- Genomics and Phylogenetic Studies
- Evolution and Paleontology Studies
- interferon and immune responses
- Cytokine Signaling Pathways and Interactions
- Chromosomal and Genetic Variations
- CRISPR and Genetic Engineering
- Algorithms and Data Compression
- Genetic diversity and population structure
- Synthesis and Biological Evaluation
- Diversity and Career in Medicine
- Innovations in Medical Education
- Immune Response and Inflammation
- Systemic Lupus Erythematosus Research
- Medical Education and Admissions
- DNA Repair Mechanisms
- HIV Research and Treatment
- Retinal Development and Disorders
- Adrenal and Paraganglionic Tumors
- Peripheral Neuropathies and Disorders
- Genetic Neurodegenerative Diseases
- Medical and Biological Ozone Research
- Synthesis of β-Lactam Compounds
- Drug Solubulity and Delivery Systems
- Fungal Plant Pathogen Control
- Head and Neck Surgical Oncology
Royal Prince Alfred Hospital
2023-2025
Boston Children's Hospital
2022-2023
University of California, Los Angeles
2020-2023
Douglass Hanly Moir Pathology
2021-2023
New South Wales Department of Health
2023
Laboratory of Molecular Genetics
2022
Albert Einstein College of Medicine
2013-2021
St Vincent's Hospital Sydney
2021
QB3
2020-2021
Georgia Southern University
2018
Nonparametric bootstrap has been a widely used tool in phylogenetic analysis to assess the clade support of trees. However, with rapidly growing amount data, this task remains computational bottleneck. Recently, approximation methods such as RAxML rapid (RBS) and Shimodaira–Hasegawa-like approximate likelihood ratio test have introduced speed up bootstrap. Here, we suggest an ultrafast approach (UFBoot) compute groups maximum (ML) based To achieve this, combine resampling estimated...
Abstract Splice-switching antisense oligonucleotides (ASOs) could be used to treat a subset of individuals with genetic diseases 1 , but the systematic identification such remains challenge. Here we performed whole-genome sequencing analyses characterize variation in 235 (from 209 families) ataxia-telangiectasia, severely debilitating and life-threatening recessive disorder 2,3 yielding complete molecular diagnosis almost all individuals. We developed predictive taxonomy assess amenability...
Retinal opsin photopigments initiate mammalian vision when stimulated by light. Most mammals possess a short wavelength-sensitive 1 (SWS1) pigment that is primarily sensitive to either ultraviolet or violet light, leading variation in colour perception across species. Despite knowledge of both ultraviolet- and violet-sensitive SWS1 classes for 25 years, the adaptive significance this has not been subjected hypothesis testing, resulting minimal understanding basis spectral tuning evolution....
Abstract Background Post-translational modifications of histone residue tails are an important component genome regulation. It is becoming increasingly clear that the combinatorial presence and absence various define discrete chromatin states which determine functional properties a locus. An emerging experimental goal to track changes in state maps across different conditions, such as treatments, cell-types or developmental time points. Results Here we present chromstaR, algorithm for...
Background: Chalcones, natural products produced by plants as a defense mechanisms against various pathogens, are molecules with structures that include two aromatic rings joined an α, β unsaturated carbonyl system. Previous research has demonstrated chalcones exhibit wide variety of biological activities, including anticancer, antifungal, and antibiotic properties. Objective: Our goal is to synthesize novel heterocyclic-containing have their activities evaluated. Methods Sixteen were...
Type I interferons (IFN) induce powerful antiviral and innate immune responses via the transcription factor, IFN-stimulated gene factor (ISGF3). However, in some pathological contexts, type IFNs are responsible for exacerbating inflammation. Here, we show that a high dose of IFN-β also activates an inflammatory expression program contrast to IFN-λ3, III IFN, which elicits only common program. We depends on second, potentiated phase ISGF3 activation. Iterating between mathematical modeling...
Abstract INI1/SMARCB1 binds to HIV-1 integrase (IN) through its Rpt1 domain and exhibits multifaceted role in replication. Determining the NMR structure of INI1-Rpt1 modeling interaction with IN-C-terminal (IN-CTD) reveal that INI1-Rpt1/IN-CTD interface residues overlap those required for IN/RNA interaction. Mutational analyses validate our model indicate same IN are involved both INI1 RNA binding. TAR compete each other binding similar IC 50 values. INI1-interaction-defective mutant viruses...
Aims To investigate trends in representation of women among authors and editorial boards surgical pathology journals over the last two decades. Secondary aims: to identify barriers potential solutions. Methods The names gender first, middle, board members were obtained from original articles seven various geopolitical regions 2002, 2011 2021. proportion compared time. Results 1097 publications 8012 individual extracted. In 2021, respectively, percentage first 28.3% (257 907), 31.9% (566...
As models of sequence evolution become more and complicated, many criteria for model selection have been proposed, tools are available to select the best an alignment under a particular criterion. However, in instances selected fails explain data adequately as reflected by large deviations between observed pattern frequencies corresponding expectation. We present MISFITS, approach evaluate goodness fit (http://www.cibiv.at/software/misfits). MISFITS introduces minimum number "extra...
Among the criteria to evaluate performance of a phylogenetic method, robustness model violation is particular practical importance as complete priori knowledge evolutionary processes typically unavailable. For studies in inference, utility add well-defined violations simulated data would be helpful. We therefore introduce ImOSM, tool imbed intermittent evolution into an alignment. Intermittent refers extra substitutions occurring randomly on branches tree, thus changing alignment site...
Abstract Background Retroviral integrase catalyzes integration of viral DNA into the host genome. Integrase interactor (INI)1/hSNF5 is a factor that binds to HIV-1 IN within context Gag-Pol and specifically incorporated virions during assembly. Previous studies have indicated INI1/hSNF5 required for late events in vivo vitro . To determine effects disrupting IN-INI1 interaction on assembly infectivity particles, we isolated mutants are defective binding tested their replication. Results A...
Abstract Background Recently one step mutation matrices were introduced to model the impact of substitutions on arbitrary branches a phylogenetic tree an alignment site. This concept works nicely for four-state nucleotide alphabet and provides efficient procedure conjectured compute minimal number needed transform site into another. The present paper delivers proof validity this algorithm. Moreover, we provide several mathematical insights generalization OSM matrix multi-state alphabets....
Interferon β (IFN- ) signaling activates the transcription factor complex ISGF3 to induce gene expression programs critical for antiviral defense and host immune responses. It has also been observed that IFN- a second complex, γ-activated (GAF), but significance of this coordinated activation is unclear. We report in murine lung epithelial cells (MLE12) high doses indeed activate both GAF, which bind distinct genomic locations defined by their respective DNA sequence motifs. In contrast, low...
Nonparametric bootstrap has been a widely used tool in phylogenetic analysis to assess the clade support of trees. However, with rapidly growing amount data, this task remains computational bottleneck. Recently, approximation methods such as RAxML rapid (RBS) and Shimodaira-Hasegawa-like approximate likelihood ratio test have introduced speed up bootstrap. Here, we suggest an ultrafast approach (UFBoot) compute groups maximum (ML) based To achieve this, combine resampling estimated...
A 37-year-old woman developed progressive symmetrical weakness with areflexia, consistent Guillain-Barré syndrome. After initially briefly responding to intravenous immunoglobulin, her progressed markedly. Further investigation identified a new diagnosis of systemic lupus erythematosus nephritis. Following additional plasma exchange and corticosteroids, the activity remitted she made complete neurological recovery.
In a recent paper, Klaere et al. modeled the impact of substitutions on arbitrary branches phylogenetic tree an alignment site by so-called One Step Mutation (OSM) matrix. By utilizing concept OSM matrix for four-state nucleotide alphabet, Nguyen presented efficient procedure to compute minimal number needed translate one into another.The present paper delivers proof this computation.Moreover, we provide several mathematical insights generalization multistate alphabets.The construction is...