Enhancement of Odor-Induced Activity in the Canine Brain by Zinc Nanoparticles: A Functional MRI Study in Fully Unrestrained Conscious Dogs.

Using noninvasive in vivo functional magnetic resonance imaging (fMRI), we demonstrate that the enhancement of odorant response of olfactory receptor neurons by zinc nanoparticles leads to increase in activity in olfaction-related and higher order areas of the dog brain. To study conscious dogs, we employed behavioral training and optical motion tracking for reducing head motion artifacts. We obtained brain activation maps from dogs in both anesthetized state and fully conscious and unrestrained state. The enhancement effect of zinc nanoparticles was higher in conscious dogs with more activation in higher order areas as compared with anesthetized dogs. In conscious dogs, voxels in the olfactory bulb and hippocampus showed higher activity to odorants mixed with zinc nanoparticles as compared with pure odorants, odorants mixed with gold nanoparticles as well as zinc nanoparticles alone. These regions have been implicated in odor intensity processing in other species including humans. If the enhancement effect of zinc nanoparticles observed in vivo are confirmed by future behavioral studies, zinc nanoparticles may provide a way for enhancing the olfactory sensitivity of canines for detection of target substances such as explosives and contraband substances at very low concentrations, which would otherwise go undetected.

Zinc Nanoparticles Enhance Brain Connectivity in the Canine Olfactory Network: Evidence From an fMRI Study in Unrestrained Awake Dogs.

Prior functional Magnetic Resonance Imaging (fMRI) studies have indicated increased neural activation when zinc nanoparticles are added to odorants in canines. Here we demonstrate that zinc nanoparticles up-regulate directional brain connectivity in parts of the canine olfactory network. This provides an explanation for previously reported enhancement in the odor detection capability of the dogs in the presence of zinc nanoparticles. In this study, we obtained fMRI data from awake and unrestrained dogs while they were being exposed to odorants with and without zinc nanoparticles, zinc nanoparticles suspended in water vapor, as well as just water vapor alone. We obtained directional connectivity between the brain regions of the olfactory network that were significantly stronger for the condition of odorant + zinc nanoparticles compared to just odorants, water vapor + zinc nanoparticles and water vapor alone. We observed significant strengthening of the paths of the canine olfactory network in the presence of zinc nanoparticles. This result indicates that zinc nanoparticles could potentially be used to increase canine detection capabilities in the environments of very low concentrations of the odorants, which would have otherwise been undetected.

Anterior-posterior dissociation of the default mode network in dogs.

The default mode network (DMN) in humans has been extensively studied using seed-based correlation analysis (SCA) and independent component analysis (ICA). While DMN has been observed in monkeys as well, there are conflicting reports on whether they exist in rodents. Dogs are higher mammals than rodents, but cognitively not as advanced as monkeys and humans. Therefore, they are an interesting species in the evolutionary hierarchy for probing the comparative functions of the DMN across species. In this study, we sought to know whether the DMN, and consequently its functions such as self-referential processing, are exclusive to humans/monkeys or can we also observe the DMN in animals such as dogs. To address this issue, resting state functional MRI data from the brains of lightly sedated dogs and unconstrained and fully awake dogs were acquired, and ICA and SCA were performed for identifying the DMN. Since anesthesia can alter resting state networks, confirming our results in awake dogs was essential. Awake dog imaging was accomplished by training the dogs to keep their head still using reinforcement behavioral adaptation techniques. We found that the anterior (such as anterior cingulate and medial frontal) and posterior regions (such as posterior cingulate) of the DMN were dissociated in both awake and anesthetized dogs.

Functional MRI of the olfactory system in conscious dogs.

We depend upon the olfactory abilities of dogs for critical tasks such as detecting bombs, landmines, other hazardous chemicals and illicit substances. Hence, a mechanistic understanding of the olfactory system in dogs is of great scientific interest. Previous studies explored this aspect at the cellular and behavior levels; however, the cognitive-level neural substrates linking them have never been explored. This is critical given the fact that behavior is driven by filtered sensory representations in higher order cognitive areas rather than the raw odor maps of the olfactory bulb. Since sedated dogs cannot sniff, we investigated this using functional magnetic resonance imaging of conscious dogs. We addressed the technical challenges of head motion using a two pronged strategy of behavioral training to keep dogs' head as still as possible and a single camera optical head motion tracking system to account for residual jerky movements. We built a custom computer-controlled odorant delivery system which was synchronized with image acquisition, allowing the investigation of brain regions activated by odors. The olfactory bulb and piriform lobes were commonly activated in both awake and anesthetized dogs, while the frontal cortex was activated mainly in conscious dogs. Comparison of responses to low and high odor intensity showed differences in either the strength or spatial extent of activation in the olfactory bulb, piriform lobes, cerebellum, and frontal cortex. Our results demonstrate the viability of the proposed method for functional imaging of the olfactory system in conscious dogs. This could potentially open up a new field of research in detector dog technology.

Novel metal clusters isolated from blood are lethal to cancer cells.

Unfolding and subsequent aggregation of proteins is a common phenomenon that is linked to many human disorders. Misfolded hemoglobin is generally manifested in various autoimmune, infectious and inherited diseases. We isolated micrometer and submicrometer particles, termed proteons, from human and animal blood. Proteons lack nucleic acids but contain two major polypeptide populations with homology to the hemoglobin alpha-chain. Proteons form by reversible seeded aggregation of proteins around proteon nucleating centers (PNCs). PNCs are comprised of 1- to 2-nm metallic nanoclusters containing 40-300 atoms. Each milliliter of human blood contained approximately 7 x 10(13) PNCs and approximately 3 x 10(8) proteons. Exposure of isolated blood plasma to elevated temperatures increased the number of proteons. When an aliquot of this heated plasma was introduced into untreated plasma that was subsequently heated, the number of proteons further increased, reaching a maximum after a total of three such iterations. Small concentrations of PNCs were lethal to cultured cancer cells, whereas noncancerous cells were much less affected.