PI(3,4,5)P3 allosteric regulation of repressor activator protein 1 controls antigenic variation in trypanosomes

Wed, 11/29/2023 - 06:00
African trypanosomes evade host immune clearance by antigenic variation, causing persistent infections in humans and animals. These parasites express a homogeneous surface coat of variant surface glycoproteins (VSGs). They transcribe one out of hundreds of VSG genes at a time from telomeric expression sites (ESs) and periodically change the VSG expressed by transcriptional switching or recombination. The mechanisms underlying the control of VSG switching and its developmental silencing remain...

High-throughput screening of compounds targeting RNA editing in Trypanosoma brucei: Novel molecular scaffolds with broad trypanocidal effects

Thu, 11/23/2023 - 06:00
Mitochondrial uridine insertion/deletion RNA editing, catalyzed by a multiprotein complex (editosome), is essential for gene expression in trypanosomes and Leishmania parasites. As this process is absent in the human host, a drug targeting this mechanism promises high selectivity and reduced toxicity. Here, we successfully miniaturized our FRET-based full-round RNA editing assay, which replicates the complete RNA editing process, adapting it into a 1536-well format. Leveraging this assay, we...

Using ExpressAnalyst for Comprehensive Gene Expression Analysis in Model and Non-Model Organisms

Mon, 11/06/2023 - 06:00
ExpressAnalyst is a web-based platform that enables intuitive, end-to-end transcriptomics and proteomics data analysis. Users can start from FASTQ files, gene/protein abundance tables, or gene/protein lists. ExpressAnalyst will perform read quantification, gene expression table processing and normalization, differential expression analysis, or meta-analysis with complex study designs. The results are presented via various interactive visualizations such as volcano plots, heatmaps, networks, and...

Impact of Language Barriers on Outcomes and Experience of COVID-19 Patients Hospitalized in Quebec, Canada, During the First Wave of the Pandemic

Mon, 10/30/2023 - 06:00
Language barriers (LB) contribute to coronavirus disease 2019 (COVID-19) health inequities. People with LB were more likely to be SARS-CoV-2 positive despite lower testing and had higher rates of hospitalization. Data on hospital outcomes among immigrants with LB, however, are limited. We aimed to investigate the clinical outcomes of hospitalized COVID-19 cases by LB, immigration status, ethnicity, and access to COVID-19 health information and services prior to admission. Adults with...

Infections with long latency in international refugees, immigrants, and migrants seen at GeoSentinel sites, 2016-2018

Wed, 10/18/2023 - 06:00
CONCLUSIONS: Several infections of long latency (TB, hepatitis B, and strongyloidiasis) with potential for long-term sequelae were seen among RIM patients across all migration administrative categories and regions of origin. Obtaining detailed epidemiologic information from RIM patients is critical to optimize detection of diseases of individual and public health importance, particularly those with long latency periods.

Two-phase Bayesian latent class analysis to assess diagnostic test performance in the absence of a gold standard: COVID-19 serological assays as a proof of concept

Wed, 10/18/2023 - 06:00
CONCLUSION: The estimated low seroprevalence (which indicates a relatively limited spread of SARS-CoV-2 in Quebec) might change rapidly-and this tool, developed using blood donors, could enable a rapid update of the prevalence estimate in the absence of a gold standard. Further, the present analysis illustrates how a two-stage BLCM sampling design, along with blood donor samples, can be used to estimate the performance of new diagnostic tests and inform public health decisions regarding a new or...

Structure-Function Analysis of RBP7910: An Editosome Z-Binding Protein in Trypanosomatids

Sat, 10/14/2023 - 06:00
RNA editing, a unique post-transcriptional modification, is observed in trypanosomatid parasites as a crucial procedure for the maturation of mitochondrial mRNAs. The editosome protein complex, involving multiple protein components, plays a key role in this process. In Trypanosoma brucei, a putative Z-DNA binding protein known as RBP7910 is associated with the editosome. However, the specific Z-DNA/Z-RNA binding activity and the interacting interface of RBP7910 have yet to be determined. In this...

Preschool child growth attainment and velocity during an agriculture intervention in rural Panama may be diminished by soil-transmitted helminths

Fri, 10/13/2023 - 06:00
CONCLUSION: In a context of preschool child growth faltering, malnutrition and STH infections, improved food security, agricultural production and diet diversity associated with VERASAN were associated with improved growth. In contrast, STH infections were negatively associated with some, but not all, growth outcomes.

Immunity of Canadians and risk of epidemics workshop - Conference report

Thu, 10/12/2023 - 06:00
On November 18-19, 2019, the Immunity of Canadians and Risk of Epidemics (iCARE) Network convened a workshop in Toronto, Ontario, Canada. The objectives of the workshop were to raise the profile of sero-epidemiology in Canada, discuss best practice and methodological innovations, and strategize on the future direction of sero-epidemiology work in Canada. In this conference report, we describe the presentations and discussions from the workshop, and comment on the impact of the COVID-19 pandemic...

High-Efficiency Transformation and Expression of Genomic Libraries in Yeast

Fri, 09/22/2023 - 06:00
Saccharomyces cerevisiae is a powerful system for the expression of genome-wide or combinatorial libraries for diverse types of screening. However, expressing large libraries in yeast requires high-efficiency transformation and controlled expression. Transformation of yeast using electroporation methods is more efficient than chemical methods; however, protocols described for electroporation require large amounts of linearized plasmid DNA and often yield approximately 10⁶ cfu/µg of plasmid DNA....

Model Nematodes as a Practical Innovation to Promote High Throughput Screening of Natural Products for Anthelmintics Discovery in South Asia: Current Challenges, Proposed Practical & Conceptual Solutions

Wed, 09/20/2023 - 06:00
With the increasing prevalence of anthelmintic resistance in animals recorded globally, and the threat of resistance in human helminths, the need for novel anthelmintic drugs is greater than ever. Most research aimed at discovering novel anthelmintic leads relies on high throughput screening (HTS) of large libraries of synthetic small molecules in industrial and academic settings in developed countries, even though it is the tropical countries that are most plagued by helminth infections....

Canadian Blood Services traceback investigation of a suspected case of transfusion-transmitted malaria

Sat, 09/16/2023 - 06:00
CONCLUSION: This was a probable transfusion-transmitted malaria (TTM) case from an eligible donor who in retrospect was found to have unrecognized, asymptomatic, semi-immune malaria infection, and who was potentially infectious. Blood donor lack of recall of prior malaria infection does not negate the risk of TTM from those who have lived in malaria-endemic countries.

Vaccine Effectiveness of non-adjuvanted and adjuvanted trivalent inactivated influenza vaccines in the prevention of influenza-related hospitalization in older adults: A pooled analysis from the Serious Outcomes Surveillance (SOS) Network of the...

Mon, 09/11/2023 - 06:00
CONCLUSIONS: Adjusting for frailty, aTIV showed statistically significantly better protection than naTIV against influenza-associated hospitalizations in older adults. In future studies, it is important to consider frailty as a significant confounder of VE.

BCG administration promotes the long-term protection afforded by a single-dose intranasal adenovirus-based SARS-CoV-2 vaccine

Wed, 09/06/2023 - 06:00
Recent publications have explored intranasal (i.n.) adenovirus-based (Ad) vaccines as an effective strategy for SARS-CoV-2 in pre-clinical models. However, the effects of prior immunizations and infections have yet to be considered. Here, we investigate the immunomodulatory effects of Mycobacterium bovis BCG pre-immunization followed by vaccination with an S-protein-expressing i.n. Ad, termed Ad(Spike). While i.n. Ad(Spike) retains some protective effect after 6 months, a single administration...

Genome structure and population genomics of the canine heartworm Dirofilaria immitis

Thu, 08/31/2023 - 06:00
The heartworm, Dirofilaria immitis, is a filarial parasitic nematode responsible for significant morbidity and mortality in wild and domesticated canids. Resistance to macrocyclic lactone drug prevention represents a significant threat to parasite control and has prompted investigations to understand the genetic determinants of resistance. This study aimed to improve the genomic resources of D. immitis to enable a more precise understanding of how genetic variation is distributed within and...

A phenome-wide association study (PheWAS) to identify the health impacts of 4-cresol sulfate in the Nagahama Study

Fri, 08/25/2023 - 06:00
Gut-microbiota derived metabolites are important regulators of host biology and metabolism. To understand the impacts of the microbial metabolite 4-cresol sulfate (4-CS) on four chronic diseases [type 2 diabetes mellitus, metabolic syndrome (MetS), non-alcoholic fatty liver disease, and chronic kidney disease (CKD)], we conducted association analyses of plasma 4-CS quantified by liquid chromatography coupled to mass spectrometry (LC-MS) in 3641 participants of the Nagahama study. Our results...

Development and characterization of a plant-derived norovirus-like particle vaccine

Fri, 08/25/2023 - 06:00
CONCLUSIONS: The plant-made NoVLP vaccine was safe and immunogenic in mice and rabbits. Multi-modal vaccination, combining oral and intramuscular administration could be considered for future clinical development to maximize systemic and mucosal immune responses.

The Native Microbiome Member <em>Chryseobacterium</em> sp. CHNTR56 MYb120 Induces Trehalose Production via a Shift in Central Carbon Metabolism during Early Life in <em>C. elegans</em>

Fri, 08/25/2023 - 06:00
Aging is the system-wide loss of homeostasis, eventually leading to death. There is growing evidence that the microbiome not only evolves with its aging host, but also directly affects aging via the modulation of metabolites involved in important cellular functions. The widely used model organism C. elegans exhibits high selectivity towards its native microbiome members which confer a range of differential phenotypes and possess varying functional capacities. The ability of one such native...
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