bluuebunny/crossref_metadata_2025 huggingface dataset:
Determinants of platelet count are different in patients with compensated and decompensated cirrhosis
Authors: Latorre Raquel , Vaquero Javier , Rincón Diego , Puerto Marta , Ponce María D. , Sarnago Fernando , Matamoros Jose A. , Ramón Enrique , Elizaga Jaime , Bañares Rafael , Ripoll Cristina
Published: July 2015

Background & Aims

Different mechanisms including portal hypertension and hypersplenism have been involved in the development of thrombocytopenia in cirrhosis. However, the relative contribution of each one is unknown. The aim was to evaluate simultaneously different mechanisms that determine platelet count in cirrhosis.

Methods

Cross‐sectional study including cirrhotics (n = 120) with hepatic venous pressure gradient (HVPG) measurement. Samples were obtained from peripheral (P) veins to evaluate thrombopoietin (TPO), stem cell factor, hepatocyte growth factor (HGF), tumour necrosis factor, interleukin‐(IL6) and (IL11) and from hepatic (H) veins to evaluate TPO. A subgroup (n = 72) had spleen volume estimation. H and P‐TPO were also measured in non‐cirrhotic patients (n = 15).

Results

Patients (Child A: 55, B: 43, C: 22) had a median platelet count of 81 000/mm3 (IQR 60 500, 110 750), which correlated with spleen volume (r = −0.38, P < 0.001). Platelets were associated also to HVPG (r = −0.47, P = 0.004) and P‐TPO (r = 0.31, P = 0.050) only in compensated patients. H‐TPO decreased, and the proportion of patients with P‐TPO > H‐TPO increased, with the presence and the severity of liver disease. H‐TPO was correlated with liver function (bilirubin r = −0.350, P < 0.001 and international normalized ratio r = −0.227, P = 0.011). Patients with H‐TPO < P‐TPO had higher levels of IL‐11 and HGF.

Conclusion

Platelet count in cirrhosis is associated mainly to spleen volume, although portal hypertension as estimated by HVPG and liver function plays a significant role in compensated patients. H‐TPO and the proportion of patients with P‐TPO > H‐TPO were associated to the presence and severity of liver disease.
Efficacy and Adherence of Flexibly Adding on a Second Antimuscarinic Agent for Patients with Refractory Overactive Bladder
Authors: WANG Chung‐Cheng , JIANG Yuan‐Hong , KUO Hann‐Chorng
Published: July 2015

Objectives

To evaluate the efficacy and adverse events (AE) of flexibly adding on oxybutynin ER in patients with overactive bladder (OAB) refractory to monotherapy with the first muscarinic antagonist.

Methods

A total of 129 patients with refractory OAB were enrolled in a prospective, open‐label protocol. Inclusion criteria were persistent symptoms or partial response to 3‐month behavioral therapy and an optimized dose of one antimuscarinic agent. At baseline, weeks 4, and 12 after the oxybutynin ER (5–15 mg once a day) was flexibly added, we assessed the OAB symptom indexes and Patient Perception of Bladder Condition, uroflowmetry, and post‐void residual, along with the therapeutic effect, AE, and tolerability. Patients continuing combined antimuscarinic therapy were followed up to 12 months.

Results

Compared with baseline, all OAB symptom indexes significantly decreased at all visits. A total of 32 (24.8%) and 25 (19.4%) patients reported successful therapeutic effect at weeks 4 and 12, respectively. Twenty‐four (18.6%) and 44 (34.1%) patients discontinued therapy at weeks 4 and 12, respectively. Only 31 (24.0%) patients continued the combined medication for up to 12 months. Discontinuation of the combined medication was noted in 28 (21.7%) patients due to AE and in 70 (54.3%) due to lack of efficacy.

Conclusions

Flexibly adding on a second antimuscarinic agent is effective and safe for only some OAB patients dissatisfied with the first antimuscarinic treatment in the short‐term period. The patients' dropout rate is high and the long‐term efficacy of the combination of two antimuscarinic agents is limited.
An Investigation of Lower Urinary Tract Symptoms in Women Aged 40 and Over
Authors: SEVER Neziha , OSKAY Umran
Published: July 2015

Objective

The objective of this study was to determine lower urinary tract symptoms (LUTS) and associated risk factors in women aged 40 years and over.

Methods

The study was carried out with a total of 312 women. The data were collected between 1 January 2009 and 30 July 2010. As research instruments, an interview form of 19 questions that questioned personal characteristics and was developed by researchers, and the Bristol Female Lower Urinary Tract Symptoms (BFLUTS) Questionnaire evaluating lower urinary tract symptoms were used. Linear regression analysis was used to detect associated risk factors.

Results

The rates of urgency, urinary incontinence, nocturia, and frequency symptoms were 61.5, 52.2, 18.9, and 25%, respectively. BFLUTS total scores increased with age, but the present study has detected no statistically significant differences (P > 0.05). BFLUTS scores of the women demonstrated statistically significant differences according to several risk factors including menopause status (P = 0.03), presence of chronic illness (P = 0.000), medicine use (P = 0.000), recurrent urinary tract infections (P = 0.000), body mass index (BMI) (P = 0.004), delivery number (P = 0.005) and chronic constipation (P = 0.002). Multiple linear regression analysis determined that frequent urinary tract infections, presence of chronic illness, chronic constipation, BMI and number of deliveries were significantly related to LUTS development.

Conclusion

The most common LUTS was urgency in women aged 40 years and older. Recurrent urinary tract infection was determined as the most significant risk factor for LUTS, followed by chronic illness, chronic constipation, higher BMI and parity.
CdiA promotes receptor‐independent intercellular adhesion
Authors: Ruhe Zachary C. , Townsley Loni , Wallace Adam B. , King Andrew , Van der Woude Marjan W. , Low David A. , Yildiz Fitnat H. , Hayes Christopher S.
Published: July 2015

CdiB/CdiA proteins mediate inter‐bacterial competition in a process termed contact‐dependent growth inhibition (CDI). Filamentous CdiA exoproteins extend from CDI+ cells and bind specific receptors to deliver toxins into susceptible target bacteria. CDI has also been implicated in auto‐aggregation and biofilm formation in several species, but the contribution of CdiA–receptor interactions to these multi‐cellular behaviors has not been examined. Using Escherichia coli isolate EC93 as a model, we show that cdiA and bamA receptor mutants are defective in biofilm formation, suggesting a prominent role for CdiA–BamA mediated cell–cell adhesion. However, CdiA also promotes auto‐aggregation in a BamA‐independent manner, indicating that the exoprotein possesses an additional adhesin activity. Cells must express CdiA in order to participate in BamA‐independent aggregates, suggesting that adhesion could be mediated by homotypic CdiA–CdiA interactions. The BamA‐dependent and BamA‐independent interaction domains map to distinct regions within the CdiA filament. Thus, CdiA orchestrates a collective behavior that is independent of its growth‐inhibition activity. This adhesion should enable ‘greenbeard’ discrimination, in which genetically unrelated individuals cooperate with one another based on a single shared trait. This kind‐selective social behavior could provide immediate fitness benefits to bacteria that acquire the systems through horizontal gene transfer.
Bacillithiol has a role in Fe–S cluster biogenesis in Staphylococcus aureus
Authors: Rosario‐Cruz Zuelay , Chahal Harsimranjit K. , Mike Laura A. , Skaar Eric P. , Boyd Jeffrey M.
Published: July 2015

Staphylococcus aureus does not produce the low‐molecular‐weight (LMW) thiol glutathione, but it does produce the LMW thiol bacillithiol (BSH). To better understand the roles that BSH plays in staphylococcal metabolism, we constructed and examined strains lacking BSH. Phenotypic analysis found that the BSH‐deficient strains cultured either aerobically or anaerobically had growth defects that were alleviated by the addition of exogenous iron (Fe) or the amino acids leucine and isoleucine. The activities of the iron–sulfur (Fe–S) cluster‐dependent enzymes LeuCD and IlvD, which are required for the biosynthesis of leucine and isoleucine, were decreased in strains lacking BSH. The BSH‐deficient cells also had decreased aconitase and glutamate synthase activities, suggesting a general defect in Fe–S cluster biogenesis. The phenotypes of the BSH‐deficient strains were exacerbated in strains lacking the Fe–S cluster carrier Nfu and partially suppressed by multicopy expression of either sufA or nfu, suggesting functional overlap between BSH and Fe–S carrier proteins. Biochemical analysis found that SufA bound and transferred Fe–S clusters to apo‐aconitase, verifying that it serves as an Fe–S cluster carrier. The results presented are consistent with the hypothesis that BSH has roles in Fe homeostasis and the carriage of Fe–S clusters to apo‐proteins in S. aureus.
Palaeoproxies: botanical monitors and recorders of atmospheric change
Authors: Lomax Barry H. , Fraser Wesley T.
Published: July 2015

The integration of plant and Earth sciences offers the opportunity to develop and test palaeobotanical monitors and recorders (palaeoproxies) of past atmospheric change that are understood from a mechanistic perspective, with the underpinning responses being identified and understood at the genetic level. This review highlights how this approach has been used to deliver two distinct palaeoproxies. The first is based on the negative relationship between stomata (breathing pores found on the leaf surface) and atmospheric CO2 concentration; the second is based on tracking chemical changes seen in the composition of pollen and spores to reconstruct changes in the flux of UV‐B radiation on the Earth's surface and from this infer changes in stratospheric processes linked to the eruption and emplacement of Large Igneous Provinces. Here, we highlight the potential of integrating a new rapid, inexpensive chemical analysis technique with existing, robust palynological methods, opening the door to a deeper understanding of past environments via the palaeobiological record. A look to the future suggests a combined solar radiation–CO2 concentration approach could be readily applied across the geological record.
Influence of body size on fecundity and sperm management in the parasitoid wasp Anisopteromalus calandrae
Authors: Kasamatsu Eiichi , Abe Jun
Published: July 2015

A large body size is considered to be advantageous to the reproductive success of females as a result of several factors, such as the allocation of more resources to reproduction and the efficient management of sperm transferred by males. In the present study, the effects of female body size, female mating status and additional food availability on fecundity and the offspring sex ratio are investigated in the parasitoid wasp Anisopteromalus calandrae Howard (Hymenoptera: Pteromalidae). Because of haplodiploid sex determination, females must fertilize eggs to produce female offspring but not to produce male offspring. As predicted, female fecundity and the number of female offspring are positively correlated with body size. However, although the volume of the spermatheca increases with female body size, the amount of sperm stored in the spermatheca is relatively constant, irrespective of body size. Consequently, larger females produce a greater proportion of male offspring, especially at the end of the oviposition sequence, suggesting that larger females that possess more resources for reproduction and produce a larger number of offspring are more likely to suffer sperm depletion. The results of the present study also show that mated females have an increased fecundity compared with virgin females, although the opportunity to feed on honey along with host feeding has no impact upon fecundity or the sex ratio.
Effectiveness of antibacterial prophylaxis with non‐absorbable polymyxin B compared to levofloxacin after allogeneic hematopoietic stem cell transplantation
Authors: Koh S. , Yamada K. , Nishimoto M. , Hayashi Y. , Koh H. , Nakashima Y. , Nakane T. , Hirose A. , Nakamae M. , Kakeya H. , Hino M. , Nakamae H.
Published: July 2015

Background

Fluoroquinolones are widely used for antibacterial prophylaxis during neutropenia following hematopoietic stem cell transplantation (HSCT). Nevertheless, data are inadequate as to whether fluoroquinolones decrease mortality rate compared with other antibiotics.

Methods

We retrospectively compared the efficacy of antibacterial prophylaxis using non‐absorbable polymyxin B (PB) (n = 106) or systemic levofloxacin (LVFX) (n = 140) after allogeneic SCT at our institute between 2004 and 2013.

Results

No significant difference was observed between the 2 groups in the cumulative incidences of failure of prophylaxis (P = 0.21), clinically documented infections (P = 0.70), or non‐relapse mortality within the first 100 days after transplantation (P = 0.42). With bacteremia, the rate of resistance to LVFX was 82% in the PB group and 100% in the LVFX group (P = 0.41). Also, no significant difference was found in overall survival between the 2 groups (P = 0.78).

Conclusion

Our results indicate no difference in the effectiveness of antibacterial prophylaxis between systemic antibiotic LVFX and non‐absorbable antibiotic PB.
Trade Liberalisation and Capital Spending by US Manufacturers
Authors: Liebman Benjamin H. , Reynolds Kara M.
Published: July 2015

This is the first paper to study the impact of long‐term tariff reductions on capital spending by US manufacturers. We investigate fluctuations in investment for approximately 400 different four‐digit industries during the period 1974–2005. Our results indicate that the dismantling of tariff and quota protection has had a stimulatory effect on US manufacturing investment, despite the relatively low average tariff rate that existed at the start of our sample period. However, our findings reveal that reductions in input tariffs rather than output tariffs were the source of this effect, suggesting that better access to foreign inputs rather than increased foreign competition at the output level served as the primary stimulus for increased US manufacturing investment.
Capacity Limitation Control of Multiple Bi-directional DC-DC Converters for Micro Grid Application
Authors: Chiang S. J. , Liao Yu-Min , Liu Ke-Chih
Published: July 2015

The micro grid system requires battery for energy storage and power management. In which, the bi-directional DC to DC converter is the key component for maintaining the DC bus voltage and controlling the charge and discharge of the battery with or without grid support. Parallel control of multiple DC to DC converters is a critical technique to enlarge the power capacity. This paper presents two capacity limitation control methods that multiple DC to DC converters can be paralleled with distributed battery banks. The first method is the capacity limitation control with cascaded load current sense needing no control interconnection. The second method is the capacity limitation control with master-slave and cascaded current command limitation. Two methods are presented to solve the limitation of droop control method and active current sharing method respectively, and can be extended without converter number limitation theoretically. Three prototype 240W bidirectional half-bridge DC to DC converters are built and paralleled in this paper. The proposed method is confirmed with some measured results.
Sensory initiation of a co‐ordinated motor response: synaptic excitation underlying simple decision‐making
Authors: Buhl Edgar , Soffe Stephen R. , Roberts Alan
Published: July 2015

Key points

Deciding whether or how to initiate a motor response to a stimulus can be surprisingly slow and the underlying processes are not well understood.

The neuronal circuitry that allows frog tadpoles to swim in response to touch is well characterized and includes excitatory reticulospinal neurons that drive swim circuit neurons.

Build‐up of excitation to reticulospinal neurons is the key decision‐making step for swimming. Asymmetry in this build‐up between the two sides allows bilateral initiation at the same time as avoiding inappropriate co‐activation of motor antagonists.

Following stronger stimuli, reticulospinal neurons are excited through a trigeminal nucleus pathway and swimming starts first on the stimulated side. If this pathway fails or is lesioned, swimming starts later on the unstimulated side.

The mechanisms underlying initiation of a simple tadpole motor response may share similarities with more complex decisions in other animals, including humans.

Animals take time to make co‐ordinated motor responses to a stimulus. How can sensory input initiate organized movements, activating all necessary elements at the same time as avoiding inappropriate co‐excitation of antagonistic muscles? In vertebrates, this process usually results in the activation of reticulospinal pathways. Young Xenopus tadpoles can respond to head‐skin touch by swimming, which may start on either side. We investigate how motor networks in the brain are organized, and whether asymmetries in touch sensory pathways avoid co‐activation of antagonists at the same time as producing co‐ordinated movements. We record from key reticulospinal neurons in the network controlling swimming. When the head skin is stimulated unilaterally, excitation builds up slowly and asymmetrically in these neurons such that those on both sides do not fire synchronously. This build‐up of excitation to threshold is the key decision‐making step and determines whether swimming will start, as well as on which side. In response to stronger stimuli, the stimulated side tends to ‘win’ because excitation from a shorter, trigeminal nucleus pathway becomes reliable and can initiate swimming earlier on the stimulated side. When this pathway fails or is lesioned, swimming starts later and on the unstimulated side. Stochasticity in the trigeminal nucleus pathway allows unpredictable turning behaviour to weaker stimuli, conferring potential survival benefits. We locate the longer, commissural sensory pathway carrying excitation to the unstimulated side and record from its neurons. These neurons fire to head‐skin stimuli but excite reticulospinal neurons indirectly. We propose that asymmetries in the sensory pathways exciting brainstem reticulospinal neurons ensure alternating and co‐ordinated swimming activity from the start.
Reliability Analysis of Repairable System With Multiple Fault Modes Based on Goal-Oriented Methodology
Authors: Yi Xiao-Jian , Shi Jian , Dong Hai-Ping , Lai Yue-Hua
Published: July 2015

This paper provides a new goal-oriented (GO) method for reliability analysis of repairable systems with multiple fault modes. First, formulas of operators describing components with multiple fault modes are derived based on Markov process theory. Second, qualitative reliability analysis of such a system is conducted by combining the existing GO method with the Fussell–Vesely method. Third, this new method is applied in reliability analysis of a hydraulic transmission oil supply system. Finally, comparing the study results with fault tree analysis (FTA) and Monte Carlo simulation shows that this new GO method is suitable for reliability analysis of repairable systems with multiple fault modes.
Current Progress in Developing Subunit Vaccines against Enterotoxigenic Escherichia coli-Associated Diarrhea
Authors: Zhang Weiping , Sack David A.
Published: July 2015

Diarrhea continues to be a leading cause of death in children <5 years of age, and enterotoxigenic
Escherichia coli
(ETEC) is the most common bacterial cause of children's diarrhea. Currently, there are no available vaccines against ETEC-associated diarrhea. Whole-cell vaccine candidates have been under development but require further improvements because they provide inadequate protection and produce unwanted adverse effects. Meanwhile, a newer approach using polypeptide or subunit vaccine candidates focusing on ETEC colonization factor antigens (CFAs) and enterotoxins, the major virulence determinants of ETEC diarrhea, shows substantial promise. A conservative CFA/I adhesin tip antigen and a CFA MEFA (multiepitope fusion antigen) were shown to induce cross-reactive antiadhesin antibodies that protected against adherence by multiple important CFAs. Genetic fusion of toxoids derived from ETEC heat-labile toxin (LT) and heat-stable toxin (STa) induced antibodies neutralizing both enterotoxins. Moreover, CFA-toxoid MEFA polypeptides, generated by fusing CFA MEFA to an STa-LT toxoid fusion, induced antiadhesin antibodies that broadly inhibited adherence of the seven most important ETEC CFAs associated with about 80% of the diarrhea cases caused by ETEC strains with known CFAs. This same antigen preparation also induced antitoxin antibodies that neutralized both toxins that are associated with all cases of ETEC diarrhea. Results from these studies suggest that polypeptide or subunit vaccines have the potential to effectively protect against ETEC diarrhea. In addition, novel adhesins and mucin proteases have been investigated as potential alternatives or, more likely, additional antigens for ETEC subunit vaccine development.
Contribution of Reduced Interleukin-10 Levels to the Pathogenesis of Osteomyelitis in Children with Sickle Cell Disease
Authors: Sarray Sameh , Almawi Wassim Y.
Published: July 2015

Osteomyelitis is a significant complication of sickle cell disease (SCD), and several factors contribute to its pathogenesis, including altered expression of proinflammatory and anti-inflammatory cytokines. In view of the role of interleukin-10 (IL-10) as an anti-inflammatory cytokine, we tested the notion that SCD osteomyelitis is associated with a reduction in IL-10 secretion and, hence, precipitation of a proinflammatory state. Study subjects comprised 52 SCD patients with confirmed diagnosis of osteomyelitis and 165 age- and gender-matched SCD patients with negative histories of osteomyelitis. Results obtained showed that IL-10 serum levels in SCD osteomyelitis patients were significantly lower than those of control SCD patients. Receiver operating characteristic (ROC) analysis demonstrated that altered IL-10 serum levels predicted the development of osteomyelitis, and the mean area under ROC curves of IL-10 was 0.810 among SCD patients with osteomyelitis. A systematic shift in IL-10 serum levels toward lower values was seen in osteomyelitis cases, with an increased osteomyelitis risk associated with decreased IL-10 levels. Multivariate logistic regression analyses confirmed the independent association of reduced IL-10 with osteomyelitis after controlling for sickle hemoglobin (HbS), fetal hemoglobin (HbF), platelet count, and white blood cell (WBC) count. These data support the strong association of decreased IL-10 levels with osteomyelitis, thereby supporting a role for IL-10 in osteomyelitis follow-up.
The Carbomer-Lecithin Adjuvant Adjuplex Has Potent Immunoactivating Properties and Elicits Protective Adaptive Immunity against Influenza Virus Challenge in Mice
Authors: Wegmann Frank , Moghaddam Amin E. , Schiffner Torben , Gartlan Kate H. , Powell Timothy J. , Russell Rebecca A. , Baart Matthijs , Carrow Emily W. , Sattentau Quentin J.
Published: July 2015

The continued discovery and development of adjuvants for vaccine formulation are important to safely increase potency and/or reduce the antigen doses of existing vaccines and tailor the adaptive immune response to newly developed vaccines. Adjuplex is a novel adjuvant platform based on a purified lecithin and carbomer homopolymer. Here, we analyzed the adjuvant activity of Adjuplex in mice for the soluble hemagglutinin (HA) glycoprotein of influenza A virus. The titration of Adjuplex revealed an optimal dose of 1% for immunogenicity, eliciting high titers of HA-specific IgG but inducing no significant weight loss. At this dose, Adjuplex completely protected mice from an otherwise lethal influenza virus challenge and was at least as effective as the adjuvants monophosphoryl lipid A (MPL) and alum in preventing disease. Adjuplex elicited balanced Th1-/Th2-type immune responses with accompanying cytokines and triggered antigen-specific CD8
+
T-cell proliferation. The use of the peritoneal inflammation model revealed that Adjuplex recruited dendritic cells (DCs), monocytes, and neutrophils in the context of innate cytokine and chemokine secretion. Adjuplex neither triggered classical maturation of DCs nor activated a pathogen recognition receptor (PRR)-expressing NF-κB reporter cell line, suggesting a mechanism of action different from that reported for classical pathogen-associated molecular pattern (PAMP)-activated innate immunity. Taken together, these data reveal Adjuplex to be a potent and well-tolerated adjuvant with application for subunit vaccines.
Mycoplasma hominis, a Rare but True Cause of Infective Endocarditis
Authors: Gagneux-Brunon Amandine , Grattard Florence , Morel Jerome , Suy Florence , Fuzellier Jean-François , Verhoeven Paul , Cazorla Celine , Guglielminotti Claire , Fresard Anne , Lucht Frederic , Botelho-Nevers Elisabeth
Published: July 2015

Mycoplasma spp. are rarely recognized agents of infective endocarditis. We report a case of
Mycoplasma hominis
prosthetic valve endocarditis diagnosed by 16S ribosomal DNA (rDNA) PCR and culture of valves in a 74-year-old man. We reviewed the literature and found only 8 other cases reported.
Characterization of Third-Generation-Cephalosporin-Resistant Shiga Toxin-Producing Strains of Escherichia coli O157:H7 in Japan
Authors: Kawahara Ryuji , Seto Kazuko , Taguchi Masumi , Nakajima Chie , Kumeda Yuko , Suzuki Yasuhiko
Published: July 2015

We isolated Shiga toxin-producingEscherichia coliO157:H7 strains resistant to third-generation cephalosporins. The resistant strains harboredblaCMY-2, a plasmid-mediated AmpC β-lactamase. Genotyping of isolates revealed the possible spread of this problematic bacterium. Results suggested the importance of the investigation and surveillance of enterobacteria with plasmids harboringblaCMY-2.
Use of Alignment-Free Phylogenetics for Rapid Genome Sequence-Based Typing of Helicobacter pylori Virulence Markers and Antibiotic Susceptibility
Authors: van Vliet Arnoud H. M. , Kusters Johannes G.
Published: July 2015

Whole-genome sequencing is becoming a leading technology in the typing and epidemiology of microbial pathogens, but the increase in genomic information necessitates significant investment in bioinformatic resources and expertise, and currently used methodologies struggle with genetically heterogeneous bacteria such as the human gastric pathogen
Helicobacter pylori
. Here we demonstrate that the alignment-free analysis method feature frequency profiling (FFP) can be used to rapidly construct phylogenetic trees of draft bacterial genome sequences on a standard desktop computer and that coupling with
in silico
genotyping methods gives useful information for comparative and clinical genomic and molecular epidemiology applications. FFP-based phylogenetic trees of seven gastric
Helicobacter
species matched those obtained by analysis of 16S rRNA genes and ribosomal proteins, and FFP- and core genome single nucleotide polymorphism-based analysis of 63
H. pylori
genomes again showed comparable phylogenetic clustering, consistent with genomotypes assigned by using multilocus sequence typing (MLST). Analysis of 377
H. pylori
genomes highlighted the conservation of genomotypes and linkage with phylogeographic characteristics and predicted the presence of an incomplete or nonfunctional
cag
pathogenicity island in 18/276 genomes.
In silico
analysis of antibiotic susceptibility markers suggests that most
H. pylori
hspAmerind and hspEAsia isolates are predicted to carry the T
2812
C mutation potentially conferring low-level clarithromycin resistance, while levels of metronidazole resistance were similar in all multilocus sequence types. In conclusion, the use of FFP phylogenetic clustering and
in silico
genotyping allows determination of genome evolution and phylogeographic clustering and can contribute to clinical microbiology by genomotyping for outbreak management and the prediction of pathogenic potential and antibiotic susceptibility.
Impact of Mutations at Amino Acid 70 in Hepatitis C Virus (HCV) Genotype 1b Core Region on Hepatocarcinogenesis following Eradication of HCV RNA
Authors: Akuta Norio , Suzuki Fumitaka , Kobayashi Masahiro , Sezaki Hitomi , Kawamura Yusuke , Hosaka Tetsuya , Kobayashi Mariko , Saitoh Satoshi , Suzuki Yoshiyuki , Arase Yasuji , Ikeda Kenji , Kumada Hiromitsu
Published: July 2015

The impact of the HCV genotype 1b core amino acid (aa) 70 mutant on the cumulative rate of hepatocellular carcinoma following eradication of HCV RNA by antiviral therapy was investigated with the Q-Invader assay. Multivariate analysis based on 649 patients indicated that a core aa70 Q-Invader mutant level ≥20% is a predictor of hepatocellular carcinoma.
Comparison of Three Commercial Molecular Assays for Detection of Rifampin and Isoniazid Resistance among Mycobacterium tuberculosis Isolates in a High-HIV-Prevalence Setting
Authors: Strydom K. , Ismail F. , Matabane M. M. Z. , Onwuegbuna O. , Omar S. V. , Ismail N.
Published: July 2015

In a head-to-head comparison of the MTBDR
plus
version 2.0 (Hain Lifescience), the Xpert MTB/RIF (Cepheid), and the Anyplex MTB/NTM (Seegene) assays, we demonstrated equal sensitivity (59/61; 96.7%) and specificity (53/54; 98.1%) for detecting rifampin resistance with further analysis of discordances. The Xpert assay does not detect isoniazid resistance while the Anyplex assay showed high false positivity.
Evolution of Influenza B Virus in Kuala Lumpur, Malaysia, between 1995 and 2008
Authors: Sam I-Ching , Su Yvonne C. F. , Chan Yoke Fun , Nor'E Siti Sarah , Hassan Ardalinah , Jafar Faizatul Lela , Joseph Udayan , Halpin Rebecca A. , Ghedin Elodie , Hooi Poh Sim , Fourment Mathieu , Hassan Hamimah , AbuBakar Sazaly , Wentworth David E. , Smith Gavin J. D.
Published: July 2015

Influenza B virus causes significant disease but remains understudied in tropical regions. We sequenced 72 influenza B viruses collected in Kuala Lumpur, Malaysia, from 1995 to 2008. The predominant circulating lineage (Victoria or Yamagata) changed every 1 to 3 years, and these shifts were associated with increased incidence of influenza B. We also found poor lineage matches with recommended influenza virus vaccine strains. While most influenza B virus lineages in Malaysia were short-lived, one circulated for 3 to 4 years.
Exploring the Balance between DNA Pressure and Capsid Stability in Herpesviruses and Phages
Authors: Bauer D. W. , Li D. , Huffman J. , Homa F. L. , Wilson K. , Leavitt J. C. , Casjens S. R. , Baines J. , Evilevitch A.
Published: July 2015

We have recently shown in both herpesviruses and phages that packaged viral DNA creates a pressure of tens of atmospheres pushing against the interior capsid wall. For the first time, using differential scanning microcalorimetry, we directly measured the energy powering the release of pressurized DNA from the capsid. Furthermore, using a new calorimetric assay to accurately determine the temperature inducing DNA release, we found a direct influence of internal DNA pressure on the stability of the viral particle. We show that the balance of forces between the DNA pressure and capsid strength, required for DNA retention between rounds of infection, is conserved between evolutionarily diverse bacterial viruses (phages λ and P22), as well as a eukaryotic virus, human herpes simplex 1 (HSV-1). Our data also suggest that the portal vertex in these viruses is the weakest point in the overall capsid structure and presents the Achilles heel of the virus's stability. Comparison between these viral systems shows that viruses with higher DNA packing density (resulting in higher capsid pressure) have inherently stronger capsid structures, preventing spontaneous genome release prior to infection. This force balance is of key importance for viral survival and replication. Investigating the ways to disrupt this balance can lead to development of new mutation-resistant antivirals.

IMPORTANCE
A virus can generally be described as a nucleic acid genome contained within a protective protein shell, called the capsid. For many double-stranded DNA viruses, confinement of the large DNA molecule within the small protein capsid results in an energetically stressed DNA state exerting tens of atmospheres of pressures on the inner capsid wall. We show that stability of viral particles (which directly relates to infectivity) is strongly influenced by the state of the packaged genome. Using scanning calorimetry on a bacterial virus (phage λ) as an experimental model system, we investigated the thermodynamics of genome release associated with destabilizing the viral particle. Furthermore, we compare the influence of tight genome confinement on the relative stability for diverse bacterial and eukaryotic viruses. These comparisons reveal an evolutionarily conserved force balance between the capsid stability and the density of the packaged genome.
P2X1 Receptor Antagonists Inhibit HIV-1 Fusion by Blocking Virus-Coreceptor Interactions
Authors: Giroud Charline , Marin Mariana , Hammonds Jason , Spearman Paul , Melikyan Gregory B.
Published: July 2015

HIV-1 Env glycoprotein-mediated fusion is initiated upon sequential binding of Env to CD4 and the coreceptor CXCR4 or CCR5. Whereas these interactions are thought to be necessary and sufficient to promote HIV-1 fusion, other host factors can modulate this process. Previous studies reported potent inhibition of HIV-1 fusion by selective P2X1 receptor antagonists, including NF279, and suggested that these receptors play a role in HIV-1 entry. Here we investigated the mechanism of antiviral activity of NF279 and found that this compound does not inhibit HIV-1 fusion by preventing the activation of P2X1 channels but effectively blocks the binding of the virus to CXCR4 or CCR5. The notion of an off-target effect of NF279 on HIV-1 fusion is supported by the lack of detectable expression of P2X1 receptors in cells used in fusion experiments and by the fact that the addition of ATP or the enzymatic depletion of ATP in culture medium does not modulate viral fusion. Importantly, NF279 fails to inhibit HIV-1 fusion with cell lines and primary macrophages when added at an intermediate stage downstream of Env-CD4-coreceptor engagement. Conversely, in the presence of NF279, HIV-1 fusion is arrested downstream of CD4 binding but prior to coreceptor engagement. NF279 also antagonizes the signaling function of CCR5, CXCR4, and another chemokine receptor, as evidenced by the suppression of calcium responses elicited by specific ligands and by recombinant gp120. Collectively, our results demonstrate that NF279 is a dual HIV-1 coreceptor inhibitor that interferes with the functional engagement of CCR5 and CXCR4 by Env.

IMPORTANCE
Inhibition of P2X receptor activity suppresses HIV-1 fusion and replication, suggesting that P2X signaling is involved in HIV-1 entry. However, mechanistic experiments conducted in this study imply that P2X1 receptor is not expressed in target cells or involved in viral fusion. Instead, we found that inhibition of HIV-1 fusion by a specific P2X1 receptor antagonist, NF279, is due to the blocking of virus interactions with both the CXCR4 and CCR5 coreceptors. The ability of NF279 to abrogate cellular calcium signaling induced by the respective chemokines showed that this compound acts as a dual-coreceptor antagonist. P2X1 receptor antagonists could thus represent a new class of dual-coreceptor inhibitors with a structure and a mechanism of action that are distinct from those of known HIV-1 coreceptor antagonists.
A Coronavirus E Protein Is Present in Two Distinct Pools with Different Effects on Assembly and the Secretory Pathway
Authors: Westerbeck Jason W. , Machamer Carolyn E.
Published: July 2015

Coronaviruses (CoVs) assemble by budding into the lumen of the early Golgi complex prior to exocytosis. The small CoV envelope (E) protein plays roles in assembly, virion release, and pathogenesis. CoV E has a single hydrophobic domain (HD), is targeted to Golgi complex membranes, and has cation channel activity
in vitro
. However, the precise functions of the CoV E protein during infection are still enigmatic. Structural data for the severe acute respiratory syndrome (SARS)-CoV E protein suggest that it assembles into a homopentamer. Specific residues in the HD regulate the ion-conducting pore formed by SARS-CoV E in artificial bilayers and the pathogenicity of the virus during infection. The E protein from the avian infectious bronchitis virus (IBV) has dramatic effects on the secretory system which require residues in the HD. Here, we use the known structural data from SARS-CoV E to infer the residues important for ion channel activity and the oligomerization of IBV E. We present biochemical data for the formation of two distinct oligomeric pools of IBV E in transfected and infected cells and the residues required for their formation. A high-order oligomer of IBV E is required for the production of virus-like particles (VLPs), implicating this form of the protein in virion assembly. Additionally, disruption of the secretory pathway by IBV E correlates with a form that is likely monomeric, suggesting that the effects on the secretory pathway are independent of E ion channel activity.

IMPORTANCE
CoVs are important human pathogens with significant zoonotic potential, as demonstrated by the emergence of SARS-CoV and Middle East respiratory syndrome (MERS)-CoV. Progress has been made toward identifying potential vaccine candidates in mouse models of CoV infection, including the use of attenuated viruses that lack the CoV E protein or express E-protein mutants. However, no approved vaccines or antiviral therapeutics exist. We previously reported that the hydrophobic domain of the IBV E protein, a putative viroporin, causes disruption of the mammalian secretory pathway when exogenously expressed in cells. Understanding the mechanism of this disruption could lead to the identification of novel antiviral therapeutics. Here, we present biochemical evidence for two distinct oligomeric forms of IBV E, one essential for assembly and the other with a role in disruption of the secretory pathway. Discovery of two forms of CoV E protein will provide additional targets for antiviral therapeutics.
Plasmids from
Euryarchaeota
Authors: Forterre Patrick , Krupovic Mart , Raymann Kasie , Soler Nicolas
Published: July 2015

Many plasmids have been described in
Euryarchaeota
, one of the three major archaeal phyla, most of them in salt-loving haloarchaea and hyperthermophilic
Thermococcales
. These plasmids resemble bacterial plasmids in terms of size (from small plasmids encoding only one gene up to large megaplasmids) and replication mechanisms (rolling circle or theta). Some of them are related to viral genomes and form a more or less continuous sequence space including many integrated elements. Plasmids from
Euryarchaeota
have been useful for designing efficient genetic tools for these microorganisms. In addition, they have also been used to probe the topological state of plasmids in species with or without DNA gyrase and/or reverse gyrase. Plasmids from
Euryarchaeota
encode both DNA replication proteins recruited from their hosts and novel families of DNA replication proteins.
Euryarchaeota
form an interesting playground to test evolutionary hypotheses on the origin and evolution of viruses and plasmids, since a robust phylogeny is available for this phylum. Preliminary studies have shown that for different plasmid families, plasmids share a common gene pool and coevolve with their hosts. They are involved in gene transfer, mostly between plasmids and viruses present in closely related species, but rarely between cells from distantly related archaeal lineages. With few exceptions (e.g., plasmids carrying gas vesicle genes), most archaeal plasmids seem to be cryptic. Interestingly, plasmids and viral genomes have been detected in extracellular membrane vesicles produced by
Thermococcales
, suggesting that these vesicles could be involved in the transfer of viruses and plasmids between cells.
Plasmid-Encoded Iron Uptake Systems
Authors: Di Lorenzo Manuela , Stork Michiel
Published: July 2015

Plasmids confer genetic information that benefits the bacterial cells containing them. In pathogenic bacteria, plasmids often harbor virulence determinants that enhance the pathogenicity of the bacterium. The ability to acquire iron in environments where it is limited, for instance the eukaryotic host, is a critical factor for bacterial growth. To acquire iron, bacteria have evolved specific iron uptake mechanisms. These systems are often chromosomally encoded, while those that are plasmid-encoded are rare. Two main plasmid types, ColV and pJM1, have been shown to harbor determinants that increase virulence by providing the cell with essential iron for growth. It is clear that these two plasmid groups evolved independently from each other since they do not share similarities either in the plasmid backbones or in the iron uptake systems they harbor. The siderophores aerobactin and salmochelin that are found on ColV plasmids fall in the hydroxamate and catechol group, respectively, whereas both functional groups are present in the anguibactin siderophore, the only iron uptake system found on pJM1-type plasmids. Besides siderophore-mediated iron uptake, ColV plasmids carry additional genes involved in iron metabolism. These systems include ABC transporters, hemolysins, and a hemoglobin protease. ColV- and pJM1-like plasmids have been shown to confer virulence to their bacterial host, and this trait can be completely ascribed to their encoded iron uptake systems.
The Hidden World within Plants: Ecological and Evolutionary Considerations for Defining Functioning of Microbial Endophytes
Authors: Hardoim Pablo R. , van Overbeek Leonard S. , Berg Gabriele , Pirttilä Anna Maria , Compant Stéphane , Campisano Andrea , Döring Matthias , Sessitsch Angela
Published: July 2015

All plants are inhabited internally by diverse microbial communities comprising bacterial, archaeal, fungal, and protistic taxa. These microorganisms showing endophytic lifestyles play crucial roles in plant development, growth, fitness, and diversification. The increasing awareness of and information on endophytes provide insight into the complexity of the plant microbiome. The nature of plant-endophyte interactions ranges from mutualism to pathogenicity. This depends on a set of abiotic and biotic factors, including the genotypes of plants and microbes, environmental conditions, and the dynamic network of interactions within the plant biome. In this review, we address the concept of endophytism, considering the latest insights into evolution, plant ecosystem functioning, and multipartite interactions.
Immediate procedural outcomes in 44 consecutive Pipeline Flex cases: the first North American single-center series
Authors: Colby Geoffrey P , Lin Li-Mei , Caplan Justin M , Jiang Bowen , Huang Judy , Tamargo Rafael J , Coon Alexander L
Published: July 2015

Background

Flow diversion is an established technique for treatment of cerebral aneurysms. The Pipeline embolization device (PED) is the only FDA-approved flow diverting stent in the USA. A second-generation device, PED Flex, has recently been released with modifications to the delivery system. Published reports of experience with this new device are limited.

Objective

To describe the initial outcomes from the first North American series using the PED Flex—a single-center experience of 44 cases.

Methods

All patients consecutively treated with the PED Flex embolization device from February 2015 through April 2015 were included in the study. Data were collected for patient demographics, aneurysm characteristics, technical procedural details, and early outcomes.

Results

PED Flex treatment was attempted in 42 patients (mean 56.6±2.0 years) with 44 aneurysms (mean size 6.5±0.6 mm), 41/44 (93%) of which were anterior circulation and 3/44 (7%) were posterior circulation. PED Flex was successfully implanted in 43/44 cases (98%). A single device was used in 41/43 cases (95%), with a mean of 1.07±0.05 devices implanted per case. Resheathing was performed in 4/44 cases (9%). Mean postprocedure hospital length of stay was 1.3±0.2 days. One significant neurological complication (2.3%) occurred, which was a stroke in a patient non-compliant with the prescribed antiplatelet regimen.

Conclusions

Pipeline Flex is a second-generation flow diverter with enhanced features compared with the first-generation PED. These modifications allow for more reliable deployment with continued improvements in procedural safety.
The normal Jacobi operator of real hypersurfaces in complex hyperbolic two-plane Grassmannians
Authors: Panagiotidou Konstantina , De Dios Pérez Juan
Published: July 2015

The aim of this paper is to introduce the notion of normal Jacobi operator of real hypersurfaces in complex hyperbolic two-plane Grassmannians. Furthermore, results concerning real hypersurfaces in complex hyperbolic two-plane Grassmannians whose normal Jacobi operator satisfies conditions of parallelism will be given.
Anti-Obesity Effects of the Mixture ofEriobotrya japonicaandNelumbo nuciferain Adipocytes and High-Fat Diet-Induced Obese Mice
Authors: Sharma Bhesh Raj , Oh Jin , Kim Hyeon-A , Kim Yong Jae , Jeong Kyu-Shik , Rhyu Dong Young
Published: July 2015

The present study is to evaluate the anti-obesity effects of Eriobotrya japonica (EJ), Nelumbo nucifera (NN), and their mixture (MIX, 1:1 ratio) in 3T3-L1 adipocytes and high-fat diet-induced obese mice. The treatment of EJ, NN, and MIX in 3T3-L1 adipocytes effectively inhibited lipid accumulation, significantly decreased expression of peroxisome proliferator-activated receptor gamma (PPARγ), sterol regulatory element binding protein (SREBP1c), and adipocyte lipid-binding protein (aP2), and significantly increased phosphorylation of AMP-activated protein kinase (AMPK). Moreover, oral treatment of MIX showed stronger effects than individual treatment. C57BL/6J mice (6 week old) were divided into two groups; low fat diet (LFD) containing 10% calories from fat and high fat diet (HFD) containing 60% calories from fat. The HFD groups were further divided into five subgroups; treated with distilled water (HFD), treated with 400 mg/kg EJ (EJ400), treated with 400 mg/kg NN (NN400), treated with 200 mg/kg MIX (MIX200), and treated with 400 mg/kg MIX (MIX400) during 13 weeks. In our results, the administration of EJ, NN, and MIX significantly decreased body weight (BW), fat weight, liver weight, hepatic triglyceride (TG) and total cholesterol (TC), lipid droplets in the liver, food efficacy ratio, and the plasma TG, TC, glucose, insulin, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in a dose-dependent manner, and MIX treatment showed stronger effect than their individual treatments. Similarly, MIX treatment decreased the expression of PPARγ, SREBP-1c, FAS, and ACC more strongly in the adipose tissue than single treatments. In conclusion, the MIX of EJ and NN extract may strongly regulate BW gain than EJ or NN alone, and its anti-obesity effect is associated with the control of lipid metabolism, including adipogenesis and lipogenesis.