Neural responses in the cerebral cortex change dramatically between the 'synchronized' state during sleep and 'desynchronized' state during wakefulness. Our understanding of cortical state emerges largely from experiments performed in sensory areas of head-fixed or tethered rodents due to technical limitations of recording from larger freely-moving animals for several hours. Here, we report a system integrating wireless electrophysiology, wireless eye tracking, and real-time video analysis to examine the dynamics of population activity in a high-level, executive areadorsolateral prefrontal cortex (dlPFC) of unrestrained monkey. This technology allows us to identify cortical substates during quiet and active wakefulness, and transitions in population activity during rest. We further show that narrow-spiking neurons exhibit stronger synchronized fluctuations in population activity than broad-spiking neurons regardless of state. Our results show that cortical state is controlled by behavioral demands and arousal by asymmetrically modulating the slow response fluctuations of local excitatory and inhibitory cell populations.

The recurrence of tumors after years of disease-free survival has spurred interest in the concept that cancers may have a stem cell basis. Current speculation holds that as few as 0.1% of the tumor mass may be chemoresistant and radioresistant, harboring stem-like properties that drive tumor survival, development, and metastasis. There are intense investigations to characterize cancer stem cells on the basis of self-renewal and multi-lineage differentiation. Thus far, no successful targeted therapies have been developed and reached the clinic, but as these cells are isolated and characterized, insights may be unraveled. In this review, we discuss the controversy over the origins of the cancer stem cell hypothesis and the unforeseen factors that may facilitate breast cancer stem cell survival and metastasis. We discuss the role of tumor microenvironment, including carcinoma-associated fibroblasts, epigenetic factors, and the Th1/Th2 balance, in supporting breast cancer stem cells. In addition, we have incorporated ideas on the epithelial-to-mesenchymal transition in metastatic dissemination of epithelial malignancies. This area is relevant since breast cancer stem cells have been suggested to revert to a mesenchymal phenotype during the progression of cancer. Finally we discuss prospects on developing targeted therapy including novel treatment modalities such as oncolytic viral therapy, differentiation therapy, and nanotechnology.

Stem cell therapy has a place for future application in the treatment of degenerative diseases. Regardless of the origin of the stem cell, when placed within a milieu of inflammatory mediator, they will show varied functions. This review focuses on human mesenchymal stem cells (MSCs) and discusses neuronal replacement using multi- and inter-disciplinary approaches. We caution the enthusiasm of scientists since there is always the potential for tumor formation, even for adult stem cells. The review places RE-1 silencing transcription factor (REST) gene as central to the understanding of stem cell behavior in the microenvironment of tissue injury. REST is relevant in the development of dopaminergic and peptidergic neurons from MSCs. Premature downregulation of REST by the pro-inflammatory mediator, IL-1alpha, can prematurely lead to the expression of neurotransmitters, which in turn, could develop rapid crosstalk with immune cells. In-depth inter- and multi-disciplinary research will lead to rapid and safe translation of MSCs to patients. An understanding of the changes induced in MSCs by cytokines and other mediators will establish future application of MSCs and other stem cells for safe and effective treatments. This study also alludes to the potential of personalized medicine through engineering and mathematics.

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Theoretical studies have long proposed that adaptation allows the brain to effectively use the limited response range of sensory neurons to encode widely varying natural inputs. However, despite this influential view, experimental studies have exclusively focused on how the neural code adapts to a range of stimuli lying along a single feature axis, such as orientation or contrast. Here, we performed electrical recordings in macaque visual cortex (area V4) to reveal significant adaptive changes in the neural code of single cells and populations across multiple feature axes. Both during free viewing and passive fixation, populations of cells improved their ability to encode image features after rapid exposure to stimuli lying on orthogonal feature axes even in the absence of initial tuning to these stimuli. These results reveal a remarkable adaptive capacity of visual cortical populations to improve network computations relevant for natural viewing despite the modularity of the functional cortical architecture.

Theoretical studies have long proposed that adaptation allows the brain to effectively use the limited response range of sensory neurons to encode widely varying natural inputs. However, despite this influential view, experimental studies have exclusively focused on how the neural code adapts to a range of stimuli lying along a single feature axis, such as orientation or contrast. Here, we performed electrical recordings in macaque visual cortex (area V4) to reveal significant adaptive changes in the neural code of single cells and populations across multiple feature axes. Both during free viewing and passive fixation, populations of cells improved their ability to encode image features after rapid exposure to stimuli lying on orthogonal feature axes even in the absence of initial tuning to these stimuli. These results reveal a remarkable adaptive capacity of visual cortical populations to improve network computations relevant for natural viewing despite the modularity of the functional cortical architecture.