In the adult, tissue repair after injury is generally compromised by fibrosis, which maintains tissue integrity with scar formation but does not restore normal architecture and function. The process ...of regeneration is necessary to replace the scar and rebuild normal functioning tissue. Here, we address this problem in the context of heart disease, and discuss the origins and characteristics of cardiac fibroblasts, as well as the crucial role that they play in cardiac development and disease. We discuss the dual nature of cardiac fibroblasts, which can lead to scarring, pathological remodelling and functional deficit, but can also promote heart function in some contexts. Finally, we review current and proposed approaches whereby regeneration could be fostered by interventions that limit scar formation.
Frailty has been recognized as an important medical syndrome in older adults. Growing literature supports the clinical application of frailty but US older adults' perceptions of frailty have not been ...explored. We aim to examine perceptions and informational needs about frailty among older adults.
This was a qualitative study involving focus groups of community-dwelling older adults with diverse age and frailty status. We explored participants' beliefs and knowledge about frailty and informational needs about frailty as a medical syndrome.
The participants' mean age was 76.3. Of the 29 participants, 21 (72%) were female, and 21 (72%) were white. We identified three major themes: 1) Older adults' perceptions of frailty differed from the definition used in medical literature; they often perceived a psychological component to being frailty and some were skeptical of the syndromic definition based on multiple symptoms. 2) Compared to participants who were non-frail or pre-frail, participants who were frail were more receptive to discussing their frailty status with clinicians; 3) Participants wanted know about how to treat or prevent frailty and the risks associated with being frail. Many participants felt that these information can be conveyed without necessarily using the specific term "frail", which they perceived to have a negative connotation.
Older adults, especially those who are frail, may be interested to discuss frailty as a medical syndrome. However, negative perceptions are associated with the term "frail" and may be a barrier to clinical application of frailty. Further research is needed to understand acceptable ways for communicating about frailty in clinical practice.
Evolution results from the interaction of stochastic and deterministic processes that create a web of historical contingency, shaping gene content and organismal function. To understand the scope of ...this interaction, we examine the relative contributions of stochasticity, determinism, and contingency in shaping gene inactivation in 34 lineages of endosymbiotic bacteria, Sodalis, found in parasitic lice, Columbicola, that are independently undergoing genome degeneration. Here we show that the process of genome degeneration in this system is largely deterministic: genes involved in amino acid biosynthesis are lost while those involved in providing B-vitamins to the host are retained. In contrast, many genes encoding redundant functions, including components of the respiratory chain and DNA repair pathways, are subject to stochastic loss, yielding historical contingencies that constrain subsequent losses. Thus, while selection results in functional convergence between symbiont lineages, stochastic mutations initiate distinct evolutionary trajectories, generating diverse gene inventories that lack the functional redundancy typically found in free-living relatives.
To determine the efficacy of a participation-focused therapy (ParticiPAte CP) on leisure-time physical activity goal performance and satisfaction and habitual physical activity (HPA) in children with ...CP.
Randomized waitlist-controlled trial.
Home and community.
Children classified at Gross Motor Function Classification System (GMFCS) levels I-III were recruited (n=37; 18 males; mean age ± SD, 10.0±1.4y) from a population-based register.
Participants were randomized to ParticiPAte CP (an 8-wk goal-directed, individualized, participation-focused therapy delivered by a physical therapist) or waitlist usual care.
The primary outcome was Canadian Occupational Performance Measure. Accelerometers were worn for objective measurement of HPA (min/d moderate-to-vigorous physical activity MVPA, sedentary time). Barriers to participation, community participation, and quality-of-life outcomes were also collected. Data were analyzed by intention-to-treat using generalized estimating equations.
ParticiPAte CP led to significant improvements in goal performance (mean difference MD=3.58; 95% confidence interval 95% CI, 2.19-4.97; P<.001), satisfaction (MD=1.87; 95% CI, 0.37-3.36, P=.014), and barriers to participation (MD=26.39; 95% CI, 6.13-46.67; P=.011) compared with usual care at 8 weeks. There were no between-group differences on minutes per day of MVPA at 8 weeks (MD=1.17; 95% CI, -13.27 to 15.61; P=.874). There was a significant difference in response to intervention between participants who were versus were not meeting HPA guidelines at baseline (MD=15.85; 95% CI, 3.80-27.89; P<.0061). After ParticiPAte CP, low active participants had increased average MVPA by 5.98±12.16 minutes per day.
ParticiPAte CP was effective at increasing perceived performance of leisure-time physical activity goals in children with CP GMFCS I-III by reducing modifiable barriers to participation. This did not translate into change in HPA on average; however, low active children may have a clinically meaningful response.
The Southern Ocean plays a critical role in regulating global climate as a major sink for atmospheric carbon dioxide (CO2), and in global ocean biogeochemistry by supplying nutrients to the global ...thermocline, thereby influencing global primary production and carbon export. Biogeochemical processes within the Southern Ocean regulate regional primary production and biological carbon uptake, primarily through iron supply, and support ecosystem functioning over a range of spatial and temporal scales. Here we assimilate existing knowledge and present new data to examine the biogeochemical cycles of iron, carbon and major nutrients, their key drivers and their responses to, and roles in, contemporary climate and environmental change. Projected increases in iron supply, coupled with increases in light availability to phytoplankton through increased near-surface stratification and longer ice-free periods, are very likely to increase primary production and carbon export around Antarctica. Biological carbon uptake is likely to increase for the Southern Ocean as a whole, whilst there is greater uncertainty around projections of primary production in the Sub-Antarctic and basin-wide changes in phytoplankton species composition, as well as their biogeochemical consequences. Phytoplankton, zooplankton, higher trophic level organisms and microbial communities are strongly influenced by Southern Ocean biogeochemistry, in particular through nutrient supply and ocean acidification. In turn, these organisms exert important controls on biogeochemistry through carbon storage and export, nutrient recycling and redistribution, and benthic-pelagic coupling. The key processes described in this paper are summarised in the graphical abstract. Climate-mediated changes in Southern Ocean biogeochemistry over the coming decades are very likely to impact primary production, sea-air CO2 exchange and ecosystem functioning within and beyond this vast and critically important ocean region.
Climate change projections have identified the Yucatan Peninsula as being vulnerable to increasing drought. Understanding spatial and temporal precipitation variability and drought occurrence are ...therefore important. Drought monitoring in Mexico has been carried out only relatively recently and often without considering the long‐term variability in both droughts and precipitation. This research explores the spatio‐temporal variability of precipitation and occurrence of droughts at a much finer spatial resolution and over a longer temporal period than previous studies. Using statistical (cluster analysis and standardized precipitation index) and geostatistical (kriging) techniques, maps of precipitation and droughts are generated for the period 1980–2011. These show that whilst many previous studies have regarded the Yucatan Peninsula as a homogenous region with respect to precipitation, there are actually four distinctive clusters of precipitation amount, showing climatic variability across the Peninsula. The analyses also show that droughts in the Peninsula are regionalised. Twelve‐month Standardized Precipitation Indices (SPI), calculated for individual stations and for precipitation surfaces, reveal distinct patterns of spatial and temporal variability. SPI surfaces indicate the occurrence of major droughts in 1981, 1986–1987, 1994, 1996, 2003, 2004 and 2009, but these rarely affect the whole Yucatan Peninsula uniformly. Wetter years, such as 1983, 1984, 1988, 1992, 1995, 2002 and 2005 sometimes reflect the impact of individual extreme events, such as hurricane Isidore in 2002. Our results show that drought can be regionalised, thus enhancing the quality of information about droughts in the area and providing evidence and support for future drought mitigation and environmental protection. These methods could usefully be applied elsewhere.
It is important to better understand spatial and temporal precipitation variability and drought occurrence. This research explores spatio‐temporal variability of precipitation and drought occurrence using statistical and geostatistical techniques to generate precipitation and droughts maps. Results reveal distinct patterns of spatial and temporal variability and help identify regional droughts patterns. This new understanding of the regional variability of droughts within the Yucatan Peninsula enhances the quality of information for the area and provides evidence that could support future drought mitigation.
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ParticiPAte CP is a participation-focused therapy intervention that is effective to increase perceived performance of physical activity (PA) participation goals in children with cerebral palsy (CP). ...We aimed to characterise the contents of ParticiPAte CP using validated behaviour change frameworks.
Data came from physiotherapist treatment notes and were used to specify: (1) physiotherapist-perceived barriers to behaviour change (using the International Classification of Functioning, Disability and Health Framework ICF and Theoretical Domains Framework), intervention content (Behaviour Change Technique Taxonomy v1), intervention functions (Behaviour Change Wheel) and mechanisms of action (Capability, Opportunity, Motivation - Behaviour model).
Physiotherapist-perceived barriers to participation were identified in all ICF and Theoretical Domains Framework domains. ParticiPAte CP consisted of 32 behaviour change techniques, delivered via six intervention functions of the Behaviour Change Wheel, especially enablement. All six possible mechanisms of action were identified according to the Capability, Opportunity, Motivation - Behaviour model. These were targeted most frequently through Theoretical Domains Framework domains social influences, environmental context and resources, intentions, skills, knowledge, and beliefs about capabilities.
The content of a PA intervention for children with CP can be specified according to behaviour change frameworks. ParticiPAte CP was complex, with multiple targets, constituent behaviour change techniques and mechanisms of action. Trial Registration: Australian New Zealand Clinical Trials Registry ACTRN12615001064594.
Implications for rehabilitation
Providing social support to families through practical actions such as motivating conversation, providing information, linking families to community services and participating in activities with children to support their self-efficacy may be a defining feature of effective participation-focused therapies.
If children with cerebral palsy (CP) and their families nominate goals for increased frequency of attendance or improved involvement in physical activities (PAs), therapists must identify all important barriers to participation, including behavioural barriers that may be thought of less often (e.g. emotions, beliefs, optimism etc.).
Promoting PA participation in children with CP may require a complex or multi-faceted therapy intervention that supports not only physical capability, but also enhances the social and physical opportunity for participation to take place and promotes the psychological capability and motivation for PA of children and families.
Therapists or researchers may consider using the Behaviour Change Wheel to prospectively design their own health behaviour intervention for children with CP.
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Operational satellite remote sensing products are transforming rangeland management and science. Advancements in computation, data storage and processing have removed barriers that previously blocked ...or hindered the development and use of remote sensing products. When combined with local data and knowledge, remote sensing products can inform decision‐making at multiple scales.
We used temporal convolutional networks to produce a fractional cover product that spans western United States rangelands. We trained the model with 52,012 on‐the‐ground vegetation plots to simultaneously predict fractional cover for annual forbs and grasses, perennial forbs and grasses, shrubs, trees, litter and bare ground. To assist interpretation and to provide a measure of prediction confidence, we also produced spatiotemporal‐explicit, pixel‐level estimates of uncertainty. We evaluated the model with 5,780 on‐the‐ground vegetation plots removed from the training data.
Model evaluation averaged 6.3% mean absolute error and 9.6% root mean squared error. Evaluation with additional datasets that were not part of the training dataset, and that varied in geographic range, method of collection, scope and size, revealed similar metrics. Model performance increased across all functional groups compared to the previously produced fractional product.
The advancements achieved with the new rangeland fractional cover product expand the management toolbox with improved predictions of fractional cover and pixel‐level uncertainty. The new product is available on the Rangeland Analysis Platform (https://rangelands.app/), an interactive web application that tracks rangeland vegetation through time. This product is intended to be used alongside local on‐the‐ground data, expert knowledge, land use history, scientific literature and other sources of information when making interpretations. When being used to inform decision‐making, remotely sensed products should be evaluated and utilized according to the context of the decision and not be used in isolation.
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Motivation: The caspase family of cysteine proteases play essential roles in key biological processes such as programmed cell death, differentiation, proliferation, necrosis and inflammation. The ...complete repertoire of caspase substrates remains to be fully characterized. Accordingly, systematic computational screening studies of caspase substrate cleavage sites may provide insight into the substrate specificity of caspases and further facilitating the discovery of putative novel substrates. Results: In this article we develop an approach (termed Cascleave) to predict both classical (i.e. following a P1 Asp) and non-typical caspase cleavage sites. When using local sequence-derived profiles, Cascleave successfully predicted 82.2% of the known substrate cleavage sites, with a Matthews correlation coefficient (MCC) of 0.667. We found that prediction performance could be further improved by incorporating information such as predicted solvent accessibility and whether a cleavage sequence lies in a region that is most likely natively unstructured. Novel bi-profile Bayesian signatures were found to significantly improve the prediction performance and yielded the best performance with an overall accuracy of 87.6% and a MCC of 0.747, which is higher accuracy than published methods that essentially rely on amino acid sequence alone. It is anticipated that Cascleave will be a powerful tool for predicting novel substrate cleavage sites of caspases and shedding new insights on the unknown caspase-substrate interactivity relationship. Availability: http://sunflower.kuicr.kyoto-u.ac.jp/∼sjn/Cascleave/ Contact: jiangning.song@med.monash.edu.au; takutsu@kuicr.kyoto-u.ac.jp; james; whisstock@med.monash.edu.au Supplementary information: Supplementary data are available at Bioinformatics online.
Spatially adjacent habitats on coral reefs can represent highly distinct environments, often harbouring different coral communities. Yet, certain coral species thrive across divergent environments. ...It is unknown whether the forces of selection are sufficiently strong to overcome the counteracting effects of the typically high gene flow over short distances, and for local adaptation to occur. We screened the coral genome (using restriction site‐associated sequencing) and characterized both the dinoflagellate photosymbiont‐ and tissue‐associated prokaryote microbiomes (using metabarcoding) of a reef flat and slope population of the reef‐building coral, Pocillopora damicornis, at two locations on Heron Island in the southern Great Barrier Reef. Reef flat and slope populations were separated by <100 m horizontally and ~5 m vertically, and the two study locations were separated by ~1 km. For the coral host, genetic divergence between habitats was much greater than between locations, suggesting limited gene flow between the flat and slope populations. Consistent with environmental selection, outlier loci primarily belonged to the conserved, minimal cellular stress response, likely reflecting adaptation to the different temperature and irradiance regimes on the reef flat and slope. The prokaryote community differed across both habitat and, to a lesser extent, location, whereas the dinoflagellate photosymbionts differed by habitat but not location. The observed intraspecific diversity associated with divergent habitats supports that environmental adaptation involves multiple members of the coral holobiont. Adaptive alleles or microbial associations present in coral populations from the environmentally variable reef flat may provide a source of adaptive variation for assisted evolution approaches, through assisted gene flow, artificial cross‐breeding or probiotic inoculations, with the aim to increase climate resilience in the slope populations.
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