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RbAp46/RBBP7 and RbAp48/RBBP4 are WD40-repeat histone chaperones and chromatin adaptors that reside in multiple complexes involved in maintenance of chromatin structure. RbAp48 is the essential subunit of the chromatin assembly factor-1 (CAF-1) complex, therefore also named as CAF-1C. A detailed in silico sequence and structure analysis of homologs of RbAp46/48 in Plasmodium falciparum (PF3D7_0110700 and PF3D7_1433300) exhibited conservation of characteristic features in both the protein-seven-bladed WD40 β-propeller conformation and different binding interfaces. A comparative structural analysis highlighted species-specific features of the parasite, yeast, drosophila, and human RbAp46/48. In the present study, we report cloning, expression, and characterization of P. falciparum PF3D7_0110700, a putative RbAp46/48 (PfRbAp46/48). PfRbAp46/48 was cloned into pTEM11 vector in fusion with 6xHistidine tag and over-expressed in Escherichia coli B834 cells. The protein was purified by Ni-NTA followed by gel permeation chromatography. The protein expressed in all the three asexual blood stages and exhibited nuclear localization. We showed direct interaction of the purified rPfRbAp46/48 with the histone H4. These findings further our understanding of RbAp46/48 proteins and role of these proteins in the parasite biology.

Objective: Our aim was to validate the prognostic relevance in NSCLC of potential residual tumor (R) descriptors, including the proposed International Association for the Study of Lung Cancer definition for uncertain resection, referred to as R(un). Methods: A total of 14,712 patients undergoing resection with full R status and survival were analyzed. The following were also evaluated: whether fewer than three N2 stations were explored, lobe-specific nodal dissection, extracapsular extension, highest lymph node station status, carcinoma in situ at the bronchial resection margin, and pleural lavage cytologic examination result. Revised categories of R0, R(un), R1, and R2 were tested for survival impact. Results: In all, 14,293 cases were R0, 263 were R1, and 156 were R2 (median survivals not reached, 33 months, and 29 months, respectively). R status correlated with T and N categories. A total of 9290 cases (63%) had three or more N2 stations explored and 6641 cases (45%) had lobespecific nodal dissection, correlated with increasing pN2. Extracapsular extension was present in 62 of 364 cases with available data (17%). The highest station was positive in 942 cases (6.4%). The pleural lavage cytologic examination result was positive in 59 of 1705 cases (3.5%): 13 had carcinoma in situ at the bronchial resection margin. After reassignment because of inadequate nodal staging in 56% of cases, 6070 cases were R0, 8185 were R(un), 301 were R1, and 156 were R2. In node-positive cases, the median survival times were 70, 50, and 30 months for RO, R(un) (p < 0.0001), and R1 (p < 0.001), respectively, with no significant difference between RO and R(un) in pN0 cases. Conclusions: R descriptors have prognostic relevance, with R(un) survival stratifying between R0 and R1. Therefore, a detailed evaluation of R factor is of particular importance in the design and analyses of clinical trials of adjuvant therapies. (C) 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Histones N-terminal tails are the sites for Post-Translational Modifications (PTMs) that regulate the chromatin structure, thus chromatin associated processes. PTMs include methylation, acetylation, phosphorylation, ubiquitination, sumoylation, and ribosylation. Histone lysine methylation is associated with both transcription activation and repression. The SET domain proteins carry out the histone lysine methylation on the N-terminal tails of histones H3 and H4 and are called Histone Lysine Methyltransferases (HKMTs). A total of ten SET domain genes have been identified in human malarial parasite Plasmodium falciparum. The present study provides detailed computational analysis of P. falciparum SET domain proteins (PfSETs). The analyses cover PfSET family in terms of domain composition, physiochemical properties, subcellular localization, expression profiling and phylogenetic relationships. The work also highlights the conservation of important catalytic residues in PfSETs. The present study provides a detailed insight into the PfSET family, thus opens a platform for further developments. How to cite this article:Kaushik M, Chahar P, Nehra A, Kumar N, Gill R. Genomic Glimpse of the Chromatin Modifier SET Domain family in Plasmodium falciparum. J Commun Dis 2019; 51(4): 29-40. DOI: https://doi.org/10.24321/0019.5138.201934

Objective.To investigate demographic, lifestyle, and serologic risk factors for isolated rheumatoid arthritis (RA)–associated bronchiectasis (RA-BR) that is not a result of interstitial lung disease (ILD).Methods.We performed a case-control study using patients with RA from the Mass General Brigham Biobank. We reviewed the records of all patients with RA meeting the 2010 American College of Rheumatology/European Alliance of Associations for Rheumatology criteria with computed tomography (CT) chest imaging to identify RA-BR cases and controls with RA and RA-related lung disease. For each patient, the CT chest imaging that was performed closest to enrollment was independently reviewed by 2 radiologists for the presence of RA-related lung diseases. Cases had clinical and radiologic evidence of RA-BR without interstitial lung abnormalities on imaging. Controls had RA and no evidence of bronchiectasis or ILD. We examined the associations between demographic, lifestyle, and serologic factors with RA-BR using multivariable logistic regression.Results.We identified 57 cases of isolated RA-BR and 360 RA controls without RA-related lung disease. In multivariable models, RA-BR was associated with older age at RA onset (OR 1.37 per 10 years, 95% CI 1.02–1.82), lower BMI at RA diagnosis (OR 0.94 per kg/m2, 95% CI 0.89–0.99), seropositive RA (OR 3.96, 95% CI 1.84–8.53), positive rheumatoid factor (OR 4.40, 95% CI 2.14–9.07), and positive anticyclic citrullinated peptide (OR 3.47, 95% CI 1.65–7.31). Higher titers of RA-related autoantibodies were associated with higher odds of RA-BR.Conclusion.Seropositivity, older age at RA diagnosis, and lower BMI at RA onset were associated with isolated bronchiectasis in RA that was not a result of ILD. These findings expand the list of potential risk factors for RA-BR and suggest a pathogenic link between airway inflammation and RA-related autoantibodies.

Objectives To investigate the associations of the common MUC5B promoter variant with timing of RA-associated interstitial lung disease (RA-ILD) and RA onset. Methods We identified patients with RA meeting 2010 ACR/EULAR criteria and available genotype information in the Mass General Brigham Biobank, a multihospital biospecimen and clinical data collection research study. We determined RA-ILD presence by reviewing all RA patients who had CT imaging, lung biopsy or autopsy results. We determined the dates of RA and RA-ILD diagnoses by manual records review. We examined the associations of the MUC5B promoter variant (G>T at rs35705950) with RA-ILD, RA-ILD occurring before or within 2 years of RA diagnosis and RA diagnosis at age >55 years. We used multivariable logistic regression to estimate odds ratios (ORs) for each outcome by MUC5B promoter variant status, adjusting for potential confounders including genetic ancestry and smoking. Results We identified 1005 RA patients with available genotype data for rs35705950 (mean age 45 years, 79% female, 81% European ancestry). The MUC5B promoter variant was present in 155 (15.4%) and was associated with RA-ILD [multivariable OR 3.34 (95% CI 1.97, 5.60)], RA-ILD before or within 2 years of RA diagnosis [OR 4.01 (95% CI 1.78, 8.80)] and RA onset after age 55 years [OR 1.52 (95% CI 1.08, 2.12)]. Conclusions The common MUC5B promoter variant was associated with RA-ILD onset earlier in the RA disease course and older age of RA onset. These findings suggest that the MUC5B promoter variant may impact RA-ILD risk early in the RA disease course, particularly in patients with older-onset RA.

The mini-chromosome maintenance (MCM) family, a large and functionally diverse protein family belonging to the AAA+ superfamily, is essential for DNA replication in all eukaryotic organisms. The MCM 2-7 form a hetero-hexameric complex which serves as licensing factor necessary to ensure the proper genomic DNA replication during the S phase of cell cycle. MCM 8-10 are also associated with the DNA replication process though their roles are particularly unclear. In this study, we report an extensive in silico analysis of MCM gene family (MCM 2-10) in Arabidopsis and rice. Comparative analysis of genomic distribution across eukaryotes revealed conservation of core MCMs 2-7 while MCMs 8-10 are absent in some taxa. Domain architecture analysis underlined MCM 2-10 subfamily specific features. Phylogenetic analyses clustered MCMs into 9 clades as per their subfamily. Duplication events are prominent in plant MCM family, however no duplications are observed in Arabidopsis and rice MCMs. Synteny analysis among Arabidopsis thaliana, Oryza sativa, Glycine max and Zea mays MCMs demonstrated orthologous relationships and duplication events. Further, estimation of synonymous and non-synonymous substitution rates illustrated evolution of MCM family under strong constraints. Expression profiling using available microarray data and qRT-PCR revealed differential expression under various stress conditions, hinting at their potential use to develop stress resilient crops. Homology modeling of Arabidopsis and rice MCM 2-7 and detailed comparison with yeast MCMs identified conservation of eukaryotic specific insertions and extensions as compared to archeal MCMs. Protein-protein interaction analysis revealed an extensive network of putative interacting partners mainly involved in DNA replication and repair. The present study provides novel insights into the MCM family in Arabidopsis and rice and identifies unique features, thus opening new perspectives for further targeted analyses.

The present research reports a detailed in silico analysis of chromatin assembly factor-1 (CAF-1) family in human malaria parasite Plasmodium falciparum. Our analysis revealed five chromatin assembly factor-1 genes in P. falciparum (PfCAF-1) and the PfCAF-1 family was divided into two classes where, Class A belongs to the CAF-1 complex and others are kept in Class B. For comparative studies, orthologs of PfCAF-1 family were identified across 53 eukaryotic species and evolutionary relationships were drawn for different CAF-1 subfamilies. The phylogenetic analysis revealed grouping of evolutionary-related species together, although, divergence was observed in branching pattern. A detailed analysis of domain composition highlighted species-specific features viz. species-specific KDDS repeats of 84 amino acids were identified in PfCAF-1A whereas, members of CAF-1C/RbAp48 and RbAp46 subfamily exhibited least variation in size and domain composition. The qRT-PCR analysis revealed upregulation of PfCAF-1 members in trophozoite or schizont stage. Furthermore, a comparative expression analysis of the available transcriptome and proteome data along with qRT-PCR analysis revealed mixed expression patterns (coordination as well as non-coordination between different studies). Protein–protein interaction network analyses of PfCAF-1 family were carried out highlighting important complexes based on interologs. The PfRbAp48 was found to be highly connected with a total of 108 PPIs followed by PfRbAp46. The results unravel insights into the PfCAF-1 family and identify unique features, thus opening new perspectives for further targeted developments to understand and combat malaria menace.

The global population is continuously increasing, and it is expected to be about 9 billion by 2050. However, the agriculturally important land area is decreasing due to urbanization and other developmental activities. Further, the crop loss due to several constraints such as salinity, drought, chilling stress, and high metal toxicity is significantly extended by the changing climatic conditions. The abiotic stresses pose additional burdens of oxidative stress in plants through excessive production of reactive oxygen species (ROS), which cause considerable damage to the cell biomolecules (nucleic acid and proteins). Therefore, understanding ROS production under stress and its scavenging machinery is very important to engineer plants to withstand the stress burden without much yield penalty.

The “civil–military gap” is a significant factor that can hinder the success of complex comprehensive approach missions. Perhaps nowhere is this gap more apparent than in the relationship between m...

The present research reports a detailed in silico analysis of chromatin assembly factor-1 (CAF-1) family in human malaria parasite Plasmodium falciparum. Our analysis revealed five chromatin assembly factor-1 genes in P. falciparum (PfCAF-1) and the PfCAF-1 family was divided into two classes where, Class A belongs to the CAF-1 complex and others are kept in Class B. For comparative studies, orthologs of PfCAF-1 family were identified across 53 eukaryotic species and evolutionary relationships were drawn for different CAF-1 subfamilies. The phylogenetic analysis revealed grouping of evolutionary-related species together, although, divergence was observed in branching pattern. A detailed analysis of domain composition highlighted species-specific features viz. species-specific KDDS repeats of 84 amino acids were identified in PfCAF-1A whereas, members of CAF-1C/RbAp48 and RbAp46 subfamily exhibited least variation in size and domain composition. The qRT-PCR analysis revealed upregulation of PfCAF-1 members in trophozoite or schizont stage. Furthermore, a comparative expression analysis of the available transcriptome and proteome data along with qRT-PCR analysis revealed mixed expression patterns (coordination as well as non-coordination between different studies). Protein–protein interaction network analyses of PfCAF-1 family were carried out highlighting important complexes based on interologs. The PfRbAp48 was found to be highly connected with a total of 108 PPIs followed by PfRbAp46. The results unravel insights into the PfCAF-1 family and identify unique features, thus opening new perspectives for further targeted developments to understand and combat malaria menace. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13205-020-2096-7) contains supplementary material, which is available to authorized users.

Background Standard imaging modalities are inaccurate in staging malignant pleural mesothelioma (MPM). Single-institution studies suggest that volumetric computed tomography (CT) is more accurate but labor intensive. We established a multicenter network to test interobserver variability, accuracy (relative to pathologic stage), and the prognostic significance of semiautomated volumetric CT. Methods Six institutions electronically submitted to an established multicenter database clinical and pathologic data for patients with MPM who had operations. Institutional radiologists reviewed preoperative CT scans for quality and then submitted by electronic network (AG Mednet, www.agmednet.com) to the biostatistical center. Two reference radiologists blinded to clinical data performed semiautomated tumor volume calculations using Vitrea Enterprise 6.0 software (Vital Images, Minnetonka, MN) and then submitted readings to the biostatistical center. Study end points included feasibility of the network, interobserver variability for volumetric CT, correlation of tumor volume to pTN stages, and overall survival (OS). Results Of 164 patients, the CT scans for 129 were analyzable and read by reference radiologists. Most tumors were less than 500 cm 3 . A small bias was observed between readers because one provided consistently larger measurements than the other (mean difference, 47.9; p = .0027), but for 80%, the absolute difference was 200 cm 3 or less. Spearman correlation between readers was 0.822. Volume correlated with pTN stages and OS, best defined by three groups with average volumes of 91.2, 245.3, and 511.3 cm 3 associated with median OS of 37, 18, and 8 months, respectively. Conclusions For the first time, a multicenter network was established and initial correlations of tumor volume with pTN stages and OS are shown. A larger multicenter international study is planned to confirm the results and refine correlations.