A promiscuous cytochrome P450 aromatic O-demethylase for lignin bioconversion

FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOMicrobial aromatic catabolism offers a promising approach to convert lignin, a vast source of renewable carbon, into useful products. Aryl-O-demethylation is an essential biochemical reaction to ultimately catabolize coniferyl and sinapyl lignin-derived a9FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO2013/08293-72014/10448-12016/22956-7We acknowledge funding from NSF grants to J.L.D. (MCB-1715176), K.N.H. (CHE-1361104), and E.L.N. (DEB-1556541 and MCB-1615365) and BBSRC grants to J.E.M. (BB/P011918/1, BB/L001926/1 and a studentship to S.J.B.M.). G.T.B., M.M.M., C.W.J., M.F.C., E.L.N.,

Imaging DNA Damage Repair In Vivo After 177Lu-DOTATATE Therapy

Molecular radiotherapy using 177Lu-DOTATATE is a most effective treatment for somatostatin receptor-expressing neuroendocrine tumors. Despite its frequent and successful use in the clinic, little or no radiobiologic considerations are made at the time of treatment planning or delivery. On positive uptake on octreotide-based PET/SPECT imaging, treatment is usually administered as a standard dose and number of cycles without adjustment for peptide uptake, dosimetry, or radiobiologic and DNA damage effects in the tumor. Here, we visualized and quantified the extent of DNA damage response after 177Lu-DOTATATE therapy using SPECT imaging with 111In-anti-γH2AX-TAT. This work was a proof-of-principle study of this in vivo noninvasive biodosimeter with β-emitting therapeutic radiopharmaceuticals. Methods: Six cell lines were exposed to external-beam radiotherapy (EBRT) or 177Lu-DOTATATE, after which the number of γH2AX foci and the clonogenic survival were measured. Mice bearing CA20948 somatostatin receptor-positive tumor xenografts were treated with 17

Large Methane Emission Fluxes Observed From Tropical Wetlands in Zambia

Methane (CH4) is a potent greenhouse gas with a warming potential 84 times that of carbon dioxide (CO2) over a 20-year period. Atmospheric CH4 concentrations have been rising since the nineteenth century but the cause of large increases post-2007 is disputed. Tropical wetlands are thought to account for ∼20% of global CH4 emissions, but African tropical wetlands are understudied and their contribution is uncertain. In this work, we use the first airborne measurements of CH4 sampled over three wetland areas in Zambia to derive emission fluxes. Three independent approaches to flux quantification from airborne measurements were used: Airborne mass balance, airborne eddy-covariance, and an atmospheric inversion. Measured emissions (ranging from 5 to 28 mg m−2 hr−1) were found to be an order of magnitude greater than those simulated by land surface models (ranging from 0.6 to 3.9 mg m−2 hr−1), suggesting much greater emissions from tropical wetlands than currently accounted for. The prevalence of such underestimated CH4 sources may necessitate additional reductions in anthropogenic greenhouse gas emissions to keep global warming below a threshold of 2°C above preindustrial levels

Isotopic signatures of methane emissions from tropical fires, agriculture and wetlands : The MOYA and ZWAMPS flights

We report methane isotopologue data from aircraft and ground measurements in Africa and South America. Aircraft campaigns sampled strong methane fluxes over tropical papyrus wetlands in the Nile, Congo and Zambezi basins, herbaceous wetlands in Bolivian southern Amazonia, and over fires in African woodland, cropland and savannah grassland. Measured methane δ 13 C CH 4 isotopic signatures were in the range -55 to -49‰ for emissions from equatorial Nile wetlands and agricultural areas, but widely -60 ± 1‰ from Upper Congo and Zambezi wetlands. Very similar δ 13 C CH 4 signatures were measured over the Amazonian wetlands of NE Bolivia (around -59‰) and the overall δ 13 C CH 4 signature from outer tropical wetlands in the southern Upper Congo and Upper Amazon drainage plotted together was -59 ± 2‰. These results were more negative than expected. For African cattle, δ 13 C CH 4 values were around -60 to -50‰. Isotopic ratios in methane emitted by tropical fires depended on the C3: C4 ratio of the biomass fuel. In smoke from tropical C3 dry forest fires in Senegal, δ 13 C CH 4 values were around -28‰. By contrast, African C4 tropical grass fire δ 13 C CH 4 values were -16 to -12‰. Methane from urban landfills in Zambia and Zimbabwe, which have frequent waste fires, had δ 13 C CH 4 around -37 to -36‰. These new isotopic values help improve isotopic constraints on global methane budget models because atmospheric δ 13 C CH 4 values predicted by global atmospheric models are highly sensitive to the δ 13 C CH 4 isotopic signatures applied to tropical wetland emissions. Field and aircraft campaigns also observed widespread regional smoke pollution over Africa, in both the wet and dry seasons, and large urban pollution plumes. The work highlights the need to understand tropical greenhouse gas emissions in order to meet the goals of the UNFCCC Paris Agreement, and to help reduce air pollution over wide regions of Africa. This article is part of a discussion meeting issue 'Rising methane: is warming feeding warming? (part 2)'

Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses

To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1–11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury. Autoantibodies are more common in COVID-19 than controls and some (including against MYL7, UCH-L1, and GRIN3B) are more frequent with altered consciousness. Additionally, convalescent participants with neurological complications show elevated GFAP and NfL, unrelated to attenuated systemic inflammatory mediators and to autoantibody responses. Overall, neurological complications of COVID-19 are associated with evidence of neuroglial injury in both acute and late disease and these correlate with dysregulated innate and adaptive immune responses acutely

A História da Alimentação: balizas historiográficas

Os M. pretenderam traçar um quadro da História da Alimentação, não como um novo ramo epistemológico da disciplina, mas como um campo em desenvolvimento de práticas e atividades especializadas, incluindo pesquisa, formação, publicações, associações, encontros acadêmicos, etc. Um breve relato das condições em que tal campo se assentou faz-se preceder de um panorama dos estudos de alimentação e temas correia tos, em geral, segundo cinco abardagens Ia biológica, a econômica, a social, a cultural e a filosófica!, assim como da identificação das contribuições mais relevantes da Antropologia, Arqueologia, Sociologia e Geografia. A fim de comentar a multiforme e volumosa bibliografia histórica, foi ela organizada segundo critérios morfológicos. A seguir, alguns tópicos importantes mereceram tratamento à parte: a fome, o alimento e o domínio religioso, as descobertas européias e a difusão mundial de alimentos, gosto e gastronomia. O artigo se encerra com um rápido balanço crítico da historiografia brasileira sobre o tema

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease