Activity driven modeling of time varying networks

Network modeling plays a critical role in identifying statistical regularities and structural principles common to many systems. The large majority of recent modeling approaches are connectivity driven. The structural patterns of the network are at the basis of the mechanisms ruling the network formation. Connectivity driven models necessarily provide a time-aggregated representation that may fail to describe the instantaneous and fluctuating dynamics of many networks. We address this challenge by defining the activity potential, a time invariant function characterizing the agents' interactions and constructing an activity driven model capable of encoding the instantaneous time description of the network dynamics. The model provides an explanation of structural features such as the presence of hubs, which simply originate from the heterogeneous activity of agents. Within this framework, highly dynamical networks can be described analytically, allowing a quantitative discussion of the biases induced by the time-aggregated representations in the analysis of dynamical processes.Comment: 10 pages, 4 figure

Discs large (Dlg1) complexes in lymphocyte activation

T cell antigen recognition involves the formation of a structured interface between antigen-presenting and T cells that facilitates the specific transmission of activating and desensitizing stimuli. The molecular machinery that organizes the signaling molecules and controls their disposition in response to activation remains poorly understood. We show here that in T cells Discs large (Dlg1), a PDZ domain-containing protein, is recruited upon activation to cortical actin and forms complexes with early participants in T cell activation. Transient overexpression of Dlg1 attenuates basal and Vav1-induced NFAT reporter activation. Reduction of Dlg1 expression by RNA interference enhances both CD3- and superantigen-mediated NFAT activation. Attenuation of antigen receptor signaling appears to be a complex, highly orchestrated event that involves the mutual segregation of important elements of the early signaling complex

Innate and adaptive humoral responses coat distinct commensal bacteria with immunoglobulin A

Immunoglobulin A (IgA) is prominently secreted at mucosal surfaces and coats a fraction of the intestinal microbiota. However, the commensal bacteria bound by IgA are poorly characterized and the type of humoral immunity they elicit remains elusive. We used bacterial flow cytometry coupled with 16S rRNA gene sequencing (IgA-Seq) in murine models of immunodeficiency to identify IgA-bound bacteria and elucidate mechanisms of commensal IgA targeting. We found that residence in the small intestine, rather than bacterial identity, dictated induction of specific IgA. Most commensals elicited strong T-independent (TI) responses that originated from the orphan B1b lineage and from B2 cells, but excluded natural antibacterial B1a specificities. Atypical commensals including segmented filamentous bacteria and Mucispirillum evaded TI responses but elicited T-dependent IgA. These data demonstrate exquisite targeting of distinct commensal bacteria by multiple layers of humoral immunity and reveal a specialized function of the B1b lineage in TI mucosal IgA responses

The novel mTOR inhibitor RAD001 (Everolimus) induces antiproliferative effects in human pancreatic neuroendocrine tumor cells

Background/Aim: Tumors exhibiting constitutively activated PI(3) K/Akt/mTOR signaling are hypersensitive to mTOR inhibitors such as RAD001 (everolimus) which is presently being investigated in clinical phase II trials in various tumor entities, including neuroendocrine tumors (NETs). However, no preclinical data about the effects of RAD001 on NET cells have been published. In this study, we aimed to evaluate the effects of RAD001 on BON cells, a human pancreatic NET cell line that exhibits constitutively activated PI(3) K/Akt/mTOR signaling. Methods: BON cells were treated with different concentrations of RAD001 to analyze its effect on cell growth using proliferation assays. Apoptosis was examined by Western blot analysis of caspase-3/PARP cleavage and by FACS analysis of DNA fragmentation. Results: RAD001 potently inhibited BON cell growth in a dose-dependent manner which was dependent on the serum concentration in the medium. RAD001-induced growth inhibition involved G0/G1-phase arrest as well as induction of apoptosis. Conclusion: In summary, our data demonstrate antiproliferative and apoptotic effects of RAD001 in NET cells in vitro supporting its clinical use in current phase II trials in NET patients. Copyright (c) 2007 S. Karger AG, Basel

Interactive effects of elevated CO2, warming, and drought on photosynthesis of Deschampsia flexuosa in a temperate heath ecosystem

Global change factors affect plant carbon uptake in concert. In order to investigate the response directions and potential interactive effects, and to understand the underlying mechanisms, multifactor experiments are needed. The focus of this study was on the photosynthetic response to elevated CO2 [CO2; free air CO2 enrichment (FACE)], drought (D; water-excluding curtains), and night-time warming (T; infrared-reflective curtains) in a temperate heath. A/Ci curves were measured, allowing analysis of light-saturated net photosynthesis (Pn), light- and CO2-saturated net photosynthesis (Pmax), stomatal conductance (gs), the maximal rate of Rubisco carboxylation (Vcmax), and the maximal rate of ribulose bisphosphate (RuBP) regeneration (Jmax) along with leaf δ13C, and carbon and nitrogen concentration on a monthly basis in the grass Deschampsia flexuosa. Seasonal drought reduced Pn via gs, but severe (experimental) drought decreased Pn via a reduction in photosynthetic capacity (Pmax, Jmax, and Vcmax). The effects were completely reversed by rewetting and stimulated Pn via photosynthetic capacity stimulation. Warming increased early and late season Pn via higher Pmax and Jmax. Elevated CO2 did not decrease gs, but stimulated Pn via increased Ci. The T×CO2 synergistically increased plant carbon uptake via photosynthetic capacity up-regulation in early season and by better access to water after rewetting. The effects of the combination of drought and elevated CO2 depended on soil water availability, with additive effects when the soil water content was low and D×CO2 synergistic stimulation of Pn after rewetting. The photosynthetic responses appeared to be highly influenced by growth pattern. The grass has opportunistic water consumption, and a biphasic growth pattern allowing for leaf dieback at low soil water availability followed by rapid re-growth of active leaves when rewetted and possibly a large resource allocation capability mediated by the rhizome. This growth characteristic allowed for the photosynthetic capacity up-regulations that mediated the T×CO2 and D×CO2 synergistic effects on photosynthesis. These are clearly advantageous characteristics when exposed to climate changes. In conclusion, after 1 year of experimentation, the limitations by low soil water availability and stimulation in early and late season by warming clearly structure and interact with the photosynthetic response to elevated CO2 in this grassland species