Kooperativer Bibliotheksverbund

Berlin Brandenburg

and
and

Your email was sent successfully. Check your inbox.

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

Proceed reservation?

Export
Filter
Language
Year
  • 1
    Language: English
    In: 2015, Vol.11(3), p.e1004712
    Description: Specific types of human papillomaviruses (HPVs) cause cervical cancer. Cervical cancers exhibit aberrant cellular microRNA (miRNA) expression patterns. By genome-wide analyses, we investigate whether the intracellular and exosomal miRNA compositions of HPV-positive cancer cells are dependent on endogenous E6/E7 oncogene expression. Deep sequencing studies combined with qRT-PCR analyses show that E6/E7 silencing significantly affects ten of the 52 most abundant intracellular miRNAs in HPV18-positive HeLa cells, downregulating miR-17-5p, miR-186-5p, miR-378a-3p, miR-378f, miR-629-5p and miR-7-5p, and upregulating miR-143-3p, miR-23a-3p, miR-23b-3p and miR-27b-3p. The effects of E6/E7 silencing on miRNA levels are mainly not dependent on p53 and similarly observed in HPV16-positive SiHa cells. The E6/E7 -regulated miRNAs are enriched for species involved in the control of cell proliferation, senescence and apoptosis, suggesting that they contribute to the growth of HPV-positive cancer cells. Consistently, we show that sustained E6/E7 expression is required to maintain the intracellular levels of members of the miR-17~92 cluster, which reduce expression of the anti-proliferative p21 gene in HPV-positive cancer cells. In exosomes secreted by HeLa cells, a distinct seven-miRNA-signature was identified among the most abundant miRNAs, with significant downregulation of let-7d-5p, miR-20a-5p, miR-378a-3p, miR-423-3p, miR-7-5p, miR-92a-3p and upregulation of miR-21-5p, upon E6/E7 silencing. Several of the E6/E7 -dependent exosomal miRNAs have also been linked to the control of cell proliferation and apoptosis. This study represents the first global analysis of intracellular and exosomal miRNAs and shows that viral oncogene expression affects the abundance of multiple miRNAs likely contributing to the E6/E7 -dependent growth of HPV-positive cancer cells. ; Oncogenic human papillomaviruses (HPVs) are major human carcinogens of broad biomedical importance. The growth of HPV-positive cervical cancer cells is critically dependent on sustained oncogene expression from endogenous viral DNA sequences. We here addressed the question of whether this process is linked to specific, -dependent alterations of the cellular micro(mi)RNA network. By comprehensive deep sequencing analyses we show that endogenous expression significantly affects the concentrations of abundant intracellular miRNAs in HPV-positive cervical cancer cells, which are linked to the control of cell proliferation, senescence and apoptosis. These include members of the miR-17~92 cluster, which are expressed at increased levels by sustained expression and repress the anti-proliferative gene in HPV-positive cancer cells. Moreover, we identified an -dependent seven-miRNA-signature in exosomes secreted from HPV-positive cancer cells. These small vesicles are involved in intercellular communication and may serve as novel diagnostic markers. Taken together, our results show that continuous expression in HPV-positive cancer cells is linked to significant alterations in the amounts of intracellular and exosomal miRNAs with growth-promoting, anti-senescent and anti-apoptotic potential.
    Keywords: Research Article
    ISSN: 1553-7366
    E-ISSN: 1553-7374
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 2
    Language: English
    In: Molecular Cell, 02 February 2017, Vol.65(3), pp.403-415.e8
    Description: Cell-autonomous induction of type I interferon must be stringently regulated. Rapid induction is key to control virus infection, whereas proper limitation of signaling is essential to prevent immunopathology and autoimmune disease. Using unbiased kinome-wide RNAi screening followed by thorough validation, we identified 22 factors that regulate RIG-I/IRF3 signaling activity. We describe a negative-feedback mechanism targeting RIG-I activity, which is mediated by death associated protein kinase 1 (DAPK1). RIG-I signaling triggers DAPK1 kinase activation, and active DAPK1 potently inhibits RIG-I stimulated IRF3 activity and interferon-beta production. DAPK1 phosphorylates RIG-I in vitro at previously reported as well as other sites that limit 5′ppp-dsRNA sensing and virtually abrogate RIG-I activation. Willemsen et al. screened the antiviral RIG-I pathway for regulators and identified and validated 22 kinases. They describe an inhibitory feedback loop mediated by DAPK1. Antiviral signaling activates DAPK1 kinase activity, which, in turn, inactivates RIG-I by direct phosphorylation.
    Keywords: Innate Immunity ; Antiviral Response ; Pattern Recognition Receptors ; Signal Transduction ; Feedback Regulation ; Interferon System ; Cytokines ; Dapk1 ; Rig-I ; Ddx58 ; Biology
    ISSN: 1097-2765
    E-ISSN: 1097-4164
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 3
    Language: English
    In: Cryobiology, April, 2013, Vol.66(2), p.131(5)
    Description: To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.cryobiol.2012.12.007 Byline: Anja Gallinat (a), Bastian Luer (b), Sandra Swoboda (a), Ursula Rauen (c), Andreas Paul (a), Thomas Minor (b) Keywords: Machine perfusion; Oxygen; Custodiol-N; Preservation Abstract: Custodiol-N is a new preservation solution specifically designed to prevent free radical-induced tissue alterations and to protect vascular integrity of the graft. Thus, Custodiol-N appears particularly suitable as base solution for oxygenated machine preservation and its putative benefit for renal preservation by hypothermic machine perfusion (HMP) was investigated using a porcine in vitro model. Kidneys were retrieved from German Landrace pigs and preserved for 20h by pulsatile oxygenated HMP on a Lifeport kidney transporter (syst. pressure 30mmHg, 30cycles/min). Each graft was randomly assigned to the use of one of the following preservation solutions: Custodiol-N solution supplemented with 50g/l dextran 40 (CND) or kidney perfusion solution 1 (KPS-1). Renal viability was evaluated upon reperfusion in vitro with diluted autologous blood from the donor for 120min at 37[degrees]C. After 2h of postischemic reperfusion CND-preserved kidneys exhibited significantly higher renal blood flow and urine production. Oxygen consumption was also higher in the CND group than in KPS-1 kidneys. Clearance of creatinine increased during reperfusion of CND kidneys but declined in KPS-1 grafts ending in significantly higher values in CND kidneys. No differences between the groups were seen for enzyme release or fractional excretion of sodium. In conclusion the data presented provide first experimental evidence for adequate organ protective potential of CND in HMP as compared to the gold standard KPS-KPS-11. Author Affiliation: (a) Dpt. for General, Visceral and Transplantation Surgery, University Hospital of Essen, Germany (b) Surgical Research Division, University Clinic of Surgery, Bonn, Germany (c) Institute of Physiological Chemistry, University Hospital Essen, Germany Article History: Received 23 August 2012; Accepted 21 December 2012
    Keywords: Enzymes -- Usage ; Enzymes -- Physiological Aspects ; Swine -- Usage ; Swine -- Physiological Aspects ; Dextrans -- Physiological Aspects
    ISSN: 0011-2240
    Source: Cengage Learning, Inc.
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 4
    Language: English
    In: The American journal of tropical medicine and hygiene, August 2003, Vol.69(2), pp.195-9
    Description: A polymerase chain reaction (PCR)-based diagnostic assay was developed that rapidly and reliably differentiates the sibling species of the Anopheles claviger complex, An. claviger s.s. and An. petragnani. The assay makes use of nucleotide differences in the internal transcribed spacer 2 ribosomal DNA sequences to generate PCR products of specific length for each of the two species. In evaluating the test, 580 of 592 field-collected An. claviger s.l. specimens were unambiguously identified as one of the two sibling species. Due to poor DNA quality, the remaining 12 specimens yielded no PCR product. Of the 592 mosquitoes, 407 larval specimens had been identified morphologically prior to species-specific DNA amplification, and in all instances PCR identification corroborated with morphologic identification. Mosquitoes identified as An. claviger s.s. came from various localities all over Europe and from Israel. Those identified as An. petragnani were collected in southern France and Spain. The species-diagnostic PCR assay would facilitate data collection on the temporal and spatial distribution of the two An. claviger sibling species because they represent possible vectors of disease in Europe, the Near and Middle East, and north Africa.
    Keywords: Anopheles -- Classification ; Insect Vectors -- Classification ; Malaria -- Transmission ; Polymerase Chain Reaction -- Standards
    ISSN: 0002-9637
    Source: MEDLINE/PubMed (U.S. National Library of Medicine)
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 5
    Language: English
    In: The American Journal of Tropical Medicine and Hygiene, 08/01/2003, Vol.69(2), pp.195-199
    Description: A polymerase chain reaction (PCR)-based diagnostic assay was developed that rapidly and reliably differentiates the sibling species of the Anopheles claviger complex, An. claviger s.s. and An. petragnani. The assay makes use of nucleotide differences in the internal transcribed spacer 2 ribosomal DNA sequences to generate PCR products of specific length for each of the two species. In evaluating the test, 580 of 592 field-collected An. claviger s.l. specimens were unambiguously identified as one of the two sibling species. Due to poor DNA quality, the remaining 12 specimens yielded no PCR product. Of the 592 mosquitoes, 407 larval specimens had been identified morphologically prior to species-specific DNA amplification, and in all instances PCR identification corroborated with morphologic identification. Mosquitoes identified as An. claviger s.s. came from various localities all over Europe and from Israel. Those identified as An. petragnani were collected in southern France and Spain. The species-diagnostic PCR assay would facilitate data collection on the temporal and spatial distribution of the two An. claviger sibling species because they represent possible vectors of disease in Europe, the Near and Middle East, and north Africa.
    Keywords: Medicine;
    ISSN: 0002-9637
    E-ISSN: 1476-1645
    Source: CrossRef
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 6
    Language: English
    In: BMC research notes, 20 November 2014, Vol.7, pp.826
    Description: Multipotent mesenchymal stromal cells (MSC) can be recovered from a variety of tissues in the body. Yet, their functional properties were shown to vary depending on tissue origin. While MSC have emerged as a favoured cell type for tendon regenerative therapies, very little is known about the influence of the MSC source on their properties relevant to tendon regeneration.The aim of this study was to assess and compare the expression of tendon extracellular matrix proteins and tendon differentiation markers in MSC derived from different sources as well as in native tendon tissue. MSC isolated from equine bone marrow, adipose tissue, umbilical cord tissue, umbilical cord blood and tendon tissue were characterized and then subjected to mRNA analysis by real-time polymerase chain reaction. MSC derived from adipose tissue displayed the highest expression of collagen 1A2, collagen 3A1 and decorin compared to MSC from all other sources and native tendon tissue (p 〈 0.01). Tenascin-C and scleraxis expressions were highest in MSC derived from cord blood compared to MSC derived from other sources, though both tenascin-C and scleraxis were expressed at significantly lower levels in all MSC compared to native tendon tissue (p 〈 0.01). These findings demonstrate that the MSC source impacts the cell properties relevant to tendon regeneration. Adipose derived MSC might be superior regarding their potential to positively influence tendon matrix reorganization.
    Keywords: Adipose Tissue -- Cytology ; Mesenchymal Stem Cells -- Physiology ; Tendons -- Cytology
    E-ISSN: 1756-0500
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 7
    Language: English
    In: Journal of neurochemistry, June 2011, Vol.117(5), pp.868-78
    Description: Aggregated α-synuclein (α-syn) is a characteristic pathological finding in Parkinson's disease and related disorders, such as dementia with Lewy bodies. Recent evidence suggests that α-syn oligomers represent the principal neurotoxic species; however, the pathophysiological mechanisms are still not well understood. Here, we studied the neurophysiological effects of various biophysically-characterized preparations of α-syn aggregates on excitatory synaptic transmission in autaptic neuronal cultures. Nanomolar concentrations of large α-syn oligomers, generated by incubation with organic solvent and Fe(3+) ions, were found to selectivity enhance evoked α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)-receptor, but not NMDA-receptor, mediated synaptic transmission within minutes. Moreover, the analysis of spontaneous AMPA-receptor-mediated miniature synaptic currents revealed an augmented frequency. These results collectively indicate that large α-syn oligomers alter both pre- and post-synaptic mechanisms of AMPA-receptor-mediated synaptic transmission. The augmented excitatory synaptic transmission may directly contribute to nerve cell death in synucleinopathies. Indeed, already low micromolar glutamate concentrations were found to be toxic in primary cultured neurons incubated with large α-syn oligomers. In conclusion, large α-syn oligomers enhance both pre- and post-synaptic AMPA-receptor-mediated synaptic transmission, thereby aggravating intracellular calcium dyshomeostasis and contributing to excitotoxic nerve cell death in synucleinopathies.
    Keywords: Iron -- Pharmacology ; Receptors, Ampa -- Physiology ; Synaptic Transmission -- Physiology ; Alpha-Synuclein -- Pharmacology
    ISSN: 00223042
    E-ISSN: 1471-4159
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 8
    Language: English
    In: Critical care (London, England), 28 January 2015, Vol.19, pp.23
    Description: Lung-protective ventilation reduced acute respiratory distress syndrome (ARDS) mortality. To minimize ventilator-induced lung injury (VILI), tidal volume is limited, high plateau pressures are avoided, and positive end-expiratory pressure (PEEP) is applied. However, the impact of specific ventilatory patterns on VILI is not well defined. Increasing inspiratory time and thereby the inspiratory/expiratory ratio (I:E ratio) may improve oxygenation, but may also be harmful as the absolute stress and strain over time increase. We thus hypothesized that increasing inspiratory time and I:E ratio aggravates VILI. VILI was induced in mice by high tidal-volume ventilation (HVT 34 ml/kg). Low tidal-volume ventilation (LVT 9 ml/kg) was used in control groups. PEEP was set to 2 cm H2O, FiO2 was 0.5 in all groups. HVT and LVT mice were ventilated with either I:E of 1:2 (LVT 1:2, HVT 1:2) or 1:1 (LVT 1:1, HVT 1:1) for 4 hours or until an alternative end point, defined as mean arterial blood pressure below 40 mm Hg. Dynamic hyperinflation due to the increased I:E ratio was excluded in a separate group of animals. Survival, lung compliance, oxygenation, pulmonary permeability, markers of pulmonary and systemic inflammation (leukocyte differentiation in lung and blood, analyses of pulmonary interleukin-6, interleukin-1β, keratinocyte-derived chemokine, monocyte chemoattractant protein-1), and histopathologic pulmonary changes were analyzed. LVT 1:2 or LVT 1:1 did not result in VILI, and all individuals survived the ventilation period. HVT 1:2 decreased lung compliance, increased pulmonary neutrophils and cytokine expression, and evoked marked histologic signs of lung injury. All animals survived. HVT 1:1 caused further significant worsening of oxygenation, compliance and increased pulmonary proinflammatory cytokine expression, and pulmonary and blood neutrophils. In the HVT 1:1 group, significant mortality during mechanical ventilation was observed. According to the "baby lung" concept, mechanical ventilation-associated stress and strain in overinflated regions of ARDS lungs was simulated by using high tidal-volume ventilation. Increase of inspiratory time and I:E ratio significantly aggravated VILI in mice, suggesting an impact of a "stress/strain × time product" for the pathogenesis of VILI. Thus increasing the inspiratory time and I:E ratio should be critically considered.
    Keywords: Exhalation ; Inhalation ; Tidal Volume ; Lung -- Pathology ; Respiration, Artificial -- Adverse Effects ; Ventilator-Induced Lung Injury -- Physiopathology
    ISSN: 13648535
    E-ISSN: 1466-609X
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 9
    In: Journal of Chemical Physics, 2018, Vol.149, pp.1-8
    ISSN: 0021-9606
    Source: NARCIS (National Academic Research and Collaborations Information System)
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 10
    In: Nature, 2012, Vol.485(7399), p.517
    Description: Oligodendrocytes, the myelin-forming glial cells of the central nervous system, maintain long-term axonal integrity (1-3). However, the underlying support mechanisms are not understood (4). Here we identify a metabolic component of axon-glia interactions by generating conditional Cox10 (protoheme IX farnesyltransferase) mutant mice, in which oligodendrocytes and Schwann cells fail to assemble stable mitochondrial cytochrome c oxidase (COX, also known as mitochondrial complex IV). In the peripheral nervous system, Cox10 conditional mutants exhibit severe neuropathy with dysmyelination, abnormal Remak bundles, muscle atrophy and paralysis. Notably, perturbing mitochondrial respiration did not cause glial cell death. In the adult central nervous system, we found no signs of demyelination, axonal degeneration or secondary inflammation. Unlike cultured oligodendrocytes, which are sensitive to COX inhibitors (5), post-myelination oligodendrocytes survive well in the absence of COX activity. More importantly, by in vivo magnetic resonance spectroscopy, brain lactate concentrations in mutants were increased compared with controls, but were detectable only in mice exposed to volatile anaesthetics. This indicates that aerobic glycolysis products derived from oligodendrocytes are rapidly metabolized within white matter tracts. Because myelinated axons can use lactate when energy-deprived6, our findings suggest a model in which axonglia metabolic coupling serves a physiological function.
    Keywords: Axons -- Physiological Aspects ; Axons -- Health Aspects ; Oligodendroglia -- Physiological Aspects ; Oligodendroglia -- Health Aspects;
    ISSN: 0028-0836
    E-ISSN: 14764687
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. Further information can be found on the KOBV privacy pages