Widespread occurrence of lysine methylation in Plasmodium falciparum proteins at asexual blood stages

Post-transcriptional and post-translational modifications play a major role in Plasmodium life cycle regulation. Lysine methylation of histone proteins is well documented in several organisms, however in recent years lysine methylation of proteins outside histone code is emerging out as an important post-translational modification (PTM). In the present study we have performed global analysis of lysine methylation of proteins in asexual blood stages of Plasmodium falciparum development. We immunoprecipitated stage specific Plasmodium lysates using anti-methyl lysine specific antibodies that immunostained the asexual blood stage parasites. Using liquid chromatography and tandem mass spectrometry analysis, 570 lysine methylated proteins at three different blood stages were identified. Analysis of the peptide sequences identified 605 methylated sites within 422 proteins. Functional classification of the methylated proteins revealed that the proteins are mainly involved in nucleotide metabolic processes, chromatin organization, transport, homeostatic processes and protein folding. The motif analysis of the methylated lysine peptides reveals novel motifs. Many of the identified lysine methylated proteins are also interacting partners/substrates of PfSET domain proteins as revealed by STRING database analysis. Our findings suggest that the protein methylation at lysine residues is widespread in Plasmodium and plays an important regulatory role in diverse set of the parasite pathways

Deep learning segmentation of triple-negative breast cancer (TNBC) patient derived tumor xenograft (PDX) and sensitivity of radiomic pipeline to tumor probability boundary

Preclinical magnetic resonance imaging (MRI) is a critical component in a co-clinical research pipeline. Importantly, segmentation of tumors in MRI is a necessary step in tumor phenotyping and assessment of response to therapy. However, manual segmentation is time-intensive and suffers from inter- and intra- observer variability and lack of reproducibility. This study aimed to develop an automated pipeline for accurate localization and delineation of TNBC PDX tumors from preclinical T1w and T2w MR images using a deep learning (DL) algorithm and to assess the sensitivity of radiomic features to tumor boundaries. We tested five network architectures including U-Net, dense U-Net, Res-Net, recurrent residual UNet (R2UNet), and dense R2U-Net (D-R2UNet), which were compared against manual delineation by experts. To mitigate bias among multiple experts, the simultaneous truth and performance level estimation (STAPLE) algorithm was applied to create consensus maps. Performance metrics (F1-Score, recall, precision, and AUC) were used to assess the performance of the networks. Multi-contrast D-R2UNet performed best with F1-score = 0.948; however, all networks scored within 1-3% of each other. Radiomic features extracted from D-R2UNet were highly corelated to STAPLE-derived features with 67.13% of T1w and 53.15% of T2w exhibiting correlation ρ ≥ 0.9

The Genome of the Zoonotic Malaria Parasite Plasmodium simium Reveals Adaptions to Host-switching

Oral Session

Consolidating Public Services in Anne Arundel County and the City of Annapolis: Impacts and Expenses

Combined final report for ECON454: Public Finance and Public Policy (Fall 2016). University of Maryland, College Park.This report is a collection of papers completed by students in the ECON454, Public Finance and Public Policy, who applied their students to a real world question as part of the PALS program. The class’s goal is understand the field of public finance and the relationship between economic theory and real world government policies. The goal of the PALS program is to use instructor expertise and student energy to advance sustainability in Maryland communities. In this effort, students explored the potential for consolidating public services in Anne Arundel County and the City of Annapolis, including the fiscal impacts and service level.Anne Arundel County & Annapoli

The genome of the zoonotic malaria parasite Plasmodium simium reveals adaptations to host switching

BACKGROUND: Plasmodium simium, a malaria parasite of non-human primates (NHP), was recently shown to cause zoonotic infections in humans in Brazil. We sequenced the P. simium genome to investigate its evolutionary history and to identify any genetic adaptions that may underlie the ability of this parasite to switch between host species. RESULTS: Phylogenetic analyses based on whole genome sequences of P. simium from humans and NHPs reveals that P. simium is monophyletic within the broader diversity of South American Plasmodium vivax, suggesting P. simium first infected NHPs as a result of a host switch of P. vivax from humans. The P. simium isolates show the closest relationship to Mexican P. vivax isolates. Analysis of erythrocyte invasion genes reveals differences between P. vivax and P. simium, including large deletions in the Duffy-binding protein 1 (DBP1) and reticulocyte-binding protein 2a genes of P. simium. Analysis of P. simium isolated from NHPs and humans revealed a deletion of 38 amino acids in DBP1 present in all human-derived isolates, whereas NHP isolates were multi-allelic. CONCLUSIONS: Analysis of the P. simium genome confirmed a close phylogenetic relationship between P. simium and P. vivax, and suggests a very recent American origin for P. simium. The presence of the DBP1 deletion in all human-derived isolates tested suggests that this deletion, in combination with other genetic changes in P. simium, may facilitate the invasion of human red blood cells and may explain, at least in part, the basis of the recent zoonotic infections

Supplementary_information_PhD_thesis_Abhinav_kaushik_ICGEB-Jamia_Hamdard.zip

a novel computational framework was designed, whereby important network topological properties of melanoma genes were first investigated. The analysis demonstrated that melanoma genes can modulate its activity by changing network connections independent of its expression profile. Most of such genes consistently rewired their connections in different melanoma networks as compared to the control network. Intriguingly, the genes which rewired its connections in multiple stages of melanoma were more conserved than the genes with differential expression

Melanoma Microarray Processed Datasets

<p>The Zip file contains processed data generated for Network-rewiring analysis for Melanoma microarray datasets from different stages of the cancer progression.</p

Pneumatic retinopexy outcomes as primary or secondary surgical option for treating rhegmatogenous retinal detachment

Purpose: To report the outcomes of pneumatic retinopexy (PR) performed as a primary surgical procedure for rhegmatogenous retinal detachment (RRD) or as a secondary procedure for recurrent RRD. Methods: We retrospectively analyzed case records of 54 patients (54 eyes) who underwent PR for RRD by injecting 0.3 ml of perfluoropropane (C3F8) in the vitreous cavity and cryopexy to break in the same sitting, followed by positioning. Results: A total 54 eyes of 54 patients aged between 17 and 84 years (mean - 51.3, median - 53 years) were included in the study. Except five eyes, all had breaks in the superior quadrants. The RRD ranged from 1 quadrant to 4 quadrants. Twenty-eight eyes (51.8%) were phakic and 26 (48.1%) were pseudophakic. The follow-up ranged from 6 to 144 months. In 25 eyes (46.2%), PR was the primary intervention and was successful in 15 (60%) eyes with a significant visual improvement (P = 0.023). Twenty-nine eyes (52.7%) with failed scleral buckle or failed pars plana vitrectomy underwent PR with a success rate of 65.5% and significant visual improvement (P = 0.0017). Progression of proliferative vitreoretinopathy changes (40%) was the most common cause of failure. The success rate was higher in phakic eyes, eyes with attached macula, superior breaks, superior RRD, and RRD limited to 3 quadrants or less. Conclusion: PR remains a minimally invasive procedure which can be used primarily or as a salvage procedure in failed surgery with moderately good success rate and minimal complications. One-step procedure reduces patient visits and ensures adequate treatment of the break