Ballistic graphene arrays for ultra-high pressure sensing

Atomically thin two-dimensional materials, such as graphene, exhibit extreme high-pressure sensitivity compared to the commercially used pressure sensors due to their high surface-to-volume ratio and excellent mechanical properties. The smaller piezoresistance of graphene across different transport regimes limits its pressure sensitivity compared to other two-dimensional materials. Using membrane theory and the thin-film adhesivity model, we show miniaturization as a means to enhance the overall performance of graphene pressure sensors. Our findings reveal that ballistic graphene can be configured to measure ultra-high pressure (≈109 Pa) with many-fold high-pressure sensitivity than other contemporary two-dimensional materials. Based on these findings, we propose an array of ballistic graphene sensors with extreme high-pressure sensitivity and ultra-high-pressure range that will find applications in next-generation nano-electro-mechanical system pressure sensors. The performance parameters of the array sensors can be further enhanced by reducing the size of graphene membranes and increasing the number of sensors in the array. The methodology developed in this paper can be used to explore similar applications using other two-dimensional materials

Differential alterations in the expression of neurotransmitter receptors in inner retina following loss of photoreceptors in rd1 mouse.

Loss of photoreceptors leads to significant remodeling in inner retina of rd1 mouse, a widely used model of retinal degeneration. Several morphological and physiological alterations occur in the second- and third-order retinal neurons. Synaptic activity in the excitatory bipolar cells and the predominantly inhibitory amacrine cells is enhanced. Retinal ganglion cells (RGCs) exhibit hyperactivity and aberrant spiking pattern, which adversely affects the quality of signals they can carry to the brain. To further understand the pathophysiology of retinal degeneration, and how it may lead to aberrant spiking in RGCs, we asked how loss of photoreceptors affects some of the neurotransmitter receptors in rd1 mouse. Using Western blotting, we measured the levels of several neurotransmitter receptors in adult rd1 mouse retina. We found significantly higher levels of AMPA, glycine and GABAa receptors, but lower levels of GABAc receptors in rd1 mouse than in wild-type. Since GABAa receptor is expressed in several retinal layers, we employed quantitative immunohistochemistry to measure GABAa receptor levels in specific retinal layers. We found that the levels of GABAa receptors in inner plexiform layer of wild-type and rd1 mice were similar, whereas those in outer plexiform layer and inner nuclear layer combined were higher in rd1 mouse. Specifically, we found that the number of GABAa-immunoreactive somas in the inner nuclear layer of rd1 mouse retina was significantly higher than in wild-type. These findings provide further insights into neurochemical remodeling in the inner retina of rd1 mouse, and how it might lead to oscillatory activity in RGCs

A copper chelate selectively triggers apoptosis in myeloid-derived suppressor cells in a drug-resistant tumor model and enhances antitumor immune response

Myeloid-derived suppressor cells (MDSCs), one of the major orchestrators of immunosuppressive network are present in the tumor microenvironment suppress antitumor immunity by subverting Th1 response in tumor site and considered as a great obstacle for advancement of different cancer immunotherapeutic protocols. Till date, various pharmacological approaches have been explored to modulate the suppressive functions of MDSCs in vivo. The present study describes our endeavor to explore a possibility of eradicating MDSCs by the application of a copper chelate, namely copper N-(2-hydroxy acetophenone) glycinate (CuNG), previously found to be a potential immunomodulator that can elicit antitumorogenic Th1 response in doxorubicin-resistant EAC (EAC/Dox) bearing mice. Herein, we demonstrated that CuNG treatment could reduce Gr-1+CD11b+ MDSC accumulation in ascitic fluid and spleen of EAC/Dox tumor model. Furthermore, we found that CuNG mediated reduction in MDSCs is associated with induction of Th1 response and reduction in Treg cells. Moreover, we observed that CuNG could deplete MDSCs by inducing Fas-FasL mediated apoptotic cell death where death receptor Fas expression is enhanced in MDSCs and FasL is provided by activated T cells. However, MDSC expansion from bone marrow cells and their differentiation was not affected by CuNG. Altogether, these findings suggest that the immunomodulatory property of CuNG is attributed to, at least in part, by its selective cytotoxic action on MDSCs. So, this preclinical study unveils a new mechanism of regulating MDSC levels in drug-resistant cancer model and holds promise of translating the findings into clinical settings

Induction of apoptosis in human colorectal cancer cell line, HCT-116 by a vanadium- Schiff base complex

Vanadium compounds are well known for their therapeutic interventions against several diseases. Various biochemical attributes of vanadium complexes inspired us to evaluate the cancer cell killing efficacy of the vanadium complex, viz., vanadyl N-(2-hydroxyacetophenone) glycinate [VO(NG)2]. Previously we showed that VO(NG)2 is an effective anticancer agent in in vitro and in vivo cancer models and imposed miniscule side effects. Herein we report that VO(NG)2 is significantly cytotoxic to various cancer cell lines. Furthermore, this redox active vanadyl complex altered the redox homeostatsis of many human cancer cell lines significantly. VO(NG)2 actuates programmed cell death in human colorectal carcinoma cells(HCT-116) through mitochondrial outer membrane permeabilization but in caspase independent manner, possibly by altering cellular redox status and by inflicting DNA damage. Thus, the present work is an attempt to provide many evidences regarding the potent and selective chemotherapeutic efficacy of the novel VO(NG)2

Glycine receptor was upregulated after loss of photoreceptors.

<p>A, B) Representative images of retinal sections of adult wild-type (A) and rd1 mouse (B) retinas immunostained for GlyR-α1,α2. Scale bar: 20 μm. C) Representative blots of GlyR-α1,α2 and β-tubulin in wild-type and rd1 mouse retinas. D) The levels of GlyR-α1,α2 (mean±SD) was significantly higher in rd1 mouse retina than in wild-type (n = 10) * p<0.05.</p