bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of α,β-Unsaturated Ketones as Antileishmanial Agents
Authors: Vasquez Miguel A. , Iniguez Eva , Das Umashankar , Beverley Stephen M. , Herrera Linda J. , Dimmock Jonathan R. , Maldonado Rosa A. 
Published: March 2015

ABSTRACT

In this study, we assessed the antileishmanial activity of 126 α,β-unsaturated ketones. The compounds NC901, NC884, and NC2459 showed high leishmanicidal activity for both the extracellular (50% effective concentration [EC
50
], 456 nM, 1,122 nM, and 20 nM, respectively) and intracellular (EC
50
, 1,870 nM, 937 nM, and 625 nM, respectively) forms of
Leishmania major
propagated in macrophages, with little or no toxicity to mammalian cells. Bioluminescent imaging of parasite replication showed that all three compounds reduced the parasite burden in the murine model, with no apparent toxicity.
High Prevalence of
bla
NDM-1
Carbapenemase-Encoding Gene and 16S rRNA
armA
Methyltransferase Gene among Acinetobacter baumannii Clinical Isolates in Egypt
Authors: El-Sayed-Ahmed Mohamed Abd El-Gawad , Amin Magdy Ali , Tawakol Wael Mustafa , Loucif Lotfi , Bakour Sofiane , Rolain Jean-Marc 
Published: March 2015

ABSTRACT

The main objective of this study was to decipher the molecular mechanism of resistance to carbapenems and aminoglycosides in a large series of 150
Acinetobacter baumannii
clinical isolates collected from July 2012 to September 2013 in Egypt. We report for the first time the emergence of
bla
NDM-1
and the cooccurrence of 16S rRNA methylase
armA
with
bla
NDM-1
and
bla
OXA-23
in Egyptian hospitals. Multilocus sequence typing identified 27 distinct sequence types, 11 of which were novel.
In Vitro
Fungicidal Activities of Anidulafungin, Caspofungin, and Micafungin against Candida glabrata, Candida bracarensis, and Candida nivariensis Evaluated by Time-Kill Studies
Authors: Gil-Alonso Sandra , Jauregizar Nerea , Cantón Emilia , Eraso Elena , Quindós Guillermo 
Published: March 2015

ABSTRACT

Anidulafungin, caspofungin, and micafungin killing activities against
Candida glabrata
,
Candida bracarensis
, and
Candida nivariensis
were evaluated by the time-kill methodology. The concentrations assayed were 0.06, 0.125, and 0.5 μg/ml, which are achieved in serum. Anidulafungin and micafungin required between 13 and 26 h to reach the fungicidal endpoint (99.9% killing) against
C. glabrata
and
C. bracarensis
. All echinocandins were less active against
C. nivariensis
.
Influence of
ABCC2
and
ABCC4
Polymorphisms on Tenofovir Plasma Concentrations in Thai HIV-Infected Patients
Authors: Rungtivasuwan Kanokrat , Avihingsanon Anchalee , Thammajaruk Narukjaporn , Mitruk Siwaporn , Burger David M. , Ruxrungtham Kiat , Punyawudho Baralee , Pengsuparp Thitima 
Published: March 2015

ABSTRACT

Tenofovir (TFV) is eliminated by renal excretion, which is mediated through multidrug-resistant protein 2 (MRP2) and MRP4, encoded by
ABCC2
and
ABCC4
, respectively. Genetic polymorphisms of these transporters may affect the plasma concentrations of tenofovir. Therefore, the aim of this study was to investigate the influence of genetic and nongenetic factors on tenofovir plasma concentrations. A cross-sectional study was performed in Thai HIV-infected patients aged ≥18 years who had been receiving tenofovir disoproxil fumarate at 300 mg once daily for at least 6 months. A middose tenofovir plasma concentration was obtained. Multivariate analysis was performed to investigate whether there was an association between tenofovir plasma concentrations and demographic data, including age, sex, body weight, estimated glomerular filtration rate (eGFR), hepatitis B virus coinfection, hepatitis C virus coinfection, duration of tenofovir treatment, concomitant use of ritonavir-boosted protease inhibitors, and polymorphisms of
ABCC2
and
ABCC4
. A total of 150 Thai HIV-infected patients were included. The mean age of the patients was 43.9 ± 7.2 years. The mean tenofovir plasma concentration was 100.3 ± 52.7 ng/ml. In multivariate analysis, a low body weight, a low eGFR, the concomitant use of ritonavir-boosted protease inhibitors, and the
ABCC4
4131T → G variation (genotype TG or GG) were independently associated with higher tenofovir plasma concentrations. After adjusting for weight, eGFR, and the concomitant use of ritonavir-boosted protease inhibitors, a 30% increase in the mean tenofovir plasma concentration was observed in patients having the
ABCC4
4131 TG or GG genotype. Both genetic and nongenetic factors affect tenofovir plasma concentrations. These factors should be considered when adjusting tenofovir dosage regimens to ensure the efficacy and safety of a drug. (This study has been registered at ClinicalTrials.gov under registration no. NCT01138241.)
Pharmacokinetics of a Novel Sublingual Spray Formulation of the Antimalarial Drug Artemether in African Children with Malaria
Authors: Salman Sam , Bendel Daryl , Lee Toong C. , Templeton David , Davis Timothy M. E. 
Published: March 2015

ABSTRACT

The pharmacokinetics of sublingual artemether (ArTiMist) was investigated in 91 young African children with severe malaria or who could not tolerate oral antimalarial therapy. Each received 3.0 mg/kg of body weight of artemether at 0, 8, 24, 36, 48, and 60 h or until the initiation of oral treatment. Few blood samples were drawn postdose. Plasma artemether and dihydroartemisinin (DHA) levels were measured using liquid chromatography-mass spectrometry, and the data were analyzed using established population compartmental pharmacokinetic models. Parasite clearance was prompt (median parasite clearance time, 24 h), and there were no serious adverse events. Consistent with studies in healthy adults (S. Salman, D. Bendel, T. C. Lee, D. Templeton, and T. M. E. Davis, Antimicrob Agents Chemother 59:3197–3207, 2015,
http://dx.doi.org/10.1128/AAC.05013-14
), the absorption of sublingual artemether was biphasic, and multiple dosing was associated with the autoinduction of the metabolism of artemether to DHA (which itself has potent antimalarial activity). In contrast to studies using healthy volunteers, pharmacokinetic modeling indicated that the first absorption phase did not avoid first-pass metabolism, suggesting that the drug is transferred to the upper intestine through postdose fluid/food intake. Simulations using the present data and those from an earlier study in older Melanesian children with uncomplicated malaria treated with artemether-lumefantrine tablets suggested that the bioavailability of sublingual artemether was at least equivalent to that after conventional oral artemether-lumefantrine (median [interquartile range] areas under the concentration-time curve for artemether, 3,403 [2,471 to 4,771] versus 3,063 [2,358 to 4,514] μg · h/liter, respectively; and for DHA, 2,958 [2,146 to 4,278] versus 2,839 [1,812 to 3,488] μg · h/liter, respectively;
P
≥ 0.42). These findings suggest that sublingual artemether could be used as prereferral treatment for sick children before transfer for definitive management of severe or moderately severe malaria.
Roles of Reactive Oxygen Species-Degrading Enzymes of Francisella tularensis SCHU S4
Authors: Binesse Johan , Lindgren Helena , Lindgren Lena , Conlan Wayne , Sjöstedt Anders 
Published: March 2015

ABSTRACTFrancisella tularensisis a facultative intracellular bacterium utilizing macrophages as its primary intracellular habitat and is therefore highly capable of resisting the effects of reactive oxygen species (ROS), potent mediators of the bactericidal activity of macrophages. We investigated the roles of enzymes presumed to be important for protection against ROS. Four mutants of the highly virulent SCHU S4 strain with deletions of the genes encoding catalase (katG), glutathione peroxidase (gpx), a DyP-type peroxidase (FTT0086), or double deletion ofFTT0086andkatGshowed much increased susceptibility to hydrogen peroxide (H2O2) and slightly increased susceptibility to paraquat but not to peroxynitrite (ONOO−) and displayed intact intramacrophage replication. Nevertheless, mice infected with the double deletion mutant showed significantly longer survival than SCHU S4-infected mice. Unlike the aforementioned mutants, deletion of the gene coding for alkyl-hydroperoxide reductase subunit C (ahpC) generated a mutant much more susceptible to paraquat and ONOO−but not to H2O2. It showed intact replication in J774 cells but impaired replication in bone marrow-derived macrophages and in internal organs of mice. The live vaccine strain, LVS, is more susceptible than virulent strains to ROS-mediated killing and possesses a truncated form of FTT0086. Expression of the SCHU S4FTT0086gene rendered LVS more resistant to H2O2, which demonstrates that the SCHU S4 strain possesses additional detoxifying mechanisms. Collectively, the results demonstrate that SCHU S4 ROS-detoxifying enzymes have overlapping functions, and therefore, deletion of one or the other does not critically impair the intracellular replication or virulence, although AhpC appears to have a unique function.
Reassessment of the Genetic Regulation of Fatty Acid Synthesis in Escherichia coli: Global Positive Control by the Dual Functional Regulator FadR
Authors: My L. , Ghandour Achkar N. , Viala J. P. , Bouveret E. 
Published: March 2015

ABSTRACTInEscherichia coli, the FadR transcriptional regulator represses the expression of fatty acid degradation (fad) genes. However, FadR is also an activator of the expression offabAandfabB, two genes involved in unsaturated fatty acid synthesis. Therefore, FadR plays an important role in maintaining the balance between saturated and unsaturated fatty acids in the membrane. We recently showed that FadR also activates the promoter upstream of thefabHgene (L. My, B. Rekoske, J. J. Lemke, J. P. Viala, R. L. Gourse, and E. Bouveret, J Bacteriol 195:3784–3795, 2013, doi:10.1128/JB.00384-13). Furthermore, recent transcriptomic and proteomic data suggested that FadR activates the majority of fatty acid (FA) synthesis genes. In the present study, we tested the role of FadR in the expression of all genes involved in FA synthesis. We found that FadR activates the transcription of all tested FA synthesis genes, and we identified the FadR binding site for each of these genes. This necessitated the reassessment of the transcription start sites foraccAandaccBgenes described previously, and we provide evidence for the presence of multiple promoters driving the expression of these genes. We showed further that regulation by FadR impacts the amount of FA synthesis enzymes in the cell. Our results show that FadR is a global regulator of FA metabolism inE. coli, acting both as a repressor of catabolism and an activator of anabolism, two directly opposing pathways.IMPORTANCEIn most bacteria, a transcriptional regulator tunes the level of FA synthesis enzymes. Oddly, such a global regulator still was missing forE. coli, which nonetheless is one of the prominent model bacteria used for engineering biofuel production using the FA synthesis pathway. Our work identifies the FadR functional dual regulator as a global activator of almost all FA synthesis genes inE. coli. Because FadR also is the repressor of FA degradation, FadR acts both as a repressor and an activator of the two opposite pathways of FA degradation and synthesis. Our results show that there are still discoveries waiting to be made in the understanding of the genetic regulation of FA synthesis, even in the very well-known bacteriumE. coli.
Evaluation of an anatomic definition of non-aneurysmal perimesencephalic subarachnhoid hemorrhage
Authors: Wallace Adam N , Vyhmeister Ross , Dines Jeffrey N , Chatterjee Arindam R , Kansagra Akash P , Viets Ryan , Whisenant Justin T , Moran Christopher J , Cross DeWitte T , Derdeyn Colin P 
Published: March 2015

Background and purposePerimesencephalic subarachnoid hemorrhage (PSAH) is not consistently defined in the existing literature. The purpose of this study was to test the inter-observer variability and specificity for non-aneurysmal subarachnoid hemorrhage (SAH) of an anatomic definition of PSAH.MethodsMedical records of all patients who underwent catheter angiography for evaluation of non-traumatic SAH between July 2002 and April 2012 were reviewed. Patients with anterior circulation aneurysms were excluded. Three blinded reviewers assessed whether each admission CT scan met the following anatomic criteria for PSAH: (1) center of bleeding located immediately anterior and in contact with the brainstem in the prepontine, interpeduncular, or posterior suprasellar cistern; (2) blood limited to the prepontine, interpeduncular, suprasellar, crural, ambient, and/or quadrigeminal cisterns and/or cisterna magna; (3) no extension of blood into the Sylvian or interhemispheric fissures; (4) intraventricular blood limited to incomplete filling of the fourth ventricle and occipital horns of the lateral ventricles (ie, consistent with reflux); (5) no intraparenchymal blood.Results56 patients with non-aneurysmal SAH and 50 patients with posterior circulation or posterior communicating artery aneurysms were identified. Seventeen (16%) of the 106 admission CT scans met the anatomic criteria for PSAH. No aneurysm was identified in this subgroup. Inter-observer agreement was excellent with κ scores of 0.89–0.96 and disagreement in 2.8% (3/106) of cases.ConclusionsOur anatomic definition of PSAH correlated with a low risk of brain aneurysm and was applied with excellent inter-observer agreement.
Pulmonary Vascular and Right Ventricular Reserve in Patients With Normalized Resting Hemodynamics After Pulmonary Endarterectomy
Authors: Claessen Guido , La Gerche Andre , Dymarkowski Steven , Claus Piet , Delcroix Marion , Heidbuchel Hein 
Published: March 2015

Background

Patients with normalized mean pulmonary artery pressure (
mPAP
) after pulmonary endarterectomy (
PEA
) for chronic thromboembolic pulmonary hypertension (
CTEPH
) do not always regain normal exercise capacity. We evaluated right ventricular function, its interaction with both pulsatile and resistive afterload, and the effect of sildenafil during exercise in these patients.

Methods and Results

Fourteen healthy controls, 15
CTEPH
patients, and 7 patients with normalized resting
mPAP
(≤25 mm Hg) post‐
PEA
underwent cardiopulmonary exercise testing, followed by cardiac magnetic resonance imaging with simultaneous invasive
mPAP
measurement during incremental supine cycling exercise. Peak oxygen consumption and peak heart rate were significantly reduced in post‐
PEA
and
CTEPH
patients compared to controls. The
mPAP
–cardiac output slope was steeper in post‐
PEA
patients than in controls and similar to
CTEPH
. Relative to controls, resting right ventricular ejection fraction was reduced in
CTEPH
, but not in post‐
PEA
patients. In contrast, peak exercise right ventricular ejection fraction was reduced both in post‐
PEA
and
CTEPH
patients. Exercise led to reduction of pulmonary arterial compliance in all groups. Nevertheless, resting pulmonary arterial compliance values in
CTEPH
and post‐
PEA
patients were even lower than those in controls at peak exercise. In post‐
PEA
patients, sildenafil did not affect resting hemodynamics nor right ventricular function, but decreased the
mPAP
/cardiac output slope and increased peak exercise right ventricular ejection fraction.

Conclusions

Exercise intolerance in post‐
PEA
patients is explained by abnormal pulmonary vascular reserve and chronotropic incompetence. The
mPAP
/cardiac output slope and pulmonary arterial compliance are sensitive measures demonstrating abnormal resistive and pulsatile pulmonary vascular function in post‐
PEA
patients. These abnormalities are partially attenuated with sildenafil.
The Timing of Regular Sequences: Production, Perception, and Covariation
Authors: Schwartze Michael , Kotz Sonja A. 
Published: March 2015

Abstract
The temporal structure of behavior provides information that allows the tracking of temporal regularity in the sensory and sensorimotor domains. In turn, temporal regularity allows the generation of predictions about upcoming events and to adjust behavior accordingly. These mechanisms are essential to ensure behavior beyond the level of mere reaction. However, efficient temporal processing is required to establish adequate internal representations of temporal structure. The current study used two simple paradigms, namely, finger-tapping at a regular self-chosen rate (spontaneous motor tempo) and ERPs of the EEG (EEG/ERP) recorded during attentive listening to temporally regular and irregular “oddball” sequences to explore the capacity to encode and use temporal regularity in production and perception. The results show that specific aspects of the ability to time a regular sequence of events in production covary with the ability to time a regular sequence in perception, probably pointing toward the engagement of domain-general mechanisms.
Auditory Perceptual Category Formation Does Not Require Perceptual Warping
Authors: Caruso Valeria C. , Balaban Evan 
Published: March 2015

Abstract
Categorical perception occurs when a perceiver's stimulus classifications affect their ability to make fine perceptual discriminations and is the most intensively studied form of category learning. On the basis of categorical perception studies, it has been proposed that category learning proceeds by the deformation of an initially homogeneous perceptual space (“perceptual warping”), so that stimuli within the same category are perceived as more similar to each other (more difficult to tell apart) than stimuli that are the same physical distance apart but that belong to different categories. Here, we present a significant counterexample in which robust category learning occurs without these differential perceptual space deformations. Two artificial categories were defined along the dimension of pitch for a perceptually unfamiliar, multidimensional class of sounds. A group of participants (selected on the basis of their listening abilities) were trained to sort sounds into these two arbitrary categories. Category formation, verified empirically, was accompanied by a heightened sensitivity along the entire pitch range, as indicated by changes in an EEG index of implicit perceptual distance (mismatch negativity), with no significant resemblance to the local perceptual deformations predicted by categorical perception. This demonstrates that robust categories can be initially formed within a continuous perceptual dimension without perceptual warping. We suggest that perceptual category formation is a flexible, multistage process sequentially combining different types of learning mechanisms rather than a single process with a universal set of behavioral and neural correlates.
Atopobathynella paraoperculata n. sp. (Syncarida, Bathynellacea, Parabathynellidae) from the River Krishna, southeastern India
Authors: Ranga Reddy Yenumula , Totakura Venkateswara Rao 
Published: March 2015

To date, the genusAtopobathynellaSchminke, 1973, is known by 11 species in the world. Here,Atopobathynella paraoperculatan. sp., the second species of this genus from India, is described from the interstitial hyporheic zone of the River Krishna in Andhra Pradesh state. It has closest similarity with its Indian congener,AtopobathynellaoperculataRanga Reddy, Drewes & Schminke, 2008, as borne out by the fusion of the inner flagellum of the antennule with the first segment of the outer flagellum, the presence of a seta on the subdistal outer surface of the uropodal sympod; the antennal organ consists exclusively of two massive lobes; the antenna has three instead of four armature elements; the proximal segment of the maxillule has two instead of four distinct claws; the uropodal sympod has an inhomonomous row of spines; and the anal operculum is massive. However, the new species can be easily separated fromA. operculataby several other criteria such as the labrum without vs. with tubular pores; the second endopodal segment of Th I has two setae vs. one seta; the uropodal sympod has four vs. eight spines; the uropodal endopod has two weak setae vs. one normal seta; the pleotelson is unarmed vs. armed; and the anal operculum has a subacute vs. a rounded tip. Further, based on the novelties observed in the two Indian congeners, some of the principal generic characters and their states are briefly discussed, and also some ecological notes are added.
Comparing Evapotranspiration from Eddy Covariance Measurements, Water Budgets, Remote Sensing, and Land Surface Models over Canadaa,b
Authors: Wang Shusen , Pan Ming , Mu Qiaozhen , Shi Xiaoying , Mao Jiafu , Brümmer Christian , Jassal Rachhpal S. , Krishnan Praveena , Li Junhua , Black T. Andrew 
Published: March 2015

AbstractThis study compares six evapotranspiration ET products for Canada’s landmass, namely, eddy covariance EC measurements; surface water budget ET; remote sensing ET from MODIS; and land surface model (LSM) ET from the Community Land Model (CLM), the Ecological Assimilation of Land and Climate Observations (EALCO) model, and the Variable Infiltration Capacity model (VIC). The ET climatology over the Canadian landmass is characterized and the advantages and limitations of the datasets are discussed. The EC measurements have limited spatial coverage, making it difficult for model validations at the national scale. Water budget ET has the largest uncertainty because of data quality issues with precipitation in mountainous regions and in the north. MODIS ET shows relatively large uncertainty in cold seasons and sparsely vegetated regions. The LSM products cover the entire landmass and exhibit small differences in ET among them. Annual ET from the LSMs ranges from small negative values to over 600 mm across the landmass, with a countrywide average of 256 ± 15 mm. Seasonally, the countrywide average monthly ET varies from a low of about 3 mm in four winter months (November–February) to 67 ± 7 mm in July. The ET uncertainty is scale dependent. Larger regions tend to have smaller uncertainties because of the offset of positive and negative biases within the region. More observation networks and better quality controls are critical to improving ET estimates. Future techniques should also consider a hybrid approach that integrates strengths of the various ET products to help reduce uncertainties in ET estimation.