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Psychopharmacology Bulletin Jun 2021Post-traumatic stress disorder (PTSD) has become one of the most common psychiatric diagnosis in the United States specifically within the veteran population. The... (Review)
Review
Post-traumatic stress disorder (PTSD) has become one of the most common psychiatric diagnosis in the United States specifically within the veteran population. The current treatment options for this debilitating diagnosis include trauma-focused psychotherapies along with selective serotonin reuptake inhibitors (SSRI) and serotonin-norepinephrine reuptake inhibitors (SNRI). MDMA has recently been shown as a novel therapeutic agent with promisingly results in the treatment of PTSD. MDMA is a psychoactive compound traditionally categorized as a psychedelic amphetamine that deemed a Schedule I controlled substance in the 1980s. Prior to its status as a controlled substance, it was used by psychotherapists for an array of psychiatric issues. In more recent times, MDMA has resurfaced as a potential therapy for PTSD and the data produced from randomized, controlled trials back the desire for MDMA to be utilized as an effective pharmacologic therapy in conjunction with psychotherapy..
Topics: Adult; Hallucinogens; Humans; N-Methyl-3,4-methylenedioxyamphetamine; Psychotherapy; Stress Disorders, Post-Traumatic; Veterans
PubMed: 34421149
DOI: No ID Found -
Nature Cell Biology Feb 2021The response to poly(ADP-ribose) polymerase inhibitors (PARPi) is dictated by homologous recombination (HR) DNA repair and the abundance of lesions that trap PARP...
The response to poly(ADP-ribose) polymerase inhibitors (PARPi) is dictated by homologous recombination (HR) DNA repair and the abundance of lesions that trap PARP enzymes. It remains unclear, however, if the established role of PARP in promoting chromatin accessibility impacts viability in these settings. Using a CRISPR-based screen, we identified the PAR-binding chromatin remodeller ALC1/CHD1L as a key determinant of PARPi toxicity in HR-deficient cells. ALC1 loss reduced viability of breast cancer gene (BRCA)-mutant cells and enhanced sensitivity to PARPi by up to 250-fold, while overcoming several resistance mechanisms. ALC1 deficiency reduced chromatin accessibility concomitant with a decrease in the association of base damage repair factors. This resulted in an accumulation of replication-associated DNA damage, increased PARP trapping and a reliance on HR. These findings establish PAR-dependent chromatin remodelling as a mechanistically distinct aspect of PARPi responses and therapeutic target in HR-deficient cancers.
Topics: BRCA1 Protein; BRCA2 Protein; CRISPR-Cas Systems; Cell Line, Tumor; Cell Proliferation; Chromatin; Chromatin Assembly and Disassembly; Chromosome Aberrations; DNA Helicases; DNA Repair; DNA-Binding Proteins; Epistasis, Genetic; Genomic Instability; Green Fluorescent Proteins; Homologous Recombination; Humans; Methyl Methanesulfonate; Mutation; Phthalazines; Piperazines; Poly Adenosine Diphosphate Ribose; Poly(ADP-ribose) Polymerase Inhibitors; Poly(ADP-ribose) Polymerases; Protein Domains
PubMed: 33462394
DOI: 10.1038/s41556-020-00624-3 -
PLoS Biology Apr 2020The correct subcellular distribution of proteins establishes the complex morphology and function of neurons. Fluorescence microscopy techniques are invaluable to...
The correct subcellular distribution of proteins establishes the complex morphology and function of neurons. Fluorescence microscopy techniques are invaluable to investigate subcellular protein distribution, but they suffer from the limited ability to efficiently and reliably label endogenous proteins with fluorescent probes. We developed ORANGE: Open Resource for the Application of Neuronal Genome Editing, which mediates targeted genomic integration of epitope tags in rodent dissociated neuronal culture, in organotypic slices, and in vivo. ORANGE includes a knock-in library for in-depth investigation of endogenous protein distribution, viral vectors, and a detailed two-step cloning protocol to develop knock-ins for novel targets. Using ORANGE with (live-cell) superresolution microscopy, we revealed the dynamic nanoscale organization of endogenous neurotransmitter receptors and synaptic scaffolding proteins, as well as previously uncharacterized proteins. Finally, we developed a mechanism to create multiple knock-ins in neurons, mediating multiplex imaging of endogenous proteins. Thus, ORANGE enables quantification of expression, distribution, and dynamics for virtually any protein in neurons at nanoscale resolution.
Topics: Animals; CRISPR-Cas Systems; Cells, Cultured; Dependovirus; Epitopes; Female; Gene Editing; Gene Knock-In Techniques; Genes, Reporter; Genetic Vectors; Genome; Green Fluorescent Proteins; Male; Mice, Transgenic; Microscopy, Fluorescence; Molecular Imaging; Neurons; Organ Culture Techniques; Proteins; Rats, Wistar; Receptors, N-Methyl-D-Aspartate; Spatio-Temporal Analysis
PubMed: 32275651
DOI: 10.1371/journal.pbio.3000665 -
IUCrData Feb 2020The title hemihydrate, CHN·0.5HO, was isolated from the condensation reaction of quinoline-2-carbaldehyde with 4-amino-4-1,2,4-triazole. The Schiff base mol-ecule...
The title hemihydrate, CHN·0.5HO, was isolated from the condensation reaction of quinoline-2-carbaldehyde with 4-amino-4-1,2,4-triazole. The Schiff base mol-ecule adopts an configuration about the C=N bond and is approximately planar, with a dihedral angle between the quinoline ring system and the 1,2,4-triazole ring of 12.2 (1)°. In the crystal, one water mol-ecule bridges two Schiff base mol-ecules O-H⋯N hydrogen bonds. The Schiff base mol-ecules are inter-connected by π-π stacking inter-actions [centroid-centroid distances of 3.7486 (7) and 3.9003 (7) Å] into columns along [10].
PubMed: 36340830
DOI: 10.1107/S2414314620001340 -
Molecules (Basel, Switzerland) Apr 2021Inorganic pyrophosphatase (PPase) is a ubiquitous enzyme that converts pyrophosphate (PP) to phosphate and, in this way, controls numerous biosynthetic reactions that... (Review)
Review
Inorganic pyrophosphatase (PPase) is a ubiquitous enzyme that converts pyrophosphate (PP) to phosphate and, in this way, controls numerous biosynthetic reactions that produce PP as a byproduct. PPase activity is generally assayed by measuring the product of the hydrolysis reaction, phosphate. This reaction is reversible, allowing PP synthesis measurements and making PPase an excellent model enzyme for the study of phosphoanhydride bond formation. Here we summarize our long-time experience in measuring PPase activity and overview three types of the assay that are found most useful for (a) low-substrate continuous monitoring of PP hydrolysis, (b) continuous and fixed-time measurements of PP synthesis, and (c) high-throughput procedure for screening purposes. The assays are based on the color reactions between phosphomolybdic acid and triphenylmethane dyes or use a coupled ATP sulfurylase/luciferase enzyme assay. We also provide procedures to estimate initial velocity from the product formation curve and calculate the assay medium's composition, whose components are involved in multiple equilibria.
Topics: Diphosphates; Enzyme Assays; Humans; Hydrolysis; Inorganic Pyrophosphatase; Luciferases; Phosphates
PubMed: 33919593
DOI: 10.3390/molecules26082356 -
Polymers Jun 2022In the present scenario, much importance has been provided to hydrogen energy systems (HES) in the energy sector because of their clean and green behavior during... (Review)
Review
In the present scenario, much importance has been provided to hydrogen energy systems (HES) in the energy sector because of their clean and green behavior during utilization. The developments of novel techniques and materials have focused on overcoming the practical difficulties in the HES (production, storage and utilization). Comparatively, considerable attention needs to be provided in the hydrogen storage systems (HSS) because of physical-based storage (compressed gas, cold/cryo compressed and liquid) issues such as low gravimetric/volumetric density, storage conditions/parameters and safety. In material-based HSS, a high amount of hydrogen can be effectively stored in materials via physical or chemical bonds. In different hydride materials, Mg-based hydrides (Mg-H) showed considerable benefits such as low density, hydrogen uptake and reversibility. However, the inferior sorption kinetics and severe oxidation/contamination at exposure to air limit its benefits. There are numerous kinds of efforts, like the inclusion of catalysts that have been made for Mg-H to alter the thermodynamic-related issues. Still, those efforts do not overcome the oxidation/contamination-related issues. The developments of Mg-H encapsulated by gas-selective polymers can effectively and positively influence hydrogen sorption kinetics and prevent the Mg-H from contaminating (air and moisture). In this review, the impact of different polymers (carboxymethyl cellulose, polystyrene, polyimide, polypyrrole, polyvinylpyrrolidone, polyvinylidene fluoride, polymethylpentene, and poly(methyl methacrylate)) with Mg-H systems has been systematically reviewed. In polymer-encapsulated Mg-H, the polymers act as a barrier for the reaction between Mg-H and O/HO, selectively allowing the H gas and preventing the aggregation of hydride nanoparticles. Thus, the H uptake amount and sorption kinetics improved considerably in Mg-H.
PubMed: 35808653
DOI: 10.3390/polym14132608 -
Journal of Oleo Science 2022Castor oil is a vegetable product extracted from Ricinus communis L (castor seed), which is primarily considered an important commercial value for the manufacturing of... (Review)
Review
Castor oil is a vegetable product extracted from Ricinus communis L (castor seed), which is primarily considered an important commercial value for the manufacturing of soaps, lubricants, coatings, etc. It is rich in hydroxylated fatty acids (ricinoleic acid, 89-92%) and is widely used in the cosmetic, pharmaceutical, oleochemical, and agricultural industries. This oil has also been confirmed as a bactericidal, anti-inflammatory, and antiherpetic agents, due to the ricinoleic acid having functional groups, such as -COOH, -OH, and -C=C-. Furthermore, it is converted into various acid derivative compounds with several applications. Therefore, this article reviewed some reaction stages to the preparation of ricinoleic acid from castor oil. Several methods or reaction pathways were employed in the preparation procedure, such as the Twitchell and Colgate-Emery processes, as well as the alkaline catalyzed, transesterification with methyl ricinoleic, and lipase-catalyzed hydrolysis, respectively. Although each of these preparation methods has advantages and disadvantages, the most effective technique was the hydrolysis through the use of the enzyme lipozyme TL IM. Besides being a green method, the conversion rate in the hydrolysis process was 96.2 ± 1.5.
Topics: Ricinus communis; Castor Oil; Esterification; Fatty Acids; Ricinoleic Acids
PubMed: 35661063
DOI: 10.5650/jos.ess21226 -
Frontiers in Nutrition 2022The green plum is a native fruit of Australia that grows on the tree . This study aimed to confirm the high level of folate in green plums by analyzing a large number of...
The green plum is a native fruit of Australia that grows on the tree . This study aimed to confirm the high level of folate in green plums by analyzing a large number of ripe samples from multiple locations and to understand how folate vitamers change as the fruit grows through maturity stages. This study analyzed green plums for five vitamers of folate, Hfolate, 5-CH-Hfolate, 5-CHO-Hfolate, 10-CHO-PteGlu, and PteGlu (folic acid) using a stable isotope dilution assay on a liquid chromatograph mass spectrometer (LC-MS). Green plums were tested from four locations, two harvests and five maturity stages. Another 11 ripe samples, each from different tree clumps from one location, were also tested as were ripe red-colored green plums. The results show the 5-CH-Hfolate in green plum increases and accumulates in the fruit through development, ripening and senescence. The ripe green plums contain between 82.4 ± 5.5 and 149.4 ± 10.7 μg/100 g Fresh Weight (FW). The red-colored green plums are even higher in folate, with total folate measured as 192.5 ± 7.0 and 293.7 ± 27.4 μg/100 g FW, and further analysis of them is suggested. There is some variation in amounts of folate between fruit from different locations and sets of trees, but all ripe green plums tested are considered good dietary sources of folate.
PubMed: 36313068
DOI: 10.3389/fnut.2022.1006393