Restriction of HIV-1 infection in sickle cell trait

Patients with sickle cell disease (SCD) have a lower risk for HIV-1 infection. We reported restriction of ex vivo HIV-1 infection in SCD peripheral blood mononuclear cells (PBMCs) that was due, in part, to the upregulation of antiviral, inflammatory, and hemolytic factors, including heme oxygenase-1 (HO-1). Here, we investigated whether individuals with sickle cell trait (SCT), who develop mild hemolysis, also restrict HIV-1 infection. Ex vivo infection of SCT PBMCs exhibited an approximately twofold reduction of HIV-1 replication and lower levels of HIV-1 reverse transcription products, 2-long terminal repeat circle, HIV-1 integration, and gag RNA expression. SCT PBMCs had higher HO-1 messenger RNA (mRNA) and protein levels and reduced ribonucleotide reductase 2 (RNR2) protein levels. HO-1 inhibition by tin porphyrin eliminated ex vivo HIV-1 restriction. Among Howard University clinic recruits, higher levels of HO-1 and RNR2 mRNA and lower HIV-1 env mRNA levels were found in SCT individuals living with HIV-1. To determine the population-level effect of SCT on HIV-1 prevalence, we assessed SCT among women living with HIV (WLH) in the WIHS (Women InteragencyHIV-1 Study). Among WIHS African-American participants, the prevalence of SCT was lower among women with HIV compared with uninfected women (8.7% vs 14.2%; odds ratio, 0.57; 95% confidence interval, 0.36-0.92; P = .020). WIHS WLH with SCT had higher levels of CD4+/CD8+ ratios over 20 years of follow-up (P = .003) than matched WLH without SCT. Together, our findings suggest that HIV-1 restriction factors, including HO-1 and RNR2, might restrict HIV-1 infection among individuals with SCT and limit the pathogenicity of HIV

Lymphocytes and the Dap12 Adaptor Are Key Regulators of Osteoclast Activation Associated with Gonadal Failure

Bone resorption by osteoclasts is necessary to maintain bone homeostasis. Osteoclast differentiation from hematopoietic progenitors and their activation depend on M-CSF and RANKL, but also requires co-stimulatory signals acting through receptors associated with DAP12 and FcRγ adaptors. Dap12 mutant mice (KΔ75) are osteopetrotic due to inactive osteoclasts but, surprisingly, these mice are more sensitive than WT mice to bone loss following an ovariectomy. Because estrogen withdrawal is known to disturb bone mass, at least in part, through lymphocyte interaction, we looked at the role of mature lymphocytes on osteoclastogenesis and bone mass in the absence of functional DAP12. Lymphocytes were found to stimulate an early osteoclast differentiation response from Dap12-deficient progenitors in vitro. In vivo, Rag1-/- mice lacking mature lymphocytes did not exhibit any bone phenotype, but lost their bone mass after ovariectomy like KΔ75 mice. KΔ75;Rag1-/- double mutant female mice exhibited a more severe osteopetrosis than Dap12-deficient animals but lost their bone mass after ovariectomy, like single mutants. These results suggest that both DAP12 and mature lymphocytes act synergistically to maintain bone mass under physiological conditions, while playing similar but not synergistic co-stimulatory roles in protecting bone loss after gonadal failure. Thus, our data support a role for lymphocytes during osteoclast differentiation and suggest that they may function as accessory cells when regular osteoclast function is compromised

Genome-Wide Analyses of Recombination Prone Regions Predict Role of DNA Structural Motif in Recombination

HapMap findings reveal surprisingly asymmetric distribution of recombinogenic regions. Short recombinogenic regions (hotspots) are interspersed between large relatively non-recombinogenic regions. This raises the interesting possibility of DNA sequence and/or other cis- elements as determinants of recombination. We hypothesized the involvement of non-canonical sequences that can result in local non-B DNA structures and tested this using the G-quadruplex DNA as a model. G-quadruplex or G4 DNA is a unique form of four-stranded non-B DNA structure that engages certain G-rich sequences, presence of such motifs has been noted within telomeres. In support of this hypothesis, genome-wide computational analyses presented here reveal enrichment of potential G4 (PG4) DNA forming sequences within 25618 human hotspots relative to 9290 coldspots (p<0.0001). Furthermore, co-occurrence of PG4 DNA within several short sequence elements that are associated with recombinogenic regions was found to be significantly more than randomly expected. Interestingly, analyses of more than 50 DNA binding factors revealed that co-occurrence of PG4 DNA with target DNA binding sites of transcription factors c-Rel, NF-kappa B (p50 and p65) and Evi-1 was significantly enriched in recombination-prone regions. These observations support involvement of G4 DNA in recombination, predicting a functional model that is consistent with duplex-strand separation induced by formation of G4 motifs in supercoiled DNA and/or when assisted by other cellular factors

Exercise and bone health across the lifespan

With ageing, bone tissue undergoes significant compositional, architectural and metabolic alterations potentially leading to osteoporosis. Osteoporosis is the most prevalent bone disorder, which is characterised by progressive bone weakening and an increased risk of fragility fractures. Although this metabolic disease is conventionally associated with ageing and menopause, the predisposing factors are thought to be established during childhood and adolescence. In light of this, exercise interventions implemented during maturation are likely to be highly beneficial as part of a long-term strategy to maximise peak bone mass and hence delay the onset of age- or menopause-related osteoporosis. This notion is supported by data on exercise interventions implemented during childhood and adolescence, which confirmed that weight-bearing activity, particularly if undertaken during peripubertal development, is capable of generating a significant osteogenic response leading to bone anabolism. Recent work on human ageing and epigenetics suggests that undertaking exercise after the fourth decade of life is still important, given the anti-ageing effect and health benefits provided, potentially occurring via a delay in telomere shortening and modification of DNA methylation patterns associated with ageing. Exercise is among the primary modifiable factors capable of influencing bone health by preserving bone mass and strength, preventing the death of bone cells and anti-ageing action provided

Daidzein Prevents the Increase in CD4+CD28null T Cells and B Lymphopoesis in Ovariectomized Mice: A Key Mechanism for Anti-Osteoclastogenic Effect

Estrogen deficiency leads to an upregulation of TNF-α producing T cells and B-lymphopoesis which augments osteoclastogenesis. Estrogen deficiency also increases the population of premature senescent CD4+CD28null T cells which secrete a higher amount of TNF-α thus leading to enhanced osteoclastogenesis. Isoflavonoids like daidzein and genistein are found mostly in soybeans, legumes, and peas. These share structural similarity with 17β-stradiol (E2) and have osteoprotective role. This study explores the effect of daidzein (Daid) on the proliferation of TNF-α producing T cells, premature senescent T cells and B cell lymphopoesis under estrogen deficient conditions. For this study adult Balb/c mice were treated with Daid at 10 mg/kg body weight dose by oral gavage daily post ovariectomy (Ovx). After six weeks animals were autopsied and bone marrow and spleen cells were collected for FACS analysis. Blood serum was collected for ELISA. It was observed that Ovx mice treated with Daid for six weeks show reduction in Ovx induced expansion of CD4+ T cells in bone marrow and spleen when analysed by flow cytometry. Estrogen deficiency led to increased prevalence of TNF-α secreting CD4+CD28null T cells, however, treatment with Daid increased the percentage of CD4+CD28+ T cells. Co-culture of CD4+CD28null T cells and bone marrow resulted in enhanced osteoclastogenesis as evident by increased tartarate resistant acid phosphatase (TRAP) expression, an osteoclast marker. However, treatment with Daid resulted in reduced osteoclastogenesis in CD4+CD28null T cells and bone marrow cell co-culture. Daid also regulated B lymphopoesis and decreased mRNA levels of RANKL in B220+ cells. Taken together, we propose that one of the mechanisms by which Daid prevents bone loss is by reversing the detrimental immune changes as a result of estrogen deficiency

Virologie / Bakteriologie / Mykologie

141 - Effizienz von Kaliumhypochlorit zur Inaktivierung ausgewählter pilzlicher, bakterieller und viraler PflanzenkrankheitserregerEfficancy of Potassium Hypochlorite (KClO) to inactivate selected plant pathogenic fungi, bacteria and virusesMarlon-Hans Rodríguez, Martina Bandte, Gerhard Fischer, Carmen Büttner142 - Eignung von elektrolytisch generiertem Kaliumhypochlorit zur Inaktivierung von Pflanzenviren in rezirkulierender Nährlösungen im Gewächshausanbau von TomatenAbility of electrolysed produced Potassium Hypochlorite (KClO) to inactivate plant viruses in recirculating nutrient solutions in greenhouse production of tomatosJanine Paulke, Martina Bandte, Carmen Büttner143 - Ultrafiltration und Ultrazentrifugation zur Konzentrierung von Pflanzenviren in NährlösungUltrafiltration and ultracentrifugation as tools to concentrate plant viruses in nutrient solutionJanina Vincenz, Martina Bandte, Carmen Büttner144 - Reinigung doppelsträngiger RNA in Verbindung mit Hochdurchsatzsequenzierung als Werkzeug zum Nachweis von RNA Viren in PflanzenThe combination of double-stranded RNA isolation and deep sequencing as an unspecific diagnostic tool to assess the presence of RNA viruses in plantsTill Lesker, Paul Rentz, Edgar Maiss145 - Impact of silica supplementation on virus infected cucumber culturesRolle der Kieselsäureapplikation Virus infizierter GurkenkulturenSabine Holz, Grzegorz Bartoszewski , Michael Kube, Carmen Büttner146 - Untersuchungen zum Auftreten des Arabis mosaic virus in Birken aus Rovaniemi (Finnland) mit Virus-spezifischen SymptomenInvestigations on the occurence of Arabis mosaic virus in birches from Rovaniemi (Finland) with virus-specific symptomsRichard Pauwels, Markus Rott, Susanne von Bargen, Carmen Büttner147 - Cherry leaf roll virus in Betula spp. in Finland: what do we know about its population diversity?Cherry leaf roll virus in Birken-Arten in Finnland: Was wissen wir über die Populationsdiversität?A. Rumbou, S. von Bargen, M. Rott, R. Jalkanen, C. Büttner148 - Viruserkrankungen im WeinbauViroses in viticultureHenriette Gruber, Patricia Bohnert, Christiane Rieger149 - Molecular analysis of Tobacco rattle virus isolates from potatoes in various parts of GermanyKerstin Lindner, Renate Koenig150 - Detektion und Diversität des European mountain ash ringspot-associated virus (EMARaV) in Ebereschen (Sorbus aucuparia L.) in NorwegenDetection and variability of European mountain ash ringspot-associated virus (EMARaV) in Sorbus aucuparia L. in NorwayTheresa Büttner, Jenny Robel, Hans-Peter Mühlbach, Susanne von Bargen, Carmen Büttner151 - Charakterisierung des European mountain ash ringspot-associated virus (EMARaV) in Mehlbeerenarten (Sorbus spp.)Characterization of the European mountain ash ringspot-associated virus (EMARaV) in whitebeam species (Sorbus spp.)Luisa Dieckmann, Jenny Robel, Susanne von Bargen, Carmen Büttner152 - Vollständige Genomsequenz eines Carrot virus S Isolates aus Meerfenchel aus SpanienW. Menzel, P. Menzel, S. Winter153 - Nachweis und vollständige Sequenzierung eines Carla- und eines Potex-virus aus Epiphyullum spec.Detection and complete sequence of a Carla- and Potexvirus in Epiphyllum spec.Edgar Maiss, Paul Rentz, Annette Hohe, Rosa Herbst154 - Analysis of mixed populations of latent viruses of apple and rubbery wood disease of apple using new generation sequencingAnalyse von Mischpopulationen latenter Apfelviren und der Gummiholzkrankheit an Apfel mittels HochdurchsatzsequenzierungVladimir Jakovljevic, Patricia Otten, Jonathon Blake, Wilhelm Jelkmann155 - Experiments on transmission of viroids under glass and longevity of viroid RNA in detached leaves under different storage conditionsThi Thu Vo, Heinz-Wilhelm Dehne, Stephan Winter, Joachim Hamacher156 - Phytoplasmen in Schleswig-HolsteinPhytoplasmas in the state of Schleswig-HolsteinG. Henkel, C. Willmer, M. Wunderlich, B. Golecki157 . Phytoplasmen verändern das Dufststoffbouquet ihres pflanzlichen LebensraumsPlant volatile emission is affected by phytoplasma infectionMargit Rid, Kai Lukat, Svenja Hoferer, Jürgen Gross159 - Ist das Wurzelbild ein Sortierungsmerkmal für durch Candidatus Phytoplasma pyri verursachten Birnenverfall?Is the root file a sorting feature for Pear decline caused by Canditatus Phytoplama pyri?Georg Henkel, Claudia Willmer, Bernd Kaland, Bettina Golecki160 - Die Bedeutung von β-Caryophyllen als Lockstoff für die Apfeltriebsucht übertragende Blattsaugerart Cacopsylla pictaThe impact of β-caryophyllene as attractant for the Apple Proliferation transmitting insect Cacopsylla pictaConstanze Mesca, Svenja Hoferer, Jürgen Gross161 - Echte Mehltauarten an Beet- und BalkonpflanzenSpecies of powdery mildews on bedding plantsUlrike Brielmaier-Liebetanz162 - Echter Mehltau an Petersilie – Untersuchungen zum WirtspflanzenspektrumPowdery Mildew of Parsley – studies on the host rangePeggy Marx, Ute Gärber163 - Falscher Mehltau an Petersilie – Untersuchungen zum Wirtspflanzenspektrum und molekularbiologische CharakterisierungDowny mildew of parsley – studies on the host range and molecular characterizationGabriele Leinhos, Hermann-Josef Krauthausen, Frank Brändle164 - Welkekrankheit an Euonymus japonicaWilt disease on Euonymus japonicaUlrike Brielmaier-Liebetanz, Roswitha Ulrich, Stefan Wagner, Sabine Werres165 - Taxonomische Analyse der mikrobiellen Gemeinschaft von Zuckerrüben unter unterschiedlichen Lagerbedingungen mittels Hochdurchsatz-Amplikonsequenzierung von unterschiedlichen MarkergenenTaxonomic analysis of the microbial community in stored sugar beets using highthroughput sequencing of different marker genesSebastian Liebe, Daniel Wibberg, Anika Winkler, Alfred Pühler, Andreas Schlüter, Mark Varrelmann166 - Molecular characterization of a novel mycovirus found in Rhizoctonia solani AG 2-2IIIBMolekulare Charakterisierung eines neuen Mycovirus aus Rhizoctonia solani AG 2-2 IIIBAnika Bartholomäus, Mark Varrelman

Interrelationships between Yeast Ribosomal Protein Assembly Events and Transient Ribosome Biogenesis Factors Interactions in Early Pre-Ribosomes

Early steps of eukaryotic ribosome biogenesis require a large set of ribosome biogenesis factors which transiently interact with nascent rRNA precursors (pre-rRNA). Most likely, concomitant with that initial contacts between ribosomal proteins (r-proteins) and ribosome precursors (pre-ribosomes) are established which are converted into robust interactions between pre-rRNA and r-proteins during the course of ribosome maturation. Here we analysed the interrelationship between r-protein assembly events and the transient interactions of ribosome biogenesis factors with early pre-ribosomal intermediates termed 90S pre-ribosomes or small ribosomal subunit (SSU) processome in yeast cells. We observed that components of the SSU processome UTP-A and UTP-B sub-modules were recruited to early pre-ribosomes independently of all tested r-proteins. On the other hand, groups of SSU processome components were identified whose association with early pre-ribosomes was affected by specific r-protein assembly events in the head-platform interface of the SSU. One of these components, Noc4p, appeared to be itself required for robust incorporation of r-proteins into the SSU head domain. Altogether, the data reveal an emerging network of specific interrelationships between local r-protein assembly events and the functional interactions of SSU processome components with early pre-ribosomes. They point towards some of these components being transient primary pre-rRNA in vivo binders and towards a role for others in coordinating the assembly of major SSU domains

Estrogen prevents bone loss through transforming growth factor β signaling in T cells

Estrogen (E) deficiency leads to an expansion of the pool of tumor necrosis factor (TNF)-producing T cells through an IFN-γ-dependent pathway that results in increased levels of the osteoclastogenic cytokine TNF in the bone marrow. Disregulated IFN-γ production is instrumental for the bone loss induced by ovariectomy (ovx), but the responsible mechanism is unknown. We now show that mice with T cell-specific blockade of type β transforming growth factor (TGFβ) signaling are completely insensitive to the bone-sparing effect of E. This phenotype results from a failure of E to repress IFN-γ production, which, in turn, leads to increased T cell activation and T cell TNF production. Furthermore, ovx blunts TGFβ levels in the bone marrow, and overexpression of TGFβ in vivo prevents ovx-induced bone loss. These findings demonstrate that E prevents bone loss through a TGFβ-dependent mechanism, and that TGFβ signaling in T cells preserves bone homeostasis by blunting T cell activation. Thus, stimulation of TGFβ production in the bone marrow is a critical “upstream” mechanism by which E prevents bone loss, and enhancement of TGFβ levels in vivo may constitute a previously undescribed therapeutic approach for preventing bone loss