Lung microvascular and arterial endothelial cells differ in their responses to intercellular adhesion molecule-1 ligation

Neutrophil adherence to tumor necrosis factor-α (TNF-α)-treated human pulmonary microvascular endothelial cells (PMECs) induces cytoskeletal changes in endothelial cells that require intercellular adhesion molecule-1 (ICAM-1)-dependent signaling events. This study determined whether similar changes occurred in rat PMECs and whether rat pulmonary arterial endothelial cells (PAECs) responded differently. Neutrophil adherence induced an increase in the formation of F-actin and in the apparent stiffness of TNF-α-treated rat PMECs. These responses, however, were absent in PAECs. To determine the mechanisms underlying these differences, ICAM-1-mediated signaling events were compared. Upregulation of ICAM-1 by TNF-α and redistribution of ICAM-1 induced by cross-linking antibodies were similar in both cell types. However, neutrophil adherence induced production of reactive oxygen species only in PMECs and not in PAECs. Moreover, phosphorylation of p38 mitogen-activated protein kinase induced by ICAM-1 cross-linking occurred only in PMECs and not in PAECs. This increase in p38 phosphorylation in PMECs was inhibited by allopurinol, a xanthine oxidase inhibitor. These data demonstrated that whereas TNF-α upregulated ICAM-1 and ICAM-1 cross-linking induced a similar redistribution of ICAM-1 on the endothelial cell surface, ICAM-1 ligation initiated p38 activation and cytoskeletal rearrangements only in PMECs and not in PAECs. Thus, neutrophil adhesion through ICAM-1 induced signaling events leading to cytoskeletal changes only in PMECs, the site of neutrophil emigration and edema formation, and not in PAECs

A new urban landscape in East–Southeast Asia, 2000–2010

East–Southeast Asia is currently one of the fastest urbanizing regions in the world, with countries such as China climbing from 20 to 50% urbanized in just a few decades. By 2050, these countries are projected to add 1 billion people, with 90% of that growth occurring in cities. This population shift parallels an equally astounding amount of built-up land expansion. However, spatially-and temporally-detailed information on regional-scale changes in urban land or population distribution do not exist; previous efforts have been either sample-based, focused on one country, or drawn conclusions from datasets with substantial temporal/spatial mismatch and variability in urban definitions. Using consistent methodology, satellite imagery and census data for >1000 agglomerations in the East–Southeast Asian region, we show that urban land increased >22% between 2000 and 2010 (from 155 000 to 189 000 km2), an amount equivalent to the area of Taiwan, while urban populations climbed >31% (from 738 to 969 million). Although urban land expanded at unprecedented rates, urban populations grew more rapidly, resulting in increasing densities for the majority of urban agglomerations, including those in both more developed (Japan, South Korea) and industrializing nations (China, Vietnam, Indonesia). This result contrasts previous sample-based studies, which conclude that cities are universally declining in density. The patterns and rates of change uncovered by these datasets provide a unique record of the massive urban transition currently underway in East–Southeast Asia that is impacting local-regional climate, pollution levels, water quality/availability, arable land, as well as the livelihoods and vulnerability of populations in the regio

Tomato: a crop species amenable to improvement by cellular and molecular methods

Tomato is a crop plant with a relatively small DNA content per haploid genome and a well developed genetics. Plant regeneration from explants and protoplasts is feasable which led to the development of efficient transformation procedures. In view of the current data, the isolation of useful mutants at the cellular level probably will be of limited value in the genetic improvement of tomato. Protoplast fusion may lead to novel combinations of organelle and nuclear DNA (cybrids), whereas this technique also provides a means of introducing genetic information from alien species into tomato. Important developments have come from molecular approaches. Following the construction of an RFLP map, these RFLP markers can be used in tomato to tag quantitative traits bred in from related species. Both RFLP's and transposons are in the process of being used to clone desired genes for which no gene products are known. Cloned genes can be introduced and potentially improve specific properties of tomato especially those controlled by single genes. Recent results suggest that, in principle, phenotypic mutants can be created for cloned and characterized genes and will prove their value in further improving the cultivated tomato.

Dynamical mean-field theory of spiking neuron ensembles: response to a single spike with independent noises

Dynamics of an ensemble of $N$-unit FitzHugh-Nagumo (FN) neurons subject to white noises has been studied by using a semi-analytical dynamical mean-field (DMF) theory in which the original $2 N$-dimensional {\it stochastic} differential equations are replaced by 8-dimensional {\it deterministic} differential equations expressed in terms of moments of local and global variables. Our DMF theory, which assumes weak noises and the Gaussian distribution of state variables, goes beyond weak couplings among constituent neurons. By using the expression for the firing probability due to an applied single spike, we have discussed effects of noises, synaptic couplings and the size of the ensemble on the spike timing precision, which is shown to be improved by increasing the size of the neuron ensemble, even when there are no couplings among neurons. When the coupling is introduced, neurons in ensembles respond to an input spike with a partial synchronization. DMF theory is extended to a large cluster which can be divided into multiple sub-clusters according to their functions. A model calculation has shown that when the noise intensity is moderate, the spike propagation with a fairly precise timing is possible among noisy sub-clusters with feed-forward couplings, as in the synfire chain. Results calculated by our DMF theory are nicely compared to those obtained by direct simulations. A comparison of DMF theory with the conventional moment method is also discussed.Comment: 29 pages, 2 figures; augmented the text and added Appendice

High frequency of inactivating tetraspanin CD37 mutations in diffuse large B-cell lymphoma at immune-privileged sites

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High prevalence of mutations in the microtubule-associated protein tau in a population study of frontotemporal dementia in the Netherlands

Mutations in microtubule-associated protein tau recently have been identified in familial cases of frontotemporal dementia (FTD). We report the frequency of tau mutations in a large population-based study of FTD carried out in the Netherlands from January 1994 to June 1998. Thirty-seven patients had >/=1 first-degree relative with dementia. A mutation in the tau gene was found in 17.8% of the group of patie

Perceptions of trekking tourism and social and environmental change in Nepal's Himalayas

The Himalayas are among the world’s youngest mountain ranges. In addition to the geologic processes of mountain building and erosion, they are also highly vulnerable to human influenced change, occurring at local, national, regional, and international scales. A photo-elicitation methodology is employed to show how residents perceive those changes from historical perspectives, as well as their current conditions and impacts on their daily lives. Nepal’s Khumbu region has undergone major social and environmental transformations since the 1960s when international trekking first began to influence the area's economy. The current perceptions of Khumbu residents of these changes is assessed through photo-elicitation interviews. Their responses are placed in the historical context of: (i) institutional and political changes, much of which have been driven by national government policies; (ii) social and economic changes, for which the tourism economy has been central; and (iii) environmental changes, reflecting the impacts of resource management and climate change. The mostly positive perceptions of Khumbu residents toward how their region has changed reflects general improvements in the physical and cultural landscapes of the Khumbu over time, as well as its continuing geographic isolation, which has helped to slow the rate of globalization, while also keeping the region a dynamic and popular tourist destination

Familial pulmonary alveolar proteinosis caused by mutations in CSF2RA

Primary pulmonary alveolar proteinosis (PAP) is a rare syndrome characterized by accumulation of surfactant in the lungs that is presumed to be mediated by disruption of granulocyte/macrophage colony-stimulating factor (GM-CSF) signaling based on studies in genetically modified mice. The effects of GM-CSF are mediated by heterologous receptors composed of GM-CSF binding (GM-CSF-Rα) and nonbinding affinity-enhancing (GM-CSF-Rβ) subunits. We describe PAP, failure to thrive, and increased GM-CSF levels in two sisters aged 6 and 8 yr with abnormalities of both GM-CSF-Rα–encoding alleles (CSF2RA). One was a 1.6-Mb deletion in the pseudoautosomal region of one maternal X chromosome encompassing CSF2RA. The other, a point mutation in the paternal X chromosome allele encoding a G174R substitution, altered an N-linked glycosylation site within the cytokine binding domain and glycosylation of GM-CSF-Rα, severely reducing GM-CSF binding, receptor signaling, and GM-CSF–dependent functions in primary myeloid cells. Transfection of cloned cDNAs faithfully reproduced the signaling defect at physiological GM-CSF concentrations. Interestingly, at high GM-CSF concentrations similar to those observed in the index patient, signaling was partially rescued, thereby providing a molecular explanation for the slow progression of disease in these children. These results establish that GM-CSF signaling is critical for surfactant homeostasis in humans and demonstrate that mutations in CSF2RA cause familial PAP