Global status and future prospects of research in cotton leaf curl disease

Abstract

Begomoviruses are economically important plant viruses with a wide host range infecting numerous vegetables, legumes and fibre crops worldwide. Pakistan cotton suffered with cotton leaf curl disease (CLCuD) epidemic in the 1990s resulting in huge crop losses. Since then CLCuD has become a continuous threat to cotton industry in Pakistan. Several monopartite begomovirus species and satellite molecules are associated with CLCuD. There is threat of disease spreading to other parts of the world which are currently free from CLCuD due to agricultural trade and spread of vector, Bemisia tabaci. Natural resistance in tetraploid cotton, Gossypium hirsutum against CLCuD is very limited and is not durable under field conditions due to emergence of new viral strains. Genetically engineered resistance towards CLCuD has had limited success due to transformation limitations in cotton and the diversity of begomoviruses. Molecular approaches and conventional breeding are underway for developing cotton with CLCuD resistance. There is need to introgress multiple resistance genes in cotton to produce durable resistance which would lost several years. The review is an update on the current status and future prospects of CLCuD.     

Structural-dynamic insights into the H. pylori cytotoxin-associated gene A (CagA) and its abrogation to interact with the tumor suppressor protein ASPP2 using decoy peptides

Abstract

Helicobacter pylori (H. pylori) is one of the most extensively studied Gram-negative bacteria due to its implication in gastric cancer. The oncogenicity of H. pylori is associated with cytotoxin-associated gene A (CagA), which is injected into epithelial cells lining the stomach. Both the C- and N-termini of CagA are involved in the interaction with several host proteins, thereby disrupting vital cellular functions, such as cell adhesion, cell cycle, intracellular signal transduction, and cytoskeletal structure. The N-terminus of CagA interacts with the tumor-suppressing protein, apoptosis-stimulating protein of p53 (ASPP2), subsequently disrupting the apoptotic function of tumor suppressor gene p53. Here, we present the in-depth molecular dynamic mechanism of the CagA–ASPP2 interaction and highlight hot-spot residues through in silico mutagenesis. Our findings are in agreement with previous studies and further suggest other residues that are crucial for the CagA–ASPP2 interaction. Furthermore, the ASPP2-binding pocket possesses potential druggability and could be engaged by decoy peptides, identified through a machine-learning system and suggested in this study. The binding affinities of these peptides with CagA were monitored through extensive computational procedures and reported herein. While CagA is crucial for the oncogenicity of H. pylori, our designed peptides possess the potential to inhibit CagA and restore the tumor suppressor function of ASPP2.     

Reconstruction of an Integrated Genome-Scale Co-Expression Network Reveals Key Modules Involved in Lung Adenocarcinoma

Our goal of this study was to reconstruct a “genome-scale co-expression network” and find important modules in lung adenocarcinoma so that we could identify the genes involved in lung adenocarcinoma. We integrated gene mutation, GWAS, CGH, array-CGH and SNP array data in order to identify important genes and loci in genome-scale. Afterwards, on the basis of the identified genes a co-expression network was reconstructed from the co-expression data. The reconstructed network was named “genome-scale co-expression network”. As the next step, 23 key modules were disclosed through clustering. In this study a number of genes have been identified for the first time to be implicated in lung adenocarcinoma by analyzing the modules. The genes EGFR, PIK3CA, TAF15, XIAP, VAPB, Appl1, Rab5a, ARF4, CLPTM1L, SP4, ZNF124, LPP, FOXP1, SOX18, MSX2, NFE2L2, SMARCC1, TRA2B, CBX3, PRPF6, ATP6V1C1, MYBBP1A, MACF1, GRM2, TBXA2R, PRKAR2A, PTK2, PGF and MYO10 are among the genes that belong to modules 1 and 22. All these genes, being implicated in at least one of the phenomena, namely cell survival, proliferation and metastasis, have an over-expression pattern similar to that of EGFR. In few modules, the genes such as CCNA2 (Cyclin A2), CCNB2 (Cyclin B2), CDK1, CDK5, CDC27, CDCA5, CDCA8, ASPM, BUB1, KIF15, KIF2C, NEK2, NUSAP1, PRC1, SMC4, SYCE2, TFDP1, CDC42 and ARHGEF9 are present that play a crucial role in cell cycle progression. In addition to the mentioned genes, there are some other genes (i.e. DLGAP5, BIRC5, PSMD2, Src, TTK, SENP2, PSMD2, DOK2, FUS and etc.) in the modules.     

Comparison of acellular and cellular bioactivity of poly 3-hydroxybutyrate/hydroxyapatite nanocomposite and poly 3-hydroxybutyrate scaffolds

Nanocomposites have recently been identified as a useful scaffolding material in tissue engineering applications. Poly (3-hydroxybutyrate)/hydroxyapatite nanoparticles (P3HB)/(nHA) porous scaffolds were successfully fabricated through a solvent casting and particulate leaching technique. P3HB/nHA and P3HB scaffolds were prepared by the same technique for comparison. The structure of the nanocomposite and P3HB scaffolds was observed by SEM. The Energy Disperssive X-ray Analysis (EDXA, map of Ca) results indicated that HA nanoparticles were homogeneously dispersed in the P3HB matrix. X-ray diffraction (XRD) analysis showed that P3HB and HA coexist in the nanocomposite. Transmission electron microscopy (TEM) images also showed that the particle size of HA was 30 ～ 40 nm. The porosity of the scaffolds was 84%, and macropores and micropores coexisted and interconnected throughout the scaffolds. Acellular bioactivity experiments showed that more HA crystals formed on the surface of the nanocomposite scaffold than on the P3HB scaffold after 4 weeks immersion in Simulated Body Fluid (SBF). Cell culture experiments demonstrated that the P3HB/nHA nanocomposite scaffold had a better tendency of proliferation and Alkaline Phosphatase (ALP) activity to MG 63 cells than the pure P3HB scaffold. It was found that nHA addition can improve acellular and cellular bioactivity of the P3HB scaffold.     

Ethanethiol degradation by Ralstonia eutropha

In the present study, a pure culture of Ralstonia eutropha was used to degrade gaseous ethanethiol. Ethane thiol at various initial concentrations ranging from 115 to 320 mg/m³ was degraded almost completely within 120 ～ 168 h, while at higher concentrations up to 452 mg/m³, removal efficiency declined. It was likely that ethanethiol was used as the source of energy by R. eutropha, since no clear increase in the biomass concentration was observed. Kinetic data of ethanethiol bidegradation could be fitted using the Monod model. The kinetic parameters were q _m = 0.23 (mg ethanethiol/g biomass/h), and K _s = 1.379 (mg/L). The mineralization pathway of ethanethiol through sulphate, as the detected product, and the energy production were discussed in some detail.     

Phylogenetic analysis of cubilin (CUBN) gene

Cubilin, (CUBN; also known as intrinsic factor-cobalamin receptor [Homo sapiens Entrez Pubmed ref {"type":"entrez-nucleotide","attrs":{"text":"NM_001081.3","term_id":"126091151","term_text":"NM_001081.3"}}NM_001081.3; {"type":"entrez-nucleotide","attrs":{"text":"NG_008967.1","term_id":"212549718","term_text":"NG_008967.1"}}NG_008967.1; GI: 119606627]), located in the epithelium of intestine and kidney acts as a receptor for intrinsic factor – vitamin B12 complexes. Mutations in CUBN may play a role in autosomal recessive megaloblastic anemia. The current study investigated the possible role of CUBN in evolution using phylogenetic testing. A total of 588 BLAST hits were found for the cubilin query sequence and these hits showed putative conserved domain, CUB superfamily (as on 27^th Nov 2012). A first-pass phylogenetic tree was constructed to identify the taxa which most often contained the CUBN sequences. Following this, we narrowed down the search by manually deleting sequences which were not CUBN. A repeat phylogenetic analysis of 25 taxa was performed using PhyML, RAxML and TreeDyn softwares to confirm that CUBN is a conserved protein emphasizing its importance as an extracellular domain and being present in proteins mostly known to be involved in development in many chordate taxa but not found in prokaryotes, plants and yeast.. No horizontal gene transfers have been found between different taxa.     

Effects of protein binding on a lipid bilayer containing local anesthetic articaine, and the potential of mean force calculation: a molecular dynamics simulation approach

Articaine, as a local anesthetic drug has been simulated in neutral and charged forms, and its interaction with the dimyristoylphosphatidylcholine (DMPC) lipid bilayer membrane is investigated by molecular dynamics simulation using GROMACS software. In order to obtain the optimum location of the drug molecules, as they penetrate into the membrane, umbrella sampling is applied and the free energy is calculated. The effect of protein binding to DMPC membrane on the process of drug diffusion through the membrane is considered. Five simulation systems are designed and by applying the potential of mean force, the molecular dynamics simulation on the system is performed. In light of the obtained results, the electrostatic potential, variation of lipid bilayer’s order parameter and the diffusion coefficient of drug are discussed.

The SKP1-Cul1-F-box and leucine-rich repeat protein 4 (SCF-FbxL4) ubiquitin ligase regulates lysine demethylase 4A (KDM4A)/Jumonji domain-containing 2A (JMJD2A) protein

Chromatin-modifying enzymes play a fundamental role in regulating chromatin structure so that DNA replication is spatially and temporally coordinated. For example, the lysine demethylase 4A/Jumonji domain-containing 2A (KDM4A/JMJD2A) is tightly regulated during the cell cycle. Overexpression of JMJD2A leads to altered replication timing and faster S phase progression. In this study, we demonstrate that degradation of JMJD2A is regulated by the proteasome. JMJD2A turnover is coordinated through the SKP1-Cul1-F-box ubiquitin ligase complex that contains cullin 1 and the F-box and leucine-rich repeat protein 4 (FbxL4). This complex interacted with JMJD2A. Ubiquitin overexpression restored turnover and blocked the JMJD2A-dependent faster S phase progression in a cullin 1-dependent manner. Furthermore, increased ubiquitin levels decreased JMJD2A occupancy and BrdU incorporation at target sites. This study highlights a finely tuned mechanism for regulating histone demethylase levels and emphasizes the need to tightly regulate chromatin modifiers so that the cell cycle occurs properly.