bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrative genomic analysis identifies a role for intercellular adhesion molecule 1 in childhood asthma
Authors: Klaassen Ester M. M. , van de Kant Kim D. G. , Jöbsis Quirijn , Penders John , van Schooten Frederik Jan , Quaak Marieke , den Hartog Gertjan J. M. , Koppelman Gerard H. , van Schayck Constant P. , van Eys Guillaume , Dompeling Edward 
Published: January 2014

AbstractBackgroundChildhood asthma is characterized by chronic airway inflammation. Integrative genomic analysis of airway inflammation on genetic and protein level may help to unravel mechanisms of childhood asthma. We aimed to employ an integrative genomic approach investigating inflammation markers on DNA, mRNA, and protein level at preschool age in relationship to asthma development.MethodsIn a prospective study, 252 preschool children (202 recurrent wheezers, 50 controls) from the Asthma DEtection and Monitoring (ADEM) study were followed until the age of six. Genetic variants, mRNA expression in peripheral blood mononuclear cells, and protein levels in exhaled breath condensate for intercellular adhesion molecule 1 (ICAM1), interleukin (IL)4, IL8, IL10, IL13, and tumor necrosis factor α were analyzed at preschool age. At six years of age, a classification (healthy, transient wheeze, or asthma) was based on symptoms, lung function, and medication use.ResultsThe ICAM1 rs5498 A allele was positively associated with asthma development (p = 0.02) and ICAM1 gene expression (p = 0.01). ICAM1 gene expression was positively associated with exhaled levels of soluble ICAM1 (p = 0.04) which in turn was positively associated with asthma development (p = 0.01). Furthermore, rs1800872 and rs1800896 in IL10 were associated with altered IL10 mRNA expression (p < 0.01). Exhaled levels of IL4, IL10, and IL13 were positively associated with asthma development (p < 0.01).ConclusionsIn this unique prospective study, we demonstrated that ICAM1 is associated with asthma development on DNA, mRNA, and protein level. Thus, ICAM1 is likely to be involved in the development of childhood asthma.
Reactive oxygen species in signalling the transcriptional activation of WIPK expression in tobacco
Authors: XU JUAN , YANG KWANG‐YEOL , YOO SEUNG JIN , LIU YIDONG , REN DONGTAO , ZHANG SHUQUN 
Published: January 2014

AbstractPlant mitogen‐activated protein kinases represented by tobacco WIPK (wounding‐induced protein kinase) and its orthologs in other species are unique in their regulation at transcriptional level in response to stress and pathogen infection. We previously demonstrated that transcriptional activation of WIPK is essential for induced WIPK activity, and activation of salicylic acid‐induced protein kinase (SIPK) by the constitutively active NtMEK2DD is sufficient to induce WIPK gene expression. Here, we report that the effect of SIPK on WIPK gene expression is mediated by reactive oxygen species (ROS). Using a combination of pharmacological and gain‐of‐function transgenic approaches, we studied the relationship among SIPK activation, WIPK gene activation in response to fungal cryptogein, light‐dependent ROS generation in chloroplasts, and ROS generated via NADPH oxidase. In the conditional gain‐of‐function GVG‐NtMEK2DD transgenic tobacco, induction of WIPK expression is dependent on the ROS generation in chloroplasts. Consistently, methyl viologen, an inducer of ROS generation in chloroplasts, highly activated WIPK expression. In addition to chloroplast‐originated ROS, H2O2 generated from the cell‐surface NADPH oxidase could also activate WIPK gene expression, and inhibition of cryptogein‐induced ROS generation also abolished WIPK gene activation. Our data demonstrate that WIPK gene activation is mediated by ROS, which provides a mechanism by which ROS influence cellular signalling processes in plant stress/defence response.
Tuberculosis management time: an alternative parameter for measuring the tuberculosis infectious pool
Authors: Yimer Solomon A. , Holm‐Hansen Carol , Storla Dag G. , Bjune Gunnar A. 
Published: January 2014

AbstractObjectiveTo demonstrate the application of TB management time as an alternative parameter to estimate the size of the tuberculosis infectious pool in West Gojjam Zone of Amhara Region, Ethiopia.MethodsIn this study, we used the TB management time, i.e. the number of days from start of cough until start of treatment, to determine the infectious period. Patients with sputum smear‐positive and smear‐negative pulmonary TB, retreatment and an estimated number of undetected cases were included. The infectious pool was then estimated as the annual number of infectious person days in a defined population.ResultsThe TB management time of presently undiagnosed TB cases and sputum smear‐positive patients contributed significantly to the infectious pool with 151 840 and 128 750 infectious person days per year, respectively. The total infectious pool including sputum smear‐negative TB cases and retreatment patients in the study area was estimated at 325 410 person days or 15 447 person days per 100 000 population during the study year.ConclusionRecording TB management time may be used to estimate the infectious pool of TB and to monitor programme performance in the community.
The alien flora of Albania: history, current status and future trends
Authors: Barina Z , Rakaj M , Somogyi G , Erős‐Honti Z , Pifkó D 
Published: January 2014

SummaryThe first synthesis of the alien flora of Albania is presented here. In order to be able to compare with other published studies, the categories of the aliens are described using widely accepted terms. However, additional terms are also introduced in the text. Altogether, 196 alien species occur outside cultivation, including 81 naturalised and 16 partly naturalised weeds, 11 remnants of the former cultivation, nine old and 38 new casuals, 41 presumably extinct aliens and no invasives. Some authors regarded 25 native species incorrectly as aliens and nine alien species were erroneously documented as members of the Albanian flora. The changes of the alien flora of Albania differ considerably from that of most European countries, and the actual proportion of aliens in the Albanian flora is the lowest in Europe. The low number of aliens, the lack of invasives and the relatively low frequency of aliens in Albania are the consequences of the long‐term seclusion of the country during the 20th century, and the low level of economic development, the extended land use and also the fact that aliens have been present only for quite a short time in the flora. All recent social and economic changes facilitate the establishment and spread of aliens in the country, especially in the lowlands.
Short‐term hypoxic vasodilation in vivo is mediated by bioactive nitric oxide metabolites, rather than free nitric oxide derived from haemoglobin‐mediated nitrite reduction
Authors: Umbrello Michele , Dyson Alex , Pinto Bernardo Bollen , Fernandez Bernadette O. , Simon Verena , Feelisch Martin , Singer Mervyn 
Published: January 2014

Key points
Hypoxia increases blood flow through vasodilation, an adaptive response that increases oxygen availability to tissues.
This response is probably mediated by nitric oxide (NO); different mechanisms have been postulated (increased de novo synthesis, release from preformed stores, reduced inactivation), but precise mechanisms remain controversial.
In a short‐term rodent model, hypoxaemia was associated with hypotension and lower plasma nitrite levels suggestive of nitrite bioactivation; this was only partially reversed by NO synthase inhibition. Administration of sodium nitrite produced marked vasodilation and increased nitrosylation. Scavenging of NO had little effect.
Early hypoxic vasodilation is mediated by a complex interaction of multiple NO‐related species, rather than by NO from haemoglobin‐mediated reduction of nitrite per se.
NO and its metabolites play a pivotal role in the body's initial adaptation to an acute decrease in oxygen supply, probably offering protection against a supply–demand mismatch.
AbstractLocal increases in blood flow – ‘hypoxic vasodilation’ – confer cellular protection in the face of reduced oxygen delivery. The physiological relevance of this response is well established, yet ongoing controversy surrounds its underlying mechanisms. We sought to confirm that early hypoxic vasodilation is a nitric oxide (NO)‐mediated phenomenon and to study putative pathways for increased levels of NO, namely production from NO synthases, intravascular nitrite reduction, release from preformed stores and reduced deactivation by cytochrome c oxidase. Experiments were performed on spontaneously breathing, anaesthetized, male Wistar rats undergoing short‐term systemic hypoxaemia, who received pharmacological inhibitors and activators of the various NO pathways. Arterial blood pressure, cardiac output, tissue oxygen tension and the circulating pool of NO metabolites (oxidation, nitrosation and nitrosylation products) were measured in plasma and erythrocytes. Hypoxaemia caused a rapid and sustained vasodilation, which was only partially reversed by non‐selective NO synthase inhibition. This was associated with significantly lower plasma nitrite, and marginally elevated nitrate levels, suggestive of nitrite bioinactivation. Administration of sodium nitrite had little effect in normoxia, but produced significant vasodilation and increased nitrosylation during hypoxaemia that could not be reversed by NO scavenging. Methodological issues prevented assessment of the contribution, if any, of reduced deactivation of NO by cytochrome c oxidase. In conclusion, acute hypoxic vasodilation is an adaptive NO‐mediated response conferred through bioactive metabolites rather than free NO from haemoglobin‐mediated reduction of nitrite.
Consequences of peripheral chemoreflex inhibition with low‐dose dopamine in humans
Authors: Niewinski Piotr , Tubek Stanislaw , Banasiak Waldemar , Paton Julian F. R. , Ponikowski Piotr 
Published: January 2014

Key points
Low‐dose dopamine reduces the ventilatory response to acute hypoxia both in animal and in human studies.
In this study we show that low‐dose dopamine also attenuates the haemodynamic responses (tachycardia, hypertension) to acute hypoxia in healthy humans.
Moreover, we found that dopamine withdrawal results in a temporary increase in minute ventilation.
The magnitude of the increase in minute ventilation after dopamine withdrawal correlates with the degree of ventilatory response to acute hypoxia and depends on the duration of dopamine administration.
Dopamine may provide a novel method for assessing differences in the level of peripheral chemoreceptor activity, which has important clinical implications given the recently reported pathological role of the carotid body in cardiovascular diseases in animals and humans.
AbstractLow‐dose dopamine inhibits peripheral chemoreceptors and attenuates the hypoxic ventilatory response (HVR) in humans. However, it is unknown: (1) whether it also modulates the haemodynamic reactions to acute hypoxia, (2) whether it also modulates cardiac baroreflex sensitivity (BRS) and (3) if there is any effect of dopamine withdrawal. We performed a double‐blind, placebo‐controlled study on 11 healthy male volunteers. At sea level over 2 days every subject was administered low‐dose dopamine (2 μg kg–1 min–1) or saline infusion, during which we assessed both ventilatory and haemodynamic responses to acute hypoxia. Separately, we evaluated effects of initiation and withdrawal of each infusion and BRS. The initiation of dopamine infusion did not affect minute ventilation (MV) or mean blood pressure (MAP), but increased both heart rate (HR) and cardiac output. Concomitantly, it decreased systemic vascular resistance. Dopamine blunted the ventilatory, MAP and HR reactions (hypertension, tachycardia) to acute hypoxia. Dopamine attenuated cardiac BRS to falling blood pressure. Dopamine withdrawal evoked an increase in MV. The magnitude of the increment in MV due to dopamine withdrawal correlated with the size of the HVR and depended on the duration of dopamine administration. The ventilatory reaction to dopamine withdrawal constitutes a novel index of peripheral chemoreceptor function.
Evaluation of Double- and Triple-Antibiotic Combinations for VIM- and NDM-Producing Klebsiella pneumoniae by
In Vitro
Time-Kill Experiments
Authors: Tängdén T. , Hickman R. A. , Forsberg P. , Lagerbäck P. , Giske C. G. , Cars O. 
Published: January 2014

ABSTRACT

Combination therapy is recommended for infections with carbapenemase-producing
Klebsiella pneumoniae
. However, limited data exist on which antibiotic combinations are the most effective. The aim of this study was to find effective antibiotic combinations against metallo-beta-lactamase-producing
K. pneumoniae
(MBL-KP). Two VIM- and two NDM-producing
K. pneumoniae
strains, all susceptible to colistin, were exposed to antibiotics at clinically relevant static concentrations during 24-h time-kill experiments. Double- and triple-antibiotic combinations of aztreonam, ciprofloxacin, colistin, daptomycin, fosfomycin, meropenem, rifampin, telavancin, tigecycline, and vancomycin were used. Synergy was defined as a ≥2 log
10
decrease in CFU/ml between the combination and its most active drug after 24 h, and bactericidal effect was defined as a ≥3 log
10
decrease in CFU/ml after 24 h compared with the starting inoculum. Synergistic or bactericidal activity was demonstrated for aztreonam, fosfomycin, meropenem, and rifampin in double-antibiotic combinations with colistin and also for aztreonam, fosfomycin, and rifampin in triple-antibiotic combinations with meropenem and colistin. Overall, the combination of rifampin-meropenem-colistin was the most effective regimen, demonstrating synergistic and bactericidal effects against all four strains. Meropenem-colistin, meropenem-fosfomycin, and tigecycline-colistin combinations were not bactericidal against the strains used. The findings of this and other studies indicate that there is great potential of antibiotic combinations against carbapenemase-producing
K. pneumoniae
. However, our results deviate to some extent from those of previous studies, which might be because most studies to date have included KPC-producing rather than MBL-producing strains. More studies addressing MBL-KP are needed.
In Vivo
Antibacterial Activity of MRX-I, a New Oxazolidinone
Authors: Li Cong-Ran , Zhai Qian-Qian , Wang Xiu-Kun , Hu Xin-Xin , Li Guo-Qing , Zhang Wei-Xin , Pang Jing , Lu Xi , Yuan Hong , Gordeev Mikhail Fedorovich , Chen Le-Tian , Yang Xin-Yi , You Xue-Fu 
Published: January 2014

ABSTRACT

MRX-I is a potent oxazolidinone antibiotic against Gram-positive pathogens, including methicillin-resistant
Staphylococcus aureus
(MRSA), penicillin-resistant
Streptococcus pneumoniae
(PRSP), penicillin-intermediate
S. pneumoniae
(PISP), and vancomycin-resistant enterococci (VRE). In this study, the
in vivo
efficacy of orally administered MRX-I was evaluated using linezolid as a comparator. MRX-I showed the same or better efficacy than linezolid in both systemic and local infection models against the tested strains.
Macrophage Reporter Cell Assay for Screening Immunopharmacological Activity of Cell Wall-Active Antifungals
Authors: Lewis Russell E. , Liao Guangling , Young Katherine , Douglas Cameron , Kontoyiannis Dimitrios P. 
Published: January 2014

ABSTRACT

Antifungal exposure can elicit immunological effects that contribute to activity
in vivo
, but this activity is rarely screened
in vitro
in a fashion analogous to MIC testing. We used RAW 264.7 murine macrophages that express a secreted embryonic alkaline phosphatase (SEAP) gene induced by transcriptional activation of NF-κB and activator protein 1 (AP-1) to develop a screen for immunopharmacological activity of cell wall-active antifungal agents. Isolates of
Candida albicans
and
Aspergillus fumigatus
that conditionally express genes involved in cell wall synthesis were also tested with the reporter macrophages. We found that growth of fungi in subinhibitory concentrations of glucan synthesis inhibitors (caspofungin and enfumafungin A) or repression of the β-glucan catalytic subunit of glucan synthase,
FKS1
, increased macrophage NF-κB/AP-1 activation in a dectin-1-dependent manner. This pattern of activation was also transiently observed with repression of chitin synthesis in
C. albicans
or when yeast cells were incubated in low concentrations of the chitin synthesis inhibitor nikkomycin Z.
Extensive Variation and Rapid Shift of the MG192 Sequence in Mycoplasma genitalium Strains from Patients with Chronic Infection
Authors: Ma Liang , Mancuso Miriam , Williams James A. , Van Der Pol Barbara , Fortenberry J. Dennis , Jia Qiuyao , Myers Leann , Martin David H. 
Published: January 2014

ABSTRACT

Mycoplasma genitalium
causes persistent urogenital tract infection in humans. Antigenic variation of the protein encoded by the MG192 gene has been proposed as one of the mechanisms for persistence. The aims of this study were to determine MG192 sequence variation in patients with chronic
M. genitalium
infection and to analyze the sequence structural features of the MG192 gene and its encoded protein. Urogenital specimens were obtained from 13 patients who were followed for 10 days to 14 months. The variable region of the MG192 gene was PCR amplified, subcloned into plasmids, and sequenced. Sequence analysis of 220 plasmid clones yielded 97 unique MG192 variant sequences. MG192 sequence shift was identified between sequential specimens from all but one patient. Despite great variation of the MG192 gene among and within clinical specimens from different patients, MG192 sequences were more related within
M. genitalium
specimens from an individual patient than between patients. The MG192 variable region consisted of 11 discrete subvariable regions with different degrees of variability. Analysis of the two most variable regions (V4 and V6) in five sequential specimens from one patient showed that sequence changes increased over time and that most sequences were present at only one time point, suggesting immune selection. Topology analysis of the deduced MG192 protein predicted a surface-exposed membrane protein. Extensive variation of the MG192 sequence may not only change the antigenicity of the protein to allow immune evasion but also alter the mobility and adhesion ability of the organism to adapt to diverse host microenvironments, thus facilitating persistent infection.
NUMERICAL INVESTIGATION OF BIFURCATIONS AND TRANSITIONS OF JOSEPHSON VORTICES IN INHOMOGENEOUS JUNCTIONS
Authors: SEMERDJIEVA E. G. , TODOROV M. D. 
Published: January 2014

We consider in-line and overlap geometry models of Josephson junctions with point or rectangular inhomogeneity and investigate the effect of their location on the Josephson vortices and the current. We analyze numerically the critical dependencies "current-magnetic field" caused by one- and two-point current injections. The obtained results elucidate the relation between these critical curves and the fractions of the injection current at the ends of the junction. We also find out similarities between the exponentially shaped junctions, and those with inhomogeneity at the end when a two-point current injection is present. We juxtapose the critical curves of the distinct junctions with inner inhomogeneity and discuss the similarity between them and the Josephson junctions with phase shifts. The transitions of Josephson junctions from a superconducting mode to a resistive one as bifurcations of the static solutions of appropriately posed multiparametric compound boundary- and eigenvalue problems are interpreted and solved using the continuous analog of Newton method.
Gene Mutations Versus Clinically Relevant Phenotypes
Authors: Niemann Markus , Rolfs Arndt , Störk Stefan , Bijnens Bart , Breunig Frank , Beer Meinrad , Ertl Georg , Wanner Christoph , Weidemann Frank 
Published: January 2014

Background—
Currently, no method is available to identify α-galactosidase A (agalA) mutations determining clinically relevant Fabry disease. In our largest European Fabry cohort, we investigated whether a biomarker, specific for the defect, could stratify persons at risk.

Methods and Results—
A total of 124 individuals with agalA mutations were investigated with a comprehensive clinical workup, genetic analysis, and laboratory testing, including measurements of agalA activity and lyso-Gb3 (degradation product of the accumulating Gb3). Additionally, an extensive family screening with a clinical workup of relatives was performed. The patient population was divided into 2 samples: previously described mutations (n=72) and novel mutations (n=52). The patients with previously described mutations were subdivided into 2 groups: classical mutations, which were known to cause the classic type of Fabry disease with specific symptoms and a high risk for major events in all 3 main organs (heart, kidney, and central nervous system), and atypical mutations without the typical presentation. All patients with atypical mutations (n=17) had lower lyso-Gb3 levels than any of the patients with classical Fabry disease (n=55). A cutoff value of 2.7 ng/mL separated the 2 groups. Six out of 52 patients with novel mutations showed a lyso-Gb3 level <2.7 ng/mL. Clinical investigation, blinded to lyso-Gb3 results, revealed no classic organ involvement in these patients or their relatives. In contrast, the characterization of patients with lyso-Gb3≥2.7ng/mL suggested classical Fabry mutations in most of the patients (93%).

Conclusions—
Our data show that the biomarker lyso-Gb3 may identify the clinically relevant agalA mutations leading to Fabry disease.
Analysis of Circulating Cholesterol Levels as a Mediator of an Association Between ABO Blood Group and Coronary Heart Disease
Authors: Chen Yequn , Chen Chang , Ke Xiayi , Xiong Longgen , Shi Yongying , Li Jiafu , Tan Xuerui , Ye Shu 
Published: January 2014

Background—
Non-O type of ABO blood group has been associated with a predisposition to coronary heart disease. It is thought that this association is partly mediated by increased cholesterol levels in non–O-type individuals. In this study, we sought to estimate the mediation effect size.

Methods and Results—

In a group of individuals (n=6476) undergoing coronary angiography, we detected associations of non-O type with significant coronary artery disease with >50% stenosis in ≥1 coronary arteries (odds ratio, 1.24; 95% confidence interval, 1.10–1.39;
P
=2.6×10
−4
) and with prevalent or incident myocardial infarction (odds ratio, 1.22; 95% confidence interval, 1.09–1.37;
P
=1.2×10
−3
). Subjects of non-O type had higher levels of total cholesterol, low-density lipoprotein cholesterol, and non–high-density lipoprotein cholesterol (mean [SEM] in mmol/L: 4.931[0.021], 3.041 [0.018], and 3.805 [0.020] in non-O type compared with 4.778 [0.026], 2.906 [0.021], and 3.669 [0.024] in O type;
P
=3.8×10
−7
,
P
=1.5×10
−7
, and
P
=3.1×10
−7
, respectively). Mediation analyses indicated that 10% of the effect of non-O type on coronary artery disease susceptibility was mediated by increased low-density lipoprotein cholesterol level (
P
=7.8×10
−4
) and that 11% of the effect of non-O type on myocardial infarction risk was mediated by raised low-density lipoprotein cholesterol level (
P
=2.0×10
−3
).

Conclusions—
In a model in which it is presumed that cholesterol is a mediator of the associations of ABO group with coronary artery disease and myocardial infarction, around 10% of the effect of non-O type on coronary artery disease and myocardial infarction susceptibility was mediated by its influence on low-density lipoprotein cholesterol level.