Incidental chest radiographic findings in adult patients with acute cough

PURPOSE Imaging may produce unexpected or incidental findings with consequences for patients and ordering of future investigations. Chest radiography in patients with acute cough is among the most common reasons for imaging in primary care, but data on associated incidental findings are lacking. We set out to describe the type and prevalence of incidental chest radiography findings in primary care patients with acute cough. METHODS We report on data from a cross-sectional study in 16 European primary care networks on 3,105 patients with acute cough, all of whom were undergoing chest radiography as part of a research study workup. Apart from assessment for specified signs of pneumonia and acute bronchitis, local radiologists were asked to evaluate any additional finding on the radiographs. For the 2,823 participants with good-quality chest radiographs, these findings were categorized according to clinical relevance based on previous research evidence and analyzed for type and prevalence by network, sex, age, and smoking status. RESULTS Incidental findings were reported in 19% of all participants, and ranged from 0% to 25% by primary care network, with the network being an independent contributor (P < .001). Of all participants 3% had clinically relevant incidental findings. Suspected nodules and shadows were reported in 1.8%. Incidental findings were more common is older participants and smokers (P < .001). CONCLUSIONS Clinically relevant incidental findings on chest radiographs in primary care adult patients with acute cough are uncommon, and prevalence varies by setting

The Genetics of Adaptation for Eight Microvirid Bacteriophages

Theories of adaptive molecular evolution have recently experienced significant expansion, and their predictions and assumptions have begun to be subjected to rigorous empirical testing. However, these theories focus largely on predicting the first event in adaptive evolution, the fixation of a single beneficial mutation. To address long-term adaptation it is necessary to include new assumptions, but empirical data are needed for guidance. To empirically characterize the general properties of adaptive walks, eight recently isolated relatives of the single-stranded DNA (ssDNA) bacteriophage φX174 (family Microviridae) were adapted to identical selective conditions. Three of the eight genotypes were adapted in replicate, for a total of 11 adaptive walks. We measured fitness improvement and identified the genetic changes underlying the observed adaptation. Nearly all phages were evolvable; nine of the 11 lineages showed a significant increase in fitness. However, fitness plateaued quickly, and adaptation was achieved through only three substitutions on average. Parallel evolution was rampant, both across replicates of the same genotype as well as across different genotypes, yet adaptation of replicates never proceeded through the exact same set of mutations. Despite this, final fitnesses did not vary significantly among replicates. Final fitnesses did vary significantly across genotypes but not across phylogenetic groupings of genotypes. A positive correlation was found between the number of substitutions in an adaptive walk and the magnitude of fitness improvement, but no correlation was found between starting and ending fitness. These results provide an empirical framework for future adaptation theory

The Lumberjack, April 27, 1988

The student newspaper of Humboldt State University.https://digitalcommons.humboldt.edu/studentnewspaper/3131/thumbnail.jp

Clinical characteristics of emergency department heart failure patients initially diagnosed as non-heart failure

BACKGROUND: Since previous studies suggest the emergency department (ED) misdiagnosis rate of heart failure is 10–20% we sought to describe the characteristics of ED patients misdiagnosed as non-decompensated heart failure in the ED. METHODS: We analyzed a prospective convenience sample of 439 patients at 4 emergency departments who presented with signs or symptoms of decompensated heart failure. Patients with a cardiology criterion standard diagnosis of decompensated heart failure and an ED diagnosis of decompensated heart failure were compared to patients with a criterion standard of decompensated heart failure but no ED diagnosis of decompensated heart failure. Two senior cardiology fellows retrospectively determined the patient's heart failure status during their acute ED presentation. The Mann-Whitney u-test for two groups, the Kruskall-Wallis test for multiple groups, or Chi-square tests, were used as appropriate. RESULTS: There were 173 (39.4%) patients with a criterion standard diagnosis of decompensated heart failure. Among those with this criterion standard diagnosis of decompensated heart failure, discordant patients without an ED diagnosis of decompensated heart failure (n = 58) were more likely to have a history of COPD (p = 0.017), less likely to have a previous history of heart failure (p = 0.014), and less likely to have an elevated b-type natriuretic peptide (BNP) level (median 518 vs 764 pg/ml; p = 0.038) than those who were given a concordant ED diagnosis of decompensated heart failure. BNP levels were higher in those with a criterion standard diagnosis of decompensated heart failure than in those without a criterion standard diagnosis (median 657 vs 62.7 pg/ml). However, 34.6% of patients with decompensated heart failure had BNP levels in the normal (<100 pg/ml; 6.1%) or indeterminate range (100–500 pg/ml; 28.5%). CONCLUSION: We found the ED diagnoses of decompensated heart failure to be discordant with the criterion standard in 14.3% of patients, the vast majority of which were due to a failure to diagnose heart failure when it was present. Patients with a previous history of COPD, without a previous history of heart failure and with lower BNP levels were more likely to have an ED misdiagnosis of non-decompensated heart failure. Readily available, accurate, objective ED tests are needed to improve the early diagnosis of decompensated heart failure in ED patients

Time-sampled population sequencing reveals the interplay of selection and genetic drift in experimental evolution of Potato virus Y

[EN] RNA viruses are one of the fastest evolving biological entities. Within their hosts, they exist as genetically diverse populations (i.e., viral mutant swarms), which are sculpted by different evolutionary mechanisms, such as mutation, natural selection and genetic drift, and also the interactions between genetic variants within the mutant swarms. To elucidate the mechanisms that modulate the population diversity of an important plant pathogenic virus, we performed evolution experiments with Potato virus Y (PVY) in potato genotypes that differ in their defense response against the virus. Using deep sequencing of small RNAs, we followed the temporal dynamics of standing and newly-generated variation in the evolving viral lineages. A time-sampled approach allowed us to: (i) reconstruct theoretical haplotypes in the starting population by using clustering of single nucleotide polymorphisms' trajectories and (ii) use quantitative population genetics approaches to estimate the contribution of selection and genetic drift, and their interplay, to the evolution of the virus. We detected imprints of strong selective sweeps and narrow genetic bottlenecks, followed by the shift in frequency of selected haplotypes. Comparison of patterns of viral evolution in differently susceptible host genotypes indicated possible diversifying evolution of PVY in the less susceptible host (efficient in the accumulation of salicylicacid).This study was supported by the Slovenian Research Agency (grants L4-5525 and P4-0165 and Ph.D. grant to D.K.). Work in Valencia was supported by Spain Ministry of Economy and Competitiveness (grant BFU2015-65037-P to S.F.E.), and short-term scientific mission support was provided to D.K. in the frame of EU-funded COST action FA1407.Kutnjak, D.; Elena Fito, SF.; Ravnikar, M. (2017). Time-sampled population sequencing reveals the interplay of selection and genetic drift in experimental evolution of Potato virus Y. Journal of Virology. 91(16):1-17. https://doi.org/10.1128/JVI.00690-17S1179116Andino, R., & Domingo, E. (2015). Viral quasispecies. Virology, 479-480, 46-51. doi:10.1016/j.virol.2015.03.022Ohshima, K., Nomiyama, R., Mitoma, S., Honda, Y., Yasaka, R., & Tomimura, K. (2016). Evolutionary rates and genetic diversities of mixed potyviruses in Narcissus. Infection, Genetics and Evolution, 45, 213-223. doi:10.1016/j.meegid.2016.08.036Froissart, R., Roze, D., Uzest, M., Galibert, L., Blanc, S., & Michalakis, Y. (2005). Recombination Every Day: Abundant Recombination in a Virus during a Single Multi-Cellular Host Infection. PLoS Biology, 3(3), e89. doi:10.1371/journal.pbio.0030089Tromas, N., Zwart, M. P., Poulain, M., & Elena, S. F. (2014). Estimation of the in vivo recombination rate for a plant RNA virus. Journal of General Virology, 95(3), 724-732. doi:10.1099/vir.0.060822-0Simon-Loriere, E., & Holmes, E. C. (2011). Why do RNA viruses recombine? Nature Reviews Microbiology, 9(8), 617-626. doi:10.1038/nrmicro2614Zwart, M. P., & Elena, S. F. (2015). Matters of Size: Genetic Bottlenecks in Virus Infection and Their Potential Impact on Evolution. Annual Review of Virology, 2(1), 161-179. doi:10.1146/annurev-virology-100114-055135Neher, R. A. (2013). Genetic Draft, Selective Interference, and Population Genetics of Rapid Adaptation. Annual Review of Ecology, Evolution, and Systematics, 44(1), 195-215. doi:10.1146/annurev-ecolsys-110512-135920Elena, S. F., Fraile, A., & García-Arenal, F. (2014). Evolution and Emergence of Plant Viruses. Advances in Virus Research, 161-191. doi:10.1016/b978-0-12-800098-4.00003-9Longdon, B., Brockhurst, M. A., Russell, C. A., Welch, J. J., & Jiggins, F. M. (2014). The Evolution and Genetics of Virus Host Shifts. PLoS Pathogens, 10(11), e1004395. doi:10.1371/journal.ppat.1004395Vassilakos, N., Simon, V., Tzima, A., Johansen, E., & Moury, B. (2015). Genetic Determinism and Evolutionary Reconstruction of a Host Jump in a Plant Virus. Molecular Biology and Evolution, 33(2), 541-553. doi:10.1093/molbev/msv222Stapleford, K. A., Coffey, L. L., Lay, S., Bordería, A. V., Duong, V., Isakov, O., … Vignuzzi, M. (2014). Emergence and Transmission of Arbovirus Evolutionary Intermediates with Epidemic Potential. Cell Host & Microbe, 15(6), 706-716. doi:10.1016/j.chom.2014.05.008Remold, S. K., Rambaut, A., & Turner, P. E. (2008). Evolutionary Genomics of Host Adaptation in Vesicular Stomatitis Virus. Molecular Biology and Evolution, 25(6), 1138-1147. doi:10.1093/molbev/msn059Foll, M., Poh, Y.-P., Renzette, N., Ferrer-Admetlla, A., Bank, C., Shim, H., … Jensen, J. D. (2014). Influenza Virus Drug Resistance: A Time-Sampled Population Genetics Perspective. PLoS Genetics, 10(2), e1004185. doi:10.1371/journal.pgen.1004185Bedhomme, S., Lafforgue, G., & Elena, S. F. (2011). Multihost Experimental Evolution of a Plant RNA Virus Reveals Local Adaptation and Host-Specific Mutations. Molecular Biology and Evolution, 29(5), 1481-1492. doi:10.1093/molbev/msr314Hillung, J., Cuevas, J. M., Valverde, S., & Elena, S. F. (2014). EXPERIMENTAL EVOLUTION OF AN EMERGING PLANT VIRUS IN HOST GENOTYPES THAT DIFFER IN THEIR SUSCEPTIBILITY TO INFECTION. Evolution, 68(9), 2467-2480. doi:10.1111/evo.12458Acevedo, A., Brodsky, L., & Andino, R. (2013). Mutational and fitness landscapes of an RNA virus revealed through population sequencing. Nature, 505(7485), 686-690. doi:10.1038/nature12861Foll, M., Shim, H., & Jensen, J. D. (2014). WFABC: a Wright-Fisher ABC-based approach for inferring effective population sizes and selection coefficients from time-sampled data. Molecular Ecology Resources, 15(1), 87-98. doi:10.1111/1755-0998.12280Bordería, A. V., Isakov, O., Moratorio, G., Henningsson, R., Agüera-González, S., Organtini, L., … Vignuzzi, M. (2015). Group Selection and Contribution of Minority Variants during Virus Adaptation Determines Virus Fitness and Phenotype. PLOS Pathogens, 11(5), e1004838. doi:10.1371/journal.ppat.1004838Kessinger, T. A., Perelson, A. S., & Neher, R. A. (2013). Inferring HIV Escape Rates from Multi-Locus Genotype Data. Frontiers in Immunology, 4. doi:10.3389/fimmu.2013.00252SCHOLTHOF, K.-B. G., ADKINS, S., CZOSNEK, H., PALUKAITIS, P., JACQUOT, E., HOHN, T., … FOSTER, G. D. (2011). Top 10 plant viruses in molecular plant pathology. Molecular Plant Pathology, 12(9), 938-954. doi:10.1111/j.1364-3703.2011.00752.xKarasev, A. V., & Gray, S. M. (2013). Continuous and Emerging Challenges of Potato virus Y in Potato. Annual Review of Phytopathology, 51(1), 571-586. doi:10.1146/annurev-phyto-082712-102332Kogovšek, P., Pompe-Novak, M., Baebler, Š., Rotter, A., Gow, L., Gruden, K., … Ravnikar, M. (2010). Aggressive and mild Potato virus Y isolates trigger different specific responses in susceptible potato plants. Plant Pathology, 59(6), 1121-1132. doi:10.1111/j.1365-3059.2010.02340.xBAEBLER, Š., KREČIČ-STRES, H., ROTTER, A., KOGOVŠEK, P., CANKAR, K., KOK, E. J., … RAVNIKAR, M. (2009). PVYNTNelicits a diverse gene expression response in different potato genotypes in the first 12 h after inoculation. Molecular Plant Pathology, 10(2), 263-275. doi:10.1111/j.1364-3703.2008.00530.xStare, T., Ramšak, Ž., Blejec, A., Stare, K., Turnšek, N., Weckwerth, W., … Gruden, K. (2015). Bimodal dynamics of primary metabolism-related responses in tolerant potato-Potato virus Y interaction. BMC Genomics, 16(1). doi:10.1186/s12864-015-1925-2Kogovšek, P., Pompe-Novak, M., Petek, M., Fragner, L., Weckwerth, W., & Gruden, K. (2016). Primary Metabolism, Phenylpropanoids and Antioxidant Pathways Are Regulated in Potato as a Response to Potato virus Y Infection. PLOS ONE, 11(1), e0146135. doi:10.1371/journal.pone.0146135Baebler, Š., Stare, K., Kovač, M., Blejec, A., Prezelj, N., Stare, T., … Gruden, K. (2011). Dynamics of Responses in Compatible Potato - Potato virus Y Interaction Are Modulated by Salicylic Acid. PLoS ONE, 6(12), e29009. doi:10.1371/journal.pone.0029009Baebler, Š., Witek, K., Petek, M., Stare, K., Tušek-Žnidarič, M., Pompe-Novak, M., … Hennig, J. (2014). Salicylic acid is an indispensable component of the Ny-1 resistance-gene-mediated response against Potato virus Y infection in potato. Journal of Experimental Botany, 65(4), 1095-1109. doi:10.1093/jxb/ert447Singh, D. P., Moore, C. A., Gilliland, A., & Carr, J. P. (2004). Activation of multiple antiviral defence mechanisms by salicylic acid. Molecular Plant Pathology, 5(1), 57-63. doi:10.1111/j.1364-3703.2004.00203.xKutnjak, D., Rupar, M., Gutierrez-Aguirre, I., Curk, T., Kreuze, J. F., & Ravnikar, M. (2015). Deep Sequencing of Virus-Derived Small Interfering RNAs and RNA from Viral Particles Shows Highly Similar Mutational Landscapes of a Plant Virus Population. Journal of Virology, 89(9), 4760-4769. doi:10.1128/jvi.03685-14Zagordi, O., Bhattacharya, A., Eriksson, N., & Beerenwinkel, N. (2011). ShoRAH: estimating the genetic diversity of a mixed sample from next-generation sequencing data. BMC Bioinformatics, 12(1). doi:10.1186/1471-2105-12-119Prosperi, M. C. F., & Salemi, M. (2011). QuRe: software for viral quasispecies reconstruction from next-generation sequencing data. Bioinformatics, 28(1), 132-133. doi:10.1093/bioinformatics/btr627Prabhakaran, S., Rey, M., Zagordi, O., Beerenwinkel, N., & Roth, V. (2014). HIV Haplotype Inference Using a Propagating Dirichlet Process Mixture Model. IEEE/ACM Transactions on Computational Biology and Bioinformatics, 11(1), 182-191. doi:10.1109/tcbb.2013.145Dynan, W., Fox, K., & Stoddard, B. (2013). Editorial: NAR Surveys the Past, Present and Future of Restriction Endonucleases. Nucleic Acids Research, 42(1), 1-2. doi:10.1093/nar/gkt1324Töpfer, A., Marschall, T., Bull, R. A., Luciani, F., Schönhuth, A., & Beerenwinkel, N. (2014). Viral Quasispecies Assembly via Maximal Clique Enumeration. PLoS Computational Biology, 10(3), e1003515. doi:10.1371/journal.pcbi.1003515Schirmer, M., Sloan, W. T., & Quince, C. (2012). Benchmarking of viral haplotype reconstruction programmes: an overview of the capacities and limitations of currently available programmes. Briefings in Bioinformatics, 15(3), 431-442. doi:10.1093/bib/bbs081Lang, G. I., Rice, D. P., Hickman, M. J., Sodergren, E., Weinstock, G. M., Botstein, D., & Desai, M. M. (2013). Pervasive genetic hitchhiking and clonal interference in forty evolving yeast populations. Nature, 500(7464), 571-574. doi:10.1038/nature12344Zwart, M. P., Daròs, J.-A., & Elena, S. F. (2012). Effects of Potyvirus Effective Population Size in Inoculated Leaves on Viral Accumulation and the Onset of Symptoms. Journal of Virology, 86(18), 9737-9747. doi:10.1128/jvi.00909-12Ruiz-Jarabo, C. M., Arias, A., Baranowski, E., Escarmís, C., & Domingo, E. (2000). Memory in Viral Quasispecies. Journal of Virology, 74(8), 3543-3547. doi:10.1128/jvi.74.8.3543-3547.2000Pruss, G. J., Lawrence, C. B., Bass, T., Li, Q. Q., Bowman, L. H., & Vance, V. (2004). The potyviral suppressor of RNA silencing confers enhanced resistance to multiple pathogens. Virology, 320(1), 107-120. doi:10.1016/j.virol.2003.11.027Alamillo, J. M., Saénz, P., & García, J. A. (2006). Salicylic acid-mediated and RNA-silencing defense mechanisms cooperate in the restriction of systemic spread of plum pox virus in tobacco. The Plant Journal, 48(2), 217-227. doi:10.1111/j.1365-313x.2006.02861.xYu, D., Fan, B., MacFarlane, S. A., & Chen, Z. (2003). Analysis of the Involvement of an Inducible Arabidopsis RNA-Dependent RNA Polymerase in Antiviral Defense. Molecular Plant-Microbe Interactions®, 16(3), 206-216. doi:10.1094/mpmi.2003.16.3.206Miyashita, S., Ishibashi, K., Kishino, H., & Ishikawa, M. (2015). Viruses Roll the Dice: The Stochastic Behavior of Viral Genome Molecules Accelerates Viral Adaptation at the Cell and Tissue Levels. PLOS Biology, 13(3), e1002094. doi:10.1371/journal.pbio.1002094Kogovšek, P., Gow, L., Pompe-Novak, M., Gruden, K., Foster, G. D., Boonham, N., & Ravnikar, M. (2008). Single-step RT real-time PCR for sensitive detection and discrimination of Potato virus Y isolates. Journal of Virological Methods, 149(1), 1-11. doi:10.1016/j.jviromet.2008.01.025Weller, S. A., Elphinstone, J. G., Smith, N. C., Boonham, N., & Stead, D. E. (2000). Detection of Ralstonia solanacearumStrains with a Quantitative, Multiplex, Real-Time, Fluorogenic PCR (TaqMan) Assay. Applied and Environmental Microbiology, 66(7), 2853-2858. doi:10.1128/aem.66.7.2853-2858.2000Gutiérrez-Aguirre, I., Rački, N., Dreo, T., & Ravnikar, M. (2015). Droplet Digital PCR for Absolute Quantification of Pathogens. Methods in Molecular Biology, 331-347. doi:10.1007/978-1-4939-2620-6_24Rupar, M., Faurez, F., Tribodet, M., Gutiérrez-Aguirre, I., Delaunay, A., Glais, L., … Ravnikar, M. (2015). Fluorescently Tagged Potato virus Y: A Versatile Tool for Functional Analysis of Plant-Virus Interactions. Molecular Plant-Microbe Interactions®, 28(7), 739-750. doi:10.1094/mpmi-07-14-0218-taLi, H., & Durbin, R. (2009). Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics, 25(14), 1754-1760. doi:10.1093/bioinformatics/btp324Li, H., Handsaker, B., Wysoker, A., Fennell, T., Ruan, J., … Homer, N. (2009). The Sequence Alignment/Map format and SAMtools. Bioinformatics, 25(16), 2078-2079. doi:10.1093/bioinformatics/btp352Nelson, C. W., Moncla, L. H., & Hughes, A. L. (2015). SNPGenie: estimating evolutionary parameters to detect natural selection using pooled next-generation sequencing data: Table 1. Bioinformatics, btv449. doi:10.1093/bioinformatics/btv449Suzuki R Shimodaira H . 2015. pvclust: hierarchical clustering with P values via multiscale bootstrap resampling. R package version 2.0-0. https://cran.r-project.org/web/packages/pvclust/

In vivo continuous directed evolution

The development and application of methods for the laboratory evolution of biomolecules has rapidly progressed over the last few decades. Advancements in continuous microbe culturing and selection design have facilitated the development of new technologies that enable the continuous directed evolution of proteins and nucleic acids. These technologies have the potential to support the extremely rapid evolution of biomolecules with tailor-made functional properties. Continuous evolution methods must support all of the key steps of laboratory evolution—translation of genes into gene products, selection or screening, replication of genes encoding the most fit gene products, and mutation of surviving genes—in a self-sustaining manner that requires little or no researcher intervention. Continuous laboratory evolution has been historically used to study problems including antibiotic resistance, organismal adaptation, phylogenetic reconstruction, and host-pathogen interactions, with more recent applications focusing on the rapid generation of proteins and nucleic acids with useful, tailor-made properties. The advent of increasingly general methods for continuous directed evolution should enable researchers to address increasingly complex questions and to access biomolecules with more novel or even unprecedented properties.Chemistry and Chemical Biolog

Do we know enough about the effect of low-dose computed tomography screening for lung cancer on mortality to act? An updated systematic review, meta-analysis and network meta-analysis of randomised controlled trials 2017 to 2021

Background For people at high risk of lung cancer, low-dose computed tomography (LDCT) is proposed as a method to reduce mortality. Methods Our objective was to estimate the effect of LDCT lung cancer screening on mortality in high-risk populations. A systematic review of randomised controlled trials (RCTs) comparing LDCT screening programmes with usual care (no screening) or other imaging screening programme (such as chest X-ray (CXR)) was conducted. RCTs of CXR screening were additionally included in the network meta-analyses. Bibliographic sources including MEDLINE, Embase, Web of Science and the Cochrane Library were searched to January 2017, and then further extended to November 2021. All key review steps were done by two persons. Quality assessment used the Cochrane Risk of Bias tool. Meta-analyses were performed. Results Nine RCTs, with up to 12.3 years of follow-up from randomisation, were included in the direct meta-analysis, which showed that LDCT screening was associated with a statistically significant decrease in lung cancer mortality (pooled relative risk (RR) 0.86, 95% confidence interval [CI] 0.77 to 0.96). There was a statistically non-significant decrease in all-cause mortality (pooled RR 0.98, 95% CI 0.95 to 1.01). The statistical heterogeneity for both outcomes was minimal. Network meta-analysis including the nine RCTs in the direct meta-analysis plus two further RCTs comparing CXR with usual care confirmed the size of the effect of LDCT on lung cancer mortality and that this was very similar irrespective of whether the comparator was usual care or CXR screening. Conclusions LDCT screening is effective in reducing lung cancer mortality in high-risk populations. The uncertainty of its effect on lung cancer mortality observed in 2018 has been much reduced with new trial results and updates to existing trials, emphasising the importance of updating systematic reviews. Although there are still a number of RCTs unreported or in progress, we predict that further evolution of summary mortality estimates is unlikely. The focus for debate now moves to resolving uncertainty about the cost-effectiveness of LDCT screening taking into account the balance between benefits and harms which occur in all screening programmes

Replicability and Recurrence in the Experimental Evolution of a Group I Ribozyme

In order to explore the variety of possible responses available to a ribozyme population evolving a novel phenotype, five Tetrahymena thermophila group I intron ribozyme pools were evolved in parallel for cleavage of a DNA oligonucleotide. These ribozyme populations were propagated under identical conditions and characterized when they reached apparent phenotypic plateaus; the populations that reached the highest plateau showed a near 100-fold improvement in DNA cleavage activity. A detailed characterization of the evolved response in these populations reveals at least two distinct phenotypic trajectories emerging as a result of the imposed selection. Not only do these distinct solutions exhibit differential DNA cleavage activity, but they also exhibit a very different correlation with a related, but unselected, phenotype: RNA cleavage activity. In turn, each of these trajectories is underwritten by differing genotypic profiles. This study underscores the complex network of possible trajectories through sequence space available to an evolving population and uncovers the diversity of solutions that result when the process of experimental evolution is repeated multiple times in a simple, engineered system

The Lumberjack, April 22, 1987

The student newspaper of Humboldt State University.https://digitalcommons.humboldt.edu/studentnewspaper/2119/thumbnail.jp

Platelets stimulate fibroblast-mediated contraction of collagen gels

BACKGROUND: Platelets are thought to play a role in a variety of inflammatory conditions in the lung, some of which may lead to fibrosis. In the current study we tested the hypothesis that whole platelets and platelet lysate can mediate remodelling of extracellular matrix in vitro by affecting fibroblast-mediated contraction of a collagen gel. We also sought to determine to what extent platelet-derived growth factor (PDGF) and transforming growth factor-β (TGF-β) contribute to this effect. METHODS: Washed platelets, isolated from healthy blood donors, and platelet lysate (freezing and thawing), were cast together with human lung fibroblasts in three-dimensional collagen gels. The gels were then released and cultured for four days. PDGF and TGF-β(1 )concentrations were measured in culture supernatants by ELISA. RESULTS: Both platelets and platelet lysate augmented fibroblast-mediated gel contraction in a time and concentration dependent manner (19.9% ± 0.1 (mean ± SEM) of initial area vs. 48.0% ± 0.4 at 48 hours; P < 0.001 and 41.5% ± 0.6 vs. 60.6% ± 0.3 at 48 hours; P < 0.001, respectively). Fixed platelets had no effect in the system. Both TGF-β(1 )and PDGF-AA/AB were released in co-culture. PDGF-AA/AB had a maximum release at 24 hours whereas TGF-β(1 )release increased with longer culture periods. Neutralising antibodies to these mediators partially inhibited platelet-induced gel contraction. CONCLUSION: We conclude that platelets may promote remodelling of extracellular matrix in vitro and that PDGF and TGF-β partially mediate this effect, also indicating a role for other mediators. The findings may be an important mechanism in regulating repair processes after injury