bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Bivalent Typhoid Live Vector Vaccine Expressing both Chromosome- and Plasmid-Encoded Yersinia pestis Antigens Fully Protects against Murine Lethal Pulmonary Plague Infection
Authors: Galen James E. , Wang Jin Yuan , Carrasco Jose A. , Lloyd Scott A. , Mellado-Sanchez Gabriela , Diaz-McNair Jovita , Franco Olga , Buskirk Amanda D. , Nataro James P. , Pasetti Marcela F. 
Published: October 2014

ABSTRACTLive attenuated bacteria hold great promise as multivalent mucosal vaccines against a variety of pathogens. A major challenge of this approach has been the successful delivery of sufficient amounts of vaccine antigens to adequately prime the immune system without overattenuating the live vaccine. Here we used a live attenuatedSalmonella entericaserovar Typhi strain to create a bivalent mucosal plague vaccine that produces both the protective F1 capsular antigen ofYersinia pestisand the LcrV protein required for secretion of virulence effector proteins. To reduce the metabolic burden associated with the coexpression of F1 and LcrV within the live vector, we balanced expression of both antigens by combining plasmid-based expression of F1 with chromosomal expression of LcrV from three independent loci. The immunogenicity and protective efficacy of this novel vaccine were assessed in mice by using a heterologous prime-boost immunization strategy and compared to those of a conventional strain in which F1 and LcrV were expressed from a single low-copy-number plasmid. The serum antibody responses to lipopolysaccharide (LPS) induced by the optimized bivalent vaccine were indistinguishable from those elicited by the parent strain, suggesting an adequate immunogenic capacity maintained through preservation of bacterial fitness; in contrast, LPS titers were 10-fold lower in mice immunized with the conventional vaccine strain. Importantly, mice receiving the optimized bivalent vaccine were fully protected against lethal pulmonary challenge. These results demonstrate the feasibility of distributing foreign antigen expression across both chromosomal and plasmid locations within a single vaccine organism for induction of protective immunity.
CFP-10 from Mycobacterium tuberculosis Selectively Activates Human Neutrophils through a Pertussis Toxin-Sensitive Chemotactic Receptor
Authors: Welin Amanda , Björnsdottir Halla , Winther Malene , Christenson Karin , Oprea Tudor , Karlsson Anna , Forsman Huamei , Dahlgren Claes , Bylund Johan 
Published: October 2014

ABSTRACT

Upon infection with
Mycobacterium tuberculosis
, neutrophils are massively recruited to the lungs, but the role of these cells in combating the infection is poorly understood. Through a type VII secretion system,
M. tuberculosis
releases a heterodimeric protein complex, containing a 6-kDa early secreted antigenic target (ESAT-6) and a 10-kDa culture filtrate protein (CFP-10), that is essential for virulence. Whereas the ESAT-6 component possesses multiple virulence-related activities, no direct biological activity of CFP-10 has been shown, and CFP-10 has been described as a chaperone protein for ESAT-6. We here show that the ESAT-6:CFP-10 complex induces a transient release of Ca
2+
from intracellular stores in human neutrophils. Surprisingly, CFP-10 rather than ESAT-6 was responsible for triggering the Ca
2+
response, in a pertussis toxin-sensitive manner, suggesting the involvement of a G-protein-coupled receptor. In line with this, the response was accompanied by neutrophil chemotaxis and activation of the superoxide-producing NADPH-oxidase. Neutrophils were unique among leukocytes in responding to CFP-10, as monocytes and lymphocytes failed to produce a Ca
2+
signal upon stimulation with the
M. tuberculosis
protein. Hence, CFP-10 may contribute specifically to neutrophil recruitment and activation during
M. tuberculosis
infection, representing a novel biological role for CFP-10 in the ESAT-6:CFP-10 complex, beyond the previously described chaperone function.
Macrophage-Inducible C-Type Lectin Mincle-Expressing Dendritic Cells Contribute to Control of Splenic Mycobacterium bovis BCG Infection in Mice
Authors: Behler Friederike , Maus Regina , Bohling Jennifer , Knippenberg Sarah , Kirchhof Gabriele , Nagata Masahiro , Jonigk Danny , Izykowski Nicole , Mägel Lavinia , Welte Tobias , Yamasaki Sho , Maus Ulrich A. 
Published: October 2014

ABSTRACTThe macrophage-inducible C-type lectin Mincle has recently been identified to be a pattern recognition receptor sensing mycobacterial infection via recognition of the mycobacterial cell wall component trehalose-6′,6-dimycolate (TDM). However, its role in systemic mycobacterial infections has not been examined so far. Mincle-knockout (KO) mice were infected intravenously withMycobacterium bovisBCG to mimic the systemic spread of mycobacteria under defined experimental conditions. After intravenous infection withM. bovisBCG, Mincle-KO mice responded with significantly higher numbers of mycobacterial CFU in spleen and liver, while reduced granuloma formation was observed only in the spleen. At the same time, reduced Th1 cytokine production and decreased numbers of gamma interferon-producing T cells were observed in the spleens of Mincle-KO mice relative to the numbers in the spleens of wild-type (WT) mice. The effect of adoptive transfer of defined WT leukocyte subsets generated from bone marrow cells of zDC+/DTRmice (which bear the human diphtheria toxin receptor [DTR] under the control of the classical dendritic cell-specific zinc finger transcription factor zDC) to specifically deplete Mincle-expressing classical dendritic cells (cDCs) but not macrophages after diphtheria toxin application on the numbers of splenic and hepatic CFU and T cell subsets was then determined. Adoptive transfer experiments revealed that Mincle-expressing splenic cDCs rather than Mincle-expressing macrophages contributed to the reconstitution of attenuated splenic antimycobacterial immune responses in Mincle-KO mice after intravenous challenge with BCG. Collectively, we show that expression of Mincle, particularly by cDCs, contributes to the control of splenicM. bovisBCG infection in mice.
Plasmid-Encoded MCP Is Involved in Virulence, Motility, and Biofilm Formation of Cronobacter sakazakii ATCC 29544
Authors: Choi Younho , Kim Seongok , Hwang Hyelyeon , Kim Kwang-Pyo , Kang Dong-Hyun , Ryu Sangryeol 
Published: October 2014

ABSTRACT

The aim of this study was to elucidate the function of the plasmid-borne
mcp
(methyl-accepting chemotaxis protein) gene, which plays pleiotropic roles in
Cronobacter sakazakii
ATCC 29544. By searching for virulence factors using a random transposon insertion mutant library, we identified and sequenced a new plasmid, pCSA2, in
C. sakazakii
ATCC 29544. An
in silico
analysis of pCSA2 revealed that it included six putative open reading frames, and one of them was
mcp
. The
mcp
mutant was defective for invasion into and adhesion to epithelial cells, and the virulence of the
mcp
mutant was attenuated in rat pups. In addition, we demonstrated that putative MCP regulates the motility of
C. sakazakii
, and the expression of the flagellar genes was enhanced in the absence of a functional
mcp
gene. Furthermore, a lack of the
mcp
gene also impaired the ability of
C. sakazakii
to form a biofilm. Our results demonstrate a regulatory role for MCP in diverse biological processes, including the virulence of
C. sakazakii
ATCC 29544. To the best of our knowledge, this study is the first to elucidate a potential function of a plasmid-encoded MCP homolog in the
C. sakazakii
sequence type 8 (ST8) lineage.
Flavobacterium johnsoniae PorV Is Required for Secretion of a Subset of Proteins Targeted to the Type IX Secretion System
Authors: Kharade Sampada S. , McBride Mark J. 
Published: October 2014

ABSTRACT

Flavobacterium johnsoniae
exhibits gliding motility and digests many polysaccharides, including chitin. A novel protein secretion system, the type IX secretion system (T9SS), is required for gliding and chitin utilization. The T9SS secretes the cell surface motility adhesins SprB and RemA and the chitinase ChiA. Proteins involved in secretion by the T9SS include GldK, GldL, GldM, GldN, SprA, SprE, and SprT.
Porphyromonas gingivalis
has orthologs for each of these that are required for secretion of gingipain protease virulence factors by its T9SS.
P. gingivalis
porU
and
porV
have also been linked to T9SS-mediated secretion, and
F. johnsoniae
has orthologs of these. Mutations in
F. johnsoniae
porU
and
porV
were constructed to determine if they function in secretion. Cells of a
porV
deletion mutant were deficient in chitin utilization and failed to secrete ChiA. They were also deficient in secretion of the motility adhesin RemA but retained the ability to secrete SprB. SprB is involved in gliding motility and is needed for formation of spreading colonies on agar, and the
porV
mutant exhibited gliding motility and formed spreading colonies. However, the
porV
mutant was partially deficient in attachment to glass, apparently because of the absence of RemA and other adhesins on the cell surface. The
porV
mutant also appeared to be deficient in secretion of numerous other proteins that have carboxy-terminal domains associated with targeting to the T9SS. PorU was not required for secretion of ChiA, RemA, or SprB, indicating that it does not play an essential role in the
F. johnsoniae
T9SS.
Noncanonical Cell-to-Cell DNA Transfer in Thermus spp. Is Insensitive to Argonaute-Mediated Interference
Authors: Blesa Alba , César Carolina Elvira , Averhoff Beate , Berenguer José 
Published: October 2014

ABSTRACT

Horizontal gene transfer drives the rapid evolution of bacterial populations. Classical processes that promote the lateral flow of genetic information are conserved throughout the prokaryotic world. However, some species have nonconserved transfer mechanisms that are not well known. This is the case for the ancient extreme thermophile
Thermus thermophilus
. In this work, we show that
T. thermophilus
strains are capable of exchanging large DNA fragments by a novel mechanism that requires cell-to-cell contacts and employs components of the natural transformation machinery. This process facilitates the bidirectional transfer of virtually any DNA locus but favors by 10-fold loci found in the megaplasmid over those in the chromosome. In contrast to naked DNA acquisition by transformation, the system does not activate the recently described DNA-DNA interference mechanism mediated by the prokaryotic Argonaute protein, thus allowing the organism to distinguish between DNA transferred from a mate and exogenous DNA acquired from unknown hosts. This Argonaute-mediated discrimination may be tentatively viewed as a strategy for safe sharing of potentially “useful” traits by the components of a given population of
Thermus
spp. without increasing the genome sizes of its individuals.
Loss of FliL Alters Proteus mirabilis Surface Sensing and Temperature-Dependent Swarming
Authors: Lee Yi-Ying , Belas Robert 
Published: October 2014

ABSTRACT

Proteus mirabilis
is a dimorphic motile bacterium well known for its flagellum-dependent swarming motility over surfaces. In liquid,
P. mirabilis
cells are 1.5- to 2.0-μm swimmer cells with 4 to 6 flagella. When
P. mirabilis
encounters a solid surface, where flagellar rotation is limited, swimmer cells differentiate into elongated (10- to 80-μm), highly flagellated swarmer cells. In order for
P. mirabilis
to swarm, it first needs to detect a surface. The ubiquitous but functionally enigmatic flagellar basal body protein FliL is involved in
P. mirabilis
surface sensing. Previous studies have suggested that FliL is essential for swarming through its involvement in viscosity-dependent monitoring of flagellar rotation. In this study, we constructed and characterized Δ
fliL
mutants of
P. mirabilis
and
Escherichia coli
. Unexpectedly and unlike other
fliL
mutants, both
P. mirabilis
and
E. coli
Δ
fliL
cells swarm (Swr
+
). Further analysis revealed that
P. mirabilis
Δ
fliL
cells also exhibit an alteration in their ability to sense a surface: e.g., Δ
fliL
P. mirabilis
cells swarm precociously over surfaces with low viscosity that normally impede wild-type swarming. Precocious swarming is due to an increase in the number of elongated swarmer cells in the population. Loss of
fliL
also results in an inhibition of swarming at <30°C.
E. coli
Δ
fliL
cells also exhibit temperature-sensitive swarming. These results suggest an involvement of FliL in the energetics and function of the flagellar motor.
The Diguanylate Cyclase GcbA Facilitates Pseudomonas aeruginosa Biofilm Dispersion by Activating BdlA
Authors: Petrova Olga E. , Cherny Kathryn E. , Sauer Karin 
Published: October 2014

ABSTRACT

Biofilm dispersion is a highly regulated process that allows biofilm bacteria to respond to changing environmental conditions and to disseminate to new locations. The dispersion of biofilms formed by the opportunistic pathogen
Pseudomonas aeruginosa
is known to require a number of cyclic di-GMP (c-di-GMP)-degrading phosphodiesterases (PDEs) and the chemosensory protein BdlA, with BdlA playing a pivotal role in regulating PDE activity and enabling dispersion in response to a wide array of cues. BdlA is activated during biofilm growth via posttranslational modifications and nonprocessive cleavage in a manner that is dependent on elevated c-di-GMP levels. Here, we provide evidence that the diguanylate cyclase (DGC) GcbA contributes to the regulation of BdlA cleavage shortly after initial cellular attachment to surfaces and, thus, plays an essential role in allowing biofilm cells to disperse in response to increasing concentrations of a variety of substances, including carbohydrates, heavy metals, and nitric oxide. DGC activity of GcbA was required for its function, as a catalytically inactive variant could not rescue impaired BdlA processing or the dispersion-deficient phenotype of
gcbA
mutant biofilms to wild-type levels. While modulating BdlA cleavage during biofilm growth, GcbA itself was found to be subject to c-di-GMP-dependent and growth-mode-specific regulation. GcbA production was suppressed in mature wild-type biofilms and could be induced by reducing c-di-GMP levels via overexpression of genes encoding PDEs. Taken together, the present findings demonstrate that the regulatory functions of c-di-GMP-synthesizing DGCs expand beyond surface attachment and biofilm formation and illustrate a novel role for DGCs in the regulation of the reverse sessile-motile transition of dispersion.
A tribal abstraction network for SNOMED CT target hierarchies without attribute relationships
Authors: Ochs Christopher , Geller James , Perl Yehoshua , Chen Yan , Agrawal Ankur , Case James T , Hripcsak George 
Published: October 2014

Abstract
Objective Large and complex terminologies, such as Systematized Nomenclature of Medicine–Clinical Terms (SNOMED CT), are prone to errors and inconsistencies. Abstraction networks are compact summarizations of the content and structure of a terminology. Abstraction networks have been shown to support terminology quality assurance. In this paper, we introduce an abstraction network derivation methodology which can be applied to SNOMED CT target hierarchies whose classes are defined using only hierarchical relationships (ie, without attribute relationships) and similar description-logic-based terminologies.
Methods We introduce the tribal abstraction network (TAN), based on the notion of a tribe—a subhierarchy rooted at a child of a hierarchy root, assuming only the existence of concepts with multiple parents. The TAN summarizes a hierarchy that does not have attribute relationships using sets of concepts, called tribal units that belong to exactly the same multiple tribes. Tribal units are further divided into refined tribal units which contain closely related concepts. A quality assurance methodology that utilizes TAN summarizations is introduced.
Results A TAN is derived for the Observable entity hierarchy of SNOMED CT, summarizing its content. A TAN-based quality assurance review of the concepts of the hierarchy is performed, and erroneous concepts are shown to appear more frequently in large refined tribal units than in small refined tribal units. Furthermore, more erroneous concepts appear in large refined tribal units of more tribes than of fewer tribes.
Conclusions In this paper we introduce the TAN for summarizing SNOMED CT target hierarchies. A TAN was derived for the Observable entity hierarchy of SNOMED CT. A quality assurance methodology utilizing the TAN was introduced and demonstrated.
Surveillance colonoscopy in low-risk postpolypectomy patients: Is it necessary?
Authors: Hornung Thomas A , Bevan Roisin , Mumtaz Saqib , Hornung Benjamin R , Rutter Matthew D 
Published: October 2014

AimPatients who have had colorectal adenomas removed are at increased risk of developing colorectal cancer in the future. We sought to determine whether surveillance colonoscopy at 5 years in low-risk postpolypectomy patients is necessary and effective.MethodUK multicentre retrospective study. Patients diagnosed with ‘low-risk’ colorectal adenomas between April 2004 and April 2007 were identified and results of all subsequent lower gastrointestinal (GI) endoscopies were noted. Where no colonoscopy had been done at or after 5 years from the index investigation, patient details were cross-checked against hospital colorectal multidisciplinary team databases to ensure no colorectal cancer had been detected in the meantime.Results641 patients were included. 131 patients (20.4%) had a ‘per protocol’ surveillance colonoscopy at 5 years. Of these, no patients were found to have colorectal cancer, 10 patients (7.6%) had advanced adenomas, 26 patients (19.8%) had non-advanced adenomas and 95 patients (72.5%) had no further adenomas. 510 patients (79.6%) did not have a surveillance colonoscopy at 5 years. Of these, 110 patients (17.2%) developed lower GI symptoms within 5 years of their index endoscopy and underwent a further lower GI endoscopy to investigate these symptoms. 3 colorectal cancers in 3 patients were found during these endoscopies and two further colorectal cancers were found at symptomatic colonoscopies at or after 5 years from index.ConclusionsPatients with low-risk adenomas should be risk profiled. Those with risk factors, such as two adenomas, male sex and advanced adenomas at index procedure should be offered 5-year surveillance colonoscopy.
Management of aneurysmal subarachnoid hemorrhage: a national survey of current practice
Authors: Al-Helli Othman , Bush Steven , Ingale Harshal , McConachie Norman 
Published: October 2014

ObjectivesThe Royal College of Physicians and American Heart Association/American Stroke Association published recommendations in 2012 for the management of aneurysmal subarachnoid hemorrhage (aSAH). This was followed by recommendations included in the National Confidential Enquiry into Patient Outcome and Death (NCEPOD) report published in November 2013. The aim of this study was to assess how many of these recommendations were being followed across the UK and Ireland 6 months after publication of the latest recommendations, and to compare current practice with the NCEPOD data collected in 2011.MethodsWe formulated a survey composed of 19 questions regarding the management of aSAH, and conducted a telephone interview with the neurosurgical registrars on call.Results22 out of 30 centers aimed to treat ruptured aneurysms by coiling or clipping within 48 h from ictus, yet only 15 units offered regular weekend interventional neuroradiological treatment. In 9 units, all aSAH patients were routinely discussed in a multidisciplinary meeting.ConclusionsAt 6 months following publication of the NCEPOD report we found that in the majority of neurosurgical units, most of the key recommendations were being met. However, in the remainder there was variability in clinical practice.
Hemodynamic analysis of fast and slow aneurysm occlusions by flow diversion in rabbits
Authors: Chung Bongjae , Mut Fernando , Kadirvel Ramanathan , Lingineni Ravi , Kallmes David F , Cebral Juan R 
Published: October 2014

PurposeTo assess hemodynamic differences between aneurysms that occlude rapidly and those occluding in delayed fashion after flow diversion in rabbits.MethodsThirty-six elastase-induced aneurysms in rabbits were treated with flow diverting devices. Aneurysm occlusion was assessed angiographically immediately before they were sacrificed at 1 (n=6), 2 (n=4), 4 (n=8) or 8 weeks (n=18) after treatment. The aneurysms were classified into a fast occlusion group if they were completely or near completely occluded at 4 weeks or earlier and a slow occlusion group if they remained incompletely occluded at 8 weeks. The immediate post-treatment flow conditions in aneurysms of each group were quantified using subject-specific computational fluid dynamics and statistically compared.ResultsNine aneurysms were classified into the fast occlusion group and six into the slow occlusion group. Aneurysms in the fast occlusion group were on average significantly smaller (fast=0.9 cm, slow=1.393 cm, p=0.024) and had smaller ostia (fast=0.144 cm2, slow=0.365 cm2, p=0.015) than aneurysms in the slow occlusion group. They also had a lower mean post-treatment inflow rate (fast=0.047 mL/s, slow=0.155 mL/s, p=0.0239), kinetic energy (fast=0.519 erg, slow=1.283 erg, p=0.0468), and velocity (fast=0.221 cm/s, slow=0.506 cm/s, p=0.0582). However, the differences in the latter two variables were only marginally significant.ConclusionsHemodynamic conditions after flow diversion treatment of cerebral aneurysms in rabbits are associated with the subsequent aneurysm occlusion time. Specifically, smaller inflow rate, kinetic energy, and velocity seem to promote faster occlusions, especially in smaller and small-necked aneurysms. These results are consistent with previous studies based on clinical series.
Gene expression comparison of flow diversion and coiling in an experimental aneurysm model
Authors: Puffer Cole , Dai Daying , Ding Yong-Hong , Cebral Juan , Kallmes David , Kadirvel Ramanathan 
Published: October 2014

Background and purposeMechanisms of both healing and complications, including spontaneous aneurysm rupture, remain unclear following flow diverter treatment. The aim of this study was to compare gene expression of various key molecules involved in the healing of aneurysms, between aneurysms treated with microcoils and flow diverters.MethodsSaccular aneurysms were created in rabbits. Aneurysms were treated with coils (n=6) or flow diverters (n=6). Aneurysms were harvested at 4 weeks following treatment and used for gene expression and zymography experiments. Genes with a fold change of 1.2 or more were considered upregulated whereas those with a fold change of 0.8 or less were considered downregulated.ResultsAll coil embolized aneurysms were completely occluded at follow-up. Two aneurysms were occluded and the remaining four samples were incompletely occluded in the flow diverter treated group. The following genes were expressed at lower levels in the flow diverter group compared with the coiled aneurysm group: proteinases (matrix metalloproteinases 2 and 9), cellular markers (endothelial nitric oxide synthase and smooth muscle actin), and structural proteins (collagens and fibronectin). Genes related to inflammation (tumor necrosis factor α and monocyte chemoattractant protein 1) were upregulated in flow diverter treated aneurysms compared with coil embolized aneurysms. Notably, the enzymatic activity of active matrix metalloproteinase 9 was high in aneurysms treated with flow diverters.ConclusionsOur findings may provide improved understanding of rupture risk and healing following aneurysm treatment and inform development of therapies aimed at lowering rupture risk and accelerating healing.