ALBERT

All Library Books, journals and Electronic Records Telegrafenberg

X
feed icon rss

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • Articles  (108)
  • Wiley  (85)
  • Oxford University Press  (23)
  • Medicine  (108)
  • Political Science
Collection
  • Articles  (108)
Source
Publisher
Years
Journal
Topic
  • 1
    facet.materialart.
    Unknown
    Mutations in PIGY: expanding the phenotype of inherited glycosylphosphatidylinositol deficiencies (2015)
    Oxford University Press
    Details
    Publication Date: 2015-10-10
    Description: Glycosylphosphatidylinositol (GPI)-anchored proteins are ubiquitously expressed in the human body and are important for various functions at the cell surface. Mutations in many GPI biosynthesis genes have been described to date in patients with multi-system disease and together these constitute a subtype of congenital disorders of glycosylation. We used whole exome sequencing in two families to investigate the genetic basis of disease and used RNA and cellular studies to investigate the functional consequences of sequence variants in the PIGY gene. Two families with different phenotypes had homozygous recessive sequence variants in the GPI biosynthesis gene PIGY . Two sisters with c.137T〉C (p.Leu46Pro) PIGY variants had multi-system disease including dysmorphism, seizures, severe developmental delay, cataracts and early death. There were significantly reduced levels of GPI-anchored proteins (CD55 and CD59) on the surface of patient-derived skin fibroblasts (~20–50% compared with controls). In a second, consanguineous family, two siblings had moderate development delay and microcephaly. A homozygous PIGY promoter variant (c.-540G〉A) was detected within a 7.7 Mb region of autozygosity. This variant was predicted to disrupt a SP1 consensus binding site and was shown to be associated with reduced gene expression. Mutations in PIGY can occur in coding and non-coding regions of the gene and cause variable phenotypes. This article contributes to understanding of the range of disease phenotypes and disease genes associated with deficiencies of the GPI-anchor biosynthesis pathway and also serves to highlight the potential importance of analysing variants detected in 5'-UTR regions despite their typically low coverage in exome data.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 2
    facet.materialart.
    Unknown
    BioNetFit: a fitting tool compatible with BioNetGen, NFsim and distributed computing environments (2016)
    Oxford University Press
    Details
    Publication Date: 2016-02-27
    Description: : Rule-based models are analyzed with specialized simulators, such as those provided by the BioNetGen and NFsim open-source software packages. Here, we present BioNetFit, a general-purpose fitting tool that is compatible with BioNetGen and NFsim. BioNetFit is designed to take advantage of distributed computing resources. This feature facilitates fitting (i.e. optimization of parameter values for consistency with data) when simulations are computationally expensive. Availability and implementation: BioNetFit can be used on stand-alone Mac, Windows/Cygwin, and Linux platforms and on Linux-based clusters running SLURM, Torque/PBS, or SGE. The BioNetFit source code (Perl) is freely available ( http://bionetfit.nau.edu ). Supplementary information: Supplementary data are available at Bioinformatics online. Contact: bionetgen.help@gmail.com
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
    Published by Oxford University Press
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 3
    facet.materialart.
    Unknown
    INRICH: interval-based enrichment analysis for genome-wide association studies (2012)
    Oxford University Press
    Details
    Publication Date: 2012-06-24
    Description: : Here we present INRICH ( IN terval en RICH ment analysis), a pathway-based genome-wide association analysis tool that tests for enriched association signals of predefined gene-sets across independent genomic intervals. INRICH has wide applicability, fast running time and, most importantly, robustness to potential genomic biases and confounding factors. Such factors, including varying gene size and single-nucleotide polymorphism density, linkage disequilibrium within and between genes and overlapping genes with similar annotations, are often not accounted for by existing gene-set enrichment methods. By using a genomic permutation procedure, we generate experiment-wide empirical significance values, corrected for the total number of sets tested, implicitly taking overlap of sets into account. By simulation we confirm a properly controlled type I error rate and reasonable power of INRICH under diverse parameter settings. As a proof of principle, we describe the application of INRICH on the NHGRI GWAS catalog. Availability: A standalone C++ program, user manual and datasets can be freely downloaded from: http://atgu.mgh.harvard.edu/inrich/ . Contact: shaun@atgu.mgh.harvard.edu Supplementary information: Supplementary data are available at Bioinformatics online.
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
    Published by Oxford University Press
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 4
    facet.materialart.
    Unknown
    The free-radical theory of ageing – older, wiser and still alive (2012)
    Wiley
    In: BioEssays
    Details
    Publication Date: 2012-05-30
    Description: The continuing viability of the free-radical theory of ageing has been questioned following apparently incompatible recent results. We show by modelling positional effects of the generation and primary targets of reactive oxygen species that many of the apparently negative results are likely to be misleading. We conclude that there is instead a need to look more closely at the mechanisms by which free radicals contribute to age-related dysfunction in living systems. There also needs to be deeper understanding of the dynamics of accumulation and removal of the various kinds of molecular damage, in particular mtDNA mutations. Finally, the expectation that free-radical damage on its own might cause ageing needs to be relinquished in favour of the recognition that the free-radical theory is just one of the multiple mechanisms driving the ageing process. The free-radical theory is more complex than commonly recognized. Spatial effects need to be considered; e.g. mitochondrial DNA, a main target of ROS, is attached to the inner mitochondrial membrane, where most radicals are produced. This influences the likely effectiveness of antioxidants (AOx) and of turnover processes to control cellular damage.
    Print ISSN: 0265-9247
    Electronic ISSN: 1521-1878
    Topics: Biology , Medicine
    Published by Wiley
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 5
    facet.materialart.
    Unknown
    Paracrine signaling mediated at cell–cell contacts (2014)
    Wiley
    In: BioEssays
    Details
    Publication Date: 2014-12-06
    Description: Recent findings in several organ systems show that cytoneme-mediated signaling transports signaling proteins along cellular extensions and targets cell-to-cell exchanges to synaptic contacts. This mechanism of paracrine signaling may be a general one that is used by many (or all) cell types in many (or all) organs. We briefly review these findings in this perspective. We also describe the properties of several signaling systems that have previously been interpreted to support a passive diffusion mechanism of signaling protein dispersion, but can now be understood in the context of the cytoneme mechanism. Also watch the Video Abstract . The importance of paracrine signaling for animal development has been recognized for almost 100 years, but the discovery that epithelial cells transport signaling proteins over long distances with filopodia that make direct contact with target cells is recent. In this perspective we review the new findings and explore some of their many implications.
    Print ISSN: 0265-9247
    Electronic ISSN: 1521-1878
    Topics: Biology , Medicine
    Published by Wiley
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 6
    facet.materialart.
    Unknown
    Whole-exome sequencing identifies rare, functional CFH variants in families with macular degeneration (2014)
    Oxford University Press
    Details
    Publication Date: 2014-09-10
    Description: We sequenced the whole exome of 35 cases and 7 controls from 9 age-related macular degeneration (AMD) families in whom known common genetic risk alleles could not explain their high disease burden and/or their early-onset advanced disease. Two families harbored novel rare mutations in CFH (R53C and D90G). R53C segregates perfectly with AMD in 11 cases (heterozygous) and 1 elderly control (reference allele) (LOD = 5.07, P = 6.7 x 10 –7 ). In an independent cohort, 4 out of 1676 cases but none of the 745 examined controls or 4300 NHBLI Exome Sequencing Project (ESP) samples carried the R53C mutation ( P = 0.0039). In another family of six siblings, D90G similarly segregated with AMD in five cases and one control (LOD = 1.22, P = 0.009). No other sample in our large cohort or the ESP had this mutation. Functional studies demonstrated that R53C decreased the ability of FH to perform decay accelerating activity. D90G exhibited a decrease in cofactor-mediated inactivation. Both of these changes would lead to a loss of regulatory activity, resulting in excessive alternative pathway activation. This study represents an initial application of the whole-exome strategy to families with early-onset AMD. It successfully identified high impact alleles leading to clearer functional insight into AMD etiopathogenesis.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 7
    facet.materialart.
    Unknown
    Methylene blue upregulates Nrf2/ARE genes and prevents tau-related neurotoxicity (2014)
    Oxford University Press
    Details
    Publication Date: 2014-06-21
    Description: Methylene blue (MB, methylthioninium chloride) is a phenothiazine that crosses the blood brain barrier and acts as a redox cycler. Among its beneficial properties are its abilities to act as an antioxidant, to reduce tau protein aggregation and to improve energy metabolism. These actions are of particular interest for the treatment of neurodegenerative diseases with tau protein aggregates known as tauopathies. The present study examined the effects of MB in the P301S mouse model of tauopathy. Both 4 mg/kg MB (low dose) and 40 mg/kg MB (high dose) were administered in the diet ad libitum from 1 to 10 months of age. We assessed behavior, tau pathology, oxidative damage, inflammation and numbers of mitochondria. MB improved the behavioral abnormalities and reduced tau pathology, inflammation and oxidative damage in the P301S mice. These beneficial effects were associated with increased expression of genes regulated by NF-E2-related factor 2 (Nrf2)/antioxidant response element (ARE), which play an important role in antioxidant defenses, preventing protein aggregation, and reducing inflammation. The activation of Nrf2/ARE genes is neuroprotective in other transgenic mouse models of neurodegenerative diseases and it appears to be an important mediator of the neuroprotective effects of MB in P301S mice. Moreover, we used Nrf2 knock out fibroblasts to show that the upregulation of Nrf2/ARE genes by MB is Nrf2 dependent and not due to secondary effects of the compound. These findings provide further evidence that MB has important neuroprotective effects that may be beneficial in the treatment of human neurodegenerative diseases with tau pathology.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 8
    facet.materialart.
    Unknown
    The agotrons: Gene regulators or Argonaute protectors? (2017)
    Wiley
    In: BioEssays
    Details
    Publication Date: 2017-03-08
    Description: Over the last decades, it has become evident that highly complex networks of regulators govern post-transcriptional regulation of gene expression. A novel class of Argonaute (Ago)-associated RNA molecules, the agotrons, was recently shown to function in a Drosha- and Dicer-independent manner, hence bypassing the maturation steps required for canonical microRNA (miRNA) biogenesis. Agotrons are found in most mammals and associate with Ago as ∼100 nucleotide (nt) long RNA species. Here, we speculate on the functional and biological relevance of agotrons: (i) agotrons could serve as non-promiscuous miRNA-like regulators with reduced off-targeting or (ii) agotrons could encompass other putative functions, such as protecting Ago proteins from taking up aberrant short RNAs or by rescuing and stabilizing otherwise unloaded Ago-proteins from degradation. Collectively, agotrons have emerged as a novel class of interesting non-coding RNA molecules, but their full functional potential and biological impact still remain to be disclosed. Agotrons are full-length, debranched introns associating with Argonaute (Ago) proteins in a Drosha- and Dicer-independent manner. The ensuring question is whether agotrons are occupying Ago to regulate target gene expression, or to protect Ago-proteins from degradation and avoid loading of aberrant RNA in Ago.
    Print ISSN: 0265-9247
    Electronic ISSN: 1521-1878
    Topics: Biology , Medicine
    Published by Wiley
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 9
    facet.materialart.
    Unknown
    Targeted NGS gene panel identifies mutations in RSPH1 causing primary ciliary dyskinesia and a common mechanism for ciliary central pair agenesis due to radial spoke defects (2014)
    Oxford University Press
    Details
    Publication Date: 2014-06-10
    Description: Primary ciliary dyskinesia (PCD) is an inherited chronic respiratory obstructive disease with randomized body laterality and infertility, resulting from cilia and sperm dysmotility. PCD is characterized by clinical variability and extensive genetic heterogeneity, associated with different cilia ultrastructural defects and mutations identified in 〉20 genes. Next generation sequencing (NGS) technologies therefore present a promising approach for genetic diagnosis which is not yet in routine use. We developed a targeted panel-based NGS pipeline to identify mutations by sequencing of selected candidate genes in 70 genetically undefined PCD patients. This detected loss-of-function RSPH1 mutations in four individuals with isolated central pair (CP) agenesis and normal body laterality, from two unrelated families. Ultrastructural analysis in RSPH1 -mutated cilia revealed transposition of peripheral outer microtubules into the ‘empty’ CP space, accompanied by a distinctive intermittent loss of the central pair microtubules. We find that mutations in RSPH1 , RSPH4A and RSPH9, which all encode homologs of components of the ‘head’ structure of ciliary radial spoke complexes identified in Chlamydomonas , cause clinical phenotypes that appear to be indistinguishable except at the gene level. By high-resolution immunofluorescence we identified a loss of RSPH4A and RSPH9 along with RSPH1 from RSPH1 -mutated cilia, suggesting RSPH1 mutations may result in loss of the entire spoke head structure. CP loss is seen in up to 28% of PCD cases, in whom laterality determination specified by CP-less embryonic node cilia remains undisturbed. We propose this defect could arise from instability or agenesis of the ciliary central microtubules due to loss of their normal radial spoke head tethering.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 10
    facet.materialart.
    Unknown
    Predicted and inferred waiting times for key mutations in the germinal centre reaction: Evidence for stochasticity in selection (1998)
    Wiley
    Details
    Publication Date: 1998-07-01
    Print ISSN: 0818-9641
    Electronic ISSN: 1440-1711
    Topics: Biology , Medicine
    Published by Wiley
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...