K channel activity and slow oscillations in pancreatic beta cells are regulated by mitochondrial ATP production.

Pancreatic beta cells secrete insulin in response to plasma glucose. The ATP-sensitive potassium channel (K ) links glucose metabolism to islet electrical activity in these cells by responding to increased cytosolic [ATP]/[ADP]. It was recently proposed that pyruvate kinase (PK) in close proximity to beta cell K locally produces the ATP that inhibits K activity.

Membrane lipid organization and nicotinic acetylcholine receptor function: A two-way physiological relationship.

Nicotinic acetylcholine receptors (nAChRs) are involved in a great range of physiological and pathological conditions. Since they are transmembrane proteins, they interact strongly with the lipids surrounding them. Thus, the plasma membrane composition and heterogeneity play an essential role for the correct nAChR function, on the one hand, and the nAChR influences its immediate lipid environment, on the other hand.

The nematode serotonin-gated chloride channel MOD-1: A novel target for anthelmintic therapy.

Anthelmintics are used to treat human and veterinary parasitic diseases and to reduce crop and livestock production loss associated with parasitosis. The free-living nematode Caenorhabditis elegans, a model system for anthelmintic drug discovery, has a serotonin (5-HT)-gated chloride channel, MOD-1, which belongs to the Cys-loop receptor family and modulates locomotory and behavioral functions. Since MOD-1 is unique to nematodes, it is emerging as an attractive anthelmintic drug target, but details of MOD-1 function are unclear.

New Synthetic Caffeine Analogs as Modulators of the Cholinergic System.

Alzheimer's disease is a multifactorial neurodegenerative disorder. Since cholinergic deficit is a major factor in this disease, two molecular targets for its treatment are the acetylcholinesterase (AChE) and the nicotinic acetylcholine receptors (nAChRs). Given that caffeine is a natural compound that behaves as an AChE inhibitor and as a partial agonist of nAChRs, the aim of this work was to synthetize more potent bifunctional caffeine analogs that modulate these two molecular targets.

Is the Pain Just Physical? The Role of Psychological Distress, Quality of Life, and Autistic Traits in Ehlers-Danlos Syndrome, an Internet-Based Survey in Italy.

Background: Ehlers-Danlos syndromes (EDS) have been associated with psychological distress, comorbid psychiatric disorders, and worsening in quality of life (QoL). Among the neurodevelopmental disorders, autism spectrum disorders (ASD) have shown the highest rates of co-occurrence with EDS. The reasons for these associations are unknown and a possible role of pain in increasing the risk of psychiatric disorders in EDS has been suggested.

Identification of a five gene signature to predict time to biochemical recurrence after radical prostatectomy.

Background: Identification of novel biomarkers associated with high-risk prostate cancer or biochemical recurrence can drive improvement in detection, prognosis, and treatment. However, studies can be limited by small sample sizes and sparse clinical follow-up data. We utilized a large sample of prostate specimens to identify a predictive model of biochemical recurrence following radical prostatectomy and we validated this model in two external data sets.

Loss of Choline Agonism in the Inner Ear Hair Cell Nicotinic Acetylcholine Receptor Linked to the α10 Subunit.

The α9α10 nicotinic acetylcholine receptor (nAChR) plays a fundamental role in inner ear physiology. It mediates synaptic transmission between efferent olivocochlear fibers that descend from the brainstem and hair cells of the auditory sensory epithelium. The α9 and α10 subunits have undergone a distinct evolutionary history within the family of nAChRs.

Delirium is an important predictor of mortality in elderly patients with ST-elevation myocardial infarction: insight from National Inpatient Sample database.

Objective: Delirium is a frequently encountered clinical condition in hospitalized patients and is known to be associated with poor outcomes. This study aims to assess the impacts of delirium in elderly patients undergoing percutaneous coronary intervention (PCI) following ST-elevation myocardial infarction (STEMI).

Methods: We queried the National Inpatient Samples from 2010 to 2014 to identify all patients aged 65 and older, and admitted with a primary diagnosis of STEMI undergoing PCI by using the International Classification of Diseases-Ninth Edition-Clinical Modification diagnosis codes.

Orthosteric and Allosteric Activation of Human 5-HTA Receptors.

The serotonin type 3 receptor (5-HT) is a ligand-gated ion channel that converts the binding of the neurotransmitter serotonin (5-HT) into a transient cation current that mediates fast excitatory responses in peripheral and central nervous systems. Information regarding the activation and modulation of the human 5-HT type A receptor has been based only on macroscopic current measurements because of its low ion conductance. By constructing a high-conductance human 5-HTA receptor, we here revealed mechanistic information regarding the orthosteric activation by 5-HT and by the partial agonist tryptamine, and the allosteric activation by the terpenoids, carvacrol, and thymol.

Mechanism of calcium potentiation of the α7 nicotinic acetylcholine receptor.

The α7 nicotinic acetylcholine receptor (nAChR) is among the most abundant types of nAChR in the brain, yet the ability of nerve-released ACh to activate α7 remains enigmatic. In particular, a major population of α7 resides in extra-synaptic regions where the ACh concentration is reduced, owing to dilution and enzymatic hydrolysis, yet ACh shows low potency in activating α7. Using high-resolution single-channel recording techniques, we show that extracellular calcium is a powerful potentiator of α7 activated by low concentrations of ACh.

Characterization of Upper Limb Impairments at Body Function, Activity, and Participation in Persons With Multiple Sclerosis by Behavioral and EMG Assessment: A Cross-Sectional Study.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating and disabling disease which primarily affects individuals in their early life between 20 and 40 years of age. MS is a complex condition, which may lead to a variety of upper limb (UL) dysfunctions and functional deficits. To explore upper limb impairments at body function, activity, and participation in persons with MS (PwMS) and severe hand dexterity impairment by behavioral and surface electromyography (sEMG) assessments.

Molecular Modulation of Human α7 Nicotinic Receptor by Amyloid-β Peptides.

Amyloid β peptide (Aβ) is a key player in the development of Alzheimer's disease (AD). It is the primary component of senile plaques in AD patients and is also found in soluble forms. Cholinergic activity mediated by α7 nicotinic receptors has been shown to be affected by Aβ soluble forms.

Prediction of Incident Delirium Using a Random Forest classifier.

Delirium is a serious medical complication associated with poor outcomes. Given the complexity of the syndrome, prevention and early detection are critical in mitigating its effects. We used Confusion Assessment Method (CAM) screening and Electronic Health Record (EHR) data for 64,038 inpatient visits to train and test a model predicting delirium arising in hospital.

Effects of High-intensity Robot-assisted Hand Training on Upper Limb Recovery and Muscle Activity in Individuals With Multiple Sclerosis: A Randomized, Controlled, Single-Blinded Trial.

Integration of robotics and upper limb rehabilitation in people with multiple sclerosis (PwMS) has rarely been investigated. To compare the effects of robot-assisted hand training against non-robotic hand training on upper limb activity in PwMS. To compare the training effects on hand dexterity, muscle activity, and upper limb dysfunction as measured with the International Classification of Functioning.

Activation of Levamisole-Sensitive and Mammalian Nicotinic Receptors by the Antiparasitic Bephenium.

Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels involved in neuromuscular transmission. In nematodes, muscle nAChRs are targets of antiparasitic drugs. Bephenium is an anthelmintic compound whose molecular action in the free-living nematode , which is a model for anthelmintic drug discovery, is poorly known.

Neuronal calcineurin transcriptional targets parallel changes observed in Alzheimer disease brain.

Unlabelled: Synaptic dysfunction and loss are core pathological features in Alzheimer disease (AD). In the vicinity of amyloid-β plaques in animal models, synaptic toxicity occurs and is associated with chronic activation of the phosphatase calcineurin (CN). Indeed, pharmacological inhibition of CN blocks amyloid-β synaptotoxicity.

A human-specific, truncated α7 nicotinic receptor subunit assembles with full-length α7 and forms functional receptors with different stoichiometries.

The cholinergic α7 nicotinic receptor gene, , encodes a subunit that forms the homopentameric α7 receptor, involved in learning and memory. In humans, exons 5-10 in are duplicated and fused to the genetic element, giving rise to the hybrid gene Its product, dupα7, is a truncated subunit lacking part of the N-terminal extracellular ligand-binding domain and is associated with neurological disorders, including schizophrenia, and immunomodulation. We combined dupα7 expression on mammalian cells with patch clamp recordings to understand its functional role.

A novel pharmacological activity of caffeine in the cholinergic system.

Cholinergic deficit is regarded as an important factor responsible for Alzheimer's disease (AD) symptoms. Acetylcholinesterase (AChE) and nicotinic receptor (AChR) are two molecular targets for the treatment of this disease. We found here that methanolic extracts of Camellia sinensis exhibited anticholinesterase activity and induced AChR conformational changes.

Molecular function of α7 nicotinic receptors as drug targets.

Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated ion channels involved in many physiological and pathological processes. In vertebrates, there are seventeen different nAChR subunits that combine to yield a variety of receptors with different pharmacology, function, and localization. The homomeric α7 receptor is one of the most abundant nAChRs in the nervous system and it is also present in non-neuronal cells.

Transcriptome alterations of prefrontal cortical parvalbumin neurons in schizophrenia.

Schizophrenia (SZ) is associated with dysfunction of the dorsolateral prefrontal cortex (DLPFC). This dysfunction is manifest as cognitive deficits that appear to arise from disturbances in gamma frequency oscillations. These oscillations are generated in DLPFC layer 3 (L3) via reciprocal connections between pyramidal cells (PCs) and parvalbumin (PV)-containing interneurons.

Statin and Its Association With Delirium in the Medical ICU.

Objectives: To examine the association between statin use and the risk of delirium in hospitalized patients with an admission to the medical ICU.

Design: Retrospective propensity-matched cohort analysis with accrual from September 1, 2012, to September 30, 2015.

Setting: Hartford Hospital, Hartford, CT.

Transcriptome Alterations in Prefrontal Pyramidal Cells Distinguish Schizophrenia From Bipolar and Major Depressive Disorders.

Background: Impairments in certain cognitive processes (e.g., working memory) are typically most pronounced in schizophrenia (SZ), intermediate in bipolar disorder, and least in major depressive disorder.