Urban-rural air humidity differences in Szeged, Hungary

Measurements of vapour pressure, taken four times a day over a 3-year period, were used to investigate the urban influence on diurnal and annual patterns of vapour pressure differences. The examined settlement is a medium-sized city without significant relief in the Great Hungarian Plain. Its regional climate is continental with a long warm season. On the basis of the results, the air in the city centre is more humid than in the rural area both by day and at night for the duration of the whole year. The diurnal pattern shows that the urban excess has its minimum at 01:00 h and its maximum at 19:00 h in the summer months, but similar regular diurnal variation does not exist during the rest of the year. The annual patterns show that the excess increases from January–February to August and then decreases until November–December at each observation time. The differences and variations of urban humidity excess can be explained by different moisture sources and by different energy balances in the urban and rural environments. Unambiguous relationships exist between the variations of urban humidity excess and a regional aridity index, between the variations of humidity excess and the water temperature of the River Tisza crossing the city, as well as between the variations of humidity excess and maximum heat island intensity. The role of combustion processes is also significant, especially in the colder half of the year

Myosin V passing over Arp2/3 junctions: branching ratio calculated from the elastic lever arm model

Myosin V is a two-headed processive motor protein that walks in a hand-over-hand fashion along actin filaments. When it encounters a filament branch, formed by the Arp2/3 complex, it can either stay on the straight mother filament, or switch to the daughter filament. We study both probabilities using the elastic lever arm model for myosin V. We calculate the shapes and bending energies of all relevant configurations in which the trail head is bound to the actin filament before Arp2/3 and the lead head is bound either to the mother or to the daughter filament. Based on the assumption that the probability for a head to bind to a certain actin subunit is proportional to the Boltzmann factor obtained from the elastic energy, we calculate the mother/daughter filament branching ratio. Our model predicts a value of 27% for the daughter and 73% for the mother filament. This result is in good agreement with recent experimental data.Comment: 9 pages, 7 figures, to appear in Biophysical Journa

Mixed Valvular Disease Following Transcatheter Aortic Valve Replacement: Quantification and Systematic Differentiation Using Clinical Measurements and Image-Based Patient‐Specific In Silico Modeling

Background: Mixed valvular disease (MVD), mitral regurgitation (MR) from pre‐existing disease in conjunction with paravalvular leak (PVL) following transcatheter aortic valve replacement (TAVR), is one of the most important stimuli for left ventricle (LV) dysfunction, associated with cardiac mortality. Despite the prevalence of MVD, the quantitative understanding of the interplay between pre‐existing MVD, PVL, LV, and post‐TAVR recovery is meager. Methods and Results: We quantified the effects of MVD on valvular‐ventricular hemodynamics using an image‐based patient‐specific computational framework in 72 MVD patients. Doppler pressure was reduced by TAVR (mean, 77%; N=72; P<0.05), but it was not always accompanied by improvements in LV workload. TAVR had no effect on LV workload in 22 patients, and LV workload post‐TAVR significantly rose in 32 other patients. TAVR reduced LV workload in only 18 patients (25%). PVL significantly alters LV flow and increases shear stress on transcatheter aortic valve leaflets. It interacts with mitral inflow and elevates shear stresses on mitral valve and is one of the main contributors in worsening of MR post‐TAVR. MR worsened in 32 patients post‐TAVR and did not improve in 18 other patients. Conclusions: PVL limits the benefit of TAVR by increasing LV load and worsening of MR and heart failure. Post‐TAVR, most MVD patients (75% of N=72; P<0.05) showed no improvements or even worsening of LV workload, whereas the majority of patients with PVL, but without that pre‐existing MR condition (60% of N=48; P<0.05), showed improvements in LV workload. MR and its exacerbation by PVL may hinder the success of TAVR

Myosin-I nomenclature.

We suggest that the vertebrate myosin-I field adopt a common nomenclature system based on the names adopted by the Human Genome Organization (HUGO). At present, the myosin-I nomenclature is very confusing; not only are several systems in use, but several different genes have been given the same name. Despite their faults, we believe that the names adopted by the HUGO nomenclature group for genome annotation are the best compromise, and we recommend universal adoption

High tumor incidence and activation of the PI3K/AKT pathway in transgenic mice define AIB1 as an oncogene

AbstractThe gene encoding AIB1, an estrogen receptor coactivator, is amplified in a subset of human breast cancers. Here we show that overexpression of AIB1 in transgenic mice (AIB1-tg) leads to mammary hypertrophy, hyperplasia, abnormal postweaning involution, and the development of malignant mammary tumors. Tumors are also increased in other organs, including the pituitary and uterus. AIB1 overexpression increases mammary IGF-I mRNA and serum IGF-I protein levels. In addition, IGF-I receptor and downstream signaling molecules are activated in primary mammary epithelial cells and mammary tumor cells derived from AIB1-tg mice. Knockdown of AIB1 expression in cultured AIB1-tg mammary tumor cells leads to reduced IGF-I mRNA levels and increased apoptosis, suggesting that an autocrine IGF-I loop underlies the mechanism of AIB1-induced oncogenesis

A Branched Kinetic Scheme Describes the Mechanochemical Coupling of Myosin Va Processivity in Response to Substrate

Myosin Va is a double-headed cargo-carrying molecular motor that moves processively along cellular actin filaments. Long processive runs are achieved through mechanical coordination between the two heads of myosin Va, which keeps their ATPase cycles out of phase, preventing both heads detaching from actin simultaneously. The biochemical kinetics underlying processivity are still uncertain. Here we attempt to define the biochemical pathways populated by myosin Va by examining the velocity, processive run-length, and individual steps of a Qdot-labeled myosin Va in various substrate conditions (i.e., changes in ATP, ADP, and Pi) under zero load in the single-molecule total internal reflection fluorescence microscopy assay. These data were used to globally constrain a branched kinetic scheme that was necessary to fit the dependences of velocity and run-length on substrate conditions. Based on this model, myosin Va can be biased along a given pathway by changes in substrate concentrations. This has uncovered states not normally sampled by the motor, and suggests that every transition involving substrate binding and release may be strain-dependent. © 2012 Biophysical Society

BCR-ABL1 tyrosine kinase sustained MECOM expression in chronic myeloid leukaemia

MECOM oncogene expression correlates with chronic myeloid leukaemia (CML) progression. Here we show that the knockdown of MECOM (E) and MECOM (ME) isoforms reduces cell division at low cell density, inhibits colony-forming cells by 34% and moderately reduces BCR-ABL1 mRNA and protein expression but not tyrosine kinase catalytic activity in K562 cells. We also show that both E and ME are expressed in CD34&lt;sup&gt;+&lt;/sup&gt; selected cells of both CML chronic phase (CML-CP), and non-CML (normal) origin. Furthermore, MECOM mRNA and protein expression were repressed by imatinib mesylate treatment of CML-CP CD34&lt;sup&gt;+&lt;/sup&gt; cells, K562 and KY01 cell lines whereas imatinib had no effect in non-CML BCR-ABL1 −ve CD34&lt;sup&gt;+&lt;/sup&gt; cells. Together these results suggest that BCR-ABL1 tyrosine kinase catalytic activity regulates MECOM gene expression in CML-CP progenitor cells and that the BCR-ABL1 oncoprotein partially mediates its biological activity through MECOM. MECOM gene expression in CML-CP progenitor cells would provide an in vivo selective advantage, contributing to CML pathogenesis

Vascular endothelial growth factor restores delayed tumor progression in tumors depleted of macrophages

Genetic depletion of macrophages in Polyoma Middle T oncoprotein (PyMT)‐induced mammary tumors in mice delayed the angiogenic switch and the progression to malignancy. To determine whether vascular endothelial growth factor A (VEGF‐A) produced by tumor‐associated macrophages regulated the onset of the angiogenic switch, a genetic approach was used to restore expression of VEGF‐A into tumors at the benign stages. This stimulated formation of a high‐density vessel network and in macrophage‐depleted mice, was followed by accelerated tumor progression. The expression of VEGF‐A led to a massive infiltration into the tumor of leukocytes that were mostly macrophages. This study suggests that macrophage‐produced VEGF regulates malignant progression through stimulating tumor angiogenesis, leukocytic infiltration and tumor cell invasion

Firm finances, weather derivatives and geography

This paper considers some intellectual, practical and political dimensions of collaboration between human and physical geographers exploring how firms are using relatively new financial products – weather derivatives – to displace any costs of weather-related uncertainty and risk. The paper defines weather derivatives and indicates how they differ from weather insurance products before considering the geo-political, cultural and economic context for their creation. The paper concludes by reflecting on the challenges of research collaboration across the human–physical geography divide and suggests that while such initiatives may be undermined by a range of institutional and intellectual factors, conversations between physical and human geographers remain and are likely to become increasingly pertinent. The creation of a market in weather derivatives raises a host of urgent political and regulatory questions and the confluence of natural and social knowledges, co-existing within and through the geography academy, provides a constructive and creative basis from which to engage with this new market and wider discourses of uneven economic development and climate change