The colony-stimulating factor 1 receptor is expressed on dendritic cells during differentiation and regulates their expansion

The lineage of dendritic cells (DC), and in particular their relationship to monocytes and macrophages, remains obscure. Furthermore, the requirement for the macrophage growth factor CSF-1 during DC homeostasis is unclear. Using a transgenic mouse in which the promoter for the CSF-1R (c-fms) directs the expression of enhanced GFP in cells of the myeloid lineage, we determined that although the c-fms promoter is inactive in DC precursors, it is up-regulated in all DC subsets during differentiation. Furthermore, plasmacytoid DC and all CD11c(high) DC subsets are reduced by 50-70% in CSF-1-deficient osteopetrotic mice, confirming that CSF-1 signaling is required for the optimal differentiation of DC in vivo. These data provide additional evidence that the majority of tissue DC is of myeloid origin during steady state and supports a close relationship between DC and macrophage biology in vivo.

Pituitary adenylate cyclase-activating polypeptide type 1 receptor (PAC1) gene is suppressed by transglutaminase 2 activation

Pituitary adenylate cyclase-activating polypeptide (PACAP) functions as a neuroprotective factor through the PACAP type 1 receptor, PAC1. In a previous work, we demonstrated that nerve growth factor augmented PAC1 gene expression through the activation of Sp1 via the Ras/MAPK pathway. We also observed that PAC1 expression in Neuro2a cells was transiently suppressed during in vitro ischemic conditions, oxygen-glucose deprivation (OGD). Because endoplasmic reticulum (ER) stress is induced by ischemia, we attempted to clarify how ER stress affects the expression of PAC1. Tunicamycin, which induces ER stress, significantly suppressed PAC1 gene expression, and salubrinal, a selective inhibitor of the protein kinase RNA-like endoplasmic reticulum kinase signaling pathway of ER stress, blocked the suppression. In luciferase reporter assay, we found that two Sp1 sites were involved in suppression of PAC1 gene expression due to tunicamycin or OGD. Immunocytochemical staining demonstrated that OGD-induced transglutaminase 2 (TG2) expression was suppressed by salubrinal or cystamine, a TG activity inhibitor. Further, the OGD-induced accumulation of cross-linked Sp1 in nuclei was suppressed by cystamine or salubrinal. Together with cystamine, R283, TG2-specific inhibitor, and siRNA specific for TG2 also ameliorated OGD-induced attenuation of PAC1 gene expression. These results suggest that Sp1 cross-linking might be crucial in negative regulation of PAC1 gene expression due to TG2 in OGD-induced ER stress. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.

Investigating G protein signalling bias at the glucagon-like peptide-1 receptor in yeast

Background and Purpose The glucagon-like peptide 1 (GLP-1) receptor performs an important role in glycaemic control, stimulating the release of insulin. It is an attractive target for treating type 2 diabetes. Recently, several reports of adverse side effects following prolonged use of GLP-1 receptor therapies have emerged: most likely due to an incomplete understanding of signalling complexities. Experimental Approach We describe the expression of the GLP-1 receptor in a panel of modified yeast strains that couple receptor activation to cell growth via single Gα/yeast chimeras. This assay enables the study of individual ligand-receptor G protein coupling preferences and the quantification of the effect of GLP-1 receptor ligands on G protein selectivity. Key Results The GLP-1 receptor functionally coupled to the chimeras representing the human Gαs, Gαi and Gαq subunits. Calculation of the dissociation constant for a receptor antagonist, exendin-3 revealed no significant difference between the two systems. We obtained previously unobserved differences in G protein signalling bias for clinically relevant therapeutic agents, liraglutide and exenatide; the latter displaying significant bias for the Gαi pathway. We extended the use of the system to investigate small-molecule allosteric compounds and the closely related glucagon receptor. Conclusions and Implications These results provide a better understanding of the molecular events involved in GLP-1 receptor pleiotropic signalling and establish the yeast platform as a robust tool to screen for more selective, efficacious compounds acting at this important class of receptors in the future. © 2014 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of The British Pharmacological Society.

Autoantibody from women with preeclampsia induces soluble Fms-like tyrosine kinase-1 production via angiotensin type 1 receptor and calcineurin/nuclear factor of activated T-cells signaling

Preeclampsia is a pregnancy-specific hypertensive syndrome that causes substantial maternal and fetal morbidity and mortality. Recent evidence indicates that maternal endothelial dysfunction in preeclampsia results from increased soluble Fms-like tyrosine kinase-1 (sFlt-1), a circulating antiangiogenic protein. Factors responsible for excessive production of sFlt-1 in preeclampsia have not been identified. We tested the hypothesis that angiotensin II type 1 (AT1) receptor activating autoantibodies, which occur in women with preeclampsia, contribute to increased production of sFlt-1. IgG from women with preeclampsia stimulates the synthesis and secretion of sFlt-1 via AT1 receptor activation in pregnant mice, human placental villous explants, and human trophoblast cells. Using FK506 or short-interfering RNA targeted to the calcineurin catalytic subunit mRNA, we determined that calcineurin/nuclear factor of activated T-cells signaling functions downstream of the AT1 receptor to induce sFlt-1 synthesis and secretion by AT1-receptor activating autoantibodies. AT1-receptor activating autoantibody–induced sFlt-1 secretion resulted in inhibition of endothelial cell migration and capillary tube formation in vitro. Overall, our studies demonstrate that an autoantibody from women with preeclampsia induces sFlt-1 production via angiotensin receptor activation and downstream calcineurin/nuclear factor of activated T-cells signaling. These autoantibodies represent potentially important targets for diagnosis and therapeutic intervention.

Cholecystokinin-1 receptor antagonists:5-hydroxy-5-aryl-pyrrol-2-ones as anticancer agents

A new class of 5-arylated 5-hydroxypyrrolones was derived from mucochloric acid in 2 synthetic steps and the chemical structure was confirmed additionally by X-ray analysis. Using a radiolabelled binding assay, potent CCK1 selective ligands were identified (CCK1: 12 nM) and the antagonism was confirmed by using isolated tissue preparations. A series of isobutyl derivatives displayed unsurmountable CCK antagonistic properties and in vitro excellent inhibition of proliferation was obtained in cholecystokinin related cancer cell lines in the nanomolar range. Finally, using xenograft studies in nude mice, two selected pyrrolone derivatives, X = H and X = F a fluorinated analogue (PNB-028), showed a strong inhibition of tumour growth in a chemo-resistant colon cancer-(MAC 16) and a human pancreatic cell line (MIAPACA) at 50 mg kg-1 by oral administration.

Implementación sobre FPGA de un algoritmo de compresión de imágenes hiperespectrales bajo el estándar CCSDS 123.0-B-1

A lo largo de la historia, nuestro planeta ha atravesado numerosas y diferentes etapas. Sin embargo, desde finales del cretácico no se vivía un cambio tan rápido como el actual. Y a la cabeza del cambio, nosotros, el ser humano. De igual manera que somos la causa, debemos ser también la solución, y el análisis a gran escala de la tierra está siendo un punto de interés para la comunidad científica en los últimos años. Prueba de ello es que, cada vez con más frecuencia, se lanzan gran cantidad de satélites cuya finalidad es el análisis, mediante fotografías, de la superficie terrestre. Una de las técnicas más versátiles para este análisis es la toma de imágenes hiperespectrales, donde no solo se captura el espectro visible, sino numerosas longitudes de onda. Suponen, eso sí un reto tecnológico, pues los sensores consumen más energía y las imágenes más memoria, ambos recursos escasos en el espacio. Dado que el análisis se hace en tierra firme, es importante una transmisión de datos eficaz y rápida. Por ello creemos que la compresión en tiempo real mediante FPGAs es la solución idónea, combinando un bajo consumo con una alta tasa de compresión, posibilitando el análisis ininterrumpido del astro en el que vivimos. En este trabajo de fin de grado se ha realizado una implementación sobre FPGA, utilizando VHDL, del estándar CCSDS 123. Este está diseñado para la compresión sin pérdida de imágenes hiperespectrales, y permite una amplia gama de configuraciones para adaptarse de manera óptima a cualquier tipo de imagen. Se ha comprobado exitosamente la validez de la implementación comparando los resultados obtenidos con otras implementaciones (software) existentes. Las principales ventajas que presentamos aquí es que se posibilita la compresión en tiempo real, obteniendo además un rendimiento energético muy prometedor. Estos resultados mejoran notablemente los de una implementación software del algoritmo, y permitirán la compresión de las imágenes a bordo de los satélites que las toman.

B-1 Monthly Report of Medical Services Provided under Title XIX of the Social Security Act, April 2016

B-1 Medicaid Reports -- The monthly Medicaid series of eight reports provide summaries of Medicaid eligibles, recipients served, and total payments by county, category of service, and aid category. These reports may also be known as the B-1 Reports. These reports are each available as a PDF for printing or as a CSV file for data analysis. Report Report name IAMM1800-R001--Medically Needy by County - No Spenddown and With Spenddown; IAMM1800-R002--Total Medically Needy, All Other Medicaid, and Grand Total by County; IAMM2200-R002--Monthly Expenditures by Category of Service; IAMM2200-R003--Fiscal YTD Expenditures by Category of Service; IAMM3800-R001--ICF & ICF-MR Vendor Payments by County; IAMM4400-R001--Monthly Expenditures by Eligibility Program; IAMM4400-R002--Monthly Expenditures by Category of Service by Program; IAMM4600-R002--Elderly Waiver Summary by County.

B-1 Monthly Report of Medical Services Provided under Title XIX of the Social Security Act, May 2016

B-1 Medicaid Reports -- The monthly Medicaid series of eight reports provide summaries of Medicaid eligibles, recipients served, and total payments by county, category of service, and aid category. These reports may also be known as the B-1 Reports. These reports are each available as a PDF for printing or as a CSV file for data analysis. Report Report name IAMM1800-R001--Medically Needy by County - No Spenddown and With Spenddown; IAMM1800-R002--Total Medically Needy, All Other Medicaid, and Grand Total by County; IAMM2200-R002--Monthly Expenditures by Category of Service; IAMM2200-R003--Fiscal YTD Expenditures by Category of Service; IAMM3800-R001--ICF & ICF-MR Vendor Payments by County; IAMM4400-R001--Monthly Expenditures by Eligibility Program; IAMM4400-R002--Monthly Expenditures by Category of Service by Program; IAMM4600-R002--Elderly Waiver Summary by County.

B-1 Monthly Report of Medical Services Provided under Title XIX of the Social Security Act, February 2016

B-1 Medicaid Reports -- The monthly Medicaid series of eight reports provide summaries of Medicaid eligibles, recipients served, and total payments by county, category of service, and aid category. These reports may also be known as the B-1 Reports. These reports are each available as a PDF for printing or as a CSV file for data analysis. Report Report name IAMM1800-R001--Medically Needy by County - No Spenddown and With Spenddown; IAMM1800-R002--Total Medically Needy, All Other Medicaid, and Grand Total by County; IAMM2200-R002--Monthly Expenditures by Category of Service; IAMM2200-R003--Fiscal YTD Expenditures by Category of Service; IAMM3800-R001--ICF & ICF-MR Vendor Payments by County; IAMM4400-R001--Monthly Expenditures by Eligibility Program; IAMM4400-R002--Monthly Expenditures by Category of Service by Program; IAMM4600-R002--Elderly Waiver Summary by County.

B-1 Monthly Report of Medical Services Provided under Title XIX of the Social Security Act, June 2016

B-1 Medicaid Reports -- The monthly Medicaid series of eight reports provide summaries of Medicaid eligibles, recipients served, and total payments by county, category of service, and aid category. These reports may also be known as the B-1 Reports. These reports are each available as a PDF for printing or as a CSV file for data analysis. Report Report name IAMM1800-R001--Medically Needy by County - No Spenddown and With Spenddown; IAMM1800-R002--Total Medically Needy, All Other Medicaid, and Grand Total by County; IAMM2200-R002--Monthly Expenditures by Category of Service; IAMM2200-R003--Fiscal YTD Expenditures by Category of Service; IAMM3800-R001--ICF & ICF-MR Vendor Payments by County; IAMM4400-R001--Monthly Expenditures by Eligibility Program; IAMM4400-R002--Monthly Expenditures by Category of Service by Program; IAMM4600-R002--Elderly Waiver Summary by County.

B-1 Monthly Report of Medical Services Provided under Title XIX of the Social Security Act, July 2016

B-1 Medicaid Reports -- The monthly Medicaid series of eight reports provide summaries of Medicaid eligibles, recipients served, and total payments by county, category of service, and aid category. These reports may also be known as the B-1 Reports. These reports are each available as a PDF for printing or as a CSV file for data analysis. Report Report name IAMM1800-R001--Medically Needy by County - No Spenddown and With Spenddown; IAMM1800-R002--Total Medically Needy, All Other Medicaid, and Grand Total by County; IAMM2200-R002--Monthly Expenditures by Category of Service; IAMM2200-R003--Fiscal YTD Expenditures by Category of Service; IAMM3800-R001--ICF & ICF-MR Vendor Payments by County; IAMM4400-R001--Monthly Expenditures by Eligibility Program; IAMM4400-R002--Monthly Expenditures by Category of Service by Program; IAMM4600-R002--Elderly Waiver Summary by County.

B-1 Monthly Report of Medical Services Provided under Title XIX of the Social Security Act, August 2016

B-1 Medicaid Reports -- The monthly Medicaid series of eight reports provide summaries of Medicaid eligibles, recipients served, and total payments by county, category of service, and aid category. These reports may also be known as the B-1 Reports. These reports are each available as a PDF for printing or as a CSV file for data analysis. Report Report name IAMM1800-R001--Medically Needy by County - No Spenddown and With Spenddown; IAMM1800-R002--Total Medically Needy, All Other Medicaid, and Grand Total by County; IAMM2200-R002--Monthly Expenditures by Category of Service; IAMM2200-R003--Fiscal YTD Expenditures by Category of Service; IAMM3800-R001--ICF & ICF-MR Vendor Payments by County; IAMM4400-R001--Monthly Expenditures by Eligibility Program; IAMM4400-R002--Monthly Expenditures by Category of Service by Program; IAMM4600-R002--Elderly Waiver Summary by County.

B-1 Monthly Report of Medical Services Provided under Title XIX of the Social Security Act, September 2016

B-1 Medicaid Reports -- The monthly Medicaid series of eight reports provide summaries of Medicaid eligibles, recipients served, and total payments by county, category of service, and aid category. These reports may also be known as the B-1 Reports. These reports are each available as a PDF for printing or as a CSV file for data analysis. Report Report name IAMM1800-R001--Medically Needy by County - No Spenddown and With Spenddown; IAMM1800-R002--Total Medically Needy, All Other Medicaid, and Grand Total by County; IAMM2200-R002--Monthly Expenditures by Category of Service; IAMM2200-R003--Fiscal YTD Expenditures by Category of Service; IAMM3800-R001--ICF & ICF-MR Vendor Payments by County; IAMM4400-R001--Monthly Expenditures by Eligibility Program; IAMM4400-R002--Monthly Expenditures by Category of Service by Program; IAMM4600-R002--Elderly Waiver Summary by County.

B-1 Monthly Report of Medical Services Provided under Title XIX of the Social Security Act, September 2016

B-1 Medicaid Reports -- The monthly Medicaid series of eight reports provide summaries of Medicaid eligibles, recipients served, and total payments by county, category of service, and aid category. These reports may also be known as the B-1 Reports. These reports are each available as a PDF for printing or as a CSV file for data analysis. Report Report name IAMM1800-R001--Medically Needy by County - No Spenddown and With Spenddown; IAMM1800-R002--Total Medically Needy, All Other Medicaid, and Grand Total by County; IAMM2200-R002--Monthly Expenditures by Category of Service; IAMM2200-R003--Fiscal YTD Expenditures by Category of Service; IAMM3800-R001--ICF & ICF-MR Vendor Payments by County; IAMM4400-R001--Monthly Expenditures by Eligibility Program; IAMM4400-R002--Monthly Expenditures by Category of Service by Program; IAMM4600-R002--Elderly Waiver Summary by County.