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"Adler, Barbara"
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Bones and the roller coaster mystery
Junior sleuth Jeffrey Bones and his grandfather enjoy a day at the amusement park until their tickets to ride the giant roller coaster mysteriously disappear.
Book
Human cytomegalovirus glycoprotein complex gH/gL/gO uses PDGFR-α as a key for entry
Herpesvirus gH/gL envelope glycoprotein complexes are key players in virus entry as ligands for host cell receptors and by promoting fusion of viral envelopes with cellular membranes. Human cytomegalovirus (HCMV) has two alternative gH/gL complexes, gH/gL/gO and gH/gL/UL128,130,131A which both shape the HCMV tropism. By studying binding of HCMV particles to fibroblasts, we could for the first time show that virion gH/gL/gO binds to platelet-derived growth factor-α (PDGFR-α) on the surface of fibroblasts and that gH/gL/gO either directly or indirectly recruits gB to this complex. PDGFR-α functions as an entry receptor for HCMV expressing gH/gL/gO, but not for HCMV mutants lacking the gH/gL/gO complex. PDGFR-α-dependent entry is not dependent on activation of PDGFR-α. We could also show that the gH/gL/gO-PDGFR-α interaction starts the predominant entry pathway for infection of fibroblasts with free virus. Cell-associated virus spread is either driven by gH/gL/gO interacting with PDGFR-α or by the gH/gL/UL128,130,131A complex. PDGFR-α-positive cells may thus be preferred first target cells for infections with free virus which might have implications for the design of future HCMV vaccines or anti-HCMV drugs.
Journal Article
Bones and the dinosaur mystery
Young Detective Jeffrey Bones investigates the disappearance of the plastic dinosaur his grandfather just bought for him in a museum gift shop.
Book
A Viral Pilot for HCMV Navigation?
gH/gL virion envelope glycoprotein complexes of herpesviruses serve as entry complexes and mediate viral cell tropism. By binding additional viral proteins, gH/gL forms multimeric complexes which bind to specific host cell receptors. Both Epstein–Barr virus (EBV) and human cytomegalovirus (HCMV) express alternative multimeric gH/gL complexes. Relative amounts of these alternative complexes in the viral envelope determine which host cells are preferentially infected. Host cells of EBV can modulate the gH/gL complex complement of progeny viruses by cell type-dependent degradation of one of the associating proteins. Host cells of HCMV modulate the tropism of their virus progenies by releasing or not releasing virus populations with a specific gH/gL complex complement out of a heterogeneous pool of virions. The group of Jeremy Kamil has recently shown that the HCMV ER-resident protein UL148 controls integration of one of the HCMV gH/gL complexes into virions and thus creates a pool of virions which can be routed by different host cells. This first mechanistic insight into regulation of the gH/gL complex complement of HCMV progenies presents UL148 as a pilot candidate for HCMV navigation in its infected host.
Journal Article
Bones and the cupcake mystery
Detective Jeffrey Bones finds he does not need fancy equipment to solve the school-lunch mystery of Not Me Amy's missing cupcake.
Book
Identification of the human cytomegalovirus gHgLgO trimer as the central player in virion infectivity
Glycoproteins in the viral envelope of human cytomegalovirus (HCMV) orchestrate virion tethering, receptor recognition and fusion with cellular membranes. The glycoprotein gB acts as fusion protein. The gHgL complexes gHgLgO and gHgLpUL(128,130,131A) define the HCMV cell tropism. Studies with HCMV lacking gO had indicated that gHgLgO, independently of binding to its cellular receptor PDGFRα, plays an important second role in infection. Here, we identified a gO mutation which abolished virus particle infectivity by preventing the interaction of gHgLgO with host cell heparan sulfate proteoglycans (HSPGs). We could not only show that gHgLgO – HSPG interactions are a genuine second role of gHgLgO, but also that gHgLgO is a main player in determining the infectivity of HCMV virus particles. This challenges long-accepted textbook knowledge on the role of gB and gMgN complexes in virion tethering. Additionally, it adds the gHgLgO complex to the antigens of interest for future HCMV vaccines or treatments.
Journal Article
Bones and the big yellow mystery
Young Detective Jeffrey Bones begins gathering clues when Mr. Green asks for his help finding the school bus he lost while shopping at the mall.
Book
Management of vesicovaginal fistulas (VVFs) in women following benign gynaecologic surgery: A systematic review and meta-analysis
Vesicovaginal fistulas (VVF) are the most commonly acquired fistulas of the urinary tract, but we lack a standardized algorithm for their management. Surgery is the most commonly preferred approach to treat women with primary VVF following benign gynaecologic surgery.
To carry out a systematic review and meta-analysis on the effectiveness of operative techniques or conservative treatment for patients with postsurgical VVF. Our secondary objective was to define the surgical time and determine the types of study designs.
PubMed, Old Medline, Embase and Cochrane Central Register of Controlled Trials were used as data sources. This systematic review was modelled on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, including a registration number (CRD42012002097).
We reviewed 282 full text articles to identify 124 studies for inclusion. In all, 1379/1430 (96.4%) patients were treated surgically. Overall, the transvaginal approach was performed in the majority of patients (39%), followed by a transabdominal/transvesical route (36%), a laparoscopic/robotic approach (15%) and a combined transabdominal-transvaginal approach in 3% of cases. Success rate of conservative treatment was 92.86% (95%CI: 79.54-99.89), 97.98% in surgical cases (95% CI: 96.13-99.29) and 91.63% (95% CI: 87.68-97.03) in patients with prolonged catheter drainage followed by surgery. 79/124 studies (63.7%) provided information for the length of follow-up, but showed a poor reporting standard regarding prognosis. Complications were studied only selectively. Due to the inconsistency of these data it was impossible to analyse them collectively.
Although the literature is imprecise and inconsistent, existing studies indicate that operation, mainly through a transvaginal approach, is the most commonly preferred treatment strategy in females with postsurgical VVF. Our data showed no clear odds-on favorite regarding disease management as well as surgical approach and current evidence on the surgical management of VVF does not allow any accurate estimation of success and complication rates. Standardisation of the terminology is required so that VVF can be managed with a proper surgical treatment algorithm based on characteristics of the fistula.
Journal Article
Bones and the dog gone mystery
While looking for his lost magnifying glass in the park, young Detective Jeffrey Bones and his grandfather discover that Curly the detective dog is missing, too, and start tracking down clues.
Book
Perinatal murine cytomegalovirus infection reshapes the transcriptional profile and functionality of NK cells
Infections in early life can elicit substantially different immune responses and pathogenesis than infections in adulthood. Here, we investigate the consequences of murine cytomegalovirus infection in newborn mice on NK cells. We show that infection severely compromised NK cell maturation and functionality in newborns. This effect was not due to compromised virus control. Inflammatory responses to infection dysregulated the expression of major transcription factors governing NK cell fate, such as Eomes, resulting in impaired NK cell function. Most prominently, NK cells from perinatally infected mice have a diminished ability to produce IFN-γ due to the downregulation of long non-coding RNA
Ifng-as1
expression. Moreover, the bone marrow’s capacity to efficiently generate new NK cells is reduced, explaining the prolonged negative effects of perinatal infection on NK cells. This study demonstrates that viral infections in early life can profoundly impact NK cell biology, including long-lasting impairment in NK cell functionality.
Early life infections are known to impact and modulate the immune response in later life. Here the authors show that perinatal infection with murine cytomegalovirus results in a modified transcriptional profile and functionality in murine NK cells.
Journal Article