336 research outputs found

    Identifying Vessel Branching from Fluid Stresses on Microscopic Robots

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    Objects moving in fluids experience patterns of stress on their surfaces determined by the geometry of nearby boundaries. Flows at low Reynolds number, as occur in microscopic vessels such as capillaries in biological tissues, have relatively simple relations between stresses and nearby vessel geometry. Using these relations, this paper shows how a microscopic robot moving with such flows can use changes in stress on its surface to identify when it encounters vessel branches.Comment: Version 2 has minor clarification

    Satellite-based model detection of recent climate-driven changes in northern high-latitude vegetation productivity

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    We applied a satellite remote sensing based production efficiency model (PEM) using an integrated AVHRR and MODIS FPAR/LAI time series with a regionally corrected NCEP/NCAR reanalysis daily surface meteorology and NASA/GEWEX Surface Radiation Budget shortwave solar radiation inputs to assess annual terrestrial net primary productivity (NPP) for the pan-Arctic basin and Alaska from 1983 to 2005. Our results show that low temperature constraints on Boreal-Arctic NPP are decreasing by 0.43% per year (P \u3c 0.001), whereas a positive trend in vegetation moisture constraints of 0.49% per year (P = 0.04) are offsetting the potential benefits of longer growing seasons and contributing to recent disturbances in NPP. The PEM simulations of NPP seasonality, annual anomalies and trends are similar to stand inventory network measurements of boreal aspen stem growth (r = 0.56; P = 0.007) and atmospheric CO2 measurement based estimates of the timing of growing season onset (r = 0.78; P \u3c 0.001). Our results indicate that summer drought led to marked NPP decreases in much of the boreal forest region after the late-1990s. However, seasonal low temperatures are still a dominant limitation on regional NPP. Despite recent drought events, mean annual NPP for the pan-Arctic region showed a positive growth trend of 0.34% per year (20.27 TgC/a; P = 0.002) from 1983 to 2005. Drought induced NPP decreases may become more frequent and widespread as regional ecosystems adjust to a warmer, drier atmosphere, though the occurrence and severity of drought events will depend on future patterns of plant-available moisture

    Reliability and Concurrent Validity of Global Physical Activity Questionnaire (GPAQ): A Systematic Review

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    This study aimed to systematically review previous studies on the reliability and concurrent validity of the Global Physical Activity Questionnaire (GPAQ). A systematic literature search was conducted (n = 26) using the online EBSCOHost databases, PubMed, Web of Science, and Google Scholar up to September 2019. A previously developed coding sheet was used to collect the data. The Modified Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies was employed to assess risk of bias and study quality. It was found that GPAQ was primarily revalidated in adult populations in Asian and European countries. The sample size ranged from 43 to 2657 with a wide age range (i.e., 15–79 years old). Di erent populations yielded inconsistent results concerning the reliability and validity of the GPAQ. Short term (i.e., one- to two-week interval) and long-term (i.e., two- to three-month apart) test–retest reliability was good to very good. The concurrent validity using accelerometers, pedometers, and physical activity (PA) log was poor to fair. The GPAQ data and accelerometer/pedometer/PA log data were not compared using the same measurements in some validation studies. Studies with more rigorous research designs are needed before any conclusions concerning the concurrent validity of GPAQ can be reached

    Upregulation of pirin expression by chronic cigarette smoking is associated with bronchial epithelial cell apoptosis

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    BACKGROUND: Cigarette smoke disrupts the protective barrier established by the airway epithelium through direct damage to the epithelial cells, leading to cell death. Since the morphology of the airway epithelium of smokers does not typically demonstrate necrosis, the most likely mechanism for epithelial cell death in response to cigarette smoke is apoptosis. We hypothesized that cigarette smoke directly up-regulates expression of apoptotic genes, which could play a role in airway epithelial apoptosis. METHODS: Microarray analysis of airway epithelium obtained by bronchoscopy on matched cohorts of 13 phenotypically normal smokers and 9 non-smokers was used to identify specific genes modulated by smoking that were associated with apoptosis. Among the up-regulated apoptotic genes was pirin (3.1-fold, p < 0.002), an iron-binding nuclear protein and transcription cofactor. In vitro studies using human bronchial cells exposed to cigarette smoke extract (CSE) and an adenovirus vector encoding the pirin cDNA (AdPirin) were performed to test the direct effect of cigarette smoke on pirin expression and the effect of pirin expression on apoptosis. RESULTS: Quantitative TaqMan RT-PCR confirmed a 2-fold increase in pirin expression in the airway epithelium of smokers compared to non-smokers (p < 0.02). CSE applied to primary human bronchial epithelial cell cultures demonstrated that pirin mRNA levels increase in a time-and concentration-dependent manner (p < 0.03, all conditions compared to controls). Overexpression of pirin, using the vector AdPirin, in human bronchial epithelial cells was associated with an increase in the number of apoptotic cells assessed by both TUNEL assay (5-fold, p < 0.01) and ELISA for cytoplasmic nucleosomes (19.3-fold, p < 0.01) compared to control adenovirus vector. CONCLUSION: These observations suggest that up-regulation of pirin may represent one mechanism by which cigarette smoke induces apoptosis in the airway epithelium, an observation that has implications for the pathogenesis of cigarette smoke-induced diseases

    Lung eQTLs to Help Reveal the Molecular Underpinnings of Asthma

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    Genome-wide association studies (GWAS) have identified loci reproducibly associated with pulmonary diseases; however, the molecular mechanism underlying these associations are largely unknown. The objectives of this study were to discover genetic variants affecting gene expression in human lung tissue, to refine susceptibility loci for asthma identified in GWAS studies, and to use the genetics of gene expression and network analyses to find key molecular drivers of asthma. We performed a genome-wide search for expression quantitative trait loci (eQTL) in 1,111 human lung samples. The lung eQTL dataset was then used to inform asthma genetic studies reported in the literature. The top ranked lung eQTLs were integrated with the GWAS on asthma reported by the GABRIEL consortium to generate a Bayesian gene expression network for discovery of novel molecular pathways underpinning asthma. We detected 17,178 cis- and 593 trans- lung eQTLs, which can be used to explore the functional consequences of loci associated with lung diseases and traits. Some strong eQTLs are also asthma susceptibility loci. For example, rs3859192 on chr17q21 is robustly associated with the mRNA levels of GSDMA (P = 3.55 × 10(-151)). The genetic-gene expression network identified the SOCS3 pathway as one of the key drivers of asthma. The eQTLs and gene networks identified in this study are powerful tools for elucidating the causal mechanisms underlying pulmonary disease. This data resource offers much-needed support to pinpoint the causal genes and characterize the molecular function of gene variants associated with lung diseases

    Age differences in physiological responses to self-paced and incremental V˙O2max\dot V O_{2max} testing

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    Purpose: A self-paced maximal exercise protocol has demonstrated higher V˙O2max\dot V O_{2max} values when compared against traditional tests. The aim was to compare physiological responses to this self-paced V˙O2max\dot V O_{2max} protocol (SPV) in comparison to a traditional ramp V˙O2max\dot V O_{2max} (RAMP) protocol in young (18–30 years) and old (50–75 years) participants. Methods: Forty-four participants (22 young; 22 old) completed both protocols in a randomised, counter-balanced, crossover design. The SPV included 5 × 2 min stages, participants were able to self-regulate their power output (PO) by using incremental ‘clamps’ in ratings of perceived exertion. The RAMP consisted of either 15 or 20 W min1^{−1}. Results: Expired gases, cardiac output (Q), stroke volume (SV), muscular deoxyhaemoglobin (deoxyHb) and electromyography (EMG) at the vastus lateralis were recorded throughout. Results demonstrated significantly higher V˙O2max\dot V O_{2max} in the SPV (49.68 ± 10.26 ml kg1^{−1} min1^{−1}) vs. the RAMP (47.70 ± 9.98 ml kg1^{−1} min1^{−1}) in the young, but not in the old group (>0.05). Q and SV were significantly higher in the SPV vs. the RAMP in the young (0.05). No differences seen in deoxyHb and EMG for either age groups (>0.05). Peak PO was significantly higher in the SPV vs. the RAMP in both age groups (<0.05). Conclusion: Findings demonstrate that the SPV produces higher V˙O2max\dot V O_{2max}, peak Q and SV values in the young group. However, older participants achieved similar V˙O2max\dot V O_{2max} values in both protocols, mostly likely due to age-related differences in cardiovascular responses to incremental exercise, despite them achieving a higher physiological workload in the SPV

    A portable RNA sequence whose recognition by a synthetic antibody facilitates structural determination

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    RNA crystallization and phasing represent major bottlenecks in RNA structure determination. Seeking to exploit antibody fragments as RNA crystallization chaperones, we have used an arginine-enriched synthetic Fab library displayed on phage to obtain Fabs against the class I ligase ribozyme. We solved the structure of a Fab–ligase complex at 3.1-Å resolution using molecular replacement with Fab coordinates, confirming the ribozyme architecture and revealing the chaperone's role in RNA recognition and crystal contacts. The epitope resides in the GAAACAC sequence that caps the P5 helix, and this sequence retains high-affinity Fab binding within the context of other structured RNAs. This portable epitope provides a new RNA crystallization chaperone system that easily can be screened in parallel to the U1A RNA-binding protein, with the advantages of a smaller loop and Fabs′ high molecular weight, large surface area and phasing power.National Institutes of Health (U.S.) (GM61835

    Phylogeographical analysis of the dominant multidrug-resistant H58 clade of Salmonella Typhi identifies inter- and intracontinental transmission events.

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    The emergence of multidrug-resistant (MDR) typhoid is a major global health threat affecting many countries where the disease is endemic. Here whole-genome sequence analysis of 1,832 Salmonella enterica serovar Typhi (S. Typhi) identifies a single dominant MDR lineage, H58, that has emerged and spread throughout Asia and Africa over the last 30 years. Our analysis identifies numerous transmissions of H58, including multiple transfers from Asia to Africa and an ongoing, unrecognized MDR epidemic within Africa itself. Notably, our analysis indicates that H58 lineages are displacing antibiotic-sensitive isolates, transforming the global population structure of this pathogen. H58 isolates can harbor a complex MDR element residing either on transmissible IncHI1 plasmids or within multiple chromosomal integration sites. We also identify new mutations that define the H58 lineage. This phylogeographical analysis provides a framework to facilitate global management of MDR typhoid and is applicable to similar MDR lineages emerging in other bacterial species
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