bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi‐scale stratigraphic forward modelling of the Surat Basin for geological storage of CO2
Authors: Ravestein Johannes J. , Griffiths Cedric M. , Dyt Chris P. , Michael Karsten 
Published: June 2015

AbstractUnderground geological storage of CO2 (GSC) requires a high level of subsurface understanding that is often hindered by a lack of data. This study demonstrates the use of stratigraphic forward modelling (SFM) in generating and characterising a static reservoir model using limited well data, with multiple potential applications within the GSC workflow. Sedsim SFM software was used to create a static model of the Surat Basin, including a high‐resolution nested model of the EPQ‐7 GSC tenement within the basin. Deposition and burial of the Jurassic Precipice Sandstone, Evergreen Formation and Hutton Sandstone were simulated. Modelling results show a close match with gamma‐ray well logs in the tenement area, and the model can be considered a credible model of the subsurface. The Sedsim‐predicted formation thicknesses and porosity and permeability distributions meet criteria set for GSC, suggesting that the EPQ‐7 tenement may be a prospective GSC location.
Yif1B Is Involved in the Anterograde Traffic Pathway and the Golgi Architecture
Authors: Alterio Jeanine , Masson Justine , Diaz Jorge , Chachlaki Konstantina , Salman Haysam , Areias Julie , Al Awabdh Sana , Emerit Michel Boris , Darmon Michèle 
Published: June 2015

AbstractYif1B is an intracellular membrane‐bound protein belonging to the Yip family, shown previously to control serotonin 5‐HT1A receptor targeting to dendrites. Because some Yip proteins are involved in the intracellular traffic between the ER and the Golgi, here we investigated the precise localization of Yif1B in HeLa cells. We found that Yif1B is not resident into the Golgi, but rather belongs to the IC compartment. After analyzing the role of Yif1B in protein transport, we showed that the traffic of the VSVG protein marker was accelerated in Yif1B depleted HeLa cells, as well as in hippocampal neurons from Yif1B KO mice. Conversely, Yif1B depletion in HeLa cells did not change the retrograde traffic of ShTx. Interestingly, in long term depletion of Yif1B as in Yif1B KO mice, we observed a disorganized Golgi architecture in CA1 pyramidal hippocampal neurons, which was confirmed by electron microscopy. However, because short term depletion of Yif1B did not change Golgi structure, it is likely that the implication of Yif1B in anterograde traffic does not rely on its role in structural organization of the Golgi apparatus, but rather on its shuttling between the ER, the IC and the Golgi compartments.
Patterns of loss of biodiversity associated with invasion by Chrysanthemoides monilifera subsp. monilifera (boneseed) across a large geographic region
Authors: French K , Watts E 
Published: June 2015

SummaryTo investigate the impact of invasion by Chrysanthemoides monilifera ssp. monilifera (boneseed) on plant communities, sites that were invaded and uninvaded were surveyed across Tasmania, South Australia and Victoria, Australia. Above‐ground cover abundance was estimated and samples of the seed bank from invaded and uninvaded sites in each state were collected and germinated in the glasshouse. We compared species richness and composition between invaded and uninvaded sites for both above‐ground and below‐ground samples. Across this broad geographic area, C. monilifera invaded sites had 25% fewer species than uninvaded sites and twice as many exotic species. Most growth forms showed reduced richness in invaded sites. There were no differences in the composition of native species communities between invaded and uninvaded sites in most regions, except South Australia. The composition of the seed bank differed from the above‐ground vegetation, but was similar within each state. Herbs and grasses were most abundant. The species composition of the seed bank was different in invaded sites only in Victoria, suggesting that invasion may negatively influence the capacity of the seed bank to restore vegetation in some areas. However, the underlying mechanisms for the observed patterns were not tested in this study. The capacity of all sites to regenerate effectively from the seed bank was limited and, in order to ensure the conservation of biodiversity into the future, monitoring of species richness at smaller scales, particularly those where management of C. monilifera has occurred, will be needed to ensure management can facilitate the establishment of missing species. This study suggests that C. monilifera impacts a range of functional groups and different species across its distribution and is therefore non‐selective in how it influences changes in communities.
Systematic Review of Mutations in Pyrazinamidase Associated with Pyrazinamide Resistance in Mycobacterium tuberculosis Clinical Isolates
Authors: Ramirez-Busby Sarah M. , Valafar Faramarz 
Published: June 2015

ABSTRACTPyrazinamide (PZA) is an important first-line drug in the treatment of tuberculosis (TB) and of significant interest to the HIV-infected community due to the prevalence of TB-HIV coinfection in some regions of the world. The mechanism of resistance to PZA is unlike that of any other anti-TB drug. The genepncA, encoding pyrazinamidase (PZase), is associated with resistance to PZA. However, because single mutations in PZase have a low prevalence, the individual sensitivities are low. Hundreds of distinct mutations in the enzyme have been associated with resistance, while some only appear in susceptible isolates. This makes interpretation of molecular testing difficult and often leads to the simplification that any PZase mutation causes resistance. This systematic review reports a comprehensive global list of mutations observed in PZase and its promoter region in clinical strains, their phenotypic association, their global frequencies and diversity, the method of phenotypic determination, their MIC values when given, and the method of MIC determination and assesses the strength of the association between mutations and phenotypic resistance to PZA. In this systematic review, we report global statistics for 641 mutations in 171 (of 187) codons from 2,760 resistant strains and 96 mutations from 3,329 susceptible strains reported in 61 studies. For diagnostics, individual mutations (or any subset) were not sufficiently sensitive. Assuming similar error profiles of the 5 phenotyping platforms included in this study, the entire enzyme and its promoter provide a combined estimated sensitivity of 83%. This review highlights the need for identification of an alternative mechanism(s) of resistance, at least for the unexplained 17% of cases.
The Agmatine-Containing Poly(Amidoamine) Polymer AGMA1 Binds Cell Surface Heparan Sulfates and Prevents Attachment of Mucosal Human Papillomaviruses
Authors: Cagno Valeria , Donalisio Manuela , Bugatti Antonella , Civra Andrea , Cavalli Roberta , Ranucci Elisabetta , Ferruti Paolo , Rusnati Marco , Lembo David 
Published: June 2015

ABSTRACTThe agmatine-containing poly(amidoamine) polymer AGMA1 was recently shown to inhibit the infectivity of several viruses, including human papillomavirus 16 (HPV-16), that exploit cell surface heparan sulfate proteoglycans (HSPGs) as attachment receptors. The aim of this work was to assess the antiviral activity of AGMA1 and its spectrum of activity against a panel of low-risk and high-risk HPVs and to elucidate its mechanism of action. AGMA1 was found to be a potent inhibitor of mucosal HPV types (i.e., types 16, 31, 45, and 6) in pseudovirus-based neutralization assays. The 50% inhibitory concentration was between 0.34 μg/ml and 0.73 μg/ml, and no evidence of cytotoxicity was observed. AGMA1 interacted with immobilized heparin and with cellular heparan sulfates, exerting its antiviral action by preventing virus attachment to the cell surface. The findings from this study indicate that AGMA1 is a leading candidate compound for further development as an active ingredient of a topical microbicide against HPV and other sexually transmitted viral infections.
Mutation Landscape of Acquired Cross-Resistance to Glycopeptide and β-Lactam Antibiotics in Enterococcus faecium
Authors: Sacco Emmanuelle , Cortes Mélanie , Josseaume Nathalie , Bouchier Christiane , Dubée Vincent , Hugonnet Jean-Emmanuel , Mainardi Jean-Luc , Rice Louis B. , Arthur Michel 
Published: June 2015

ABSTRACT

Bypass of the
d
,
d
-transpeptidase activity of penicillin-binding proteins by an
l
,
d
-transpeptidase (Ldt
fm
) results in resistance to ampicillin and glycopeptides in
Enterococcus faecium
M9, a mutant obtained by nine consecutive selection steps. Resistance requires activation of a cryptic locus for production of the essential tetrapeptide-containing substrate of Ldt
fm
and impaired activity of protein phosphatase StpA. Here, whole-genome sequencing revealed a high mutation rate for the entire selection procedure (79 mutations in 900 generations). Acquisition of a mutation in the mismatch repair gene
mutL
had little impact on the frequency of rifampin-resistant mutants although the mutation spectrum of M9 was typical of impaired MutL with high transversion to transition (40/11) and substitution to deletion (51/28) ratios. M9 did not mainly accumulate neutral mutations since base substitutions occurred more frequently in coding sequences than expected (χ
2
= 5.0;
P
< 0.05) and silent mutations were underrepresented (χ
2
= 5.72;
P
< 0.02). None of the mutations directly affected recognition of the tetrapeptide substrate of Ldt
fm
by peptidoglycan synthesis enzymes. Instead, mutations appear to remodel regulatory circuits involving two-component regulatory systems and sugar metabolism. The high number of mutations required for activation of the
l
,
d
-transpeptidase pathway may strongly limit emergence of cross-resistance to ampicillin and glycopeptides by this mechanism.
Influenza A(H7N9) Virus Acquires Resistance-Related Neuraminidase I222T Substitution When Infected Mallards Are Exposed to Low Levels of Oseltamivir in Water
Authors: Gillman Anna , Nykvist Marie , Muradrasoli Shaman , Söderström Hanna , Wille Michelle , Daggfeldt Annika , Bröjer Caroline , Waldenström Jonas , Olsen Björn , Järhult Josef D. 
Published: June 2015

ABSTRACT

Influenza A virus (IAV) has its natural reservoir in wild waterfowl, and new human IAVs often contain gene segments originating from avian IAVs. Treatment options for severe human influenza are principally restricted to neuraminidase inhibitors (NAIs), among which oseltamivir is stockpiled in preparedness for influenza pandemics. There is evolutionary pressure in the environment for resistance development to oseltamivir in avian IAVs, as the active metabolite oseltamivir carboxylate (OC) passes largely undegraded through sewage treatment to river water where waterfowl reside. In an
in vivo
mallard (
Anas platyrhynchos
) model, we tested if low-pathogenic avian influenza A(H7N9) virus might become resistant if the host was exposed to low levels of OC. Ducks were experimentally infected, and OC was added to their water, after which infection and transmission were maintained by successive introductions of uninfected birds. Daily fecal samples were tested for IAV excretion, genotype, and phenotype. Following mallard exposure to 2.5 μg/liter OC, the resistance-related neuraminidase (NA) I222T substitution, was detected within 2 days during the first passage and was found in all viruses sequenced from subsequently introduced ducks. The substitution generated 8-fold and 2.4-fold increases in the 50% inhibitory concentration (IC
50
) for OC (
P
< 0.001) and zanamivir (
P
= 0.016), respectively. We conclude that OC exposure of IAV hosts, in the same concentration magnitude as found in the environment, may result in amino acid substitutions, leading to changed antiviral sensitivity in an IAV subtype that can be highly pathogenic to humans. Prudent use of oseltamivir and resistance surveillance of IAVs in wild birds are warranted.
Effective Inhibition of HIV-1 Production by Short Hairpin RNAs and Small Interfering RNAs Targeting a Highly Conserved Site in HIV-1 Gag RNA Is Optimized by Evaluating Alternative Length Formats
Authors: Scarborough Robert J. , Adams Kelsey L. , Daher Aïcha , Gatignol Anne 
Published: June 2015

ABSTRACT
We have previously identified a target site in HIV-1 RNA that was particularly accessible to a ribozyme and a short hairpin RNA (shRNA). To design small interfering RNAs (siRNAs) targeting this site, we evaluated the effects of siRNAs with different lengths on HIV-1 production. The potency and efficacy of these siRNAs were dependent on the length of their intended sense strand with trends for symmetrical and asymmetrical formats that were similar. Although a typical canonical format with a 21-nucleotide (nt) sense strand was effective at inhibiting HIV-1 production, Dicer substrate siRNAs (dsiRNAs) with the longest lengths (27 to 29 nucleotides) were the most effective. Induction of double-stranded RNA immune responses and effects on cell viability were not detected in cells transfected with different siRNAs, suggesting that the differences observed were not related to indirect effects on HIV-1 production. For the corresponding shRNA designs, a different trend in potency and efficacy against HIV-1 production was observed, with the most effective shRNAs having stem lengths from 20 to 27 bp. Our results highlight the importance of evaluating different designs to identify the best siRNA and shRNA formats for any particular target site and provide a set of highly effective molecules for further development as drug and gene therapies for HIV-1 infection.
Tir Triggers Expression of CXCL1 in Enterocytes and Neutrophil Recruitment during Citrobacter rodentium Infection
Authors: Crepin Valerie F. , Habibzay Maryam , Glegola-Madejska Izabela , Guenot Marianne , Collins James W. , Frankel Gad 
Published: June 2015

ABSTRACT

The hallmarks of enteropathogenic
Escherichia coli
(EPEC) infection are formation of attaching and effacing (A/E) lesions on mucosal surfaces and actin-rich pedestals on cultured cells, both of which are dependent on the type III secretion system effector Tir. Following translocation into cultured cells and clustering by intimin, Tir Y474 is phosphorylated, leading to recruitment of Nck, activation of N-WASP, and actin polymerization via the Arp2/3 complex. A secondary, weak, actin polymerization pathway is triggered via an NPY motif (Y454). Importantly, Y454 and Y474 play no role in A/E lesion formation on mucosal surfaces following infection with the EPEC-like mouse pathogen
Citrobacter rodentium
. In this study, we investigated the roles of Tir segments located upstream of Y451 and downstream of Y471 in
C. rodentium
colonization and A/E lesion formation. We also tested the role that Tir residues Y451 and Y471 play in host immune responses to
C. rodentium
infection. We found that deletion of amino acids 382 to 462 or 478 to 547 had no impact on the ability of Tir to mediate A/E lesion formation, although deletion of amino acids 478 to 547 affected Tir translocation. Examination of enterocytes isolated from infected mice revealed that a
C. rodentium
strain expressing Tir_Y451A/Y471A recruited significantly fewer neutrophils to the colon and triggered less colonic hyperplasia on day 14 postinfection than the wild-type strain. Consistently, enterocytes isolated from mice infected with
C. rodentium
expressing Tir_Y451A/Y471A expressed significantly less CXCL1. These result show that Tir-induced actin remodeling plays a direct role in modulation of immune responses to
C. rodentium
infection.
Neisseria gonorrhoeae Modulates Cell Death in Human Endocervical Epithelial Cells through Export of Exosome-Associated cIAP2
Authors: Nudel Kathleen , Massari Paola , Genco Caroline A. 
Published: June 2015

ABSTRACT

Several bacterial pathogens persist and survive in the host by modulating host cell death pathways. We previously demonstrated that
Neisseria gonorrhoeae
, a Gram-negative pathogen responsible for the sexually transmitted infection gonorrhea, protects against exogenous induction of apoptosis in human cervical epithelial cells. However, induction of cell death by
N. gonorrhoeae
has also been reported in other cell types. The mechanisms by which
N. gonorrhoeae
modulates cell death are not clear, although a role for the inhibitor of apoptosis-2 (cIAP2) has been proposed. In this study, we confirmed that
N. gonorrhoeae
induces production of cIAP2 in human cervical epithelial cells. High levels of intracellular cIAP2 were detected early after
N. gonorrhoeae
stimulation, which was followed by a marked decrease at 24 h. At this time point, we observed increased levels of extracellular cIAP2 associated with exosomes and an overall increase in production of exosomes. Inhibition of cIAP2 in
N. gonorrhoeae
-stimulated epithelial cells resulted in increased cell death and interleukin-1β (IL-1β) production. Collectively these results indicate that
N. gonorrhoeae
stimulation of human endocervical epithelial cells induces the release of cIAP2, an essential regulator of cell death and immune signaling.
Identification of YsaP, the Pilotin of the Yersinia enterocolitica Ysa Type III Secretion System
Authors: Rau Reina , Darwin Andrew J. 
Published: June 2015

ABSTRACT

Secretins are multimeric outer membrane pore-forming proteins found in complex export systems in Gram-negative bacteria. All type III secretion systems (T3SSs) have a secretin, and one of these is the YsaC secretin of the chromosomally encoded Ysa T3SS of
Yersinia enterocolitica
. In some cases, pilotin proteins, which are outer membrane lipoproteins, are required for their cognate secretins to multimerize and/or localize to the outer membrane. However, if secretin multimers mislocalize to the inner membrane, this can trigger the protective phage shock protein (Psp) stress response. During a screen for mutations that suppress YsaC toxicity to a
psp
null strain, we isolated several independent mutations predicted to increase expression of the YE3559 gene within the Ysa pathogenicity island. YE3559, which we have named
ysaP
, is predicted to encode a small outer membrane lipoprotein, and this location was confirmed by membrane fractionation. Elevated
ysaP
expression increased the steady-state level of YsaC but made it less toxic to a
psp
null strain, and it also decreased YsaC-dependent induction of
psp
gene expression. Subsequent experiments showed that YsaP was not required for YsaC multimerization but was required for the multimers to localize to the outer membrane. Consistent with this, a
ysaP
null mutation compromised protein export by the Ysa T3SS. All these observations suggest that YsaP is the pilotin for the YsaC secretin. This is only the second pilotin to be characterized for
Yersinia
and one of only a small number of pilotins described for all bacteria.

IMPORTANCE
Secretins are essential for the virulence of many bacterial pathogens and also play roles in surface attachment, motility, and competence. This has generated considerable interest in understanding how secretins function. However, their fundamental differences from typical outer membrane proteins have raised various questions about secretins, including how they are assembled into outer membrane multimers. Pilotin proteins facilitate the assembly of some secretins, but only a small number of pilotins have been identified, slowing efforts to understand common and distinct features of secretin assembly. This study provides an important advance by identifying a novel member of the pilotin family and also demonstrating a method of pilotin discovery that could be broadly applied.
Functional Dependence between Septal Protein SepJ from Anabaena sp. Strain PCC 7120 and an Amino Acid ABC-Type Uptake Transporter
Authors: Escudero Leticia , Mariscal Vicente , Flores Enrique 
Published: June 2015

ABSTRACT

In the diazotrophic filaments of heterocyst-forming cyanobacteria, two different cell types, the CO
2
-fixing vegetative cells and the N
2
-fixing heterocysts, exchange nutrients, including some amino acids. In the model organism
Anabaena
sp. strain PCC 7120, the SepJ protein, composed of periplasmic and integral membrane (permease) sections, is located at the intercellular septa joining adjacent cells in the filament. The unicellular cyanobacterium
Synechococcus elongatus
strain PCC 7942 bears a gene,
Synpcc7942_1024
(here designated
dmeA
), encoding a permease homologous to the SepJ permease domain.
Synechococcus
strains lacking
dmeA
or lacking
dmeA
and expressing
Anabaena
sepJ
were constructed. The
Synechococcus
dmeA
mutant showed a significant 22 to 32% decrease in the uptake of aspartate, glutamate, and glutamine, a phenotype that could be partially complemented by
Anabaena
sepJ
.
Synechococcus
mutants of an ATP-binding-cassette (ABC)-type transporter for polar amino acids showed >98% decreased uptake of glutamate irrespective of the presence of
dmeA
or
Anabaena
sepJ
in the same strain. Thus,
Synechococcus
DmeA or
Anabaena
SepJ is needed to observe full (or close to full) activity of the ABC transporter. An
Anabaena
sepJ
deletion mutant was significantly impaired in glutamate and aspartate uptake, which also in this cyanobacterium requires the activity of an ABC-type transporter for polar amino acids. SepJ appears therefore to generally stimulate the activity of cyanobacterial ABC-type transporters for polar amino acids. Conversely, an
Anabaena
mutant of three ABC-type transporters for amino acids was impaired in the intercellular transfer of 5-carboxyfluorescein, a SepJ-related property. Our results unravel possible functional interactions in transport elements important for diazotrophic growth.

IMPORTANCE
Membrane transporters are essential for many aspects of cellular life, from uptake and export of substances in unicellular organisms to intercellular molecular exchange in multicellular organisms. Heterocyst-forming cyanobacteria such as
Anabaena
represent a unique case of multicellularity, in which two cell types exchange nutrients and regulators. The SepJ protein located at the intercellular septa in the filaments of
Anabaena
contains a permease domain of the drug/metabolite transporter (DMT) superfamily that somehow contributes to intercellular molecular transfer. In this work, we have found that SepJ stimulates the activity of a polar amino acid uptake transporter of the ATP-binding-cassette (ABC) superfamily, which could itself affect an intercellular transfer activity related to SepJ, thus unraveling possible functional interactions between these different transporters.