112 research outputs found
Virtual image out-the-window display system study. Volume 2 - Appendix
Virtual image out-the-window display system imaging techniques and simulation devices - appendices containing background materia
Virtual image out-the-window display system study, volume I
Virtual image out-the-window display system and current approaches to visual simulatio
Construction and evaluation of a whole genome microarray of Chlamydomonas reinhardtii
Toepel J, Albaum S, Arvidsson S, et al. Construction and evaluation of a whole genome microarray of Chlamydomonas reinhardtii. BMC Genomics. 2011;12(1): 579.ABSTRACT: BACKGROUND: Chlamydomonas reinhardtii is widely accepted as a model organism regarding photosynthesis, circadian rhythm, cell mobility, phototaxis, and biotechnology. The complete annotation of the genome allows transcriptomic studies, however a new microarray platform was needed. Based on the completed annotation of Chlamydomonas reinhardtii a new microarray on an Agilent platform was designed using an extended JGI 3.1 genome data set which included 15000 transcript models. RESULTS: In total 44000 probes were determined (3 independent probes per transcript model) covering 93% of the transcriptome. Alignment studies with the recently published AUGUSTUS 10.2 annotation confirmed 11000 transcript models resulting in a very good coverage of 70% of the transcriptome (17000). Following the estimation of 10000 predicted genes in Chlamydomonas reinhardtii our new microarray, nevertheless, covers the expected genome by 90-95%. CONCLUSIONS: To demonstrate the capabilities of the new microarray, we analyzed transcript levels for cultures grown under nitrogen as well as sulfate limitation, and compared the results with recently published microarray and RNA-seq data. We could thereby confirm previous results derived from data on nutrient-starvation induced gene expression of a group of genes related to protein transport and adaptation of the metabolism as well as genes related to efficient light harvesting, light energy distribution and photosynthetic electron transport
Alternative Complement Pathway Deregulation Is Correlated with Dengue Severity
BACKGROUND:The complement system, a key component that links the innate and adaptive immune responses, has three pathways: the classical, lectin, and alternative pathways. In the present study, we have analyzed the levels of various complement components in blood samples from dengue fever (DF) and dengue hemorrhagic fever (DHF) patients and found that the level of complement activation is associated with disease severity. METHODS AND RESULTS:Patients with DHF had lower levels of complement factor 3 (C3; p = 0.002) and increased levels of C3a, C4a and C5a (p<0.0001) when compared to those with the less severe form, DF. There were no significant differences between DF and DHF patients in the levels of C1q, immunocomplexes (CIC-CIq) and CRP. However, small but statistically significant differences were detected in the levels of MBL. In contrast, the levels of two regulatory proteins of the alternative pathway varied widely between DF and DHF patients: DHF patients had higher levels of factor D (p = 0.01), which cleaves factor B to yield the active (C3bBb) C3 convertase, and lower levels of factor H (p = 0.03), which inactivates the (C3bBb) C3 convertase, than did DF patients. When we considered the levels of factors D and H together as an indicator of (C3bBb) C3 convertase regulation, we found that the plasma levels of these regulatory proteins in DHF patients favored the formation of the (C3bBb) C3 convertase, whereas its formation was inhibited in DF patients (p<0.0001). CONCLUSION:The data suggest that an imbalance in the levels of regulatory factors D and H is associated with an abnormal regulation of complement activity in DHF patients
Design and development of a peptide-based adiponectin receptor agonist for cancer treatment
<p>Abstract</p> <p>Background</p> <p>Adiponectin, a fat tissue-derived adipokine, exhibits beneficial effects against insulin resistance, cardiovascular disease, inflammatory conditions, and cancer. Circulating adiponectin levels are decreased in obese individuals, and this feature correlates with increased risk of developing several metabolic, immunological and neoplastic diseases. Thus, pharmacological replacement of adiponectin might prove clinically beneficial, especially for the obese patient population. At present, adiponectin-based therapeutics are not available, partly due to yet unclear structure/function relationships of the cytokine and difficulties in converting the full size adiponectin protein into a viable drug.</p> <p>Results</p> <p>We aimed to generate adiponectin-based short peptide that can mimic adiponectin action and be suitable for preclinical and clinical development as a cancer therapeutic. Using a panel of 66 overlapping 10 amino acid-long peptides covering the entire adiponectin globular domain (residues 105-254), we identified the 149-166 region as the adiponectin active site. Three-dimensional modeling of the active site and functional screening of additional 330 peptide analogs covering this region resulted in the development of a lead peptidomimetic, ADP 355 (H-DAsn-Ile-Pro-Nva-Leu-Tyr-DSer-Phe-Ala-DSer-NH<sub>2</sub>). In several adiponectin receptor-positive cancer cell lines, ADP 355 restricted proliferation in a dose-dependent manner at 100 nM-10 μM concentrations (exceeding the effects of 50 ng/mL globular adiponectin). Furthermore, ADP 355 modulated several key signaling pathways (AMPK, Akt, STAT3, ERK1/2) in an adiponectin-like manner. siRNA knockdown experiments suggested that ADP 355 effects can be transmitted through both adiponectin receptors, with a greater contribution of AdipoR1. <it>In vivo</it>, intraperitoneal administration of 1 mg/kg/day ADP 355 for 28 days suppressed the growth of orthotopic human breast cancer xenografts by ~31%. The peptide displayed excellent stability (at least 30 min) in mouse blood or serum and did not induce gross toxic effects at 5-50 mg/kg bolus doses in normal CBA/J mice.</p> <p>Conclusions</p> <p>ADP 355 is a first-in-class adiponectin receptor agonist. Its biological activity, superior stability in biological fluids as well as acceptable toxicity profile indicate that the peptidomimetic represents a true lead compound for pharmaceutical development to replace low adiponectin levels in cancer and other malignancies.</p
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Bioinformatic analysis reveals the expression of unique transcriptomic signatures in Zika virus infected human neural stem cells
BACKGROUND: The single-stranded RNA Flavivirus, Zika virus (ZIKV), has recently re-emerged and spread rapidly across the western hemisphere’s equatorial countries, primarily through Aedes mosquito transmission. While symptoms in adult infections appear to be self-limiting and mild, severe birth defects, such as microcephaly, have been linked to infection during early pregnancy. Recently, Tang et al. (Cell Stem Cell 2016, doi: 10.1016/j.stem.2016.02.016) demonstrated that ZIKV efficiently infects induced pluripotent stem cell (iPSC) derived human neural progenitor cells (hNPCs), resulting in cell cycle abnormalities and apoptosis. Consequently, hNPCs are a suggested ZIKV target. METHODS: We analyzed the transcriptomic sequencing (RNA-seq) data (GEO: GSE78711) of ZIKV (Strain: MR766) infected hNPCs. For comparison to the ZIKV-infected hNPCs, the expression data from hNPCs infected with human cytomegalovirus (CMV) (Strain: AD169) was used (GEO: GSE35295). Utilizing a combination of Gene Ontology, database of human diseases, and pathway analysis, we generated a putative systemic model of infection supported by known molecular pathways of other highly related viruses. RESULTS: We analyzed RNA-sequencing data for transcript expression alterations in ZIKV-infected hNPCs, and then compared them to expression patterns of iPSC-derived hNPCs infected with CMV, a virus that can also induce severe congenital neurological defects in developing fetuses. We demonstrate for the first time that many of cellular pathways correlate with clinical pathologies following ZIKV infection such as microcephaly, congenital nervous system disorders and epilepsy. Furthermore, ZIKV activates several inflammatory signals within infected hNPCs that are implicated in innate and acquired immune responses, while CMV-infected hNPCs showed limited representation of these pathways. Moreover, several genes related to pathogen responses are significantly upregulated upon ZIKV infection, but not perturbed in CMV-infected hNPCs. CONCLUSION: The presented study is the first to report enrichment of numerous pro-inflammatory pathways in ZIKV-infected hNPCs, indicating that hNPCs are capable of signaling through canonical pro-inflammatory pathways following viral infection. By defining gene expression profiles, new factors in the pathogenesis of ZIKV were identified which could help develop new therapeutic strategies
A multi-analytical approach for the characterization of black crusts on the facade of an historical cathedral
This study focuses on the characterization of black crusts collected from the Monza cathedral located in the homonymous city (N Italy), a hot spot from the point of view of the atmospheric pollution. Black crusts and substrate marble specimens were analyzed by a multi-analytical approach including X-ray Diffraction (XRD), Fourier Transform-Infrared spectroscopy (FT-IR), Stereomicroscopy (SM), Polarized Light Microscopy (PLM), High Resolution Scanning Electron Microscopy coupled with Energy Dispersive X-ray spectroscopy (HRSEM-EDX) and Laser Ablation Inductively Coupled Plasma Mass Spectrometry (LA-ICP/MS). The characterization of the carbon fraction (organic carbon, OC, and elemental carbon, EC) was performed using a new approach based on the use of Carbon Hydrogen Nitrogen (CHN) analysis and Thermogravimetric Analysis (TGA). The integrated approach allowed the identification of the pollution sources responsible for black crusts forming process. The precise identification of the main substances responsible for the surface degradation phenomena, in particular those leading to the blackening and disintegration of the carbonate substrates, is essential for the definition of conservative intervention and maintenance strategies, as well as for the development of emission reduction policies on a local scale
Environmental impact assessment on the Monza cathedral (Italy): A multi-analytical approach
This research deals with the characterization of black crusts collected from the Dome of Monza (Milan, Italy). Air pollution is responsible for the degradation of historical buildings surfaces. In urban and industrial areas, the degradation process is accelerated, due to carbonaceous particles and heavy metals emitted by combustion processes which contribute to the formation of black crust (BCs). In this study the characterization of BC was performed using different analytical techniques such as: HRSEM-EDX, IC, LA-ICP/MS and digital image analysis. In particular, the research focused on the study of "heavy metals" which contribute to the identify the main sources of pollution responsible for the surface's deterioration over time. BCs variability in composition also depends on the exposure of the analyzed surfaces
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