As humans cause the redistribution of species ranges, hybridization between previously allopatric species is on the rise. Such hybridization can have complex effects on overall fitness of native ...species as new allelic combinations are tested. Widespread species introductions provide a unique opportunity to study selection on introgressed alleles in independent, replicated populations. We examined selection on alleles that repeatedly introgressed from introduced rainbow trout (Oncorhynchus mykiss) into native westslope cutthroat trout (Oncorhynchus clarkii lewisi) populations in western Canada. We found that the degree of introgression of individual single nucleotide polymorphisms from the invasive species into the native is correlated between independent watersheds. A number of rainbow trout alleles have repeatedly swept to high frequency in native populations, suggesting parallel adaptive advantages. Using simulations, we estimated large selection coefficients up to 0.05 favoring several rainbow trout alleles in the native background. Although previous studies have found reduced hybrid fitness and genome‐wide resistance to introgression in westslope cutthroat trout, our results suggest that some introduced genomic regions are strongly favored by selection. Our study demonstrates the utility of replicated introductions as case studies for understanding parallel adaptation and the interactions between selection and introgression across the genome. We suggest that understanding this variation, including consideration of beneficial alleles, can inform management strategies for hybridizing species.
Osteoarthritis (OA) is the most common form of arthritic disease, and a major cause of disability and impaired quality of life in the elderly. OA is a complex disease of the entire joint, affecting ...bone, cartilage and synovium that thereby presents multiple targets for treatment. This manuscript will summarise emerging observations from cell biology, preclinical and preliminary clinical trials that elucidate interactions between the bone and cartilage components in particular. Bone and cartilage health are tightly associated. Ample evidence has been found for bone changes during progression of OA including, but not limited to, increased turnover in the subchondral bone, undermineralisation of the trabecular structure, osteophyte formation, bone marrow lesions and sclerosis of the subchondral plate. Meanwhile, a range of investigations has shown positive effects on cartilage health when bone resorption is suppressed, or deterioration of the cartilage when resorption is increased. Known bone therapies, namely oestrogens, selective oestrogen receptor modifiers (SERMs), bisphosphonates, strontium ranelate, calcitonin and parathyroid hormone, might prove useful for treating two critical tissue components of the OA joint, the bone and the cartilage. An optimal treatment for OA likely targets at least these two tissue components. The patient subgroups for whom these therapies are most appropriate have yet to be fully defined but would likely include, at a minimum, those with high bone turnover.
Parkinson's disease (PD) affects both men and women with documented gender differences across functional domains, with findings varying among reports. Knowledge regarding gender differences in PD for ...different geographic locations is important for further understanding of the disease and for developing personalized gender-specific PD assessment tools and therapies.
This study aimed to examine gender differences in PD-related motor, motor-cognitive, cognitive, and psychosocial function in people with PD from the southern United States (US).
199 (127 men and 72 women; M age: 69.08±8.94) individuals with mild-moderate idiopathic PD (Hoehn &Yahr (H&Y) Median = 2, stages I-III) from a large metro area in the southeastern US were included in this retrospective, cross-sectional study. Motor, motor-cognitive, cognitive, and psychosocial data were obtained using standardized and validated clinical tests. Univariate analyses were performed, adjusting for age and housing type.
After adjustment for age, housing, PD duration and fall rate, men exhibited statistically significantly greater motor (Movement Disorders Society (MDS)-Unified Parkinson Disease Rating Scale (UPDRS)-II) and non-motor (MDS-UPDRS-I) impact of PD, and more severe motor signs (MDS-UPDRS-III). Men exhibited worse PD-specific health-related quality of life related to mobility, activities of daily living, emotional well-being, cognitive impairment, communication, and more depressive symptoms. Men performed worse on a subtraction working memory task. Women had slower fast gait speed.
In the southeastern United States, men may experience worse PD-related quality of life and more depression than women. Many non-motor and motor variables that are not PD specific show no differences between genders in this cohort. These findings can contribute to the development of gender-sensitive assessment and rehabilitation policies and protocols for people with PD.
Rheumatoid arthritis (RA) is a chronic inflammatory disease with fluctuating course of progression. Despite substantial improvement in treatments in recent years, treatment response is still not ...guaranteed. The aim of this study was to identify variation in Disease Activity Score 28 (DAS28) of RA patients in response to Tocilizumab, and to investigate both molecular and clinical factors influencing response. Clinical and biochemical data for 485 RA patients receiving Tocilizumab in combination with methotrexate were extracted from the LITHE phase III clinical study (NCT00106535), and post-hoc analysis conducted. Latent class mixed models were used to identify statistically distinct trajectories of DAS28 after the initiation of treatment. Biomarker measurements were then analysed cross-sectionally and temporally, to characterise patients by serological biomarkers and clinical factors. We identified three distinct trajectories of drug response: class 1 (n = 85, 17.5%), class 2 (n = 338, 69.7%) and class 3 (n = 62, 12.8%). All groups started with high DAS28 on average (DAS28 > 5.1). Class 1 showed the least reduction in DAS28, with significantly more patients seeking escape therapy (p < 0.001). Class 3 showed significantly higher rates of improvement in DAS28, with 58.1% achieving ACR response levels compared to 2.4% in class 1 (p < 0.0001). Biomarkers of inflammation, MMP-3, CRP, C1M, showed greater reduction in class 3 compared to the other classes. Identification of more homogenous patient sub-populations of drug response may allow for more targeted therapeutic treatment regimens and a better understanding of disease aetiology.
Population genomic surveys suggest that climate-associated genetic variation occurs widely across species, but whether it is sufficient to allow population persistence via evolutionary adaptation has ...seldom been quantified. To ask whether rapid adaptation in reef-building corals can keep pace with future ocean warming, we measured genetic variation at predicted warm-adapted loci and simulated future evolution and persistence in a high-latitude population of corals from Rarotonga, Cook Islands. Alleles associated with thermal tolerance were present but at low frequencies in this cooler, southerly locality. Simulations based on predicted ocean warming in Rarotonga showed rapid evolution of heat tolerance resulting in population persistence under mild warming scenarios consistent with low CO
emission plans, RCP2.6 and RCP4.5. Under more severe scenarios, RCP6.0 and RCP8.5, adaptation was not rapid enough to prevent extinction. Population adaptation was faster for models based on smaller numbers of additive loci that determine thermal tolerance and for higher population growth rates. Finally, accelerated migration via transplantation of thermally tolerant individuals (1 to 5%/year) sped adaptation. These results show that cool-water corals can adapt to warmer oceans but only under mild scenarios resulting from international emissions controls. Incorporation of genomic data into models of species response to climate change offers a promising method for estimating future adaptive processes.
To investigate acute changes in biochemical markers of cartilage turnover in response to moderate intensity exercise with and without joint impact in humans with knee osteoarthritis.
We conducted a ...randomized, cross-over, exploratory clinical study. Twenty subjects with knee osteoarthritis (OA) were randomized, of which twenty completed 30 min of cycling and 15 completed 30 min of running on days 1 week apart. Fasting blood samples were taken before, immediately after and 1, 2, 3, and 24 h after activity was initiated. Midstream spot urine was sampled before and after activity. Serum samples were analyzed for concentrations of fragment of type II collagen degradation, C2M, fragment of type VI collagen degradation, C6M, cartilage oligomeric matrix protein, COMP, marker of type II collagen formation, PRO-C2, and urine for marker of crosslinked type II collagen degradation, CTX-II. To establish a reference, all subjects had similar samples taken during rest on a separate day. Data was analyzed in a restricted maximum likelihood based random effects linear mixed model.
C2M trended to increase after cycling compared running (13.49%, 95%CI: −0.36–27.34%) and resting (12.88%, 95%CI: 0.2–25.6%) and the type II collagen formation/degradation ratio switched towards degradation after cycling, but not running. C6M trended to decrease after cycling (−8.1%, 95%CI: −14.8 to −1.4%) and running (−6.8%, 95%CI: −14.16–0.55%).
In persons with knee OA moderate intensity exercise without joint impact may induce acute changes in circulating levels of biochemical markers reflecting type II and VI collagen degradation.
Concern over rapid environmental shifts associated with climate change has led to a search for molecular markers of environmental tolerance. Climate‐associated gene expression profiles exist for a ...number of systems, but have rarely been tied to fitness outcomes, especially in nonmodel organisms. We reciprocally transplanted corals between two backreef locations with more and less variable temperature regimes to disentangle effects of recent and native environment on survival and growth. Coral growth over 12 months was largely determined by local environment. Survival, however, was impacted by native environment; corals from the more variable environment had 22% higher survivorship. By contrast, corals native to the less variable environment had more variable survival. This might represent a “selective sieve” where poor survivors are filtered from the more stressful environment. We also find a potential fitness trade‐off—corals with high survival under stressful conditions grew less in the more benign environment. Transcriptome samples taken a year before transplantation were used to examine gene expression patterns that predicted transplant survival and growth. Two separate clusters of coexpressed genes were predictive of survival in the two locations. Genes from these clusters are candidate biomarkers for predicting persistence of corals under future climate change scenarios.
Correlated gene expression across a cluster of 110 genes predicts the trade‐off between survival and growth in reef‐building corals.
To investigate the association of the lipidomic profile with osteoarthritis (OA) severity, considering the outcomes radiographic knee and hand OA, pain and function.
We used baseline data from the ...Applied Public-Private Research enabling OsteoArthritis Clinical Headway (APPROACH) cohort, comprising persons with knee OA fulfilling the clinical American College of Rheumatology classification criteria. Radiographic knee and hand OA severity was quantified with Kellgren–Lawrence sum scores. Knee and hand pain and function were assessed with validated questionnaires. We quantified fasted plasma higher order lipids and oxylipins with liquid chromatography with tandem mass spectrometry (LC-MS/MS)-based platforms. Using penalised linear regression, we assessed the variance in OA severity explained by lipidomics, with adjustment for clinical covariates (age, sex, body mass index (BMI) and lipid lowering medication), measurement batch and clinical centre.
In 216 participants (mean age 66 years, mean BMI 27.3 kg/m2, 75% women) we quantified 603 higher order lipids (triacylglycerols, diacylglycerols, cholesteryl esters, ceramides, free fatty acids, sphingomyelins, phospholipids) and 28 oxylipins. Lipidomics explained 3% and 2% of the variance in radiographic knee and hand OA severity, respectively. Lipids were not associated with knee pain or function. Lipidomics accounted for 12% and 6% of variance in hand pain and function, respectively. The investigated OA severity outcomes were associated with the lipidomic fraction of bound and free arachidonic acid, bound palmitoleic acid, oleic acid, linoleic acid and docosapentaenoic acid.
Within the APPROACH cohort lipidomics explained a minor portion of the variation in OA severity, which was most evident for the outcome hand pain. Our results suggest that eicosanoids may be involved in OA severity.
We consider the derivation from the least action principle of relativistic and weakly relativistic Vlasov–Einstein equations. We also use the Vlasov–Einstein equations to analyze the dynamics and the ...evolution of certain structures. This approach enables to describe broad class of systems and their evolution, including the accelerated expansion of the universe with the cosmological constant and the recently arisen tensions.
The concept of osteoarthritis (OA) heterogeneity is evolving and gaining renewed interest. According to this concept, distinct subtypes of OA need to be defined that will likely require recognition ...in research design and different approaches to clinical management. Although seemingly plausible, a wide range of views exist on how best to operationalize this concept. The current project aimed to provide consensus-based definitions and recommendations that together create a framework for conducting and reporting OA phenotype research.
A panel of 25 members with expertise in OA phenotype research was composed. First, panel members participated in an online Delphi exercise to provide a number of basic definitions and statements relating to OA phenotypes and OA phenotype research. Second, panel members provided input on a set of recommendations for reporting on OA phenotype studies.
Four Delphi rounds were required to achieve sufficient agreement on 11 definitions and statements. OA phenotypes were defined as subtypes of OA that share distinct underlying pathobiological and pain mechanisms and their structural and functional consequences. Reporting recommendations pertaining to the study characteristics, study population, data collection, statistical analysis, and appraisal of OA phenotype studies were provided.
This study provides a number of consensus-based definitions and recommendations relating to OA phenotypes. The resulting framework is intended to facilitate research on OA phenotypes and increase combined efforts to develop effective OA phenotype classification. Success in this endeavor will hopefully translate into more effective, differentiated OA management that will benefit a multitude of OA patients.
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