Chlorpyrifos fate in the Arctic: Importance of analyte structure in interactions with Arctic dissolved organic matter.

The insecticide and current use pesticide chlorpyrifos (CLP) is transported via global distillation to the Arctic where it may pose a threat to this ecosystem. CLP is readily detected in Arctic environmental compartments, but current research has not studied its partitioning between water and dissolved organic matter (DOM) nor the role of photochemistry in CLP's fate in aquatic systems. Here, the partition coefficients of CLP were quantified with various types of DOM isolated from the Arctic and an International Humic Substances Society (IHSS) reference material Suwannee River natural organic matter (SRNOM).

Comparison of breath-guards and face-masks on droplet spread in eye clinics.

Introduction: COVID-19 has impacted ophthalmic care delivery, with many units closed and several ophthalmologists catching COVID-19. Understanding droplet spread in clinical and training settings is paramount in maintaining productivity, while keeping patients and practitioners safe.

Objectives: We aimed to assess the effectiveness of a breath-guard and a face mask in reducing droplet spread within an eye clinic.

Desmin intermediate filaments and tubulin detyrosination stabilize growing microtubules in the cardiomyocyte.

In heart failure, an increased abundance of post-translationally detyrosinated microtubules stiffens the cardiomyocyte and impedes its contractile function. Detyrosination promotes interactions between microtubules, desmin intermediate filaments, and the sarcomere to increase cytoskeletal stiffness, yet the mechanism by which this occurs is unknown. We hypothesized that detyrosination may regulate the growth and shrinkage of dynamic microtubules to facilitate interactions with desmin and the sarcomere.

A Balance Between Intermediate Filaments and Microtubules Maintains Nuclear Architecture in the Cardiomyocyte.

Mechanical forces are transduced to nuclear responses via the linkers of the nucleoskeleton and cytoskeleton (LINC) complex, which couples the cytoskeleton to the nuclear lamina and associated chromatin. While disruption of the LINC complex can cause cardiomyopathy, the relevant interactions that bridge the nucleoskeleton to cytoskeleton are poorly understood in the cardiomyocyte, where cytoskeletal organization is unique. Furthermore, while microtubules and desmin intermediate filaments associate closely with cardiomyocyte nuclei, the importance of these interactions is unknown.

Suppression of detyrosinated microtubules improves cardiomyocyte function in human heart failure.

Detyrosinated microtubules provide mechanical resistance that can impede the motion of contracting cardiomyocytes. However, the functional effects of microtubule detyrosination in heart failure or in human hearts have not previously been studied. Here, we utilize mass spectrometry and single-myocyte mechanical assays to characterize changes to the cardiomyocyte cytoskeleton and their functional consequences in human heart failure.

Microtubule mechanics in the working myocyte.

The mechanical role of cardiac microtubules (MTs) has been a topic of some controversy. Early studies, which relied largely on pharmacological interventions that altered the MT cytoskeleton as a whole, presented no consistent role. Recent advances in the ability to observe and manipulate specific properties of the cytoskeleton have strengthened our understanding.

Impaired calcium signaling in muscle fibers from intercostal and foot skeletal muscle in a cigarette smoke-induced mouse model of COPD.

Introduction: Respiratory and locomotor skeletal muscle dysfunction are common findings in chronic obstructive pulmonary disease (COPD); however, the mechanisms that cause muscle impairment in COPD are unclear. Because Ca signaling in excitation-contraction (E-C) coupling is important for muscle activity, we hypothesized that Ca dysregulation could contribute to muscle dysfunction in COPD.

Methods: Intercostal and flexor digitorum brevis muscles from control and cigarette smoke-exposed mice were investigated.

Detyrosinated microtubules buckle and bear load in contracting cardiomyocytes.

The microtubule (MT) cytoskeleton can transmit mechanical signals and resist compression in contracting cardiomyocytes. How MTs perform these roles remains unclear because of difficulties in observing MTs during the rapid contractile cycle. Here, we used high spatial and temporal resolution imaging to characterize MT behavior in beating mouse myocytes.

Detyrosinated microtubules modulate mechanotransduction in heart and skeletal muscle.

In striated muscle, X-ROS is the mechanotransduction pathway by which mechanical stress transduced by the microtubule network elicits reactive oxygen species. X-ROS tunes Ca(2+) signalling in healthy muscle, but in diseases such as Duchenne muscular dystrophy (DMD), microtubule alterations drive elevated X-ROS, disrupting Ca(2+) homeostasis and impairing function. Here we show that detyrosination, a post-translational modification of α-tubulin, influences X-ROS signalling, contraction speed and cytoskeletal mechanics.

Atypical behavior of NFATc1 in cultured intercostal myofibers.

Background: The NFATc transcription factor family is responsible for coupling cytoplasmic calcium signals to transcription programs in a wide variety of cell types. In skeletal muscle, these transcription factors control the fiber type in response to muscle activity. This excitation-transcription (E-T) coupling permits functional adaptation of muscle according to use.

Elevated extracellular glucose and uncontrolled type 1 diabetes enhance NFAT5 signaling and disrupt the transverse tubular network in mouse skeletal muscle.

The transcription factor nuclear factor of activated T-cells 5 (NFAT5) is a key protector from hypertonic stress in the kidney, but its role in skeletal muscle is unexamined. Here, we evaluate the effects of glucose hypertonicity and hyperglycemia on endogenous NFAT5 activity, transverse tubular system morphology and Ca(2+) signaling in adult murine skeletal muscle fibers. We found that exposure to elevated glucose (25-50 mmol/L) increased NFAT5 expression and nuclear translocation, and NFAT-driven transcriptional activity.

Adherent primary cultures of mouse intercostal muscle fibers for isolated fiber studies.

Primary culture models of single adult skeletal muscle fibers dissociated from locomotor muscles adhered to glass coverslips are routine and allow monitoring of functional processes in living cultured fibers. To date, such isolated fiber cultures have not been established for respiratory muscles, despite the fact that dysfunction of core respiratory muscles leading to respiratory arrest is the most common cause of death in many muscular diseases. Here we present the first description of an adherent culture system for single adult intercostal muscle fibers from the adult mouse.

Stereoselective neuroprotection by novel 2,3-benzodiazepine non-competitive AMPA antagonist against non-NMDA receptor-mediated excitotoxicity in primary rat hippocampal cultures.

Glutamate excitotoxicity has been implicated in a variety of acute and chronic neurodegenerative diseases but early phase clinical trials with competitive antagonists at both N-methyl-D-aspartate (NMDA)-receptors and alpha-amino-3-hydroxy-5-methyl-isoxazolepropionate (AMPA) receptors have been disappointing. A family of atypical 2,3 benzodiazepines, exemplified by GYKI 52466, have been described recently which function as non-competitive AMPA-receptor antagonists. We have investigated the neuroprotective efficacy of LY303070 and LY300164, two analogs of GYKI-52466, in an embryonic rat hippocampal culture model of non-NMDA receptor-mediated excitotoxicity using kainic acid (KA) as an agonist at the AMPA/KA receptor.

Decrease in amyloid precursor protein precedes hippocampal degeneration in rat brain following transient global ischemia.

We have studied amyloid precursor protein (APP) expression in rat brain following transient global ischemia. Ischemic damage 24 h after 30 min of four-vessel occlusion (4VO) was limited to the caudate nucleus; hippocampal pyramidal neurons appeared histologically normal by light microscopy. Consistent with ongoing neurodegeneration in the caudate nucleus, microtubule-associated protein-2 (MAP-2) levels assessed by immunoblots were significantly reduced in homogenates of caudate nucleus after 4VO.

GYKI 52466 protects against non-NMDA receptor-mediated excitotoxicity in primary rat hippocampal cultures.

Glutamate excitotoxicity is mediated by both N-methyl-D-aspartate (NMDA)-receptor and non-NMDA receptor (alpha-amino-3-hydroxy-5-methyl-isoxazolepropionate (AMPA)/kainate (KA)) mechanisms but the lack of specific antagonists has limited the characterization of AMPA/KA receptor-mediated excitotoxicity. The 2,3-benzodiazepine GYKI 52466 is a newly described non-competitive AMPA/KA receptor antagonist. We have investigated the neuroprotective efficacy of GYKI 52466 in an embryonic rat hippocampal culture model of non-NMDA receptor-mediated excitotoxicity using KA as an agonist at the AMPA/KA receptor.

Measurement of oxygen consumption and arterial-venous oxygen saturation following total artificial heart implantation.

Current algorithms for control of the total artificial heart are directed at maintaining hemodynamic homeostasis. Future control systems will also need to modify cardiac output in response to metabolic needs. This study was undertaken to evaluate oxygen metabolism monitoring as an indicator of the adequacy of organ and tissue perfusion.

Cyclothiazide treatment unmasks AMPA excitotoxicity in rat primary hippocampal cultures.

Mechanisms of non-NMDA receptor-mediated excitotoxicity were studied in embryonic rat hippocampal cultures using kainic acid (KA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) as agonists. Under basal culture conditions, overnight treatment with AMPA resulted in negligible excitotoxicity as assessed by phase-contrast microscopy and measurement of lactate dehydrogenase (LDH) release. In contrast, similar treatment with KA resulted in marked excitotoxic morphologic changes and release of LDH.

beta-Amyloid peptide in vitro toxicity: lot-to-lot variability.

beta A4 peptide (beta AP) accumulates in amyloid plaques of Alzheimer's disease and may contribute to neuronal degeneration. Conflicting observations have been reported regarding the direct in vitro and in vivo neurotoxicity of beta AP. We have assessed in vitro beta AP toxicity in high density primary rat hippocampal cultures and found marked lot-to-lot differences in the neurotoxic properties of beta AP.

Sulfated glycoprotein-2 expression increases in rodent brain after transient global ischemia.

Sulfated glycoprotein-2 (SGP-2) is emerging as a prominent marker of neurodegeneration in mammalian brain. Regulation of brain SGP-2 was studied in adult male Wistar rats subjected to 30 min of forebrain ischemia by four vessel occlusion. By 3 days after the ischemic insult, SGP-2 RNA levels were increased two fold in caudate nucleus and hippocampus.

Evidence that the acidic polysaccharide secreted by Agrobacterium radiobacter (ATCC 53271) has a seventeen glycosyl-residue repeating unit.

The extracellular anionic polysaccharide produced by the bacterium Agrobacterium radiobacter (ATCC 53271) contains D-galactose, D-glucose, and pyruvic acid in the molar ratio 2:15:2. Analysis of the methylated polysaccharide indicated the presence of terminal, non-reducing glucosyl, 3-, 4-, 6-, 2,4-, and 4,6-linked glucosyl residues, 3-linked 4,6-O-[(S)-1-carboxyethylidene]glucosyl residues, and 3-linked galactosyl residues. Partial acid hydrolysis of the methylated polysaccharide, followed by reduction with NaB2H4 and then O-ethylation, gave a mixture of alkylated oligoglycosyl alditols that were separated by reversed-phase h.

Calves chronically implanted with a total artificial heart as a pharmacological model.

Pharmacological therapy for congestive heart failure includes drugs that have both inotropic and vasoactive effects, although it is sometimes difficult to differentiate between the two effects. An animal with an implanted total artificial heart (TAH) allows the investigation of the vascular effect of these drugs in the absence of the effect on the myocardium. An advantage of the TAH model is its sensitivity to changes in right and left ventricular preload and afterload.

Evidence for microbial polysaccharide preparations containing polyester substituents.

CPMAS 13C-n.m.r.

Microbiologic survey of prosthetic blood pumps presterilization and poststerilization and at explant retrieval.

Device-associated infection remains a major complication of implanted total artificial hearts (TAH). The possibility of microbes being introduced on the device was investigated by conducting a gross microbial assay, pre- and poststerilization, and following explant retrieval. Culture samples were obtained from the housing, base, and blood-contacting diaphragm of Utah-100 artificial ventricles.