particularly glycosylation and phosphorylation. Such PTMs are common and important regulatory modifications of proteins, playing a key role in many biological processes. This review explores the most recent methods in isolating and characterizing the plant extracellular proteome with a focus on the model plant Arabidopsis thaliana, highlighting the current challenges yet to be overcome. Moreover, the crucial role of protein PTMs in cell wall signalling, development, and plant responses to biotic and abiotic stress is discussed

Improving education in electrochemistry via a modeling approach and focusing on green chemistry applications

Chemistry is understood and practiced by research chemists by models and visualization. Electrochemistry is no exception. This study shows how a modeling approach focusing on green chemistry applications holds great potential in improving electrochemistry education. Green electrosynthesis, for instance, is ideally suited to understand electrochemical phenomena and to foster the student’s interest and learning in this cross-disciplinary field of chemical knowledge, reinforcing also laboratory education

Biochemical and molecular characterization of AtPAP17: a dual-localized, low molecular weight Arabidopsis purple acid phosphatase upregulated during phosphate deprivation, senescence, and oxidative stress

A 35 kDa monomeric purple acid phosphatase (APase) was purified from cell wall extracts of Pi starved (–Pi) Arabidopsis thaliana suspension cells and identified as AtPAP17 (At3g17790) by mass spectrometry and N-terminal microsequencing. AtPAP17 was de novo synthesized and dual-localized to the secretome and/or intracellular fraction of –Pi or salt-stressed plants, or senescing leaves. Transiently expressed AtPAP17–green fluorescent protein localized to lytic vacuoles of the Arabidopsis suspension cells. No significant biochemical or phenotypical changes associated with AtPAP17 loss of function were observed in an atpap17 mutant during Pi deprivation, leaf senescence, or salinity stress. Nevertheless, AtPAP17 is hypothesized to contribute to Pi metabolism owing to its marked up-regulation during Pi starvation and leaf senescence, broad APase substrate selectivity and pH activity profile, and rapid repression and turnover following Pi resupply to –Pi plants. While AtPAP17 also catalyzed the peroxidation of luminol, which was optimal at pH 9.2, it exhibited a low Vmax and affinity for hydrogen peroxide relative to horseradish peroxidase. These results, coupled with absence of a phenotype in the salt-stressed or –Pi atpap17 mutant, do not support proposals that the peroxidase activity of AtPAP17 contributes to the detoxification of reactive oxygen species during stresses that trigger AtPAP17 up-regulation.This is a manuscript of an article published as O’Gallagher, Bryden, Mina Ghahremani, Kyla Stigter, Emma JL Walker, Michal Pyc, Ang-Yu Liu, Gustavo C. MacIntosh, Robert T. Mullen, and William C. Plaxton. "Arabidopsis PAP17 is a dual-localized purple acid phosphatase up-regulated during phosphate deprivation, senescence, and oxidative stress." Journal of Experimental Botany 73 (2022): 382-399. doi:10.1093/jxb/erab409. Posted with permission

Implications for SARS-CoV-2 Vaccine Design: Fusion of Spike Glycoprotein Transmembrane Domain to Receptor-Binding Domain Induces Trimerization

The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic presents an urgent need for an effective vaccine. Molecular characterization of SARS-CoV-2 is critical to the development of effective vaccine and therapeutic strategies. In the present study, we show that the fusion of the SARS-CoV-2 spike protein receptor-binding domain to its transmembrane domain is sufficient to mediate trimerization. Our findings may have implications for vaccine development and therapeutic drug design strategies targeting spike trimerization. As global efforts for developing SARS-CoV-2 vaccines are rapidly underway, we believe this observation is an important consideration for identifying crucial epitopes of SARS-CoV-2

Synthetic virology approaches to improve the safety and efficacy of oncolytic virus therapies

The large coding potential of vaccinia virus (VV) vectors is a defining feature. However, limited regulatory switches are available to control viral replication as well as timing and dosing of transgene expression in order to facilitate safe and efficacious payload delivery. Herein, we adapt drug-controlled gene switches to enable control of virally encoded transgene expression, including systems controlled by the FDA-approved rapamycin and doxycycline. Using ribosome profiling to characterize viral promoter strength, we rationally design fusions of the operator element of different drug-inducible systems with VV promoters to produce synthetic promoters yielding robust inducible expression with undetectable baseline levels. We also generate chimeric synthetic promoters facilitating additional regulatory layers for VV-encoded synthetic transgene networks. The switches are applied to enable inducible expression of fusogenic proteins, dose-controlled delivery of toxic cytokines, and chemical regulation of VV replication. This toolbox enables the precise modulation of transgene circuitry in VV-vectored oncolytic virus design

Characterization of Critical Determinants of ACE2–SARS CoV-2 RBD Interaction

Despite sequence similarity to SARS-CoV-1, SARS-CoV-2 has demonstrated greater widespread virulence and unique challenges to researchers aiming to study its pathogenicity in humans. The interaction of the viral receptor binding domain (RBD) with its main host cell receptor, angiotensin-converting enzyme 2 (ACE2), has emerged as a critical focal point for the development of anti-viral therapeutics and vaccines. In this study, we selectively identify and characterize the impact of mutating certain amino acid residues in the RBD of SARS-CoV-2 and in ACE2, by utilizing our recently developed NanoBiT technology-based biosensor as well as pseudotyped-virus infectivity assays. Specifically, we examine the mutational effects on RBD-ACE2 binding ability, efficacy of competitive inhibitors, as well as neutralizing antibody activity. We also look at the implications the mutations may have on virus transmissibility, host susceptibility, and the virus transmission path to humans. These critical determinants of virus–host interactions may provide more effective targets for ongoing vaccines, drug development, and potentially pave the way for determining the genetic variation underlying disease severity

Synthetic virology approaches to improve the safety and efficacy of oncolytic virus therapies.

The large coding potential of vaccinia virus (VV) vectors is a defining feature. However, limited regulatory switches are available to control viral replication as well as timing and dosing of transgene expression in order to facilitate safe and efficacious payload delivery. Herein, we adapt drug-controlled gene switches to enable control of virally encoded transgene expression, including systems controlled by the FDA-approved rapamycin and doxycycline. Using ribosome profiling to characterize viral promoter strength, we rationally design fusions of the operator element of different drug-inducible systems with VV promoters to produce synthetic promoters yielding robust inducible expression with undetectable baseline levels. We also generate chimeric synthetic promoters facilitating additional regulatory layers for VV-encoded synthetic transgene networks. The switches are applied to enable inducible expression of fusogenic proteins, dose-controlled delivery of toxic cytokines, and chemical regulation of VV replication. This toolbox enables the precise modulation of transgene circuitry in VV-vectored oncolytic virus design