Post-capillary venules are the key locus for transcytosis-mediated brain delivery of therapeutic nanoparticles.

Effective treatments of neurodegenerative diseases require drugs to be actively transported across the blood-brain barrier (BBB). However, nanoparticle drug carriers explored for this purpose show negligible brain uptake, and the lack of basic understanding of nanoparticle-BBB interactions underlies many translational failures. Here, using two-photon microscopy in mice, we characterize the receptor-mediated transcytosis of nanoparticles at all steps of delivery to the brain in vivo.

Chest x-ray findings in tuberculosis patients identified by passive and active case finding: A retrospective study.

Background: Chest x-ray is central in screening and diagnosis of tuberculosis. However, sputum culture remains gold standard for diagnosis.

Aim: To establish the rate of normal chest x-rays in tuberculosis patients found by spot sputum culture screening, and compare them to a group identified through passive case finding.

Next-generation sequencing of RNA and DNA isolated from paired fresh-frozen and formalin-fixed paraffin-embedded samples of human cancer and normal tissue.

Formalin-fixed, paraffin-embedded (FFPE) tissues are an invaluable resource for clinical research. However, nucleic acids extracted from FFPE tissues are fragmented and chemically modified making them challenging to use in molecular studies. We analysed 23 fresh-frozen (FF), 35 FFPE and 38 paired FF/FFPE specimens, representing six different human tissue types (bladder, prostate and colon carcinoma; liver and colon normal tissue; reactive tonsil) in order to examine the potential use of FFPE samples in next-generation sequencing (NGS) based retrospective and prospective clinical studies.

Extraction of polycyclic aromatic hydrocarbons from smoked fish using pressurized liquid extraction with integrated fat removal.

Quantification of polycyclic aromatic hydrocarbons (PAHs) in smoked fish products often requires multiple clean-up steps to remove fat and other compounds that may interfere with the chemical analysis. We present a novel pressurized liquid extraction (PLE) method that integrates exhaustive extraction with fat retention in one single analytical step. The PLE parameters: type of fat retainer, flush volume, solvent composition, fat-to-fat retainer ratio (FFR), and the dimensions of the extraction cells were the most important factors for obtaining fat-free extracts with high recoveries of PAHs.

Autoregulation of Npl3, a yeast SR protein, requires a novel downstream region and serine phosphorylation.

Npl3 is an SR-like protein with documented roles in mRNA export and transcription termination. Maintaining appropriate levels of Npl3 protein is critical for cell survival. Here we show that Npl3 negatively regulates its own expression via modulation of its mRNA levels.

A quantitative analysis of biodiversity and the recreational value of potential national parks in Denmark.

Denmark has committed itself to the European 2010 target to halt the loss of biodiversity. Currently, Denmark is in the process of designating larger areas as national parks, and 7 areas (of a possible 32 larger nature areas) have been selected for pilot projects to test the feasibility of establishing national parks. In this article, we first evaluate the effectiveness of the a priori network of national parks proposed through expert and political consensus versus a network chosen specifically for biodiversity through quantitative analysis.

Comparison of chromatographic ion-exchange resins VI. Weak anion-exchange resins.

A comparative study on weak anion exchangers was performed to investigate the pH dependence, binding strength, particle size distribution, and static and dynamic capacity of the chromatographic resins. The resins tested included: DEAE Sepharose FF, Poros 50 D, Fractogel EMD DEAE (M), MacroPrep DEAE Support, DEAE Ceramic HyperD 20, and Toyopearl DEAE 650 M. Testing was performed with five different model proteins: Anti-FVII mAb (immunoglobulin G), aprotinin, bovine serum albumin (BSA), Lipolase (Novozymes), and myoglobin.

The DEAD-box protein Dbp5p is required to dissociate Mex67p from exported mRNPs at the nuclear rim.

Eukaryotic mRNAs are exported from the nucleus to the cytoplasm as complex mRNA-protein particles (mRNPs), and translocation through the nuclear pore complex (NPC) is accompanied by extensive structural changes of the mRNP. We have tested the hypothesis that the DEAD-box ATPase Dbp5p is required for such an mRNP rearrangement. In dbp5 mutant cells, the mRNA export receptor Mex67p accumulates on mRNA.

Defining a 5' splice site by functional selection in the presence and absence of U1 snRNA 5' end.

Pre-mRNA splicing in metazoans is mainly specified by sequences at the termini of introns. We have selected functional 5' splice sites from randomized intron sequences through repetitive rounds of in vitro splicing in HeLa cell nuclear extract. The consensus sequence obtained after one round of selection in normal extract closely resembled the consensus of natural occurring 5' splice sites, suggesting that the selection pressures in vitro and in vivo are similar.