The adult mammalian heart contains multiple cell types that work in unison under tightly regulated conditions to maintain homeostasis. Cardiac fibroblasts are a significant and unique population of ...non-muscle cells in the heart that have recently gained substantial interest in the cardiac biology community. To better understand this renaissance cell, it is essential to systematically survey what has been known in the literature about the cellular and molecular processes involved. We have built CARFMAP (http://visionet.erc.monash.edu.au/CARFMAP), an interactive cardiac fibroblast pathway map derived from the biomedical literature using a software-assisted manual data collection approach. CARFMAP is an information-rich interactive tool that enables cardiac biologists to explore the large body of literature in various creative ways. There is surprisingly little overlap between the cardiac fibroblast pathway map, a foreskin fibroblast pathway map, and a whole mouse organism signalling pathway map from the REACTOME database. Among the use cases of CARFMAP is a common task in our cardiac biology laboratory of identifying new genes that are (1) relevant to cardiac literature, and (2) differentially regulated in high-throughput assays. From the expression profiles of mouse cardiac and tail fibroblasts, we employed CARFMAP to characterise cardiac fibroblast pathways. Using CARFMAP in conjunction with transcriptomic data, we generated a stringent list of six genes that would not have been singled out using bioinformatics analyses alone. Experimental validation showed that five genes (Mmp3, Il6, Edn1, Pdgfc and Fgf10) are differentially regulated in the cardiac fibroblast. CARFMAP is a powerful tool for systems analyses of cardiac fibroblasts, facilitating systems-level cardiovascular research.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Aim
To determine the predictors of magnitude of change in response to a participation‐focused leisure‐time physical activity intervention in children with cerebral palsy (CP) using the ParticiPAte CP ...protocol.
Method
We included 33 children (16 males, 17 females) aged 8 to 12 years (mean age=10y, SD=1y 6mo) with CP with pre/postintervention data from a wait‐list randomized trial. The hypothesized linear predictors of change in primary outcomes (Canadian Occupational Performance Measure COPM‐performance and COPM‐satisfaction, Belief in Goal Self‐Competence Scale (BiGSS), and minutes per day moderate‐to‐vigorous physical activity MVPA) were: age; Gross Motor Function Classification System level; comorbid autism spectrum disorder (ASD); Goal Attainment Scaling T score; Problems in Schools Questionnaire; Physical Activity Climate Questionnaire; Motives for Physical Activities Measure‐Revised; and stage of behaviour change. Multivariable models were selected using the Bayesian information criterion.
Results
Overcoming barriers to participation, age, and comorbid ASD explained 49% of the variance in change in COPM‐performance. Being motivated by interest and/or enjoyment and age explained 32% of the variance in change in COPM‐satisfaction. Being motivated by physical activity competence or appearance (extrinsic motivation) explained 24% of the variance in change in BiGSS. Parental autonomy supportiveness, overcoming barriers to participation, appearance motivation, and baseline MVPA explained 59% of the variance in change in MVPA.
Interpretation
These findings support a behaviour paradigm for conceptualizing physical activity in children with CP.
What this paper adds
Children who met their treatment goals showed a greater increase in physical activity participation.
Children who were more intrinsically motivated by physical activity at baseline improved more.
Being older and having a comorbid diagnosis of autism spectrum disorder were associated with an attenuated effect of the therapy.
What this paper adds
Children who met their treatment goals showed a greater increase in physical activity participation.
Children who were more intrinsically motivated by physical activity at baseline improved more.
Being older and having a comorbid diagnosis of autism spectrum disorder were associated with an attenuated effect of the therapy.
Editor's Choice
More and more, participation in any life situation is rightly highlighted as a goal for intervention, and a most relevant outcome measure.1 This contrasts with previews views that focused on the ability to perform tasks as expected. My Editor’s Choice for the May issue is this study of change observed in children with cerebral palsy following an individualized family‐centred, ecological leisure‐time physical activity intervention focused on motivation and participation. It illustrates that participation can be supported meaningfully by organizing therapy in settings that are natural to the child and family.
REFERENCE
1. Imms C, Green D, editors. Participation: Optimising Outcomes in Childhood‐Onset Neurodisability. London: Mac Keith Press, 2020.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Many older women are screened for breast cancer beyond guideline-recommended thresholds. One contributor is pro-screening messaging from health care professionals, media, and family/friends. In this ...project, we developed and evaluated messages for reducing overscreening in older women.
We surveyed women ages 65+ who were members of a nationally representative online panel. We constructed 8 messages describing reasons to consider stopping mammograms, including guideline recommendations, false positives, overdiagnosis, and diminishing benefits from screening due to competing risks. Messages varied in their format; some presented statistical evidence, and some described short anecdotes. Each participant was randomized to read 4 of 8 messages. We also randomized participants to one of 3 message sources (clinician, family member, and news story). We assessed whether the message would make participants "want to find out more information" and "think carefully" about mammograms.
Participants (N=790) had a mean age of 73.5 years; 25.8% were non-White. Across all messages, 73.0% of the time, participants agreed that the messages would make them seek more information (range among different messages=64.2%-78.2%); 46.5% of the time participants agreed that the messages would make them think carefully about getting mammograms (range =36.7%-50.7%). Top-rated messages mentioned false-positive anecdotes and overdiagnosis evidence. Ratings were similar for messages from clinicians and news sources, but lower from the family member source.
Overall, participants positively evaluated messages designed to reduce breast cancer overscreening regarding perceived effects on information seeking and deliberation. Combining the top-rated messages into messaging interventions may be a novel approach to reduce overscreening.
Tumor microenvironments can promote stem cell maintenance, tumor growth, and therapeutic resistance, findings linked by the tumor-initiating cell hypothesis. Standard of care for glioblastoma (GBM) ...includes temozolomide chemotherapy, which is not curative, due, in part, to residual therapy-resistant brain tumor-initiating cells (BTICs). Temozolomide efficacy may be increased by targeting carbonic anhydrase 9 (CA9), a hypoxia-responsive gene important for maintaining the altered pH gradient of tumor cells. Using patient-derived GBM xenograft cells, we explored whether CA9 and CA12 inhibitor SLC-0111 could decrease GBM growth in combination with temozolomide or influence percentages of BTICs after chemotherapy. In multiple GBMs, SLC-0111 used concurrently with temozolomide reduced cell growth and induced cell cycle arrest via DNA damage in vitro. In addition, this treatment shifted tumor metabolism to a suppressed bioenergetic state in vivo. SLC-0111 also inhibited the enrichment of BTICs after temozolomide treatment determined via CD133 expression and neurosphere formation capacity. GBM xenografts treated with SLC-0111 in combination with temozolomide regressed significantly, and this effect was greater than that of temozolomide or SLC-0111 alone. We determined that SLC-0111 improves the efficacy of temozolomide to extend survival of GBM-bearing mice and should be explored as a treatment strategy in combination with current standard of care.
Circuit diagrams and Unified Modeling Language diagrams are just two examples of standard visual languages that help accelerate work by promoting regularity, removing ambiguity and enabling software ...tool support for communication of complex information. Ironically, despite having one of the highest ratios of graphical to textual information, biology still lacks standard graphical notations. The recent deluge of biological knowledge makes addressing this deficit a pressing concern. Toward this goal, we present the Systems Biology Graphical Notation (SBGN), a visual language developed by a community of biochemists, modelers and computer scientists. SBGN consists of three complementary languages: process diagram, entity relationship diagram and activity flow diagram. Together they enable scientists to represent networks of biochemical interactions in a standard, unambiguous way. We believe that SBGN will foster efficient and accurate representation, visualization, storage, exchange and reuse of information on all kinds of biological knowledge, from gene regulation, to metabolism, to cellular signaling.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Adaptive radiation is an important mechanism of organismal diversification and can be triggered by new ecological opportunities. Although poorly studied in this regard, parasites are an ideal group ...in which to study adaptive radiations because of their close associations with host species. Both experimental and comparative studies suggest that the ectoparasitic wing lice of pigeons and doves have adaptively radiated, leading to differences in body size and overall coloration. Here, we show that long-distance dispersal by dove hosts was central to parasite diversification because it provided new ecological opportunities for parasites to speciate after host-switching. We further show that among extant parasite lineages host-switching decreased over time, with cospeciation becoming the more dominant mode of parasite speciation. Taken together, our results suggest that host dispersal, followed by host-switching, provided novel ecological opportunities that facilitated adaptive radiation by parasites.
Aggregation of Aβ peptides is a key contributor to the etiology of Alzheimer's disease. Being intrinsically disordered, monomeric Aβ is susceptible to conformational excursions, especially in the ...presence of important interacting partners such as membrane lipids, to adopt specific aggregation pathways. Furthermore, components such as gangliosides in membranes and lipid rafts are known to play important roles in the adoption of pathways and the generation of discrete neurotoxic oligomers. Yet, what roles do carbohydrates on gangliosides play in this process remains unknown. Here, using GM1, GM3, and GD3 ganglioside micelles as models, we show that the sugar distributions and cationic amino acids within Aβ N-terminal region modulate oligomerization of Aβ temporally, and dictate the stability and maturation of oligomers. These results demonstrate the selectivity of sugar distributions on the membrane surface toward oligomerization of Aβ and thus implicate cell-selective enrichment of oligomers.
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•Gangliosides are important membrane components linked to the etiology of Alzheimer's disease.•Sugar distributions on gangliosides GM1, GM3, and GD3 differentially affect the oligomerization of Aβ42.•Aβ-sugar interactions are affected by the cationic residues in the N-terminal of Aβ.•Sugar distribution on ganglioside confers specificity of interaction for the formation and stability of oligomers.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Introduction
In the United States, approximately 2.7 million grandparents have permanent custody of their grandchildren. Prevalence of primary dental caries has remained steady for those living in ...poverty, and among children of color. Children in the care of their grandparents frequently live in socioeconomically disadvantaged households, where dental disparities continue to exist. Research regarding the grandfamily dynamic as it relates to oral health, is limited. The purpose of this study was to investigate oral health perceptions, behaviors, and knowledge of grandparents raising/caring for their grandchildren; and explore how a grandparent caregiver’s oral health knowledge influences their perceptions/behaviors regarding their grandchild’s oral health.
Methods
This descriptive, cross-sectional survey research used non-probability sampling strategies to recruit grandparents who were the primary caregiver of their grandchildren, aged birth to eighteen years. A validated questionnaire was employed, both in-person and electronically.
Results
A total of 75 grandparents participated and answered 52% (SD = 27%) of oral health knowledge questions correctly. The study showed a correlation between low-income grandparents (M = 3.94, SD = 1.02) having higher pediatric oral health knowledge. Additionally, results indicated the greater the knowledge, the more positive intent to assist grandchildren with routine brushing and in checking their teeth for cavities.
Conclusions
This study demonstrated that regardless of socioeconomic status, grandparent caregiver’s oral health knowledge can positively affect their oral health-related behaviors and values, which could influence their grandchildren’s' oral health. Further research regarding grandparent caregiver utilization of public health pediatric services and dental education programs, and the potential influence of these programs on pediatric oral health, should be explored.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
This review provides insight for the judicious selection of nicotine dose ranges and routes of administration for in vivo studies. The literature is replete with reports in which a dosaging regimen ...chosen for a specific nicotine-mediated response was suboptimal for the species used. In many cases, such discrepancies could be attributed to the complex variables comprising species-specific in vivo responses to acute or chronic nicotine exposure.
This review capitalizes on the authors' collective decades of in vivo nicotine experimentation to clarify the issues and to identify the variables to be considered in choosing a dosaging regimen. Nicotine dose ranges tolerated by humans and their animal models provide guidelines for experiments intended to extrapolate to human tobacco exposure through cigarette smoking or nicotine replacement therapies. Just as important are the nicotine dosaging regimens used to provide a mechanistic framework for acquisition of drug-taking behavior, dependence, tolerance, or withdrawal in animal models.
Seven species are addressed: humans, nonhuman primates, rats, mice, Drosophila, Caenorhabditis elegans, and zebrafish. After an overview on nicotine metabolism, each section focuses on an individual species, addressing issues related to genetic background, age, acute vs chronic exposure, route of administration, and behavioral responses.
The selected examples of successful dosaging ranges are provided, while emphasizing the necessity of empirically determined dose-response relationships based on the precise parameters and conditions inherent to a specific hypothesis. This review provides a new, experimentally based compilation of species-specific dose selection for studies on the in vivo effects of nicotine.
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DOBA, EMUNI, FIS, FSPLJ, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
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