Miracle-dz/UniFAR-FTUs huggingface dataset:
HIV neutralising antibody delivered by gene therapy with a hybrid Vaccinia/retrovirus or BacMam/retrovirus expression systems

2.1. Production of an effective vaccine against human immunodeficiency virus (HIV) is elusive. This project used a novel replication-restricted, poxvirus split-vector system to insert HIV-neutralising monoclonal antibody sequences into a simian retroviral gene therapy agent pseudo-typed with vesicular stomatitis virus glycoprotein, all encoded within a poxvirus. Recombination between split-vector recombinants does not produce viable, fully replication-competent retroviruses. To circumvent this, a recombinant modified vaccinia Ankara (MVA) was constructed for functional retrovirus production. Production of these gene therapy retroviral particles delivered in vivo by a safe, stable poxvirus promises to produce long-lasting, high titres of neutralising anti-HIV monoclonal antibody. A hybrid dual-vector system using the large packaging capacity of MVA was used. The expression cassette of the gene therapy agent was split into two independent MVA vectors. The ultimate aim is to insert IgG1 b12 antibody genes into the human genome. The first rMVA (rMVA/IgG1b12/T7) carried the HIVneutralising monoclonal antibody (mAb) sequence as well as a T7 polymerase for delivery into the cytoplasm of mammalian cells. A second recombinant MVA (rMVA/gag/pol/VSV-G) encoded a simian retroviral particle pseudo-typed with vesicular stomatitis virus glycoprotein to facilitate the delivery of the mAb genes into the human genome inside the nucleus. The second rMVA expressed heterologous polypeptides capable of assembling into defective non -self-propagating viral particles mimicking the packaging structure of SIV. The new non-infectious artificial lentivirus that results from
First detection of infectious spleen and kidney necrosis virus (ISKNV) associated with massive mortalities in farmed tilapia in Africa

In late 2018, unusual patterns of very high mortality (>50% production) were reported in intensive tilapia cage culture systems across Lake Volta in Ghana. Affected fish showed darkening, erratic swimming and abdominal distension with associated ascites. Histopathological observations of tissues taken from moribund fish at different farms revealed the presence of lesions indicative of viral infection. These included haematopoietic cell nuclear and cytoplasmic pleomorphism with marginalisation of chromatin and fine granulation. Transmission electron microscopy showed tilapia cells contained conspicuous virions with typical Iridovirus morphology i.e. enveloped, with icosahedral and or polyhedral geometries and with a diameter c.160 nm. PCR confirmation and DNA sequencing identified the virions in the tissues of the diseased fish as Infectious Spleen and Kidney Necrosis Virus (ISKNV). Samples of fry and older animals were all strongly positive for the presence of the virus by qPCR. All samples tested negative for TiLV and Nodavirus by qPCR. All samples collected from farms in the year prior to the mortality event were negative for ISKNV. The results suggest that ISKNV was the cause of disease on the investigated farms and likely had a primary role in the mortality events. A common observation of coinfections with Streptococcus agalactiae and other tilapia bacterial pathogens further suggests that these may interact to cause severe pathology, particularly in larger fish. The present results demonstrate that there are a range of potential threats to the sustainability of tilapia aquaculture that need to be guarded against.
Genome-wide DNA methylation and RNA expression profiles identified RIPK3 as a differentially methylated gene in Chlamydia pneumoniae infection lung carcinoma patients in China

Aim: To explore the relationship between Chlamydia pneumonia (Cpn) infection and lung cancer using integrative methylome and transcriptome analyses. Methods: Twelve primary lung cancer patients who were positive for Cpn and twelve patients who were negative were selected for demographic, clinicopathological, and lifestyle matching. Genomic DNA and RNA were extracted and DNA methylation and mRNA levels were detected using the Infinium Human Methylation 450 Beadchip array and mRNA + lncRNA Human Gene Expression Microarray. We identified differentially expressed methylation and genes profiles. Results: Integrative analysis revealed an inverse correlation between differentially expressed genes and DNA methylation. Cpn-related lung cancer methylated genes (target genes) were introduced into the gene ontology and KEGG, PID, BioCarta, Reactome, BioCyc and PANTHER enrichment analyses using a q-value cutoff of 0.05 to identify potentially functional methylation of abnormal genes associated with Cpn infection. Gene sets enrichment analysis was evaluated according to MsigDB. Levels of differentially expressed methylated sites were quantitatively verified. The promoter methylation sites of 62 genes were inversely related to expression levels. According to the quantitative analysis of DNA methylation, the methylation level of the RIPK3 promoter region was significantly different between Cpn-positive cancerous and adjacent tissues, but not between Cpn-negative cancerous and adjacent tissues. Conclusion: Hypomethylation of the RIPK3 promoter region increases RIPK3 expression, leading to regulated programmed necrosis and activation of NF-κB transcription factors, which may contribute to the development and progression of Cpn-related lung cancer.
Verwandtschaftsbeziehungen innerhalb von Prüfgliedern in Herkunftsversuchen - Beispiel Buche (Fagus sylvatica L.)

Aus Herkunftsversuchen konnen wertvolle Informationen zu phanotypischen Merkmalsauspragungen und zur Anpassungsfahigkeit von Baumarten im Verbreitungsgebiet und unter verschiedenen Umweltbedingungen gewonnen werden. Das Saatgut fur Herkunftsversuche oder Nachkommenschaftsprufungen sollte dabei fur den jeweiligen Ausgangsbestand reprasentativ sein, um die verschiedenen phanotypischen Merkmale in ihrer typischen Auspragung und Variationsbreite zu erfassen. In dieser Studie wurden Stichproben aus sechs Nachkommenschaften aus einem Buchen-Herkunftsversuch (Fagus sylvatica L.) mit 14 hochvariablen nuklearen Mikrosatellitenmarkern genotypisiert. Die genetische Diversitat erreichte in den Herkunften aus Osterreich, Rumanien und Tschechien hohere Werte, mittlere Werte in den beiden Herkunften aus Deutschland und geringere Werte in der spanischen Herkunft. Zusatzliche Informationen wurden aus den Multilocus-Genotypen der Nachkommen durch die Rekonstruktion von Verwandtschaftsbeziehungen und der Elterngeneration mit einer effizienten Likelihood-Methode gewonnen. Die Software COLONY wurde eingesetzt, um die effektiven Populationsgrosen und die Anzahl der beteiligten Eltern zu ermittelten. Die Rangfolge der sechs Herkunftsnachkommenschaften bei den effektiven Populationsgrosen war hoch reproduzierbar, ebenso die gefundenen Halbgeschwisterfamilien. Die maximale Grose der Halbgeschwisterfamilien befand sich im Bereich zwischen 5 und 15 Individuen in Stichproben von 50 bis 55 je Nachkommenschaft. Aus engen Verwandtschaftsverhaltnissen innerhalb der Nachkommenschaft kann eine kleinere effektive Populationsgrose abgeleitet werden, die trotz groser genetischer Diversitat auftreten kann. Mogliche Ursachen fur die unterschiedliche Reprasentativitat der Prufglieder werden in einer geringen Anzahl Erntebaume oder unausgewogenen Saatgutmengen vermutet.
Development and Application of Methods for Real-time fMRI Neurofeedback

Magnetic Resonance in Medicine Distinguished Reviewer (2016) Guarantors of Brain Travel Grant (2015) University of Oxford Lockey Bequest Grant (2014) OHBM Trainee Abstract Award (2014) ISMRM Trainee Stipend Award (2014) University of Oxford Lockey Bequest Grant (2013) ISMRM Trainee Stipend Award (2013) ISMRM Trainee Stipend Award (2011) Medical Biophysics Excellence Award (2010) Jack and Rita Catherall Fund Travel Award (2010) ISMRM Trainee Stipend (2009) Jack and Rita Catherall Fund Travel Award (2009) UBC Undergraduate Scholars Program Award (2005) UBC Undergraduate Scholars Program Award (2004)
Phenotypic and Genotypic Features of Macrophage Tropism in HIV-1

Kathryn Twigg Arrildt: Phenotypic and Genotypic Features of Macrophage Tropism in HIV-1. (Under the direction of Ron Swanstrom.) HIV-1 preferentially attaches and enters specific cell types by recognizing cell-specific receptors. HIV-1 typically targets memory CD4+ T cells by restricting attachment to cells expressing high CD4 densities and by using the CCR5 coreceptor. HIV-1 can adapt to enter CD4+ nave T cells by evolving to use CXCR4 in addition to CCR5. Alternatively, HIV-1 can adapt infecting macrophages by enhancing the entry using low CD4 densities. Early classification confusion and the lack of a reproducible, high-throughput method to assess cellular tropism has hindered robust identification and characterization of macrophage tropism. We developed cellular tropism assays using a novel cell line to perform both high-throughput identification screens and detailed analyses of receptor and coreceptor interactions. Clarified definitions of cellular tropism enabled us to probe the mechanism and consequences of evolving macrophage tropism through genotypic and phenotypic characterizations of subject-matched T-tropic and M-tropic env genes. M-tropic Env proteins are mostly indistinguishable from T-tropic Env proteins, except for subtle differences in the CD4-binding site (CD4bs) revealed by differences in interactions with CD4, competitive inhibition by soluble CD4, anti-CD4bs antibody sensitivity, and the ability of CD4-binding proximal residues to affect CD4 usage. CD4 usage is highly correlated with entry of monocyte-derived macrophages over a continuous range, making CD4 usage a useful proxy for macrophage tropism. Other stages of binding and entry are not major factors in the evolution of macrophage tropism and M-tropic Env proteins are not generally sensitive to antibodies. Nor does the antibody environment appear as a major selective pressure on the evolution of macrophage tropism. The genetic determinants are complex; evolving macrophage tropism requires unique
Assessment of genotoxic effects of a fungicide product and its active substances on human peripheral blood mononuclear cells

The genotoxic potential of the plant protection product Signum? and its two active substances (pyraclostrobin and boscalid) was investigated by the comet assay (pH>13). Leukocytes isolated from whole blood were treated with different concentrations (0.1-25 ? g/ml) of the fungicide for 2 h and 20 h. The Trypan Blue exclusion test showed higher cell viability (>84%) under all three concentrations and in the two treatment periods. The obtained results revealed that both Signum? and pyraclostrobin induced statistically significant DNA damage. In contrast, boscalid did not cause statistically significant DNA damage after 2 h exposure although it caused DNA damage at higher concentrations after a longer time exposure (20 h). It is deducible that pyraclostrobin and Signum? might be genotoxic. However, within the studied concentration ranges, none of the fungicides was found to be cytotoxic in the two treatment periods.
Investigating the role of integrin beta 3 in dendritic arborization in the supragranular developing cerebral cortex

Integrin strong positive association between mutations in integrin beta 3 ( Itgb3 ) and autism spectrum disorder, little is known about neuronal Itgb3 function in vivo. Many forms of autism spectrum disorder are thought to arise from dysfunctional dendritic arborization and synaptic pruning. Global knockout of Itgb3 in mice leads to autistic-like behaviors. Itgb3 -/- mice also have reduced callosal volume, a key neuroanatomical correlate of autism. Here, we test the hypothesis that Itgb3 is required for normal dendritic arborization in layer II/III pyramidal neurons of mouse neocortex. This was achieved by causing Itgb3 loss of function through Cre-lox-mediated excision of Itgb3 in a subset of layer II/III cortical neurons. Layer II/III cortical neurons were targeted for excision via in utero electroporation of GFP/Cre DNA constructs to the ventricular zone of developing telencephalon of mice in which exon 1 of Itgb3 is flanked by loxP sites. Laminar positioning, regional targeting, and dendritic arborization of targeted neurons in juvenile mice (P23) were analyzed. Male and female mice were used for the study and analysis was blind to genotype. Results point to aberrant basal dendritic arborization of mutant neurons, when compared to C57BL6/J controls. Thus, integrin beta 3 appears to regulate basal dendritic arborization of layer II/III pyramidal neurons in the developing neocortex.
Fast Subsequence Matching in Time-series Database

This paper proposes a new algorithm of fast subsequence matching in time-series database. Dramatically differing from FRM algorithm, we develop an index structure using VA-file, which maps data points directly into the index structure. We also propose a new algorithm for Range Query on this index structure. We implement our method and carry out experiments in different ways on three kinds of time-series data. The result shows that our algorithm accelerated the search time significantly.
The Development of the Ten-Year English Textbook Series for Vietnamese Schools under the National Foreign Language 2020 Project: A Cross-Cultural Collaborative Experience

This paper attempts to give an account of the cross-cultural collaborative project between Vietnamese textbook writers and those of MacMillan Education and Pearson Education – two leading international second/foreign language textbook publishers – in producing the ten-year English textbook series for Vietnamese schools under the National Foreign Language 2020 Project. The paper is organized around three parts. Part one provides backgrounds to and bases for developing the textbook series. Part two describes in some detail the cross-cultural textbook development process the Vietnamese textbook writers and their collaborative colleagues of MacMillan Education and Pearson Education have been undertaking in developing the textbook series. Part three gives a resume of what has been discussed, points out the advantages of the cross-cultural collaboration in producing the textbook series, and argues for a close collaboration between local textbook writers and writers who speak English as their mother tongue in producing high quality English textbooks that are suited to the general educational system of Vietnam.
The combined approach matrix: a priority-setting tool for health research

A publicacao “The Combined Approach Matrix” (A matriz de abordagens combinadas) e um recurso desenvolvido pelo Global Forum for Health Research que permite a recolha, a organizacao e a analise de informacoes necessarias para o estabelecimento de prioridades de pesquisa com base em um processo cientifico envolvendo todos os interessados diretos em saude e em pesquisa para a saude. O recurso facilita as comparacoes entre os provaveis valores de custo-eficacia de diferentes tipos de intervencoes.
Tree survival and growth responses in the aftermath of a strong earthquake

The infrequent and unpredictable nature of earthquakes means that their landslide‐generated impacts on forests are rarely investigated. In montane forests, landslides are the main cause of tree death and injury during earthquakes. Landslides range from soil movements that uproot and bury trees over extensive areas to rock falls that strike individual trees. We examined unexplored relationships between tree survival and distance from an epicentre, soil‐available phosphorus (P) as an indicator of soil development and tree diameter. We expected decreased tree growth in damaged forests because of tree injury. We used a plot network, established in 1974 and resurveyed regularly ever since, to quantify survival and growth responses 6–30 km from the epicentre of a 1994 earthquake in New Zealand's Southern Alps. Our Bayesian analysis used 8,518 trees from 250 plots that representatively sampled a naturally monospecific Nothofagus forest. As the time‐scales over which responses could emerge were unknown, we compared relationships for a pre‐earthquake period with 0–5 years post‐earthquake, and with 5+ years post‐earthquake. Not all plots were affected by the earthquake. We found that 0–5 years post‐earthquake survival increased logarithmically with distance from the epicentre with lowered survival up to 20 km from the epicentre. Survival was low on plots with high soil‐available P. An inverted U‐shaped relationship between survival and diameter pre‐earthquake was not found 0–5 years post‐earthquake. This was because of surprisingly high survival by large trees. The earthquake most often suppressed 0–5 years post‐earthquake growth up to 15 km from the epicentre, but this was only apparent after accounting for more general growth differences among periods. The positive relationship between growth and soil‐available P pre‐earthquake and 5+ years post‐earthquake reflected enhanced growth on young soils. This contrasted with a negative effect of soil‐available P on growth 0–5 years post‐earthquake. Synthesis. Soil‐available P, tree diameter and distance from the epicentre independently determined how tree survival and growth responded to an earthquake. The impacts on survival and growth largely occurred 0–5 years post‐earthquake and suggests a level of resilience in mountain beech forests.
Improving ATAC-seq Data Analysis with AIAP, a Quality Control and Integrative Analysis Package

ATAC-seq is a technique widely used to investigate genome-wide chromatin accessibility. The recently published Omni-ATAC-seq protocol substantially improves the signal/noise ratio and reduces the input cell number. High-quality data are critical to ensure accurate analysis. Several tools have been developed for assessing sequencing quality and insertion size distribution for ATAC-seq data; however, key quality control (QC) metrics have not yet been established to accurately determine the quality of ATAC-seq data. Here, we optimized the analysis strategy for ATAC-seq and defined a series of QC metrics, including reads under peak ratio (RUPr), background (BG), promoter enrichment (ProEn), subsampling enrichment (SubEn), and other measurements. We incorporated these QC tests into our recently developed ATAC-seq Integrative Analysis Package (AIAP) to provide a complete ATAC-seq analysis system, including quality assurance, improved peak calling, and downstream differential analysis. We demonstrated a significant improvement of sensitivity (20%~60%) in both peak calling and differential analysis by processing paired-end ATAC-seq datasets using AIAP. AIAP is compiled into Docker/Singularity, and with one command line execution, it generates a comprehensive QC report. We used ENCODE ATAC-seq data to benchmark and generate QC recommendations, and developed qATACViewer for the user-friendly interaction with the QC report.
The quality of life of caregivers of children with atopic dermatitis in a South African setting

Background. Atopic dermatitis (AD) is known to adversely affect patients’ quality of life (QOL). However, less is known about the extent to which caregivers are affected, particularly in developing countries. Objectives. To investigate factors affecting QOL in caregivers of children with AD in the South African (SA) setting and to document the associated effect of disease severity. Methods. This was a prospective study of 142 AD patients and their caregivers attending Grey’s Hospital in KwaZulu-Natal, SA, between May and September 2016. Disease severity was assessed according to the Objective Scoring of Atopic Dermatitis (Objective SCORAD) index. The Dermatitis Family Impact (DFI) questionnaire was used to assess QOL. Results. The study population included 119 (84%) black, 20 (14%) Indian and 3 (2%) coloured patients. Among the group, 44% of cases ( n =62) were classified as mild, 53% ( n =76) as moderate and 3% ( n =4) as severe. The DFI score was significantly associated with the Objective SCORAD index ( p <0.0001). QOL factors significantly affected were emotional distress of the caregiver ( p <0.0001), tiredness of the caregiver ( p <0.0001) and family leisure activities ( p <0.0001). Involvement in treatment ( p =0.016), food preparation and feeding ( p =0.003), the family’s sleep ( p =0.001) and the caregiver’s relationships ( p =0.025) were moderately affected. Conclusion. The QOL of caregivers of children with AD in this setting was adversely affected and declined with increasing disease severity. An evaluation of the psychosocial health of caregivers and appropriate referral where necessary are important for holistic management of both the patient and the caregiver and to improve disease outcome.
Application of precise genome editing tools in the zebrafish model to elucidate protein function with regards to developmental phenotypes

Genetic engineering is a powerful tool for biologists and geneticists to study the natural world. In general, it allows for asking and answering precise gene or DNA level questions about biological systems. The drawback of genetic engineering is that many applications requires a deep knowledge of multiple disciplines from biology to chemistry, which can make it inaccessible. Here I give a brief history of the field and define four tenets of necessary actions to begin engineering DNA, and four classes of applications using genetic engineering. I present three papers that define an accessible method of genome editing using CRISPR/Cas called GeneWeld, and describe two series of tools pGTag and pPRISM that reduce the materials cost of beginning genetic engineering experiments. I describe use cases for each tool, and finally present an expansion of the methodology and tools to generate synthetic alleles and examine their function in living zebrafish. We expect that these tools and methods will increase the accessibility of genetic engineering using and enable new kinds of research questions.
Molecular insights from conformational ensembles using Machine Learning

Biomolecular simulations are intrinsically high dimensional and generate noisy datasets of ever increasing size. Extracting important features in the data is crucial for understanding the biophysical properties of molecular processes, but remains a big challenge. Machine learning (ML) provides powerful dimensionality reduction tools. However, such methods are often criticized to resemble black boxes with limited human-interpretable insight. We use methods from supervised and unsupervised ML to efficiently create interpretable maps of important features from molecular simulations. We benchmark the performance of several methods including neural networks, random forests and principal component analysis, using a toy model with properties reminiscent of macromolecular behavior. We then analyze three diverse biological processes: conformational changes within the soluble protein calmodulin, ligand binding to a G protein-coupled receptor and activation of an ion channel voltage-sensor domain, unravelling features critical for signal transduction, ligand binding and voltage sensing. This work demonstrates the usefulness of ML in understanding biomolecular states and demystifying complex simulations. STATEMENT OF SIGNIFICANCE Understanding how biomolecules function requires resolving the ensemble of structures they visit. Molecular dynamics simulations compute these ensembles and generate large amounts of data that can be noisy and need to be condensed for human interpretation. Machine learning methods are designed to process large amounts of data, but are often criticized for their black-box nature and have historically been modestly used in the analysis of biomolecular systems. We demonstrate how machine learning tools can provide an interpretable overview of important features in a simulation dataset. We develop a protocol to quickly perform data-driven analysis of molecular simulations. This protocol is applied to identify the molecular basis of ligand binding to a receptor and of voltage sensitivity of an ion channel.