bluuebunny/crossref_metadata_2025_split huggingface dataset:
The E3 ubiquitin ligase UBR5 regulates centriolar satellite stability and primary cilia formation via ubiquitylation of CSPP-L
Authors: Shearer Robert F. , Frikstad Kari-Anne Myrum , McKenna Jessie , McCloy Rachael A. , Deng Niantao , Burgess Andrew , Stokke Trond , Patzke Sebastian , Saunders Darren N. 
Published: December 2016

AbstractPrimary cilia are crucial for signal transduction in a variety of pathways, including Hedgehog and Wnt. Disruption of primary cilia formation (ciliogenesis) is linked to numerous developmental disorders (known as ciliopathies) and diseases, including cancer. The Ubiquitin-Proteasome System (UPS) component UBR5 was previously identified as a putative modulator of ciliogenesis in a functional genomics screen. UBR5 is an E3 Ubiquitin ligase that is frequently deregulated in tumours, but its biological role in cancer is largely uncharacterised, partly due to a lack of understanding of interacting proteins and pathways. We validated the effect of UBR5 depletion on primary cilia formation using a robust model of ciliogenesis, and identified CSPP1, a centrosomal and ciliary protein required for cilia formation, as a UBR5-interacting protein. We show that UBR5 ubiquitylates CSPP1, and that UBR5 is required for cytoplasmic organization of CSPP1-comprising centriolar satellites in centrosomal periphery. Hence, we have established a key role for UBR5 in ciliogenesis that may have important implications in understanding cancer pathophysiology.
Inter-Subject Alignment of MEG Datasets in a Common Representational Space
Authors: Zhang Qiong , Borst Jelmer P. , Kass Robert E. , Anderson John R. 
Published: December 2016

AbstractPooling neural imaging data across subjects requires aligning recordings from different subjects. In magnetoencephalography (MEG) recordings, sensors across subjects are poorly correlated both because of differences in the exact location of the sensors, and structural and functional differences in the brains. It is possible to achieve alignment by assuming that the same regions of different brains correspond across subjects. However, this relies on both the assumption that brain anatomy and function are well correlated, and the strong assumptions that go into solving the underdetermined inverse problem given the high dimensional source space. In this paper, we investigated an alternative method that bypasses source-localization. Instead, it analyzes the sensor recordings themselves and aligns their temporal signatures across subjects. We used a multivariate approach, multi-set canonical correlation analysis (M-CCA), to transform individual subject data to a low dimensional common representational space. We evaluated the robustness of this approach over a synthetic dataset, by examining the effect of different factors that add to the noise and individual differences in the data. On a MEG dataset, we demonstrated that M-CCA performs better than a method that assumes perfect sensor correspondence and a method that applies source localization. Lastly, we described how the standard M-CCA algorithm could be further improved with a regularization term that incorporates spatial sensor information.
Rampant Reverse Evolution towards Specialization in Commensal Bacteria Colonizing the Gut
Authors: Sousa A. , Ramiro R. S. , Barroso-Batista J. , Güleresi D. , Lourenço M. , Gordo I. 
Published: December 2016

AbstractThe maintenance of diversity in the gut microbiota is a signature of host health. Yet how strain variation emerges and changes over time in this ecosystem is poorly understood. Here we use a natural yet controlled system to track the effects of natural selection by the genetic signatures it leaves in evolving populations. By following the emergence of intra-species diversity in anEscherichia colistrain, we unravel a recurrent case of violation of Dollo’s law, which proposes that evolution is unidirectional and irreversible. We demonstratede novoacquisition of a primordial lost phenotype via compensatory mutation and also genetic reversion, the latter leaving no trace of the past. We show that this reverse evolution generates two coexisting phenotypes, resource generalist and specialist, whose abundance can be controlled by diet supplementation. While specialists’ abundance is low, they avoid competition with the gut microbiota, whereas generalist abundance is dependent on microbiota composition. Our results highlight how a single genetic change can have large ecological consequences.
Inferring hidden causal relations between pathway members using reduced Google matrix of directed biological networks
Authors: Lages José , Shepelyansky Dima L. , Zinovyev Andrei 
Published: December 2016

AbstractSignaling pathways represent parts of the global biological network which connects them into a seamless whole through complex direct and indirect (hidden) crosstalk whose structure can change during development or in pathological conditions. We suggest a novel methodology, called Googlomics, for the structural analysis of directed biological networks using spectral analysis of their Google matrices, using parallels with quantum scattering theory, developed for nuclear and mesoscopic physics and quantum chaos. We introduce the reduced Google matrix method for the regulatory biological networks and demonstrate how its computation allows inferring hidden causal relations between the members of a signaling pathway or a functionally related group of genes. We investigate how the structure of hidden causal relations can be reprogrammed as the result of changes in the transcriptional network layer during cancerogenesis. The suggested Googlomics approach rigorously characterizes complex systemic changes in the wiring of large causal biological networks.
Unicycler: resolving bacterial genome assemblies from short and long sequencing reads
Authors: Wick Ryan R. , Judd Louise M. , Gorrie Claire L. , Holt Kathryn E. 
Published: December 2016

1.AbstractThe Illumina DNA sequencing platform generates accurate but short reads, which can be used to produce accurate but fragmented genome assemblies. Pacific Biosciences and Oxford Nanopore Technologies DNA sequencing platforms generate long reads that can produce more complete genome assemblies, but the sequencing is more expensive and error prone. There is significant interest in combining data from these complementary sequencing technologies to generate more accurate “hybrid” assemblies. However, few tools exist that truly leverage the benefits of both types of data, namely the accuracy of short reads and the structural resolving power of long reads. Here we present Unicycler, a new tool for assembling bacterial genomes from a combination of short and long reads, which produces assemblies that are accurate, complete and cost-effective. Unicycler builds an initial assembly graph from short reads using thede novoassembler SPAdes and then simplifies the graph using information from short and long reads. Unicycler utilises a novel semi-global aligner, which is used to align long reads to the assembly graph. Tests on both synthetic and real reads show Unicycler can assemble larger contigs with fewer misassemblies than other hybrid assemblers, even when long read depth and accuracy are low. Unicycler is open source (GPLv3) and available atgithub.com/rrwick/Unicycler.
Analysing animal social network dynamics: the potential of stochastic actor‐oriented models
Authors: Fisher David N. , Ilany Amiyaal , Silk Matthew J. , Tregenza Tom 
Published: December 2016

Summary

Animals are embedded in dynamically changing networks of relationships with conspecifics. These dynamic networks are fundamental aspects of their environment, creating selection on behaviours and other traits. However, most social network‐based approaches in ecology are constrained to considering networks as static, despite several calls for such analyses to become more dynamic.

There are a number of statistical analyses developed in the social sciences that are increasingly being applied to animal networks, of which stochastic actor‐oriented models (SAOMs) are a principal example. SAOMs are a class of individual‐based models designed to model transitions in networks between discrete time points, as influenced by network structure and covariates. It is not clear, however, how useful such techniques are to ecologists, and whether they are suited to animal social networks.

We review the recent applications of SAOMs to animal networks, outlining findings and assessing the strengths and weaknesses of SAOMs when applied to animal rather than human networks. We go on to highlight the types of ecological and evolutionary processes that SAOMs can be used to study.

SAOMs can include effects and covariates for individuals, dyads and populations, which can be constant or variable. This allows for the examination of a wide range of questions of interest to ecologists. However, high‐resolution data are required, meaning SAOMs will not be useable in all study systems. It remains unclear how robust SAOMs are to missing data and uncertainty around social relationships.

Ultimately, we encourage the careful application of SAOMs in appropriate systems, with dynamic network analyses likely to prove highly informative. Researchers can then extend the basic method to tackle a range of existing questions in ecology and explore novel lines of questioning.
Novel thermostable antibiotic resistance enzymes from the Atlantis II Deep Red Sea brine pool
Authors: Elbehery Ali H. A. , Leak David J. , Siam Rania 
Published: December 2016

SummaryThe advent of metagenomics has greatly facilitated the discovery of enzymes with useful biochemical characteristics for industrial and biomedical applications, from environmental niches. In this study, we used sequence‐based metagenomics to identify two antibiotic resistance enzymes from the secluded, lower convective layer of Atlantis II Deep Red Sea brine pool (68°C, ~2200 m depth and 250‰ salinity). We assembled > 4 000 000 metagenomic reads, producing 43 555 contigs. Open reading frames (ORFs) called from these contigs were aligned to polypeptides from the Comprehensive Antibiotic Resistance Database using BLASTX. Two ORFs were selected for further analysis. The ORFs putatively coded for 3′‐aminoglycoside phosphotransferase [APH(3′)] and a class A beta‐lactamase (ABL). Both genes were cloned, expressed and characterized for activity and thermal stability. Both enzymes were active in vitro, while only APH(3′) was active in vivo. Interestingly, APH(3′) proved to be thermostable (Tm = 61.7°C and ~40% residual activity after 30 min of incubation at 65°C). On the other hand, ABL was not as thermostable, with a Tm = 43.3°C. In conclusion, we have discovered two novel AR enzymes with potential application as thermophilic selection markers.
Activation tagging of Arabidopsis POLYGALACTURONASE INVOLVED IN EXPANSION2 promotes hypocotyl elongation, leaf expansion, stem lignification, mechanical stiffening, and lodging
Authors: Xiao Chaowen , Barnes William J. , Zamil M. Shafayet , Yi Hojae , Puri Virendra M. , Anderson Charles T. 
Published: December 2016

SummaryPectin is the most abundant component of primary cell walls in eudicot plants. The modification and degradation of pectin affects multiple processes during plant development, including cell expansion, organ initiation, and cell separation. However, the extent to which pectin degradation by polygalacturonases affects stem development and secondary wall formation remains unclear. Using an activation tag screen, we identified a transgenic Arabidopsis thaliana line with longer etiolated hypocotyls, which overexpresses a gene encoding a polygalacturonase. We designated this gene as POLYGALACTURONASE INVOLVED IN EXPANSION2 (PGX2), and the corresponding activation tagged line as PGX2AT. PGX2 is widely expressed in young seedlings and in roots, stems, leaves, flowers, and siliques of adult plants. PGX2‐GFP localizes to the cell wall, and PGX2AT plants show higher total polygalacturonase activity and smaller pectin molecular masses than wild‐type controls, supporting a function for this protein in apoplastic pectin degradation. A heterologously expressed, truncated version of PGX2 also displays polygalacturonase activity in vitro. Like previously identified PGX1AT plants, PGX2AT plants have longer hypocotyls and larger rosette leaves, but they also uniquely display early flowering, earlier stem lignification, and lodging stems with enhanced mechanical stiffness that is possibly due to decreased stem thickness. Together, these results indicate that PGX2 both functions in cell expansion and influences secondary wall formation, providing a possible link between these two developmental processes.
The putative kinase substrate MUSE7 negatively impacts the accumulation of NLR proteins
Authors: Johnson Kaeli C. M. , Zhao Jin , Wu Zhongshou , Roth Charlotte , Lipka Volker , Wiermer Marcel , Li Xin 
Published: December 2016

SummaryStringent modulation of immune signaling in plants is necessary to enable a rapid response to pathogen attack without spurious defense activation. To identify genes involved in plant immunity, a forward genetic screen for enhancers of the autoimmune snc1 (suppressor of npr1, constitutive 1) mutant was conducted. The snc1 mutant contains a gain‐of‐function mutation in a gene encoding a NOD‐like receptor (NLR) protein. The isolated muse7 (mutant, snc1‐enhancing, 7) mutant was shown to confer a reversion to autoimmune phenotypes in the wild‐type‐like mos4 (modifier of snc1, 4) snc1 background. Positional cloning revealed that MUSE7 encodes an evolutionarily conserved putative kinase substrate of unknown function. The muse7 single mutants display enhanced resistance to the bacterial pathogen Pseudomonas syringae pv. tomato DC3000. While transcription of SNC1 is not enhanced, elevated SNC1 protein accumulation is associated with mutations in muse7. Accumulation of two additional NLR proteins, RPS2 (RESISTANCE TO PSEUDOMONAS SYRINGAE 2) and RPM1 (RESISTANCE TO PSEUDOMONAS SYRINGAE pv. MACULICOLA 1), was also observed in muse7 plants. Although proteasome‐mediated degradation of NLR proteins is a well studied event in plant immunity, no interactions were detected between MUSE7 and selected components of this pathway. This study has demonstrated a role for MUSE7 in modulating plant immune responses through negatively affecting NLR accumulation, and will benefit future studies of MUSE7 homologs in other species.
Repurposing Toremifene for Treatment of Oral Bacterial Infections
Authors: Gerits Evelien , Defraine Valerie , Vandamme Katleen , De Cremer Kaat , De Brucker Katrijn , Thevissen Karin , Cammue Bruno P. A. , Beullens Serge , Fauvart Maarten , Verstraeten Natalie , Michiels Jan 
Published: December 2016

ABSTRACT

The spread of antibiotic resistance and the challenges associated with antiseptics such as chlorhexidine have necessitated a search for new antibacterial agents against oral bacterial pathogens. As a result of failing traditional approaches, drug repurposing has emerged as a novel paradigm to find new antibacterial agents. In this study, we examined the effects of the FDA-approved anticancer agent toremifene against the oral bacteria
Porphyromonas gingivalis
and
Streptococcus mutans
. We found that the drug was able to inhibit the growth of both pathogens, as well as prevent biofilm formation, at concentrations ranging from 12.5 to 25 μM. Moreover, toremifene was shown to eradicate preformed biofilms at concentrations ranging from 25 to 50 μM. In addition, we found that toremifene prevents
P. gingivalis
and
S. mutans
biofilm formation on titanium surfaces. A time-kill study indicated that toremifene is bactericidal against
S. mutans
. Macromolecular synthesis assays revealed that treatment with toremifene does not cause preferential inhibition of DNA, RNA, or protein synthesis pathways, indicating membrane-damaging activity. Biophysical studies using fluorescent probes and fluorescence microscopy further confirmed the membrane-damaging mode of action. Taken together, our results suggest that the anticancer agent toremifene is a suitable candidate for further investigation for the development of new treatment strategies for oral bacterial infections.
Various Sequence Types of Escherichia coli Isolates Coharboring
bla
NDM-5
and
mcr-1
Genes from a Commercial Swine Farm in China
Authors: Kong Ling-Han , Lei Chang-Wei , Ma Su-Zhen , Jiang Wei , Liu Bi-Hui , Wang Yong-Xiang , Guan Ru , Men Shuai , Yuan Qi-Wu , Cheng Guang-Yang , Zhou Wen-Cheng , Wang Hong-Ning 
Published: December 2016

ABSTRACT

Sixteen different sequence types (STs) of
Escherichia coli
isolates from a commercial swine farm in China were confirmed to coharbor the carbapenem resistance gene
bla
NDM-5
and the colistin resistance gene
mcr-1
. Whole-genome sequencing revealed that
bla
NDM-5
and
mcr-1
were located on a 46-kb IncX3 plasmid and a 32-kb IncX4 plasmid, respectively. The two plasmids can transfer together with a low fitness cost, which might explain the presence of various STs of
E. coli
coharboring
bla
NDM-5
and
mcr-1
.
Mycobacterium tuberculosis Is Selectively Killed by Rifampin and Rifapentine in Hypoxia at Neutral pH
Authors: Iacobino Angelo , Piccaro Giovanni , Giannoni Federico , Mustazzolu Alessandro , Fattorini Lanfranco 
Published: December 2016

ABSTRACT

The activities of rifampin, rifapentine, bedaquiline, PA-824, clofazimine, nitazoxanide, isoniazid, amikacin, moxifloxacin, niclosamide, thioridazine, and pyrazinamide were tested against nonreplicating (dormant)
Mycobacterium tuberculosis
H37Rv under conditions of hypoxia at pHs 5.8 and 7.3, mimicking environments of cellular granulomas and caseous granulomas, respectively. At pH 5.8, several drugs killed dormant bacilli, with the best being rifampin and rifapentine. At pH 7.3, only rifampin and rifapentine efficiently killed dormant bacilli, while all other drugs showed little activity.
Nephrotoxicity of Polymyxins: Is There Any Difference between Colistimethate and Polymyxin B?
Authors: Zavascki Alexandre P. , Nation Roger L. 
Published: December 2016

ABSTRACT

Nephrotoxicity is a common adverse effect of the clinically used polymyxins, colistin and polymyxin B. This adverse effect is dose limiting for both polymyxins, as the plasma polymyxin concentrations associated with renal damage overlap those required for antibacterial effect. Since development of acute kidney injury (AKI) during therapy is highly undesirable, it is extremely important to know whether there is any difference between the nephrotoxic potential of colistin (administered as its inefficient prodrug, colistimethate) and polymyxin B (administered as the active form). Both polymyxins are cytotoxic to renal tubular cells and are prone to cause nephrotoxicity
in vivo
because of the renal handling mechanisms that facilitate accumulation of these compounds in these cells, processes that are reviewed in this article. Also reviewed are the emerging data that strongly suggest significantly higher rates of AKI in patients treated with colistimethate compared to patients treated with polymyxin B. This finding may be due to differences in pharmacokinetics and renal handling mechanisms of colistimethate and formed colistin versus polymyxin B, and consequently the relative amount of polymyxin material delivered to tubular cells. A lower risk of AKI with polymyxin B is one of several potential advantages over colistimethate. The relative safety and efficacy of the two agents require closer examination in well-designed clinical studies.
Pharmacological Blockade of the Chemokine Receptor CCR1 Protects Mice from Systemic Candidiasis of Hematogenous Origin
Authors: Lionakis Michail S. , Albert Nathaniel D. , Swamydas Muthulekha , Lee Chyi-Chia R. , Loetscher Pius , Kontoyiannis Dimitrios P. 
Published: December 2016

ABSTRACTSystemic candidiasis is a leading cause of nosocomial bloodstream infection with a high mortality rate despite treatment. Immune-based strategies are needed to improve outcomes. We previously reported that genetic deficiency in the chemokine receptor CCR1 improves survival and ameliorates tissue damage inCandida-infected mice. Here, we found that treatment of immunocompetentCandida-infected mice with the CCR1-selective antagonist BL5923 improves survival, decreases the kidney fungal burden, and protects from renal tissue injury.
Burkholderia humptydooensis sp. nov., a New Species Related to Burkholderia thailandensis and the Fifth Member of the Burkholderia pseudomallei Complex
Authors: Tuanyok Apichai , Mayo Mark , Scholz Holger , Hall Carina M. , Allender Christopher J. , Kaestli Mirjam , Ginther Jennifer , Spring-Pearson Senanu , Bollig Molly C. , Stone Joshua K. , Settles Erik W. , Busch Joseph D. , Sidak-Loftis Lindsay , Sahl Jason W. , Thomas Astrid , Kreutzer Lisa , Georgi Enrico , Gee Jay E. , Bowen Richard A. , Ladner Jason T. , Lovett Sean , Koroleva Galina , Palacios Gustavo , Wagner David M. , Currie Bart J. , Keim Paul 
Published: December 2016

ABSTRACT

During routine screening for
Burkholderia pseudomallei
from water wells in northern Australia in areas where it is endemic, Gram-negative bacteria (strains MSMB43
T
, MSMB121, and MSMB122) with a similar morphology and biochemical pattern to
B. pseudomallei
and
B. thailandensis
were coisolated with
B. pseudomallei
on Ashdown's selective agar. To determine the exact taxonomic position of these strains and to distinguish them from
B. pseudomallei
and
B. thailandensis
, they were subjected to a series of phenotypic and molecular analyses. Biochemical and fatty acid methyl ester analysis was unable to distinguish
B. humptydooensis
sp. nov. from closely related species. With matrix-assisted laser desorption ionization–time of flight analysis, all isolates grouped together in a cluster separate from other
Burkholderia
spp. 16S rRNA and
recA
sequence analyses demonstrated phylogenetic placement for
B. humptydooensis
sp. nov. in a novel clade within the
B. pseudomallei
group. Multilocus sequence typing (MLST) analysis of the three isolates in comparison with MLST data from 3,340
B. pseudomallei
strains and related taxa revealed a new sequence type (ST318). Genome-to-genome distance calculations and the average nucleotide identity of all isolates to both
B. thailandensis
and
B. pseudomallei
, based on whole-genome sequences, also confirmed
B. humptydooensis
sp. nov. as a novel
Burkholderia
species within the
B. pseudomallei
complex. Molecular analyses clearly demonstrated that strains MSMB43
T
, MSMB121, and MSMB122 belong to a novel
Burkholderia
species for which the name
Burkholderia humptydooensis
sp. nov. is proposed, with the type strain MSMB43
T
(American Type Culture Collection BAA-2767; Belgian Co-ordinated Collections of Microorganisms LMG 29471; DDBJ accession numbers
CP013380
to
CP013382
).

IMPORTANCE
Burkholderia pseudomallei
is a soil-dwelling bacterium and the causative agent of melioidosis. The genus
Burkholderia
consists of a diverse group of species, with the closest relatives of
B. pseudomallei
referred to as the
B. pseudomallei
complex. A proposed novel species,
B. humptydooensis
sp. nov., was isolated from a bore water sample from the Northern Territory in Australia.
B. humptydooensis
sp. nov. is phylogenetically distinct from
B. pseudomallei
and other members of the
B. pseudomallei
complex, making it the fifth member of this important group of bacteria.
Genome Sequence of KP-Rio/2015, a Novel Klebsiella pneumoniae (
Podoviridae
) Phage
Authors: Meira Guilherme L. S. , Campos Fabricio S. , Albuquerque Julia P. , Cabral Maulori C. , Fracalanzza Sergio E. L. , Campos Renata M. , Vermelho Alane B. , Ferreira Davis F. 
Published: December 2016

ABSTRACT

Klebsiella pneumoniae
is a pathogen frequently associated with antibiotic-resistant nosocomial infections. Here, we describe the genome of KP-Rio/2015, a novel phage of
K. pneumoniae
belonging to the family
Podoviridae
.