Decoding effects of psychoactive drugs in a high-dimensional space of eye movements in monkeys.

Oculomotor behavior has been shown to be correlated with mental disorders in clinics, making it promising for disease diagnosis. Here we developed a thorough oculomotor test toolkit, involving saccade, smooth pursuit, and fixation, allowing the examination of multiple oculomotor parameters in monkey models induced by psychoactive drugs. Eye movements were recorded after daily injections of phencyclidine (PCP) (3.0 mg/kg), ketamine (0.8 mg/kg) or controlled saline in two macaque monkeys. Both drugs led to robust reduction in accuracy and increment in reaction time during high cognitive-demanding tasks. Saccades, smooth pursuit, and fixation stability were also significantly impaired. During fixation, the involuntary microsaccades exhibited increased amplitudes and were biased toward the lower visual field. Pupillary response was reduced during cognitive tasks. Both drugs also increased sensitivity to auditory cues as reflected in auditory evoked potentials (AEPs). Thus, our animal model induced by psychoactive drugs produced largely similar abnormalities to that in patients with schizophrenia. Importantly, a classifier based on dimension reduction and machine learning could reliably identify altered states induced by different drugs (PCP, ketamine and saline, accuracy = 93%). The high performance of the classifier was reserved even when data from one monkey were used for training and testing the other subject (averaged classification accuracy = 90%). Thus, despite heterogeneity in baseline oculomotor behavior between the two monkeys, our model allows data transferability across individuals, which could be beneficial for future evaluation of pharmaceutical or physical therapy validity.

Impact of inflammation and immunotherapy in renal cell carcinoma.

Substantial research attention has been directed at exploring the mechanisms and treatment of renal cell carcinoma (RCC). Indeed, the association between inflammation and tumor phenotypes has been at the center of cancer research. Concomitant with research on the inflammation response and inflammatory molecules involved in RCC, new breakthroughs have emerged. A large body of knowledge now shows that treatments targeting inflammation and immunity in RCC provide substantial clinical benefits. Adequate analysis and a better understanding of the mechanisms of inflammatory factors in the occurrence and progression of RCC are highly desirable. Currently, numerous RCC treatments targeted at inflammation and immunotherapy are available. The current review describes in detail the link between inflammation and RCC.

Vestibular System and Self-Motion.

Detection of the state of self-motion, such as the instantaneous heading direction, the traveled trajectory and traveled distance or time, is critical for efficient spatial navigation. Numerous psychophysical studies have indicated that the vestibular system, originating from the otolith and semicircular canals in our inner ears, provides robust signals for different aspects of self-motion perception. In addition, vestibular signals interact with other sensory signals such as visual optic flow to facilitate natural navigation. These behavioral results are consistent with recent findings in neurophysiological studies. In particular, vestibular activity in response to the translation or rotation of the head/body in darkness is revealed in a growing number of cortical regions, many of which are also sensitive to visual motion stimuli. The temporal dynamics of the vestibular activity in the central nervous system can vary widely, ranging from acceleration-dominant to velocity-dominant. Different temporal dynamic signals may be decoded by higher level areas for different functions. For example, the acceleration signals during the translation of body in the horizontal plane may be used by the brain to estimate the heading directions. Although translation and rotation signals arise from independent peripheral organs, that is, otolith and canals, respectively, they frequently converge onto single neurons in the central nervous system including both the brainstem and the cerebral cortex. The convergent neurons typically exhibit stronger responses during a combined curved motion trajectory which may serve as the neural correlate for complex path perception. During spatial navigation, traveled distance or time may be encoded by different population of neurons in multiple regions including hippocampal-entorhinal system, posterior parietal cortex, or frontal cortex.

Distributed Representation of Curvilinear Self-Motion in the Macaque Parietal Cortex.

Information about translations and rotations of the body is critical for complex self-motion perception during spatial navigation. However, little is known about the nature and function of their convergence in the cortex. We measured neural activity in multiple areas in the macaque parietal cortex in response to three different types of body motion applied through a motion platform: translation, rotation, and combined stimuli, i.e., curvilinear motion. We found a continuous representation of motion types in each area. In contrast to single-modality cells preferring either translation-only or rotation-only stimuli, convergent cells tend to be optimally tuned to curvilinear motion. A weighted summation model captured the data well, suggesting that translation and rotation signals are integrated subadditively in the cortex. Interestingly, variation in the activity of convergent cells parallels behavioral outputs reported in human psychophysical experiments. We conclude that representation of curvilinear self-motion perception is widely distributed in the primate sensory cortex.

Multisensory Convergence of Visual and Vestibular Heading Cues in the Pursuit Area of the Frontal Eye Field.

Both visual and vestibular sensory cues are important for perceiving one's direction of heading during self-motion. Previous studies have identified multisensory, heading-selective neurons in the dorsal medial superior temporal area (MSTd) and the ventral intraparietal area (VIP). Both MSTd and VIP have strong recurrent connections with the pursuit area of the frontal eye field (FEFsem), but whether FEFsem neurons may contribute to multisensory heading perception remain unknown. We characterized the tuning of macaque FEFsem neurons to visual, vestibular, and multisensory heading stimuli. About two-thirds of FEFsem neurons exhibited significant heading selectivity based on either vestibular or visual stimulation. These multisensory neurons shared many properties, including distributions of tuning strength and heading preferences, with MSTd and VIP neurons. Fisher information analysis also revealed that the average FEFsem neuron was almost as sensitive as MSTd or VIP cells. Visual and vestibular heading preferences in FEFsem tended to be either matched (congruent cells) or discrepant (opposite cells), such that combined stimulation strengthened heading selectivity for congruent cells but weakened heading selectivity for opposite cells. These findings demonstrate that, in addition to oculomotor functions, FEFsem neurons also exhibit properties that may allow them to contribute to a cortical network that processes multisensory heading cues.

Batch affinity adsorption of His-tagged proteins with EDTA-based chitosan.

Affinity adsorption purification of hexahistidine-tagged (His-tagged) proteins using EDTA-chitosan-based adsorption was designed and carried out. Chitosan was elaborated with ethylenediaminetetraacetic acid (EDTA), and the resulting polymer was characterized by FTIR, TGA, and TEM. Different metals including Ni(2+), Cu(2+), and Zn(2+) were immobilized with EDTA-chitosan, and their capability to the specific adsorption of His-tagged proteins were then investigated. The results showed that Ni(2+)-EDTA-chitosan and Zn(2+)-EDTA-chitosan had high affinity toward the His-tagged proteins, thus isolating them from protein mixture. The target fluorescent-labeled hexahistidine protein remained its fluorescent characteristic throughout the purification procedure when Zn(2+)-EDTA-chitosan was used as a sorbent, wherein the real-time monitor was performed to examine the immigration of fluorescent-labeled His-tagged protein. Comparatively, Zn(2+)-EDTA-chitosan showed more specific binding ability for the target protein, but with less binding capacity. It was further proved that this purification system could be recovered and reused at least for 5 times and could run on large scales. The presented M(2+)-EDTA-chitosan system, with the capability to specifically bind His-tagged proteins, make the purification of His-tagged proteins easy to handle, leaving out fussy preliminary treatment, and with the possibility of continuous processing and a reduction in operational cost in relation to the costs of conventional processes.