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Hartvig Davis posted an update 1 week, 3 days ago
Discriminating between monozygotic twins (MZ) remains a challenge in the field of forensics globally. It is very difficult to find sequence variants within MZ twins, despite using ultra-deep next generation sequencing (NGS) for nuclear DNA. However, mitochondrial DNA might be a potential marker owing to its higher mutation rate and easier sequencing via NGS. Here, we aimed to introduce a long-read single molecule real-time sequencing (SMRT) strategy, with better continuity and fewer alignment errors, to obtain more accurate mitochondrial genome (mtGenome) sequence on the Sequel platform. Compared to Ion Torrent Personal Genome Machine (PGM), the long-read SMRT sequencing strategy generated highly accurate and mapped circular consensus sequence (CCS) reads and exhibited robust performance in terms of reliable repeatability, consistent coverage pattern, and balanced strands in mtGenome recovery. Moreover, the long-read SMRT strategy exhibited superior ability to not only identify accurate haplotypes but also discover a total of 785 low-level variants within 16 MZ twin pairs with threshold of 2% and 20 CCS reads with Q30 quality. Taken together, our findings suggested the long-read SMRT technology as an appreciable strategy for obtaining accurate mitotypes and providing a promising solution for distinguishing between MZ twin pairs in forensic genetics.In this case report, SS-OCTA identified the key diagnostic features of JRCH seen with multimodal imaging. Serial SS-OCTA imaging showed transient decreases in vascular congestion and exudation after intravitreal anti-VEGF injections. SS-OCTA may be the sole imaging modality needed for the diagnosis of JRCH, an important entity that is commonly misdiagnosed as disc edema or choroidal neovascularization. Transient responses to anti-VEGF therapy suggests that higher dose or sustained-release anti-VEGF therapy may be effective for retinal capillary hemangioblastomas.Mycobacterium tuberculosis (Mtb) is a successful pathogen in the history of mankind. A high rate of mortality and morbidity raises the need for vaccine development. Mechanism of pathogenesis, survival strategy and virulence determinant are needed to be explored well for this pathogen. The involvement of DNA binding proteins in the regulation of virulence genes, transcription, DNA replication, repair make them more significant. In present work, we have identified 1453 DNA binding proteins (DBPs) in the 4173 genes of Mtb through the DNABIND tool and they were subjected for further screening by incorporating different bioinformatics tools. The eighteen DBPs were selected for the B-cell epitope prediction by using ABCpred server. Moreover, the B-cell epitope bearing the antigenic and non- allergenic property were selected for T-cell epitope prediction using ProPredI, and ProPred server. Finally, DGIGSAVSV (Rv1088), IRALPSSRH (Rv3923c), LTISPIANS (Rv3235), VQPSGKGGL (Rv2871) VPRPGPRPG (Rv2731) and VGQKINPHG (Rv0707) were identified as T-cell epitopes. selleck chemicals llc The structural modelling of these epitopes and DBPs was performed to ensure the localization of these epitopes on the respective proteins. The interaction studies of these epitopes with human HLA confirmed their validation to be used as potential vaccine candidates. Collectively, these results revealed that the DBPs- Rv2731, Rv3235, Rv1088, Rv0707, Rv3923c and Rv2871 are the most appropriate vaccine candidates. In our knowledge, it is the first report of using the DBPs of Mtb for epitope prediction. Significantly, this study also provides evidence to be useful for designing a peptide-based vaccine against tuberculosis.Among the various strategies of curbing tuberculosis, suppression of Mycobacterium tuberculosis (Mtb) is a primary goal of the WHO to stop its infection, which is further strengthened by the presence of a massive reservoir of latently infected individuals. Several efforts have been made to explore potential candidates, including drug-repurposing, phytomolecules evaluation, and de novo designs. Compared to other strategies, investigation of phytomolecules with known experimental evidence represents a highly cost-effective and less time-consuming approach. Interestingly, some of the phytomolecules, previously known to show anti-tuberculosis effects, are known. While, these compounds have not yet been tested for their additional abilities to interact with resuscitation-promoting factor B (RpfB), an essential protein involved in revoking of Mtb dormancy. We, therefore, performed an initial computational study to evaluate the binding affinity of 38 phytomolecules to select the most effective ligands against RpfB. The studies were carried out using AutoDock and associated tools for static interaction analysis, while molecular dynamics (MD) simulations were performed to examine the stability of predicted protein-ligand complexes using the Desmond MD package. As an outcome of this study, we have reported four potential compounds, viz. diospyrin, 2′-Nortiliacorinine, 5,4′-dihydroxy-3,7,8,3′-tetramethoxyflavone, and tiliacorine which showed a putative binding affinity with significant intermolecular interactions, docking energy of -8.0 kcal/mol or higher, and vital complex stability (~2.4 Å RMSD) during 100 ns MD simulation. The findings of this study indicated that phytomolecules are capable to efficiently inhibit the RpfB, which is vital for reactivation of dormant Mtb. Characterization of the molecular targets for hits with intriguingly selective activity against dormant Mtb would be helpful to elucidate the essential mechanisms underlying the survival of dormant Mtb during latent infections.No data are available on rivaroxaban use in renal transplant recipients and on its surmised interaction with immunosuppressants. The aim was to investigate potential interactions between rivaroxaban and immunosuppressants in this setting. Renal transplant recipients with a stable renal function treated with rivaroxaban and tacrolimus with or without everolimus were investigated. All drugs and creatinine concentrations were determined daily for 2 weeks after the start of anticoagulation. Blood samples were drawn at 8.00 am and 3-4 h later for trough and peak concentrations, respectively. Bleeding and thrombotic events were recorded during a minimum follow-up of 6 months. In 8 renal transplant patients, rivaroxaban levels showed a predictable pharmacokinetic trend, both at Ctrough (30-61 μg/L) and at Cpeak (143-449 μg/L), with limited variability in the 25th-75th percentile range. Tacrolimus (Ctrough 3-13 μg/L; Cpeak 3-16 μg/L), everolimus (Ctrough 3-11 μg/L; Cpeak 5-17 μg/L) and creatinine concentrations were stable as well.