Tissue-specific calibration of extracellular matrix material properties by transforming growth factor-beta and Runx2 in bone is required for hearing

Publisher version: http://www.nature.com/embor/journal/v11/n10/full/embor2010135.htmlDA - 20100917 IS - 1469-3178 (Electronic) IS - 1469-221X (Linking) LA - ENG PT - JOURNAL ARTICLEDA - 20100917 IS - 1469-3178 (Electronic) IS - 1469-221X (Linking) LA - ENG PT - JOURNAL ARTICLEDA - 20100917 IS - 1469-3178 (Electronic) IS - 1469-221X (Linking) LA - ENG PT - JOURNAL ARTICLEPhysical cues, such as extracellular matrix stiffness, direct cell differentiation and support tissue-specific function. Perturbation of these cues underlies diverse pathologies, including osteoarthritis, cardiovascular disease and cancer. However, the molecular mechanisms that establish tissue-specific material properties and link them to healthy tissue function are unknown. We show that Runx2, a key lineage-specific transcription factor, regulates the material properties of bone matrix through the same transforming growth factor-beta (TGFbeta)-responsive pathway that controls osteoblast differentiation. Deregulated TGFbeta or Runx2 function compromises the distinctly hard cochlear bone matrix and causes hearing loss, as seen in human cleidocranial dysplasia. In Runx2(+/-) mice, inhibition of TGFbeta signalling rescues both the material properties of the defective matrix, and hearing. This study elucidates the unknown cause of hearing loss in cleidocranial dysplasia, and demonstrates that a molecular pathway controlling cell differentiation also defines material properties of extracellular matrix. Furthermore, our results suggest that the careful regulation of these properties is essential for healthy tissue functio

Feature Improvement and Cost Reduction of Baitcasting Fishing Reels for Emerging Markets

Baitcasting fishing reels are a challenging product to sell to new users in emerging markets. Their complex and less-than-intuitive design make them poor candidates for a novice fisherman selecting his or her first fishing reel. Based upon manufacturer constraints and design requirements, our team lowered the price point and improved the usability of the Okuma Cerros baitcasting fishing reel to make it more appealing to a wider range of consumers, especially in emerging markets. This project resulted in a three-phase redesign: reducing cost via alternative materials and replacing bearings with bushings; prototyping a simplified cast control system; and proposing an improved user interface

First draft genome and transcriptome of \u3ci\u3eCercosporidium personatum\u3c/i\u3e, causal agent of late leaf spot disease of peanut

Objective Two main fungal leaf spot diseases occur in peanut, namely early leaf spot (ELS) and late leaf spot (LLS), these cause a yearly average of $44 million losses. Limited genetic information, 3534 bp of sequencing, exists about the causal agent of LLS, Cercosporidium personatum (syn. Nothopassalora personata, syn. Phaeoisariopsis personata). The extremely slow growth of this fungus, approximately 1 cm colony in 6 months, and challenges in nucleic acid extractions have hindered research on LLS. Our goal in this work is to provide a reference genome for research on this pathogen. Results Whole genome and transcriptome sequencing of the LLS fungus were obtained. A total of 233,542,110 reads of the genome were de novo assembled resulting in 1061 scaffolds, and estimated genome size 27,597,787 bp. RNA sequencing resulted in 11,848,198 reads that were de novo assembled into 13,343 contigs. Genome annotation resulted in 10,703 putative genes. BUSCO analysis of the genome and annotation resulted in 91.1% and 89.5% completeness, respectively. Phylogenetic dendrograms for 5442 bp and 4401 bp of RNA Polymerase II largest and second largest subunits, and for 5474 bp of the ribosomal RNA cistron of C. personatum are presented in relation to closely related fungi

Regression, developmental trajectory and associated problems in disorders in the autism spectrum: the SNAP study

We report rates of regression and associated findings in a population derived group of 255 children aged 9-14 years, participating in a prevalence study of autism spectrum disorders (ASD); 53 with narrowly defined autism, 105 with broader ASD and 97 with non-ASD neurodevelopmental problems, drawn from those with special educational needs within a population of 56,946 children. Language regression was reported in 30% with narrowly defined autism, 8% with broader ASD and less than 3% with developmental problems without ASD. A smaller group of children were identified who underwent a less clear setback. Regression was associated with higher rates of autistic symptoms and a deviation in developmental trajectory. Regression was not associated with epilepsy or gastrointestinal problems

Morpholino Gene Knockdown in Adult Fundulus heteroclitus: Role of SGK1 in Seawater Acclimation

The Atlantic killifish (Fundulus heteroclitus) is an environmental sentinel organism used extensively for studies on environmental toxicants and salt (NaCl) homeostasis. Previous research in our laboratory has shown that rapid acclimation of killifish to seawater is mediated by trafficking of CFTR chloride channels from intracellular vesicles to the plasma membrane in the opercular membrane within the first hour in seawater, which enhances chloride secretion into seawater, thereby contributing to salt homeostasis. Acute transition to seawater is also marked by an increase in both mRNA and protein levels of serum glucocorticoid kinase 1 (SGK1) within 15 minutes of transfer. Although the rise in SGK1 in gill and its functional analog, the opercular membrane, after seawater transfer precedes the increase in membrane CFTR, a direct role of SGK1 in elevating membrane CFTR has not been established in vivo. To test the hypothesis that SGK1 mediates the increase in plasma membrane CFTR we designed two functionally different vivo-morpholinos to knock down SGK1 in gill, and developed and validated a vivo-morpholino knock down technique for adult killifish. Injection (intraperitoneal, IP) of the splice blocking SGK1 vivo-morpholino reduced SGK1 mRNA in the gill after transition from fresh to seawater by 66%. The IP injection of the translational blocking and splice blocking vivo-morpholinos reduced gill SGK1 protein abundance in fish transferred from fresh to seawater by 64% and 53%, respectively. Moreover, knock down of SGK1 completely eliminated the seawater induced rise in plasma membrane CFTR, demonstrating that the increase in SGK1 protein is required for the trafficking of CFTR from intracellular vesicles in mitochondrion rich cells to the plasma membrane in the gill during acclimation to seawater. This is the first report of the use of vivo-morpholinos in adult killifish and demonstrates that vivo-morpholinos are a valuable genetic tool for this environmentally relevant model organism

A Mix of Old British and Modern European Breeds: Genomic Prediction of Breed Composition of Smallholder Pigs in Uganda

Pig herds in Africa comprise genotypes ranging from local ecotypes to commercial breeds. Many animals are composites of these two types and the best levels of crossbreeding for particular production systems are largely unknown. These pigs are managed without structured breeding programs and inbreeding is potentially limiting. The objective of this study was to quantify ancestry contributions and inbreeding levels in a population of smallholder pigs in Uganda. The study was set in the districts of Hoima and Kamuli in Uganda and involved 422 pigs. Pig hair samples were taken from adult and growing pigs in the framework of a longitudinal study investigating productivity and profitability of smallholder pig production. The samples were genotyped using the porcine GeneSeek Genomic Profiler (GGP) 50K SNP Chip. The SNP data was analyzed to infer breed ancestry and autozygosity of the Uganda pigs. The results showed that exotic breeds (modern European and old British) contributed an average of 22.8% with a range of 2–50% while “local” blood contributed 69.2% (36.9–95.2%) to the ancestry of the pigs. Runs of homozygosity (ROH) greater than 2 megabase (Mb) quantified the average genomic inbreeding coefficient of the pigs as 0.043. The scarcity of long ROH indicated low recent inbreeding. We conclude that the genomic background of the pig population in the study is a mix of old British and modern pig ancestries. Best levels of admixture for smallholder pigs are yet to be determined, by linking genotypes and phenotypic records

The effect of the proportion of Modern European ancestry on grower and sow performance of pigs in smallholder systems in Uganda

Several factors, including breed, lead to divergent performance of pigs for production and reproduction traits in different environments. A recent genomics study showed that Modern European (ME) pig breeds contribute to the ancestry of smallholder pigs in the Hoima and Kamuli districts, Uganda. These pigs were also involved in a longitudinal study with several traits recorded, including 540 body weights (WT) of 374 growing pigs, 195 records of total number of piglets born alive (TBA) of 157 sows, and 110 total number weaned (TNW) records of 94 sows. Linear mixed-effects models were used to test for the significance of environmental effects, including housing system, geographic location, and the season when the events occurred as well as animal-specific effects like age, sex, parity, and farrow-to-weaning interval. Stepwise model reduction starting from models with all main effects and pairwise interactions was applied. The final models were then expanded to include proportions of Modern European (ME) ancestry for the subset of animals genotyped, following genomic ancestry analysis based on a Porcine 50K SNP Chip. ME ancestry proportions ranged from 0.02 to 0.50 and were categorized into three classes (low/medium/high ME) based on 33.3% quantiles. The effects of ME classes on WT and TBA were not significant. ME showed a significant effect on TNW. Sows with a high proportion of ME weaned 2.4 piglets more than the low group, the medium ME group being intermediate. This study used genomic data to investigate the effects of genetic ancestry on the performance of smallholder pigs in Uganda. The proportion of Modern European ancestry did not exceed 0.50, therefore not allowing for the comparison of local versus pure “exotic” types of pigs. For the range of ancestries observed, which is the relevant one for current smallholder systems in Uganda, differences were small for the body weight of growing pigs and the number of piglets born alive, while higher proportions of ME ancestry resulted in significantly more piglets weaned. The availability of genotypes of a higher number of growing pigs would have been beneficial for drawing conclusions on the effect of ME ancestry on the growth rates of smallholder pigs in Uganda

Effectiveness of registered nurses on system outcomes in primary care: a systematic review

Background Internationally, policy-makers and health administrators are seeking evidence to inform further integration and optimal utilization of registered nurses (RNs) within primary care teams. Although existing literature provides some information regarding RN contributions, further evidence on the impact of RNs towards quality and cost of care is necessary to demonstrate the contribution of this role on health system outcomes. In this study we synthesize international evidence on the effectiveness of RNs on care delivery and system-level outcomes in primary care. Methods A systematic review was conducted in accordance with Joanna Briggs Institute methodology. Searches were conducted in CINAHL, MEDLINE Complete, PsycINFO, and Embase for published literature and ProQuest Dissertations and Theses and MedNar for unpublished literature between 2019 and 2022 using relevant subject headings and keywords. Additional literature was identified through Google Scholar, websites, and reference lists of included articles. Studies were included if they measured effectiveness of a RN-led intervention (i.e., any care/activity performed by a primary care RN within the context of an independent or interdependent role) and reported outcomes of these interventions. Included studies were published in English; no date or location restrictions were applied. Risk of bias was assessed using the Integrated Quality Criteria for Review of Multiple Study Designs tool. Due to the heterogeneity of included studies, a narrative synthesis was undertaken. Results Seventeen articles were eligible for inclusion, with 11 examining system outcomes (e.g., cost, workload) and 15 reporting on outcomes related to care delivery (e.g., illness management, quality of smoking cessation support). The studies suggest that RN-led care may have an impact on outcomes, specifically in relation to the provision of medication management, patient triage, chronic disease management, sexual health, routine preventative care, health promotion/education, and self-management interventions (e.g. smoking cessation support). Conclusions The findings suggest that primary care RNs impact the delivery of quality primary care, and that RN-led care may complement and potentially enhance primary care delivered by other primary care providers. Ongoing evaluation in this area is important to further refine nursing scope of practice policy, determine the impact of RN-led care on outcomes, and inform improvements to primary care infrastructure and systems management to meet care needs. Protocol registration ID PROSPERO: International prospective register of systematic reviews. 2018. ID= CRD42018090767

The influence of marketing on the sports betting attitudes and consumption behaviours of young men: Implications for harm reduction and prevention strategies

Background: Gambling can cause significant health and social harms for individuals, their families, and communities. While many studies have explored the individual factors that may lead to and minimise harmful gambling, there is still limited knowledge about the broader range of factors that may contribute to gambling harm. There are significant regulations to prevent the marketing of some forms of gambling but comparatively limited regulations relating to the marketing of newer forms of online gambling such as sports betting. There is a need for better information about how marketing strategies may be shaping betting attitudes and behaviours and the range of policy and regulatory responses that may help to prevent the risky or harmful consumption of these products. Methods: We conducted qualitative, semi-structured interviews with 50 Australian men (aged 20-37 years) who gambled on sports. We explored their attitudes and opinions regarding sports betting marketing, the embedding of marketing within sports and other non-gambling community environments, and the implications this had for the normalisation of betting. Results: Our findings indicate that most of the environments in which participants reported seeing or hearing betting advertisements were not in environments specifically designed for betting. Participants described that the saturation of marketing for betting products, including through sports-based commentary and sports programming, normalised betting. Participants described that the inducements offered by the industry were effective marketing strategies in getting themselves and other young men to bet on sports. Inducements were also linked with feelings of greater control over betting outcomes and stimulated some individuals to sign up with more than one betting provider. Conclusions: This research suggests that marketing plays a strong role in the normalisation of gambling in sports. This has the potential to increase the risks and subsequent harms associated with these products. Legislators must begin to consider the cultural lag between an evolving gambling landscape, which supports sophisticated marketing strategies, and effective policies and practices which aim to reduce and prevent gambling harm. © 2017 The Author(s)