This study describes the features of LRTIs associated with newly identified viruses in children, compared with those associated with known viruses. Additional investigations are required to define the role of HBoV in LRTI.
Dendritic cells (DCs) that orchestrate mucosal immunity have been studied in mice. Here we characterize human gut DC populations, and define their relationship to previously studied human and mouse DCs. CD103+Sirpα− DCs were related to human blood CD141+ and to mouse intestinal CD103+CD11b− DCs and expressed markers of cross-presenting DCs. CD103+Sirpα+ DCs aligned with human blood CD1c+ DCs and mouse intestinal CD103+CD11b+ DCs and supported regulatory T cell induction. Both CD103+ DC subsets induced TH17 cells, while CD103−Sirpα+ DCs induced TH1 cells. Comparative transcriptomics revealed conserved transcriptional programs among CD103+ DC subsets and uncovered a selective role for Bcl-6 and Blimp-1 in CD103+Sirpα− and intestinal CD103+CD11b+ DC specification, respectively. These results highlight evolutionarily conserved and divergent programming of intestinal DCs.
Spinal cord injury (SCI) causes a permanent neurological disability, and no satisfactory treatment is currently available. After SCI, pro-nerve growth factor (proNGF) is known to play a pivotal role in apoptosis of oligodendrocytes, but the cell types producing proNGF and the signaling pathways involved in proNGF production are primarily unknown. Here, we show that minocycline improves functional recovery after SCI in part by reducing apoptosis of oligodendrocytes via inhibition of proNGF production in microglia. After SCI, the stress-responsive p38 mitogen-activated protein kinase (p38MAPK) was activated only in microglia, and proNGF was produced by microglia via the p38MAPK-mediated pathway. Minocycline treatment significantly reduced proNGF production in microglia in vitro and in vivo by inhibition of the phosphorylation of p38MAPK. Furthermore, minocycline treatment inhibited p75 neurotrophin receptor expression and RhoA activation after injury. Finally, minocycline treatment inhibited oligodendrocyte death and improved functional recovery after SCI. These results suggest that minocycline may represent a potential therapeutic agent for acute SCI in humans.
Phagocytosis of apoptotic cells usually results in an anti-inflammatory state with inhibition of proinflammatory cytokines such as IL-12. How apoptotic cell-derived signals regulate IL-12 gene expression is not understood. We demonstrate that cell-cell contact with apoptotic cells is sufficient to induce profound inhibition of IL-12 production by activated macrophages. Phosphatidylserine could mimic the inhibitory effect. The inhibition does not involve autocrine or paracrine actions of IL-10 and TGF-beta. We report the identification, purification, and cloning of a novel zinc finger nuclear factor, named GC binding protein (GC-BP), that is induced following phagocytosis of apoptotic cells by macrophages or by treatment with phosphatidylserine. GC-BP selectively inhibits IL-12 p35 gene transcription by binding to its promoter in vitro and in vivo, thus decreasing IL-12 production. Blocking GC-BP by RNA interference restores IL-12 p35 transcription and IL-12 p70 synthesis. Finally, GC-BP itself undergoes functionally significant tyrosine dephosphorylation in response to apoptotic cells.
A single, multidrug-resistant strain was responsible for increased incidence of this serotype before introduction of the pneumococcal 7-valent conjugate vaccine.
We examined the effects of minocycline, an anti-inflammatory drug, on functional recovery following spinal cord injury (SCI). Rats received a mild, weight-drop contusion injury to the spinal cord and were treated with the vehicle or minocycline at a dose of 90 mg/kg immediately after SCI and then twice at a dose of 45 mg/kg every 12 h. Injecting minocycline after SCI improved hind limb motor function as determined by the Basso-Beattie-Bresnahan (BBB) locomotor open field behavioral rating test. Twenty four to 38 days after SCI, BBB scores were significantly higher in minocycline-treated rats as compared with those in vehicle-treated rats. Morphological analysis showed that lesion size increased progressively in both vehicle-treated and minocycline-treated spinal cords. However, in response to treatment with minocycline, the lesion size was significantly reduced at 21-38 days after SCI when compared to the vehicle control. Minocycline treatment significantly reduced the number of terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL)-positive cells 24 h after SCI as compared to that of the vehicle control. DNA gel electrophoresis also revealed a marked decrease in DNA laddering in response to treatment with minocycline. In addition, minocycline treatment significantly reduced the specific caspase-3 activity after SCI as compared to that of vehicle control. Furthermore, RT-PCR analyses revealed that minocycline treatment increased expression of interleukin-10 mRNA but decreased tumor necrosis factor-alpha expression. These data suggest that, after SCI, minocycline treatment modulated expression of cytokines, attenuated cell death and the size of lesions, and improved functional recovery in the injured rat. This approach may provide a therapeutic intervention enabling us to reduce cell death and improve functional recovery after SCI.
The effect of Ag decoration on the gas sensing characteristics of SnO(2) nanowire (NW) networks was investigated. The Ag layers with thicknesses of 5-50 nm were uniformly coated on the surface of SnO(2) NWs via e-beam evaporation, which were converted into isolated or continuous configurations of Ag islands by heat treatment at 450 °C for 2 h. The SnO(2) NWs decorated by isolated Ag nano-islands displayed a 3.7-fold enhancement in gas response to 100 ppm C(2)H(5)OH at 450 °C compared to pristine SnO(2) NWs. In contrast, as the Ag decoration layers became continuous, the response to C(2)H(5)OH decreased significantly. The enhancement and deterioration of the C(2)H(5)OH sensing characteristics by the introduction of the Ag decoration layer were strongly governed by the morphological configurations of the Ag catalysts on SnO(2) NWs and their sensitization mechanism.
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