Bright Fluorescent Chemosensor Platforms for Imaging Endogenous Pools of Neuronal Zinc

AbstractA series of new fluorescent Zinpyr (ZP) chemosensors based on the fluorescein platform have been prepared and evaluated for imaging neuronal Zn2+. A systematic synthetic survey of electronegative substitution patterns on a homologous ZP scaffold provides a basis for tuning the fluorescence responses of “off-on” photoinduced electron transfer (PET) probes by controlling fluorophore pKa values and attendant proton-induced interfering fluorescence of the metal-free (apo) probes at physiological pH. We further establish the value of these improved optical tools for interrogating the metalloneurochemistry of Zn2+; the novel ZP3 fluorophore images endogenous stores of Zn2+ in live hippocampal neurons and slices, including the first fluorescence detection of Zn2+ in isolated dentate gyrus cultures. Our findings reveal that careful control of fluorophore pKa can minimize proton-induced fluorescence of the apo probes and that electronegative substitution offers a general strategy for tuning PET chemosensors for cellular studies. In addition to providing improved optical tools for Zn2+ in the neurosciences, these results afford a rational starting point for creating superior fluorescent probes for biological applications

Flow characteristics of Newtonian and non-Newtonian fluids in a vessel stirred by a 60° pitched blade impeller

Mean and rms velocity characteristics of two Newtonian flows at Reynolds numbers of 12,800 (glycerin solution) and 48,000 (water) and of a non-Newtonian flow (0.2% CMC solution, at a power number similar to the Newtonian glycerin flow) in a mixing vessel stirred by a 60° pitched blade impeller have been measured by laser Doppler velocimetry (LDV). The velocity measurements, resolved over 360° and 1.08° of impeller rotation, showed that the mean flow of the two power number matched glycerin and CMC flows were similar to within 3% of the impeller tip velocity and the turbulence intensities generally lower in the CMC flow by up to 5% of the tip velocity. The calculated mean flow quantities showed similar discharge coefficient and pumping efficiency in all three flows and similar strain rate between the two power number matched glycerin and CMC flows; the strain rate of the higher Reynolds number Newtonian flow was found to be slightly higher. The energy balance around the impeller indicated that the CMC flow dissipated up to 9% more of the total input power and converted 7% less into the turbulence compared to the glycerin flow with the same power input which could lead to less effective mixing processes where the micro-mixing is important

Supporting new product commercialization through managerial social ties and market knowledge development in an emerging economy

University of Tasmania, Australi

Synapse Pathology in Psychiatric and Neurologic Disease

Inhibitory and excitatory synapses play a fundamental role in information processing in the brain. Excitatory synapses usually are situated on dendritic spines, small membrane protrusions that harbor glutamate receptors and postsynaptic density components and help transmit electrical signals. In recent years, it has become evident that spine morphology is intimately linked to synapse function—smaller spines have smaller synapses and support reduced synaptic transmission. The relationship between synaptic signaling, spine shape, and brain function is never more apparent than when the brain becomes dysfunctional. Many psychiatric and neurologic disorders, ranging from mental retardation and autism to Alzheimer’s disease and addiction, are accompanied by alterations in spine morphology and synapse number. In this review, we highlight the structure and molecular organization of synapses and discuss functional effects of synapse pathology in brain disease

Inducible cAMP Early Repressor (ICER) and Brain Functions

The inducible cAMP early repressor (ICER) is an endogenous repressor of cAMP-responsive element (CRE)-mediated gene transcription and belongs to the CRE-binding protein (CREB)/CRE modulator (CREM)/activating transcription factor 1 (ATF-1) gene family. ICER plays an important role in regulating the neuroendocrine system and the circadian rhythm. Other aspects of ICER function have recently attracted heightened attention. Being a natural inducible CREB antagonist, and more broadly, an inducible repressor of CRE-mediated gene transcription, ICER regulates long-lasting plastic changes that occur in the brain in response to incoming stimulation. This review will bring together data on ICER and its functions in the brain, with a special emphasis on recent findings highlighting the involvement of ICER in the regulation of long-term plasticity underlying learning and memory