Emerging infectious diseases threaten wildlife globally. While the effects of infectious diseases on hosts with severe infections and high mortality rates often receive considerable attention, ...effects on hosts that persist despite infection are less frequently studied. To understand how persisting host populations change in the face of disease, we quantified changes to the capture rates of Eptesicus fuscus (big brown bats), a persisting species susceptible to infection by the invasive fungal pathogen Pseudogymnoascus destructans (Pd; causative agent for white‐nose syndrome), across the eastern US using a 30‐year dataset. Capture rates of male and female E. fuscus increased from preinvasion to pathogen establishment years, with greater increases to the capture rates of females than males. Among females, capture rates of pregnant and post‐lactating females increased by pathogen establishment. We outline potential mechanisms for these broad demographic changes in E. fuscus capture rates (i.e., increases to foraging from energy deficits created by Pd infection, increases to relative abundance, or changes to reproductive cycles), and suggest future research for identifying mechanisms for increasing capture rates across the eastern US. These data highlight the importance of understanding how populations of persisting host species change following pathogen invasion across a broad spatial scale. Understanding changes to population composition following pathogen invasion can identify broad ecological patterns across space and time, and open new avenues for research to identify drivers of those patterns.
To understand how persisting host populations change in the face of disease, we quantified changes to the capture rates of Eptesicus fuscus (big brown bats), a species that is annualy exposed and infected by the invasive fungal pathogen Pseudogymnoascus destructans (Pd); causative agent for white‐nose syndrome), using a 30‐year dataset across the eastern US. Here, the overall capture rates of adult E. fuscus increased from preinvasion to Pd establishment years across the eastern US. In conclusion, our work highlights the need to better understand how host populations change across broad spatial scales with continued pathogen exposure.
The protozoan parasite, Trypanosoma congolense, is one of the most economically important pathogens of livestock in Africa and, through its impact on cattle health and productivity, has a significant ...effect on human health and well being. Despite the importance of this parasite our knowledge of some of the fundamental biological processes is limited. For example, it is unknown whether mating takes place. In this paper we have taken a population genetics based approach to address this question. The availability of genome sequence of the parasite allowed us to identify polymorphic microsatellite markers, which were used to genotype T. congolense isolates from livestock in a discrete geographical area of The Gambia. The data showed a high level of diversity with a large number of distinct genotypes, but a deficit in heterozygotes. Further analysis identified cryptic genetic subdivision into four sub-populations. In one of these, parasite genotypic diversity could only be explained by the occurrence of frequent mating in T. congolense. These data are completely inconsistent with previous suggestions that the parasite expands asexually in the absence of mating. The discovery of mating in this species of trypanosome has significant consequences for the spread of critical traits, such as drug resistance, as well as for fundamental aspects of the biology and epidemiology of this neglected but economically important pathogen.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Galactose Oxidase (GOase) has been used for the scalable and selective C-6′ oxidation of lactose, a waste material from the dairy industry. Generation of the 6′-oxo lactose was achieved with full ...conversion in batch mode at milligram scale, but further scale-up to gram quantities proved to be challenging because of requirements for high enzyme concentrations and limitation in oxygen cosubstrate availability. To overcome these issues, a continuous-flow system was developed for the bio-oxidation of lactose yielding multigram quantities of product. Using the variant GOase F2, terminal selective oxidations were also observed on a range of oligoglucosides such as maltose. The carbohydrate dialdehydes that were obtained by this highly selective oxidation were chemically further functionalized, establishing the biooxidation as a route to valorize cheap carbohydrates, including waste materials, for building blocks of polymers.
Genome of the African Trypanosome Trypanosoma brucei Berriman, Matthew; Ghedin, Elodie; Hertz-Fowler, Christiane ...
Science (American Association for the Advancement of Science),
07/2005, Letnik:
309, Številka:
5733
Journal Article
Recenzirano
African trypanosomes cause human sleeping sickness and livestock trypanosomiasis in sub-Saharan Africa. We present the sequence and analysis of the 11 megabase-sized chromosomes of Trypanosoma ...brucei. The 26-megabase genome contains 9068 predicted genes, including approximately900 pseudogenes and approximately1700 T. brucei-specific genes. Large subtelomeric arrays contain an archive of 806 variant surface glycoprotein (VSG) genes used by the parasite to evade the mammalian immune system. Most VSG genes are pseudogenes, which may be used to generate expressed mosaic genes by ectopic recombination. Comparisons of the cytoskeleton and endocytic trafficking systems with those of humans and other eukaryotic organisms reveal major differences. A comparison of metabolic pathways encoded by the genomes of T. brucei, T. cruzi, and Leishmania major reveals the least overall metabolic capability in T. brucei and the greatest in L. major. Horizontal transfer of genes of bacterial origin has contributed to some of the metabolic differences in these parasites, and a number of novel potential drug targets have been identified.
Functionally related homologues of known genes can be difficult to identify in divergent species. In this paper, we show how multi-character analysis can be used to elucidate the relationships among ...divergent members of gene superfamilies. We used probabilistic modelling in conjunction with protein structural predictions and gene-structure analyses on a whole-genome scale to find gene homologies that are missed by conventional similarity-search strategies and identified a variant gene superfamily in six species of malaria (Plasmodium interspersed repeats, pir). The superfamily includes rif in P.falciparum, vir in P.vivax, a novel family kir in P.knowlesi and the cir/bir/yir family in three rodent malarias. Our data indicate that this is the major multi-gene family in malaria parasites. Protein localization of products from pir members to the infected erythrocyte membrane in the rodent malaria parasite P.chabaudi, demonstrates phenotypic similarity to the products of pir in other malaria species. The results give critical insight into the evolutionary adaptation of malaria parasites to their host and provide important data for comparative immunology between malaria parasites obtained from laboratory models and their human counterparts.
Aims
Morphological studies of pancreas samples obtained from young people with recent‐onset type 1 diabetes have revealed distinct patterns of immune cell infiltration of the pancreatic islets ...suggestive of two age‐associated type 1 diabetes endotypes that differ by inflammatory responses and rates of disease progression. The objective of this study was to investigate whether these proposed disease endotypes are associated with pathological differences in immune cell activation and cytokine secretion by applying multiplexed gene expression analysis to pancreatic tissue from recent‐onset type 1 diabetes cases.
Methods
RNA was extracted from samples of fixed, paraffin‐embedded pancreas tissue from type 1 diabetes cases characterised by endotype and from controls without diabetes. Expression levels of 750 genes associated with autoimmune inflammation were determined by hybridisation to a panel of capture and reporter probes and these were counted as a measure of gene expression. Normalised counts were analysed for differences in expression between 29 type 1 diabetes cases and 7 controls without diabetes, and between the two type 1 diabetes endotypes.
Results
Ten inflammation‐associated genes, including INS, were significantly under‐expressed in both endotypes and 48 genes were more highly expressed. A different set of 13 genes associated with the development, activation and migration of lymphocytes was uniquely overexpressed in the pancreas of people developing diabetes at younger age.
Conclusions
The results provide evidence that histologically defined type 1 diabetes endotypes differ in their immunopathology and identify inflammatory pathways specifically involved in disease developing at a young age, essential for a better understanding of disease heterogeneity.
Mindfulness-based interventions (MBI) have been shown to reduce subjective symptoms of insomnia but the effects on objective measures remain unclear. The purpose of this study was to examine sleep ...EEG microarchitecture patterns from a randomized controlled trial of Mindfulness-Based Stress Reduction (MBSR) and Mindfulness-Based Therapy for Insomnia (MBTI).
Sleep EEG spectral analysis was conducted on 36 participants with chronic insomnia (>6 months) randomized to 8-week MBSR, MBTI, or self-monitoring control (SM). Overnight polysomnography with 6-channel EEG was conducted at baseline, post-treatment, and 6-month follow-up. Spectral power averaged from channels C3/C4 across NREM epochs (excluding N1) was examined for within-group changes and relationships with self-report measures.
Increases in absolute NREM beta (16–25 Hz) power were observed from baseline to post-treatment (p = .02, d = 0.53) and maintained at 6-month follow-up (p = .01, d = 0.57) in the combined MBI groups, and additionally in the gamma (25–40 Hz) range at follow-up for the MBTI group only. No significant changes in these frequency bands were observed for SM. Following mindfulness intervention, NREM beta was positively associated with Five-Facet Mindfulness (FFM) score (rho = 0.37, p = .091) and negatively associated with Insomnia Severity Index (rho = −0.43, p = .047).
These results in people with insomnia corroborate prior reports of increased high-frequency sleep EEG power associated with mindfulness training. This change in beta EEG pattern merits further evaluation as a potential marker of the effects of mindfulness meditation on sleep, especially given the paradoxical findings in the context of insomnia.
clinicaltrials.gov, NCT00768781.
•NREM EEG beta (16–25 Hz) power during sleep increased following mindfulness-based interventions.•Pre-treatment, this NREM EEG activity was not associated with mindfulness or insomnia.•Post-treatment, NREM EEG beta power was positively associated with mindfulness and negatively associated with insomnia.
Invasive pathogens threaten wildlife health and biodiversity. Physiological responses of species highly susceptible to pathogen infections following invasion are well described. However, the ...responses of less susceptible species (relative to highly susceptible species) are not well known. Latitudinal gradients, which can influence body condition via Bergmann's rule and/or reflect the time it takes for an introduced pathogen to spread geographically, add an additional layer for how mammalian species respond to pathogen exposure. Our goal was to understand how hosts less susceptible to pathogen infections respond to long‐term pathogen exposure across a broad latitudinal gradient. We examined changes in body mass throughout pathogen exposure time across the eastern United States (latitude ranging 30.5° N–44.8° N) in Eptesicus fuscus, a bat species classified as less susceptible to infection (relative to highly susceptible species) by the invasive fungal pathogen that causes white‐nose syndrome, Pseudogymnoascus destructans (Pd). Using 30 years of spring through fall adult capture records, we created linear mixed‐effects models for female and male bats to determine how mass or mass variation changed across the eastern United States from pre‐Pd invasion years through Pd invasion (0–1 years with Pd), epidemic (2–4 years with Pd), and established years (5+ years with Pd). By Pd establishment, all female and male bats decreased body mass with increasing latitude across a spatial threshold at 39.6° N. Differences in bat mass north and south of the spatial threshold progressively increased over Pd exposure time‐steps such that body mass was lower in northern latitudes compared to southern latitudes by Pd establishment. Results indicated that the progressive differences in E. fuscus body mass with latitude across the eastern United States are due to long‐term pathogen exposure; however, other environmental and ecological pressures may contribute to decreases in E. fuscus body mass with latitude and long‐term pathogen exposure. As pathogen introductions and emerging infectious diseases become more prevalent on the landscape, it is imperative that we understand how less susceptible species directly and indirectly respond to long‐term pathogen exposure in order to maintain population health in surviving species.
Infectious salmon anemia virus (ISAV; Isavirus salaris) causes an economically important disease of Atlantic salmon (Salmo salar L.). ISA outbreaks have resulted in significant losses of farmed ...salmon globally, often with a sudden onset. However, 2 phenotypically distinct variants of ISAV exist, each with divergent disease outcomes, associated regulations, and control measures. ISAV-HPRΔ, also known as ISAV-HPR deleted, is responsible for ISA outbreaks; ISAV-HPR0, is avirulent and is not known to cause fish mortality. Current detection methodology requires genetic sequencing of ISAV-positive samples to differentiate phenotypes, which may slow responses to disease management. To increase the speed of phenotypic determinations of ISAV, we developed a new, rapid multiplex RT-qPCR method capable of 1) detecting if a sample contains any form of ISAV, 2) discriminating whether positive samples contain HPRΔ or HPR0, and 3) validating RNA extractions with an internal control, all in a single reaction. Following assay development and optimization, we validated this new multiplex on 31 ISAV strains collected from North America and Europe (28 ISAV-HPRΔ, 3 ISAV-HPR0). Finally, we completed an inter-laboratory comparison of this multiplex qPCR with commercial ISAV testing and found that both methods provided equivalent results for ISAV detection.
Copy number variants and indels in 251 families with evidence of X-linked intellectual disability (XLID) were investigated by array comparative genomic hybridization on a high-density oligonucleotide ...X chromosome array platform. We identified pathogenic copy number variants in 10% of families, with mutations ranging from 2 kb to 11 Mb in size. The challenge of assessing causality was facilitated by prior knowledge of XLID-associated genes and the ability to test for cosegregation of variants with disease through extended pedigrees. Fine-scale analysis of rare variants in XLID families leads us to propose four additional genes,
PTCHD1,
WDR13,
FAAH2, and
GSPT2, as candidates for XLID causation and the identification of further deletions and duplications affecting X chromosome genes but without apparent disease consequences. Breakpoints of pathogenic variants were characterized to provide insight into the underlying mutational mechanisms and indicated a predominance of mitotic rather than meiotic events. By effectively bridging the gap between karyotype-level investigations and X chromosome exon resequencing, this study informs discussion of alternative mutational mechanisms, such as noncoding variants and non-X-linked disease, which might explain the shortfall of mutation yield in the well-characterized International Genetics of Learning Disability (IGOLD) cohort, where currently disease remains unexplained in two-thirds of families.