Difference between human and guinea pig Hageman factors in activation by bacterial proteinases: cleavage site shift due to local amino acid substitutions may determine the activation efficiency of serine proteinase zymogens

Human and guinea pig Hageman factors have been subjected to the action of pseudomonal elastase and serratial E15 proteinase. The pseudomonal elastase cleaved 22-24% of the human molecule at Arg353-Val354, and the remainder at Gly357-Leu358 resulting in the generation of about 20% of potential activity as activated Hageman factor, compared with trypsin activation, while it hydrolyzed Arg340-Ile341 bond in guinea pig molecule and generated about 75% of activity as activated Hageman factor. The serratial proteinase did not hydrolyze the essential cleavage site (Arg353-Val354) of the human zymogen but Gly356-Gly357 (30%) and Gly357-Leu358 (70%) bonds. Both products showed no activity. The guinea pig zymogen, in contrast, was cleaved mostly at Arg340-Ile341 (70%) and less abundantly at Gly344-Leu345 (30%), generating about 85% of the whole potential activity as activated Hageman factor. From the high correspondence between the proportions of activation and of hydrolysis at the essential cleavage site in activation, it was concluded that hydrolysis of the bonds different from the essential bond did not cause activation, even when the spatial separation was only 3 or 4 residues. Considering the amino acid differences between human and guinea pig Hageman factors, -Met351-Thr-Arg-Val-Val-Gly-Gly-Leu-Val-Ala360- and -Leu338-Ser-Arg-Ile-Val-Gly-Gly-Leu-Val-Ala347-, respectively, it was realized that even the minor amino acid substitutions caused the cleavage site shift which resulted in significant differences in activation efficiency of the proteinase zymogens.     

Imaging of the optic disc and retinal nerve fiber layer: the effects of age, optic disc area, refractive error, and gender.

We cross-sectionally examined the relationship between age, optic disc area, refraction, and gender and optic disc topography and retinal nerve fiber layer (RNFL) measurements, using optical imaging techniques. One eye from each of 155 Caucasian subjects (age range 23.0-80.8 y) without ocular pathology was included. Measurements were obtained by using the Heidelberg Retina Tomography (HRT), the GDx Nerve Fiber Analyzer, and the Optical Coherence Tomograph (OCT). The effects of age were small (R2 < 17%) and were limited to specific HRT, GDx, and OCT parameters. Disc area was significantly associated with most HRT parameters and isolated GDx and OCT parameters. Refraction and gender were not significantly associated with any optic disc or RNFL parameters. Although effects of age on the optic disc and RNFL are small, they should be considered in monitoring ocular disease. Optic disc area should be considered when cross-sectionally evaluating disc topography and, to a lesser extent, RNFL thickness.     

Educational recommender systems and their application in lifelong learning

The almost unlimited access to educational information plethora came with a drawback: finding meaningful material is not a straightforward task anymore. Recommender algorithms can be used to make smart decisions in complex information systems and help the users decide upon useful materials; therefore, they become a promising area in academia and industry. The current paper presents a survey on educational recommender systems (RS): a set of analysis criteria are exposed and the technological specifications and challenges of each analysed system are provided, in the context of the main trends in the development of RS. Also, an ontology-based educational recommendation mechanism is proposed and its application to lifelong learning is highlighted, proving that RS can successfully support new learning paradigms.     

Sensitivity of SAR data to post-fire forest regrowth in Mediterranean and boreal forests

Disturbed forests may need decades to reach a mature stage and optically-based vegetation indices are usually poorly suited for monitoring purposes due to the rapid saturation of the signal with increasing canopy cover. Spaceborne synthetic aperture radar (SAR) data provide an alternate monitoring approach since the backscattered microwave energy is sensitive to the vegetation structure. Images from two regions in Spain and Alaska were used to analyze SAR metrics (cross-polarized backscatter and co-polarized interferometric coherence) from regrowing forests previously affected by fire. TerraSAR-X X-band backscatter showed the lowest sensitivity to forest regrowth, with the average backscatter increasing by 1-2 dB between the most recent fire scar and the unburned forest. Increased sensitivity (around 3-4 dB) was observed for C-band Envisat Advanced Synthetic Aperture (ASAR) backscatter. The Advanced Land Observing Satellite (ALOS) Phased Array-type L-band Synthetic Aperture Radar (PALSAR) L-band backscatter presented the highest dynamic range from unburned to recently burned forests (approximately 8 dB). The interferometric coherence showed low sensitivity to forest regrowth at all SAR frequencies. For Mediterranean forests, five phases of forest regrowth were discerned whereas for boreal forest, up to four different regrowth phases could be discerned with L-band SAR data. In comparison, the Normalized Difference Vegetation Index (NDVI) provided reliable differentiation only for the most recent development stages. The results obtained were consistent in both environments.     

Bacterial polymers as materials for the development of micro/nanoparticles

Bacterial polysaccharides and polyhydroxyalkanoates present physical and chemical characteristics that impart them diverse functional properties, including the ability to produce structures from nano- to macroscale (e.g., spheres, capsules, beads). Such structures may be specially designed to fulfill the requirements of specific applications in different areas, either alone or conjugated with other polymers by means of ionic interactions, hydrogen bonding, or chemical reactions. The interest on using such biomaterials has been increasing due to their unique functional properties, nontoxicity, biodegradability, and biocompatibility. The fields of application of bacterial polymers-based structures include drug delivery, biomedicine, food products, environment, and agriculture, among others.     

Molecularly imprinted poly(acrylonitrile‐co‐acrylic acid) matrix with sclareol

There are presented results regarding a new set of molecularly imprinted polymers (MIPs) based on acrylonitrile:acrylic acid (AN:AA) copolymer matrix. As template, it was used sclareol, an important anticancer bioactive compound, never used before for molecular imprinting. An emerging and insufficient studied MIP preparation method, namely the phase inversion, was used to prepare 0.8 mm spherical sclareol MIPs (S‐MIPs). Three AN:AA copolymers, having the initial monomer ratios 90:10, 80:20, and 70:30, were synthesized by radical copolymerization in emulsion, without emulsifier. After that, each copolymer was dissolved in the presence of the template (sclareol) in dimethylformamide. The imprinting and the morphology of these new materials were analyzed by rheology, elemental analysis, infrared spectroscopy, size exclusion chromatography, thermogravimetric analysis, differential scanning calorimetry, batch rebinding tests, and Scatchard analysis. The conclusion was that the AN:AA‐80:20 matrix proved to be the optimized solution between high rigidity (given by the AN segments) and high affinity for the template (given by AA segments), the average imprinting factor for this system being 2.67. POLYM. ENG. SCI., 54:1484–1494, 2014. © 2013 Society of Plastics Engineers     

The terminal protein of the linear DNA plasmid pGKL2 shares an N-terminal domain of the plasmid-encoded DNA polymerase

The 36K protein attached at the 5′ end of the linear DNA plasmid pGKL2 from the yeast Kluyveromyces lactis was first purified and characterized. The terminal protein was purified from cells (1 kg wet weight) by ammonium sulphate precipitation and two rounds of centrifugation to equilibrium in CsCl gradients. The pGKL2 was present only in the post-microsomal supernatant. Approximately 10 mg of the purified pGKL2 was recovered and digested with DNase I. The terminal protein (final ca. 0·8 mg) was homogeneous by electrophoresis and we determined the N-terminal amino acid sequence up to ten residues, showing that it existed in the cryptic N-terminal domain of pGKL2-ORF2 (DNA polymerase) sequence.     

Fatty Acids,CD36, Thrombospondin-1, and CD47 in Glioblastoma: Together and/or Separately?

Glioblastoma (GBM) is one of the most aggressive tumors of the central nervous system, characterized by a wide range of inter- and intratumor heterogeneity. Accumulation of fatty acids (FA) metabolites was associated with a low survival rate in high-grade glioma patients. The diversity of brain lipids, especially polyunsaturated fatty acids (PUFAs), is greater than in all other organs and several classes of proteins, such as FA transport proteins (FATPs), and FA translocases are considered principal candidates for PUFAs transport through BBB and delivery of PUFAs to brain cells. Among these, the CD36 FA translocase promotes long-chain FA uptake as well as oxidated lipoproteins. Moreover, CD36 binds and recognizes thrombospondin-1 (TSP-1), an extracellular matrix protein that was shown to play a multifaceted role in cancer as part of the tumor microenvironment. Effects on tumor cells are mediated by TSP-1 through the interaction with CD36 as well as CD47, a member of the immunoglobulin superfamily. TSP-1/CD47 interactions have an important role in the modulation of glioma cell invasion and angiogenesis in GBM. Separately, FA, the two membrane receptors CD36, CD47, and their joint ligand TSP-1 all play a part in GBM pathogenesis. The last research has put in light their interconnection/interrelationship in order to exert a cumulative effect in the modulation of the GBM molecular network.     

Targeting the DNA Damage Response to Increase Anthracycline-Based Chemotherapy Cytotoxicity in T-Cell Lymphoma

Mature T-cell lymphomas (MTCLs) represent a heterogeneous group of aggressive non-Hodgkin lymphomas comprising different entities. Anthracycline-based regimens are considered the standard of care in the front-line treatment. However, responses to these approaches have been neither adequate nor durable, and new treatment strategies are urgently needed to improve survival. Genomic instability is a common feature of cancer cells and can be caused by aberrations in the DNA damage response (DDR) and DNA repair mechanisms. Consistently, molecules involved in DDR are being targeted to successfully sensitize cancer cells to chemotherapy. Recent studies showed that some hematological malignancies display constitutive DNA damage and intrinsic DDR activation, but these features have not been investigated yet in MTCLs. In this study, we employed a panel of malignant T cell lines, and we report for the first time the characterization of intrinsic DNA damage and basal DDR activation in preclinical models in T-cell lymphoma. Moreover, we report the efficacy of targeting the apical kinase ATM using the inhibitor AZD0156, in combination with standard chemotherapy to promote apoptotic cell death. These findings suggest that DDR is an attractive pathway to be pharmacologically targeted when developing novel therapies and improving MTCL patients’ outcomes.