bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biogeography of scorpions in thePseudouroctonus minimuscomplex (Vaejovidae) from south‐western North America: implications of ecological specialization for pre‐Quaternary diversification
Authors: Bryson Robert W. , Savary Warren E. , Prendini Lorenzo 
Published: May 2013

AbstractAimThe aim of this study was to assess the impact of pre‐Quaternary tectonics and orogeny relative to that of Pleistocene climate change on diversification within thePseudouroctonus minimuscomplex, a group of vaejovid scorpions with stenotopic habitat requirements.LocationSouth‐western North America (United States and Mexico).MethodsMultilocus sequence data (1899 base pairs from two mitochondrial and two nuclear genes) were generated from 65 samples of scorpions in theminimuscomplex. Phylogeographical structure within theminimuscomplex was explored using model‐based phylogenetic methods and a general mixed Yule coalescent model to identify independent geographical clusters. A time‐calibrated multilocus species tree was reconstructed using a multispecies coalescent approach. Ancestral areas were estimated at divergence events across the tree using a probabilistic Bayesian approach.ResultsExtensive geographical structure was evident within two well‐supported clades. These clades probably diverged over 25 million years ago (Ma), based on estimated mean divergence dates, followed by 14 divergences in the Miocene (25–5 Ma) and 4 divergences in the Pliocene and Pleistocene (< 5 Ma). The ancestral origin of theminimuscomplex was reconstructed to be across California and the Mexican Highlands. The Chihuahuan Desert was colonized twice from the Mexican Highlands, and one dispersal event occurred from the Mexican Highlands back to California.Main conclusionsSpatial and temporal patterns of evolution in theminimuscomplex support predictions that stenotopy promoted pre‐Quaternary diversification. Miocene and Pliocene geomorphology, perhaps in concert with climate change, induced allopatric divergence across the heterogeneous landscape of south‐western North America. Stenotopic scorpions such as theminimuscomplex provide a model for exploring correlations between Earth history and biological diversification.
International experiences of promoting generics use and its implications to China
Authors: Sun Jing 
Published: May 2013

AbstractObjectiveTo summarize international experiences in promoting use of generics and to extract essence for China's reference.MethodThis is a commentary of two systematic reviews about policies to promote use of generics and its implications to China.ResultPrice, reimbursement, and generic substitution policies in European countries, and approaches in low and middle income countries in promoting market competition, appropriate intellectual property right protection strategy, and necessary demand side incentives, are all meaningful for China to contain soaring pharmaceutical expenditures, and to maintain the achievements and outcomes of the national health system reform.ConclusionEffective promotion of generics use must be practice based on the real situation. Tailor‐made and comprehensive measures are needed to address both demand and supply sides barriers before achieving tangible cost containment effect without unexpected side effects.
Deciphering Ascorbic Acid Regulatory Pathways in Ripening Tomato Fruit Using a Weighted Gene Correlation Network Analysis Approach
Authors: Gao Chao , Ju Zheng , Li Shan , Zuo Jinhua , Fu Daqi , Tian Huiqin , Luo Yunbo , Zhu Benzhong 
Published: May 2013

AbstractGenotype is generally determined by the co‐expression of diverse genes and multiple regulatory pathways in plants. Gene co‐expression analysis combining with physiological trait data provides very important information about the gene function and regulatory mechanism. L‐Ascorbic acid (AsA), which is an essential nutrient component for human health and plant metabolism, plays key roles in diverse biological processes such as cell cycle, cell expansion, stress resistance, hormone synthesis, and signaling. Here, we applied a weighted gene correlation network analysis approach based on gene expression values and AsA content data in ripening tomato (Solanum lycopersicum L.) fruit with different AsA content levels, which leads to identification of AsA relevant modules and vital genes in AsA regulatory pathways. Twenty‐four modules were compartmentalized according to gene expression profiling. Among these modules, one negatively related module containing genes involved in redox processes and one positively related module enriched with genes involved in AsA biosynthetic and recycling pathways were further analyzed. The present work herein indicates that redox pathways as well as hormone‐signal pathways are closely correlated with AsA accumulation in ripening tomato fruit, and allowed us to prioritize candidate genes for follow‐up studies to dissect this interplay at the biochemical and molecular level.
An open‐label study of anidulafungin for the treatment of candidaemia/invasive candidiasis in Latin America
Authors: Nucci Marcio , Colombo Arnaldo L. , Petti Marco , Magana Martin , Abreu Paula , Schlamm Haran T. , Sanchez Sonia P. 
Published: May 2013

SummaryIncidence and mortality of candidaemia/invasive candidiasis (C/IC) is relatively high in Latin America versus North America and Europe. To assess efficacy and safety of intravenous (IV) anidulafungin in Latin American adults with documented C/IC. All patients in this open‐label study received initial IV anidulafungin with optional step‐down to oral voriconazole after 5 days; total treatment duration was 14–42 days. The primary endpoint was global response (clinical + microbiological response) at end of treatment (EOT); missing/indeterminate responses were failures. The study enrolled 54 patients; 44 had confirmed C/IC within 96 h before study entry and comprised the modified intent‐to‐treat population. Global response at EOT was 59.1% (95% CI: 44.6, 73.6), with 13 missing/indeterminate assessments. Thirty‐day all‐cause mortality was 43.1%. Fourteen patients (31.8%) were able to step‐down to oral voriconazole; these patients had lower baseline acute physiological assessment and chronic health evaluation (APACHE) II scores and were less likely to have solid tumours or previous abdominal surgery. Anidulafungin was generally well tolerated with few treatment‐related adverse events. Anidulafungin was associated with relatively low response rates influenced by a high rate of missing/indeterminate assessments and mortality comparable to other recent candidaemia studies in Latin America. In a subset of patients with lower APACHE II scores, short‐course anidulafungin followed by oral voriconazole was successful.
Systemic inflammation with enhanced brain activation contributes to more severe delay in postoperative ileus
Authors: van Bree S. H. W. , Cailotto C. , Di Giovangiulio M. , Jansen E. , van der Vliet J. , Costes L. , Depoortere I. , Gomez‐Pinilla P. J. , Matteoli G. , Boeckxstaens G. E. E. 
Published: May 2013

AbstractBackgroundThe severity of postoperative ileus (POI) has been reported to result from decreased contractility of the muscularis inversely related to the number of infiltrating leukocytes. However, we previously observed that the severity of POI is independent of the number of infiltrating leukocytes, indicating that different mechanisms must be involved. Here, we hypothesize that the degree of tissue damage in response to intestinal handling determines the upregulation of local cytokine production and correlates with the severity of POI.MethodsIntestinal transit, the inflammatory response, I‐FABP (marker for tissue damage) levels and brain activation were determined after different intensities of intestinal handling.Key ResultsIntense handling induced a more pronounced ileus compared with gentle intestinal manipulation (IM). No difference in leukocytic infiltrates in the handled and non‐handled parts of the gut was observed between the two intensities of intestinal handling. However, intense handling resulted in significantly more tissue damage and was accompanied by a systemic inflammation with increased plasma levels of pro‐inflammatory cytokines. In addition, intense but not gentle handling triggered enhanced c‐Fos expression in the nucleus of the solitary tract (NTS) and area postrema (AP). In patients, plasma levels of I‐FABP and inflammatory cytokines were significantly higher after open compared with laparoscopic surgery, and were associated with more severe POI.Conclusions & InferencesNot the influx of leukocytes, rather the manipulation‐induced damage and subsequent inflammatory response determine the severity of POI. The release of tissue damage mediators and pro‐inflammatory cytokines into the systemic circulation most likely contribute to the impaired motility of non‐manipulated intestine.
Gingipain‐dependent degradation of mammalian target of rapamycin pathway proteins by the periodontal pathogen Porphyromonas gingivalis during invasion
Authors: Stafford P. , Higham J. , Pinnock A. , Murdoch C. , Douglas C.W.I. , Stafford G.P. , Lambert D.W. 
Published: May 2013

SummaryPorphyromonas gingivalis and Tannerella forsythia are gram‐negative pathogens strongly associated with periodontitis. Their abilities to interact, invade and persist within host cells are considered crucial to their pathogenicity, but the mechanisms by which they subvert host defences are not well understood. In this study, we set out to investigate whether P. gingivalis and T. forsythia directly target key signalling molecules that may modulate the host cell phenotype to favour invasion and persistence. Our data identify, for the first time, that P. gingivalis, but not T. forsythia, reduces levels of intracellular mammalian target of rapamycin (mTOR) in oral epithelial cells following invasion over a 4‐h time course, via the action of gingipains. The ability of cytochalasin D to abrogate P. gingivalis‐mediated mTOR degradation suggests that this effect is dependent upon cellular invasion. We also show that levels of several other proteins in the mTOR signalling pathway are modulated by gingipains, either directly or as a consequence of mTOR degradation including p‐4E‐BP1. Taken together, our data suggest that P. gingivalis manipulates the mTOR pathway, providing evidence for a potentially novel mechanism by which P. gingivalis mediates its effects on host cell responses to infection.
Knowledge, Credit, and Cognitive Agency
Authors: Breyer Daniel S. 
Published: May 2013

AbstractAccording to credit theories of knowledge, S knows that p only if S deserves credit for truly believing that p. This article argues that any adequate credit theory has to explain the conditions under which beliefs are attributable to subjects. It then presents a general account of these conditions and defends two models of cognitive agency. Finally, the article explains how an agent‐based approach rescues the credit theory from an apparent counterexample. The article's defense of the credit theory is qualified, however, for one lesson that emerges is that credit theories are theories of subjective justification, not theories of knowledge.
Hematopoietic stem cell transplantation with a reduced‐intensity conditioning regimen in pediatric patients withGriscelli syndrome type 2
Authors: Hamidieh Amir Ali , Pourpak Zahra , Yari Kolsoum , Fazlollahi Mohammad Reza , Hashemi Susan , Behfar Maryam , Moin Mostafa , Ghavamzadeh Ardeshir 
Published: May 2013

AbstractPartial albinism with variable immunodeficiency are the two major characteristics ofGriscelli syndrome type 2 (GS‐2). This syndrome is usually associated with a high mortality rate and commonly results in early childhood death. Patients suffer from different infections and experience crisis ofHLH.HSCTremains the sole curative treatment forGS‐2. We prospectively analyzed the outcomes of transplantation withRICregimen in five patients. The median age at transplantation was 21.6 months (range: 12–30). All of the patients underwentHSCTfromHLA‐matched related donors. Currently, four patients are cured, and symptoms of recurrent infections andHLHcrisis are not seen in them. The only patient who died had undergoneHSCTin the accelerated phase ofHLH. One patient who developed acuteGvHDhad a favorable response to therapy. No chronicGvHDoccurred in patients. It seems that the use ofRICregimen as a method of transplant preparation is effective and tolerable in this group of patients with various comorbidities. It is recommended to carry outHSCTin these patients at lower ages, before presentations of different infections andHLHcrisis.
Characterization of the Exonic Regions of the JY‐1 Gene in Zebu Cattle and Buffaloes
Authors: de Camargo GMF , Baldi F , Regitano LCA , Tonhati H 
Published: May 2013

ContentsProtein JY‐1 is an oocyte‐specific protein that plays an important regulatory role in the granulosa cell layer and during the early embryo development stages. It is the first specific protein of maternal origin discovered in a single‐ovulating species. In this study, the exon regions of the JY‐1 gene were characterized by sequencing in 20 unrelated cattle (Bos taurus indicus) and 20 unrelated buffaloes (Bubalus bubalis). Eighteen polymorphisms were detected in cattle and 10 polymorphisms in buffaloes. Some of the polymorphisms were identified in codifying regions and caused amino acid changes. The insertion of a thymine was detected in the codifying region of exon 3 of the buffalo sequence when compared to the cattle one. This insertion causes a change in the codons frameshift from this point onwards, modifying the 19 terminal amino acids of the buffalo protein and creating a premature stop codon. This finding may explain reproductive differences between cattle and buffaloes in terms of follicle recruitment, embryo development and incidence of twin pregnancies.
Goodness‐of‐fit Test for Directional Data
Authors: Boente Graciela , Rodriguez Daniela , Manteiga Wenceslao González 
Published: May 2013

ABSTRACTIn this paper, we study the problem of testing the hypothesis on whether the density f of a random variable on a sphere belongs to a given parametric class of densities. We propose two test statistics based on the L2 and L1 distances between a non‐parametric density estimator adapted to circular data and a smoothed version of the specified density. The asymptotic distribution of the L2 test statistic is provided under the null hypothesis and contiguous alternatives. We also consider a bootstrap method to approximate the distribution of both test statistics. Through a simulation study, we explore the moderate sample performance of the proposed tests under the null hypothesis and under different alternatives. Finally, the procedure is illustrated by analysing a real data set based on wind direction measurements.
Using Reverse Viewshed Analysis to Assess the Location Correctness of Visually Generated VGI
Authors: Senaratne Hansi , Bröring Arne , Schreck Tobias 
Published: May 2013

AbstractWith the increased availability of user generated data, assessing the quality and credibility of such data becomes important. In this article, we propose to assess the location correctness of visually generated Volunteered Geographic Information (VGI) as a quality reference measure. The location correctness is determined by checking the visibility of the point of interest from the position of the visually generated VGI (observer point); as an example we utilize Flickr photographs. Therefore we first collect all Flickr photographs that conform to a certain point of interest through their textual labelling. Then we conduct a reverse viewshed analysis for the point of interest to determine if it lies within the area of visibility of the observer points. If the point of interest lies outside the visibility of a given observer point, the respective geotagged image is considered to be incorrectly geotagged. In this way, we analyze sample datasets of photographs and make observations regarding the dependency of certain user/photo metadata and (in)correct geotags and labels. In future the dependency relationship between the location correctness and user/photo metadata can be used to automatically infer user credibility. In other words, attributes such as profile completeness, together with location correctness, can serve as a weighted score to assess credibility.
Inductively coupled plasma mass‐spectrometric determination of platinum in excretion products of client‐owned pet dogs
Authors: Janssens T. , Brouwers E. E. M. , de Vos J. P. , de Vries N. , Schellens J. H. M. , Beijnen J. H. 
Published: May 2013

AbstractResidues of antineoplastic drugs in canine excretion products may represent exposure risks to veterinary personnel, owners of pet dogs and other animal care‐takers. The aim of this study was to measure the extent and duration of platinum (Pt) excretion in pet dogs treated with carboplatin. Samples were collected before and up to 21 days after administration of carboplatin. We used validated, ultra‐sensitive, inductively coupled plasma‐mass spectrometry assays to measure Pt in canine urine, faeces, saliva, sebum and cerumen. Results showed that urine is the major route of elimination of Pt in dogs. In addition, excretion occurs via faeces and saliva, with the highest amounts eliminated during the first 5 days. The amount of excreted Pt decreased over time but was still quantifiable at 21 days after administration of carboplatin. In conclusion, increased Pt levels were found in all measured excretion products up to 21 days after administration of carboplatin to pet dogs, with urine as the main route of excretion. These findings may be used to further adapt current veterinary guidelines on safe handling of antineoplastic drugs and treated animals.
Methylation of 23S rRNA Nucleotide G748 by RlmA
II
Methyltransferase Renders Streptococcus pneumoniae Telithromycin Susceptible
Authors: Takaya Akiko , Sato Yoshiharu , Shoji Tatsuma , Yamamoto Tomoko 
Published: May 2013

ABSTRACT

Several posttranscriptional modifications of bacterial rRNAs are important in determining antibiotic resistance or sensitivity. In all Gram-positive bacteria, dimethylation of nucleotide A2058, located in domain V of 23S rRNA, by the dimethyltransferase Erm(B) results in low susceptibility and resistance to telithromycin (TEL). However, this is insufficient to produce high-level resistance to TEL in
Streptococcus pneumoniae
. Inactivation of the methyltransferase RlmA
II
, which methylates the N-1 position of nucleotide G748, located in hairpin 35 of domain II of 23S rRNA, results in increased resistance to TEL in
erm
(B)-carrying
S. pneumoniae
. Sixteen TEL-resistant mutants (MICs, 16 to 32 μg/ml) were obtained from a clinically isolated
S. pneumoniae
strain showing low TEL susceptibility (MIC, 2 μg/ml), with mutation resulting in constitutive dimethylation of A2058 because of nucleotide differences in the regulatory region of
erm
(B) mRNA. Primer extension analysis showed that the degree of methylation at G748 in all TEL-resistant mutants was significantly reduced by a mutation in the gene encoding RlmA
II
to create a stop codon or change an amino acid residue. Furthermore, RNA footprinting with dimethyl sulfate and a molecular modeling study suggested that methylation of G748 may contribute to the stable interaction of TEL with domain II of 23S rRNA, even after dimethylation of A2058 by Erm(B). This novel finding shows that methylation of G748 by RlmA
II
renders
S. pneumoniae
TEL susceptible.
Two Multidrug-Resistant Clinical Isolates of Bacteroides fragilis Carry a Novel Metronidazole Resistance
nim
Gene (
nimJ
)
Authors: Husain Fasahath , Veeranagouda Yaligara , Hsi Justin , Meggersee Rosemary , Abratt Valerie , Wexler Hannah M. 
Published: May 2013

ABSTRACT

Two multidrug-resistant
Bacteroides fragilis
clinical isolates contain and express a novel
nim
gene,
nimJ
, that is not recognized by the “universal”
nim
primers and can confer increased resistance to metronidazole when introduced into a susceptible strain on a multicopy plasmid. HMW615, an appendiceal isolate, contains at least two copies of
nimJ
on its genome, while HMW616, an isolate from a patient with sepsis, contains one genomic copy of
nimJ. B. fragilis
NimJ is phylogenetically closer to
Prevotella baroniae
NimI and
Clostridium botulinum
NimA than to the other known
Bacteroides
Nim proteins. The predicted protein structure of NimJ, based on fold recognition analysis, is consistent with the crystal structures derived for known Nim proteins, and specific amino acid residues important for substrate binding in the active site are conserved. This study demonstrates that the “universal”
nim
primers will not detect all
nim
genes with the ability to confer metronidazole resistance, but
nimJ
alone cannot account for the very high metronidazole MICs of these resistant clinical isolates.
Multicenter Study of Isavuconazole MIC Distributions and Epidemiological Cutoff Values for Aspergillus spp. for the CLSI M38-A2 Broth Microdilution Method
Authors: Espinel-Ingroff A. , Chowdhary A. , Gonzalez G. M. , Lass-Flörl C. , Martin-Mazuelos E. , Meis J. , Peláez T. , Pfaller M. A. , Turnidge J. 
Published: May 2013

ABSTRACTEpidemiological cutoff values (ECVs) were established for the new triazole isavuconazole andAspergillusspecies wild-type (WT) MIC distributions (organisms in a species-drug combination with no detectable acquired resistance mechanisms) that were defined with 855Aspergillus fumigatus, 444A. flavus, 106A. nidulans, 207A. niger, 384A. terreus, and 75A. versicolorspecies complex isolates; 22AspergillussectionUstiisolates were also included. CLSI broth microdilution MIC data gathered in Europe, India, Mexico, and the United States were aggregated to statistically define ECVs. ECVs were 1 μg/ml for theA. fumigatusspecies complex, 1 μg/ml for theA. flavusspecies complex, 0.25 μg/ml for theA. nidulansspecies complex, 4 μg/ml for theA. nigerspecies complex, 1 μg/ml for theA. terreusspecies complex, and 1 μg/ml for theA. versicolorspecies complex; due to the small number of isolates, an ECV was not proposed forAspergillussectionUsti. These ECVs may aid in detecting non-WT isolates with reduced susceptibility to isavuconazole due tocyp51A(anA. fumigatusspecies complex resistance mechanism among the triazoles) or other mutations.
Interrogating a Hexokinase-Selected Small-Molecule Library for Inhibitors of Plasmodium falciparum Hexokinase
Authors: Harris Michael T. , Walker Dawn M. , Drew Mark E. , Mitchell William G. , Dao Kevin , Schroeder Chad E. , Flaherty Daniel P. , Weiner Warren S. , Golden Jennifer E. , Morris James C. 
Published: May 2013

ABSTRACT

Parasites in the genus
Plasmodium
cause disease throughout the tropic and subtropical regions of the world.
P. falciparum
, one of the deadliest species of the parasite, relies on glycolysis for the generation of ATP while it inhabits the mammalian red blood cell. The first step in glycolysis is catalyzed by hexokinase (HK). While the 55.3-kDa
P. falciparum
HK (PfHK) shares several biochemical characteristics with mammalian HKs, including being inhibited by its products, it has limited amino acid identity (∼26%) to the human HKs, suggesting that enzyme-specific therapeutics could be generated. To that end, interrogation of a selected small-molecule library of HK inhibitors has identified a class of PfHK inhibitors, isobenzothiazolinones, some of which have 50% inhibitory concentrations (IC
50
s) of <1 μM. Inhibition was reversible by dilution but not by treatment with a reducing agent, suggesting that the basis for enzyme inactivation was not covalent association with the inhibitor. Lastly, six of these compounds and the related molecule ebselen inhibited
P. falciparum
growth
in vitro
(50% effective concentration [EC
50
] of ≥0.6 and <6.8 μM). These findings suggest that the chemotypes identified here could represent leads for future development of therapeutics against
P. falciparum
.