Can the Ag Credit Survey predict national credit conditions?

With the farm boom ending in 2009, many farmers have become less able to repay short-term loans. As farm profit margins erode and farm loan delinquencies rise, some in the agricultural industry worry that lending standards will tighten—as they did in the farm debt crisis of the 1980s. ; One barometer of future agricultural credit conditions is agricultural bankers. Experience and access to information give these bankers a unique perspective on agricultural credit conditions. In fact, several Federal Reserve banks survey agricultural bankers in their district to tap this source of information. But how reliable are regional Federal Reserve agricultural credit surveys? And can a regional survey shed light on future loan delinquencies and credit standards nationwide? ; Briggeman examines the Federal Reserve Bank of Kansas City’s Survey of Agricultural Credit Conditions to explore these questions. He concludes that the Survey of Agricultural Credit Conditions reliably predicts farm loan repayment rates in the district and provides valuable insight into future farm loan delinquencies and credit standards nationwide. The most recent Survey data suggest that the nation’s farm loan delinquencies will continue to rise in the year ahead, which may cause collateral requirements to stay elevated heading into 2010.

Can the Federal Reserve Bank’s Survey of Agricultural Credit Conditions Forecast Land Values?

The value of land dominates the financial structure of most American agricultural production firms, and land values are an important factor in long-term agricultural planning and risk management. As the primary source of collateral for farm loans, farmland values have significant implications for both producers as well as bankers financing agricultural loans. The Federal Reserve Bank of Kansas City’s Survey of Agricultural Credit Conditions is an expert opinion survey in which agricultural bankers provide land value forecasts. As the survey has drawn increased attention, the survey has drawn criticism regarding its use qualitative data to forecast land values. Our research examines the value of the survey data with respect to its ability to forecast movement in land values. Three techniques are used in the analysis. Interpreting the aggregate forecasts as probability estimates, Brier’s probability scores are used to evaluate aggregate bankers’ predictions. Next, turning points are evaluated using contingency tables. Finally, Granger causality tests are used to determine the dynamic relationship between land value predictions and actual land value changes reported by bankers. Bankers’ forecasts predict land values for irrigated and ranchland well, but non-irrigated forecasts were only marginally helpful in prediction non-irrigated farmland values. Forecasts provided in the survey may be beneficial, especially considering the scarcity of other publicly available data.farmland, forecasting, land values, Federal Reserve Bank, Agribusiness, Financial Economics,

Functional analysis of RACK1 as a novel interaction partner of BMPRII in pulmonary arterial hypertension

Die Pulmonalarterielle Hypertonie (PAH) ist charakterisiert durch eine selektive Erhöhung des pulmonalarteriellen Blutdrucks. Das pathologische Korrelat der PAH ist ein Verschluss der pulmonalen Arteriolen durch eine Proliferation/Fehlfunktion der glatten Gefässmuskelzellen und des Endothels. Heterozygote Keimbahnmutationen im Bone Morphogenetic Receptor Type II (BMPRII) kodierenden Genlokus zeigen eine Assoziation mit PAH, was für einen Einfluss des BMPRII auf die Pathogenese der PAH spricht. Um die Funktion von BMPRII zu charakterisieren, war es das Ziel unserer Arbeit, neue potentielle Interaktionspartner dieses Rezeptors mittels Yeast Two-Hybrid Analyse zu identifizieren. Unter den vielen bisher unbekannten Interaktionspartnern von BMPRII wurde RACK (receptor for activated protein kinase C)-1 für weitergehende Untersuchungen ausgewählt. Glutathion S-Transferase (GST)-pulldown Experimente sowie Ko-Immunopräzipitationen bestätigten die Interaktion von RACK1 und der BMPRII Kinasedomäne. Immunohistochemische Analysen von Lungenschnitten und Immunofluoreszenzanalysen isolierter glatter Muskelzellen aus der Pulmonalarterie zeigten eine Ko-Lokalisation von BMPRII und RACK1 in vitro und in vivo. Für weitere funktionelle Analysen wurde das RACK1 Gen kloniert und in einem BMP-Reportergenassay überexprimiert. RACK1 Expression führte zu einer zweifach erhöhten Reportergenaktivität nach BMP-2 Stimulation, was einen synergistischen Einfluss der BMPRII-RACK1 Interaktion auf die BMP Signalkaskade zeigt. Dieser Befund wird durch die Tatsache unterstüzt, dass die Depletion von RACK1 mittels small interfering RNA (siRNA) Technologie zu einer verstärkten Proliferation von glatten Gefässmuskelzellen der A. Pulmonalis führt, was für eine regulatorische Rolle von RACK1 auf das Zellwachstum spricht. Mehrere BMPRII Varianten, welche aus dem internationalen PAH Patientenpool stammen, zeigten eine reduzierte Affinität für RACK1. Im Tiermodell der durch Monokrotalin induzierten pulmonalen Hypertonie wurde eine signifikant erniedrigte Expression von RACK1 auf RNA und Proteinebene gefunden. Die vorliegende Arbeit beschreibt daher einen funktionell bedeutenden Einfluss der neu identifizierten Interaktion zwischen BMPRII und RACK1 auf die BMP Signaltransduktion. Die reduzierte Affinität von RACK1 für BMPRII Varianten und die erniedrigte RACK1 Expression im Tiermodell der pulmonalen Hypertonie sprechen für einen bedeutenden Einfluss von RACK1 und der RACK1-BMPRII Interaktion auf die Pathogenese der PAH.Pulmonary arterial hypertension (PAH) is characterised by selective elevation of pulmonary arterial pressure. The pathological hallmark of PAH is the occlusion of pulmonary arterioles due to proliferation and dysfunction of smooth muscle and endothelial cells. Heterozygous mutations in BMPR2, encoding the type II BMP receptor (BMPRII), were identified in PAH suggesting that alterations to BMPRII function are involved in disease onset and/or progression. To further elucidate the function of BMPRII, we sought to identify novel interaction partners of BMPRII by yeast two-hybrid analysis using the kinase domain of BMPRII as a bait. Using this technology, several novel interaction partners of BMPRII were identified. Among these, the receptor for activated protein kinase C (RACK)-1 was selected for further investigation. The interaction between RACK1 and the BMPRII kinase domain was confirmed by Glutathione S-transferase (GST)-pull-down and co-immunoprecipitation. Immunofluorescent staining of human pulmonary artery smooth muscle cells (paSMC), as well immunohistochemistry of human lungs from healthy donors and PAH patients, demonstrated the co-localisation of BMPRII and RACK1 in vitro and in vivo. Overexpression of RACK1 in paSMC led to a two-fold increase in induction of a BMP-responsive promoter in a luciferase-based promoter reporter assay, indicating that the BMPRII-RACK1 interaction may potentiate BMP signalling. RACK1 depletion using small interfering RNA (siRNA) technology resulted in enhanced proliferation of paSMC, thus implicating a role for RACK1 and the RACK1-BMPRII interaction in paSMC growth regulation. In contrast, overexpression of RACK1 led to enhanced proliferation of paSMC. Several BMPRII variants that contained amino acid substitutions present in PAH patients exhibited a reduced affinity for RACK1. Furthermore, in the monocrotaline-induced rat model of PAH, the expression of RACK1 was significantly down-regulated at the RNA and protein level, two and four weeks after monocrotaline administration. Thus, the novel interaction of RACK1 with BMPRII is functionally significant in BMP signal transduction. The reduced affinity of RACK1 for BMPRII variants that are peculiar to PAH patients, and the reduced levels of RACK1 evident in the pulmonary vasculature in an animal model of PAH, suggest a potential role for RACK1, and the RACK1-BMPRII interaction, in the pathogenesis of PAH

Asymmetric dimethylarginine metabolism and its involvement in the pathogenesis of pulmonary arterial hypertension

Protein arginine methylation represents a posttranslational modification undertaken by protein arginine methyltransferases (PRMT) that results in production of protein-incorporated omega-NG-monomethylarginine (L-NMMA), asymmetric omega-NG, NG-dimethylarginine (ADMA), or omega-NG, N G-dimethylarginine (SDMA). Free cellular L-NMMA, ADMA and SDMA can be generated via the proteolytic cleavage of intracellular proteins, thereby also affecting methylarginine content in the plasma. Free methylarginines can be cleared from the body by renal excretion. L-NMMA and ADMA, but not SDMA, can be degraded via enzymes called NG, NG–dimmethylarginine dimethylaminohydrolase (DDAH). ADMA is an endogenous inhibitor of nitric oxide synthases (NOS) and a marker of endothelial dysfunction. Increased plasma ADMA levels have been reported in patients with cardiovascular disorders including pulmonary arterial hypertension (PAH), a fatal disease characterized by elevated blood pressure in the pulmonary circulation, due to increased resistance of pulmonary arterioles. The major pathophysiologic hallmark of PAH is pulmonary arterial smooth muscle cell (PASMC) hypertrophy and proliferation, leading to the occlusion of pulmonary arterioles. The interplay between methylarginine synthesis and degradation in vivo, as well as specific alterations to intrapulmonary ADMA levels or distorted generation of ADMA in PAH, however, remains to be elucidated. In the current study, we hypothesized that methylarginine production and degradation is tissue-specific and that the lung has a significant impact on serum/plasma ADMA levels, possibly leading to endothelial dysfunction observed in PAH. To this end, we sought to address the following specific aims: 1) to develop a novel, HPLC-based method to assess protein-incorporated and free cellular methylarginine content in biological samples, 2) to analyze the tissue-specific methylarginine metabolism in normal subjects, and 3) to analyze the methylarginine content in the lungs of patients with PAH compared with healthy donors. First, to analyze tissue-specific methylarginine metabolism in the normal physiological state, we performed high performance liquid chromatography (HPLC)-driven assessment of protein-incorporated and free cellular methylarginine levels, together with Western blot analyses of PRMT and DDAH expression, in organs of the cardiovascular system. Our results revealed that pulmonary expression of type I PRMT was correlated with enhanced protein arginine methylation in the lung. Moreover, our studies also revealed that the kidney and the liver provide complementary routes for clearance and metabolic conversion of circulating ADMA. To address the impact of intrapulmonary ADMA metabolism in pathogenic conditions, we next analyzed lung homogenates of PAH patients. HPLC analysis revealed significantly lower levels of protein-incorporated ADMA in the lungs of PAH patients (n=12), compared with controls (n=10, transplant donors). Western Blot analyses confirmed a significantly decreased content of asymmetrically dimethylated proteins in PAH lungs. The expression of PRMT, in particular PRMT1, was decreased in PAH. Immunohistochemical staining of IPAH and control lungs localized PRMT1 to pulmonary arterial vascular smooth muscle cells (PASMC). Moreover, PRMT1 knockdown in primary PASMC by siRNA technology significantly increased PASMC proliferation. Our results demonstrate that, in the normal physiological state, methylarginine metabolism by the pulmonary system significantly contributes to circulating methylarginine levels. In pathogenic conditions, protein-incorporated ADMA concentrations do not reflect free cellular levels of ADMA in the lung. This may be explained by the alterations of DDAH activity in the lung, which, consequently, regulate ADMA content in the serum of IPAH patients. In addition, our studies demonstrated a novel regulatory role of PRMT1 in progression of PAH, by the alteration of PASMC proliferation, a major characteristic of PAH. This led to conclusions that protein arginine methylation plays a pivotal role in the pathogenesis of PAH.Posttranslationale Protein-Arginin Methylierung erfolgt durch eine Gruppe spezifischer Protein-Arginin Methyltransferasen (PRMTs), die neben der Bildung von asymmetrischem Dimethylarginin (ADMA) auch für die Synthese von Monomethylarginin (L-NMMA) und symmetrischem Dimethylarginin (SDMA) verantwortlich sind. Die Freisetzung von Methylarginine in das Blutplasma erfolgt nach heutigem Wissensstand über die Proteolyse zellulärer, methylierter Proteine. Alle Methylargininformen werden über renale Exkretion aus dem Körper eliminiert. Neuere Studien heben die Metabolisierung von ADMA und L-NMMA durch das Enzym Dimethylarginin-Dimethylaminohydrolase (DDAH) als Hauptabbauweg hervor. ADMA ist ein endogener Inhibitor der NO-Synthase und ein Marker für endotheliale Fehlfunktion. Eine erhöhte ADMA Konzentration im Blut wird bei verschiedenen kardiovaskulären Erkrankungen, so auch bei pulmonal-arterieller Hypertonie (PAH), für einen Mangel an biologisch verfügbarem NO verantwortlich gemacht. Die pulmonal-arterielle Hypertonie ist durch eine pathologische Hypertrophie und Proliferation pulmonalarterieller glatter Muskelzellen (PASMC) gekennzeichnet, die eine Okklusion pulmonaler Arteriolen zur Folge hat. Ob ein Zusammenhang zwischen Arginin- und Dimethylargininstoffwechsel und den bei PAH zu beobachtenden Symptomen vorliegt, wurde bislang nicht untersucht. Deshalb sollte in der vorliegenden Studie geprüft werden, ob der Methylarginin-metabolismus der Lunge signifikant zur ADMA Konzentration im Blut beiträgt und somit an der Ausbildung endothelialer Fehlfunktionen beteiligt sein könnte. Im Konkreten sollten hierfür folgende Vorhaben realisiert werden: (1) Entwicklung einer auf Hochdruckflüssigkeitschromatographie-basierenden Methode zur Quantifizierung von protein-inkorporiertem und freiem Methylarginin in biologischen Proben, (2) Analyse des gewebespezifischen Methylargininmetabolismus und (3) Bestimmung des pulmonalen Methylarginingehaltes von PAH Patienten und gesunden Organspendern. Zur Beschreibung des Methylargininmetabolismus unter normalen physiologischen Bedingungen wurden protein-inkorporiertes und freies Methylarginin in Organen des kardiovaskulären Systems bestimmt. Zudem wurde vergleichend Proteinexpression und Aktivität der PRMTs und DDAHs ermittelt. Unsere Untersuchungen ergaben eine klare Korrelation zwischen pulmonaler Typ I PRMT Proteinexpression und erhöhter Protein-Arginin Methylierung. Zudem konnte gezeigt werden, dass Niere und Leber komplementär an der Eliminierung und Metabolisierung von ADMA und L-NMMA beteiligt sind. Zur Beurteilung der Frage, ob bei PAH ein geänderter Dimethylargininstoffwechsel zu beobachten ist, wurde Lungenhomogenat mittels HPLC untersucht. Die Analyse bei PAH Patienten (n=12) und gesunden Organspendern (n=10) ergab eine signifikante Abnahme an protein-inkorporiertem ADMA bei PAH Patienten. Zudem konnte über Western-Blot Analyse ein reduzierter Gehalt an asymmetrisch dimethylierten Proteinen nachgewiesen werden. Bei PAH Patienten zeigte sich auch eine signifikant reduzierte Expression jener Protein-Arginin-Methyltransferasen, insbesondere PRMT 1, die für eine asymmetrische Dimethylierung von Zielproteinen verantwortlich sind. Immunohistochemische Untersuchungen führten zu dem Ergebnis, dass PRMT 1 überwiegend in PASMCs lokalisiert ist. Zudem resultierte die Reduktion der PRMT 1 Expression mittels siRNA Technologie in einer Zunahme der PASMC Proliferation. Aus den vorliegenden Ergebnissen lässt sich somit schlussfolgern, dass der pulmonale Dimethylargininmetabolismus maßgeblich zum Plasma ADMA-Spiegel beiträgt. Bei PAH Patienten konnte keine Korrelation zwischen protein-inkorporiertem ADMA und freiem Methylarginin nachgewiesen werden. Dieses Ergebnis deutet auf eine Änderung der pulmonalen DDAH Aktivität und Plasma ADMA-Werte bei PAH Patienten hin. Des Weiteren konnte eindeutig demonstriert werden, dass PRMT 1 an der Regulation der PASMC Proliferation beteiligt ist. Zusammenfassend lässt sich somit feststellen, dass Protein-Arginin Methylierung an der Entwicklung und am Fortschreiten von PAH beteiligt sein könnte

Measures and Forecasts of Agricultural Land Values

This thesis is comprised of two articles that examine farmland values and farmland value forecasts for non-irrigated cropland, irrigated cropland, and pasture. The first article considers the collection and reporting procedures each of three data sources: the United States Department of Agriculture's (USDA) annual report, the Federal Reserve's quarterly 10th District Survey of Agricultural Credit Conditions, and sales data. The objective of this essay is to determine if the land value estimates from opinion based surveys are consistent with values observed from land sales. Additionally, Granger causality tests are used to determine if land values published by the Federal Reserve prior to the release of the USDA report are indicators of USDA land values. The second essay examines forecasts from the Federal Reserve's survey to determine if bankers can accurately forecast land values. Various forecasting techniques are used to compare bankers' quarterly forecasts to their own reported changes in land value. In the first essay, land values from each source are found to be highly correlated, but land value averages from sales data is often higher than averages derived from survey data. With respect to the survey data, first quarter Federal Reserve Bank estimates are indicators of USDA land value estimates. The second essay finds that agricultural lenders have some ability to forecast land values for the next quarter. For each of the forecasting methods used, bankers' one-step-ahead forecasts produced had lower root mean squared errors than forecasts produced by nave forecasting models.Department of Agricultural Economic

Comparison of Alternative Sources of Farmland Values

Consistent and reliable data on farmland values is critical to assessing the overall financial health of agricultural producers. However, little is known about the idiosyncrasies and similarities of standard land value data sources – U.S. Department of Agriculture, Federal Reserve Bank land value surveys, and transaction prices. All three data sources are highly correlated, but transaction prices tend to be higher, especially for irrigated cropland and ranchland. USDA land values are reported as representing land values on January first, but instead they more closely represent first and second quarter land values according to a multi-state comparison to changes in quarterly Federal Reserve land values. Given the finding that first quarter Federal Reserve Bank land values lead USDA land values and that they are published before the USDA release, Federal Reserve land values are a timely indicator of agricultural producers’ financial position.Land Economics/Use,

Phosphocholine – an agonist of metabotropic but not of ionotropic functions of alpha9-containing nicotinic acetylcholine receptors

We demonstrated previously that phosphocholine and phosphocholine-modified macromolecules efficiently inhibit ATP-dependent release of interleukin-1beta from human and murine monocytes by a mechanism involving nicotinic acetylcholine receptors (nAChR). Interleukin-1beta is a potent pro-inflammatory cytokine of innate immunity that plays pivotal roles in host defence. Control of interleukin-1beta release is vital as excessively high systemic levels cause life threatening inflammatory diseases. In spite of its structural similarity to acetylcholine, there are no other reports on interactions of phosphocholine with nAChR. In this study, we demonstrate that phosphocholine inhibits ion-channel function of ATP receptor P2X7 in monocytic cells via nAChR containing alpha9 and alpha10 subunits. In stark contrast to choline, phosphocholine does not evoke ion current responses in Xenopus laevis oocytes, which heterologously express functional homomeric nAChR composed of alpha9 subunits or heteromeric receptors containing alpha9 and alpha10 subunits. Preincubation of these oocytes with phosphocholine, however, attenuated choline-induced ion current changes, suggesting that phosphocholine may act as a silent agonist. We conclude that phophocholine activates immuno-modulatory nAChR expressed by monocytes but does not stimulate canonical ionotropic receptor functions

The Methyltransferase Smyd1 Mediates LPS-Triggered Up-Regulation of IL-6 in Endothelial Cells

The lysine methyltransferase Smyd1 with its characteristic catalytic SET-domain is highly enriched in the embryonic heart and skeletal muscles, participating in cardiomyogenesis, sarcomere assembly and chromatin remodeling. Recently, significant Smyd1 levels were discovered in endothelial cells (ECs) that responded to inflammatory cytokines. Based on these biochemical properties, we hypothesized that Smyd1 is involved in inflammation-triggered signaling in ECs and therefore, investigated its role within the LPS-induced signaling cascade. Human endothelial cells (HUVECs and EA.hy926 cells) responded to LPS stimulation with higher intrinsic Smyd1 expression. By transfection with expression vectors containing gene inserts encoding either intact Smyd1, a catalytically inactive Smyd1-mutant or Smyd1-specific siRNAs, we show that Smyd1 contributes to LPS-triggered expression and secretion of IL-6 in EA.hy926 cells. Further molecular analysis revealed this process to be based on two signaling pathways: Smyd1 increased the activity of NF-kappa B and promoted the trimethylation of lysine-4 of histone-3 (H3K4me3) within the IL-6 promoter, as shown by ChIP-RT-qPCR combined with IL-6-promoter-driven luciferase reporter gene assays. In summary, our experimental analysis revealed that LPS-binding to ECs leads to the up-regulation of Smyd1 expression to transduce the signal for IL-6 up-regulation via activation of the established NF-κB pathway as well as via epigenetic trimethylation of H3K4

Differential Expression of VEGFA, TIE2, and ANG2 but not ADAMTS1 in Rat Mesenteric Microvascular Arteries and Veins

Summary Microvessels respond to metabolic stimuli (e.g. pO 2 ) and hemodynamic forces (e.g. shear stress and wall stress) with structural adaptations including angiogenesis, remodeling an