Aging exacerbates acute lung injury-induced changes of the air-blood barrier, lung function, and inflammation in the mouse DOI Open Access

Katharina Maria Kling,

Elena López-Rodríguez, Christiane Pfarrer

et al.

AJP Lung Cellular and Molecular Physiology, Journal Year: 2016, Volume and Issue: 312(1), P. L1 - L12

Published: Nov. 5, 2016

Acute lung injury (ALI) is characterized by hypoxemia, enhanced permeability of the air-blood barrier, and pulmonary edema. Particularly in elderly, ALI associated with increased morbidity mortality. The reasons for this, however, are poorly understood. We hypothesized that age-related changes structure, function, inflammation lead to a worse prognosis ALI. was induced young (10 wk old) old (18 mo male C57BL/6 mice intranasal application 2.5 mg lipopolysaccharide (LPS)/kg body wt or saline (control mice). After 24 h, function assessed, lungs were either processed stereological inflammatory analysis, such as bronchoalveolar lavage fluid (BALF) cytometry qPCR. Both developed severe signs ALI, including alveolar septal edema BALF cells. However, pathology more pronounced compared nearly sixfold higher protein concentration, twice number neutrophils, significantly expression neutrophil chemokine Cxcl1, adhesion molecule Icam-1, metalloprotease-9, whereas tight junction occludin decreased. LPS had thicker septa attributable volumes interstitial cells extracellular matrix. Tissue resistance elastance reflected observed at ultrastructural level parenchyma mice. In summary, advanced age greater neutrophilic inflammation, leakier altered which line findings elderly patients.

Language: Английский

Effects of screentime on the health and well-being of children and adolescents: a systematic review of reviews DOI Creative Commons

Neza Stiglic,

Russell Viner

BMJ Open, Journal Year: 2019, Volume and Issue: 9(1), P. e023191 - e023191

Published: Jan. 1, 2019

To systematically examine the evidence of harms and benefits relating to time spent on screens for children young people's (CYP) health well-being, inform policy.Systematic review reviews undertaken answer question 'What is well-being effects screentime in adolescents (CYP)?' Electronic databases were searched systematic February 2018. Eligible reported associations between (screentime; any type) health/well-being outcome CYP. Quality was assessed strength across evaluated.13 identified (1 high quality, 9 medium 3 low quality). 6 addressed body composition; diet/energy intake; 7 mental health; 4 cardiovascular risk; fitness; sleep; 1 pain; asthma. We found moderately strong greater obesity/adiposity higher depressive symptoms; moderate an association energy intake, less healthy diet quality poorer life. There weak with behaviour problems, anxiety, hyperactivity inattention, self-esteem, psychosocial health, metabolic syndrome, cardiorespiratory fitness, cognitive development lower educational attainments poor sleep outcomes. no or insufficient eating disorders suicidal ideation, individual risk factors, asthma prevalence pain. Evidence threshold weak. that small amounts daily screen use not harmful may have some benefits.There levels associated a variety CYP, strongest adiposity, unhealthy diet, symptoms guide policy safe CYP exposure limited.CRD42018089483.

Language: Английский

Citations

916

Obesity-associated exosomal miRNAs modulate glucose and lipid metabolism in mice DOI Open Access
Carlos Castaño, Susana G. Kalko, Anna Novials

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2018, Volume and Issue: 115(48), P. 12158 - 12163

Published: Nov. 14, 2018

Significance The presence of extracellular miRNAs in body fluids has been exploited as a brand-new source biomarkers for different diseases. A fraction those miRNAs, contained vesicles and exosomes, are additionally being revealed novel mediators intercellular communication. Here, we show that systemic injection exosomes transfected with synthetic simulating enriched the plasma obese mice robustly induces glucose intolerance, adipose inflammation, hepatic steatosis lean mice. These results support role exosomal modulation lipid metabolism may help us uncover thus far unexplored pathological mechanisms provide therapeutic targets.

Language: Английский

Citations

347

Sequestration of macroalgal carbon: the elephant in the Blue Carbon room DOI Creative Commons
Dorte Krause‐Jensen, Paul S. Lavery, Óscar Serrano

et al.

Biology Letters, Journal Year: 2018, Volume and Issue: 14(6), P. 20180236 - 20180236

Published: June 1, 2018

Macroalgae form the most extensive and productive benthic marine vegetated habitats globally but their inclusion in Blue Carbon (BC) strategies remains controversial. We review arguments offered to reject or include macroalgae BC framework, identify challenges that have precluded from being incorporated so far. Evidence support significant carbon burial is compelling. The they supply sediment stocks angiosperm already included current assessments, are de facto recognized as important donors of BC. key (i) documenting macroalgal sequestered beyond habitat, (ii) tracing it back source habitats, (iii) showing management actions at habitat lead increased sequestration sink site. These apply equally exported coastal habitats. Because large support, incorporation into accounting an imperative. This requires a paradigm shift procedures well developing methods enable capacity trace donor ocean.

Language: Английский

Citations

297

A Cas9-based toolkit to program gene expression inSaccharomyces cerevisiae DOI Creative Commons

Amanda Reider Apel,

Leo d’Espaux,

Maren Wehrs

et al.

Nucleic Acids Research, Journal Year: 2016, Volume and Issue: 45(1), P. 496 - 508

Published: Oct. 19, 2016

Despite the extensive use of Saccharomyces cerevisiae as a platform for synthetic biology, strain engineering remains slow and laborious. Here, we employ CRISPR/Cas9 technology to build cloning-free toolkit that addresses commonly encountered obstacles in metabolic engineering, including chromosomal integration locus promoter selection, well protein localization solubility. The includes 23 Cas9-sgRNA plasmids, 37 promoters various strengths temporal expression profiles, 10 protein-localization, degradation solubility tags. We facilitated these parts via web-based tool, automates generation DNA fragments integration. Our system builds upon existing gene editing methods thoroughness with which are standardized characterized, types number available ease our methodology can be used perform genetic edits yeast. demonstrated applicability this by optimizing challenging but industrially important enzyme, taxadiene synthase (TXS). This approach enabled us diagnose an issue TXS solubility, resolution yielded 25-fold improvement production.

Language: Английский

Citations

254

Chitinase: diversity, limitations, and trends in engineering for suitable applications DOI Open Access

Ayokunmi Oyeleye,

Yahaya M. Normi

Bioscience Reports, Journal Year: 2018, Volume and Issue: 38(4)

Published: July 24, 2018

Chitinases catalyze the degradation of chitin, a ubiquitous polymer generated from cell walls fungi, shells crustaceans, and cuticles insects. They are gaining increasing attention in medicine, agriculture, food drug industries, environmental management. Their roles chitin for production industrially useful products control fungal pathogens insect pests render them attractive such purposes. However, chitinases have diverse sources, characteristics, mechanisms action that seem to restrain optimization procedures standardization techniques enhanced practical applications complex. Hence, results laboratory trials not usually consistent with real-life applications. With growing field protein engineering, these complexities can be overcome by modifying or redesigning enhance specific features required In this review, variations limit their exploitation biotechnological compiled. Recent attempts engineer improved efficiency also highlighted.

Language: Английский

Citations

201

Independent evolution of baleen whale gigantism linked to Plio-Pleistocene ocean dynamics DOI Creative Commons
Graham J. Slater, Jeremy A. Goldbogen, Nicholas D. Pyenson

et al.

Proceedings of the Royal Society B Biological Sciences, Journal Year: 2017, Volume and Issue: 284(1855), P. 20170546 - 20170546

Published: May 24, 2017

Vertebrates have evolved to gigantic sizes repeatedly over the past 250 Myr, reaching their extreme in today's baleen whales (Mysticeti). Hypotheses for evolution of exceptionally large size mysticetes range from niche partitioning predator avoidance, but there has been no quantitative examination body evolutionary dynamics this clade and it remains unclear when, why or how gigantism evolved. By fitting phylogenetic macroevolutionary models a dataset consisting living extinct species, we show that underwent clade-wide shift mode during Plio-Pleistocene. This transition, Brownian motion-like trended random walk towards larger size, is temporally linked onset seasonally intensified upwelling along coastal ecosystems. High prey densities resulting wind-driven upwelling, rather than abundant resources alone, are primary determinant efficient foraging extant Late Pliocene changes ocean may provided an ecological pathway multiple independent lineages.

Language: Английский

Citations

198

Dry habitats were crucibles of domestication in the evolution of agriculture in ants DOI Creative Commons
Michael G. Branstetter, Ana Ješovnik, Jeffrey Sosa‐Calvo

et al.

Proceedings of the Royal Society B Biological Sciences, Journal Year: 2017, Volume and Issue: 284(1852), P. 20170095 - 20170095

Published: April 12, 2017

The evolution of ant agriculture, as practised by the fungus-farming 'attine' ants, is thought to have arisen in wet rainforests South America about 55-65 Ma. Most subsequent attine agricultural evolution, including domestication event that produced ancestor higher cultivars, likewise hypothesized occurred American rainforests. 'out-of-the-rainforest' hypothesis, while generally accepted, has never been tested a phylogenetic context. It also presents problem for explaining how fungal might occurred, given isolation from free-living populations required. Here, we use phylogenomic data ultra-conserved element (UCE) loci reconstruct evolutionary history reduce topological uncertainty, and identify closest non-fungus-growing relative. Using phylogeny infer systems, habitat preference biogeography. Our results show out-of-the-rainforest hypothesis correct with regard origin agriculture; however, contrary expectation, find transition lower agriculture very likely seasonally dry habitat, inhospitable growth cultivars. We suggest habitats favoured cultivars over time spans necessary occur.

Language: Английский

Citations

181

Emerging roles of mechanical forces in chromatin regulation DOI Creative Commons
Yekaterina A. Miroshnikova, Michele M. Nava, Sara A. Wickström

et al.

Journal of Cell Science, Journal Year: 2017, Volume and Issue: 130(14), P. 2243 - 2250

Published: June 24, 2017

ABSTRACT Cells are constantly subjected to a spectrum of mechanical cues, such as shear stress, compression, differential tissue rigidity and strain, which they adapt by engaging mechanisms mechanotransduction. While the central role cell adhesion receptors in this process is established, it has only recently been appreciated that cues reach far beyond plasma membrane cytoskeleton, directly transmitted nucleus. Furthermore, changes properties perinuclear nuclear lamina chromatin critical for cellular responses adaptation external cues. In respect, dynamic surrounding cytoskeleton modify nucleus, thereby protecting genetic material from damage. The importance mechanism highlighted debilitating diseases, termed laminopathies, result impaired mechanoresistance lamina. What less evident, represents one exciting emerging concepts, itself an active rheological element undergoes upon application force, facilitating adaption force environments. This Review aims highlight these concepts discussing latest literature area proposing integrative model cytoskeletal chromatin-mediated stress.

Language: Английский

Citations

181

Militarization fails to enhance police safety or reduce crime but may harm police reputation DOI Creative Commons
Jonathan Mummolo

Proceedings of the National Academy of Sciences, Journal Year: 2018, Volume and Issue: 115(37), P. 9181 - 9186

Published: Aug. 20, 2018

Significance National debates over heavy-handed police tactics, including so-called “militarized” policing, are often framed as a trade-off between civil liberties and public safety, but the costs benefits of controversial practices remain unclear due to data limitations. Using an array administrative sources original experiments I show that militarized “special weapons tactics” (SWAT) teams more deployed in communities color, and—contrary claims by administrators—provide no detectable terms officer safety or violent crime reduction, on average. However, survey suggest seeing news reports erodes opinion toward law enforcement. Taken together, these findings curtailing policing may be interest both citizens.

Language: Английский

Citations

179

MYC-Driven Small-Cell Lung Cancer is Metabolically Distinct and Vulnerable to Arginine Depletion DOI Open Access

Milind D. Chalishazar,

Sarah J. Wait,

Fang Huang

et al.

Clinical Cancer Research, Journal Year: 2019, Volume and Issue: 25(16), P. 5107 - 5121

Published: June 4, 2019

Small-cell lung cancer (SCLC) has been treated clinically as a homogeneous disease, but recent discoveries suggest that SCLC is heterogeneous. Whether metabolic differences exist among subtypes largely unexplored. In this study, we aimed to determine whether vulnerabilities between can be therapeutically exploited.We performed steady state metabolomics on tumors isolated from distinct genetically engineered mouse models (GEMM) representing the MYC- and MYCL-driven of SCLC. Using genetic pharmacologic approaches, validated our findings in chemo-naïve -resistant human cell lines, multiple GEMMs, four line xenografts, newly derived PDX models.We discover driven by different MYC family members have profiles. MYC-driven preferentially depends arginine-regulated pathways including polyamine biosynthesis mTOR pathway activation. Chemo-resistant cells exhibit increased expression similar liabilities cells. Arginine depletion with pegylated arginine deiminase (ADI-PEG 20) dramatically suppresses tumor growth promotes survival mice specifically tumors, patient-derived xenograft relapsed patient. Finally, ADI-PEG 20 significantly more effective than standard-of-care chemotherapy.These data identify heterogeneity within deprivation subtype-specific therapeutic vulnerability for

Language: Английский

Citations

157