3,652 research outputs found
Airborne Measurements of Gravity Wave Breaking at the Tropopause
2000 FLORIDA AVE NW, WASHINGTON, DC,
2000
Persistent Vascular Collagen Accumulation Alters Hemodynamic Recovery from Chronic Hypoxia
Pulmonary arterial hypertension (PAH) is caused by narrowing and stiffening of the pulmonary arteries that increase pulmonary vascular impedance (PVZ). In particular, small arteries narrow and large arteries stiffen. Large pulmonary artery (PA) stiffness is the best current predictor of mortality from PAH. We have previously shown that collagen accumulation leads to extralobar PA stiffening at high strain (Ooi et al. 2010). We hypothesized that collagen accumulation would increase PVZ, including total pulmonary vascular resistance (Z0), characteristic impedance (ZC), pulse wave velocity (PWV) and index of global wave reflections (Pb/Pf), which contribute to increased right ventricular afterload. We tested this hypothesis by exposing mice unable to degrade type I collagen (Col1a1R/R) to 21 days of hypoxia (hypoxia), some of which were allowed to recover for 42 days (recovery). Littermate wild-type mice (Col1a1+/+) were used as controls. In response to hypoxia, mean PA pressure (mPAP) increased in both mouse genotypes with no changes in cardiac output (CO) or PA inner diameter (ID); as a consequence, Z0 (mPAP/CO) increased by ∼100% in both genotypes (pZC, PWV and Pb/Pf did not change. However, with recovery, ZC and PWV decreased in the Col1a1+/+ mice and remained unchanged in the Col1a1R/R mice. Z0 decreased with recovery in both genotypes. Microcomputed tomography measurements of large PAs did not show evidence of stiffness changes as a function of hypoxia exposure or genotype. We conclude that hypoxia-induced PA collagen accumulation does not affect the pulsatile components of pulmonary hemodynamics but that excessive collagen accumulation does prevent normal hemodynamic recovery, which may have important consequences for right ventricular function
A range inventory and condition survey of part of the Western Australian Nullarbor Plain, 1974
ATP prevents Woronin bodies from sealing septal pores in unwounded cells of the fungus Zymoseptoria tritici
This is the author accepted manuscript. The final version is available from Wiley via the DOI in this record.Septa of filamentous ascomycetes are perforated by septal pores that allow communication between individual hyphal compartments. Upon injury, septal pores are plugged rapidly by Woronin bodies (WBs), thereby preventing extensive cytoplasmic bleeding. The mechanism by which WBs translocate into the pore is not known, but it has been suggested that wound-induced cytoplasmic bleeding "flushes" WBs into the septal opening. Alternatively, contraction of septum-associated tethering proteins may pull WBs into the septal pore. Here, we investigate Woronin body dynamics in the wheat pathogen Zymoseptoria tritici. Ultrastructural studies showed that 3.4 ± 0.2 WBs reside on each side of a septum and that single WBs of 128.5 ± 3.6 nm in diameter seal the septal pore (41±1.5 nm). Live cell imaging of green-fluorescent ZtHex1, a major protein in WBs, and the integral plasma membrane protein ZtSso1 confirms WB translocation into the septal pore. This was associated with the occasional formation of a plasma membrane "balloon", extruding into the dead cell, suggesting that the plasma membrane rapidly seals the wounded septal pore wound. Minor amounts of fluorescent ZtHex1-eGFP appeared associated with the "ballooning" plasma membrane, indicating that cytoplasmic ZtHex1-eGFP is recruited to the extending plasma membrane. Surprisingly, in ~15% of all cases, WBs moved from the ruptured cell into the septal pore. This translocation against the cytoplasmic flow suggests that an active mechanism drives in WB plugging. Indeed, treatment of unwounded and intact cells with the respiration inhibitor CCCP induced WB translocation into the pores. Moreover, CCCP treatment recruited cytoplasmic ZtHex1-eGFP to the lateral plasma membrane of the cells. Thus, keeping the WBs out of the septal pores, in Z. tritici, is an ATP-dependent process
Challenges to evaluation of multilingual geographic information retrieval in GeoCLEF
This is the third year of the evaluation of
geographic information retrieval (GeoCLEF)
within the Cross-Language Evaluation Forum
(CLEF). GeoCLEF 2006 presented topics and
documents in four languages (English,
German, Portuguese and Spanish). After two
years of evaluation we are beginning to
understand the challenges to both Geographic
Information Retrieval from text and of
evaluation of the results of geographic
information retrieval. This poster enumerates
some of these challenges to evaluation and
comments on the limitations encountered in the
first two evaluations
Recommended from our members
Serving GODAE Data and Products to the Ocean Community
The Global Ocean Data Assimilation Experiment (GODAE [http://
www.godae.org]) has spanned a decade of rapid technological development. The ever-increasing volume and diversity of oceanographic data produced by in situ instruments, remote-sensing platforms, and computer simulations have driven
the development of a number of innovative technologies that are essential for connecting scientists with the data that they need. This paper gives an overview of the technologies that have been developed and applied in the course of GODAE, which now provide users of oceanographic data with the capability to discover, evaluate, visualize, download, and analyze data from all over the world. The key to this
capability is the ability to reduce the inherent complexity of oceanographic data by providing a consistent, harmonized view of the various data products. The challenges of data serving have been addressed over the last 10 years through the cooperative skills and energies of many individuals
Lenvatinib Targets PDGFR-β Pericytes and Inhibits Synergy with Thyroid Carcinoma Cells: Novel Translational Insights
Context: Pericyte populations abundantly express tyrosine kinases (eg, platelet-derived growth factor receptor-β [PDGFR-β]) and impact therapeutic response. Lenvatinib is a clinically available tyrosine kinase inhibitor that also targets PDGFR-β. Duration of therapeutic response was shorter in patients with greater disease burden and metastasis. Patients may develop drug resistance and tumor progression. Objectives: Develop a gene signature of pericyte abundance to assess with tumor aggressiveness and determine both the response of thyroid-derived pericytes to lenvatinib and their synergies with thyroid carcinoma-derived cells. Design: Using a new gene signature, we estimated the relative abundance of pericytes in papillary thyroid carcinoma (PTC) and normal thyroid (NT) TCGA samples. We also cocultured CD90+;PAX8- thyroid-derived pericytes and BRAFWT/V600E-PTC-derived cells to determine effects of coculture on paracrine communications and lenvatinib response. Results: Pericyte abundance is significantly higher in BRAFV600E-PTC with hTERT mutations and copy number alterations compared with NT or BRAFWT-PTC samples, even when data are corrected for clinical-pathologic confounders. We have identified upregulated pathways important for tumor survival, immunomodulation, RNA transcription, cell-cycle regulation, and cholesterol metabolism. Pericyte growth is significantly increased by platelet-derived growth factor-BB, which activates phospho(p)-PDGFR-β, pERK1/2, and pAKT. Lenvatinib strongly inhibits pericyte viability by down-regulating MAPK, pAKT, and p-p70S6-kinase downstream PDGFR-β. Critically, lenvatinib significantly induces higher BRAFWT/V600E-PTC cell death when cocultured with pericytes, as a result of pericyte targeting via PDGFR-β. Conclusions: This is the first thyroid-specific model of lenvatinib therapeutic efficacy against pericyte viability, which disadvantages BRAFWT/V600E-PTC growth. Assessing pericyte abundance in patients with PTC could be essential to selection rationales for appropriate targeted therapy with lenvatinib
Host specificity and species colouration mediate the regional decline of nocturnal moths in central European forests
The high diversity of insects has limited the volume of long-term community data with a high taxonomic resolution and considerable geographic replications, especially in forests. Therefore, trends and causes of changes are poorly understood. Here we analyse trends in species richness, abundance and biomass of nocturnal macro moths in three quantitative data sets collected over four decades in forests in southern Germany. Two local data sets, one from coppiced oak forests and one from high oak forests included 125K and 48K specimens from 559 and 532 species, respectively. A third regional data set, representing all forest types in the temperate zone of central Europe comprised 735K specimens from 848 species. Generalized additive mixed models revealed temporal declines in species richness (−38%), abundance (−53%) and biomass (−57%) at the regional scale. These were more pronounced in plant host specialists and in dark coloured species. In contrast, the local coppiced oak forests showed an increase, in species richness (+62%), while the high oak forests showed no clear trends. Left and right censoring as well as cross validation confirmed the robustness of the analyses, which led to four conclusions. First, the decline in insects appears in hyper diverse insect groups in forests and affects species richness, abundance and biomass. Second, the pronounced decline in host specialists suggests habitat loss as an important driver of the observed decline. Third, the more severe decline in dark species might be an indication of global warming as a potential driver. Fourth, the trends in coppiced oak forests indicate that maintaining complex and diverse forest ecosystems through active management may be a promising conservation strategy in order to counteract negative trends in biodiversity, alongside rewilding approaches
Cardiac Restricted Overexpression of Caveolin-3 Prevents Arrhythmia, Ventricular Hypertrophy and Cardiac Dysfunction in Aging Mice
- …