ps4 70 anti phosphatidylserine prothrombin antibodies and cardiovascular risk in a sle cohort of patients

Introduction Clinical activity of SLE may wax and wane, but persistent, active systemic inflammation leads to organ damage and rises morbidity and mortality. Early damage is mostly related to disease activity, whereas later damage, in particular atherosclerosis, infections and malignancies are usual complications of long-standing disease and treatment with immunosuppressive agents. One of the major late causes of death in SLE is thrombosis, in particular stroke and myocardial infarction due to CAD. In these patients, the increased cardiovascular morbidity is not fully explained by traditional risk factors and this may lead to under-recognition and under-treatment. Petri, et al. proposed an equation for cardiovascular disease risk in SLE, which combines classical parameters and disease activity markers. Other scores such as the GAPSS(Global AntiPhospholipid Syndrome Score) have been recently evaluated. The importance of aPL in thrombosis in general is well defined, as they constitute the culprit of the so-called anti-phospholipid syndrome(APS). Their role in sustaining the high risk of cardiovascular complications of SLE patients is under-debated. Objective To study the role of the anti-phosphatidylserine/prothrombin(aPS/PT) antibodies, included in the GAPSS score, in contributing to the thrombotic risk of SLE patients. Methods We enrolled 172 patients from Ospedale San Raffaele. 132 patients with SLE(111/132, 84% without secondary APS, SAPS, and 21/132, 16% with SAPS), 19 with primary APS(PAPS) and 21 healthy controls. Each recruited patient was tested for aPS/PT IgG and IgM through ELISA by INOVA Diagnostic, Inc. San Diego, CA USA. Results 36/111 (32.4%) SLE without APS, 15/21 (71.4%) SAPS, 13/19 (68.4%) PAPS and 3/21 (14.3%) healthy donors were aPS/PT+. aPS/PT+SLE patients had a higher cardiovascular risk according to the Petri's score, when compared to aPS/PT-patients, irrespectively of a positive or negative history of overt APS(Mean ±SD Petri' score=20.8±18.1, 14.0±12.8 and 23.8±22.5, 11.6±9.3 respectively, p 10 had also higher prevalence of pregnancy complications. Conclusion aPS/PT antibodies are associated with a high risk of thrombosis and CAD in SLE. aPS/PT assays should be routinely introduced in the management of these patients

A systematic analysis of orphan cyclins reveals CNTD2 as a new oncogenic driver in lung cancer

As lung cancer has increased to the most common cause of cancer death worldwide, prognostic biomarkers and effective targeted treatments remain lacking despite advances based on patients' stratification. Multiple core cyclins, best known as drivers of cell proliferation, are commonly deregulated in lung cancer where they may serve as oncogenes. The recent expansion of the cyclin family raises the question whether new members might play oncogenic roles as well. Here, we investigated the protein levels of eight atypical cyclins in lung cancer cell lines and formalin-fixed and paraffin-embedded (FFPE) human tumors, as well as their functional role in lung cancer cells. Of the new cyclins evaluated, CNTD2 was significantly overexpressed in lung cancer compared to adjacent normal tissue, and exhibited a predominant nuclear location. CNTD2 overexpression increased lung cancer cell viability, Ki-67 intensity and clonogenicity and promoted lung cancer cell migration. Accordingly, CNTD2 enhanced tumor growth in vivo on A549 xenograft models. Finally, the analysis of gene expression data revealed a high correlation between elevated levels of CNTD2 and decreased overall survival in lung cancer patients. Our results reveal CNTD2 as a new oncogenic driver in lung cancer, suggesting value as a prognostic biomarker and therapeutic target in this disease

The atypical cyclin CNTD2 promotes colon cancer cell proliferation and migration

Colorectal cancer (CRC) is one of the most common cancers worldwide, with 8-10% of these tumours presenting a BRAF (V600E) mutation. Cyclins are known oncogenes deregulated in many cancers, but the role of the new subfamily of atypical cyclins remains elusive. Here we have performed a systematic analysis of the protein expression levels of eight atypical cyclins in human CRC tumours and several cell lines, and found that CNTD2 is significantly upregulated in CRC tissue compared to the adjacent normal one. CNTD2 overexpression in CRC cell lines increases their proliferation capacity and migration, as well as spheroid formation capacity and anchorage-independent growth. Moreover, CNTD2 increases tumour growth in vivo on xenograft models of CRC with wild-type BRAF. Accordingly, CNTD2 downregulation significantly diminished the proliferation of wild-type BRAF CRC cells, suggesting that CNTD2 may represent a new prognostic factor and a promising drug target in the management of CRC

The Role of Native Language and the Fundamental Design of the Auditory System in Detecting Rhythm Changes

Accepted December 13, 2018Purpose: We investigated whether rhythm discrimination is mainly driven by the native language of the listener or by the fundamental design of the human auditory system and universal cognitive mechanisms shared by all people irrespective of rhythmic patterns in their native language. Method: In multiple experiments, we asked participants to listen to 2 continuous acoustic sequences and to determine whether their rhythms were the same or different (AX discrimination). Participants were native speakers of 4 languages with different rhythmic properties (Spanish, French, English, and German) to understand whether the predominant rhythmic patterns of a native language affect sensitivity, bias, and reaction time in detecting rhythmic changes in linguistic (Experiment 2) and in nonlinguistic (Experiments 1 and 2) acoustic sequences. We examined sensitivity and bias measures, as well as reaction times. We also computed Bayes factors in order to assess the effect of native language. Results: All listeners performed better (i.e., responded faster and manifested higher sensitivity and accuracy) when detecting the presence or absence of a rhythm change when the 1st stimulus in an AX test pair exhibited regular rhythm (i.e., a syllable-timed rhythmic pattern) than when the 1st stimulus exhibited irregular rhythm (i.e., stress-timed rhythmic pattern). This result pattern was observed both on linguistic and nonlinguistic stimuli and was not modulated by the native language of the participant. Conclusion: We conclude that rhythm change detection is a fundamental function of a processing system that relies on general auditory mechanisms and is not modulated by linguistic experience.The authors acknowledge support from Spanish Ministry of Economy and Competitiveness Grant PSI2017-82563-P (awarded to A. G. S.), the “Severo Ochoa” Programme for Centres/Units of Excellence in R&D Grant SEV-2015-490 (BCBL), and the Basque Foundation for Science Grant IKERBASQUE (awarded to A. G. S. and M. O.). D. M. G. was supported by Grant PIA/Basal FB0003 from the Chilean Research Council. L. P. was supported by the Spanish Ministry of Economy and Competitiveness via Juan de la Cierva fellowship

Microscopy Characterization of Silica-Rich Agrowastes to be used in Cement Binders: Bamboo and Sugarcane Leaves

Agrowastes are produced worldwide in huge quantities and they contain interesting elements for producing inorganic cementing binders, especially silicon. Conversion of agrowastes into ash is an interesting way of yielding raw material used in the manufacture of low-CO2 binders. Silica-rich ashes are preferred for preparing inorganic binders. Sugarcane leaves (Saccharum officinarum, SL) and bamboo leaves (Bambusa vulgaris, BvL and Bambusa gigantea, BgL), and their corresponding ashes (SLA, BvLA, and BgLA), were chosen as case studies. These samples were analyzed by means of optical microscopy, Cryo-scanning electron microscopy (SEM), SEM, and field emission scanning electron microscopy. Spodograms were obtained for BvLA and BgLA, which have high proportions of silicon, but no spodogram was obtained for SLA because of the low silicon content. Different types of phytoliths (specific cells, reservoirs of silica in plants) in the studied leaves were observed. These phytoliths maintained their form after calcination at temperatures in the 350¿850°C range. Owing to the chemical composition of these ashes, they are of interest for use in cements and concrete because of their possible pozzolanic reactivity. However, the presence of significant amounts of K and Cl in the prepared ashes implies a limitation of their applications.The authors thank the Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (Projeto CNPq 40174/2013-1) of Brazil for funding the research. The authors thank the Electron Microscopy Service of the Universitat Politecnica de Valencia and Materials Department of Universidade Estadual Paulista at Ilha Solteira.Rosello Caselles, J.; Soriano Martínez, L.; Santamarina Siurana, MP.; Akasaki, JL.; Melges, JLP.; Paya Bernabeu, JJ. (2015). Microscopy Characterization of Silica-Rich Agrowastes to be used in Cement Binders: Bamboo and Sugarcane Leaves. Microscopy and Microanalysis. 21(5):1314-1326. https://doi.org/10.1017/S1431927615015019S13141326215Villar-Cociña, E., Morales, E. V., Santos, S. F., Savastano, H., & Frías, M. (2011). Pozzolanic behavior of bamboo leaf ash: Characterization and determination of the kinetic parameters. Cement and Concrete Composites, 33(1), 68-73. doi:10.1016/j.cemconcomp.2010.09.003Tuck, C. O., Perez, E., Horvath, I. T., Sheldon, R. A., & Poliakoff, M. (2012). Valorization of Biomass: Deriving More Value from Waste. Science, 337(6095), 695-699. doi:10.1126/science.1218930Savastano Jr, H., Santos, S. F., Tonoli, G. H. D., Mejia, J. E. B., & Fiorelli, J. (2015). Non-conventional cement-based composites reinforced with vegetable fibers: A review of strategies to improve durability. Materiales de Construcción, 65(317), e041. doi:10.3989/mc.2015.05514Neethirajan, S., Gordon, R., & Wang, L. (2009). Potential of silica bodies (phytoliths) for nanotechnology. Trends in Biotechnology, 27(8), 461-467. doi:10.1016/j.tibtech.2009.05.002Kameník, J., Mizera, J., & Řanda, Z. (2013). Chemical composition of plant silica phytoliths. Environmental Chemistry Letters, 11(2), 189-195. doi:10.1007/s10311-012-0396-9Madani Hosseini, M., Shao, Y., & Whalen, J. K. (2011). Biocement production from silicon-rich plant residues: Perspectives and future potential in Canada. Biosystems Engineering, 110(4), 351-362. doi:10.1016/j.biosystemseng.2011.09.010GALLEGO, L. (2004). Phytolith Assemblages in Grasses Native to Central Argentina. Annals of Botany, 94(6), 865-874. doi:10.1093/aob/mch214Epstein, E. (1999). SILICON. Annual Review of Plant Physiology and Plant Molecular Biology, 50(1), 641-664. doi:10.1146/annurev.arplant.50.1.641Diamond, S. (1975). A review of alkali-silica reaction and expansion mechanisms 1. Alkalies in cements and in concrete pore solutions. Cement and Concrete Research, 5(4), 329-345. doi:10.1016/0008-8846(75)90089-7Le Blond, J. S., Williamson, B. J., Horwell, C. J., Monro, A. K., Kirk, C. A., & Oppenheimer, C. (2008). Production of potentially hazardous respirable silica airborne particulate from the burning of sugarcane. Atmospheric Environment, 42(22), 5558-5568. doi:10.1016/j.atmosenv.2008.03.018Diamond, S. (1976). A review of alkali-silica reaction and expansion mechanisms 2. Reactive aggregates. Cement and Concrete Research, 6(4), 549-560. doi:10.1016/0008-8846(76)90083-1Li, B., Song, Z., Wang, H., Li, Z., Jiang, P., & Zhou, G. (2014). Lithological control on phytolith carbon sequestration in moso bamboo forests. Scientific Reports, 4(1). doi:10.1038/srep05262Frías, M., Savastano, H., Villar, E., Sánchez de Rojas, M. I., & Santos, S. (2012). Characterization and properties of blended cement matrices containing activated bamboo leaf wastes. Cement and Concrete Composites, 34(9), 1019-1023. doi:10.1016/j.cemconcomp.2012.05.005Prychid, C. J., Rudall, P. J., & Gregory, M. (2003). Systematics and Biology of Silica Bodies in Monocotyledons. The Botanical Review, 69(4), 377-440. doi:10.1663/0006-8101(2004)069[0377:sabosb]2.0.co;2Nzihou, A. (2010). Toward the Valorization of Waste and Biomass. Waste and Biomass Valorization, 1(1), 3-7. doi:10.1007/s12649-010-9014-xFrías, M., Villar-Cociña, E., & Valencia-Morales, E. (2007). Characterisation of sugar cane straw waste as pozzolanic material for construction: Calcining temperature and kinetic parameters. Waste Management, 27(4), 533-538. doi:10.1016/j.wasman.2006.02.017Ma, J. F., & Yamaji, N. (2006). Silicon uptake and accumulation in higher plants. Trends in Plant Science, 11(8), 392-397. doi:10.1016/j.tplants.2006.06.007Rodrigues, M. S., Beraldo, A. L., Savastano Júnior, H., & Santos, S. F. (2013). Cinza de palha de cana-de-açúcar como adição mineral em fibrocimento. Revista Brasileira de Engenharia Agrícola e Ambiental, 17(12), 1347-1354. doi:10.1590/s1415-43662013001200014Le Blond, J. S., Horwell, C. J., Williamson, B. J., & Oppenheimer, C. (2010). Generation of crystalline silica from sugarcane burning. Journal of Environmental Monitoring, 12(7), 1459. doi:10.1039/c0em00020eTeixeira, S. R., Souza, A. E., Carvalho, C. L., Reynoso, V. C. S., Romero, M., & Rincón, J. M. (2014). Characterization of a wollastonite glass-ceramic material prepared using sugar cane bagasse ash (SCBA) as one of the raw materials. Materials Characterization, 98, 209-214. doi:10.1016/j.matchar.2014.11.003Aprianti, E., Shafigh, P., Bahri, S., & Farahani, J. N. (2015). Supplementary cementitious materials origin from agricultural wastes – A review. Construction and Building Materials, 74, 176-187. doi:10.1016/j.conbuildmat.2014.10.010Mohapatra, S., Sakthivel, R., Roy, G. S., Varma, S., Singh, S. K., & Mishra, D. K. (2011). Synthesis of β-SiC Powder from Bamboo Leaf in a DC Extended Thermal Plasma Reactor. Materials and Manufacturing Processes, 26(11), 1362-1368. doi:10.1080/10426914.2011.557127MOTOMURA, H., FUJII, T., & SUZUKI, M. (2006). Silica Deposition in Abaxial Epidermis before the Opening of Leaf Blades of Pleioblastus chino (Poaceae, Bambusoideae). Annals of Botany, 97(4), 513-519. doi:10.1093/aob/mcl01

Snazer: the simulations and networks analyzer

<p>Abstract</p> <p>Background</p> <p>Networks are widely recognized as key determinants of structure and function in systems that span the biological, physical, and social sciences. They are static pictures of the interactions among the components of complex systems. Often, much effort is required to identify networks as part of particular patterns as well as to visualize and interpret them.</p> <p>From a pure dynamical perspective, simulation represents a relevant <it>way</it>-<it>out</it>. Many simulator tools capitalized on the "noisy" behavior of some systems and used formal models to represent cellular activities as temporal trajectories. Statistical methods have been applied to a fairly large number of replicated trajectories in order to infer knowledge.</p> <p>A tool which both graphically manipulates reactive models and deals with sets of simulation time-course data by aggregation, interpretation and statistical analysis is missing and could add value to simulators.</p> <p>Results</p> <p>We designed and implemented <it>Snazer</it>, the simulations and networks analyzer. Its goal is to aid the processes of visualizing and manipulating reactive models, as well as to share and interpret time-course data produced by stochastic simulators or by any other means.</p> <p>Conclusions</p> <p><it>Snazer </it>is a solid prototype that integrates biological network and simulation time-course data analysis techniques.</p

Synthetic Mimic of Antimicrobial Peptide with Nonmembrane-Disrupting Antibacterial Properties

Proteolysis in dairy lactic acid bacteria has been studied in great detail by genetic, biochemical and ultrastructural methods. From these studies the picture emerges that the proteolytic systems of lactococci and lactobacilli are remarkably similar in their components and mode of action. The proteolytic system consists of an extracellularly located serine-proteinase, transport systems specific for di-tripeptides and oligopeptides (> 3 residues), and a multitude of intracellular peptidases. This review describes the properties and regulation of individual components as well as studies that have led to identification of their cellular localization. Targeted mutational techniques developed in recent years have made it possible to investigate the role of individual and combinations of enzymes in vivo. Based on these results as well as in vitro studies of the enzymes and transporters, a model for the proteolytic pathway is proposed. The main features are: (i) proteinases have a broad specificity and are capable of releasing a large number of different oligopeptides, of which a large fraction falls in the range of 4 to 8 amino acid residues; (ii) oligopeptide transport is the main route for nitrogen entry into the cell; (iii) all peptidases are located intracellularly and concerted action of peptidases is required for complete degradation of accumulated peptides.