Chemometric Tools to Highlight the Variability of the Chemical Composition and Yield of Lebanese Origanum syriacum L. Essential Oil

This study deals with the variation in the yield and composition of Lebanese Origanum syriacum L. essential oil (EO) according to harvesting time, drying methods used, and geographical location. Plant material was harvested twice a month all over 2013 and 2014 from Qartaba and Achkout located at high altitude and from Byblos at low altitude. EOs of the aerial parts were obtained by hydrodistillation. The highest yields were obtained at full flowering stage and slightly reduced after flowering. The GC/MS analysis revealed the presence of 50 components representing 90.49 – 99.82%, 88.79 – 100%, and 95.28 – 100% of the total oil extracted from plants harvested from Qartaba, Achkout, and Byblos, respectively. The major components in the oils were: carvacrol (2.1 – 79.8%), thymol (0.3 – 83.7%), p‐cymene (2.8 – 43.8%), thymoquinone (0.4 – 27.7%), γ‐terpinene (0.4 – 10.0%), octan‐3‐ol (0.3 – 4.9%), caryophyllene oxide (0.2 – 4.7%), oct‐1‐en‐3‐ol (0.3 – 3.7%), β‐caryophyllene (0.7 – 3.2%), cis‐sabinene hydrate (0.1 – 2.8%), terpinen‐4‐ol (0.1 – 2.8%), and α‐terpinene (0.2 – 2.2%). Independent components analysis (ICA) revealed that two groups were discriminated, reflecting compositional differences in the EOs profiles of the Lebanese oregano samples: O. syriacum grown in Qartaba and Achkout belongs to carvacrol chemotype, while O. syriacum grown in Byblos belongs to thymol chemotype. The flowering phase was the most productive period in terms of yield, bringing marked changes in the EO composition by increasing the amounts of carvacrol or thymol, and decreasing those of thymoquinone and p‐cymene.     

A novel regeneration system through micrografting for Argania spinosa (L.) Skeels,and confirmation of successful rootstock-scion union by histological analysis

Plant Cell, Tissue and Organ Culture (PCTOC) - European mistletoe (Viscum album) is a medicinal plant with significant anticancer properties. In vitro callus production provides an essential...     

Two Panels of Plasma MicroRNAs as Non-Invasive Biomarkers for Prediction of Recurrence in Resectable NSCLC

The diagnosis of non-small cell lung carcinoma (NSCLC) at an early stage, as well as better prediction of outcome remains clinically challenging due to the lack of specific and robust non-invasive markers. The discovery of microRNAs (miRNAs), particularly those found in the bloodstream, has opened up new perspectives for tumor diagnosis and prognosis. The aim of our study was to determine whether expression profiles of specific miRNAs in plasma could accurately discriminate between NSCLC patients and controls, and whether they are able to predict the prognosis of resectable NSCLC patients. We therefore evaluated a series of seventeen NSCLC-related miRNAs by quantitative real-time (qRT)-PCR in plasma from 52 patients with I-IIIA stages NSCLC, 10 patients with chronic obstructive pulmonary disease (COPD) and 20-age, sex and smoking status-matched healthy individuals. We identified an eleven-plasma miRNA panel that could distinguish NSCLC patients from healthy subjects (AUC = 0.879). A six-plasma miRNA panel was able to discriminate between NSCLC patients and COPD patients (AUC = 0.944). Furthermore, we identified a three-miRNA plasma signature (high miR-155-5p, high miR-223-3p, and low miR-126-3p) that significantly associated with a higher risk for progression in adenocarcinoma patients. In addition, a three-miRNA plasma panel (high miR-20a-5p, low miR-152-3p, and low miR-199a-5p) significantly predicted survival of squamous cell carcinoma patients. In conclusion, we identified two plasma miRNA expression profiles that may be useful for predicting the outcome of patients with resectable NSCLC.     

Determination of antioxidant activity,total phenolics and fatty acids in essential oils and other extracts from callus culture,seeds and leaves of Argania spinosa (L.) Skeels

Plant Cell, Tissue and Organ Culture (PCTOC) - Argan (Argania spinosa (L.) Skeels) is an endangered and endemic agroforestry species of Morocco highly appreciated for its nutraceutical properties....     

Risk of second bone sarcoma following childhood cancer: role of radiation therapy treatment

Bone sarcoma as a second malignancy is rare but highly fatal. The present knowledge about radiation-absorbed organ dose–response is insufficient to predict the risks induced by radiation therapy techniques. The objective of the present study was to assess the treatment-induced risk for bone sarcoma following a childhood cancer and particularly the related risk of radiotherapy. Therefore, a retrospective cohort of 4,171 survivors of a solid childhood cancer treated between 1942 and 1986 in France and Britain has been followed prospectively. We collected detailed information on treatments received during childhood cancer. Additionally, an innovative methodology has been developed to evaluate the dose–response relationship between bone sarcoma and radiation dose throughout this cohort. The median follow-up was 26 years, and 39 patients had developed bone sarcoma. It was found that the overall incidence was 45-fold higher [standardized incidence ratio 44.8, 95 % confidence interval (CI) 31.0–59.8] than expected from the general population, and the absolute excess risk was 35.1 per 100,000 person-years (95 % CI 24.0–47.1). The risk of bone sarcoma increased slowly up to a cumulative radiation organ absorbed dose of 15 Gy [hazard ratio (HR) = 8.2, 95 % CI 1.6–42.9] and then strongly increased for higher radiation doses (HR for 30 Gy or more 117.9, 95 % CI 36.5–380.6), compared with patients not treated with radiotherapy. A linear model with an excess relative risk per Gy of 1.77 (95 % CI 0.6213–5.935) provided a close fit to the data. These findings have important therapeutic implications: Lowering the radiation dose to the bones should reduce the incidence of secondary bone sarcomas. Other therapeutic solutions should be preferred to radiotherapy in bone sarcoma-sensitive areas.     

Understanding the Rate Capability of High‐Energy‐Density Li‐Rich Layered Li1.2Ni0.15Co0.1Mn0.55O2 Cathode Materials

The high‐energy‐density, Li‐rich layered materials, i.e., xLiMO₂(1‐x)Li₂MnO₃, are promising candidate cathode materials for electric energy storage in plug‐in hybrid electric vehicles (PHEVs) and electric vehicles (EVs). The relatively low rate capability is one of the major problems that need to be resolved for these materials. To gain insight into the key factors that limit the rate capability, in situ X‐ray absorption spectroscopy (XAS) and X‐ray diffraction (XRD) studies of the cathode material, Li_1.2Ni_0.15Co_0.1Mn_0.55O₂ [0.5Li(Ni_0.375Co_0.25 Mn_0.375)O₂·0.5Li₂MnO₃], are carried out. The partial capacity contributed by different structural components and transition metal elements is elucidated and correlated with local structure changes. The characteristic reaction kinetics for each element are identified using a novel time‐resolved XAS technique. Direct experimental evidence is obtained showing that Mn sites have much poorer reaction kinetics both before and after the initial activation of Li₂MnO₃, compared to Ni and Co. These results indicate that Li₂MnO₃ may be the key component that limits the rate capability of Li‐rich layered materials and provide guidance for designing Li‐rich layered materials with the desired balance of energy density and rate capability for different applications.     

An Experimental Analysis of Overcoming Obstacle in Human Walking

In this paper, an experimental analysis of overcoming obstacle in human walking is carried out by means of a motion capture system. In the experiment, the lower body of an adult human is divided into seven segments, and three markers are pasted to each segment with the aim to obtain moving trajectory and to calculate joint variation during walking. Moreover, kinematic data in terms of displacement, velocity and acceleration are acquired as well. In addition, ground reaction forces are measured using force sensors. Based on the experimental results, features of overcoming obstacle in human walking are ana- lyzed. Experimental results show that the reason which leads to smooth walking can be identified as that the human has slight movement in the vertical direction during walking; the reason that human locomotion uses gravity effectively can be identified as that feet rotate around the toe joints during toe-off phase aiming at using gravitational potential energy to provide propulsion for swing phase. Furthermore, both normal walking gait and obstacle overcoming gait are characterized in a form that can provide necessary knowledge and useful databases for the implementation of motion planning and gait planning towards overcoming obstacle for humanoid robots.     

Acoustic cell filter: a proven cell retention technology for perfusion of animal cell cultures

This article is a review highlighting the application of the acoustic filter as a reliable cell retention device during the long-term perfusion of animal cell cultures. Critical operating parameters such as duty cycle, perfusion and re-circulation flow rates, acoustic power and backflush frequency are discussed with regard to influence on the separation efficiency and optimal operating ranges have been identified. Perfusion data gathered from the literature have been complemented with original data from a series of perfusion experiments carried out in the context of industrial projects for industrially relevant cell lines including NS0, HEK-293, SP2-derived hybridoma and insect cells in different serum-supplemented and serum-free media at different perfusion rates and acoustic chamber volumes. Finally, scale-up potential of the acoustic filter for large-scale industrial applications is discussed.     

Novel fatty acid elongases and their use for the reconstitution of docosahexaenoic acid biosynthesis

In algae, the biosynthesis of docosahexaenoic acid (22:6omega3; DHA) proceeds via the elongation of eicosapentaenoic acid (20:5omega3; EPA) to 22:5omega3, which is required as a substrate for the final Delta4 desaturation. To isolate the elongase specific for this step, we searched expressed sequence tag and genomic databases from the algae Ostreococcus tauri and Thalassiosira pseudonana, from the fish Oncorhynchus mykiss, from the frog Xenopus laevis, and from the sea squirt Ciona intestinalis using as a query the elongase sequence PpPSE1 from the moss Physcomitrella patens. The open reading frames of the identified elongase candidates were expressed in yeast for functional characterization. By this, we identified two types of elongases from O. tauri and T. pseudonana: one specific for the elongation of (Delta6-)C18-PUFAs and one specific for (Delta5-)C20-PUFAs, showing highest activity with EPA. The clones isolated from O. mykiss, X. laevis, and C. intestinalis accepted both C18- and C20-PUFAs. By coexpression of the Delta6- and Delta5-elongases from T. pseudonana and O. tauri, respectively, with the Delta5- and Delta4-desaturases from two other algae we successfully implemented DHA synthesis in stearidonic acid-fed yeast. This may be considered an encouraging first step in future efforts to implement this biosynthetic sequence into transgenic oilseed crops.     

NADPH Oxidase 1 Controls the Persistence of Directed Cell Migration by a Rho-Dependent Switch of α2/α3 Integrins

NADPH oxidase 1 (Nox1) is expressed mainly in colon epithelial cells and produces superoxide ions as a primary function. We showed that Nox1 knockdown inhibits directional persistence of migration on collagen I. This paper dissects the mechanism by which Nox1 affects the direction of colonic epithelial cell migration in a two-dimensional model. Transient activation of Nox1 during cell spreading on collagen 1 temporarily inactivated RhoA and led to efficient exportation of α2β1 integrin to the cell surface, which supported persistent directed migration. Nox1 knockdown led to a loss of directional migration which takes place through a RhoA-dependent α2/α3 integrin switch. Transient RhoA overactivation upon Nox1 inhibition led to transient cytoskeletal reorganization and increased cell-matrix contact associated with a stable increase in α3 integrin cell surface expression. Blocking of α3 integrin completely reversed the loss of directional persistence of migration. In this model, Nox1 would represent a switch between random and directional migration through RhoA-dependent integrin cell surface expression modulation.The two well-recognized defining hallmarks of cancer are uncontrolled proliferation and invasion (14). The conversion of a static primary tumor into an invasive disseminating metastasis involves an enhanced migratory ability of the tumor cells. Tumor cells use migration mechanisms that are similar, if not identical, to those that occur in normal cells during physiological processes such as embryonic morphogenesis, wound healing, and immune-cell trafficking (10). To migrate, cells must acquire a spatial asymmetry that enables them to turn intracellularly generated forces into net cell body translocation. Dynamic assembly and disassembly of integrin-mediated adhesion and cytoskeletal reorganization are necessary for efficient migration (29). Integrins are heterodimeric integral membrane proteins composed of an α chain and a β chain. Depending on the cell type and extracellular matrix (ECM) substrate, focal contact assembly and migration can be regulated by different integrins. Collagen receptors include α1β1, α2β1, and α3β1 integrins. α1β1 and α3β1 integrins also bind laminin and have less affinity for collagen than does integrin α2β1 (47). The intrinsic propensity of cells to continue migrating in the same direction without turning is closely related to integrin/cytoskeletal interaction, which is known to regulate tractional forces, resulting in modulation of the speed and direction of cell migration (33). Interestingly, different integrin-ECM associations might have opposite effects on the regulation of the directionality of migration. Danen et al. have shown that adhesion to fibronectin by αvβ3 promotes persistent migration through activation of the actin-severing protein cofilin, which results in a polarized phenotype with a single broad lamellipod at the leading edge. In contrast, adhesion to fibronectin by α5β1 instead leads to phosphorylation/inactivation of cofilin and these cells fail to polarize their cytoskeleton and adopt a random/nonpersistent mode of migration (5). Members of the Rho GTPase family (including RhoA, Rac1, and Cdc42) are known as key modulators of cytoskeletal dynamics that occur during cell migration (37). RhoA regulates stress fiber and focal adhesion assembly, Rac regulates the formation of lamellipodial protrusions and membrane ruffles, and Cdc42 triggers filopodial extensions at the cell periphery (13).One of the earliest characterized functions of the Rho GTPase Rac was regulation of the activity of the NADPH oxidase complex in phagocytic cells to produce reactive oxygen species (ROS) (1, 19). Moreover, it has been shown that Rac-dependent ROS production leads to downregulation of RhoA through oxidative inactivation of the low-molecular-weight (LMW) protein tyrosine phosphatase (PTP) and the subsequent activation of p190RhoGAP (31). ROS are also known to directly affect important regulators of cell migration such as PTEN, FAK, or Src (4, 20, 22). ROS are generated in cells from several sources, including the mitochondrial respiratory chain, xanthine oxidase, cytochrome P450, nitric oxide synthase, and NADPH oxidase. The seven known human catalytic subunits of NADPH oxidase include Nox1 to -5 and Duox1 and -2, with Nox2 (gp91phox) being the founding member (21). These oxidases participate in several adaptive functions, ranging from mitogenesis to immune cell signaling (11). A growing body of data points to a key role for ROS production by NADPH oxidase in the control of cell migration and cytoskeletal reorganization (30, 44). Among NADPH oxidase homologs, Nox1 has been detected in different cell types, with major expression in vascular smooth muscle cells and colonic epithelial cells (42). Nox1 involvement in the control of cytoskeletal organization and cellular migration has been only recently reported. Shinohara et al. demonstrated that oncogenic Ras transformation involves Nox1-dependent signaling and leads to inactivation of RhoA. Abrogation of Nox1-dependent ROS production by diphenyleneiodonium (DPI) or small interfering RNA restores RhoA activation and actin stress fiber formation (41). More recently, several groups have highlighted a key role of Nox1 in the control of growth factor-induced migration (16, 38, 40). Cancer cells probably undergo random migration during metastasis, but their migration can be directed by cytokine gradients and/or associated with ECM fibers (29, 55). In a recent report, we showed that Nox1 downregulation decreased the persistence of colonic adenocarcinoma cell migration over collagen I (Col-I) without affecting either the mean velocity or the total distance of migration.In the present study, we investigated the molecular mechanism by which Nox1-dependent ROS production controls the directionality of migration of colonic adenocarcinoma cells. We showed that Nox1-dependent ROS production, which occurs during cell spreading after 4 h of adhesion to Col-I, transiently inhibited RhoA activity. Nox1 inhibition during cell spreading led to a transient increase in cell-matrix contact and initiated a sustained decrease in α2β1 integrin cell surface expression, which was compensated for by an increase in α3 integrin cell surface expression. While Nox1-dependent RhoA inhibition was transient, the observed α2/α3 integrin switch was sustained over 24 h. The loss of directionality observed in cell migration upon Nox1 inhibition may be reversed by α3 integrin blockade. This work shows that Nox1 is involved in the control of integrin surface expression during migration on Col-I, which is critical for persistent directed migration through transient modulation of a RhoA/ROCK-dependent pathway.