Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Tasa de preñez en vaquillas anéstricas tratadas con CIDR más Benzoato de Estradiol, Cipionato de Estradiol o GnRH e inseminadas a celo detectado

12 p.Bueno, A.; Dunn, R. 2008. Tasa de preñez en vaquillas anéstricas tratadas con CIDR más Benzoato de Estradiol, Cipionato de Estradiol o GnRH e inseminadas a celo detectado. Proyecto especial del programa de Ingeniero Agrónomo, Escuela Agrícola Panamericana, El Zamorano.12p. Los obstáculos reproductivos existen dentro de casi todas las explotaciones ganaderas. Dentro de los obstáculos más importantes se encuentra la inactividad ovárica (anestro). El anestro es considerado como el factor más determinante en la presentación de la infertilidad de los hatos, debido a que determina cuantos de los vientres disponibles no han iniciado la actividad ovulatoria en la fecha programada de empadre. Se utilizaron 83 vaquillas Pardo Suizo, Holstein y Jersey, distribuidas en tres grupos en los que se usó CIDR®+BE (n=29) CIDR®+ECP (n=26) y CIDR®+GnRH (n=28). En el porcentaje de inducción de celo no se encontró diferencia (P>0.05), sin embargo, se obtuvo un 100% de presencia de celo con el tratamiento CIDR®+ECP. El porcentaje de preñez obtuvo una mejor respuesta en el primer servicio con CIDR®+BE de 59.25% y CIDR®+GnRH de 75%. En el segundo, tercer servicio y la preñez acumulada no se encontró diferencia P>0.05. En los Servicios por Concepción (S/C) se encontró diferencia (P0.05. La Tasa de Concepción (TC) tanto el CIDR®+GnRH como CIDR®+BE obtuvieron un 66.66% de TC. El costo por vaquilla preñada con CIDR®+BE, CIDR®+ECP y CIDR®+GnRH fue de US $ 7.41, 8.46 y 9.28 respectivamente. Los tratamientos utilizados estimulan en forma similar el inicio de la actividad ovárica y la presentación de celo en vaquillas anéstricas. Siendo los resultados similares la decisión de escoger un protocolo recae sobre el factor económico siendo CIDR®+BE la mejor opción

Nanotechnology for environmentally sustainable electromobility

ABSTRACT: Electric vehicles (EVs) powered by lithium-ion batteries (LIBs) or proton exchange membrane hydrogen fuel cells (PEMFCs) offer important potential climate change mitigation effects when combined with clean energy sources. The development of novel nanomaterials may bring about the next wave of technical improvements for LIBs and PEMFCs. If the next generation of EVs is to lead to not only reduced emissions during use but also environmentally sustainable production chains, the research on nanomaterials for LIBs and PEMFCs should be guided by a life-cycle perspective. In this Analysis, we describe an environmental life-cycle screening framework tailored to assess nanomaterials for electromobility. By applying this framework, we offer an early evaluation of the most promising nanomaterials for LIBs and PEMFCs and their potential contributions to the environmental sustainability of EV life cycles. Potential environmental trade-offs and gaps in nanomaterials research are identified to provide guidance for future nanomaterial developments for electromobility