Modeling Bond yields in finance and macroeconomics

From a macroeconomic perspective, the short-term interest rate is a policy instrument under the direct control of the central bank. From a finance perspective, long rates are risk-adjusted averages of expected future short rates. Thus, as illustrated by much recent research, a joint macro-finance modeling strategy will provide the most comprehensive understanding of the term structure of interest rates. We discuss various questions that arise in this research, and we also present a new examination of the relationship between two prominent dynamic, latent factor models in this literature: the Nelson-Siegel and affine no-arbitrage term structure models. JEL Klassifikation: G1, E4, E5

Modeling Bond Yields in Finance and Macroeconomics

From a macroeconomic perspective, the short-term interest rate is a policy instrument under the direct control of the central bank. From a finance perspective, long rates are risk-adjusted averages of expected future short rates. Thus, as illustrated by much recent research, a joint macro-finance modeling strategy will provide the most comprehensive understanding of the term structure of interest rates. We discuss various questions that arise in this research, and we also present a new examination of the relationship between two prominent dynamic, latent factor models in this literature: the Nelson-Siegel and affne no-arbitrage term structure models.

Modeling Bond Yields in Finance and Macroeconomics

From a macroeconomic perspective, the short-term interest rate is a policy instrument under the direct control of the central bank. From a finance perspective, long rates are risk-adjusted averages of expected future short rates. Thus, as illustrated by much recent research, a joint macro-finance modeling strategy will provide the most comprehensive understanding of the term structure of interest rates. We discuss various questions that arise in this research, and we also present a new examination of the relationship between two prominent dynamic, latent factor models in this literature: the Nelson-Siegel and affine no-arbitrage term structure models.term structure, yield curve, Nelson-Siegel model, affine equilibrium model

Modeling Bond Yields in Finance and Macroeconomics

From a macroeconomic perspective, the short-term interest rate is a policy instrument under the direct control of the central bank. From a finance perspective, long rates are risk-adjusted averages of expected future short rates. Thus, as illustrated by much recent research, a joint macro-finance modeling strategy will provide the most comprehensive understanding of the term structure of interest rates. We discuss various questions that arise in this research, and we also present a new examination of the relationship between two prominent dynamic, latent factor models in this literature: the Nelson-Siegel and affine no-arbitrage term structure models.Term structure, yield curve, Nelson-Siegel model, affine equilibrium model

Epicutaneous immunization with ovalbumin and CpG induces TH1/TH17 cytokines, which regulate IgE and IgG2a production

Background: Subcutaneous allergen-specific immunotherapy is a standard route for the immunotherapy of allergic diseases. It modulates the course of allergy and can generate long-term remission. However, subcutaneous allergen-specific immunotherapy can also induce anaphylaxis in some patients, and therefore additional routes of administration should be investigated to improve the safety and tolerability of immunotherapy. Objective: We sought to determine whether epicutaneous treatment with antigen in the presence of a Toll-like receptor 9 agonist can suppress TH2-mediated responses in an antigenspecific manner. Methods: Epicutaneous immunization was performed by applying a skin patch soaked with ovalbumin (OVA) plus CpG, and its suppressor activity was determined by using the mouse model of atopic dermatitis. Finally, adoptive cell transfers were implemented to characterize the regulatory cells that are induced by epicutaneous immunization. Results: Epicutaneous immunization with OVA and CpG reduces the production of OVA-specific IgE and increases the synthesis of OVA-specific IgG2a antibodies in an antigen-specific manner. Moreover, eosinophil peroxidase activity in the skin and production of IL-4, IL-5, IL-10, and IL-13 are suppressed. The observed reduction of IgE synthesis is transferable with T-cell receptor (TCR) ab1CD41CD252 cells, whereas IgG2a production is dependent on both TCRab1 and TCRgd1 T cells. Further experiments show that the described phenomenon is myeloid differentiation primary response 88, IFN-g, and IL-17A dependent. Finally, the results suggest that epicutaneous immunization with OVA and CpG decreases the synthesis of OVA-specific IgE and skin eosinophil peroxidase activity in mice with ongoing skin allergy. Conclusion: Epicutaneous application of protein antigen in the presence of adjuvant could be an attractive needle-free and self-administered immunotherapy for allergic diseases

SLC7A11 Overexpression in Glioblastoma Is Associated with Increased Cancer Stem Cell-Like Properties

System x_c^− is a sodium-independent electroneutral transporter, comprising a catalytic subunit xCT (SLC7A11), which is involved in importing cystine. Certain cancers such as gliomas upregulate the expression of system x_c^−, which confers a survival advantage against the detrimental effects of reactive oxygen species (ROS) by increasing generation of the antioxidant glutathione. However, ROS have also been shown to function as targeted, intracellular second messengers in an array of physiological processes such as proliferation. Several studies have implicated ROS in important cancer features such as migration, invasion, and contribution to a cancer stem cell (CSC)-like phenotype. The role of system x_c^− in regulating these ROS-sensitive processes in glioblastoma multiforme (GBM), the most aggressive malignant primary brain tumor in adults, remains unknown. Stable SLC7A11 knockdown and overexpressing U251 glioma cells were generated and characterized to understand the role of redox and system x_c^− in glioma progression. SLC7A11 knockdown resulted in higher endogenous ROS levels and enhanced invasive properties. On the contrary, overexpression of SLC7A11 resulted in decreased endogenous ROS levels as well as decreased migration and invasion. However, SLC7A11-overexpressing cells displayed actin cytoskeleton changes reminiscent of epithelial-like cells and exhibited an increased CSC-like phenotype. The enhanced CSC-like phenotype may contribute to increased chemoresistance and suggests that overexpression of SLC7A11 in the context of GBM may contribute to tumor progression. These findings have important implications for cancer management where targeting system x_C^− in combination with other chemotherapeutics can reduce cancer resistance and recurrence and improve GBM patient survival

Integrins Have Cell-Type-Specific Roles in the Development of Motor Neuron Connectivity

Formation of the nervous system requires a complex series of events including proper extension and guidance of neuronal axons and dendrites. Here we investigate the requirement for integrins, a class of transmembrane cell adhesion receptors, in regulating these processes across classes of C. elegans motor neurons. We show alpha integrin/ina-1 is expressed by both GABAergic and cholinergic motor neurons. Despite this, our analysis of hypomorphic ina-1(gm144) mutants indicates preferential involvement of alpha integrin/ina-1 in GABAergic commissural development, without obvious involvement in cholinergic commissural development. The defects in GABAergic commissures of ina-1(gm144) mutants included both premature termination and guidance errors and were reversed by expression of wild type ina-1 under control of the native ina-1 promoter. Our results also show that alpha integrin/ina-1 is important for proper outgrowth and guidance of commissures from both embryonic and post-embryonic born GABAergic motor neurons, indicating an ongoing requirement for integrin through two phases of GABAergic neuron development. Our findings provide insights into neuron-specific roles for integrin that would not be predicted based solely upon expression analysis

Endocytic turnover of Rab8 controls cell polarization

Adaptation of cell shape and polarization through the formation and retraction of cellular protrusions requires balancing of endocytosis and exocytosis combined with fine-tuning of the local activity of small GTPases like Rab8. Here, we show that endocytic turnover of the plasma membrane at protrusions is directly coupled to surface removal and inactivation of Rab8. Removal is induced by reduced membrane tension and mediated by the GTPase regulator associated with focal adhesion kinase-1 (GRAF1, also known as ARHGAP26), a regulator of clathrin-independent endocytosis. GRAF1-depleted cells were deficient in multi-directional spreading and displayed elevated levels of GTP-loaded Rab8, which was accumulated at the tips of static protrusions. Furthermore, GRAF1 depletion impaired lumen formation and spindle orientation in a 3D cell culture system, indicating that GRAF1 activity regulates polarity establishment. Our data suggest that GRAF1-mediated removal of Rab8 from the cell surface restricts its activity during protrusion formation, thereby facilitating dynamic adjustment of the polarity axis.Peer reviewe