Insulin in the ventral tegmental area reduces cocaine-evoked dopamine in the nucleus accumbens in vivo.

Mesolimbic dopamine circuits, implicated in incentive motivation, are sensitive to changes in metabolic state such as weight loss and diet-induced obesity. These neurons are important targets for metabolic hormones such as leptin, glucagon-like peptide-1, ghrelin and insulin. Insulin receptors are located on dopamine neurons in the ventral tegmental area (VTA) and we have previously demonstrated that insulin induces long-term depression of excitatory synapses onto VTA dopamine neurons. While insulin can decrease dopamine concentration in somatodendritic regions, it can increase dopamine in striatal slices. Whether insulin directly targets the VTA to alter dopamine release in projection areas, such as the nucleus accumbens (NAc), remains unknown. The main goal of the present experiments was to examine NAc dopamine concentration following VTA administration of insulin. Using in vivo FSCV to detect rapid fluctuations in dopamine concentration, we showed that intra-VTA insulin via action at insulin receptors reduced pedunculopontine nucleus-evoked dopamine release in the NAc. Furthermore, intra-VTA insulin reduced cocaine-potentiated NAc dopamine. Finally, intra-VTA or intranasal insulin decreased locomotor responses to cocaine, an effect blocked by an intra-VTA administered insulin receptor antagonist. Together, these data demonstrate that mesolimbic dopaminergic projections are important targets of the metabolic hormone, insulin.

In Situ Transmission Electron Microscope Liquid Cell 3D Profile Reconstruction and Analysis of Nanoscale Liquid Water Contact Line Movements.

Static nanodroplets and dynamic contact line (CL) movements were visualized by an in situ transmission electron microscope (TEM) liquid cell technique at nanometer spatial resolution. Crawling and sliding movements of nanoscale CL were observed. The crawling happened at a capillary number (Ca) range of ∼10-9 to ∼10-8, and the sliding happened at a Ca range of ∼10-8 to ∼10-7. Three dimensional (3D) image construction had been employed to study static and dynamic contact angles (CAs) at nanoscale. CA hysteresis at nanoscale was observed in the sliding but not in the crawling. The energies associated with sliding were analyzed to investigate the CA hysteresis. An empirical model of the relationship between nanoscale CAs and Ca was developed. Both the experimental observation and the empirical analysis suggested that the competition among substrate defect, CL elastic, and molecular activation energies dictated different CL movements at nanoscale.

Group B streptococcal leptomeningitis, ventriculitis, right cerebellitis, and cerebritis in an immunocompetent patient.

BACKGROUND: Group B streptococcal (GBS) meningitis is uncommon in non-puerperal adults outside of significant immunocompromise or structural abnormalities. CASE PRESENTATION: We describe a relatively healthy 62-year-old man with GBS bacteremia, abnormal lumbar puncture, and MRI-confirmed leptomeningitis, ventriculitis, right cerebellitis, and cerebritis who presented without overt symptoms of meningitis. DIAGNOSIS: The suspected source of infection was a high-inoculum genitourinary infection in the setting of hydronephrosis and recent cystoscopy. We performed a literature review of previous cases and clusters of GBS meningitis. DISCUSSION: With increasing recognition of invasive GBS infection among adult patients, and in light of our patient's atypical presentation, we propose that an index of suspicion for GBS meningitis be maintained, even for patients who would traditionally have been considered at lower risk.

HISTORIQUE: La méningite à streptocoque du groupe B (SGB) est rare chez les adultes qui ne viennent pas d'accoucher s'ils ne présentent pas une immunodépression importante ou des anomalies structurelles. PRÉSENTATION DE CAS: Les chercheurs décrivent le cas d'un homme de 62 ans relativement en santé atteint d'une bactériémie à SGB qui présentait une ponction lombaire anormale, une léptoméningite confirmés par l'imagerie à résonance magnétique, une ventriculite, une cérébellite droite et une cérébrite qui se sont manifestées sans symptômes évidents de méningite. DIAGNOSTIC: La source présumée de l'infection était une infection génito-urinaire dans le contexte d'une hydronéphrose et d'une récente cytoscopie. Les chercheurs ont procédé à une analyse bibliographique des cas antérieurs et des grappes de méningite à SGB. DISCUSSION: Puisque les infections à SGB invasives sont de plus en plus diagnostiquées chez les patients adultes, et compte tenu de la présentation atypique du patient, les chercheurs proposent de savoir évoquer une méningite à SGB, même chez les patients qui seraient habituellement considérés comme à faible risque.

Independent and collective roles of surface structures at different length scales on pool boiling heat transfer.

Spherical Cu nanocavity surfaces are synthesized to examine the individual role of contact angles in connecting lateral Rayleigh-Taylor wavelength to vertical Kevin-Helmholtz wavelength on hydrodynamic instability for the onset of pool boiling Critical Heat Flux (CHF). Solid and porous Cu pillar surfaces are sintered to investigate the individual role of pillar structure pitch at millimeter scale, named as module wavelength, on hydrodynamic instability at CHF. Last, spherical Cu nanocavities are coated on the porous Cu pillars to create a multiscale Cu structure, which is studied to examine the collective role and relative significance of contact angles and module wavelength on hydrodynamic instability at CHF, and the results indicate that module wavelength plays the dominant role on hydrodynamic instability at CHF when the height of surface structures is equal or above » Kelvin-Helmholtz wavelength. Pool boiling Heat Transfer Coefficient (HTC) enhancements on spherical Cu nanocavity surfaces, solid and porous Cu pillar surfaces, and the integrated multiscale structure have been investigated, too. The experimental results reveal that the nanostructures and porous pillar structures can be combined together to achieve even higher enhancement of HTC than that of individual structures.

Monitoring signaling by the p75(NTR) receptor utilizing a caspase-3 activation assay amenable to small-molecule screening.

p75(NTR) is a neurotrophin receptor that can mediate either survival or death of neurons depending on the cell context. Modulation of p75(NTR) is a promising strategy to promote neuronal survival for treatment of cognitive disorders such as Alzheimer's disease. Despite years of investigation into the signaling mechanisms of p75(NTR), no p75(NTR) signaling assay has yet been developed that is compatible with efficient screening of small-molecule modulators. In this work, we developed a homogeneous cell-based assay for screening p75(NTR) modulators and studying p75(NTR) function. Stimulation of p75(NTR)-transfected cells using either nerve growth factor (NGF) or Pro-NGF resulted in an enhanced caspase-3 activity as assessed by cleavage of a fluorescent caspase-3 substrate. Optimization of the assay with respect to time, cell density, NGF and Pro-NGF concentration, and other factors provided a twofold increase in the caspase-3 activity compared to background. Withdrawal of serum during the NGF or Pro-NGF treatment period was found to be essential for p75(NTR)-dependent caspase-3 activation. We validated the method by demonstrating that a signaling-incompetent p75(NTR) mutant could not substitute for wild-type p75(NTR) in mediating caspase-3 activation. A focused library screen identified new inhibitors of p75(NTR) signaling. This method will be useful for identifying small-molecule modulators of p75(NTR) as well as further characterizing downstream signaling events.

Experimental study of combustion characteristics of nanoscale metal and metal oxide additives in biofuel (ethanol).

An experimental investigation of the combustion behavior of nano-aluminum (n-Al) and nano-aluminum oxide (n-Al2O3) particles stably suspended in biofuel (ethanol) as a secondary energy carrier was conducted. The heat of combustion (HoC) was studied using a modified static bomb calorimeter system. Combustion element composition and surface morphology were evaluated using a SEM/EDS system. N-Al and n-Al2O3 particles of 50- and 36-nm diameters, respectively, were utilized in this investigation. Combustion experiments were performed with volume fractions of 1, 3, 5, 7, and 10% for n-Al, and 0.5, 1, 3, and 5% for n-Al2O3. The results indicate that the amount of heat released from ethanol combustion increases almost linearly with n-Al concentration. N-Al volume fractions of 1 and 3% did not show enhancement in the average volumetric HoC, but higher volume fractions of 5, 7, and 10% increased the volumetric HoC by 5.82, 8.65, and 15.31%, respectively. N-Al2O3 and heavily passivated n-Al additives did not participate in combustion reactively, and there was no contribution from Al2O3 to the HoC in the tests. A combustion model that utilized Chemical Equilibrium with Applications was conducted as well and was shown to be in good agreement with the experimental results.