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1.
metaBIT,an integrative and automated metagenomic pipeline for analysing microbial profiles from high‐throughput sequencing shotgun data 下载免费PDF全文
Guillaume Louvel Clio Der Sarkissian Kristian Hanghøj Ludovic Orlando 《Molecular ecology resources》2016,16(6):1415-1427
Micro‐organisms account for most of the Earth's biodiversity and yet remain largely unknown. The complexity and diversity of microbial communities present in clinical and environmental samples can now be robustly investigated in record times and prices thanks to recent advances in high‐throughput DNA sequencing (HTS). Here, we develop metaBIT, an open‐source computational pipeline automatizing routine microbial profiling of shotgun HTS data. Customizable by the user at different stringency levels, it performs robust taxonomy‐based assignment and relative abundance calculation of microbial taxa, as well as cross‐sample statistical analyses of microbial diversity distributions. We demonstrate the versatility of metaBIT within a range of published HTS data sets sampled from the environment (soil and seawater) and the human body (skin and gut), but also from archaeological specimens. We present the diversity of outputs provided by the pipeline for the visualization of microbial profiles (barplots, heatmaps) and for their characterization and comparison (diversity indices, hierarchical clustering and principal coordinates analyses). We show that metaBIT allows an automatic, fast and user‐friendly profiling of the microbial DNA present in HTS shotgun data sets. The applications of metaBIT are vast, from monitoring of laboratory errors and contaminations, to the reconstruction of past and present microbiota, and the detection of candidate species, including pathogens. 相似文献
2.
Darryl J. Hill Natalie J. Griffiths Elena Borodina Clio A. Andreae Richard B. Sessions Mumtaz Virji 《PloS one》2015,10(3)
The human pathogen Neisseria meningitides (Nm) attains serum resistance via a number of mechanisms, one of which involves binding to the host complement regulator protein vitronectin. We have shown previously that the Meningococcal surface fibril (Msf), a trimeric autotransporter, binds to the activated form of vitronectin (aVn) to increase Nm survival in human serum. In this study, we aimed to identify the aVn-binding region of Msf to assess its potential as an antigen which can elicit antibodies that block aVn binding and/or possess bactericidal properties. Using several recombinant Msf fragments spanning its surface-exposed region, the smallest aVn-binding recombinants were found to span residues 1-86 and 39-124. The use of further deletion constructs and overlapping recombinant Msf fragments suggested that a region of Msf comprising residues 39-82 may be primarily important for aVn binding and that other regions may also be involved but to a lesser extent. Molecular modelling implicated K66 and K68, conserved in all available Msf sequences, to be involved in the interaction. Recombinant fragments which bound to aVn were able to reduce the survival advantage conveyed by aVn-interaction in serum bactericidal assays. Antibodies raised against one such fragment inhibited aVn binding to Msf. In addition, the antibodies enhanced specific killing of Msf-expressing Nm in a dose-dependent manner. Overall, this study identifies an aVn-binding region of Msf, an adhesin known to impart serum resistance properties to the pathogen; and shows that this region of Msf can elicit antibodies with dual properties which reduce pathogen survival within the host and thus has potential as a vaccine antigen. 相似文献
3.
Introduction
While the role of mycophenolate mofetil (MMF) in the management of lupus nephritis has been increasingly recognized, limited information is available regarding its efficacy and safety as a long-term maintenance treatment. The aim of the present study was to evaluate the efficacy and safety profile of MMF as maintenance therapy for proliferative lupus nephritis. 相似文献4.
Relic B Benoit V Franchimont N Ribbens C Kaiser MJ Gillet P Merville MP Bours V Malaise MG 《The Journal of biological chemistry》2004,279(21):22399-22403
We have previously shown that nuclear factor-kappaB inhibition by adenovirus expressing mutated IkappaB-alpha or by proteasome inhibitor increases human articular chondrocytes sensibility to apoptosis. Moreover, the nuclear factor-kappaB inhibitor BAY11-7085, a potent anti-inflammatory drug in rat adjuvant arthritis, is itself a proapoptotic agent for chondrocytes. In this work, we show that BAY 11-7085 but not the proteasome inhibitor MG-132 induced a rapid and sustained phosphorylation of extracellular signal-regulated kinases (ERK1/2) in human articular chondrocytes. The level of ERK1/2 phosphorylation correlated with BAY 11-7085 concentration and chondrocyte apoptosis. 15-Deoxy-delta(12,14)-prostaglandin J2 (15d-PGJ2) and its precursor prostaglandin (PG) D2 but not PGE2 and PGF2alpha rescued chondrocytes from BAY 11-7085-induced apoptosis. 15d-PGJ2 markedly inhibited BAY 11-7085-induced phosphorylation of ERK1/2. BAY 11-7085 also induced ERK1/2 phosphorylation and apoptosis in human synovial fibroblasts, and these reactions were down-regulated by 15d-PGJ2. Further analysis in synovial fibroblasts showed that only molecules that suppressed BAY 11-7085-induced phosphorylation of ERK1/2 (i.e. 15d-PGJ2, PGD2, and to a lesser extent, MEK1/2 inhibitor UO126, but not prostaglandins E2 and F2alpha or peroxisome proliferator-activated receptor-gamma agonist ciglitazone) were able protect cells from apoptosis. These results suggested that the antiapoptotic effect of 15d-PGJ2 on chondrocytes and synovial fibroblasts might involve inhibition of ERK1/2 phosphorylation. 相似文献
5.
Clio Andris David Lee Marcus J. Hamilton Mauro Martino Christian E. Gunning John Armistead Selden 《PloS one》2015,10(4)
It is widely reported that partisanship in the United States Congress is at an historic high. Given that individuals are persuaded to follow party lines while having the opportunity and incentives to collaborate with members of the opposite party, our goal is to measure the extent to which legislators tend to form ideological relationships with members of the opposite party. We quantify the level of cooperation, or lack thereof, between Democrat and Republican Party members in the U.S. House of Representatives from 1949–2012. We define a network of over 5 million pairs of representatives, and compare the mutual agreement rates on legislative decisions between two distinct types of pairs: those from the same party and those formed of members from different parties. We find that despite short-term fluctuations, partisanship or non-cooperation in the U.S. Congress has been increasing exponentially for over 60 years with no sign of abating or reversing. Yet, a group of representatives continue to cooperate across party lines despite growing partisanship. 相似文献
6.
Three-dimensional in vivo imaging of green fluorescent protein-expressing T cells in mice with noncontact fluorescence molecular tomography 总被引:1,自引:0,他引:1
Garofalakis A Zacharakis G Meyer H Economou EN Mamalaki C Papamatheakis J Kioussis D Ntziachristos V Ripoll J 《Molecular imaging》2007,6(2):96-107
Given that optical tomography is capable of quantitatively imaging the distribution of several important chromophores and fluorophores in vivo, there has been a great deal of interest in developing optical imaging systems with increased numbers of measurements under optimal experimental conditions. In this article, we present a novel system that enables three-dimensional imaging of fluorescent probes in whole animals using a noncontact setup, in parallel with a three-dimensional surface reconstruction algorithm. This approach is directed toward the in vivo imaging of fluorophore or fluorescent protein concentration in small animals. The system consists of a rotating sample holder and a lens-coupled charge-coupled device camera in combination with a fiber-coupled laser scanning device. By measuring multiple projections, large data sets can be obtained, thus improving the accuracy of the inversion models used for quantitative three-dimensional reconstruction of fluorochrome distribution, as well as facilitating a higher spatial resolution. In this study, the system was applied to determining the distribution of green fluorescent protein (GFP)-expressing T lymphocytes in a transgenic mouse model, thus demonstrating the potential of the system for studying immune system function. The technique was used to image and reconstruct fluorescence originating from 32 x 10(6) T cells in the thymus and 3 x 10(5) T cells in the spleen. 相似文献
7.
Clio Der Sarkissian Julia T. Vilstrup Mikkel Schubert Andaine Seguin-Orlando David Eme Jacobo Weinstock Maria Teresa Alberdi Fabiana Martin Patricio M. Lopez Jose L. Prado Alfredo Prieto Christophe J. Douady Tom W. Stafford Eske Willerslev Ludovic Orlando 《Biology letters》2015,11(3)
Hippidions were equids with very distinctive anatomical features. They lived in South America 2.5 million years ago (Ma) until their extinction approximately 10 000 years ago. The evolutionary origin of the three known Hippidion morphospecies is still disputed. Based on palaeontological data, Hippidion could have diverged from the lineage leading to modern equids before 10 Ma. In contrast, a much later divergence date, with Hippidion nesting within modern equids, was indicated by partial ancient mitochondrial DNA sequences. Here, we characterized eight Hippidion complete mitochondrial genomes at 3.4–386.3-fold coverage using target-enrichment capture and next-generation sequencing. Our dataset reveals that the two morphospecies sequenced (H. saldiasi and H. principale) formed a monophyletic clade, basal to extant and extinct Equus lineages. This contrasts with previous genetic analyses and supports Hippidion as a distinct genus, in agreement with palaeontological models. We date the Hippidion split from Equus at 5.6–6.5 Ma, suggesting an early divergence in North America prior to the colonization of South America, after the formation of the Panamanian Isthmus 3.5 Ma and the Great American Biotic Interchange. 相似文献
8.
Vytas K. Verselis Maria P. Trelles Clio Rubinos Thaddeus A. Bargiello Miduturu Srinivas 《The Journal of biological chemistry》2009,284(7):4484-4493
Unapposed connexin hemichannels exhibit robust closure in response to
membrane hyperpolarization and extracellular calcium. This form of gating,
termed “loop gating,” is largely responsible for regulating
hemichannel opening, thereby preventing cell damage through excessive flux of
ions and metabolites. The molecular components and structural rearrangements
underlying loop gating remain unknown. Here, using cysteine mutagenesis in
Cx50, we demonstrate that residues at the TM1/E1 border undergo movement
during loop gating. Replacement of Phe43 in Cx50 with a cysteine
resulted in small or no appreciable membrane currents. Bath application of
dithiothreitol or TPEN
(N,N,N′,N′-tetrakis(2-pyridylmethyl)
ethylenediamine), reagents that exhibit strong transition metal chelating
activity, led to robust currents indicating that the F43C substitution
impaired hemichannel function, producing “lock-up” in a closed or
poorly functional state due to formation of metal bridges. In support,
Cd2+ at submicromolar concentrations (50–100 nm)
enhanced lock-up of F43C hemichannels. Moreover, lock-up occurred under
conditions that favored closure, indicating that the sulfhydryl groups come
close enough to each other or to other residues to coordinate metal ions with
high affinity. In addition to F43C, metal binding was also found for G46C, and
to a lesser extent, D51C substitutions, positions found to be pore-lining in
the open state using the substituted-cysteine accessibility method, but not
for A40C and A41C substitutions, which were not found to reside in the open
pore. These results indicate that metal ions access the cysteine side chains
through the open pore and that closure of the loop gate involves movement of
the TM1/E1 region that results in local narrowing of the large aqueous
connexin pore.Connexins are a large family of homologous integral membrane proteins that
form gap junction (intercellular) channels that provide a direct communication
pathway between neighboring cells. Gap junctions are formed by the docking of
two hemichannels, which themselves can function in an undocked or unapposed
configuration as ion channels that signal across the plasma membrane. Each
hemichannel is composed of a hexamer of connexin subunits. The accepted
membrane topology of a connexin subunit has four transmembrane domains
(TM1–TM4)3 and
two extracellular loops (E1 and E2) with amino and carboxyl termini located
intracellularly (reviewed in Ref.
1).Connexin cell-cell channels and hemichannels are voltage dependent and two
distinct voltage-sensitive gating mechanisms appear to be built into each
hemichannel (2). One gating
mechanism proposed to be located at the cytoplasmic end of the hemichannel is
termed Vj gating, a name derived from studies of gap junction
(cell-cell) channels describing sensitivity to transjunctional voltage,
Vj, the voltage difference between coupled cells. The other gating
mechanism is putatively ascribed to the extracellular end of the hemichannel
and has been provisionally termed loop gating, because of the resemblance of
gating transitions to those associated with initial opening of newly formed
cell-cell channels (3,
4), a process that conceivably
involves the extracellular loop domains.Loop gating is a robust gating mechanism that together with extracellular
divalent cations, principally Ca2+, is largely responsible for
keeping unapposed hemichannels closed at resting membrane potentials
(5). Reports have suggested
that extracellular divalent cations act as gating particles that enter and
block the pore upon hyperpolarization
(6,
7). An alternative model was
recently proposed whereby extracellular divalent cations act as modulators of
loop gating, an intrinsically voltage-sensitive mechanism, by stabilizing the
closed conformation and shifting activation such that opening occurs at more
positive potentials (8).Although loop gating plausibly involves conformational changes associated
with the extracellular loops, molecular components underlying loop gating as
well as the location of the putative gate remain unknown. A recent study using
chick homologues to the mammalian connexins, Cx46 and Cx50, reported that two
charged residues were important determinants of the different gating
characteristics exhibited by these two connexin hemichannels
(9). The implicated residues
are at position 9 located in the NH2-terminal domain and position
43 in the E1 domain. In Cx46 hemichannels, Glu43 and other flanking
residues at the TM1/E1 border (Ala39, Gly46, and
Asp51) were shown to reside in the aqueous pore in the open state
(10). Because it is likely
that domains involved in permeation and gating of connexin channels are
closely linked (reviewed in Ref.
11), we examined whether these
residues are involved in structural rearrangements associated with loop
gating. In this study, we engineered cysteines at residues in the TM1/E1
border in Cx50 hemichannels and used the ability of sulfhydryl groups to form
disulfide bonds and/or to complex with heavy metal ions to report
conformational changes that occur during gating. 相似文献
9.
Marleen De Troch Clio Cnudde Anne Willems Tom Moens Ann Vanreusel 《Microbial ecology》2010,60(3):581-591
Fecal pellets make up a significant fraction of the global flux of organic matter in oceans, and the associated bacterial
communities in particular are a potential food source for marine organisms. However, these communities remain largely unknown.
In the present study, the bacterial communities on fecal pellets of the benthic copepod Paramphiascella fulvofasciata feeding on the diatoms Navicula phyllepta and Seminavis robusta were analyzed. The aim of this study was to characterize the bacterial communities associated with the diatoms and the fecal
pellets by means of DGGE profiling. Furthermore, isolated bacteria were characterized by means of partial 16S rRNA gene sequencing.
The composition of the bacterial microflora on fecal pellets was studied in terms of the effect of the original food source,
the age of the fecal pellets and the copepod’s identity. Alphaproteobacteria, Flavobacteria, and Bacilli were found on the
fecal pellets; whereas on diatoms, exclusively Gammaproteobacteria were identified. Especially after eating N. phyllepta, there was an important increase in bacterial diversity, although the diatom N. phyllepta harbored a less diverse bacterial community than S. robusta. Our data suggest that the additional bacteria originate from the copepod’s digestive tract and largely depends on the initial
food source. 相似文献
10.