A 66-year-old woman reported 10 days of generalised weakness, falls and memory 'glitches'. She had developed left-sided ophthalmic herpes zoster 3 months before but was otherwise well. MR scan of brain showed acute left-sided ischaemic strokes and CT cerebral angiogram identified marked stenoses of the left anterior and middle cerebral arteries.
View Article and Find Full Text PDFHigh competence in fundamental motor skills (FMS) and adequate physical fitness (PF) levels are a solid foundation for acquiring an active and healthy lifestyle during childhood and adolescence. In this cross-sectional study, we aimed to compare gender and age groups and identify correlations between FMS and PF in young elementary school students. We used a structured questionnaire to gather sociodemographic information from parents, and we characterized the children's economic profile with the Brazil Social Economic Status Criterion.
View Article and Find Full Text PDFObjective: To assess feasibility of a novel video directly observed therapy (DOT)-based digital asthma program intended to support correct inhaled corticosteroid (ICS) use among children.
Methods: We conducted a 60-day pilot study among patients 2-18 years attending a primary care clinic with prescribed ICS and sub-optimally controlled asthma (recent hospitalization, ICS nonadherence, frequent rescue inhaler use, therapy escalation, or Asthma Control Test <20). Participants used a mobile application to receive reminders, submit videos of ICS doses (video DOT), and receive asynchronous feedback on adherence and inhaler technique.
Exosomes represent a promising delivery tool for nucleic acid-based pharmaceuticals. They are highly suitable for transporting therapeutic miRNAs to tumor cells, due to their natural membrane components. Further, exosomes are capable of effectively protecting nucleic acids against ribonucleases and enable the delivery of their content through cell membranes.
View Article and Find Full Text PDFrRNA processing and assembly of ribosomal proteins during maturation of ribosomes involve many ribosome biogenesis factors (RBFs). Recent studies identified differences in the set of RBFs in humans and yeast, and the existence of plant-specific RBFs has been proposed as well. To identify such plant-specific RBFs, we characterized T-DNA insertion mutants of 15 Arabidopsis thaliana genes encoding nuclear proteins with nucleotide binding properties that are not orthologues to yeast or human RBFs.
View Article and Find Full Text PDFChinese hamster ovary (CHO) cells still represent the major production host for therapeutic proteins. However, multiple limitations have been acknowledged leading to the search for alternative expression systems. CEVEC's amniocyte production (CAP) cells are human production cells demonstrated to enable efficient overexpression of recombinant proteins with human glycosylation pattern.
View Article and Find Full Text PDFApoptosis is a genetically directed process of programmed cell death. A variety of microRNAs (miRNAs), endogenous single-stranded non-coding RNAs of about 22 nucleotides in length have been shown to be involved in the regulation of the intrinsic or extrinsic apoptotic pathways. There is increasing evidence that the aberrant expression of miRNAs plays a causal role in the development of diseases such as cancer.
View Article and Find Full Text PDFRibosome biogenesis is an essential process initiated in the nucleolus. In eukaryotes, multiple ribosome biogenesis factors (RBFs) can be found in the nucleolus, the nucleus and in the cytoplasm. They act in processing, folding and modification of the pre-ribosomal (r)RNAs, incorporation of ribosomal proteins (RPs), export of pre-ribosomal particles to the cytoplasm, and quality control mechanisms.
View Article and Find Full Text PDFBackground: Recent advances in biomedical prevention strategies, including pre-exposure prophylaxis (PrEP) and achieving an undetectable viral load (UVL) among HIV-infected persons, show promise in curbing the rising incidence of HIV among men who have sex with men (MSM) in the United States. This mixed-methods study aimed to investigate the frequency with which MSM encounter potential sex partners on geosocial networking apps who disclose biomedical prevention use, and how MSM make decisions about condom use after these disclosures.
Method: Participants were recruited through advertisements placed on a large geosocial networking app for MSM.
Unlabelled: Optic glioma (OPG) accounts for 4-8% of all brain tumors in children. En-block removal of intraorbital tumor is recommended in cases with disfiguring exophthalmos and impaired vision. Surgical resection of intraorbital optic nerve (ON) poses the risks of permanent ptosis and globe atrophy.
View Article and Find Full Text PDFThe biogenesis of eukaryotic ribosomes is a fundamental process involving hundreds of ribosome biogenesis factors (RBFs) in three compartments of the cell, namely the nucleolus, nucleus, and cytoplasm. Many RBFs are involved in the processing of the primary ribosomal (r)RNA transcript, in which three of the four rRNAs are imbedded. While pre-rRNA processing is well described for yeast and mammals, a detailed processing scheme for plants is lacking.
View Article and Find Full Text PDFRibosome biogenesis is an essential process in all organisms. In eukaryotes, multiple ribosome biogenesis factors (RBFs) act in the processing of ribosomal (r)RNAs, assembly of ribosomal subunits and their export to the cytoplasm. We characterized two genes in Arabidopsis thaliana coding for orthologs of yeast BRX1, a protein involved in maturation of the large ribosomal subunit.
View Article and Find Full Text PDFRibosome biogenesis involves a large ensemble of trans-acting factors, which catalyse rRNA processing, ribosomal protein association and ribosomal subunit assembly. The circularly permuted GTPase Lsg1 is such a ribosome biogenesis factor, which is involved in maturation of the pre-60S ribosomal subunit in yeast. We identified two orthologues of Lsg1 in Arabidopsis thaliana.
View Article and Find Full Text PDFAberrant de novo methylation of DNA is considered an important mediator of tumorigenesis. To investigate the role of de novo DNA methyltransferase 3a (Dnmt3a) in intestinal tumor development, we analyzed the expression of Dnmt3a in murine colon crypts, murine colon adenomas and human colorectal cancer using RNA fluorescence in situ hybridization (FISH), quantitative PCR and immunostaining. Following conditional deletion of Dnmt3a in the colon of APC((Min/+)) mice, we analyzed tumor numbers, genotype of macroadenomas and laser dissected microadenomas, global and regional DNA methylation and gene expression.
View Article and Find Full Text PDFReproductive interactions among cytotypes in their contact zones determine whether these cytotypes can co-exist and form stable contact zones or not. In autopolyploids, heteroploid cross-compatibilities might depend on parental ploidy, but tests of this hypothesis in autopolyploid systems with more than two ploidies are lacking. Here, we study Jacobaea carniolica, which comprises diploid, tetraploid, and hexaploid individuals regularly forming contact zones.
View Article and Find Full Text PDFFactor activating Pos9 (Fap7) is an essential ribosome biogenesis factor important for the assembly of the small ribosomal subunit with an uncommon dual ATPase and adenylate kinase activity. Depletion of Fap7 or mutations in its ATPase motifs lead to defects in small ribosomal subunit rRNA maturation, the absence of ribosomal protein Rps14 from the assembled subunit, and retention of the nascent small subunit in a quality control complex with the large ribosomal subunit. The molecular basis for the role of Fap7 in ribosome biogenesis is, however, not yet understood.
View Article and Find Full Text PDFBackground: Glutaredoxins (Grxs) catalyze the reduction of protein disulfides via the dithiol mechanism and the de-/glutathionylation of substrates via the monothiol mechanism. These rapid, specific, and generally also reversible modifications are part of various signaling cascades regulating for instance cell proliferation, differentiation and apoptosis. Even though crucial functions of the conserved, mitochondrial Grx2a and the cytosolic/nuclear Grx2c isoforms have been proposed, only a few substrates have been identified in vitro or in vivo.
View Article and Find Full Text PDFBiochim Biophys Acta
February 2013
Cells have complex membranous organelles for the compartmentalization and the regulation of most intracellular processes. Organelle biogenesis and maintenance requires newly synthesized proteins, each of which needs to go from the ribosome translating its mRNA to the correct membrane for insertion or transclocation to an a organellar subcompartment. Decades of research have revealed how proteins are targeted to the correct organelle and translocated across one or more organelle membranes ro the compartment where they function.
View Article and Find Full Text PDFRibosome biogenesis is well described in Saccharomyces cerevisiae. In contrast only very little information is available on this pathway in plants. This study presents the characterization of five putative protein co-factors of ribosome biogenesis in Arabidopsis thaliana, namely Rrp5, Pwp2, Nob1, Enp1 and Noc4.
View Article and Find Full Text PDFLarge prospective cohort studies are critical for identifying etiologic factors for disease, but they require substantial long-term research investment. Such studies can be conducted as multisite consortia of academic medical centers, combinations of smaller ongoing studies, or a single large site such as a dominant regional health-care provider. Still another strategy relies upon centralized conduct of most or all aspects, recruiting through multiple temporary assessment centers.
View Article and Find Full Text PDFEukaryotic ribosome biogenesis requires the concerted action of numerous ribosome assembly factors, for most of which structural and functional information is currently lacking. Nob1, which can be identified in eukaryotes and archaea, is required for the final maturation of the small subunit ribosomal RNA in yeast by catalyzing cleavage at site D after export of the preribosomal subunit into the cytoplasm. Here, we show that this also holds true for Nob1 from the archaeon Pyrococcus horikoshii, which efficiently cleaves RNA-substrates containing the D-site of the preribosomal RNA in a manganese-dependent manner.
View Article and Find Full Text PDFTic20 is a central, membrane-embedded component of the precursor protein translocon of the inner envelope of chloroplasts (TIC). In Arabidopsis thaliana, four different isoforms of Tic20 exist. They are annotated as atTic20-I, -II, -IV and -V and form two distinct phylogenetic subfamilies in embryophyta.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
August 2011
The majority of outer membrane proteins (OMPs) from gram-negative bacteria and many of mitochondria and chloroplasts are β-barrels. Insertion and assembly of these proteins are catalyzed by the Omp85 protein family in a seemingly conserved process. All members of this family exhibit a characteristic N-terminal polypeptide-transport-associated (POTRA) and a C-terminal 16-stranded β-barrel domain.
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