The role of p44/42 activation in tributyltin-induced inhibition of human natural killer cells: effects of MEK inhibitors

Destruction of tumor cells is a key function of natural killer (NK) cells. Previous studies have shown that tributyltin (TBT) can significantly reduce the lytic function of the human NK cells with accompanying increases in the phosphorylation (activation) states of the mitogen activated protein kinases (MAPKs), p44/42. The current studies examine the role of p44/42 activation in the TBT-induced reduction of NK-lytic function, by using MAPK kinase (MEK) inhibitors, PD98059 and U0126. A 1 h treatment with PD98059 or U0126 or both decreased the ability of NK cells to lyse K562 tumor cells. PD98059, U0126 or a combination of both inhibitors were able to completely block TBT-induced activation of p44/42. However, when p44/42 activation was blocked by the presence of PD98059, U0126 or the combination, subsequent exposure to TBT was still able to decrease the lytic function of NK cells. These results indicate that TBT-induced activation of p44/42 occurs via the activation of its upstream activator, MEK, and not by a TBT-induced inhibition of p44/42 phosphatase activity. Additionally, as lytic function was never completely blocked by MEK inhibitors, the results indicate that activation of p44/42 pathway is not solely responsible for the activation of lytic function of freshly isolated human NK cells. Finally, the results showed that TBT-induced activation of p44/42 is not solely responsible for the loss of lytic function

Interactions between eagles and humans in the James River Bald Eagle Concentration Area

The lower James River supports the largest known concentration of summering eagles in eastern North America. In recent years, both the number of eagles using the river and their distribution along the shoreline appear to have increased substantially. At the same time, an increase in the human population surrounding the lower river has lead to an increase in the use of the river for recreational activities. These trends have heightened concerns within the management community about potential interactions and conflicts between these two user populations. In the summer of 1997, an investigation was initiated to collect data for the purpose of: 1) redefining the boundaries of the James River Bald Eagle concentration area, 2) determining the current level of human use within a section of the lower James River, and 3) investigating potential interactions between the human and eagle populations during the summer months. These objectives were accomplished using a combination of an extended shoreline survey and intensive observations of humans and eagles within the heart of the historic concentration area. The James River Bald Eagle concentration area has expanded well beyond the historic survey area. Elevated numbers of eagles now extend from Jones Neck down river to Fort Eustis, a distance of 140 river kilometers that contains 235 km of primary shoreline. The peak count of 448 eagles on 11 June approaches an average of 2 birds/krn of shoreline for the entire study area. In addition to the expansion of eagles along the shoreline, an increase in both the number and distribution of sites used for nocturnal roosts was documented. Four new communal roost sites spanning the length of the study area were located

Role of Protein Kinase C in TBT-Induced Inhibition of Lytic Function and MAPK Activation in Human Natural Killer Cells

Human natural killer (NK) cells are lymphocytes that destroy tumor and virally infected cells. Previous studies have shown that exposure of NK cells to tributyltin (TBT) greatly diminishes their ability to destroy tumor cells (lytic function) while activating mitogen-activated protein kinases (MAPK) (p44/42, p38, and JNK) in NK cells. The signaling pathway that regulates NK lytic function appears to include activation of protein kinase C (PKC) as well as MAPK activity. TBT-induced activation of MAPKs would trigger a portion of the NK lytic signaling pathway, which would then leave the NK cell unable to trigger this pathway in response to a subsequent encounter with a target cell. In the present study we evaluated the involvement of PKC in inhibition of NK lysis of tumor cells and activation of MAPKs caused by TBT exposure. TBT caused a 2–3-fold activation of PKC at concentrations ranging from 50 to 300 nM (16–98 ng/ml), indicating that activation of PKC occurs in response to TBT exposure. This would then leave the NK cell unable to respond to targets. Treatment with the PKC inhibitor, bisindolylmaleimide I, caused an 85% decrease in the ability of NK cells to lyse tumor cells, validating the involvement of PKC in the lytic signaling pathway. The role of PKC in the activation of MAPKs by TBT was also investigated using bisindolylmaleimide I. The results indicated that, in NK cells where PKC activation was blocked, there was no activation of the MAPK, p44/42 in response to TBT. However, TBT-induced activation of the MAPKs, p38 and JNK did not require PKC activation. These results indicate the pivotal role of PKC in the TBT-induced loss of NK lytic function including activation of p44/42 by TBT in NK cells

Differing effect of systemic anti psoriasis therapies on platelet physiology - a case report and review of literature

<p>Abstract</p> <p>Background</p> <p>Psoriasis is a common, chronic relapsing inflammatory skin disease. Lately, there is increasing evidence that psoriasis is more than "skin deep". Epidemiological studies showed that severe psoriasis might have also important systemic manifestations such as metabolic deregulations, cardiovascular disease (CVD) and increased mortality. Moreover, recently psoriasis patients were found to have platelet hyperactivity.</p> <p>Case Presentation</p> <p>This is a case report and review of the literature. We present a patient with long standing severe psoriasis vulgaris with marked thrombocytosis. His thrombocytosis did not correlate with disease severity but rather with the different treatments that he was exposed to, subsiding only during treatment with anti Tumor Necrosis Factor (TNF)- agents. A literature review revealed that in rheumatoid arthritis, another systemic inflammatory disease; interleukin (IL)-6 might be implicated in causing thrombocytosis.</p> <p>Conclusion</p> <p>This unique case report illustrates that different systemic treatments for psoriasis might have implications beyond the care of skin lesions. This insight is especially important in psoriasis patients in view of their deranged hemostatic balance toward a prothrombotic state, which might increase the risk of thrombosis and CVD. Therefore, further studies analyzing the effect of different drugs on platelets physiology are warranted.</p

Probing Nonlocal Spatial Correlations in Quantum Gases with Ultra-long-range Rydberg Molecules

We present photo-excitation of ultra-long-range Rydberg molecules as a probe of spatial correlations in quantum gases. Rydberg molecules can be created with well-defined internuclear spacing, set by the radius of the outer lobe of the Rydberg electron wavefunction $R_n$. By varying the principal quantum number $n$ of the target Rydberg state, the molecular excitation rate can be used to map the pair-correlation function of the trapped gas $g^{(2)}(R_n)$. We demonstrate this with ultracold Sr gases and probe pair-separation length scales ranging from $R_n = 1400 - 3200$ $a_0$, which are on the order of the thermal de Broglie wavelength for temperatures around 1 $\mu$K. We observe bunching for a single-component Bose gas of $^{84}$Sr and anti-bunching due to Pauli exclusion at short distances for a polarized Fermi gas of $^{87}$Sr, revealing the effects of quantum statistics.Comment: 6 pages, 5 figure

Clifford Gates by Code Deformation

Topological subsystem color codes add to the advantages of topological codes an important feature: error tracking only involves measuring 2-local operators in a two dimensional setting. Unfortunately, known methods to compute with them were highly unpractical. We give a mechanism to implement all Clifford gates by code deformation in a planar setting. In particular, we use twist braiding and express its effects in terms of certain colored Majorana operators.Comment: Extended version with more detail

Climate drives the geography of marine consumption by changing predator communities

The global distribution of primary production and consumption by humans (fisheries) is well-documented, but we have no map linking the central ecological process of consumption within food webs to temperature and other ecological drivers. Using standardized assays that span 105° of latitude on four continents, we show that rates of bait consumption by generalist predators in shallow marine ecosystems are tightly linked to both temperature and the composition of consumer assemblages. Unexpectedly, rates of consumption peaked at midlatitudes (25 to 35°) in both Northern and Southern Hemispheres across both seagrass and unvegetated sediment habitats. This pattern contrasts with terrestrial systems, where biotic interactions reportedly weaken away from the equator, but it parallels an emerging pattern of a subtropical peak in marine biodiversity. The higher consumption at midlatitudes was closely related to the type of consumers present, which explained rates of consumption better than consumer density, biomass, species diversity, or habitat. Indeed, the apparent effect of temperature on consumption was mostly driven by temperature-associated turnover in consumer community composition. Our findings reinforce the key influence of climate warming on altered species composition and highlight its implications for the functioning of Earth’s ecosystems

Factors in Daily Physical Activity Related to Calcaneal Mineral Density in Men

To determine the factors in daily physical activity that influence the mineral density of the calcaneus, we recorded walking steps and the type and duration of exercise in 43 healthy 26-to 51-yr-old men. Areal (g/sq cm) calcaneal bone mineral density (CBMD) was measured by single energy x-ray densitometry. Subjects walked a mean (+/- SD) of 7902(+/-2534) steps per day or approximately 3.9(+/-1.2) miles daily. Eight subjects reported no exercise activities. The remaining 35 subjects spent 143(2-772) (median and range) min/wk exercising. Twenty-eight men engaged in exercise activities that generate single leg peak vertical ground reaction forces (GRF(sub z)) of 2 or more body weights (high loaders, HL), and 15 reported exercise or daily activities that typically generate GRF(sub z) less than 1.5 body weights (low loaders, LL). CBMD was 12% higher in HL than LL (0.668 +/- 0.074 g/sq cm vs 0.597 +/- 0.062 g/sq cm, P less than 0.004). In the HL group, CBMD correlated to reported minutes of high load exercise (r = 0.41, P less than 0.03). CBMD was not related to the number of daily walking steps (N = 43, r = 0.03, NS). The results of this study support the concept that the dominant factor in daily physical activity relating to bone mineral density is the participation in site specific high loading activities, i.e., for the calcaneus, high calcaneal loads

Synthesising interprocedural bit-precise termination proofs

Proving program termination is key to guaranteeing absence of undesirable behaviour, such as hanging programs and even security vulnerabilities such as denial-of-service attacks. To make termination checks scale to large systems, interprocedural termination analysis seems essential, which is a largely unexplored area of research in termination analysis, where most effort has focussed on difficult single-procedure problems. We present a modular termination analysis for C programs using template-based interprocedural summarisation. Our analysis combines a context-sensitive, over-approximating forward analysis with the inference of under-approximating preconditions for termination. Bit-precise termination arguments are synthesised over lexicographic linear ranking function templates. Our experimental results show that our tool 2LS outperforms state-of-the-art alternatives, and demonstrate the clear advantage of interprocedural reasoning over monolithic analysis in terms of efficiency, while retaining comparable precision