Psilocin, the Psychoactive Metabolite of Psilocybin, Modulates Select Neuroimmune Functions of Microglial Cells in a 5-HT Receptor-Dependent Manner.

Neuroinflammation that is caused by microglia, the main immune cells of the brain, contributes to neurodegenerative diseases. Psychedelics, including psilocybin and lysergic acid diethylamide (LSD), possess certain anti-inflammatory properties and, therefore, should be considered as drug candidates for treating neuroinflammatory pathologies. When ingested, psilocybin is rapidly dephosphorylated to yield psilocin, which crosses the blood-brain barrier and exerts psychotropic activity by interacting with the 5-hydroxytryptamine 2A receptors (5-HTRs) on neurons.

Structural journey of an insecticidal protein against western corn rootworm.

The broad adoption of transgenic crops has revolutionized agriculture. However, resistance to insecticidal proteins by agricultural pests poses a continuous challenge to maintaining crop productivity and new proteins are urgently needed to replace those utilized for existing transgenic traits. We identified an insecticidal membrane attack complex/perforin (MACPF) protein, Mpf2Ba1, with strong activity against the devastating coleopteran pest western corn rootworm (WCR) and a novel site of action.

Dynamic changes in metabolites of the kynurenine pathway in Alzheimer's disease, Parkinson's disease, and Huntington's disease: A systematic Review and meta-analysis.

Background: Tryptophan (TRP) is an essential amino acid that must be provided in the diet. The kynurenine pathway (KP) is the main route of TRP catabolism into nicotinamide adenosine dinucleotide (NAD), and metabolites of this pathway may have protective or degenerative effects on the nervous system. Thus, the KP may be involved in neurodegenerative diseases.

Comparing prehistoric constructed languages: world-building and its role in understanding prehistoric languages.

In this paper, we compare the languages each of the authors invented as prehistoric languages for popular culture media. Schreyer's language, , was created for the film (2018), while Adger's language, was created for a television series on how early hominins spread throughout the world (the series was green-lit but then cancelled). We argue that though this creative process may seem far removed from classical research paradigms on language evolution, it can provide some insight into how disparate research on the possible properties of prehistoric languages can be brought together to illustrate how these languages might have worked as whole linguistic systems within these imagined worlds, as well as in prehistory.

A Fold Type II PLP-Dependent Enzyme from Functions as a Serine Synthase and Cysteine Synthase.

Serine synthase (SS) from is a fold type II pyridoxal 5'-phosphate (PLP)-dependent enzyme that catalyzes the β-replacement of l-cysteine with water to form l-serine and HS. Herein, we show that SS can also function as a cysteine synthase, catalyzing the β-replacement of l-serine with bisulfide to produce l-cysteine and HO. The forward (serine synthase) and reverse (cysteine synthase) reactions occur with comparable turnover numbers and catalytic efficiencies for the amino acid substrate.

Quantification of North American and European Crataegus flavonoids by nuclear magnetic resonance spectrometry.

Crataegus (Rosaceae; hawthorn), are small trees that grow in the Northern Hemisphere. Plant materials of Crataegus show promising benefits in adjunctive treatment of cardiovascular disorders, primarily attributed to flavonoids and other phenolic derivatives. H NMR was used in quantification of four flavonoids (naringenin, hyperoside, rutin, and vitexin-2″-O-rhamnoside) and chlorogenic acid in leaf extracts of four Crataegus species.

Egg white consumption increases GSH and lowers oxidative damage in 110-week-old geriatric mice hearts.

The number of geriatrics with an advanced age is rising worldwide, with attendant cardiovascular disorders, characterized by elevated oxidative stress. Such oxidative stress is accelerated by an age-related loss of critical antioxidants like glutathione (GSH) and dietary solutions to combat this loss does not exist. While egg white is rich in sulphur amino acids (AAs), precursors for GSH biosynthesis, whether they can increase sulphur AA in vivo and augment GSH in the aged myocardium remain unclear.

Sleep-disordered breathing is associated with brain vascular reactivity in spinal cord injury.

Objective: To determine the population-level odds of individuals with spinal cord injury (SCI) experiencing fatigue and sleep apnea, to elucidate relationships with level and severity of injury, and to examine associations with abnormal cerebrovascular responsiveness.

Methods: We used population-level data, meta-analyses, and primary physiologic assessments to provide a large-scale integrated assessment of sleep-related complications after SCI. Population-level and meta-analyses included more than 60,000 able-bodied individuals and more than 1,800 individuals with SCI.

Structural and Kinetic Insight into the Biosynthesis of HS and l-Lanthionine from l-Cysteine by a Pyridoxal l-Phosphate-Dependent Enzyme from .

is a common oral bacterium and a major producer of HS, a toxic gas linked to the pathogenesis of periodontal disease. The bacterium encodes a fold type II pyridoxal l-phosphate (PLP)-dependent enzyme, Fn1220 or lanthionine synthase (LS), that generates HS and l-lanthionine (a component of the peptidoglycan layer) through β-replacement of l-cysteine by a second molecule of l-cysteine. Herein, we show through detailed kinetic analysis that LS elicits catalytic promiscuity as demonstrated for other fold type II PLP-dependent homologues, namely, -acetylserine sulfhydrylase (OASS) and cystathionine β-synthase (CBS).

Synthesis and Evaluation of Novel Pyrazole Ethandiamide Compounds as Inhibitors of Human THP-1 Monocytic Cell Neurotoxicity.

Neuroinflammation and microglia-mediated neurotoxicity contribute to the pathogenesis of a broad range of neurodegenerative diseases; therefore, identifying novel compounds that can suppress adverse activation of glia is an important goal. We have previously identified a class of trisubstituted pyrazoles that possess neuroprotective and anti-inflammatory properties. Here, we describe a second generation of pyrazole analogs that were designed to improve their neuroprotective activity toward neurons under inflammatory conditions.

MDMA-assisted psychotherapy for treatment of PTSD: study design and rationale for phase 3 trials based on pooled analysis of six phase 2 randomized controlled trials.

Background: Posttraumatic stress disorder is a prevalent mental health condition with substantial impact on daily functioning that lacks sufficient treatment options. Here we evaluate six phase 2 trials in a pooled analysis to determine the study design for phase 3 trials of MDMA-assisted psychotherapy for PTSD.

Methods: Six randomized, double-blind, controlled clinical trials at five study sites were conducted from April 2004 to February 2017.

Characterization of novel kainic acid analogs as inhibitors of select microglial functions.

Alzheimer's disease (AD) is characterized by abnormal accumulation of extracellular amyloid beta protein (Aβ) plaques and intracellular neurofibrillary tangles, as well as by a state of chronic inflammation in the central nervous system (CNS). Adverse activation of microglia, the brain immune cells, is believed to contribute to AD pathology including excessive neuronal death. Thus, normalizing immune functions of microglia could slow neurodegeneration, and identification of novel compounds capable of modifying microglial functions is an important goal.

Palliative care and the arts: vehicles to introduce medical students to patient-centred decision-making and the art of caring.

Background: Medical Schools are challenged to improve palliative care education and to find ways to introduce and nurture attitudes and behaviours such as empathy, patient-centred care and wholistic care. This paper describes the curriculum and evaluation results of a unique course centred on palliative care decision-making but aimed at introducing these other important competencies as well.

Methods: The 20 h-long optional course, presented in an art museum, combined different learning methods, including reflections on art, case studies, didactic sessions, personal experiences of faculty, reflective trigger videos and group discussions.

The use of propidium monoazide in conjunction with qPCR and Illumina sequencing to identify and quantify live yeasts and bacteria.

Culture-independent methods of microbial identification have been developed, which allow for DNA extraction directly from environmental samples without subjecting microbes to growth on nutrient media. These methods often involve next generation DNA sequencing (NGS) for identifying microbes and qPCR for quantifying them. Despite the benefits of extracting all DNA from the sample, results may be compromised by amplifying DNA from dead cells.

Determination of β-N-methylamino-L-alanine, N-(2-aminoethyl)glycine, and 2,4-diaminobutyric acid in Food Products Containing Cyanobacteria by Ultra-Performance Liquid Chromatography and Tandem Mass Spectrometry: Single-Laboratory Validation.

A single-laboratory validation study was completed for the determination of β-N-methylamino-L-alanine (BMAA), N-(2-aminoethyl)glycine (AEG), and 2,4-diaminobutyric acid (DAB) in bulk natural health product supplements purchased from a health food store in Canada. BMAA and its isomers were extracted with acid hydrolysis to free analytes from protein association. Acid was removed with the residue evaporated to dryness and reconstituted with derivatization using 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AccQ-Fluor).

Identification of new flavan-3-ol monoglycosides by UHPLC-ESI-Q-TOF in grapes and wine.

Flavan-3-ol monoglycosides, having four aglycons (+)-catechin, (-)-epicatechin, (-)-epigallocatechin and epicatechin gallate monomeric units, are detected for the first time in Vitis vinifera L. cv. Merlot grape seeds and wine.

A genetic predisposition to produce low levels of IL-10 is related to depressive symptoms: a pilot study of patients with end stage renal disease.

Objective: Heightened levels of inflammation may be associated with an increased risk of depression, particularly among those with inflammatory medical conditions. Although elevated rates of both systemic inflammation and depression have been documented among patients with end stage renal disease (ESRD), the link between these factors has received little empirical evaluation. The goal of this pilot study was to investigate the association between cytokine gene polymorphisms (that are known to influence pro- and anti-inflammatory cytokine production) and depressive symptoms among patients with ESRD.

Paradoxical effects of alcohol information on alcohol outcome expectancies.

Background: Cognitive associations with alcohol predict both current and future use in youth and young adults. Much cognitive and social cognitive research suggests that exposure to information may have unconscious influences on thinking and behavior. The present study assessed the impact of information statements on the accessibility of alcohol outcome expectancies.

Localization and characterization of phenamil-sensitive Na+ influx in isolated rainbow trout gill epithelial cells.

Percoll density-gradient separation, combined with peanut lectin agglutinin (PNA) binding and magnetic bead separation, was used to separate dispersed fish gill cells into sub-populations. Functional characterization of each of the sub-populations was performed to determine which displayed acid-activated phenamil- and bafilomycin-sensitive Na(+) uptake. Analysis of the mechanism(s) of (22)Na(+) influx was performed in control and acid-activated (addition of 10 mmoll(-1) proprionic acid) cells using a variety of Na(+) transport inhibitors (ouabain, phenamil, HOE-694 and bumetanide) and a V-type ATPase inhibitor (bafilomycin).