Monitoring and Determining Mitochondrial Network Parameters in Live Lung Cancer Cells.

Mitochondria are dynamic organelles that constantly fuse and divide, forming dynamic tubular networks. Abnormalities in mitochondrial dynamics and morphology are linked to diverse pathological states, including cancer. Thus, alterations in mitochondrial parameters could indicate early events of disease manifestation or progression. However, finding reliable and quantitative tools for monitoring mitochondria and determining the network parameters, particularly in live cells, has proven challenging. Here, we present a 2D confocal imaging-based approach that combines automatic mitochondrial morphology and dynamics analysis with fractal analysis in live small cell lung cancer (SCLC) cells. We chose SCLC cells as a test case since they typically have very little cytoplasm, but an abundance of smaller mitochondria compared to many of the commonly used cell types. The 2D confocal images provide a robust approach to quantitatively measure mitochondrial dynamics and morphology in live cells. Furthermore, we performed 3D reconstruction of electron microscopic images and show that the 3D reconstruction of the electron microscopic images complements this approach to yield better resolution. The data also suggest that the parameters of mitochondrial dynamics and fractal dimensions are sensitive indicators of cellular response to subtle perturbations, and hence, may serve as potential markers of drug response in lung cancer

Differentially expressed genes between drought-tolerant and drought-sensitive barley genotypes in response to drought stress during the reproductive stage

Drought tolerance is a key trait for increasing and stabilizing barley productivity in dry areas worldwide. Identification of the genes responsible for drought tolerance in barley (Hordeum vulgare L.) will facilitate understanding of the molecular mechanisms of drought tolerance, and also facilitate the genetic improvement of barley through marker-assisted selection or gene transformation. To monitor the changes in gene expression at the transcriptional level in barley leaves during the reproductive stage under drought conditions, the 22K Affymetrix Barley 1 microarray was used to screen two drought-tolerant barley genotypes, Martin and Hordeum spontaneum 41-1 (HS41-1), and one drought-sensitive genotype Moroc9-75. Seventeen genes were expressed exclusively in the two drought-tolerant genotypes under drought stress, and their encoded proteins may play significant roles in enhancing drought tolerance through controlling stomatal closure via carbon metabolism (NADP malic enzyme, NADP-ME, and pyruvate dehydrogenase, PDH), synthesizing the osmoprotectant glycine-betaine (C-4 sterol methyl oxidase, CSMO), generating protectants against reactive-oxygen-species scavenging (aldehyde dehydrogenase,ALDH, ascorbate-dependent oxidoreductase, ADOR), and stabilizing membranes and proteins (heat-shock protein 17.8, HSP17.8, and dehydrin 3, DHN3). Moreover, 17 genes were abundantly expressed in Martin and HS41-1 compared with Moroc9-75 under both drought and control conditions. These genes were possibly constitutively expressed in drought-tolerant genotypes. Among them, seven known annotated genes might enhance drought tolerance through signalling [such as calcium-dependent protein kinase (CDPK) and membrane steroid binding protein (MSBP)], anti-senescence (G2 pea dark accumulated protein, GDA2), and detoxification (glutathione S-transferase, GST) pathways. In addition, 18 genes, including those encoding Δl-pyrroline-5-carboxylate synthetase (P5CS), protein phosphatase 2C-like protein (PP2C), and several chaperones, were differentially expressed in all genotypes under drought; thus they were more likely to be general drought-responsive genes in barley. These results could provide new insights into further understanding of drought-tolerance mechanisms in barley

Muscle activation patterns and muscle synergies reflect different modes of coordination during upper extremity movement

A core issue in motor control is how the central nervous system generates and selects the muscle activation patterns necessary to achieve a variety of behaviors and movements. Extensive studies have verified that it is the foundation to induce a complex movement by the modular combinations of several muscles with a synergetic relationship. However, a few studies focus on the synergetic similarity and dissimilarity among different types of movements, especially for the upper extremity movements. In this study, we introduced the non-negative matrix factorization (NMF) method to explore the muscle activation patterns and synergy structure under 6 types of movements, involving the hand open (HO), hand close (HC), wrist flexion (WF), wrist extension (WE), supination (SU), and pronation (PR). For this, we enrolled 10 healthy subjects to record the electromyography signal for NMF calculation. The results showed a highly modular similarity of the muscle synergy among subjects under the same movement. Furthermore, Spearman’s correlation analysis indicated significant similarities among HO-WE, HO-SU, and WE-SU (p < 0.001). Additionally, we also found shared synergy and special synergy in activation patterns among different movements. This study confirmed the theory of modular structure in the central nervous system, which yields a stable synergetic pattern under the same movement. Our findings on muscle synergy will be of great significance to motor control and even to clinical assessment techniques

Cancer-Secreted miR-105 Destroys Vascular Endothelial Barriers to Promote Metastasis

SummaryCancer-secreted microRNAs (miRNAs) are emerging mediators of cancer-host crosstalk. Here we show that miR-105, which is characteristically expressed and secreted by metastatic breast cancer cells, is a potent regulator of migration through targeting the tight junction protein ZO-1. In endothelial monolayers, exosome-mediated transfer of cancer-secreted miR-105 efficiently destroys tight junctions and the integrity of these natural barriers against metastasis. Overexpression of miR-105 in nonmetastatic cancer cells induces metastasis and vascular permeability in distant organs, whereas inhibition of miR-105 in highly metastatic tumors alleviates these effects. miR-105 can be detected in the circulation at the premetastatic stage, and its levels in the blood and tumor are associated with ZO-1 expression and metastatic progression in early-stage breast cancer

Active substrate integrated terahertz waveguide using periodic graphene stack

The transmission properties of a substrate integrated waveguide (SIW) based on periodic graphene stacks have been theoretically investigated in the terahertz (THz) region. The effects of the dielectric-graphene-dielectric structure of the stack on the propagation properties are shown to be significant and different from the conventional active SIW based on active components. By varying the graphene chemical potential, the cut-off frequency of the proposed waveguide can be dynamically tuned from 3 to 3.7 THz. Moreover, the tunable waveguide displays low leakage loss and single-mode propagation with −120 dB stop-band attenuation. These primary results are very promising for THz integration devices and SIW-based systems

Tunable Coupled-Resonator-Induced Transparency in a Photonic Crystal System Based on a Multilayer-Insulator Graphene Stack

We achieve the effective modulation of coupled-resonator-induced transparency (CRIT) in a photonic crystal system which consists of photonic crystal waveguide (PCW), defect cavities, and a multilayer graphene-insulator stack (MGIS). Simulation results show that the wavelength of transparency window can be effectively tuned through varying the chemical potential of graphene in MGIS. The peak value of the CRIT effect is closely related to the structural parameters of our proposed system. Tunable Multipeak CRIT is also realized in the four-resonator-coupled photonic crystal system by modulating the chemical potentials of MGISs in different cavity units. This system paves a novel way toward multichannel-selective filters, optical sensors, and nonlinear devices

ADNP is associated with immune infiltration and radiosensitivity in hepatocellular carcinoma for predicting the prognosis

Abstract Background Hepatocellular carcinoma (HCC) is one of the most lethal diseases due to its high faculty of invasiveness and metastasis. Activity-dependent neuroprotective protein (ADNP) has been regarded as an oncogene in bladder cancer and ovarian cancer. However, the role of ADNP in the regulation of tumor immune response, development, and treatment resistance in HCC remains unknown and is worth exploring. Methods The correlation between ADNP and prognosis, immune cell infiltration, immune checkpoints, chemokines, tumor mutation burden, microsatellite instability, and genomic mutation of pan-cancer cohorts in The Cancer Genome Atlas was analyzed. ADNP expression in HCC cell lines, HCC and the adjacent normal tissues was measured by western blotting and immunochemistry. Nomogram was constructed to predict the survival of patients with HCC based on the ADNP expression and significant clinical characteristics. The potential biological functions and impacts on radiotherapy of ADNP in HCC cell lines were verified by vitro experiments. Results ADNP was upregulated in most cancers and patients with elevated ADNP expression were related to poor survival in several types of cancers including HCC. Functional enrichment analysis showed ADNP participated in the pathways correlated with coagulation cascades and DNA double strand break repair. Further, ADNP exhibited a negative correlation with the immune score, stromal score, estimated score, and chemokines, and a positive correlation with cancer-associated fibroblasts, myeloid-derived suppressor cells, neutrophils, regulatory T cells, and endothelial cells. Immunochemistry and western blotting results demonstrated ADNP was up-regulated in HCC. Vitro experiments verified that suppressing the ADNP expression significantly inhibited the proliferation, invasion and migration and elevated the radiosensitivity via decreasing DNA damage repair in HCC. Conclusion ADNP might play an oncogene and immunosuppression role in tumor immune infiltration and response, thus influencing the prognosis. Its downregulation could attenuate the proliferation, invasion, migration, radioresistance of HCC. Our results indicated the potential of ADNP as a promising biomarker to predict the survival of HCC patients, providing a theoretical basis for novel integrative strategies