Mackinnonmcpherson6019

Inhibition of GluN1-N2B NMDARs, which hardly affected the NMDAR EPSC in wild-type mice, rescued the increased and prolonged activation of NMDARs as well as the facilitation of CSD induction and propagation in FHM2 mice. Our data suggest that the enhanced susceptibility to CSD in FHM2 is mainly due to specific activation of extrasynaptic GluN1-N2B NMDARs and point to these receptors as possible therapeutic targets for prevention of CSD and migraine.Stimuli responsive materials are found in a broad range of applications, from energy harvesters to biomolecular sensors. read more Here, we report the production of poly (L-lactic acid) (PLLA) thin films that exhibit a mechanical stress responsive behaviour. By simply applying a mechanical stress through an AFM tip, a local electrical polarization was generated and measured by Kelvin Probe Force Microscopy. We showed that the magnitude of the stress generated electrical polarization can be manipulated by varying the thickness or crystallization state of the PLLA thin films. Besides exhibiting a mechanical stress-response behaviour with potential for energy harvesting and sensor applications, we show by AFM that these platforms react to mechanical forces with physiological relevance interaction forces as low as a cell sheet migrating over a substrate or larger ones as the fluid induced stresses in bone tissue. In living tissues, as most mechanical stimuli are transduced as strain gradients for the anatomical structures,lms. We further demonstrate the biofunctionality of such platforms by exploiting the mechanically-induced charge for adhesion protein adsorption.Conducting polymers (CPs) possess unique electrical and electrochemical properties and hold great potential for different applications in the field of bioelectronics. However, the widespread implementation of CPs in this field has been critically hindered by their poor processibility. There are four key elements that determine the processibility of CPs, which are thermal tunability, chemical stability, solvent compatibility and mechanical robustness. Recent research efforts have focused on enhancing the processibility of these materials through pre- or post-synthesis chemical modifications, the fabrication of CP-based complexes and composites, and the adoption of additive manufacturing techniques. link2 In this review, the physicochemical and structural properties that underlie the performance and processibility of CPs are examined. In addition, current research efforts to overcome technical limitations and broaden the potential applications of CPs in bioelectronics are discussed. STATEMENT OF SIGNIFICANCE This review details the inherent properties of CPs that have hindered their use in additive manufacturing for the creation of 3D bioelectronics. A fundamental approach is presented with consideration of the chemical structure and how this contributes to their electrical, thermal and mechanical properties. The review then considers how manipulation of these properties has been addressed in the literature including areas where improvements can be made. Finally, the review details the use of CPs in additive manufacturing and the future scope for the use of CPs and their composites in the development of 3D bioelectronics.The concept of 4D printing of phase change materials is gaining attention in the potential development of self-healing materials for tissue engineering and manufacturing applications, but there has been limited utilization of the technology in agriculture/farm-based applications. The temperature-responsiveness, magneto-responsiveness, pH-responsiveness, and osmotic pressure-responsiveness of shape-memory materials have potential applications in green/compostable plastics for agricultural applications such as food packaging and mulching films, shade nets, and greenhouse polymer covers. The application of 4D printing in augmenting the biodegradability, environmental, economic, and production benefits of polymers in agriculture is the main focus of this review. So far,; little scholarly and industry attention have been directed to agricultural applications even though shape memory polymers are ideal for such applications compared to existing materials due to smart/intelligent behavior, optimized performance through fiber/nanomaterial reinforcement and multilayered composites. The practical constraints relate to the newness of the 4D printing process, customized synthetic routes for application-specific materials. The constraints can be resolved using novel and customized processes such as fused deposition modeling (FDM) and stereo-lithography and ink-jet printing, which are facile, scalable and affordable 4D printing techniques, that are highly effective compared to powder bed printing, and other droplet-based printing technologies, and photo-polymerization methods. FDM has led to the generation of PLA and other polymers with self-deformation and controllable shape memory effects. Future applications should overcome constraints linked to machine workload limitations and 3D/4D printing constraints.The functionality of central vision is different from peripheral vision. Central vision is used for fixation and has higher acuity, making it useful for everyday activities such as reading and object identification. The central and peripheral representations in primary visual cortex (V1) also differ in how higher-order processing areas modulate their responses. For example, attention and expectation are top-down processes (i.e., high-order cognitive functions) that influence visual information processing during behavioral tasks. This top-down control is different for central vs. link3 peripheral vision. Since functional networks can influence visual information processing in different ways, networks (such as the Fronto-Parietal (FPN), Default Mode (DMN), and Cingulo-Opercular (CON)) likely differ in how they connect to representations of the visual field across V1. Prior work indicated the central representing portion of V1 was more functionally connected to regions belonging to the FPN, and the far-peripheral repr connectivity to V1. There are stronger structural connections to central representations in V1, particularly for lateral frontal regions, implying that the functional relationship between central V1 and frontal regions is built upon direct, long-distance connections via the IFOF. Overlapping structural and functional connections reflect differences in V1 eccentricities, with central V1 preferentially connected to attention-associated regions. Understanding how V1 is functionally and structurally connected to higher-order brain areas contributes to our understanding of how the human brain processes visual information and forms a baseline for understanding any modifications in processing that might occur with training or experience.Developing sensitive and reliable methods to distinguish normal and abnormal brain states is a key neuroscientific challenge. Topological Data Analysis, despite its relative novelty, already generated many promising applications, including in neuroscience. We conjecture its prominent tool of persistent homology may benefit from going beyond analysing structural and functional connectivity to effective connectivity graphs capturing the direct causal interactions or information flows. Therefore, we assess the potential of persistent homology to directed brain network analysis by testing its discriminatory power in two distinctive examples of disease-related brain connectivity alterations epilepsy and schizophrenia. We estimate connectivity from functional magnetic resonance imaging and electrophysiology data, employ Persistent Homology and quantify its ability to distinguish healthy from diseased brain states by applying a support vector machine to features quantifying persistent homology structure. We show howology, this could be due to notorious technical problems of accurate effective connectivity estimation.Our perception of the external world is influenced by internal bodily signals. For example, we recently showed that timing of stimulation along the cardiac cycle and spontaneous fluctuations of heartbeat-evoked potential (HEP) amplitudes influence somatosensory perception and the associated neural processing (Al et al., 2020). While cardiac phase affected detection sensitivity and late components of the somatosensory-evoked potentials (SEPs), HEP amplitudes affected detection criterion and both early and late SEP components. In a new EEG study, we investigate whether these results are replicable in a modified paradigm, which includes two succeeding temporal intervals. In one of the intervals, subjects received a weak electrical finger stimulation and reported first whether they detected any stimulation and then allocated the stimulus to one of the two intervals. Our results confirm the previously reported cardiac cycle and prestimulus HEP effects on somatosensory perception and evoked potentials. In addition, we obtained two new findings. Source analyses in this and our original study show that the increased likelihood of conscious perception goes along with HEP fluctuations in parietal and posterior cingulate regions, known to play important roles in interoceptive processes. Furthermore, HEP amplitudes were shown to decrease when subjects engaged in the somatosensory task compared to a resting state condition. Our findings are consistent with the view that HEP amplitudes are a marker of interoceptive (versus exteroceptive) attention and provide a neural underpinning for this view.Mutations in KRAS frequently occur in human cancer and are especially prevalent in pancreatic ductal adenocarcinoma (PDAC), where they have been shown to promote aggressive phenotypes. However, targeting this onco-protein has proven to be challenging, highlighting the need to further identify the various mechanisms used by KRAS to drive cancer progression. Here, we considered the role played by exosomes, a specific class of extracellular vesicles (EVs) derived from the endocytic cellular trafficking machinery, in mediating the ability of KRAS to promote cell survival. We found that exosomes isolated from the serum of PDAC patients, as well as from KRAS-transformed fibroblasts and pancreatic cancer cells, were all highly enriched in the cell survival protein Survivin. Exosomes containing Survivin, upon engaging serum-starved cells, strongly enhanced their survival. Moreover, they significantly compromised the effectiveness of the conventional chemotherapy drug paclitaxel, as well as a novel therapy that combines an ERK inhibitor with chloroquine, which is currently in clinical trials for PDAC. The survival benefits provided by oncogenic KRAS-derived exosomes were markedly reduced when depleted of Survivin using siRNA or upon treatment with the Survivin inhibitor YM155. Taken together, these findings demonstrate how KRAS mutations give rise to exosomes that provide a unique form of intercellular communication to promote cancer cell survival and therapy resistance, as well as raise interesting possibilities regarding their potential for serving as therapeutic targets and diagnostic markers for KRAS-dependent cancers.This study aimed to evaluate the effects of repeated bimodal transcranial direct current stimulation (tDCS) on alcohol consumption and immunohistological and neurochemical parameters in nerve-injured rats. Forty-eight adult male Wistar rats were distributed into six groups control, neuropathic pain (NP) + sham-tDCS, NP + alcohol + sham-tDCS, alcohol + sham-tDCS, alcohol + tDCS, and NP + alcohol + tDCS. NP is induced by chronic sciatic nerve constriction (CCI). The rats were exposed to a 10% alcohol solution by voluntary consumption for 14 days. From the 16th day after surgery, bimodal tDCS was applied for 20 min/day for 8 days. Brain structures were collected to evaluate the number of neuropeptide Y (NPY)-positive neurons, neurites, and argyrophilic grains by immunohistochemistry, and brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), interleukin (IL)-6, and IL-10 by ELISA. Nerve-injured rats showed a progressive increase in alcohol consumption compared to the non-injured rats. In addition, there was a reduction in voluntary alcohol consumption over time induced by tDCS.