alkaloid complanadine A, isolated by Kobayashi et al. in 2000, is a complex and unsymmetrical dimer of lycodine. Biologically, it is a novel and promising lead compound for the development of new treatment for neurodegenerative disorders and persistent pain management.
View Article and Find Full Text PDFTheory without relevance for practice in a professional graduate degree has been critiqued by some scholars as a deficit approach when preparing MBA students for the workforce. Scholars and practitioners alike call for more pedagogy in the curriculum with a focus on innovation, creativity, and the involvement of industry practitioners. This paper serves as a case study of a moment in time on Monday, 14 June 2021, when the concept of "pracademics" was realized between two artists and two faculty.
View Article and Find Full Text PDFBack pain is one of the largest drivers of workplace injury and lost productivity in industries around the world. Back injuries were one of the leading reasons in resulting in days away from work at 38.5% across all occupations, increasing for manual laborers to 43%.
View Article and Find Full Text PDFComplanadine A and lycodine are representative members of the alkaloids with a characteristic pyridine-containing tetracyclic skeleton. Complanadine A has demonstrated promising neurotrophic activity and potential for persistent pain management. Herein we report a pyrrole strategy enabled by one-carbon insertion and polarity inversion for concise total syntheses of complanadine A and lycodine.
View Article and Find Full Text PDFObjectives: To compare participant-reported bleeding and pain with two medication regimens for early pregnancy loss (EPL).
Study Design: We performed a secondary analysis of a randomized trial in which participants took either mifepristone 200 mg orally followed by misoprostol 800 mcg vaginally 24 hours later or misoprostol alone for medical management of EPL. Participants reported bleeding and pain (Numeric Pain Rating Scale, NPRS, 0-10) with daily paper diaries and at study visits on trial days 3, 8, and 30.
Abiespiroside A (1), beshanzuenone C (2), and beshanzuenone D (3) belong to the Abies sesquiterpenoid family. Beshanzuenones C (2) and D (3) are isolated from the critically endangered Chinese fir tree species Abies beshanzuensis and demonstrated weak inhibiting activity against protein tyrosine phosphatase 1B (PTP1B). We describe herein the first total syntheses of these Abies sesquiterpenoids relying on the sustainable and inexpensive chiral pool molecule (+)-carvone.
View Article and Find Full Text PDFCovering: 2000-2018In this review, we highlight recent examples of natural product total syntheses employing transition metal-mediated/catalyzed carbonylative cyclization strategies to build key ring systems. It mainly covers carbonylative cyclizations for the construction of O-heterocycles, N-heterocycles and carbocycles including cyclic ketones and phenols. The reaction types include carbonylation of epoxide to β-lactones, carbonylative (macro)lactonization/lactamization, the Semmelhack reaction, tandem hydroformylation-cyclization, the Pauson-Khand reaction, carbonylative C-H activation cyclization, the Stille/Suzuki carbonylation, [n + m + 1] carbonylative cycloaddition, the Dötz annulation, and others.
View Article and Find Full Text PDFBecause molecular mechanisms underlying refractory focal epilepsy are poorly defined, we performed transcriptome analysis on human epileptogenic tissue. Compared with controls, expression of Circadian Locomotor Output Cycles Kaput (CLOCK) is decreased in epileptogenic tissue. To define the function of CLOCK, we generated and tested the Emx-Cre; Clock and PV-Cre; Clock mouse lines with targeted deletions of the Clock gene in excitatory and parvalbumin (PV)-expressing inhibitory neurons, respectively.
View Article and Find Full Text PDFAlterations in the ratio of excitatory to inhibitory transmission are emerging as a common component of many nervous system disorders, including autism spectrum disorders (ASDs). Tonic γ-aminobutyric acidergic (GABAergic) transmission provided by peri- and extrasynaptic GABA type A (GABAA ) receptors powerfully controls neuronal excitability and plasticity and, therefore, provides a rational therapeutic target for normalizing hyperexcitable networks across a variety of disorders, including ASDs. Our previous studies revealed tonic GABAergic deficits in principal excitatory neurons in the basolateral amygdala (BLA) in the Fmr1(-/y) knockout (KO) mouse model fragile X syndrome.
View Article and Find Full Text PDFContext: Competitive sports are recognized as having unique health benefits and risks, and the effect of sports on life-span health among elite athletes has received increasing attention. However, supporting scientific data are sparse and do not represent modern athletes.
Objective: To assess holistic life-span health and health-related quality-of-life (HRQL) among current and former National Collegiate Athletic Association student-athletes (SAs).
Fragile X syndrome (FXS) is the leading cause of inherited intellectual disability. Comorbidities of FXS such as autism are increasingly linked to imbalances in excitation and inhibition (E/I) as well as dysfunction in GABAergic transmission in a number of brain regions including the amygdala. However, the link between E/I imbalance and GABAergic transmission deficits in the FXS amygdala is poorly understood.
View Article and Find Full Text PDFMicrobiology (Reading)
March 2014
The oligotrophic bacterium Caulobacter crescentus has the ability to metabolize various organic molecules, including plant structural carbohydrates, as a carbon source. The nature of β-glucosidase (BGL)-mediated gluco-oligosaccharide degradation and nutrient transport across the outer membrane in C. crescentus was investigated.
View Article and Find Full Text PDFFragile X syndrome (FXS) is a debilitating neurodevelopmental disorder thought to arise from disrupted synaptic communication in several key brain regions, including the amygdala, a central processing center for information with emotional and social relevance. Recent studies reveal defects in both excitatory and inhibitory neurotransmission in mature amygdala circuits in Fmr1(-/y) mutants, the animal model of FXS. However, whether these defects are the result of altered synaptic development or simply faulty mature circuits remains unknown.
View Article and Find Full Text PDFDeficits in neuronal plasticity are common hallmarks of many neurodevelopmental disorders. In the case of fragile-X syndrome (FXS), disruption in the function of a single gene, FMR1, results in a variety of neurological consequences directly related to problems with the development, maintenance, and capacity of plastic neuronal networks. In this paper, we discuss current research illustrating the mechanisms underlying plasticity deficits in FXS.
View Article and Find Full Text PDFFragile X syndrome (FXS) is a neurodevelopmental disorder characterized by intellectual disability, sensory hypersensitivity, and high incidences of autism spectrum disorders and epilepsy. These phenotypes are suggestive of defects in neural circuit development and imbalances in excitatory glutamatergic and inhibitory GABAergic neurotransmission. While alterations in excitatory synapse function and plasticity are well-established in Fmr1 knockout (KO) mouse models of FXS, a number of recent electrophysiological and molecular studies now identify prominent defects in inhibitory GABAergic transmission in behaviorally relevant forebrain regions such as the amygdala, cortex, and hippocampus.
View Article and Find Full Text PDFPathogenic mitochondrial DNA (mtDNA) mutations leading to mitochondrial dysfunction can cause cardiomyopathy and heart failure. Owing to a high mutation rate, mtDNA defects may occur at any nucleotide in its 16 569 bp sequence. Complete mtDNA sequencing may detect pathogenic mutations, which can be difficult to interpret because of normal ethnic/geographic-associated haplogroup variation.
View Article and Find Full Text PDFThe mitochondrial DNA (mtDNA) encompasses two classes of functionally important sequence variants: recent pathogenic mutations and ancient adaptive polymorphisms. To rapidly and cheaply evaluate both classes of single nucleotide variants (SNVs), we have developed an integrated system in which mtDNA SNVs are analyzed by multiplex primer extension using the SNaPshot system. A multiplex PCR amplification strategy was used to amplify the entire mtDNA, a computer program identifies optimal extension primers, and a complete global haplotyping system is also proposed.
View Article and Find Full Text PDFFragile X syndrome (FXS) is a neurodevelopmental disorder characterized by variable cognitive impairment and behavioral disturbances such as exaggerated fear, anxiety and gaze avoidance. Consistent with this, findings from human brain imaging studies suggest dysfunction of the amygdala. Underlying alterations in amygdala synaptic function in the Fmr1 knock-out (KO) mouse model of FXS, however, remain largely unexplored.
View Article and Find Full Text PDFInhibitory neurosteroids, molecules generated in glia from circulating steroid hormones and de novo from cholesterol, keep seizures in check in epileptic animals. They can enhance inhibitory transmission mediated by gamma-aminobutyric acid receptors and have anticonvulsant action.
View Article and Find Full Text PDFPurpose: New treatments are needed for status epilepticus (SE) that is refractory to drugs modulating GABA(A) receptors, and NMDA receptor antagonists are candidate drugs.
Methods: Clinically available NMDA receptor antagonist ketamine was tested for effectiveness in terminating prolonged SE induced by a combination of lithium and pilocarpine. Animals were treated 10 min after first grade 5 behavioral seizure (Racine scoring scale) by intraperitoneal administration of ketamine, diazepam, or saline.
Objective: No clear consensus exists regarding the effect of sustained, heavy drinking on hippocampal volume. Our prior work hypothesized significantly lowered total hippocampus volumes in heavy chronically drinking alcohol-dependent (AD) subjects compared with light-drinking nondependent control subjects matched for age and gender.
Method: Using a series of applicable exclusion criteria culled from previous published studies, we measured hippocampal volumes from MRI scan data acquired on a 3T scanner and subjected those data to automated volume analysis blind to the drinking history.
Objective: The effects of hypercortisolism on hippocampal volume have not been studied in heavy drinkers. Prior work suggested increased hypothalamic-pituitary-adrenal activity in relation to lowered total hippocampus volume (THV) in heavy-drinking alcohol-dependent (AD) subjects. The present study hypothesized the following: (1) that chronic heavy-drinking subjects would demonstrate significantly higher salivary cortisol concentrations than light-drinking control subjects and (2) that data from the whole sample group would present an inverse relationship between cortisol concentration and THV.
View Article and Find Full Text PDFPsychological treatment studies, uncontrolled for ego defense (adaptive) styles, report conflicting survival results. The authors hypothesized that "immature" adaptive styles and frequent depression symptoms would independently predict lower survival rates. This study followed 86 consecutive, mostly late-stage, cancer outpatients for up to 5 years; their survival data were analyzed in relation to the Beck Depression Inventory and the Defense Style Questionnaire scores at study entry.
View Article and Find Full Text PDFHaving reported high adherence to court-mandated disulfiram treatment, we hypothesized that other Department of Veterans Affairs (DVA) medical centers would report frequent use of this modality. Telephone interviews with DVA substance abuse clinics in 48 of the 50 states matched the national DVA frequencies. Phone survey responders reported disulfiram prescription as never/rarely 63%, sometimes 32%, and often 5%, while court-ordered disulfiram was used never/rarely 95%, sometimes 3%, and often 2%.
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