Resident microbiota activate regulatory cells that modulate intestinal inflammation and promote and maintain intestinal homeostasis. IL-10 is a key mediator of immune regulatory function. Our studies ...described the functional importance and mechanisms by which gut microbiota and specific microbial components influenced the development of intestinal IL-10-producing B cells. We used fecal transplant to germ-free (GF) Il10+/EGFP reporter and Il10-/- mice to demonstrate that microbiota from specific pathogen-free mice primarily stimulated IL-10-producing colon-specific B cells and T regulatory-1 cells in ex-GF mice. IL-10 in turn down-regulated microbiota-activated mucosal inflammatory cytokines. TLR2/9 ligands and enteric bacterial lysates preferentially induced IL-10 production and regulatory capacity of intestinal B cells. Analysis of Il10+/EGFP mice crossed with additional gene-deficient strains and B cell co-transfer studies demonstrated that microbiota-induced IL-10-producing intestinal B cells ameliorated chronic T cell-mediated colitis in a TLR2, MyD88 and PI3K-dependent fashion. In vitro studies implicated PI3Kp110δ and AKT downstream signaling. These studies demonstrated that resident enteric bacteria activated intestinal IL-10-producing B cells through TLR2, MyD88 and PI3K pathways. These B cells reduced colonic T cell activation and maintained mucosal homeostasis in response to intestinal microbiota.
PHAST: A Fast Phage Search Tool Zhou, You; Liang, Yongjie; Lynch, Karlene H ...
Nucleic acids research,
07/2011, Letnik:
39, Številka:
suppl_2
Journal Article
Recenzirano
Odprti dostop
PHAge Search Tool (PHAST) is a web server designed to rapidly and accurately identify, annotate and graphically display prophage sequences within bacterial genomes or plasmids. It accepts either raw ...DNA sequence data or partially annotated GenBank formatted data and rapidly performs a number of database comparisons as well as phage 'cornerstone' feature identification steps to locate, annotate and display prophage sequences and prophage features. Relative to other prophage identification tools, PHAST is up to 40 times faster and up to 15% more sensitive. It is also able to process and annotate both raw DNA sequence data and Genbank files, provide richly annotated tables on prophage features and prophage 'quality' and distinguish between intact and incomplete prophage. PHAST also generates downloadable, high quality, interactive graphics that display all identified prophage components in both circular and linear genomic views. PHAST is available at (http://phast.wishartlab.com).
Two standard Tropical Rainfall Measuring Mission (TRMM) Multisatellite Precipitation Analysis (TMPA) products, 3B42RT and 3B42V6, were quantitatively evaluated in the Laohahe basin, China, located ...within the TMPA product latitude band (50°NS) but beyond the inclined TRMM satellite latitude band (36°NS). In general, direct comparison of TMPA rainfall estimates to collocated rain gauges from 2000 to 2005 show that the spatial and temporal rainfall characteristics over the region are well captured by the 3B42V6 estimates. Except for a few months with underestimation, the 3B42RT estimates show unrealistic overestimation nearly year round, which needs to be resolved in future upgrades to the real‐time estimation algorithm. Both model‐parameter error analysis and hydrologic application suggest that the three‐layer Variable Infiltration Capacity (VIC‐3L) model cannot tolerate the nonphysical overestimation behavior of 3B42RT through the hydrologic integration processes, and as such the 3B42RT data have almost no hydrologic utility, even at the monthly scale. In contrast, the 3B42V6 data can produce much better hydrologic predictions with reduced error propagation from input to streamflow at both the daily and monthly scales. This study also found the error structures of both RT and V6 have a significant geo‐topography‐dependent distribution pattern, closely associated with latitude and elevation bands, suggesting current limitations with TRMM‐era algorithms at high latitudes and high elevations in general. Looking into the future Global Precipitation Measurement (GPM) era, the Geostationary Infrared (GEO‐IR) estimates still have a long‐term role in filling the inevitable gaps in microwave coverage, as well as in enabling sub‐hourly estimates at typical 4‐km grid scales. Thus, this study affirms the call for a real‐time systematic bias removal in future upgrades to the IR‐based RT algorithm using a simple scaling factor. This correction is based on MW‐based monthly rainfall climatologies applied to the combined monthly satellite‐gauge research products.
Cooperation and competition (jointly called "coopetition") are two modes of interactions among a set of concurrent topics on social media. How do topics cooperate or compete with each other to gain ...public attention? Which topics tend to cooperate or compete with one another? Who plays the key role in coopetition-related interactions? We answer these intricate questions by proposing a visual analytics system that facilitates the in-depth analysis of topic coopetition on social media. We model the complex interactions among topics as a combination of carry-over, coopetition recruitment, and coopetition distraction effects. This model provides a close functional approximation of the coopetition process by depicting how different groups of influential users (i.e., "topic leaders") affect coopetition. We also design EvoRiver, a time-based visualization, that allows users to explore coopetition-related interactions and to detect dynamically evolving patterns, as well as their major causes. We test our model and demonstrate the usefulness of our system based on two Twitter data sets (social topics data and business topics data).
Kinase signaling in the tiered activation of inflammasomes and associated pyroptosis is a prime therapeutic target for inflammatory diseases. While MAPKs subsume pivotal roles during inflammasome ...priming, specifically the MAP3K7/JNK1/NLRP3 licensing axis, their involvement in successive steps of inflammasome activation is poorly defined. Using live-cell MAPK biosensors to focus on the inflammasome triggering event allowed us to identify a subsequent process of biphasic JNK activation. We find that this biphasic post-trigger JNK signaling initially facilitates the mitochondrial reactive oxygen species generation needed to support core inflammasome formation, then supports the gasdermin-mediated cell permeation required for release of active IL-1β from human macrophages. We further identify and characterize a xanthine oxidase-ROS activated MAP3K5/JNK2 substrate licensing complex as a novel regulator of the GSDMD mobilization which precedes pyroptosis. We show that inhibitors targeting this MAP3K5 cascade alleviate morbidity in mouse models of colitis and dampen both augmented IL-1β release and cell permeation in monocytes derived from patients with gain-of-function inflammasomopathies.
Metal‐Free Directed C−H Borylation of Pyrroles Wang, Zheng‐Jun; Chen, Xiangyang; Wu, Lei ...
Angewandte Chemie (International ed.),
April 6, 2021, Letnik:
60, Številka:
15
Journal Article
Recenzirano
Robust strategies to enable the rapid construction of complex organoboronates in selective, practical, low‐cost, and environmentally friendly modes remain conspicuously underdeveloped. Here, we ...develop a general strategy for the site‐selective C−H borylation of pyrroles by using only BBr3 directed by pivaloyl groups, avoiding the use of any metal. The site‐selectivity is generally dominated by chelation and electronic effects, thus forming diverse C2‐borylated pyrroles against the steric effect. The formed products can readily engage in downstream transformations, enabling a step‐economic process to access drugs such as Lipitor. DFT calculations (wB97X‐D) demonstrate the preferred positional selectivity of this reaction.
An efficient metal‐free system has been uncovered for the site‐selective C−H borylation of pyrroles by using only BBr3 directed by pivaloyl groups. The site‐selectivity is generally dominated by chelation and electronic effects, thus forming diverse C2‐borylated pyrroles against the steric effect.
Population-level national networks on social media are precious and essential for network science and behavioural science. This study collected a population-level Twitter network, based on both ...language and geolocation tags. We proposed a set of validation approaches to evaluate the validity of our datasets. Finally, we re-examined classical network and communication propositions (e.g., 80/20 rule, six degrees of separation) on the national network. Our dataset and strategy would flourish the data collection pool of population-level social networks and further develop the research of network analysis in digital media environment.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Inflammation driven by the NLRP3 inflammasome in macrophages is an important contributor to chronic metabolic diseases that affect growing numbers of individuals. Many of these diseases involve the ...pathologic accumulation of endogenous lipids or their oxidation products, which can activate NLRP3. Other endogenous lipids, however, can inhibit the activation of NLRP3. The intracellular mechanisms by which these lipids modulate NLRP3 activity are now being identified. This review discusses emerging evidence suggesting that organelle stress, particularly involving mitochondria, lysosomes, and the endoplasmic reticulum, may be key in lipid-induced modification of NLRP3 inflammasome activity.
Multiple classes of endogenous lipids, including oxidized low-density lipoprotein (LDL), saturated fatty acids, and sphingolipids, activate the mammalian NLRP3 inflammasome and can contribute to the progression of certain inflammatory diseases.Lipid activators of NLRP3 often share common features, such as slow-onset kinetics and the ability to provide both priming and triggering signals for inflammasome activation.Organelle stress, especially at mitochondria, lysosomes, and the endoplasmic reticulum, is required for lipid activation of NLRP3, while attenuation of organelle stress by certain lipids can inhibit NLRP3 activity.
We present a new data set of annual historical (1750–2014) anthropogenic chemically reactive gases (CO, CH4, NH3, NOx, SO2, NMVOCs), carbonaceous aerosols (black carbon – BC, and organic carbon – ...OC), and CO2 developed with the Community Emissions Data System (CEDS). We improve upon existing inventories with a more consistent and reproducible methodology applied to all emission species, updated emission factors, and recent estimates through 2014. The data system relies on existing energy consumption data sets and regional and country-specific inventories to produce trends over recent decades. All emission species are consistently estimated using the same activity data over all time periods. Emissions are provided on an annual basis at the level of country and sector and gridded with monthly seasonality. These estimates are comparable to, but generally slightly higher than, existing global inventories. Emissions over the most recent years are more uncertain, particularly in low- and middle-income regions where country-specific emission inventories are less available. Future work will involve refining and updating these emission estimates, estimating emissions' uncertainty, and publication of the system as open-source software.
Klebsiella pneumoniae causes significant morbidity and mortality worldwide, particularly amongst hospitalized individuals. The principle mechanism for pathogenesis in hospital environments involves ...the formation of biofilms, primarily on implanted medical devices. In this study, we constructed a transposon mutant library in a clinical isolate, K. pneumoniae AJ218, to identify the genes and pathways implicated in biofilm formation. Three mutants severely defective in biofilm formation contained insertions within the mrkABCDF genes encoding the main structural subunit and assembly machinery for type 3 fimbriae. Two other mutants carried insertions within the yfiN and mrkJ genes, which encode GGDEF domain- and EAL domain-containing c-di-GMP turnover enzymes, respectively. The remaining two isolates contained insertions that inactivated the mrkH and mrkI genes, which encode for novel proteins with a c-di-GMP-binding PilZ domain and a LuxR-type transcriptional regulator, respectively. Biochemical and functional assays indicated that the effects of these factors on biofilm formation accompany concomitant changes in type 3 fimbriae expression. We mapped the transcriptional start site of mrkA, demonstrated that MrkH directly activates transcription of the mrkA promoter and showed that MrkH binds strongly to the mrkA regulatory region only in the presence of c-di-GMP. Furthermore, a point mutation in the putative c-di-GMP-binding domain of MrkH completely abolished its function as a transcriptional activator. In vivo analysis of the yfiN and mrkJ genes strongly indicated their c-di-GMP-specific function as diguanylate cyclase and phosphodiesterase, respectively. In addition, in vitro assays showed that purified MrkJ protein has strong c-di-GMP phosphodiesterase activity. These results demonstrate for the first time that c-di-GMP can function as an effector to stimulate the activity of a transcriptional activator, and explain how type 3 fimbriae expression is coordinated with other gene expression programs in K. pneumoniae to promote biofilm formation to implanted medical devices.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
PDF
