bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inborn errors of ketone body utilization
Authors: Hori Tomohiro , Yamaguchi Seiji , Shinkaku Haruo , Horikawa Reiko , Shigematsu Yosuke , Takayanagi Masaki , Fukao Toshiyuki 
Published: January 2015

AbstractSuccinyl‐CoA:3‐ketoacid CoA transferase (SCOT) deficiency and mitochondrial acetoacetyl‐CoA thiolase (beta‐ketothiolase or T2) deficiency are classified as autosomal recessive disorders of ketone body utilization characterized by intermittent ketoacidosis. Patients with mutations retaining no residual activity on analysis of expression of mutant cDNA are designated as severe genotype, and patients with at least one mutation retaining significant residual activity, as mild genotype. Permanent ketosis is a pathognomonic characteristic of SCOT‐deficient patients with severe genotype. Patients with mild genotype, however, may not have permanent ketosis, although they may develop severe ketoacidotic episodes similar to patients with severe genotype. Permanent ketosis has not been reported in T2 deficiency. In T2‐deficient patients with severe genotype, biochemical diagnosis is done on urinary organic acid analysis and blood acylcarnitine analysis to observe characteristic findings during both ketoacidosis and non‐episodic conditions. In Japan, however, it was found that T2‐deficient patients with mild genotype are common, and typical profiles were not identified on these analyses. Based on a clinical study of ketone body utilization disorders both in Japan and worldwide, we have developed guidelines for disease diagnosis and treatment. These diseases are treatable by avoiding fasting and by providing early infusion of glucose, which enable the patients to grow without sequelae.
Immune System‐Related Differentially Expressed Genes, Transcription Factors and microRNAs in Post‐Menopausal Females with Osteopenia
Authors: Ma M. , Luo S. , Chen X. , Yuan F. , Cai J. , Lu L. , Yin F. 
Published: January 2015

AbstractThis study was to identify differentially expressed genes (DEGs) in post‐menopausal females with osteopenia and further screened the potentially involved transcription factors (TFs) and microRNAs (miRNAs). Data set GSE13850 of circulating B lymphocytes from post‐menopausal females with low or high bone mineral density (BMD) was downloaded from Gene Expression Omnibus. Limma package in R was used to identify DEGs following raw data processing. Enrichment analysis was performed using DAVID (Database for Annotation, Visualization and Integrated Discovery) and visualized using plug‐in EnrichmentMap of Cytoscape software. The TFs of DEGs were screened using UCSC (University of California, Santa Cruz) Genome Browser, and miRNAs targeting DEGs were predicted using TarBase, TargetScan and miRecord databases, followed by constructing regulatory networks using Cytoscape software. Totally 52 DEGs were obtained from post‐menopausal females with low BMD compared with those with high BMD. Those DEGs including IL‐4R, IL‐2RG, TGF‐β1 and CD74 were mostly related to functions associated with immune response, lymphocyte activation, T cell differentiation, leucocyte activation and immune system process. NFAT, NF‐κB and EGR family members might have a regulatory effect on these DEGs. PAX5 could regulate 15 DEGs including ZFP36L2 and KLF13. Abundant miRNAs were also found to target dysregulated ZFP36L2 and KLF13. Dysregulated IL‐4R, IL‐2RG, TGF‐β1 and CD74 may mediate the interplay of immune changes and oestrogen deficiency‐induced osteopenia, and disorder functions of NF‐κB, NFAT and EGR family members. PAX5 and various miRNAs might exert regulatory effect on osteopenia via targeting ZFP36L2 and KLF13.
Phylogeny, divergence times and biogeography of window flies (Scenopinidae) and the therevoid clade (Diptera: Asiloidea)
Authors: WINTERTON SHAUN L. , WARE JESSICA L. 
Published: January 2015

AbstractThe evolution of the ‘therevoid’ clade, with an emphasis on window flies (Scenopinidae), is presented by combining DNA sequence data with morphological characters for living and fossil species. The therevoid clade represents a group of four families (Apsilocephalidae, Evocoidae, Scenopinidae and Therevidae) of lower brachyceran Diptera in the superfamily Asiloidea. A comprehensive phylogenetic analysis using parsimony and likelihood methods was undertaken using extensive taxon sampling from all families and subfamilies, and compared with outgroup taxa sampled from the related families Asilidae, Mydidae, Apioceridae and Empididae. Fifty‐nine morphological characters (adult, larval and pupal) were combined with 6.4 kb of DNA sequences for two ribosomal genes (16S and 18S ribosomal DNA) and three protein‐encoding genes [cytochrome oxidase I (COI), triose phosphate isomerase (TPI) and the CPSase region of carbamoyl‐phosphate synthase‐aspartate transcarbamoylase‐dihydroorotase (CAD)]. Results from combined analyses of morphological and molecular data for 78 taxa representing all families of the therevoid clade are presented. Specific hypotheses of the relationship between respective families and subfamilies were tested statistically using four‐cluster likelihood mapping. The therevoid clade is a well‐supported monophyletic group within Asiloidea, with Evocoidae sister to Apsilocephalidae and Therevidae sister to Scenopinidae. Temporal and zoogeographical aspects of therevoid clade evolution were investigated using Bayesian divergence time estimates and Lagrange ancestral range scenarios. The effect of inclusion of fossils as terminal taxa on phylogenetic and divergence time estimation was investigated, with morphological scoring for fossil representatives included in the analyses rather than used simply as minimum age constraints. In each analysis there was either improvement in estimation, or only marginal and localized loss in tree resolution, and with younger estimates of divergence time across the tree. The historical biogeography of the therevoid clade was examined with multiple trans‐Antarctic vicariance events between Australasia and South America evident during the Late Cretaceous to early Palaeogene. Scenopininae is newly subdivided into two tribes, Metatrichini trib.n. and Scenopinini Fallén stat.r.This published work has been registered in ZooBank, http://zoobank.org/urn:lsid:zoobank.org:pub:4974EBF8‐3117‐4189‐B6DE‐7D5BF9B23E53.
Detective quantum efficiency of photon‐counting x‐ray detectors
Authors: Tanguay Jesse , Yun Seungman , Kim Ho Kyung , Cunningham Ian A. 
Published: January 2015

Purpose:Single‐photon‐counting (SPC) x‐ray imaging has the potential to improve image quality and enable novel energy‐dependent imaging methods. Similar to conventional detectors, optimizing image SPC quality will require systems that produce the highest possible detective quantum efficiency (DQE). This paper builds on the cascaded‐systems analysis (CSA) framework to develop a comprehensive description of the DQE of SPC detectors that implement adaptive binning.Methods:The DQE of SPC systems can be described using the CSA approach by propagating the probability density function (PDF) of the number of image‐forming quanta through simple quantum processes. New relationships are developed to describe PDF transfer through serial and parallel cascades to accommodate scatter reabsorption. Results are applied to hypothetical silicon and selenium‐based flat‐panel SPC detectors including the effects of reabsorption of characteristic/scatter photons from photoelectric and Compton interactions, stochastic conversion of x‐ray energy to secondary quanta, depth‐dependent charge collection, and electronic noise. Results are compared with a Monte Carlo study.Results:Depth‐dependent collection efficiency can result in substantial broadening of photopeaks that in turn may result in reduced DQE at lower x‐ray energies (20–45 keV). Double‐counting interaction events caused by reabsorption of characteristic/scatter photons may result in falsely inflated image signal‐to‐noise ratio and potential overestimation of the DQE.Conclusions:The CSA approach is extended to describe signal and noise propagation through photoelectric and Compton interactions in SPC detectors, including the effects of escape and reabsorption of emission/scatter photons. High‐performance SPC systems can be achieved but only for certain combinations of secondary conversion gain, depth‐dependent collection efficiency, electronic noise, and reabsorption characteristics.
Klebsiella pneumoniae Carbapenemase (KPC)-Producing K. pneumoniae at a Single Institution: Insights into Endemicity from Whole-Genome Sequencing
Authors: Mathers Amy J. , Stoesser Nicole , Sheppard Anna E. , Pankhurst Louise , Giess Adam , Yeh Anthony J. , Didelot Xavier , Turner Stephen D. , Sebra Robert , Kasarskis Andrew , Peto Tim , Crook Derrick , Sifri Costi D. 
Published: January 2015

ABSTRACT

The global emergence of
Klebsiella pneumoniae
carbapenemase-producing
K. pneumoniae
(KPC-
Kp
) multilocus sequence type ST258 is widely recognized. Less is known about the molecular and epidemiological details of non-ST258
K. pneumoniae
in the setting of an outbreak mediated by an endemic plasmid. We describe the interplay of
bla
KPC
plasmids and
K. pneumoniae
strains and their relationship to the location of acquisition in a U.S. health care institution. Whole-genome sequencing (WGS) analysis was applied to KPC-
Kp
clinical isolates collected from a single institution over 5 years following the introduction of
bla
KPC
in August 2007, as well as two plasmid transformants. KPC-
Kp
from 37 patients yielded 16 distinct sequence types (STs). Two novel conjugative
bla
KPC
plasmids (pKPC_UVA01 and pKPC_UVA02), carried by the hospital index case, accounted for the presence of
bla
KPC
in 21/37 (57%) subsequent cases. Thirteen (35%) isolates represented an emergent lineage, ST941, which contained pKPC_UVA01 in 5/13 (38%) and pKPC_UVA02 in 6/13 (46%) cases. Seven (19%) isolates were the epidemic KPC-
Kp
strain, ST258, mostly imported from elsewhere and not carrying pKPC_UVA01 or pKPC_UVA02. Using WGS-based analysis of clinical isolates and plasmid transformants, we demonstrate the unexpected dispersal of
bla
KPC
to many non-ST258 lineages in a hospital through spread of at least two novel
bla
KPC
plasmids. In contrast, ST258 KPC-
Kp
was imported into the institution on numerous occasions, with other
bla
KPC
plasmid vectors and without sustained transmission. Instead, a newly recognized KPC-
Kp
strain, ST941, became associated with both novel
bla
KPC
plasmids and spread locally, making it a future candidate for clinical persistence and dissemination.
In Vitro
Prediction of the Evolution of GES-1 β-Lactamase Hydrolytic Activity
Authors: Bontron Séverine , Poirel Laurent , Nordmann Patrice 
Published: January 2015

ABSTRACT

Resistance to β-lactams is constantly increasing due to the emergence of totally new enzymes but also to the evolution of preexisting β-lactamases. GES-1 is a clinically relevant extended-spectrum β-lactamase (ESBL) that hydrolyzes penicillins and broad-spectrum cephalosporins but spares monobactams and carbapenems. However, several GES-1 variants (i.e., GES-2 and GES-5) previously identified among clinical isolates display an extended spectrum of activity toward carbapenems. To study the evolution potential of the GES-1 β-lactamase, this enzyme was submitted to
in vitro
-directed evolution, with selection on increasing concentrations of the cephalosporin cefotaxime, the monobactam aztreonam, or the carbapenem imipenem. The highest resistance levels were conferred by a combination of up to four substitutions. The A6T-E104K-G243A variant selected on cefotaxime and the A6T-E104K-T237A-G243A variant selected on aztreonam conferred high resistance to cefotaxime, ceftazidime, and aztreonam. Conversely, the A6T-G170S variant selected on imipenem conferred high resistance to imipenem and cefoxitin. Of note, the A6T substitution involved in higher MICs for all β-lactams is located in the leader peptide of the GES enzyme and therefore is not present in the mature protein. Acquired cross-resistance was not observed, since selection with cefotaxime or aztreonam did not select for resistance to imipenem, and vice versa. Here, we demonstrate that the β-lactamase GES-1 exhibits peculiar properties, with a significant potential to gain activity against broad-spectrum cephalosporins, monobactams, and carbapenems.
Phenotypic Heterogeneity Enables Uropathogenic Escherichia coli To Evade Killing by Antibiotics and Serum Complement
Authors: Putrinš Marta , Kogermann Karin , Lukk Eliisa , Lippus Markus , Varik Vallo , Tenson Tanel 
Published: January 2015

ABSTRACTUropathogenic strains ofEscherichia coli(UPEC) are the major cause of bacteremic urinary tract infections. Survival in the bloodstream is associated with different mechanisms that help to resist serum complement-mediated killing. While the phenotypic heterogeneity of bacteria has been shown to influence antibiotic tolerance, the possibility that it makes cells refractory to killing by the immune system has not been experimentally tested. In the present study we sought to determine whether the heterogeneity of bacterial cultures is relevant to bacterial targeting by the serum complement system. We monitored cell divisions in the UPEC strain CFT073 with fluorescent reporter protein. Stationary-phase cells were incubated in active or heat-inactivated human serum in the presence or absence of different antibiotics (ampicillin, norfloxacin, and amikacin), and cell division and complement protein C3 binding were measured by flow cytometry and immunofluorescence microscopy. Heterogeneity in the doubling times of CFT073 cells in serum enabled three phenotypically different subpopulations to be distinguished, all of them being recognized by the C3 component of the complement system. The population of rapidly growing cells resists serum complement-mediated lysis. The dominant subpopulation of cells with intermediate growth rate is susceptible to serum. The third population, which does not resume growth upon dilution from stationary phase, is simultaneously protected from serum complement and antibiotics.
Fap2 of Fusobacterium nucleatum Is a Galactose-Inhibitable Adhesin Involved in Coaggregation, Cell Adhesion, and Preterm Birth
Authors: Coppenhagen-Glazer S. , Sol A. , Abed J. , Naor R. , Zhang X. , Han Y. W. , Bachrach G. 
Published: January 2015

ABSTRACTFusobacterium nucleatumis a common oral anaerobe involved in periodontitis that is known to translocate and cause intrauterine infections. In the oral environment,F. nucleatumadheres to a large diversity of species, facilitating their colonization and creating biological bridges that stabilize the multispecies dental biofilm. Many of these interactions (called coadherences or coaggregations) are galactose sensitive. Galactose-sensitive interactions are also involved in the binding ofF. nucleatumto host cells. Hemagglutination of someF. nucleatumstrains is also galactose sensitive, suggesting that a single galactose-sensitive adhesin might mediate the interaction of fusobacteria with many partners and targets. In order to identify the fusobacterial galactose-sensitive adhesin, a system for transposon mutagenesis in fusobacteria was created. The mutant library was screened for hemagglutination deficiency, and three clones were isolated. All three clones were found to harbor the transposon in the gene coding for the Fap2 outer membrane autotransporter. The threefap2mutants failed to show galactose-inhibitable coaggregation withPorphyromonas gingivalisand were defective in cell binding. Afap2mutant also showed a 2-log reduction in murine placental colonization compared to that of the wild type. Our results suggest that Fap2 is a galactose-sensitive hemagglutinin and adhesin that is likely to play a role in the virulence of fusobacteria.
Vibrio cholerae Represses Polysaccharide Synthesis To Promote Motility in Mucosa
Authors: Liu Zhenyu , Wang Yuning , Liu Shengyan , Sheng Ying , Rueggeberg Karl-Gustav , Wang Hui , Li Jie , Gu Frank X. , Zhong Zengtao , Kan Biao , Zhu Jun 
Published: January 2015

ABSTRACT

The viscoelastic mucus layer of gastrointestinal tracts is a host defense barrier that a successful enteric pathogen, such as
Vibrio cholerae
, must circumvent.
V. cholerae
, the causative agent of cholera, is able to penetrate the mucosa and colonize the epithelial surface of the small intestine. In this study, we found that mucin, the major component of mucus, promoted
V. cholerae
movement on semisolid medium and in liquid medium. A genome-wide screen revealed that
Vibrio
polysaccharide (VPS) production was inversely correlated with mucin-enhanced motility. Mucin adhesion assays indicated that VPS bound to mucin. Moreover, we found that
vps
expression was reduced upon exposure to mucin. In an infant mouse colonization model, mutants that overexpressed VPS colonized less effectively than wild-type strains in more distal intestinal regions. These results suggest that
V. cholerae
is able to sense mucosal signals and modulate
vps
expression accordingly so as to promote fast motion in mucus, thus allowing for rapid spread throughout the intestines.
TfoX-Based Genetic Mapping Identifies Vibrio fischeri Strain-Level Differences and Reveals a Common Lineage of Laboratory Strains
Authors: Brooks John F. , Gyllborg Mattias C. , Kocher Acadia A. , Markey Laura E. H. , Mandel Mark J. 
Published: January 2015

ABSTRACT

Bacterial strain variation exists in natural populations of bacteria and can be generated experimentally through directed or random mutation. The advent of rapid and cost-efficient whole-genome sequencing has facilitated strain-level genotyping. Even with modern tools, however, it often remains a challenge to map specific traits to individual genetic loci, especially for traits that cannot be selected under culture conditions (e.g., colonization level or pathogenicity). Using a combination of classical and modern approaches, we analyzed strain-level variation in
Vibrio fischeri
and identified the basis by which some strains lack the ability to utilize glycerol as a carbon source. We proceeded to reconstruct the lineage of the commonly used
V. fischeri
laboratory strains. Compared to the wild-type ES114 strain, we identify in ES114-L a 9.9-kb deletion with endpoints in
tadB2
and
glpF
; restoration of the missing portion of
glpF
restores the wild-type phenotype. The widely used strains ESR1, JRM100, and JRM200 contain the same deletion, and ES114-L is likely a previously unrecognized intermediate strain in the construction of many ES114 derivatives. ES114-L does not exhibit a defect in competitive squid colonization but ESR1 does, demonstrating that glycerol utilization is not required for early squid colonization. Our genetic mapping approach capitalizes on the recently discovered chitin-based transformation pathway, which is conserved in the
Vibrionaceae
; therefore, the specific approach used is likely to be useful for mapping genetic traits in other
Vibrio
species.
A long-term follow-up of residual mass neuroblastoma in a patient with cystic fibrosis
Authors: Naselli Aldo , Cresta Federico , Favilli Federica , Casciaro Rosaria 
Published: January 2015

PurposeTo report a long-term follow-up of a young woman affected by cystic fibrosis (CF) with a residual retroperitoneal mass of neuroblastoma (NBL) after treatment.Case reportWe reviewed the patient's database and analysed a 20-year follow-up by considering pulmonary exacerbation, nutritional condition, pulmonary function (forced expiratory volume in 1 s), microbiological data and residual retroperitoneal mass volume. We observed stable pulmonary and nutritional conditions. No variation was found in the residual retroperitoneal mass volume.DiscussionWe report this case of a patient with CF with previous NBL because such a long time of follow-up of a NBL with a stable retroperitoneal remaining tumour is uncommon and needs to be reported. Multidisciplinary management has been crucial in this case because of the presence of concomitant diseases and consequently, differential diagnosis challenges.
New Strategies in Renal Cell Carcinoma: Targeting the Genetic and Metabolic Basis of Disease
Authors: Srinivasan Ramaprasad , Ricketts Christopher J. , Sourbier Carole , Linehan W. Marston 
Published: January 2015

Abstract
The development of new forms of treatment of advanced renal cell carcinoma over the past two decades has been primarily focused on targeting the VHL/HIF pathway. The recent identification of mutations of chromatin-remodeling genes in clear-cell renal carcinoma (ccRCC), of genomic heterogeneity, and of a Warburg-like metabolic phenotype in advanced disease has had a profound effect on our understanding of the evolution of ccRCC and on potential approaches to personalized therapy. Early approaches to therapy for patients with advanced type I papillary RCC that have centered around the MET/HGF pathway will expand as more genomic information becomes available. Sporadic and familial type II papillary renal cell carcinoma are characterized by enhanced aerobic glycolysis and share an antioxidant response phenotype. In fumarate hydratase–deficient RCC, fumarate-induced succination of KEAP1 activates Nrf2 signaling. CUL3 and Nrf2 mutations as well as an Nrf2 activation phenotype are found in sporadic type II papillary RCC. Therapeutic approaches designed to target the Nrf2 pathway as well as to impair blood flow and glucose delivery in these cancers that are highly dependent on a robust tumor vasculature and on ready availability of glucose for energy production and glycolysis are in development. Clin Cancer Res; 21(1); 10–17. ©2015 AACR.
22q11.2 Deletion Status and Disease Burden in Children and Adolescents With Tetralogy of Fallot
Authors: Mercer-Rosa Laura , Paridon Stephen M. , Fogel Mark A. , Rychik Jack , Tanel Ronn E. , Zhao Huaqing , Zhang Xuemei , Yang Wei , Shults Justine , Goldmuntz Elizabeth 
Published: January 2015

Background—
Patients with repaired tetralogy of Fallot experience variable outcomes for reasons that are incompletely understood. We hypothesize that genetic variants contribute to this variability. We sought to investigate the association of 22q11.2 deletion status with clinical outcome in patients with repaired tetralogy of Fallot.

Methods and Results—

We performed a cross-sectional study of tetralogy of Fallot subjects who were tested for 22q11.2 deletion, and underwent cardiac magnetic resonance, exercise stress test, and review of medical history. We studied 165 subjects (12.3±3.1 years), of which 30 (18%) had 22q11.2 deletion syndrome (22q11.2DS). Overall, by cardiac magnetic resonance the right ventricular ejection fraction was 60±8%, pulmonary regurgitant fraction was 34±17%, and right ventricular end-diastolic volume was 114±39 cc/m
2
. On exercise stress test, maximum oxygen consumption was 76±16% predicted. Despite comparable right ventricular function and pulmonary regurgitant fraction, on exercise stress test the 22q11.2DS had significantly lower percent predicted: forced vital capacity (61.5±16 versus 80.5±14;
P
<0.0001), maximum oxygen consumption (61±17 versus 80±12;
P
<0.0001), and work (64±18 versus 86±22,
P
=0.0002). Similarly, the 22q11.2DS experienced more hospitalizations (6.5 [5–10] versus 3 [2–5];
P
<0.0001), saw more specialists (3.5 [2–9] versus 0 [0–12];
P
<0.0001), and used ≥1 medications (67% versus 34%;
P
<0.001).

Conclusions—
22q11.2DS is associated with restrictive lung disease, worse aerobic capacity, and increased morbidity, and may explain some of the clinical variability seen in tetralogy of Fallot. These findings may provide avenues for intervention to improve outcomes, and should be re-evaluated longitudinally because these associations may become more pronounced with time.