Elucidating transmission patterns of endemic Mycobacterium avium subsp. paratuberculosis using molecular epidemiology
Mitchell, Rebecca M. ; Beaver, Annabelle ; Knupfer, Elena ; Pradhan, Abani K. ; Fyock, Terry ; Whitlock, Robert H. ; Schukken, Ynte H. - \ 2019
Veterinary Sciences 6 (2019)1. - ISSN 2306-7381
MLSSR typing - Mutation rate - Mycobacterial co-infections - Mycobacterium avium subsp. paratuberculosis (MAP) - Vertical transmission - Within-host evolution
Mycobacterial diseases are persistent and characterized by lengthy latent periods. Thus, epidemiological models require careful delineation of transmission routes. Understanding transmission routes will improve the quality and success of control programs. We aimed to study the infection dynamics of Mycobacterium avium subsp. paratuberculosis (MAP), the causal agent of ruminant Johne's disease, and to distinguish within-host mutation from individual transmission events in a longitudinally MAP-defined dairy herd in upstate New York. To this end, semi-annual fecal samples were obtained from a single dairy herd over the course of seven years, in addition to tissue samples from a selection of culled animals. All samples were cultured for MAP, and multi-locus short-sequence repeat (MLSSR) typing was used to determine MAP SSR types. We concluded from these precise MAP infection data that, when the tissue burden remains low, the majority of MAP infections are not detectable by routine fecal culture but will be identified when tissue culture is performed after slaughter. Additionally, we determined that in this herd vertical infection played only a minor role in MAP transmission. By means of extensive and precise longitudinal data from a single dairy herd, we have come to new insights regarding MAP co-infections and within-host evolution.
Impact of the shedding level on transmission of persistent infections in Mycobacterium avium subspecies paratuberculosis (MAP)
Slater, Noa ; Mitchell, Rebecca Mans ; Whitlock, Robert H. ; Fyock, Terry ; Pradhan, Abani Kumar ; Knupfer, Elena ; Schukken, Ynte Hein ; Louzoun, Yoram - \ 2016
Veterinary Research 47 (2016)1. - ISSN 0928-4249
Super-shedders are infectious individuals that contribute a disproportionate amount of infectious pathogen load to the environment. A super-shedder host may produce up to 10 000 times more pathogens than other infectious hosts. Super-shedders have been reported for multiple human and animal diseases. If their contribution to infection dynamics was linear to the pathogen load, they would dominate infection dynamics. We here focus on quantifying the effect of super-shedders on the spread of infection in natural environments to test if such an effect actually occurs in Mycobacterium avium subspecies paratuberculosis (MAP). We study a case where the infection dynamics and the bacterial load shed by each host at every point in time are known. Using a maximum likelihood approach, we estimate the parameters of a model with multiple transmission routes, including direct contact, indirect contact and a background infection risk. We use longitudinal data from persistent infections (MAP), where infectious individuals have a wide distribution of infectious loads, ranging upward of three orders of magnitude. We show based on these parameters that the effect of super-shedders for MAP is limited and that the effect of the individual bacterial load is limited and the relationship between bacterial load and the infectiousness is highly concave. A 1000-fold increase in the bacterial contribution is equivalent to up to a 2-3 fold increase in infectiousness.
Differences in intermittent and continuous fecal shedding patterns between natural and experimental Mycobacterium avium subspecies paratuberculosis infections in cattle
Mitchell, R.M. ; Schukken, Ynte ; Koets, A.P. ; Weber, Maarten ; Bakker, D. ; Stabel, Judy ; Whitlock, R.H. ; Louzoun, Yoram - \ 2015
Veterinary Research 46 (2015). - ISSN 0928-4249 - 10 p.
The objective of this paper is to study shedding patterns of cows infected with Mycobacterium avium subsp. paratuberculosis (MAP). While multiple single farm studies of MAP dynamics were reported, there is not large scale meta-analysis of both natural and experimental infections. Large difference in shedding patterns between experimentally and naturally infected cows were observed. Experimental infections are thus probably driven by different pathological mechanisms. For further evaluations of shedding patterns only natural infections were used. Within such infections, the transition to high shedding was studied as a proxy to the development of a clinical disease. The majority of studied cows never developed high shedding levels. Those that do, typically never reduced their shedding level to low or no shedding. Cows that eventually became high shedders showed a pattern of continuous shedding. In contrast, cows with an intermittent shedding pattern had a low probability to ever become high shedders. In addition, cows that start shedding at a younger age (less than three years of age) have a lower hazard of becoming high shedders compared to cows starting to shed at an older age. These data suggest the presence of three categories of immune control. Cows that are intermittent shedders have the infection process under control (no progressive infection). Cows that start shedding persistently at a young age partially control the infection, but eventually will be high shedders (slow progressive infection), while cows that start shedding persistently at an older age cannot effectively control the infection and become high shedders rapidly.
Evolutionary impact assessment: accounting for evolutionary consequences of fishing in an ecosystem approach to fisheries management
Laugen, A.T. ; Engelhard, G.H. ; Whitlock, R. ; Mollet, F.M. ; Rijnsdorp, A.D. - \ 2014
Fish and Fisheries 15 (2014)1. - ISSN 1467-2960 - p. 65 - 96.
cod gadus-morhua - maturation reaction norms - effective population-size - life-history evolution - north-sea plaice - pike esox-lucius - herring clupea-harengus - eco-genetic model - atlantic cod - marine fish
Managing fisheries resources to maintain healthy ecosystems is one of the main goals of the ecosystem approach to fisheries (EAF). While a number of international treaties call for the implementation of EAF, there are still gaps in the underlying methodology. One aspect that has received substantial scientific attention recently is fisheries-induced evolution (FIE). Increasing evidence indicates that intensive fishing has the potential to exert strong directional selection on life-history traits, behaviour, physiology, and morphology of exploited fish. Of particular concern is that reversing evolutionary responses to fishing can be much more difficult than reversing demographic or phenotypically plastic responses. Furthermore, like climate change, multiple agents cause FIE, with effects accumulating over time. Consequently, FIE may alter the utility derived from fish stocks, which in turn can modify the monetary value living aquatic resources provide to society. Quantifying and predicting the evolutionary effects of fishing is therefore important for both ecological and economic reasons. An important reason this is not happening is the lack of an appropriate assessment framework. We therefore describe the evolutionary impact assessment (EvoIA) as a structured approach for assessing the evolutionary consequences of fishing and evaluating the predicted evolutionary outcomes of alternative management options. EvoIA can contribute to EAF by clarifying how evolution may alter stock properties and ecological relations, support the precautionary approach to fisheries management by addressing a previously overlooked source of uncertainty and risk, and thus contribute to sustainable fisheries.
Body-mass index and cause-specific mortality in 900 000 adults: collaborative analyses of 57 prospective studies.
Whitlock, G. ; Lewington, S. ; Sherliker, P. ; Clarke, R. ; Kromhout, D. - \ 2009
The Lancet 373 (2009)9669. - ISSN 0140-6736 - p. 1083 - 1096.
coronary-heart-disease - blood-pressure - abdominal adiposity - vascular mortality - randomized-trials - individual data - united-states - korean men - risk - obesity
Background - The main associations of body-mass index (BMI) with overall and cause-specific mortality can best be assessed by long-term prospective follow-up of large numbers of people. The Prospective Studies Collaboration aimed to investigate these associations by sharing data from many studies. Methods- -Collaborative analyses were undertaken of baseline BMI versus mortality in 57 prospective studies with 894 576 participants, mostly in western Europe and North America (61% [n=541 452] male, mean recruitment age 46 [SD 11] years, median recruitment year 1979 [IQR 1975–85], mean BMI 25 [SD 4] kg/m2). The analyses were adjusted for age, sex, smoking status, and study. To limit reverse causality, the first 5 years of follow-up were excluded, leaving 66 552 deaths of known cause during a mean of 8 (SD 6) further years of follow-up (mean age at death 67 [SD 10] years): 30 416 vascular; 2070 diabetic, renal or hepatic; 22 592 neoplastic; 3770 respiratory; 7704 other. Findings - In both sexes, mortality was lowest at about 22·5–25 kg/m2. Above this range, positive associations were recorded for several specific causes and inverse associations for none, the absolute excess risks for higher BMI and smoking were roughly additive, and each 5 kg/m2 higher BMI was on average associated with about 30% higher overall mortality (hazard ratio per 5 kg/m2 [HR] 1·29 [95% CI 1·27–1·32]): 40% for vascular mortality (HR 1·41 [1·37–1·45]); 60–120% for diabetic, renal, and hepatic mortality (HRs 2·16 [1·89–2·46], 1·59 [1·27–1·99], and 1·82 [1·59–2·09], respectively); 10% for neoplastic mortality (HR 1·10 [1·06–1·15]); and 20% for respiratory and for all other mortality (HRs 1·20 [1·07–1·34] and 1·20 [1·16–1·25], respectively). Below the range 22·5–25 kg/m2, BMI was associated inversely with overall mortality, mainly because of strong inverse associations with respiratory disease and lung cancer. These inverse associations were much stronger for smokers than for non-smokers, despite cigarette consumption per smoker varying little with BMI. Interpretation - Although other anthropometric measures (eg, waist circumference, waist-to-hip ratio) could well add extra information to BMI, and BMI to them, BMI is in itself a strong predictor of overall mortality both above and below the apparent optimum of about 22·5–25 kg/m2. The progressive excess mortality above this range is due mainly to vascular disease and is probably largely causal. At 30–35 kg/m2, median survival is reduced by 2–4 years; at 40–45 kg/m2, it is reduced by 8–10 years (which is comparable with the effects of smoking). The definite excess mortality below 22·5 kg/m2 is due mainly to smoking-related diseases, and is not fully explained
Experimental challenge models for Johne's disease: a review and proposed international guidelines
Hines, M.E. ; Stabel, J.R. ; Sweeney, R.W. ; Griffin, F. ; Talaat, A.M. ; Bakker, D. ; Benedictus, G. ; Davis, W.C. ; Lisle, G.W. de; Gardner, I.A. ; Juste, R.A. ; Kapur, V. ; Koets, A. ; McNair, J. ; Pruitt, G. ; Whitlock, R.H. - \ 2007
Veterinary Microbiology 122 (2007)39541. - ISSN 0378-1135 - p. 197 - 222.
avium subsp paratuberculosis - swiss white mice - deer cervus-elaphus - experimental para-tuberculosis - experimental-infection model - experimental oral infection - linked-immunosorbent-assay - american wild ruminants - small-intestinal mucosa - mycobacterium-avi
An international committee of Johne's disease (JD) researchers was convened to develop guidelines for JD challenge studies in multiple animal species. The intent was to develop and propose international standard guidelines for models based on animal species that would gain acceptance worldwide. Parameters essential for the development of long-term and short-term infection models were outlined and harmonized to provide a ¿best fit¿ JD challenge model for cattle, goats, sheep, cervids, and mice. These models will be useful to study host¿pathogen interactions, host immunity at the local and systemic level, and for evaluating vaccine candidates and therapeutics. The consensus guidelines herein list by animal species strains of Mycobacterium avium subsp. paratuberculosis used, challenge dose, dose frequency, age of challenge, route of challenge, preparation of inoculum, experimental animal selection, quality control, minimal experimental endpoints and other parameters.
Phylogenetic analyses of basal angiosperms based on nine plastid, mitochondrial, and nuclear genes
Qiu, Y.L. ; Dombrovska, O. ; Lee, J. ; Li, L. ; Whitlock, B.A. ; Bernasconi-Quadroni, F. ; Rest, J.S. ; Davis, C.C. ; Borsch, T. ; Hilu, K.W. ; Renner, S.S. ; Soltis, D.E. ; Soltis, P.E. ; Zanis, M.J. ; Cannone, J.J. ; Powell, M. ; Savolainen, V. ; Chatrou, L.W. ; Chase, M.W. - \ 2005
International Journal of Plant Sciences 166 (2005)5. - ISSN 1058-5893 - p. 815 - 842.
inferring complex phylogenies - ribosomal dna-sequences - 3 genomic compartments - group-ii intron - mads-box genes - land plants - flowering plants - chloroplast genome - rdna sequences - molecular-data
DNA sequences of nine genes (plastid: atpB, matK, and rbcL; mitochondrial: atp1, matR, mtSSU, and mtLSU; nuclear: 18S and 26S rDNAs) from 100 species of basal angiosperms and gymnosperms were analyzed using parsimony, Bayesian, and maximum likelihood methods. All of these analyses support the following consensus of relationships among basal angiosperms. First, Amborella, Nymphaeaceae, and Austrobaileyales are strongly supported as a basal grade in the angiosperm phylogeny, with either Amborella or Amborella and Nymphaeales as sister to all other angiosperms. An examination of nucleotide substitution patterns of all nine genes ruled out any possibility of analytical artifacts because of RNA editing and GC-content bias in placing these taxa at the base of the angiosperm phylogeny. Second, Magnoliales are sister to Laurales and Piperales are sister to Canellales. These four orders together constitute the magnoliid clade. Finally, the relationships among Ceratophyllum, Chloranthaceae, monocots, magnoliids, and eudicots are resolved in different ways in various analyses, mostly with low support. Our study indicates caution in total evidence approaches in that some of the genes employed (e.g., mtSSU, mtLSU, and nuclear 26S rDNA) added signal that conflicted with the other genes in resolving certain parts of the phylogenetic tree
Perspective: Evolution and detection of genetic robustness
Visser, J.A.G.M. de; Hermisson, J. ; Wagner, G.P. ; Ancel Meyers, L. ; Bagheri-Chaichian, H. ; Blanchard, J.L. ; Chao, L. ; Cheverud, J.M. ; Elena, S.F. ; Fontana, W. ; Gibson, G. ; Hansen, T.F. ; Krakauer, D. ; Lewontin, R.C. ; Ofria, C. ; Rice, S.H. ; Dassow, G. von; Wagner, A. ; Whitlock, M.C. - \ 2003
Evolution 57 (2003)9. - ISSN 0014-3820 - p. 1959 - 1972.
drosophila-melanogaster - developmental stability - deleterious mutations - fitness components - heat-shock - canalization - dominance - epistasis - selection - plasticity
Robustness is the invariance of phenotypes in the face of perturbation. The robustness of phenotypes appears at various levels of biological organization, including gene expression, protein folding, metabolic flux, physiological homeostasis, development, and even organismal fitness. The mechanisms underlying robustness are diverse, ranging from thermodynamic stability at the RNA and protein level to behavior at the organismal level. Phenotypes can be robust either against heritable perturbations (e.g., mutations) or nonheritable perturbations (e.g., the weather). Here we primarily focus on the first kind of robustness-genetic robustness-and survey three growing avenues of research: (1) measuring genetic robustness in nature and in the laboratory; (2) understanding the evolution of genetic robustness; and (3) exploring the implications of genetic robustness for future evolution.