By integrating signaling research with an institutional perspective we examine how country of origin, corporate governance, and host market effects impact foreign IPO performance. Using a sample of 202 foreign IPOs listed in the U.S. or U.K in 2002-2007 results indicate both the legal environment surrounding these organizations in their countries of origin and board independence impact the success of foreign firms at IPO. However, the institutional environment of the chosen IPO market impacts the salience of country and corporate governance signals for foreign IPO firms suggesting a more contextualized framework of IPO valuation is necessary.

Plants are sessile organisms and constantly encounter a myriad of pathogens; therefore, they rely on highly effective defense system for their survival. Our understanding of how plant immunity is triggered and regulated has seen tremendous progress over the last two decades, with many important players identified in the model systems, Arabidopsis thaliana. Mitogen activated protein kinases play a central role in signal transduction in biotic and abiotic stresses. MAPK pathways are regulated by three-interlinked protein kinases (MAPKKK, MAPKK, MAPK), which are sequentially activated by phosphorylation. The activation of the three MAPKs MPK3, MPK4 and MPK6 is one of the earliest cellular responses following pathogen attack leading to the phosphorylation of appropriate cytosolic or nuclear targets to regulate cellular processes. However, only few targets of MPK3, MPK4 and MPK6 have been identified and validated so far and many MAPK substrates remain to be discovered. We performed largescale phosphoproteomics on mock treated and flg22 treated WT and the three loss-of-function mutants mpk3, mpk4 and mpk6 to identify novel MAPKs substrates and their cellular functions in response to pathogen attack. We identify and validated some of the differentially phosphorylated cytosolic and chromatin targets of MPK3, MPK4 and MPK6. DEK2, a nuclear protein involved in multiple chromatin-related processes, was identified in the phosphoproteomics screen as an in vivo target of MPK6 and it interacts in planta and is phosphorylated in vitro by the three immune MAPKs. dek2 loss-of-function mutants were susceptible to bacterial as well as fungal pathogens. Additionally, transcriptome data of the dek2-1 mutant show that DEK2 is a transcriptional repressor inclusive of defense related genes and hormone synthesis and signaling genes. We determined that DEK2 is a reader of the histone mark, H3K9me1, by Microscale thermophoresis. From ChIP-Seq analysis, DEK2 was found to be enriched at class I TCP binding motif regions. We further need to determine whether DEK2 binds to TCP transcription factors directly or indirectly. Finally, based on our data we postulate a hypothetical working model for the function of DEK2 as a transcriptional repressor and a reader of H3K9me1 mark.

No description available.

No description available.

Much effort today in the Internet research community isaimed at providing network services for applications that werenot under consideration when the Internet was originallydesigned. Nowadays the network has to support real-timecommunication services that allow clients to transportinformation with expectations on network performance in termsof loss rate, maximum end-to-end delay, and maximum delayjitter. Today there exist two quality of service (QoS)architecture for the Internet: The integrated services, whichis usually referred to as intserv, and the differentiatedservices referred to as diffserv. Although the intserv clearlydefines the quality levels for each of its three serviceclasses, the limited scalability of this QoS architecture is acontinuous topic for discussion among the researchers. Theanalysis of the tradeoffs of the two QoS architecturesmotivated us to design a new QoS architecture which will takethe strength of the existing approaches and will combine themin a simpler, efficient and more scalable manner. In this LicentiateThesis we introduce a guaranteed servicefor the Internet, which definition is similar to the one inintserv: The guaranteed service (GS) is a network servicerecommended for applications with firm requirements on qualityof end-to-end communication. The service should provide zeropacket loss in routers and tightly bound the end-to-end delay.The capacity for a GS connection should be explicitly reservedin every router along a path of a connection. However, incontrary to intserv the necessary quality level will beprovided without per-flow scheduling in the core routers, whichis the major drawback of the intserv architecture. We use thediffserv principle of dealing with aggregates in the corenetwork since this approach is proven to be scalable andefficient. The thesis considers two major building blocks of the newarchitecture: The packet scheduling and the signaling protocol.We have developed a special scheduling algorithm. Our formaland experimental analysis of its delay properties shows thatthe maximum end-to-end delay is acceptable for real-timecommunication. Moreover, our scheme provides a fair service tothe traffic of other service classes. In order to achieve thedesired QoS level, a sufficient amount of capacity should bereserved for the GS connections in all intermediate routersend-to-end. We have developed a both simple and robustsignaling protocol. The realization of our protocol shows thatrouters are able to process up to 700,000 signaling messagesper second without overloading the processor. / NR 20140805

Indiana University-Purdue University Indianapolis (IUPUI) / Bone is a common location for breast cancer cell metastasis, and progression of tumor in bone can lead to bone loss and affect human health. Osteocytes have important roles in bone homeostasis and osteogenesis, and their interaction with metastasized cancer cells are known to affect progression of metastasized tumor. However, the potential role of metabolic signaling and actin- cytoskeleton-associated moesin in the interaction of osteocytes and tumor cells remain poorly understood. In this study, we first examined the roles of metabolic signaling, specifically global AMPK modulators and mitochondria-specific AMPK inhibitor (Mito-AIP), as well as mechanical force in beta catenin signaling through interaction between osteocytes and precursor osteoblasts as well as osteocytes and breast cancer cells. We also evaluated the role of metabolic signaling in Rho GTPases including RhoA, Rac1 and Cdc42. We observed that AMPK activator (A769662) and Mito-AMPK stimulated beta catenin translocation to the nucleus, indicating the activation of Wnt signaling, while Mito-AIP did not significantly affect beta catenin activation in osteoblasts. We also observed that osteocyte conditioned medium (CM) treated with Mito-AIP substantially increased beta catenin signaling in osteoblasts, while decreasing beta catenin signaling in breast cancer cells. CM of osteocytes treated with fluid flow increased beta catenin signaling in breast cancer cells. A769662 and Mito-AIP also decreased the activities of RhoA, Rac1, and Cdc42 in cancer cells which are known to regulate cancer cell migration. Additionally, we evaluated the roles of intracellular and extracellular moesin (MSN) protein in well-established oncogenic signaling proteins, such as FAK, Src, and RhoA as well beta catenin signaling. Constitutively active MSN (MSN+) significantly increased FAK and Src activities in cancer cells, but decreased the activity of RhoA. Surprisingly, CM of mesenchymal stem cells treated with MSN+ decreased the activities of FAK, Src, and RhoA, suggesting the inhibitory role of extracellular MSN in tumor-promoting signaling. Our results suggest the distinct role of AMPK signaling, specifically at mitochondria of osteocytes, in the activities of beta-catenin signaling in osteoblasts and breast cancer cells and the distinct role of intracellular and extracellular MSN in these two types of cell.

Endocannabinoid signaling is well studied in mammals and known to be involved in numerous pathological and physiological processes. Fatty acid amide hydrolase (FAAH) terminates endocannabinoid signaling in mammals. In Physcomitrella patens, we identified nine orthologs of FAAH (PpFAAH1 to PpFAAH9) with the characteristic catalytic triad and amidase signature sequence. Kinetics of PpFAAH1 showed specificity towards anandamide (AEA) at 37°C and pH 8.0. Further biophysical and bioinformatic analyses revealed that, structurally, PpFAAH1 to PpFAAH4 were closely associated to the plant FAAH whereas PpFAAH6 to PpFAAH9 were more closely associated to the animal FAAH. A substrate entry gate or ‘dynamic paddle’ in FAAH is fully formed in vertebrates but absent or not fully developed in non-vertebrates and plants. In planta analysis revealed that PpFAAH responded differently with saturated and unsaturated N-acylethanolamines (NAEs). In vivo amidohydrolase activity showed specificity associated with developmental stages. Additionally, overexpression of PpFAAH1 indicated the need for NAEs in developmental transition. To understand and identify key molecules related to endocannabinoid signaling in P. patens, we used high-throughput RNA sequencing. We analyzed temporal expression of mRNA and long non-coding RNA (lncRNA) in response not only to exogenous anandamide but also its precursor arachidonic acid and abscisic acid (ABA, a stress hormone). From the 40 RNA-seq libraries generated, we identified 4244 novel lncRNAs. The highest number of differentially expressed genes (DEGs) for both mRNA and lncRNA were detected on short-term exposure (1 h) to AEA. Furthermore, gene ontology enrichment analysis showed that 17 genes related to activation of the G protein-coupled receptor signaling pathway were highly expressed along with a number of genes associated with organelle relocation and localization. We identified key signaling components of AEA that showed significant difference when compared with ABA. This study provides a fundamental understanding of novel endocannabinoid signaling in early land plants and a future direction to elucidate its functional role.

No description available.

Obesity is often associated with multiple other clinical conditions, including hypertension and cardiovascular disease. Currently, more than one-third of the world’s population is classified as obese. Leptin is a neuropeptide that is released from adipose cells and is responsible for reducing appetite and increasing metabolism. Leptin also has a role in the activation of cardiovascular and metabolic pre-sympathetic neurons and has been reported to increase blood pressure and heart rate. Thus, understanding the activation of the autonomic nervous system by leptin has implications in the development and safety of drugs to avoid activation of cardiovascular pre-sympathetic neurons. This is important because a drug that causes an increase in blood pressure or heart rate would not be effective in diminishing cardiovascular-related comorbidities. This study tests the hypothesis that intracerebroventricular leptin activates sympathetic metabolically-related neurons in the hypothalamus. To identify leptin receptor-expressing neurons, we created a colony of transgenic reporter mice expressing tdTomato in the presence of the leptin receptor (ObRb) gene. To determine if treatment with leptin activated sympathetic metabolically-related neurons, we performed neuroanatomical tracer studies in the mice. The metabolically-related neurons were identified by microinjection of green FluoSpheres (505/515) into medullary raphe nucleus which is considered the sympathetic metabolic regulatory output center. After microinjection, hypothalamic neurons that express green Fluosphere project to the raphe and therefore are considered metabolic. To identify neuronal activation, we stained for cells expressing c-fos. We found that intracerebroventricular leptin activates hypothalamic neurons, however c-fos positive neurons were not retrogradely labelled raphe-projecting sympathetic metabolic neurons.

The mechanisms responsible for myocardial dysfunction in the setting of sepsis remain undefined. Fas ligation with its cognate ligand (FasL) induces apoptosis and activates cellular inflammatory responses associated with tissue injury. We determined whether interruption of Fas/FasL interaction by cardiac-specific expression of soluble Fas (sFas), a competitive inhibitor of FasL, would improve myocardial dysfunction and inflammation in a lipopolysacharide (LPS)-induced mouse model of sepsis. Wild-type (WT) and sFas transgenic mice were injected intraperitoneally with 10 mg/kg LPS or with an equivalent volume of saline. At 18 h after LPS administration, echocardiographic evaluation revealed a significant decrease in left ventricular fractional shortening in the WT mice, whereas the fractional shortening was preserved in the sFas mice. Activation of nuclear factor-kappa B (NF-κB) and the increase in the transcript levels of proinflammatory cytokines, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 resulting from LPS treatment were attenuated in the myocardium of sFas mice. sFas expression also inhibited LPS-induced upregulation of Toll-like receptor 4 (TLR-4) and inducible nitric oxide synthase (iNOS), and formation of peroxynitrite in the myocardium. LPS-induced increase in caspase-3/7 activity and apoptotic cell death were suppressed in sFas mice compared with WT mice. LPS-induced lung injury and increase in lung water content were also significantly reduced in sFas mice. These data indicate that neutralization of FasL by expression of sFas significantly preserves cardiac function and reduces inflammatory responses in the heart, suggesting that Fas/FasL signaling pathway is important in mediating the deleterious effects of LPS on myocardial function.