Prion meeting 2023: implications of a growing field

\ua9 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.The history of human prion diseases began with the original description, by Hans Gerhard Creutzfeldt and by Alfons Maria Jakob, of patients with a severe brain disease that included speech abnormalities, confusion, and myoclonus, in a disease that was then named Creutzfeldt Jakob disease (CJD). Later, in Papua New Guinea, a disease characterized by trembling was identified, and given the name “Kuru”. Neuropathological examination of the brains from CJD and Kuru patients, and of brains of sheep with scrapie disease revealed significant similarities and suggested a possible common mode of infection that, at the time, was thought to derive from an unknown virus that caused slow infections. John Stanley Griffith hypothesized that the agent causing these diseases was “probably a protein without nucleic acid” and, in 1982, Stanley Prusiner reported the identification of a proteinaceous infectious particle (coining the term prion) that was resistant to inactivation methods that were at the time standard for nucleic acids, and identified PrP as the major protein component of the infectious agent in scrapie and in Creutzfeldt-Jakob disease, classifying this also as a prion disease. Interestingly, the prion concept had been previously expanded to yeast proteins capable of replicating their conformation, seeding their own aggregation and transmitting phenotypic information. The prion concept has been more recently expanded to refer to misfolded proteins that are capable of converting a normal form of a protein into an abnormal form. The quest to understand and treat prion diseases has united a specific research community around the topic, and regular meetings (Prion Meetings) have taken place over the years to enable discussions, train junior researchers, and inspire research in the field

Private Drinking Water Wells as a Source of Exposure to Perfluorooctanoic Acid (PFOA) in Communities Surrounding a Fluoropolymer Production Facility

BACKGROUND: The C8 Health Project was established in 2005 to collect data on perfluorooctanoic acid (PFOA, or C8) and human health in Ohio and West Virginia communities contaminated by a fluoropolymer production facility. OBJECTIVE: We assessed PFOA exposure via contaminated drinking water in a subset of C8 Health Project participants who drank water from private wells. METHODS: Participants provided demographic information and residential, occupational, and medical histories. Laboratory analyses were conducted to determine serum-PFOA concentrations. PFOA data were collected from 2001 through 2005 from 62 private drinking water wells. We examined the relationship between drinking water and PFOA levels in serum using robust regression methods. As a comparison with regression models, we used a first-order, single-compartment pharmacokinetic model to estimate the serum:drinking-water concentration ratio at steady state. RESULTS: The median serum PFOA concentration in 108 study participants who used private wells was 75.7 μg/L, approximately 20 times greater than the levels in the U.S. general population but similar to those of local residents who drank public water. Each 1 μg/L increase in PFOA levels in drinking water was associated with an increase in serum concentrations of 141.5 μg/L (95% confidence interval, 134.9-148.1). The serum:drinking-water concentration ratio for the steady-state pharmacokinetic model was 114. CONCLUSIONS: PFOA-contaminated drinking water is a significant contributor to PFOA levels in serum in the study population. Regression methods and pharmacokinetic modeling produced similar estimates of the relationship

Pleosporales

One hundred and five generic types of Pleosporales are described and illustrated. A brief introduction and detailed history with short notes on morphology, molecular phylogeny as well as a general conclusion of each genus are provided. For those genera where the type or a representative specimen is unavailable, a brief note is given. Altogether 174 genera of Pleosporales are treated. Phaeotrichaceae as well as Kriegeriella, Zeuctomorpha and Muroia are excluded from Pleosporales. Based on the multigene phylogenetic analysis, the suborder Massarineae is emended to accommodate five families, viz. Lentitheciaceae, Massarinaceae, Montagnulaceae, Morosphaeriaceae and Trematosphaeriaceae

TRY plant trait database - enhanced coverage and open access

Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Basin-wide variations in Amazon forest nitrogen-cycling characteristics as inferred from plant and soil ¹⁵N:¹⁴N measurements

Background: Patterns in tropical forest nitrogen cycling are poorly understood. In particular, the extent to which leguminous trees in these forests fix nitrogen is unclear. Aims: We aimed to determine factors that explain variation in foliar δ¹⁵N (δ¹⁵NF) for Amazon forest trees, and to evaluate the extent to which putatively N₂-fixing Fabaceae acquire nitrogen from the atmosphere. Methods: Upper-canopy δ¹⁵NF values were determined for 1255 trees sampled across 65 Amazon forest plots. Along with plot inventory data, differences in δ¹⁵NF between nodule-forming Fabaceae and other trees were used to estimate the extent of N² fixation. Results: δ¹⁵NF ranged from −12.1‰ to +9.3‰. Most of this variation was attributable to site-specific conditions, with extractable soil phosphorus and dry-season precipitation having strong influences, suggesting a restricted availability of nitrogen on both young and old soils and/or at low precipitation. Fabaceae constituted fewer than 10% of the sampled trees, and only 36% were expressed fixers. We estimated an average Amazon forest symbiotic fixation rate of 3 kg N ha¯¹ year‾¹. Conclusion: Plant δ¹⁵N indicate that low levels of nitrogen availability are only likely to influence Amazon forest function on immature or old weathered soils and/or where dry-season precipitation is low. Most Fabaceae species that are capable of nodulating do not fix nitrogen in Amazonia

Heritable patterns of tooth decay in the permanent dentition: principal components and factor analyses

<p>Abstract</p> <p>Background</p> <p>Dental caries is the result of a complex interplay among environmental, behavioral, and genetic factors, with distinct patterns of decay likely due to specific etiologies. Therefore, global measures of decay, such as the DMFS index, may not be optimal for identifying risk factors that manifest as specific decay patterns, especially if the risk factors such as genetic susceptibility loci have small individual effects. We used two methods to extract patterns of decay from surface-level caries data in order to generate novel phenotypes with which to explore the genetic regulation of caries.</p> <p>Methods</p> <p>The 128 tooth surfaces of the permanent dentition were scored as carious or not by intra-oral examination for 1,068 participants aged 18 to 75 years from 664 biological families. Principal components analysis (PCA) and factor analysis (FA), two methods of identifying underlying patterns without <it>a priori </it>surface classifications, were applied to our data.</p> <p>Results</p> <p>The three strongest caries patterns identified by PCA recaptured variation represented by DMFS index (correlation, r = 0.97), pit and fissure surface caries (r = 0.95), and smooth surface caries (r = 0.89). However, together, these three patterns explained only 37% of the variability in the data, indicating that <it>a priori </it>caries measures are insufficient for fully quantifying caries variation. In comparison, the first pattern identified by FA was strongly correlated with pit and fissure surface caries (r = 0.81), but other identified patterns, including a second pattern representing caries of the maxillary incisors, were not representative of any previously defined caries indices. Some patterns identified by PCA and FA were heritable (h²= 30-65%, p = 0.043-0.006), whereas other patterns were not, indicating both genetic and non-genetic etiologies of individual decay patterns.</p> <p>Conclusions</p> <p>This study demonstrates the use of decay patterns as novel phenotypes to assist in understanding the multifactorial nature of dental caries.</p

Pathogen Proteins Eliciting Antibodies Do Not Share Epitopes with Host Proteins: A Bioinformatics Approach

The best way to prevent diseases caused by pathogens is by the use of vaccines. The advent of genomics enables genome-wide searches of new vaccine candidates, called reverse vaccinology. The most common strategy to apply reverse vaccinology is by designing subunit recombinant vaccines, which usually generate an humoral immune response due to B-cell epitopes in proteins. A major problem for this strategy is the identification of protective immunogenic proteins from the surfome of the pathogen. Epitope mimicry may lead to auto-immune phenomena related to several human diseases. A sequence-based computational analysis has been carried out applying the BLASTP algorithm. Therefore, two huge databases have been created, one with the most complete and current linear B-cell epitopes, and the other one with the surface-protein sequences of the main human respiratory bacterial pathogens. We found that none of the 7353 linear B-cell epitopes analysed shares any sequence identity region with human proteins capable of generating antibodies, and that only 1% of the 2175 exposed proteins analysed contain a stretch of shared sequence with the human proteome. These findings suggest the existence of a mechanism to avoid autoimmunity. We also propose a strategy for corroborating or warning about the viability of a protein linear B-cell epitope as a putative vaccine candidate in a reverse vaccinology study; so, epitopes without any sequence identity with human proteins should be very good vaccine candidates, and the other way around

The Inflammatory Kinase MAP4K4 Promotes Reactivation of Kaposi's Sarcoma Herpesvirus and Enhances the Invasiveness of Infected Endothelial Cells

Kaposi's sarcoma (KS) is a mesenchymal tumour, which is caused by Kaposi's sarcoma herpesvirus (KSHV) and develops under inflammatory conditions. KSHV-infected endothelial spindle cells, the neoplastic cells in KS, show increased invasiveness, attributed to the elevated expression of metalloproteinases (MMPs) and cyclooxygenase-2 (COX-2). The majority of these spindle cells harbour latent KSHV genomes, while a minority undergoes lytic reactivation with subsequent production of new virions and viral or cellular chemo- and cytokines, which may promote tumour invasion and dissemination. In order to better understand KSHV pathogenesis, we investigated cellular mechanisms underlying the lytic reactivation of KSHV. Using a combination of small molecule library screening and siRNA silencing we found a STE20 kinase family member, MAP4K4, to be involved in KSHV reactivation from latency and to contribute to the invasive phenotype of KSHV-infected endothelial cells by regulating COX-2, MMP-7, and MMP-13 expression. This kinase is also highly expressed in KS spindle cells in vivo. These findings suggest that MAP4K4, a known mediator of inflammation, is involved in KS aetiology by regulating KSHV lytic reactivation, expression of MMPs and COX-2, and, thereby modulating invasiveness of KSHV-infected endothelial cells. © 2013 Haas et al