The genetic landscape of Parkinson's disease (PD) is characterised by rare high penetrance pathogenic variants causing familial disease, genetic risk factor variants driving PD risk in a significant ...minority in PD cases and high frequency, low penetrance variants, which contribute a small increase of the risk of developing sporadic PD. This knowledge has the potential to have a major impact in the clinical care of people with PD. We summarise these genetic influences and discuss the implications for therapeutics and clinical trial design.
Abstract
The ascomycete fungus
Ophidiomyces ophiodiicola
(
Oo
) is the causative agent of ophidiomycosis (Snake Fungal Disease), which has been detected globally. However, surveillance efforts in the ...central U.S., specifically Texas, have been minimal. The threatened and rare Brazos water snake (
Nerodia harteri harteri
) is one of the most range restricted snakes in the U.S. and is sympatric with two wide-ranging congeners,
Nerodia
erythrogaster transversa
and
Nerodia
rhombifer
, in north central Texas; thus, providing an opportunity to test comparative host–pathogen associations in this system. To accomplish this, we surveyed a portion of the Brazos river drainage (~ 400 river km) over 29 months and tested 150
Nerodia
individuals for the presence of
Oo
via quantitative PCR and recorded any potential signs of
Oo
infection. We found
Oo
was distributed across the entire range of
N. h. harteri
,
Oo
prevalence was 46% overall, and there was a significant association between
Oo
occurrence and signs of infection in our sample. Models indicated adults had a higher probability of
Oo
infection than juveniles and subadults, and adult
N. h. harteri
had a higher probability of infection than adult
N. rhombifer
but not higher than adult
N. e. transversa
. High
Oo
prevalence estimates (94.4%) in adult
N. h. harteri
has implications for their conservation and management owing to their patchy distribution, comparatively low genetic diversity, and threats from anthropogenic habitat modification.
The last 2 decades represent a period of unparalleled advancement in the understanding of the pathogenesis of Parkinson disease (PD). The discovery of several forms of familial parkinsonism with ...mendelian inheritance has elucidated insights into the mechanisms underlying the degeneration of dopaminergic neurons of the substantia nigra that histologically characterize PD. α-Synuclein, the principal component of Lewy bodies, remains the presumed pathogen at the heart of the current model; however, concurrently, a diverse range of other mechanisms have been implicated. The creation of a coherent disease model will be crucial to the development of effective disease modifying therapies for sporadic PD.
•Energy is a finite resource and must be allocated among important physiological processes such as reproduction, the stress response, and immunity.•Snakes exhibit a wide variety of reproductive ...strategies and provide a unique study organism.•Timing of the acute stress response shifts throughout the breeding season.•Snakes appear to prioritize reproduction over immunity during energetically expensive processes such as vitellogenesis.
Energy is a finite resource required for all physiological processes and must be allocated efficiently among essential activities to ensure fitness and survival. During the active season, adult organisms are expected to prioritize investment in reproduction over other energetically expensive processes, such as responding to immunological challenges. Furthermore, when encountering a stressor, the balance between reproduction and immunity might be disrupted in order to fuel the stress response. Because of the distinct differences in life histories across species, watersnakes provide a unique group of study in which to examine these tradeoffs. Over a two-year period, we captured three watersnake species throughout Northeast Arkansas. Animals were subjected to restraint stress and blood samples were collected throughout the acute stress response. Blood samples were used to assess innate immunity and steroid hormone concentrations. We found the peak in corticosterone concentration is season-specific, potentially because energetic reserves fluctuate with reproductive activities. We also found body condition was positively related to acute stress and negatively related to immunity. Watersnakes evidently prioritize reproduction over immunity, especially during the energetically intensive process of vitellogenesis. Energetic tradeoffs between reproduction, immunity, and the stress response are complex, and this study contributes to our understanding of energetic shifts in free-living organisms in the context of stress.
The institutional affiliations of all authors must be disclosed in the by-line of the ms. All funding sources supporting the work and in the ms, and information on any conflicts of interest (personal ...or financial) must be noted by the author(s) in the Acknowledgments section of the ms. Duplicate or prior publication, plagiarism, and fraud.-When submitting an article, the corresponding author should disclose in the cover letter any related ms that have been submitted to, or are in press with, another journal. Important exceptions: * Reuse of control data in experimental studies might not be considered duplicate publication providing that the methodology is identical. * Doctoral dissertations and Master's theses that are made available in institutional repositories are not considered prior publication. * Republishing data to make a direct, illustrative comparison with new findings might be appropriate when the purpose of republication is to provide explicit comparisons with the new information.\n nov., gen. nov., fam. nov., unranked clade, or similar.
Wild animal diets are challenging to quantify, and the various methods for doing so have strengths and weaknesses. Combining multiple methods can allow ecologists to assess their level of confidence ...in particular results, increase sample size, and investigate diet over varying time scales. The biases of traditional gut content–based methods are mostly well understood. Newer methods may have important biases that can only be worked out through comparison to established ones. We collected data on the diet of wild Plains Hog-nosed Snakes (Heterodon nasicus) using multiple, fundamentally dissimilar methods, combined analytically using a Bayesian framework to describe an ontogenetic dietary shift. Gut contents were the most straightforward, but yielded a small sample size that fell below any reasonable threshold for making generalizations. Stable isotopes indicated an obvious ontogenetic dietary shift, but were labor-intensive, and conclusions are limited by multiple methodological caveats including similarity among prey groups, maternal carryover effects, and uncertainty in trophic enrichment factors. Fecal environmental DNA (eDNA) was intermediate in terms of effort, yielding results congruent with the other two methods, but the interpretation of which would likely have been confounded by contaminants had we not used all three methods in tandem. Several apparent artifacts are discussed. There are some reassuring similarities among methods. There are also several differences. The most complete picture uses data from all methods taken together. Future studies should attempt to compare the biases, expense, and potential drawbacks of these and other methods in greater detail.
Many hypotheses have been advanced to explain the K/Pg extinctions, yet none closely examines the likely interactions between dinosaurs and contemporary taxa within their communities. The diversity ...of predators of dinosaur nests and hatchlings increased toward the end of the Cretaceous. In addition to large snakes having been found fossilized in the act of foraging in dinosaur nests, mammals and birds had also evolved new forms potentially capable of exploiting this resource. The constraints on mammal size and niche diversity lessened prior to the K/Pg boundary. Using comparisons of predator/prey size ratios between extant species and known fossils, we demonstrate that mammalian and avian clades had members large enough to prey on dinosaur eggs and hatchlings. We argue that the reproductive strategy of obligatory nest defense was likely practiced by most non-avian dinosaur species. This strategy was highly susceptible to the increasing numbers of mammalian, avian, and reptilian predators, which rendered this strategy obsolete. Continued selection against large oviparous species in the Cenozoic has limited this life-history strategy to habitats that provide concealment - primarily grasslands, a habitat that did not exist until the Miocene. We urge the evaluation of multiple, perhaps synergistic, hypotheses when considering extinction events of this magnitude.
•We combined traditional methods and stable isotopes to study wild snake diets.•Heterodon nasicus shifts from eating lizards and their eggs to eating aquatic turtle eggs.•Following numerous best ...practices enhances the rigor of this result.•Simulation work with trophic enrichment factors suggests minimal effects.
Wild snake diets are difficult to study using traditional methods, but stable isotopes offer several advantages, including integrating dietary information over time, providing data from individuals that have not fed recently, and avoiding bias towards slowly-digesting prey items. We used stable isotope signatures of carbon and nitrogen from scale tissue, red blood cells, and blood plasma to assess the diet of wild plains hog-nosed snakes (Heterodon nasicus) in Illinois. We developed Bayesian mixing models which, taken together, predicted that H. nasicus shifted from a juvenile diet predominantly (31–63%) composed of six-lined racerunners (Aspidoscelis sexlineatus) and their eggs to an adult diet predominantly (44–56%) composed of eggs of the aquatic turtles Chrysemys picta and Chelydra serpentina, with a contribution from toads (Anaxyrus sp.; 6–27%) during their adolescent years. These results agreed with sparse data from gut contents. Combining traditional and isotopic techniques for studying the diets of wild snakes can increase the utility of both types of data.
IntroductionMany people with Parkinson’s (PwP) are not given the opportunity or do not have adequate access to participate in clinical research. To address this, we have codeveloped with users an ...online platform that connects PwP to clinical studies in their local area. It enables site staff to communicate with potential participants and aims to increase the participation of the Parkinson’s community in research. This protocol outlines the mixed methods study protocol for the usability testing of the platform.Methods and analysisWe will seek user input to finalise the platform’s design, which will then be deployed in a limited launch for beta testing. The beta version will be used as a recruitment tool for up to three studies with multiple UK sites. Usability data will be collected from the three intended user groups: PwP, care partners acting on their behalf and site study coordinators. Usability questionnaires and website analytics will be used to capture user experience quantitatively, and a purposive sample of users will be invited to provide further feedback via semistructured interviews. Quantitative data will be analysed using descriptive statistics, and a thematic analysis undertaken for interview data. Data from this study will inform future platform iterations.Ethics and disseminationEthical approval was obtained from the University of Plymouth (3291; 3 May 2022). We will share our findings via a ‘Latest News’ section within the platform, presentations, conference meetings and national PwP networks.
PDF
