Effect of low molecular weight proteins and dextran on renal cathepsin B and L activity

Effect of low molecular weight proteins and dextran on renal cathepsin B and L activity. Renal extraction of low molecular weight proteins (LMWP) accounts for 30% to 80% of their total metabolic clearance. Extraction includes glomerular filtration, proximal tubular uptake, and intralysosomal proteolysis. To characterize the anatomic sites and enzymes involved in digestion of reabsorbed LMWP, the lysosomal proteases, cathepsin B and L, were measured by ultramicroassay in isolated S1, S2 and S3 segments of the proximal tubule of proteinuric rats. Increased glomerular filtration and tubular uptake of LMWP were induced by i.v. and i.p. injections of myoglobin and cationic and anionic lysozyme. Both cationic lysozyme and myoglobin increased cathepsin B and L activities in the proximal tubule, while anionic lysozyme had no effect. Morphologic examination of kidney tissue suggested that proximal tubular uptake of anionic lysozyme was negligible in comparison with the cationic form. Hence, only LMWP absorbed by the proximal tubule cells stimulated cathepsin B and L activities. Proximal tubular uptake of cationic lysozyme was determined by measurement of lysozyme activities in S1, S2, and S3. S1 segments contained the highest lysozyme activity, while S2 and S3 had much lower activities, and cathepsin B and L activity following cationic lysozyme injection was stimulated only in S1 segments. These results suggest that cathepsin B and L participate in lysosomal digestion of certain LMWP. Furthermore, the activities of cathepsin B and L adapt to increased uptake of LMWP. To gain additional insight into the mechanism of cathepsin adaptation, the cathepsin B and L activities were measured following injection of dextran with a similar low molecular weight. Dextran uptake in proximal tubules was confirmed by morphologic examination of kidney tissue. Dextran increased cathepsin B and L activities in the proximal tubule. Hence, increased endocytic activity of proximal tubule cells or increased lysosomal load of macromolecules or both rather than direct protein-enzyme interaction seem to be involved in cathepsin stimulation

Velopark : a linked open data platform for bicycle parkings

Cycling as a mean of urban transportation is positively correlated with cleaner, healthier and happier cities. By providing more infrastructure, such as secure parking facilities, cities aim on attracting more cyclists. However, authoritative information about parking facilities is heavily decentralized and heterogeneous, which makes secure parking facilities harder to be discovered by cyclists. Can an open dataset about bike parkings be managed decentrally? In this paper, we present the results of the Velopark project, carried out in Belgium by different actors that include local public authorities, public transport operators and pro-cycling organizations. During the project execution we (i) introduced the Open Velopark Vocabulary as a common semantic data model; and (ii) implemented the Velopark platform, an open data publishing environment for both static and live authoritative parking data. So far, 1599 parking facilities were published through the Velopark platform, 31 different Belgian municipalities and 4 parking related organizations use the platform to describe, publish and manage their parking facilities. A common data publishing environment supports organizations for providing access to their information, while guaranteeing data reliability for cyclists. In future work we will further extend our data model to cover other kinds of infrastructure and bicycle-related services

A Kinetic Model for Blood Biomarker Levels after Mild Traumatic Brain Injury

Traumatic brain injury (TBI) imposes a significant economic and social burden. The diagnosis and prognosis of mild TBI, also called concussion, is challenging. Concussions are common among contact sport athletes. After a blow to the head, it is often difficult to determine who has had a concussion, who should be withheld from play, if a concussed athlete is ready to return to the field, and which concussed athlete will develop a post-concussion syndrome. Biomarkers can be detected in the cerebrospinal fluid and blood after traumatic brain injury and their levels may have prognostic value. Despite significant investigation, questions remain as to the trajectories of blood biomarker levels over time after mild TBI. Modeling the kinetic behavior of these biomarkers could be informative. We propose a one-compartment kinetic model for S100B, UCH-L1, NF-L, GFAP, and tau biomarker levels after mild TBI based on accepted pharmacokinetic models for oral drug absorption. We approximated model parameters using previously published studies. Since parameter estimates were approximate, we did uncertainty and sensitivity analyses. Using estimated kinetic parameters for each biomarker, we applied the model to an available post-concussion biomarker dataset of UCH-L1, GFAP, tau, and NF-L biomarkers levels. We have demonstrated the feasibility of modeling blood biomarker levels after mild TBI with a one compartment kinetic model. More work is needed to better establish model parameters and to understand the implications of the model for diagnostic use of these blood biomarkers for mild TBI

A Tale of Two Tantalum Borides as Potential Saturable Absorbers for Q-Switched Fiber Lasers

In this paper, we analyze the performance of two tantalum-based boride (TaB and TaB 2 ) microparticles as potential saturable absorbers for high-power fiber lasers. Both materials are ultrahigh temperature ceramics with melting points above 3000 °C, but with different crystalline structures: TaB has an orthorhombic structure (nearly isotropic), whereas TaB 2 has a hexagonal structure (uniaxial, anisotropic). Despite their different crystalline structures, the microparticles have a similar low fluence attenuation (between 2.3 and 2.60 dB/μm) and modulation depths (around 2.0 dB/μm), but remarkable different saturation fluences: TaB has a saturation fluence of 160 μJ/cm 2 , whereas TaB 2 has a saturation fluence of 110 μJ/cm 2 . The measured damage thresholds are 112 and 10 6 mJ/cm 2 /pulse for TaB and TaB 2 , respectively. When incorporated to a fiber laser, the materials produce pulses with durations of 345 ns, lower than those reported by our group in previous papers. The results show that the materials can find potential applications in high-power Q-switched lasers

High Fluence Chromium and Tungsten Bowtie Nano-antennas

Nano-antennas are replicas of antennas that operate at radio-frequencies, but with considerably smaller dimensions when compared with their radio frequency counterparts. Noble metals based nano-antennas have the ability to enhance photoinduced phenomena such as localized electric fields, therefore-they have been used in various applications ranging from optical sensing and imaging to performance improvement of solar cells. However, such nano-structures can be damaged in high power applications such as heat resisted magnetic recording, solar thermo-photovoltaics and nano-scale heat transfer systems. Having a small footprint, nano-antennas cannot handle high fluences (energy density per unit area) and are subject to being damaged at adequately high power (some antennas can handle just a few milliwatts). In addition, given that nano-antennas are passive devices driven by external light sources, the potential damage of the antennas limits their use with high power lasers: this liability can be overcome by employing materials with high melting points such as chromium (Cr) and tungsten (W). In this article, we fabricate chromium and tungsten nano-antennas and demonstrate that they can handle 110 and 300 times higher fluence than that of gold (Au) counterpart, while the electric field enhancement is not significantly reduced.Te authors gratefully acknowledge the fabrication facilities provided by Australian National Fabrication Facility (ANFF ACT node, Australia). We would acknowledge the fnancial support from UNSW Canberra, Australia. We also would like to thank Te Asian Ofce of Aerospace Research and Development (AOARD US Air Force FA2386-15-1-4084), Australian Research Council (ARC LP160100253, DP170103778 and DE190100413) to provide the funding

Great Cause—Small Effect: Undeclared Genetically Engineered Orange Petunias Harbor an Inefficient Dihydroflavonol 4-Reductase

A recall campaign for commercial, orange flowering petunia varieties in spring 2017 caused economic losses worldwide. The orange varieties were identified as undeclared genetically engineered (GE)-plants, harboring a maize dihydroflavonol 4-reductase (DFR, A1), which was used in former scientific transgenic breeding attempts to enable formation of orange pelargonidin derivatives from the precursor dihydrokaempferol (DHK) in petunia. How and when the A1 cDNA entered the commercial breeding process is unclear. We provide an in-depth analysis of three orange petunia varieties, released by breeders from three countries, with respect to their transgenic construct, transcriptomes, anthocyanin composition, and flavonoid metabolism at the level of selected enzymes and genes. The two possible sources of the A1 cDNA in the undeclared GE-petunia can be discriminated by PCR. A special version of the A1 gene, the A1 type 2 allele, is present, which includes, at the 3′-end, an additional 144 bp segment from the non-viral transposable Cin4-1 sequence, which does not add any functional advantage with respect to DFR activity. This unequivocally points at the first scientific GE-petunia from the 1980s as the A1 source, which is further underpinned e.g., by the presence of specific restriction sites, parts of the untranslated sequences, and the same arrangement of the building blocks of the transformation plasmid used. Surprisingly, however, the GE-petunia cannot be distinguished from native red and blue varieties by their ability to convert DHK in common in vitro enzyme assays, as DHK is an inadequate substrate for both the petunia and maize DFR. Recombinant maize DFR underpins the low DHK acceptance, and, thus, the strikingly limited suitability of the A1 protein for a transgenic approach for breeding pelargonidin-based flower color. The effect of single amino acid mutations on the substrate specificity of DFRs is demonstrated. Expression of the A1 gene is generally lower than the petunia DFR expression despite being under the control of the strong, constitutive p35S promoter. We show that a rare constellation in flavonoid metabolism—absence or strongly reduced activity of both flavonol synthase and B-ring hydroxylating enzymes—allows pelargonidin formation in the presence of DFRs with poor DHK acceptance.Peer Reviewe

Independent mutations in a single locus, the transcriptional factor MYB10, control natural variation in fruit color among Fragaria species

External and internal fruit color are important traits in strawberry (Fragaria spp.) breeding programs, where different preferences are sought depending on whether the fruits are produced for fresh consumption or processing. Therefore, there is a great interest in the development of predictive markers that effectively speed the development of new cultivars with increased consumer acceptance and/or which address processed fruit industry´s preferences. In order to identify loci controlling fruit color variation, two mapping populations were generated: one crossing diploid F. vesca parentals and another interspecific population between two octoploid species: the cultivated and the Chilean strawberry, F. x ananassa and F. chiloensis. Both populations allowed the detection of a QTL spanning a region of the F. vesca linkage group 1 (LG I) that includes the MYB10 gene, a known key regulator of anthocyanin biosynthesis. Mapping by sequencing in the F. vesca population revealed an LTR retrotransposon inserted in the third exon of FvMYB10, which produces a premature stop codon, and co-segregates with white fruits in the entire population. Genotyping by Sanger sequencing of additional white-fruited F. vesca accessions resulted in the identification of another three independent mutations in MYB10, two of them not previously described1. In octoploid strawberry, a mayor QTL on LG I-3 controls about 55% variation in internal flesh color and is associated with an insertion in the promoter region of FcMYB10. Similar insertions have been detected in other F. chiloensis accessions bearing white fruits. In all cases, transient over-expression of FvMYB10 restored anthocyanin biosynthesis and red color in fruit flesh and skin, indicating that lack of function of MYB10 was the underlying cause of white fruits in all analyzed cases

Efficacy and safety of tacrolimus compared with ciclosporin A in renal transplantation: three-year observational results

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1970: Abilene Christian College Bible Lectures - Full Text

THE APOSTLES’ DOCTRINE Being the Abilene Christian College Annual Bible Lectures 1970 Published by ABILENE CHRISTIAN COLLEGE BOOK STORE ACC Station Abilene, Texas 7960

Allelic Variation of MYB10 is the Major Force Controlling Natural Variation of Skin and Flesh Color in Strawberry (Fragaria spp.) fruit

Anthocyanins are the principal color-producing compounds synthesized in developing fruits of strawberry (Fragaria spp.). Substantial natural variation in color have been observed in fruits of diploid and octoploid accessions, resulting from distinct accumulation and distribution of anthocyanins in fruits. Anthocyanin biosynthesis is controlled by a clade of R2R3 MYB transcription factors, among which MYB10 has been shown as the main activator in strawberry fruit. Here, we show that MYB10 mutations cause most of the anthocyanin variation observed in diploid woodland strawberry (F. vesca) and octoploid cultivated strawberry (F. ×ananassa). Using a mapping-by-sequencing approach, we identified a gypsytransposon insertion in MYB10 that truncates the protein and knocks out anthocyanin biosynthesis in a white-fruited F. vesca ecotype. Two additional lossof-function MYB10 mutations were identified among geographically diverse whitefruited F. vesca ecotypes. Genetic and transcriptomic analyses in octoploid Fragaria spp. revealed that FaMYB10-2, one of three MYB10 homoeologs identified, residing in the F. iinumae-derived subgenome, regulates the biosynthesis of anthocyanins in developing fruit. Furthermore, independent mutations in MYB10-2 are the underlying cause of natural variation in fruit skin and flesh color in octoploid strawberry. We identified a CACTA-like transposon (FaEnSpm-2) insertion in the MYB10-2 promoter of red-fleshed accessions that was associated with enhanced expression and anthocyanin accumulation. Our findings suggest that putative cis regulatory elements provided by FaEnSpm-2 are required for high and ectopic MYB10-2 expression and induction of anthocyanin biosynthesis in fruit flesh. We developed MYB10-2 (sub-genome) specific DNA markers for marker-assisted selection that accurately predicted anthocyanin phenotypes in octoploid segregating populations