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Understanding the physiological and pathological roles of factors that regulate angiogenesis and lymphangiogenesis in the kidney has led to the development of novel therapeutic strategies for kidney diseases.C-glycosylated flavones (CGFs) are promising candidates as anti-nociceptive compounds. The leaves of bamboo and related crops in the grass family are a largely unexploited bioresource with a wide array of CGFs. We report here pathway-specific enzymes including C-glycosyltransferases (CGTs) and P450 hydroxylases from cereal crops and bamboo species accumulating abundant CGFs. Mining of CGTs and engineering of P450s that decorate the flavonoid skeleton allowed the production of desired CGFs (with yield of 20-40 mg/L) in an Escherichia coli cell factory. We further explored the antinociceptive activity of major CGFs in mice models and identified isoorientin as the most potent, with both neuroanalgesic and anti-inflammatory effects superior to clinical drugs such as rotundine and aspirin. Our discovery of the pain-alleviating flavonoids elicited from bamboo and crop leaves establishes this previously underutilized source, and sheds light on the pathway and pharmacological mechanisms of the compounds.Wolbachia can reduce the capability of mosquitoes to transmit infectious diseases to humans and is currently exploited in campaigns for the control of arboviruses, like dengue and Zika. Under the assumption that Wolbachia-mediated activation of insect immunity plays a role in the reduction of mosquito vectorial capacity, we focused our attention on the Wolbachia surface protein (WSP), a potential inductor of innate immunity. We hypothesized that the heterologous expression of this protein in gut- and tissue-associated symbionts may reduce parasite transmission. We thus engineered the mosquito bacterial symbiont Asaia to express WSP (AsaiaWSP). AsaiaWSP induced activation of the host immune response in Aedes aegypti and Anopheles stephensi mosquitoes, and inhibited the development of the heartworm parasite Dirofilaria immitis in Ae. aegypti. These results consolidate previous evidence on the immune-stimulating property of WSP and make AsaiaWSP worth of further investigations as a potential tool for the control of mosquito-borne diseases.At Abu Hureyra (AH), Syria, the 12,800-year-old Younger Dryas boundary layer (YDB) contains peak abundances in meltglass, nanodiamonds, microspherules, and charcoal. AH meltglass comprises 1.6 wt.% of bulk sediment, and crossed polarizers indicate that the meltglass is isotropic. High YDB concentrations of iridium, platinum, nickel, and cobalt suggest mixing of melted local sediment with small quantities of meteoritic material. Approximately 40% of AH glass display carbon-infused, siliceous plant imprints that laboratory experiments show formed at a minimum of 1200°-1300 °C; however, reflectance-inferred temperatures for the encapsulated carbon were lower by up to 1000 °C. Alternately, melted grains of quartz, chromferide, and magnetite in AH glass suggest exposure to minimum temperatures of 1720 °C ranging to >2200 °C. This argues against formation of AH meltglass in thatched hut fires at 1100°-1200 °C, and low values of remanent magnetism indicate the meltglass was not created by lightning. Low meltglass water content (0.02-0.05% H2O) is consistent with a formation process similar to that of tektites and inconsistent with volcanism and anthropogenesis. The wide range of evidence supports the hypothesis that a cosmic event occurred at Abu Hureyra ~12,800 years ago, coeval with impacts that deposited high-temperature meltglass, melted microspherules, and/or platinum at other YDB sites on four continents.Lakes and reservoirs contribute substantially to atmospheric concentrations of the potent greenhouse gas methane. Lake sediments produce large amounts of methane, which accumulate in the oxygen-depleted bottom waters of stratified lakes. Climate change and eutrophication may increase the number of lakes with methane storage in the future. Whether stored methane escapes to the atmosphere during annual lake overturn is a matter of controversy and depends critically on the response of the methanotroph assemblage. Here we show, by combining 16S rRNA gene and pmoA mRNA amplicon sequencing, qPCR, CARD-FISH and potential methane-oxidation rate measurements, that the methanotroph assemblage in a mixing lake underwent both a substantial bloom and ecological succession. As a result, methane oxidation kept pace with the methane supplied from methane-rich bottom water and most methane was oxidized. This aspect of freshwater methanotroph ecology represents an effective mechanism limiting methane transfer from lakes to the atmosphere.Many diseases, including cancer, have been associated with impaired regulation of angiogenesis, of which vascular endothelial growth factor (VEGF)-A is a key regulator. Here, we test the contribution of N-myc downstream regulated gene 1 (NDRG1) to VEGF-A-induced angiogenesis in vascular endothelial cells (ECs). Ndrg1-/- mice exhibit impaired VEGF-A-induced angiogenesis in corneas. Tumor angiogenesis induced by cancer cells that express high levels of VEGF-A was also reduced in a mouse dorsal air sac assay. Furthermore, NDRG1 deficiency in ECs prevented angiogenic sprouting from the aorta and the activation of phospholipase Cγ1 (PLCγ1) and ERK1/2 by VEGF-A without affecting the expression and function of VEGFR2. https://www.selleckchem.com/products/Decitabine.html Finally, we show that NDRG1 formed a complex with PLCγ1 through its phosphorylation sites, and the inhibition of PLCγ1 dramatically suppressed VEGF-A-induced angiogenesis in the mouse cornea, suggesting an essential role of NDRG1 in VEGF-A-induced angiogenesis through PLCγ1 signaling.Patient satisfaction with the shape and appearance of their nose after orthognathic surgery-based skeletofacial reconstruction is an important, but often overlooked, outcome. We assessed the nose-related outcomes through a recently developed patient-reported outcome instrument and a widely adopted 3D computer-based objective outcome instrument, to verify any correlation in the results produced by these tools. We collected FACE-Q nose appearance reports (2 scales) and 3D nasal morphometry (10 parameters) from patients with class III skeletal pattern and congenital cleft lip palate deformity (n = 23) or developmental dentofacial deformity (n = 23) after (>12 months) skeletofacial reconstruction. The cleft and dentofacial cohorts demonstrated significantly (p  less then  0.001) poorer satisfaction scores with regard to the FACE-Q nostrils scale than the normal age-, gender-, and ethnicity-matched subjects (n = 107), without any significant difference in FACE-Q nose scale. The cleft cohort had significantly (p  less then  0.

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