Idiopathic generalized epilepsy (IGE) has been linked with disrupted intra-network connectivity of multiple resting-state networks (RSNs); however, whether impairment is present in inter-network interactions between RSNs, remains largely unclear. Here, 50 patients with IGE characterized by generalized tonic-clonic seizures (GTCS) and 50 demographically matched healthy controls underwent resting-state fMRI scans. A dynamic method was implemented to investigate functional network connectivity (FNC) in patients with IGE-GTCS. Specifically, independent component analysis was first carried out to extract RSNs, and then sliding window correlation approach was employed to obtain dynamic FNC patterns. Finally, k-mean clustering was performed to characterize six discrete functional connectivity states, and state analysis was conducted to explore the potential alterations in FNC and other dynamic metrics. Our results revealed that state-specific FNC disruptions were observed in IGE-GTCS and the majority of aberrant functional connectivity manifested itself in default mode network. In addition, temporal metrics derived from state transition vectors were altered in patients including the total number of transitions across states and the mean dwell time, the fraction of time spent and the number of subjects in specific FNC state. Furthermore, the alterations were significantly correlated with disease duration and seizure frequency. It was also found that dynamic FNC could distinguish patients with IGE-GTCS from controls with an accuracy of 77.91% (P < 0.001). Taken together, this study not only provided novel insights into the pathophysiological mechanisms of IGE-GTCS but also suggested that the dynamic FNC analysis was a promising avenue to deepen our understanding of this disease. Hum Brain Mapp 38:957-973, 2017. © 2016 Wiley Periodicals, Inc.

Melanoma is the cancer with the highest increase in incidence, and transformation of radial growth to vertical growth (i.e., noninvasive to invasive) melanoma is required for invasive disease and metastasis. We have previously shown that p42/p44 MAP kinase is activated in radial growth melanoma, suggesting that further signaling events are required for vertical growth melanoma. The molecular events that accompany this transformation are not well understood. Akt, a signaling molecule downstream of PI3K, was introduced into the radial growth WM35 melanoma in order to test whether Akt overexpression is sufficient to accomplish this transformation. Overexpression of Akt led to upregulation of VEGF, increased production of superoxide ROS, and the switch to a more pronounced glycolytic metabolism. Subcutaneous implantation of WM35 cells overexpressing Akt led to rapidly growing tumors in vivo, while vector control cells did not form tumors. We demonstrated that Akt was associated with malignant transformation of melanoma through at least 2 mechanisms. First, Akt may stabilize cells with extensive mitochondrial DNA mutation, which can generate ROS. Second, Akt can induce expression of the ROS-generating enzyme NOX4. Akt thus serves as a molecular switch that increases angiogenesis and the generation of superoxide, fostering more aggressive tumor behavior. Targeting Akt and ROS may be of therapeutic importance in treatment of advanced melanoma.

The large‐scale production of metal–air batteries, an appealing solution for next‐generation energy storage, requires low‐cost, earth‐abundant, and efficient oxygen electrode materials, yet insights into active catalyst structures and synergistic reactivity remain largely unknown. Here, a new bifunctional oxygen electrode based on nitrogen‐doped carbon nanotubes decorated by spinel CuCo2O4 quantum dots (CuCo2O4/N‐CNTs) is reported, outperforming the benchmark of state‐of‐the‐art noble metal catalysts. Combining spectroscopic characterization and electrochemical studies, a prominent synergetic effect between CuCo2O4 and N‐doped carbon nanotubes is uncovered: the high conductivity, large active surface area, and increase in the number of catalytic sites induced by Cu doping (i.e., Cu2+ and CuN) can be beneficial to the overall electrocatalytic activities. Remarkably, the native flexibility of CuCo2O4/N‐CNTs allows its direct use as reversible oxygen electrodes in Zn–air batteries either with liquid alkaline electrolyte or in the all‐solid‐state configuration. The prepared devices demonstrate excellent discharging/charging performance, large energy density (83.83 mW cm−2 in liquid state, 1.86 W g−1 in all‐solid‐state), and long lifetime (48 h in liquid state, 9 h in all‐solid‐state), holding great promise in the practical application of rechargeable metal–air batteries and other fuel cells.

Functional MRI (fMRI) studies have traditionally relied on intersubject normalization based on global brain morphology, which cannot establish proper functional correspondence between subjects due to substantial intersubject variability in functional organization. Here, we reliably identified a set of discrete, homologous functional regions in individuals to improve intersubject alignment of fMRI data. These functional regions demonstrated marked intersubject variability in size, position, and connectivity. We found that previously reported intersubject variability in functional connectivity maps could be partially explained by variability in size and position of the functional regions. Importantly, individual differences in network topography are associated with individual differences in task-evoked activations, suggesting that these individually specified regions may serve as the “localizer” to improve the alignment of task-fMRI data. We demonstrated that aligning task-fMRI data using the regions derived from resting state fMRI may lead to increased statistical power of task-fMRI analyses. In addition, resting state functional connectivity among these homologous regions is able to capture the idiosyncrasies of subjects and better predict fluid intelligence (gF) than connectivity measures derived from group-level brain atlases. Critically, we showed that not only the connectivity but also the size and position of functional regions are related to human behavior. Collectively, these findings suggest that identifying homologous functional regions across individuals can benefit a wide range of studies in the investigation of connectivity, task activation, and brain-behavior associations.