bluuebunny/crossref_metadata_2025_split huggingface dataset:
Revealing insect herbivory‐induced phenolamide metabolism: from single genes to metabolic network plasticity analysis
Authors: Gaquerel Emmanuel , Gulati Jyotasana , Baldwin Ian T. 
Published: March 2014

SummaryThe phenylpropanoid metabolic space comprises a network of interconnected metabolic branches that contribute to the biosynthesis of a large array of compounds with functions in plant development and stress adaptation. During biotic challenges, such as insect attack, a major rewiring of gene networks associated with phenylpropanoid metabolism is observed. This rapid reconfiguration of gene expression allows prioritized production of metabolites that help the plant solve ecological problems. Phenolamides are a group of phenolic derivatives that originate from diversion of hydroxycinnamoyl acids from the main phenylpropanoid pathway after N–acyltransferase‐dependent conjugation to polyamines or aryl monoamines. These structurally diverse metabolites are abundant in the reproductive organs of many plants, and have recently been shown to play roles as induced defenses in vegetative tissues. In the wild tobacco, Nicotiana attenuata, in which herbivory‐induced regulation of these metabolites has been studied, rapid elevations of the levels of phenolamides that function as induced defenses result from a multi‐hormonal signaling network that re‐shapes connected metabolic pathways. In this review, we summarize recent findings in the regulation of phenolamides obtained by mass spectrometry‐based metabolomics profiling, and outline a conceptual framework for gene discovery in this pathway. We also introduce a multifactorial approach that is useful in deciphering metabolic pathway reorganizations among tissues in response to stress.
Review on Combustion Control of Marine Engine by Fuzzy Logic Control Concerning the Air to Fuel Ratio
Authors: Javad Nekooei Mohammad , Jaswar Jaswar , Priyanto A. 
Published: March 2014

This research reviews a close loop control-oriented model, combined with air to fuel ratio, to regulate combustion phasing in a spark- ignition marine engine operation. On the other hand ,Stoichiometric air-to-fuel ratio () control plays a significant role on the three way catalysts in the reduction of exhaust pollutants of the SI marine engine. Air to fuel management for SI marine engines is a major challenge from the control point of view because of the highly nonlinear behavior of this system. For this reason, linear control techniques are unable to provide the required performance, and nonlinear controllers are used instead. Therefore, a fuzzy MIMO Control system is designed for robust control of lambda. As an accurate and control oriented model, an air to fuel ratio model of a Spark Ignition (SI) marine engine is developed to generate simulation data of the engine's subsystems. The Goal of this control is to maintain the A/F ratio at stoichiometry.
Experimental and Numerical Studies of Vortex Induced Vibration on Cylinder
Authors: Mobassher Tofa M. , Maimun Adi , M. Ahmed Yasser , Jamei Saeed , Abyn Hassan 
Published: March 2014

Study of vibrations due to vortex shedding (VIV) in the wake of a cylinder that is exposed to current or oscillatory flow is very important, especially for marine risers which are used to extract oil and gas from the sea bed. The phenomenon of vortex induced vibration (VIV) has been one of the major concerns for hydrodynamic researchers due to its potential ability to cause severe fatigue damage. The hydrodynamics of VIV is very complex and still not fully understood. In this paper, some results (amplitude over diameter, lift and drag coefficients) of high Reynolds VIV experiments that are performed in UTM towing tank with an in-house test set-up are presented. A circular cylinder of 114 mm in diameter and 3 min length was towed at constant speed through the basin at Reynolds numbers up to 1.1x105. Model tests with a stationary cylinder and tests with a freely vibrating cylinder were carried out to investigate the influence of VIV on drag coefficient. Later these results are compared with results obtained through 3D numerical simulation, LES is used to solve turbulence flow. It was found that CFD results showed similar trends with experimental results. Results of this paper can be very important to design riser system and future endeavor to perform similar kind of experiments. Successful numerical study of the VIV can also be fruitful for designing efficient VIV suppression devices.
Mg2+ block properties of triheteromeric GluN1–GluN2B–GluN2D NMDA receptors on neonatal rat substantia nigra pars compacta dopaminergic neurones
Authors: Huang Zhuo , Gibb Alasdair J. 
Published: March 2014

Key points
NMDAR receptors (NMDARs) are tetrameric cation channels permeable to calcium and blocked by Mg2+.
Voltage‐dependent Mg2+ block of NMDARs is crucial to several forms of synaptic plasticity and to the integration of synaptic activity with neuronal activity. Although diheteromeric GluN1–GluN2A or GluN1–GluN2B NMDARs display stronger voltage‐dependent Mg2+ block than GluN1–GluN2C or GluN1–GluN2D NMDARs, the extracellular Mg2+ block properties for triheteromeric NMDARs are still elusive.
Here, we show that in dopaminergic neurones the voltage dependence of Mg2+ block is less steep than previously observed in hippocampus or cortex, consistent with the presence of triheteromeric GluN1–GluN2B–GluN2D NMDARs.
These results may help to understand the role of triheteromeric NMDARs in dopaminergic neurone synaptic plasticity and to inform simulations of dopaminergic neurone physiology.
AbstractNative NMDA receptors (NMDARs) are tetrameric channels formed by two GluN1 and two GluN2 subunits. So far, seven NMDARs subunits have been identified and they can form diheteromeric or triheteromeric NMDARs (more than one type of GluN2 subunit). Extracellular Mg2+ is an important regulator of NMDARs, and particularly the voltage dependence of Mg2+ block is crucial to the roles of NMDARs in synaptic plasticity and the integration of synaptic activity with neuronal activity. Although the Mg2+ block properties of diheteromeric NMDARs are fully investigated, properties of triheteromeric NMDARs are still not clear. Our previous data suggested that dopaminergic neurones expressed triheteromeric GluN1–GluN2B–GluN2D NMDARs. Here, using NMDARs in dopaminergic neurones from postnatal day 7 (P7) rats as a model system, we characterize the voltage‐dependent Mg2+ block properties of triheteromeric NMDARs. In control conditions, external Mg2+ significantly inhibits the whole cell NMDA‐evoked current in a voltage‐dependent manner with IC50 values of 20.9 μm, 53.3 μm and 173 μm at −90 mV, −70 mV and −50 mV, respectively. When the GluN2B‐selective antagonist ifenprodil was applied, the Mg2+ sensitivity of the residual NMDA‐mediated currents (which is mainly carried by GluN1–GluN2B–GluN2D NMDARs) is reduced to IC50 values of 45.9 μm (−90 mV), 104 μm (−70 mV) and 276 μm (−50 mV), suggesting that triheteromeric GluN1–GluN2B–GluN2D NMDARs have less affinity for external Mg2+ than GluN1–GluN2B receptors. In addition, fitting INMDA–V curves with a trapping Mg2+ block model shows the triheteromeric GluN1–GluN2B–GluN2D NMDARs have weaker voltage‐dependent Mg2+ block (δ = 0.56) than GluN1–GluN2B NMDARs. Finally, our concentration jump and single channel recordings suggest that GluN1–GluN2B–GluN2D rather than GluN1–GluN2D NMDARs are present. These data provide information relevant to Mg2+ block characteristics of triheteromeric NMDARs and may help to better understand synaptic plasticity, which is dependent on these triheteromeric NMDARs.
Modulation of ionotropic glutamate receptor function by vertebrate galectins
Authors: Copits Bryan A. , Vernon Claire G. , Sakai Ryuichi , Swanson Geoffrey T. 
Published: March 2014

Key points
Lectins are a family of small evolutionarily conserved sugar‐binding proteins that regulate a diverse array of physiological processes ranging from immune system activation to cancer cell metastasis.
Ionotropic glutamate receptor function can be modulated by plant‐derived lectins, but the physiological relevance of this activity is unclear as no analogous function has been identified in animal lectins.
We found that a variety of vertebrate lectins, including human brain‐expressed galectin‐1, modulated glutamate receptor kinetics in a subunit and lectin‐dependent manner, which critically depended on complex oligosaccharide processing.
Galectin application slowed neuronal kainate receptor currents from nociceptive dorsal root ganglion neurons.
We propose that brain‐expressed galectins are potential endogenous modulators of neuronal glutamate receptors, which may play important roles in diseases of altered cellular excitability, such as epilepsy or chronic pain.
AbstractAMPA and kainate receptors are glutamate‐gated ion channels whose function is known to be altered by a variety of plant oligosaccharide‐binding proteins, or lectins, but the physiological relevance of this activity has been uncertain because no lectins with analogous allosteric modulatory effects have been identified in animals. We report here that members of the prototype galectin family, which are β‐galactoside‐binding lectins, exhibit subunit‐specific allosteric modulation of desensitization of recombinant homomeric and heteromeric AMPA and kainate receptors. Galectin modulation of GluK2 kainate receptors was dependent upon complex oligosaccharide processing of N‐glycosylation sites in the amino‐terminal domain and downstream linker region. The sensitivity of GluA4 AMPA receptors to human galectin‐1 could be enhanced by supplementation of culture media with uridine and N‐acetylglucosamine (GlcNAc), precursors for the hexosamine pathway that supplies UDP‐GlcNAc for synthesis of complex oligosaccharides. Neuronal kainate receptors in dorsal root ganglia were sensitive to galectin modulation, whereas AMPA receptors in cultured hippocampal neurons were insensitive, which could be a reflection of differential N‐glycan processing or receptor subunit selectivity. Because glycan content of integral proteins can be modified dynamically, we postulate that physiological or pathological conditions in the CNS could arise in which galectins alter excitatory neurotransmission or neuronal excitability through their actions on AMPA or kainate receptors.
Comparative Genomic Analysis of KPC-Encoding pKpQIL-Like Plasmids and Their Distribution in New Jersey and New York Hospitals
Authors: Chen Liang , Chavda Kalyan D. , Melano Roberto G. , Jacobs Michael R. , Koll Brian , Hong Tao , Rojtman Albert D. , Levi Michael H. , Bonomo Robert A. , Kreiswirth Barry N. 
Published: March 2014

ABSTRACT

The global spread of
Klebsiella pneumoniae
carbapenemase (KPC) is predominately associated with
K. pneumoniae
strains genotyped as sequence type 258 (ST258). The first ST258-associated plasmid, pKpQIL, was described in Israel in 2006, but its history in the northeastern United States remains unknown. Six pKpQIL-like plasmids from four
K. pneumoniae
isolates (three ST258 and one ST234), one
Escherichia coli
isolate, and one
Enterobacter aerogenes
isolate, collected from 2003 to 2010 in New York (NY) and New Jersey (NJ) hospitals, were completely sequenced. The sequences and overall sizes of the six plasmids are highly similar to those of pKpQIL; the major difference is that five of six NJ/NY strains harbor
bla
KPC-2
, while pKpQIL contains
bla
KPC-3
. Moreover, a 26.7-kb fragment was inverted in pKpQIL-234 (from ST234
K. pneumoniae
), while a 14.5-kb region was deleted in pKpQIL-Ec (from ST131
E. coli
). PCR screening of 284 other clinical
K. pneumoniae
isolates identified 101 (35.6%) harboring pKpQIL-like plasmids from 9 of 10 surveyed hospitals, demonstrating the wide dissemination of pKpQIL in this region of endemicity. Among the positive isolates, 87.1% were typed as ST258 and 88.1% carried
bla
KPC-2
. The finding of pKpQIL-like plasmid in this study from strains that predate the initial report of KPC in Israel provides evidence that pKpQIL may have originated in the United States. Our findings demonstrate that pKpQIL plasmids are both spreading clonally in ST258 strains and spreading horizontally to different sequence types and species, further highlighting the clinical and public health concerns associated with carbapenem resistance.
Characterization of the Proliferating Cell Nuclear Antigen of Leishmania donovani Clinical Isolates and Its Association with Antimony Resistance
Authors: Tandon Rati , Chandra Sharat , Baharia Rajendra Kumar , Das Sanchita , Misra Pragya , Kumar Awanish , Siddiqi Mohammad Imran , Sundar Shyam , Dube Anuradha 
Published: March 2014

ABSTRACTPreviously, through a proteomic analysis, proliferating cell nuclear antigen (PCNA) was found to be overexpressed in the sodium antimony gluconate (SAG)-resistant clinical isolate compared to that in the SAG-sensitive clinical isolate ofLeishmania donovani. The present study was designed to explore the potential role of the PCNA protein in SAG resistance inL. donovani. For this purpose, the protein was cloned, overexpressed, purified, and modeled. Western blot (WB) and real-time PCR (RT-PCR) analyses confirmed that PCNA was overexpressed by ≥3-fold in the log phase, stationary phase, and peanut agglutinin isolated procyclic and metacyclic stages of the promastigote form and by ∼5-fold in the amastigote form of the SAG-resistant isolate compared to that in the SAG-sensitive isolate.L. donovaniPCNA (LdPCNA) was overexpressed as a green fluorescent protein (GFP) fusion protein in a SAG-sensitive clinical isolate ofL. donovani, and modulation of the sensitivities of the transfectants to pentavalent antimonial (SbV) and trivalent antimonial (SbIII) drugs was assessedin vitroagainst promastigotes and intracellular (J774A.1 cell line) amastigotes, respectively. Overexpression of LdPCNA in the SAG-sensitive isolate resulted in an increase in the 50% inhibitory concentrations (IC50) of SbV(from 41.2 ± 0.6 μg/ml to 66.5 ± 3.9 μg/ml) and SbIII(from 24.0 ± 0.3 μg/ml to 43.4 ± 1.8 μg/ml). Moreover, PCNA-overexpressing promastigote transfectants exhibited less DNA fragmentation compared to that of wild-type SAG-sensitive parasites upon SbIIItreatment. In addition, SAG-induced nitric oxide (NO) production was found to be significantly inhibited in the macrophages infected with the transfectants compared with that in wild-type SAG-sensitive parasites. Consequently, we infer that LdPCNA has a significant role in SAG resistance inL. donovaniclinical isolates, which warrants detailed investigations regarding its mechanism.
Population Pharmacokinetics of Rifapentine and Desacetyl Rifapentine in Healthy Volunteers: Nonlinearities in Clearance and Bioavailability
Authors: Savic Radojka M. , Lu Yanhui , Bliven-Sizemore Erin , Weiner Marc , Nuermberger Eric , Burman William , Dorman Susan E. , Dooley Kelly E. 
Published: March 2014

ABSTRACT

Rifapentine is under active investigation as a potent drug that may help shorten the tuberculosis (TB) treatment duration. A previous rifapentine dose escalation study with daily dosing indicated a possible decrease in bioavailability as the dose increased and an increase in clearance over time for rifapentine and its active metabolite, desacetyl rifapentine. This study aimed to assess the effects of increasing doses on rifapentine absorption and bioavailability and to evaluate the clearance changes over 14 days. A population analysis was performed with nonlinear mixed-effects modeling. Absorption, time-varying clearance, bioavailability, and empirical and semimechanistic autoinduction models were investigated. A one-compartment model linked to a transit compartment absorption model best described the data. The bioavailability of rifapentine decreased linearly by 2.5% for each 100-mg increase in dose. The autoinduction model suggested a dose-independent linear increase in clearance of the parent drug and metabolite over time from 1.2 and 3.1 liters · h
−1
, respectively, after a single dose to 2.2 and 5.0 liters · h
−1
, respectively, after 14 once-daily doses, with no plateau being reached by day 14. In clinical trial simulations using the final model, rifapentine demonstrated less-than-dose-proportional pharmacokinetics, but there was no plateau in exposures over the dose range tested (450 to 1,800 mg), and divided dosing increased exposures significantly. Thus, the proposed compartmental model incorporating daily dosing of rifapentine over a wide range of doses and time-related changes in bioavailability and clearance provides a useful tool for estimation of drug exposure that can be used to optimize rifapentine dosing for TB treatment. (This study has been registered at ClinicalTrials.gov under registration no. NCT01162486.)
Quantification of Cell-Associated Atazanavir, Darunavir, Lopinavir, Ritonavir, and Efavirenz Concentrations in Human Mononuclear Cell Extracts
Authors: Podany Anthony T. , Winchester Lee C. , Robbins Brian L. , Fletcher Courtney V. 
Published: March 2014

ABSTRACT
An ultrasensitive assay utilizing high-pressure liquid chromatography and mass spectrometry detection was developed and validated for the quantification of the antiretrovirals atazanavir (ATV), darunavir (DRV), lopinavir (LPV), ritonavir (RTV), and efavirenz (EFV) in human mononuclear cell (MNC) extracts. The assay utilizes 20 μl of cellular extract that contains as few as 50,000 MNCs. The analytical range of the assay is 0.0200 to 10.0 fmol/μl for ATV, 0.0500 to 25.0 fmol/μl for DRV, LPV, and RTV, and 0.200 to 100 fmol/μl for EFV. The assay has proven to be a clinically useful tool for investigating antiretroviral drug concentrations in virologic sanctuaries where harvested cell numbers are extremely low. The assay provides a tool for investigators to explore the clinical pharmacology of strategies for prevention, treatment, and cure in pathophysiologically relevant sites.
Modulation of Alternaria infectoria Cell Wall Chitin and Glucan Synthesis by Cell Wall Synthase Inhibitors
Authors: Fernandes Chantal , Anjos Jorge , Walker Louise A. , Silva Branca M. A. , Cortes Luísa , Mota Marta , Munro Carol A. , Gow Neil A. R. , Gonçalves Teresa 
Published: March 2014

ABSTRACT

The present work reports the effects of caspofungin, a β-1,3-glucan synthase inhibitor, and nikkomycin Z, an inhibitor of chitin synthases, on two strains of
Alternaria infectoria
, a melanized fungus involved in opportunistic human infections and respiratory allergies. One of the strains tested, IMF006, bore phenotypic traits that conferred advantages in resisting antifungal treatment. First, the resting cell wall chitin content was higher and in response to caspofungin, the chitin level remained constant. In the other strain, IMF001, the chitin content increased upon caspofungin treatment to values similar to basal IMF006 levels. Moreover, upon caspofungin treatment, the
FKS1
gene was upregulated in IMF006 and downregulated in IMF001. In addition, the resting β-glucan content was also different in both strains, with higher levels in IMF001 than in IMF006. However, this did not provide any advantage with respect to echinocandin resistance. We identified eight different chitin synthase genes and studied relative gene expression when the fungus was exposed to the antifungals under study. In both strains, exposure to caspofungin and nikkomycin Z led to modulation of the expression of class V and VII chitin synthase genes, suggesting its importance in the robustness of
A. infectoria
. The pattern of
A. infectoria
phagocytosis and activation of murine macrophages by spores was not affected by caspofungin. Monotherapy with nikkomycin Z and caspofungin provided only fungistatic inhibition, while a combination of both led to fungal cell lysis, revealing a strong synergistic action between the chitin synthase inhibitor and the β-glucan synthase inhibitor against this fungus.
2-Aminothiazolones as Anti-HIV Agents That Act as gp120-CD4 Inhibitors
Authors: Tiberi Marika , Tintori Cristina , Ceresola Elisa Rita , Fazi Roberta , Zamperini Claudio , Calandro Pierpaolo , Franchi Luigi , Selvaraj Manikandan , Botta Lorenzo , Sampaolo Michela , Saita Diego , Ferrarese Roberto , Clementi Massimo , Canducci Filippo , Botta Maurizio 
Published: March 2014

ABSTRACT
We report here the synthesis of 2-aminothiazolones along with their biological properties as novel anti-HIV agents. Such compounds have proven to act through the inhibition of the gp120-CD4 protein-protein interaction that occurs at the very early stage of the HIV-1 entry process. No cytotoxicity was found for these compounds, and broad antiviral activities against laboratory strains and pseudotyped viruses were documented. Docking simulations have also been applied to predict the mechanism, at the molecular level, by which the inhibitors were able to interact within the Phe43 cavity of HIV-1 gp120. Furthermore, a preliminary absorption, distribution, metabolism, and excretion (ADME) evaluation was performed. Overall, this study led the basis for the development of more potent HIV entry inhibitors.
Differential Requirement for PBP1a and PBP1b in
In Vivo
and
In Vitro
Fitness of Vibrio cholerae
Authors: Dörr Tobias , Möll Andrea , Chao Michael C. , Cava Felipe , Lam Hubert , Davis Brigid M. , Waldor Matthew K. 
Published: March 2014

ABSTRACT

We investigated the roles of the
Vibrio cholerae
high-molecular-weight bifunctional penicillin binding proteins, PBP1a and PBP1b, in the fitness of this enteric pathogen. Using a screen for synthetic lethality, we found that the
V. cholerae
PBP1a and PBP1b proteins, like their
Escherichia coli
homologues, are each essential in the absence of the other and in the absence of the other's putative activator, the outer membrane lipoproteins LpoA and LpoB, respectively. Comparative analyses of
V. cholerae
mutants suggest that PBP1a/LpoA of
V. cholerae
play a more prominent role in generating and/or maintaining the pathogen's cell wall than PBP1b/LpoB.
V. cholerae
lacking PBP1b or LpoB exhibited wild-type growth under all conditions tested. In contrast,
V. cholerae
lacking PBP1a or LpoA exhibited growth deficiencies in minimal medium, in the presence of deoxycholate and bile, and in competition assays with wild-type cells both
in vitro
and in the infant mouse small intestine. PBP1a pathway mutants are particularly impaired in stationary phase, which renders them sensitive to a product(s) present in supernatants from stationary-phase wild-type cells. The marked competitive defect of the PBP1a pathway mutants
in vivo
was largely absent when exponential-phase cells rather than stationary-phase cells were used to inoculate suckling mice. Thus, at least for
V. cholerae
PBP1a pathway mutants, the growth phase of the inoculum is a key modulator of infectivity.