To determine longitudinal change in sedentary behavior in children with cerebral palsy (CP) from 1.5 to 12 years.
Ninety-one children, Gross Motor Function Classification System (GMFCS) levels I to ...III, who participated in a large longitudinal cohort study were participants. Longitudinal change was analyzed in objectively measured sedentary behavior and associations with sex, body mass index Z score, and socioeconomic status. Moderate-vigorous intensity physical activity (MVPA) was estimated at 8 to 12 years.
Average sedentary minutes/day peaked at 4 years in children at GMFCS I and 5 years in children at GMFCS II to III, then plateaued. Male sex was associated with increased sedentary behavior. At 8 to 12 years, children at GMFCS I, II, and III accumulated on average 54, 47, and 14 minutes/day, respectively, of MVPA.
When measured to 12 years, sedentary behavior peaks by 5 years for children with CP who are walking with differences in trajectory according to GMFCS.
Photoreceptor degeneration leads to irreversible vision loss in humans with retinal dystrophies such as retinitis pigmentosa. Whereas photoreceptor loss is permanent in mammals, zebrafish possesses ...the ability to regenerate retinal neurons and restore visual function. Following acute damage, Müller glia (MG) re-enter the cell cycle and produce multipotent progenitors whose progeny differentiate into mature neurons. Both MG reprogramming and proliferation of retinal progenitor cells require reactive microglia and associated inflammatory signaling. Paradoxically, in zebrafish models of retinal degeneration, photoreceptor death does not induce the MG to reprogram and regenerate lost cells. Here, we used male and female zebrafish
mutants to demonstrate that progressive cone degeneration generates an immune response but does not stimulate MG proliferation. Acute light damage triggered photoreceptor regeneration in
mutants but cones were only restored to prelesion densities. Using
mutant zebrafish, we found that the chronic absence of microglia reduced inflammation and rescued cone degeneration in
mutants. Finally, single-cell RNA-sequencing revealed sustained expression of
in MG of
mutants and inhibition of Notch signaling induced MG to re-enter the cell cycle. Our findings provide new insights on the requirements for MG to proliferate and the potential for immunosuppression to prolong photoreceptor survival.
Inherited retinal degenerations (IRDs) are genetic diseases that lead to the progressive loss of photoreceptors and the permanent loss of vision. Zebrafish can regenerate photoreceptors after acute injury by reprogramming Müller glia (MG) into stem-like cells that produce retinal progenitors, but this regenerative process fails to occur in zebrafish models of IRDs. Here, we show that Notch pathway inhibition can promote photoreceptor regeneration in models of progressive degeneration and that immunosuppression can prevent photoreceptor loss. These results offer insight into the pathways that promote MG-dependent regeneration and the role of inflammation in photoreceptor degeneration.
As Arctic ice recedes, future oil spills pose increasing risk to keystone species and the ecosystems they support. We show that Polar cod (Boreogadus saida), an energy-rich forage fish for marine ...mammals, seabirds, and other fish, are highly sensitive to developmental impacts of crude oil. Transient oil exposures ≥300 μg/L during mid-organogenesis disrupted the normal patterning of the jaw as well as the formation and function of the heart, in a manner expected to be lethal to post-hatch larvae. More importantly, we found that exposure to lower levels of oil caused a dysregulation of lipid metabolism and growth that persisted in morphologically normal juveniles. As lipid content is critical for overwinter survival and recruitment, we anticipate Polar cod losses following Arctic oil spills as a consequence of both near-term and delayed mortality. These losses will likely influence energy flow within Arctic food webs in ways that are as-yet poorly understood.
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•Polar cod eggs are buoyant and accumulate crude oil droplets on the chorion•Crude oil disrupts embryonic cardiac function and larval lipid metabolism•Juvenile growth and lipid content are reduced following brief embryonic oil exposure•Polycyclic aromatic hydrocarbons are toxic to cod in parts per trillion concentrations
Environmental Science; Ecology; Biological Sciences; Developmental System Toxicology
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Respiratory tract infections (RTIs) drive many outpatient encounters and, despite being predominantly viral, are associated with high rates of antibiotic prescriptions. With rising antibacterial ...resistance, optimization of prescribing of antibiotics in outpatients with RTIs is a critical need. Fortunately, this challenge arises at a time of increasing availability of novel RTI diagnostics to help discern which patients have bacterial infections warranting treatment. Effective implementation of antibiotic stewardship is needed, but optimal approaches for ambulatory settings are unknown. Future research needs are reviewed in this summary of a research summit convened by the Infectious Diseases Society of America in the fall of 2019.
Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease. SLE is characterized by high inter-patient variability, including fluctuations over time, a factor which most biomarker studies ...omit from consideration. We investigated relationships between disease activity and biomarker expression in SLE, using novel methods to control for time-dependent variability, in a proof-of-concept study to evaluate whether doing so revealed additional information.
We measured 4 serum biomarkers (MIF, CCL2, CCL19, and CXCL10) and 13 routine clinical laboratory parameters, alongside disease activity measured by the SLE disease activity index-2k (SLEDAI-2k), collected longitudinally. We analyzed these data with unsupervised learning methods via ensemble clustering, incorporating temporal relationships using dynamic time warping for distance metric calculation.
Data from 843 visits in 110 patients (median age 47, 83% female) demonstrated highly heterogeneous time-dependent relationships between disease activity and biomarkers. Unbiased magnitude-based hierarchical clustering of biomarker expression levels isolated a patient subset (
= 9) with distinctively heterogeneous expression of the 17 biological parameters, and who had MIF, CCL2, CCL19, and CXCL10 levels that were higher and more strongly associated with disease activity, based on leave-one-out cross-validated regression analysis. In the remaining subgroup, a time-dependent regression model revealed significantly stronger predictive power of biomarkers for disease activity, compared to a time-agnostic regression model. Despite no significant difference in simple magnitude, using dynamic time warping analysis to align longitudinal profiles revealed a large subset (
= 69) with significantly stronger associations between biological parameters and disease activity. This subgroup had significantly lower flare rates, disease activity and damage scores, suggesting this clustering is clinically meaningful.
These results suggest associations between biological parameters and disease activity in SLE exist in a multi-dimensional time-dependent pattern, with implications for the analysis of biomarkers in SLE often used to identify therapeutic targets. Novel methods to analyse high-dimensional data and control for time-dependent variability may have broad utility in the study complex relationships between clinical and biological parameters.
Parasitic “wing lice” (Phthiraptera: Columbicola) and their dove and pigeon hosts are a well-recognized model system for coevolutionary studies at the intersection of micro- and macroevolution. ...Selection on lice in microevolutionary time occurs as pigeons and doves defend themselves against lice by preening. In turn, behavioral and morphological adaptations of the lice improve their ability to evade host defense. Over macroevolutionary time wing lice tend to cospeciate with their hosts; yet, some species of Columbicola have switched to new host species. Understanding the ecological and evolutionary factors that influence coadaptation and codiversification in this system will substantially improve our understanding of coevolution in general. However, further work is hampered by the lack of a robust phylogenetic framework for Columbicola spp. and their hosts. Previous attempts to resolve the phylogeny of Columbicola based on sequences from a few genes provided limited support. Here, we apply a new approach, target restricted assembly, to assemble 977 orthologous gene sequences from whole-genome sequence data generated from very small, ethanol-preserved specimens, representing up to 61 species of wing lice. Both concatenation and coalescent methods were used to estimate the species tree. These two approaches yielded consistent and well-supported trees with 90% of all relationships receiving 100% support, which is a substantial improvement over previous studies. We used this new phylogeny to show that biogeographic ranges are generally conserved within clades of Columbicola wing lice. Limited inconsistencies are probably attributable to intercontinental dispersal of hosts, and host switching by some of the lice.
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BFBNIB, DOBA, IZUM, KILJ, NMLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Caspase-2 is an evolutionarily conserved but enigmatic protease whose biological role remains poorly understood. To date, research into the functions of caspase-2 has been hampered by an absence of ...reagents that can distinguish its activity from that of the downstream apoptotic caspase, caspase-3. Identification of protein substrates of caspase-2 that are efficiently cleaved within cells may also provide clues to the role of this protease. We used a yeast-based transcriptional reporter system to define the minimal substrate specificity of caspase-2. The resulting profile enabled the identification of candidate novel caspase-2 substrates. Caspase-2 cleaved one of these proteins, the cancer-associated transcription factor Runx1, although with relatively low efficiency. A fluorogenic peptide was derived from the sequence most efficiently cleaved in the context of the transcriptional reporter. This peptide, Ac-VDTTD-AFC, was efficiently cleaved by purified caspase-2 and auto-activating caspase-2 in mammalian cells, and exhibited better selectivity for caspase-2 relative to caspase-3 than reagents that are currently available. We suggest that this reagent, used in parallel with the traditional caspase-3 substrate Ac-DEVD-AFC, will enable researchers to monitor caspase-2 activity in cell lysates and may assist in the determination of stimuli that activate caspase-2 in vivo.
Perceptions of climate change, the impacts of and responses to climatic variability and extreme weather are explored in three communities in the Yucatan Peninsula, Mexico, in relation to livelihood ...resilience. These communities provide examples of the most common livelihood strategies across the region: small-scale fisheries (San Felipe) and semi-subsistence small-holder farming (Tzucacab and Calakmul). Although the perception that annual rainfall is reducing is not supported by instrumental records, changes in the timing of vital summer rainfall and an intensification of the mid-summer drought (
canicula
) are confirmed. The impact of both droughts and hurricanes on livelihoods and crop yields was reported across all communities, although the severity varied. Changes in traditional
milpa
cultivation were seen to be driven by less reliable rainfall but also by changes in Mexico’s agricultural and wider economic policies. Diversification was a common adaptation response across all communities and respondents, resulting in profound changes in livelihood strategies. Government attempts to reduce vulnerability were found to lack continuity, be hard to access and too orientated toward commercial scale producers. Population growth, higher temperatures and reduced summer rainfall will increase the pressures on communities reliant on small-scale farming and fishing, and a more nuanced understanding of both impacts and adaptations is required for improved livelihood resilience. Greater recognition of such local-scale adaptation strategies should underpin the developing Mexican National Adaptation Policy and provide a template for approaches internationally as adaptation becomes an increasingly important part of the global strategy to cope with climate change.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The emergence of partnerships between state wildlife agencies and public or private organizations has allowed for more efficient and effective strategies to address conservation concerns. Cultivating ...such partnerships can increase public engagement in decision-making processes and ensure better relationships with constituents. Grant programs are a proven method for many state wildlife agencies to create, improve, and maintain habitat with partners, and may also facilitate partnership development among constituents. This research evaluated the effectiveness of grant programs in building partnerships among grant-receiving organizations and others by using social network analysis to identify factors associated with establishing partnerships. Major factors in partnership selection were receiving a grant, receiving support prior to the grant, scale of partner organizations, and distance between organizations. Understanding elements that drive partnership development provides state wildlife agencies with the means to encourage more strategic partnerships and may facilitate state wildlife agencies meet their management objectives.
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BFBNIB, GIS, IJS, KISLJ, NUK, PNG, UL, UM, UPUK
The scabies mite, Sarcoptes scabiei var. hominis, infests human skin, causing allergic reactions and facilitating bacterial infection by Streptococcus sp., with serious consequences such as rheumatic ...fever and rheumatic heart disease. To identify a possible drug target or vaccine candidate protein, we searched for homologues of the group 3 allergen of house dust mites, which we subsequently identified in a cDNA library. The native protein, designated Sar s 3, was shown to be present in the mite gut and excreted in fecal pellets into mite burrows within the upper epidermis. The substrate specificity of proteolytically active recombinant rSar s 3 was elucidated by screening a bacteriophage library. A preference for substrates containing a RS(G/A) sequence at the P1-P2′ positions was revealed. A series of peptides synthesized as internally quenched fluorescent substrates validated the phage display data and high performance liquid chromatography/mass spectrometry analysis of the preferred cleaved substrate and confirmed the predicted cleavage site. Searches of the human proteome using sequence data from the phage display allowed the in silico prediction of putative physiological substrates. Among these were numerous epidermal proteins, with filaggrin being a particularly likely candidate substrate. We showed that recombinant rSar s 3 cleaves human filaggrin in vitro and obtained immunohistological evidence that the filaggrin protein is ingested by the mite. This is the first report elucidating the substrate specificity of Sar s 3 and its potential role in scabies mite biology.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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