Perception, a cognitive construct, emerges through sensorimotor integration (SMI). The genetic mechanisms that shape SMI required for perception are unknown. Here, we demonstrate in mice that expression of the autism/intellectual disability gene, , in cortical excitatory neurons is required for formation of somatomotor networks that promote SMI-mediated perception.
View Article and Find Full Text PDFOrganotypic slice cultures (OTCs) have been employed in the laboratory since the early 1980s and have proved to be useful for the study of a number of neural systems. Our recent work focuses on the development of behavioral stress resilience induced by repeated daily injections of neuropeptide Y into the basolateral amygdala (BLA). Resilience develops over weeks, persisting to 8 weeks.
View Article and Find Full Text PDFA significant proportion of autism risk genes regulate synapse function, including plasticity, which is believed to contribute to behavioral abnormalities. However, it remains unclear how impaired synapse plasticity contributes to network-level processes linked to adaptive behaviors, such as experience-dependent ensemble plasticity. We found that , a major autism risk gene, promoted measures of experience-dependent excitatory synapse strengthening in the mouse cortex, including spike-timing-dependent glutamatergic synaptic potentiation and presynaptic bouton formation.
View Article and Find Full Text PDFWe introduce and demonstrate a new approach for nitrogen-vacancy (NV) patterning in diamond, achieving a deterministic, nanometer-thin, and dense delta-doped layer of negatively charged NV centers in diamond. We employed a pure nitridation stage using microwave plasma and a subsequent diamond overgrowth. We present the highest reported nitrogen concentration in a delta-doped layer (1.
View Article and Find Full Text PDFEndogenous neuropeptide Y (NPY) and corticotrophin-releasing factor (CRF) modulate the responses of the basolateral amygdala (BLA) to stress and are associated with the development of stress resilience and vulnerability, respectively. We characterized persistent effects of repeated NPY and CRF treatment on the structure and function of BLA principal neurons in a novel organotypic slice culture (OTC) model of male rat BLA, and examined the contributions of specific NPY receptor subtypes to these neural and behavioral effects. In BLA principal neurons within the OTCs, repeated NPY treatment caused persistent attenuation of excitatory input and induced dendritic hypotrophy via Y receptor activation; conversely, CRF increased excitatory input and induced hypertrophy of BLA principal neurons.
View Article and Find Full Text PDFAlthough NPY has potent anxiolytic actions within the BLA, selective activation of BLA NPY Y receptors (YRs) acutely increases anxiety by an unknown mechanism. Using male rat brain slice electrophysiology, we show that the selective YR agonist, [ahx]NPY, reduced the frequency of GABA-mediated mIPSCs in BLA principal neurons (PNs). [ahx]NPY also reduced tonic activation of GABA receptors (GABAR), which increased PN excitability through inhibition of a tonic, inwardly rectifying potassium current ( ).
View Article and Find Full Text PDFIn addition to cognitive impairments, neurodevelopmental disorders often result in sensory processing deficits. However, the biological mechanisms that underlie impaired sensory processing associated with neurodevelopmental disorders are generally understudied and poorly understood. We found that SYNGAP1 haploinsufficiency in humans, which causes a sporadic neurodevelopmental disorder defined by cognitive impairment, autistic features, and epilepsy, also leads to deficits in tactile-related sensory processing.
View Article and Find Full Text PDFNeuropeptide Y (NPY) expression is tightly linked with the development of stress resilience in rodents and humans. Local NPY injections targeting the basolateral amygdala (BLA) produce long-term behavioral stress resilience in male rats via an unknown mechanism. Previously, we showed that activation of NPY Y receptors hyperpolarizes BLA principal neurons (PNs) through inhibition of the hyperpolarization-activated, depolarizing H-current, The present studies tested whether NPY treatment induces stress resilience by modulating NPY (10 pmol) was delivered daily for 5 d bilaterally into the BLA to induce resilience; thereafter, the electrophysiological properties of PNs and the expression of in the BLA were characterized.
View Article and Find Full Text PDFIn our organization, nursing staff are required to complete a work load measurement tool (GRASP) every shift. This information is used to determine nurse/patient ratios and perform cost analysis. On a Surgical Oncology and Medical Short-Stay Unit, the nursing staff had not completed the GRASP over several years.
View Article and Find Full Text PDFIn layer 5 neocortical pyramidal neurons, backpropagating action potentials (bAPs) firing at rates above a critical frequency (CF) induce supralinear Ca²⁺ influx and regenerative potentials in apical dendrites. Paired temporally with an EPSP, this Ca²⁺ influx can result in synaptic plasticity. We studied the actions of neuropeptide Y (NPY), an abundant neocortical neuropeptide, on Ca²⁺ influx in layer 5 pyramidal neurons of somatosensory neocortex in Sprague Dawley and Wistar rats, using a combination of somatic and dendritic intracellular recordings and simultaneous Ca²⁺ imaging.
View Article and Find Full Text PDFThe 5-HT₃ receptor is a cation selective member of the pentameric Cys-loop ligand-gated ion channels. While five subunits are known to exist, only two receptor subtypes have been significantly characterized: the homomeric receptor consisting of five A subunits and the heteromeric receptor containing both A and B subunits. The agonist recognition and activation of these receptors is orchestrated by six recognition loops three, A-C, on the principal subunit, and three, D-F, on the complementary subunit.
View Article and Find Full Text PDFPrader-Willi Syndrome is the most common syndromic form of human obesity and is caused by the loss of function of several genes, including MAGEL2. Mice lacking Magel2 display increased weight gain with excess adiposity and other defects suggestive of hypothalamic deficiency. We demonstrate Magel2-null mice are insensitive to the anorexic effect of peripherally administered leptin.
View Article and Find Full Text PDFElectron energy loss spectrum, elastic reflectivity and selected vibrational excitation functions were measured by High Resolution Electron Energy Loss Spectroscopy (HREELS) for deuterated nanocrystalline dc GD CVD diamond films. The electron elastic reflectivity is strongly enhanced at about 13 eV, as a consequence of the second absolute band gap of diamond preserved up to the surface for D-nano-crystallites. The pure bending modes δ(CD(x)) at 88 meV and 107 meV are dominantly excited through the impact mechanism and their vibration excitation functions mimic the electron elastic reflectivity curve.
View Article and Find Full Text PDFIn this work we report on an investigation of hydrogen bonding and thermal stability on the surface of poly-crystalline diamond by high resolution electron energy loss spectroscopy (HR-EELS). Diamond films were grown on silicon substrates from CH(4)/H(2) as well as from CD(4)/D(2) gas mixtures by hot filament chemical vapor deposition (HF-CVD). The impact of ex situ ambient exposure on hydrogen bonding and its thermal stability was examined for: (i) as deposited films from a CH(4)/H(2) gas mixture; (ii) the same sample treated ex situ in micro-wave activated hydrogen plasma; and (iii) as deposited films from a CD(4)/D(2) gas mixture.
View Article and Find Full Text PDFBackground: This study explored the efficacy and tolerability of sunitinib, an inhibitor of tyrosine kinase receptors, in men with castration-resistant prostate cancer (CRPC).
Methods: Men with no prior chemotherapy (group A) and men with docetaxel (Taxotere)-resistant prostate cancer (group B) were treated with sunitinib. The primary end point was confirmed 50% prostate-specific antigen (PSA) decline.
Background: The clinical presentation of Bordetella pertussis can overlap with that of respiratory syncytial virus (RSV), and coinfection does occur, but management differs.
Hypothesis: The prevalence of B. pertussis is < 2% among Emergency Department (ED) patients with bronchiolitis.
A nylon flocked swab/universal transport medium collection method developed for bacterial sexually transmitted infections was adapted to detect respiratory viruses in infants and toddlers. This method significantly outperformed the traditional use of nasal aspirates in terms of PCR-based virus detection (P = 0.016), and the samples were easier for clinicians to evaluate, store, and transport.
View Article and Find Full Text PDFWe present a family of human sst(4)-selective, high-affinity (IC(50) = 2-4 nM) cyclic somatostatin (SRIF) octapeptides. These peptides result from the substitution of dTrp(8) in H-c[Cys(3)-Phe(6)-Phe(7)-DTrp(8)-Lys(9)-Thr(10)-Phe(11)-Cys(14)]-OH (SRIF numbering) (ODT-8) by one of the four conformationally biased stereoisomers of beta-methyl-3-(2-naphthyl)alanine (beta-Me2Nal). Whereas H-c[Cys-Phe-Phe-DNal-Lys-Thr-Phe-Cys]-OH (ODN-8, 2) has high affinity and marginal selectivity for human sst(3) (Reubi et al.
View Article and Find Full Text PDFThe Americans with Disabilities Act (ADA), and Sections 504 and 508 of the Rehabilitation Act, prohibit discrimination against people with disabilities in all aspects of daily life, including education, work, and access to places of public accommodations. Increasingly, these antidiscrimination laws are used by persons with disabilities to ensure equal access to e-commerce, and to private and public Internet websites. To help assess the impact of the anti-discrimination mandate for educational communities, this study examined 157 website home pages of Iowa public high schools (52% of high schools in Iowa) in terms of their electronic accessibility for persons with disabilities.
View Article and Find Full Text PDFPurpose: This study aimed to establish the reliability, validity, and sensitivity of the Cardiovascular Limitations and Symptoms Profile (CLASP) in a group of patients with chronic stable angina.
Methods: After 226 patients with angina had been recruited, they were randomly allocated to one of three groups: a 10-week hospital-based angina management program (n = 75; men = 56; age = 60 +/- 8 years), routine care (n = 74; men = 52; age = 61 +/- 7 years), and exercise therapy (n = 77; men = 60; age = 60 +/- 7 years). All the patients were assessed with CLASP on two occasions: at baseline and at 10 weeks.
Chem Biol Interact
February 2000
Sulphur mustard (HD) is a blister agent for which no specific therapy exists. The mechanism of cell injury caused by HD is not well understood. This study examined DNA damage in thymocytes exposed to a range of HD concentrations over a time course of 1-24 h.
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