In vitro culture and plant regeneration derived from ray florets of Chrysanthemum morifolium

Nine cultivars of Chrysanthemum morifolium were screened using the ray floret explants to determine the capability for plant regeneration on four media protocols and subsequently to find out the best genotype source linked with the optimum medium conditions for the high potentiality of shoot formation. The results indicated that all in vitro culture traits were highly significantly influenced by the differences in genotypes, medium protocols and their interaction. The percentage of explants whichdeveloped calli ranged from 73.83% “Ping Pong” to 25.67% “Palisade White” among the cultivars across the four medium protocols with an average of 48.28%. The highest percentage of embryogenic callus, shoot formation and mean value of shoot length was produced by cultivar "Delistar White" when calli were differentiated on medium protocol B. The medium protocol B showed the greatest potential for shoot length across the cultivars and it was significantly superior to all other medium protocolsexcept the medium protocol A. The present study indicated that the medium protocol “B” and then "A" appear to be the best protocols for plant regeneration. The cultivar "Delistar White" with the medium protocols B and then A, could be successfully utilized for further in vitro mutagenesis investigations

Early and delayed suture adjustments after adjustable suture strabismus surgery: a randomized controlled trial

Background: Adjustable sutures increase the success rate of strabismus surgery. However, the optimal timing of postoperative suture adjustment remains controversial. This trial was aimed at comparing the surgical outcomes and pain scores of early or 2 – 4 h and delayed or 24 h postoperative suture adjustment in adult patients undergoing strabismus surgery. Methods: An open-label, prospective, randomized, comparative interventional study was performed in consecutive adult patients scheduled for eye muscle surgery. Patients were randomized into two groups: the early group, with suture adjustment 2 – 4 h postoperatively, and the delayed group, with suture adjustment 24 h postoperatively. Subjective pain scores during the adjustment were also analyzed. The angles of misalignment at 1 and 3 months and the success rate at 3 months postoperatively were compared. Results: Forty-five (90%) patients completed the follow-up, including 23 (92%) in the early adjustment group and 22 (88%) in the delayed adjustment group, with a mean (standard deviation) age of 25.6 (9.5) years and a male-to-female ratio of 46.7:53.3. Thirty patients (66.7%) had exotropia, and 15 (33.3%) patients had esotropia. Both groups had comparable baseline characteristics (all P > 0.05). The mean pain scores during adjustment did not differ significantly between groups (P > 0.05). The postoperative angles of alignment were comparable between the groups before suture adjustment and at the 1- and 3-month follow-ups (all P > 0.05). The success rate in the early adjustment group was slightly higher (87.0% versus 63.6%), but the difference was not statistically significant (P > 0.05). The success rate was comparable between the groups in patients with esotropia or exotropia (both P > 0.05). Conclusions: Although the early adjustment group had a slightly higher success rate, the difference was not significant. Both groups had comparable subjective pain scores during adjustment. Future clinical trials should be performed different time intervals for postoperative suture adjustment, and subjective and objective outcomes, such as diplopia and stereopsis, should be compared between patients with a first strabismus surgery and those who underwent reoperation. This could better resolve the persistent controversy related to the optimal time for suture adjustment

Use of production functions in assessing the profitability of shares of insurance companies

In this study the production functions (Cobb-Douglas, Zener-Rivanker, and the transcendental production function) have been used to assess the profitability of insurance companies, by reformulating these nonlinear functions based on the introduction of a set of variables that contribute to increase the explanatory capacity of the model. Then the best production function commensurate with the nature of the variable representing the profitability of insurance companies was chosen, to use it to assess the efficiency of their profitability versus the use of different factors of production and thus the possibility of using it in forecasting. It was found that the proposed model of the production function "Zener-Rivanker" is the best production functions representing the profitability of the Tawuniya and Bupa Insurance Companies. The proposed model of the Cobb-Douglas production function is suitable for the results of both Enaya and Sanad Cooperative Insurance Companies. The explanatory capacity of the production functions was also increased when the proposed variables were added (net subscribed premiums-net claims incurred)

A blockchain protocol for authenticating space communications between satellites constellations

Blockchain has found many applications, apart from Bitcoin, in different fields and it has the potential to be very useful in the satellite communications and space industries. Decentralized and secure protocols for processing and manipulating space transactions of satellite swarms in the form of Space Digital Tokens (SDT) can be built using blockchain technology. Tokenizing space transactions using SDTs will open the door to different new blockchain-based solutions for the advancement of constellation-based satellite communications in the space industry. Developing blockchain solutions using smart contracts could be used in securely authenticating various P2P satellite communications and transactions within/between satellite swarms. To manage and secure these transactions, using the proposed SDT concept, this paper suggested a blockchain-based protocol called Proof of Space Transactions (PoST). This protocol was adopted to manage and authenticate the transactions of satellite constellations in a P2P connection. The PoST protocol was prototyped using the Ethereum blockchain and experimented with to evaluate its performance using four metrics: read latency, read throughput, transaction latency, and transaction throughput. The simulation results clarified the efficiency of the proposed PoST protocol in processing and verifying satellite transactions in a short time according to read and transaction latency results. Moreover, the security results showed that the proposed PoST protocol is secure and efficient in verifying satellite transactions according to true positive rate (TPR), true negative rate (TNR), and accuracy metrics. These findings may shape a real attempt to develop a new generation of Blockchain-based satellite constellation systems

A Mycobacterium avium subsp. paratuberculosis relA deletion mutant and a 35 kDa major membrane protein elicit development of cytotoxic T lymphocytes with ability to kill intracellular bacteria

Efforts to develop live attenuated vaccines against Mycobacterium avium subspecies paratuberculosis (Map), using indirect methods to screen Map deletion mutants for potential efficacy, have not been successful. A reduction in the capacity to survive in macrophages has not predicted the ability of mutants to survive in vivo. Previous studies for screening of three deletion mutants in cattle and goats revealed one mutant, with a deletion in relA (ΔMap/relA), could not establish a persistent infection. Further studies, using antigen presenting cells (APC), blood dendritic cells and monocyte derived DC, pulsed with ΔMap/relA or a 35 kDa Map membrane protein (MMP) revealed a component of the response to ΔMap/relA was directed towards MMP. As reported herein, we developed a bacterium viability assay and cell culture assays for analysis and evaluation of cytotoxic T cells generated against ΔMap/relA or MMP. Analysis of the effector activity of responding cells revealed the reason ΔMap/relA could not establish a persistent infection was that vaccination elicited development of cytotoxic CD8 T cells (CTL) with the capacity to kill intracellular bacteria. We demonstrated the same CTL response could be elicited with two rounds of antigenic stimulation of APC pulsed with ΔMap/relA or MMP ex vivo. Cytotoxicity was mediated through the perforin granzyme B pathway. Finally, cognate recognition of peptides presented in context of MHC I and II molecules to CD4 and CD8 T cells is required for development of CTL

Oleanolic Acid Initiates Apoptosis in Non-Small Cell Lung Cancer Cell Lines and Reduces Metastasis of a B16F10 Melanoma Model In Vivo

Drug resistance, a process mediated by multiple mechanisms, is a critical determinant for treating lung cancer. The aim of this study is to determine if oleanolic acid (OA), a pentacyclic triterpene present in several plants, is able to circumvent the mechanisms of drug resistance present in non-small cell lung cancer (NSCLC) cell lines and to induce their death.OA decreased the cell viability of the NSCLC cell lines A459 and H460 despite the presence of active, multidrug-resistant (MDR) MRP1/ABCC1 proteins and the anti-apoptotic proteins Bcl-2 and survivin. These effects are due to apoptosis, as evidenced by the capacity of OA to induce fragmentation of DNA and activate caspase 3. Induction of NSCLC cell death by OA cannot be explained by inhibition of the MDR proteins, since treatment with triterpene had little or no effect on the activity or expression of MRP1. Moreover, treatment with OA had no effect on the expression of the anti-apoptotic protein Bcl-2, but increased the expression of the pro-apoptotic protein Bax, altering the Bcl-2/Bax balance towards a pro-apoptotic profile. OA also decreased the expression of the anti-apoptotic protein survivin. Furthermore, OA decreased the expression of the angiogenic vascular endothelial growth factor (VEGF) and decreased the development of melanoma-induced lung metastasis.Our data provide a significant insight into the antitumoral and antimetastatic activity of OA in NSCLC and suggest that including OA in the NSCLC regimens may help to decrease the number of relapses and reduce the development of metastases

Influence of angiogenetic factors and matrix metalloproteinases upon tumour progression in non-small-cell lung cancer

We attempted to investigate immunohistochemical expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), platelet-derived growth factor (PD-ECGF), c-erbB-2, matrix metalloproteinase-2 (MMP-2), and MMP-9 using surgical specimens of 119 non-small-cell lung carcinoma (NSCLC) cases and to evaluate the relationship between the expression levels of each molecule and clinicopathological factors or prognosis. VEGF expression levels were significantly associated with the local invasion (P = 0.0001), lymph node involvement (pN-factor) (P = 0.0019), pathological stage (p-stage) (P = 0.0027) and lymphatic permeation (P = 0.0389). PD-ECGF expression levels were associated with pN-factor (P = 0.0347). MMP-2 expression levels were associated with pN-factor (P = 0.004) and lymphatic permeation (P = 0.0056). Also, MMP-9 expression levels showed a significant correlation to local invasion (P = 0.0012), pN-factor (P = 0.0093) and p-stage (P = 0.0142). Multivariate analysis showed VEGF to be the most related to local invasion (P = 0.0084), and MMP-2 was the only factor with significant independent impact on lymphatic permeation (P = 0.0228). Furthermore, log-rank analysis showed significant association with poor survival by VEGF, bFGF, MMP-2 and MMP-9. Especially, combined overexpression of VEGF and MMP-2 revealed poor prognosis, our study might provide a basis for the better evaluation of biological characteristics and a new therapeutic strategy based on chemotherapy. © 2001 Cancer Research Campaign http://www.bjcancer.co

ATP-binding cassette (ABC) transporters in normal and pathological lung

ATP-binding cassette (ABC) transporters are a family of transmembrane proteins that can transport a wide variety of substrates across biological membranes in an energy-dependent manner. Many ABC transporters such as P-glycoprotein (P-gp), multidrug resistance-associated protein 1 (MRP1) and breast cancer resistance protein (BCRP) are highly expressed in bronchial epithelium. This review aims to give new insights in the possible functions of ABC molecules in the lung in view of their expression in different cell types. Furthermore, their role in protection against noxious compounds, e.g. air pollutants and cigarette smoke components, will be discussed as well as the (mal)function in normal and pathological lung. Several pulmonary drugs are substrates for ABC transporters and therefore, the delivery of these drugs to the site of action may be highly dependent on the presence and activity of many ABC transporters in several cell types. Three ABC transporters are known to play an important role in lung functioning. Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene can cause cystic fibrosis, and mutations in ABCA1 and ABCA3 are responsible for respectively Tangier disease and fatal surfactant deficiency. The role of altered function of ABC transporters in highly prevalent pulmonary diseases such as asthma or chronic obstructive pulmonary disease (COPD) have hardly been investigated so far. We especially focused on polymorphisms, knock-out mice models and in vitro results of pulmonary research. Insight in the function of ABC transporters in the lung may open new ways to facilitate treatment of lung diseases

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease