bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence
of Scan Resolution, Thresholding, and Reconstruction Algorithm on Computed Tomography-Based
Kinematic Measurements
Authors: Tan Christopher
John , Parr William C.
H. , Walsh William
R. , Makara Mariano , Johnson Kenneth
A. 
Published: August 2017

Abstract
Radiographic data, including computed tomography (CT) and planar X-ray, is increasingly used for human and animal kinematic studies. There is a tendency toward using as high-resolution imaging as possible. Higher resolution imaging is one factor (in conjunction with the reconstruction algorithm), which may increase the precision of reconstructed three-dimensional (3D) surface models in representing true bone shape. However, to date no study has tested the effects of scan resolution, threshold, and 3D model reconstruction algorithm on the accuracy of bone kinematic results. The present study uses a novel method to do this where canine tarsal bones were positioned on a radiolucent Lego™ board and scanned before and after undergoing known translations and/or rotations. The digital imaging and communications in medicine (DICOM) images were acquired using two different CT scanning resolutions and processed using three different segmentation threshold levels and three different reconstruction algorithms. Using one bone as the reference bone, an iterative closest point (ICP) algorithm was used to register bones to a global co-ordinate system and allow measurement of other bone kinematics in terms of translations and rotations in and around the x-, y-, and z-axes. The measured kinematics were compared to the “known” kinematics, which were obtained from the Lego™ board's manufacturing standards and tolerances, to give accuracy error metrics for all bones. The results showed error in accuracy of measured kinematics was at subvoxel levels (less than 0.5 mm). Despite altering the volume and surface area of the 3D bone models, variation in resolution, segmentation threshold and reconstruction algorithm had no significant influence upon the accuracy of the calculated tarsal bone kinematics.
Step-Down Test Assessment of Postural Stability in Patients With Chronic Ankle Instability
Authors: Bolt Doris , Giger René , Wirth Stefan , Swanenburg Jaap 
Published: August 2017

Context: The underlying mechanism in 27% of ankle sprains is a fall while navigating stairs. Therefore, the step-down test (SDT) may be useful to investigate dynamic postural stability deficits in individuals with chronic ankle instability (CAI). Objective: To investigate the test–retest reliability and validity of the forward and lateral SDT protocol between individuals with CAI and uninjured controls. Design: Test–retest study. Setting: University hospital. Participants: A total of 46 individuals, 23 with CAI and 23 uninjured controls. Main Outcome Measures: Time to stabilization of the forward and lateral SDT. Results: The absolute reliability (SEM = 0.04–0.12 s; SDD = 0.11–0.33 s) of the SDT protocol was acceptable, whereas the relative reliability (ICC3, k = 0.12–0.63) and discriminant validity (P = .42–.99; AUC = 0.50–0.57) were not. Conclusions: The SDT appears to not be challenging enough to detect dynamic postural stability differences between individuals with and without CAI. However, the SDT may be capable of measuring change over time based on its good absolute reliability.
Effect of Low- Versus High-Intensity Exercise Training on Biomarkers of Inflammation and Endothelial Dysfunction in Adolescents With Obesity: A 6-Month Randomized Exercise Intervention Study
Authors: Tenório Thiago R.S. , Balagopal P. Babu , Andersen Lars B. , Ritti-Dias Raphael M. , Hill James O. , Lofrano-Prado Mara C. , Prado Wagner L. 
Published: August 2017

Purpose:
To investigate the effects of a low- versus high-intensity aerobic training on biomarkers of inflammation and endothelial dysfunction in adolescents with obesity. Methods: Sixty-two adolescents with obesity [age = 15 (14) y, body mass index = 34.87 (4.22) kg·m−2] were randomized to receive either a high-intensity training (HIT, n = 31) or a low-intensity training (LIT, n = 31) for 24 weeks. All participants also received nutritional, psychological, and clinical counseling. Leptin, total and subtype leukocyte counts, tumor necrosis factor-alpha, interleukin-6, myeloperoxidase, soluble intercellular adhesion molecule-1, and soluble vascular cell adhesion molecule-1 were obtained at baseline and after 24 weeks. Results: HIT reduced neutrophils [from 4.4 (1.9) to 3.6 (1.3) µL−1 × 103; P = .01] and monocytes [from 7.2 (2.5) to 5.2 (1.8) µL−1 × 102; P < .01], but LIT increased neutrophils [from 4.5 (1.7) to 5.2 (3.3) µL−1 × 103; P = .01]. Although tumor necrosis factor-alpha increased in LIT [from 13.3 (7.5) to 17.7 (10.8) pg·mL−1; P = .01], it decreased in HIT [from 12.4 (7.5) to 11.3 (6.2) pg·mL−1; P = .01]. No changes in leukocyte counts, soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, and homeostasis assessment model for insulin resistance were observed. Conclusions: Both HIT and LIT improved the inflammatory profile. The study, however, indicated that the number of biomarkers and the magnitude of changes were higher in the HIT compared with LIT.
Nutrition Status of Young Elite Female German Football Players
Authors: Braun Hans , von Andrian-Werburg Judith , Schänzer Wilhelm , Thevis Mario 
Published: August 2017

Purpose: To investigate energy intake, energy expenditure, and the nutritional status of young female elite football players using 7-day food and activity records and blood parameters. Methods: A total of 56 female elite football players [14.8 (0.7) y] completed the requested food and activity protocols. Misreporting was assessed by the ratio of energy intake to energy expenditure. The food records were analyzed concerning energy and macronutrient and micronutrient intakes, and energy expenditure was calculated using predictive equations. Hematological data and 25-hydroxyvitamin D serum concentrations were determined. Results: Mean energy intake was 2262 (368) kcal/d [40.5 (7.0) kcal/kg/d] and estimated EE averaged 2403 (195) kcal/d. Fifty-three percent of the players exhibited an energy availability <30 kcal/kg lean body mass; 31% of the athletes consumed <5 g/kg carbohydrates and 34% consumed <1.2 g/kg proteins. A large proportion of players (%) had intakes below the recommended daily allowance of folate (75%), vitamin D (100%), iron (69%), and calcium (59%). Ferritin and 25-hydroxyvitamin D serum levels were below the recommendations of 59% and 38%, respectively. Conclusions: A remarkable number of players failed to meet the energy balance and the recommended carbohydrate and protein intakes. Low iron and 25-hydroxyvitamin D serum levels were observed showing a suboptimal nutrition status of some young female football players. As a consequence, strategies have to be developed for a better information and application of sport nutrition practice among young female football players.
Monitoring Antifungal Resistance in a Global Collection of Invasive Yeasts and Molds: Application of CLSI Epidemiological Cutoff Values and Whole-Genome Sequencing Analysis for Detection of Azole Resistance in Candida albicans
Authors: Castanheira Mariana , Deshpande Lalitagauri M. , Davis Andrew P. , Rhomberg Paul R. , Pfaller Michael A. 
Published: August 2017

ABSTRACT

The activity of 7 antifungal agents against 3,557 invasive yeasts and molds collected in 29 countries worldwide in 2014 and 2015 was evaluated. Epidemiological cutoff values (ECVs) published in the Clinical and Laboratory Standards Institute (CLSI) M59 document were applied for species with no clinical breakpoints. Echinocandin susceptibility rates were 95.9% to 100.0% for the 5 most common
Candida
species, except for the rates for
Candida parapsilosis
to anidulafungin (88.7% susceptible, 100.0% wild type). Rates of fluconazole resistance ranged from 8.0% for
Candida glabrata
to 0.4% for
Candida albicans
. Seven
Candida
species displayed 100.0% wild-type amphotericin B MIC results, and
Candida dubliniensis
and
Candida lusitaniae
exhibited wild-type echinocandin MIC results. The highest fluconazole, voriconazole, and posaconazole MIC values for
Cryptococcus neoformans
var.
grubii
were 8 μg/ml, 0.12 μg/ml, and 0.25 μg/ml, respectively.
Aspergillus fumigatus
isolates were 100.0% wild type for caspofungin and amphotericin B, but 3 (0.8%) of these isolates were non-wild type to itraconazole (2 isolates) or voriconazole (1 isolate). Mutations in
FKS
hot spot (HS) regions were detected among 13/20
Candida
isolates displaying echinocandin MICs greater than the ECV (16 of these 20 isolates were
C. glabrata
). Most isolates carrying mutations in
FKS
HS regions were resistant to 2 or more echinocandins. Five fluconazole-nonsusceptible
C. albicans
isolates were submitted to whole-genome sequencing analysis. Gain-of-function,
Erg11
heterozygous, and
Erg3
homozygous mutations were observed in 1 isolate each. One isolate displayed MDR1 promoter allele alterations associated with azole resistance. Elevated levels of expression of MDR1 or CDR2 were observed in 3 isolates and 1 isolate, respectively. Echinocandin and azole resistance is still uncommon among contemporary fungal isolates; however, mechanisms of resistance to antifungals were observed among
Candida
spp., showing that resistance can emerge and monitoring is warranted.
Translocation of Carbapenemase Gene
bla
KPC-2
both Internal and External to Transposons Occurs via Novel Structures of Tn
1721
and Exhibits Distinct Movement Patterns
Authors: Tang Yu , Li Gang , Liang Wei , Shen Pinghua , Zhang Ying , Jiang Xiaofei 
Published: August 2017

ABSTRACT

The
bla
KPC-2
gene encodes a carbapenemase that hydrolyzes almost all β-lactams, including carbapenems. The rapid emergence and international spread of this gene in
Enterobacteriaceae
seriously limit clinical treatment, posing an alarming threat for public health. Transposable elements, such as Tn
4401
, a proven transposon in Europe, the United States, and elsewhere, often play a role in the dissemination of the
bla
KPC-2
gene. In eastern China, the
bla
KPC-2
gene is frequently associated with several novel structures of Tn
1721
, but their transposition ability and mechanism of movement remain unclear. Here, we experimentally demonstrate that Tn
1721
-like transposons are capable of transferring
bla
KPC-2
both internal and external to the Tn
1721
element from one strain to another and that distinct transposon structures exhibit different movement patterns and transposition frequencies. This process did not involve homologous recombination. Moreover, a 5-bp duplication of the target site, a characterized signature of transposition events in the Tn
3
family, was confirmed. Tn
1721
-like transposons were found to insert preferentially into a 5-bp region that gradually exhibits a degenerated degree of AT-rich regions from both sides to the middle and that is immediately flanked by GC-rich regions. The observation in clinical isolates of diverse sequences flanking the transposons and a 5-bp duplication of the target site, as well as the prevalence of Tn
1721
-like transposons, also sustained our experimental results. This study first gives evidence about the functional role of Tn
1721
-like transposons in transferring the
bla
KPC-2
gene and provides new sight into the transposable element and the dissemination of antibiotic resistance in
Enterobacteriaceae
.
Comparative Pharmacodynamics of Single-Dose Oritavancin and Daily High-Dose Daptomycin Regimens against Vancomycin-Resistant Enterococcus faecium Isolates in an
In Vitro
Pharmacokinetic/Pharmacodynamic Model of Infection
Authors: Belley Adam , Lalonde-Séguin David , Arhin Francis F. , Moeck Greg 
Published: August 2017

ABSTRACT

There are limited therapeutic options to treat infections caused by vancomycin-resistant
Enterococcus faecium
(VREfm). The lipoglycopeptide oritavancin exhibits
in vitro
activity against this pathogen, although its utility against infections caused by VREfm has not been clinically established. In this study, the pharmacodynamic activity of free-drug levels associated with 12 mg/kg/day of daptomycin and a single 1,200-mg dose of oritavancin were determined against three VanA VREfm isolates in an
in vitro
pharmacokinetic/pharmacodynamic model.
In Vivo
Analysis of Staphylococcus aureus-Infected Mice Reveals Differential Temporal and Spatial Expression Patterns of
fhuD2
Authors: Bacconi Marta , Haag Andreas F. , Chiarot Emiliano , Donato Paolo , Bagnoli Fabio , Delany Isabel , Bensi Giuliano 
Published: August 2017

ABSTRACT

Staphylococcus aureus
is an opportunistic human pathogen and a major cause of invasive infections such as bacteremia, endocarditis, pneumonia, and wound infections. FhuD2 is a staphylococcal lipoprotein involved in the uptake of iron-hydroxymate and is under the control of the iron uptake regulator Fur. This protein is part of an investigational multicomponent vaccine formulation that has shown protective efficacy in several murine models of infection. Even though
fhuD2
expression has been shown to be upregulated in murine kidneys infected with
S. aureus
, it is not known whether the bacterium undergoes increased iron deprivation during prolonged infection. Furthermore, different
S. aureus
infection niches might provide different environments and levels of iron availability, resulting in different
fhuD2
expression patterns among organs of the same host. To address these questions, we characterized the
in vitro
expression of the
fhuD2
gene and confirmed Fur-dependent regulation of its expression. We further investigated its expression in mice infected with a bioluminescent reporter strain of
S. aureus
expressing the luciferase operon under the control of the
fhuD2
promoter. The emission of bioluminescence in different organs was followed over a 7-day time course, and quantitative real-time PCR analysis of the RNA transcribed from the endogenous
fhuD2
gene was performed. Using this approach, we were able to show that
fhuD2
expression was induced during infection in all organs analyzed and that differences in expression were observed at different time points and in different infected organs. Our data suggest that
S. aureus
undergoes increased iron deprivation during the progression of infection in diverse host organs and accordingly induces dedicated iron acquisition mechanisms. Since FhuD2 plays a central role in providing the pathogen with the required iron, further knowledge of the patterns of
fhuD2
expression
in vivo
during infection will be instrumental in better defining the role of this antigen in
S. aureus
pathogenesis and as a vaccine antigen.
Type Three Secretion System-Dependent Microvascular Thrombosis and Ischemic Enteritis in Human Gut Xenografts Infected with Enteropathogenic Escherichia coli
Authors: Nissim-Eliraz Einat , Nir Eilam , Shoval Irit , Marsiano Noga , Nissan Israel , Shemesh Hadar , Nagy Nandor , Goldstein Allan M. , Gutnick Michael , Rosenshine Ilan , Yagel Simcha , Shpigel Nahum Y. 
Published: August 2017

ABSTRACT

Enteropathogenic
Escherichia coli
(EPEC) is a leading cause of severe intestinal disease and infant mortality in developing countries. Virulence is mediated by a type three secretion system (T3SS), causing the hallmark attaching and effacing (AE) lesions and actin-rich pedestal formation beneath the infecting bacteria on the apical surface of enterocytes. EPEC is a human-specific pathogen whose pathogenesis cannot be studied in animal models. We therefore established an EPEC infection model in human gut xenografts in SCID mice and used it to study the role of T3SS in the pathogenesis of the disease. Following EPEC O127:H6 strain E2348/69 infection, T3SS-dependent AE lesions and pedestals were demonstrated in all infected xenografts. We report here the development of T3SS-dependent intestinal thrombotic microangiopathy (iTMA) and ischemic enteritis in ∼50% of infected human gut xenografts. Using species-specific CD31 immunostaining, we showed that iTMA was limited to the larger human-mouse chimeric blood vessels, which are located between the muscularis mucosa and circular muscular layer of the human gut. These blood vessels were massively invaded by bacteria, which adhered to and formed pedestals on endothelial cells and aggregated with mouse neutrophils in the lumen. We conclude that endothelial infection, iTMA, and ischemic enteritis might be central mechanisms underlying severe EPEC-mediated disease.
Guanylate Binding Proteins Regulate Inflammasome Activation in Response to Hyperinjected Yersinia Translocon Components
Authors: Zwack Erin E. , Feeley Eric M. , Burton Amanda R. , Hu Baofeng , Yamamoto Masahiro , Kanneganti Thirumala-Devi , Bliska James B. , Coers Jörn , Brodsky Igor E. 
Published: August 2017

ABSTRACT

Gram-negative bacterial pathogens utilize virulence-associated secretion systems to inject, or translocate, effector proteins into host cells to manipulate cellular processes and promote bacterial replication. However, translocated bacterial products are sensed by
n
ucleotide binding domain and
l
eucine-rich
r
epeat-containing proteins (NLRs), which trigger the formation of a multiprotein complex called the inflammasome, leading to secretion of interleukin-1 (IL-1) family cytokines, pyroptosis, and control of pathogen replication. Pathogenic
Yersinia
bacteria inject effector proteins termed Yops, as well as pore-forming proteins that comprise the translocon itself, into target cells. The
Yersinia
translocation regulatory protein YopK promotes bacterial virulence by limiting hyperinjection of the translocon proteins YopD and YopB into cells, thereby limiting cellular detection of
Yersinia
virulence activity. How hyperinjection of translocon proteins leads to inflammasome activation is currently unknown. We found that translocated YopB and YopD colocalized with the late endosomal/lysosomal protein LAMP1 and that the frequency of YopD and LAMP1 association correlated with the level of caspase-1 activation in individual cells. We also observed colocalization between YopD and Galectin-3, an indicator of endosomal membrane damage. Intriguingly, YopK limited the colocalization of Galectin-3 with YopD, suggesting that YopK limits the induction or sensing of endosomal membrane damage by components of the type III secretion system (T3SS) translocon. Furthermore, guanylate binding proteins (GBPs) encoded on chromosome 3 (
Gbp

Chr3

), which respond to pathogen-induced damage or alteration of host membranes, were necessary for inflammasome activation in response to hyperinjected YopB/-D. Our findings indicate that lysosomal damage by
Yersinia
translocon proteins promotes inflammasome activation and implicate GBPs as key regulators of this process.
Phosphoserine Phosphatase Is Required for Serine and One-Carbon Unit Synthesis in Hydrogenobacter thermophilus
Authors: Kim Keugtae , Chiba Yoko , Kobayashi Azusa , Arai Hiroyuki , Ishii Masaharu 
Published: August 2017

ABSTRACT

Hydrogenobacter thermophilus
is an obligate chemolithoautotrophic bacterium of the phylum
Aquificae
and is capable of fixing carbon dioxide through the reductive tricarboxylic acid (TCA) cycle. The recent discovery of two novel-type phosphoserine phosphatases (PSPs) in
H. thermophilus
suggests the presence of a phosphorylated serine biosynthesis pathway; however, the physiological role of these novel-type metal-independent PSPs (iPSPs) in
H. thermophilus
has not been confirmed. In the present study, a mutant strain with a deletion of
pspA
, the catalytic subunit of iPSPs, was constructed and characterized. The generated mutant was a serine auxotroph, suggesting that the novel-type PSPs and phosphorylated serine synthesis pathway are essential for serine anabolism in
H. thermophilus.
As an autotrophic medium supplemented with glycine did not support the growth of the mutant, the reversible enzyme serine hydroxymethyltransferase does not appear to synthesize serine from glycine and may therefore generate glycine and 5,10-CH
2
-tetrahydrofolate (5,10-CH
2
-THF) from serine. This speculation is supported by the lack of glycine cleavage activity, which is needed to generate 5,10-CH
2
-THF, in
H. thermophilus
. Determining the mechanism of 5,10-CH
2
-THF synthesis is important for understanding the fundamental anabolic pathways of organisms, because 5,10-CH
2
-THF is a major one-carbon donor that is used for the synthesis of various essential compounds, including nucleic and amino acids. The findings from the present experiments using a
pspA
deletion mutant have confirmed the physiological role of iPSPs as serine producers and show that serine is a major donor of one-carbon units in
H. thermophilus
.

IMPORTANCE
Serine biosynthesis and catabolism pathways are intimately related to the metabolism of 5,10-CH
2
-THF, a one-carbon donor that is utilized for the biosynthesis of various essential compounds. For this reason, determining the mechanism of serine synthesis is important for understanding the fundamental anabolic pathways of microorganisms. In the present study, we experimentally confirmed that a novel phosphoserine phosphatase in the obligate chemolithoautotrophic bacterium
Hydrogenobacter thermophilus
is essential for serine biosynthesis. This finding indicates that serine is synthesized from an intermediate of gluconeogenesis in
H. thermophilus
. In addition, because glycine cleavage system activity and genes encoding an enzyme capable of producing 5,10-CH
2
-THF were not detected, serine appears to be the major one-carbon donor to tetrahydrofolate (THF) in
H. thermophilus
.
Application of Distributive Conjugal DNA Transfer in Mycobacterium smegmatis To Establish a Genome-Wide Synthetic Genetic Array
Authors: Judd Julius , Boucher Nathalie , Van Roey Erik , Gray Todd A. , Derbyshire Keith M. 
Published: August 2017

ABSTRACT

Genetic redundancy can obscure phenotypic effects of single-gene mutations. Two individual mutations may be viable separately but are lethal when combined, thus synthetically linking the two gene products in an essential process. Synthetic genetic arrays (SGAs), in which defined mutations are combined, provide a powerful approach to identify novel genetic interactions and redundant pathways. A genome-scale SGA can offer an initial assignment of function to hypothetical genes by uncovering interactions with known genes or pathways. Here, we take advantage of the chromosomal conjugation system of
Mycobacterium smegmatis
to combine individual donor and recipient mutations on a genome-wide scale. We demonstrated the feasibility of a high-throughput mycobacterial SGA (mSGA) screen by using mutants of
esx3
,
fxbA
, and
recA
as query genes, which were combined with an arrayed library of transposon mutants by conjugation. The mSGA identified interacting genes that we had predicted and, most importantly, identified novel interacting genes—encoding both proteins and a noncoding RNA (ncRNA). In combination with other molecular genetic approaches, the mSGA has great potential to both reduce the high number of conserved hypothetical protein annotations in mycobacterial genomes and further define mycobacterial pathways and gene interactions.

IMPORTANCE
Mycobacterium smegmatis
is the model organism of choice for the study of mycobacterial pathogens, because it is a fast-growing nonpathogenic species harboring many genes that are conserved throughout mycobacteria. In this work, we describe a synthetic genetic array (mSGA) approach for
M. smegmatis
, which combines mutations on a genome-wide scale with high efficiency. Analysis of the double mutant strains enables the identification of interacting genes and pathways that are normally hidden by redundant biological pathways. The mSGA is a powerful genetic tool that enables functions to be assigned to the many conserved hypothetical genes found in all mycobacterial species.