bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coincidence of virulence shifts and population genetic changes of Pseudoperonospora cubensis in the Czech Republic
Authors: Kitner M. , Lebeda A. , Sharma R. , Runge F. , Dvořák P. , Tahir A. , Choi Y.‐J. , Sedláková B. , Thines M. 
Published: March 2015

Pseudoperonospora cubensis is an oomycete pathogen causing downy mildew disease on a variety of Cucurbitaceae, and has recently re‐emerged as a destructive disease on crops in this family, mainly on cucumber and squash. Multilocus sequence analysis (MLSA) of four mitochondrial and two nuclear DNA regions was used to detect changes in the genetic structure of P. cubensis populations occurring in the Czech Republic that might be associated with recently reported shifts in virulence. The analysed sample set contains 67 P. cubensis isolates collected from 1995 to 2012 in the Czech Republic and some other European countries. Sequence analyses revealed differences and changes in the genetic backgrounds of P. cubensis isolates. While all isolates sampled before 2009 exhibited the genotype of the subspecies of Clade II and were collected from cucumber, all samples collected from other hosts belonged to Clade I (P. cubensis sensu stricto) or were sampled from 2009 onwards. In addition, 67·16% of all post‐2009 isolates from Clade II had two heterozygous positions in their nrITS sequence, which suggests sexual reproduction and/or a mutational origin. Thus, the results indicate that, apart from the rise in prevalence of Clade I, the change in the genetic structure of P. cubensis populations may be linked with a hybridization or, less likely, a mutation event that rendered strains able to infect a broader spectrum of host species.
The glucosinolate breakdown product indole‐3‐carbinol acts as an auxin antagonist in roots of Arabidopsis thaliana
Authors: Katz Ella , Nisani Sophia , Yadav Brijesh S. , Woldemariam Melkamu G. , Shai Ben , Obolski Uri , Ehrlich Marcelo , Shani Eilon , Jander Georg , Chamovitz Daniel A. 
Published: March 2015

SummaryThe glucosinolate breakdown product indole‐3‐carbinol functions in cruciferous vegetables as a protective agent against foraging insects. While the toxic and deterrent effects of glucosinolate breakdown on herbivores and pathogens have been studied extensively, the secondary responses that are induced in the plant by indole‐3‐carbinol remain relatively uninvestigated. Here we examined the hypothesis that indole‐3‐carbinol plays a role in influencing plant growth and development by manipulating auxin signaling. We show that indole‐3‐carbinol rapidly and reversibly inhibits root elongation in a dose‐dependent manner, and that this inhibition is accompanied by a loss of auxin activity in the root meristem. A direct interaction between indole‐3‐carbinol and the auxin perception machinery was suggested, as application of indole‐3‐carbinol rescues auxin‐induced root phenotypes. In vitro and yeast‐based protein interaction studies showed that indole‐3‐carbinol perturbs the auxin‐dependent interaction of Transport Inhibitor Response (TIR1) with auxin/3‐indoleacetic acid (Aux/IAAs) proteins, further supporting the possibility that indole‐3‐carbinol acts as an auxin antagonist. The results indicate that chemicals whose production is induced by herbivory, such as indole‐3‐carbinol, function not only to repel herbivores, but also as signaling molecules that directly compete with auxin to fine tune plant growth and development.
Light stress and photoprotection in Chlamydomonas reinhardtii
Authors: Erickson Erika , Wakao Setsuko , Niyogi Krishna K. 
Published: March 2015

SummaryPlants and algae require light for photosynthesis, but absorption of too much light can lead to photo‐oxidative damage to the photosynthetic apparatus and sustained decreases in the efficiency and rate of photosynthesis (photoinhibition). Light stress can adversely affect growth and viability, necessitating that photosynthetic organisms acclimate to different environmental conditions in order to alleviate the detrimental effects of excess light. The model unicellular green alga, Chlamydomonas reinhardtii, employs diverse strategies of regulation and photoprotection to avoid, minimize, and repair photo‐oxidative damage in stressful light conditions, allowing for acclimation to different and changing environments.
Validation of sterility testing of cord blood: challenges and results
Authors: Ramirez‐Arcos Sandra , Kou Yuntong , Yang Lin , Perkins Heather , Taha Mariam , Halpenny Mike , Elmoazzen Heidi 
Published: March 2015

BACKGROUNDSterility testing for cord blood (CB) products is mandatory to prevent transplantation‐transmitted microbial infections. Here, the automated BacT/ALERT (bioMérieux) culture system was validated to detect microbial contamination in CB units processed at the Canadian National Public Cord Blood Bank.STUDY DESIGN AND METHODSA three‐phase validation was developed. CB units were prepared with pentastarch (Phases 1 and 2) or hetastarch (Phase 3). In Phase 1, CB was spiked with approximately 100 colony‐forming units/mL of Pseudomonas aeruginosa, Klebsiella pneumoniae, Staphylococcus aureus, Staphylococcus epidermidis, Bacteroides fragilis, and Candida albicans. Plasma (8 mL) and buffy coat (BC; 0.5 and 8 mL) were inoculated into culture bottles. In Phases 2 and 3, a mix of red blood cells (RBCs) and plasma (4 mL each) was used as the inoculant. In Phase 3, Aspergillus brasiliensis was added as a test organism and microbial concentrations in the by‐product RBCs and plasma were determined. The BC fractions were cryopreserved and tested 3 months later.RESULTSIn Phase 1, bacteria failed to grow in CB units containing antibiotics. Thus, antibiotic‐free units were used for the other phases. C. albicans was not always captured in plasma, but using a mix of RBCs and plasma, all organisms were detected. The use of pentastarch or hetastarch did not affect microbial recovery. C. albicans and A. brasiliensis were preferentially recovered in RBCs and BC. Cryopreservation did not affect microbial survival during CB processing.CONCLUSIONSA mix of plasma and RBCs is appropriate for CB sterility testing. Interestingly, fungi preferentially segregate to cellular fractions. The clinical significance of the bactericidal /or bacteriostatic effect of antibiotics in CB merits further investigation.
Dinotefuran/pyriproxyfen/permethrin pemphigus‐like drug reaction in three dogs
Authors: Bizikova Petra , Moriello Karen A. , Linder Keith E. , Sauber Leslie 
Published: March 2015

BackgroundPemphigus foliaceus (PF) can occur spontaneously or as a reaction pattern associated with cutaneous adverse drug reactions.Hypothesis/ObjectivesTo provide clinical, histological and immunological assessments of three dogs that developed cutaneous adverse drug reactions following application of a topical flea and tick control product, which contained dinotefuran, pyriproxyfen and permethrin.AnimalsThree client‐owned dogs.ResultsThe dogs exhibited rapid onset of papules, pustules and crusts at the site of application of the flea control product. In two dogs, the lesions became generalized, while the third exhibited a localized phenotype. Both dogs with generalized lesions required immunosuppressive treatment; one achieved remission after 1 year of treatment and one was euthanized due to adverse effects of glucocorticoids. The dog with a localized phenotype was treated with topical glucocorticoids exclusively and achieved remission after 10 months. Histology revealed subcorneal pustular dermatitis, with acantholysis of keratinocytes and focal to multifocal full‐thickness epidermal necrosis. These features are similar to those previously reported for pesticide‐triggered and spontaneous PF. Tissue‐bound IgG was detected in two of three dogs, and autoantibodies targeting canine desmocollin‐1 were identified in the serum of the one dog from which a sample was available.Conclusions and clinical importanceCutaneous adverse drug reaction caused by a flea control product containing dinotefuran, pyriproxyfen and permethrin closely resembled those reported for other pesticide‐associated PF‐like cutaneous adverse drug reactions. Although it appears to be a rare entity, clinicians and pathologists should be aware of the potential for flea and tick control products to trigger PF‐like reactions.
The application of cultured epithelial autografts improves survival in burns
Authors: Kym Dohern , Yim Haejun , Yoon Jaechul , Yang Hyeong‐Tae , Cho Yong Suk , Hur Jun , Chun Wook , Kim Jong‐Hyun 
Published: March 2015

ABSTRACTThis prospective observational study was performed to analyze the clinical outcomes of patients with massive burns treated using cultured epithelial autografts (CEAs) and to determine the association of this treatment with survival outcomes. During 2006–2013, total 177 massive‐burns subjects treated with (96 subjects) or without (81 subjects) CEAs. Data were analyzed using the independent t test or chi‐square test. Multivariate logistic regression, Kaplan–Meier survival, and Cox regression analyses were performed to evaluate the factors that influenced mortality. Age, percentage of total body surface area burned, incidence of inhalation injury, allograft‐application rate, Abbreviated Burn Severity Index score, length of hospital stay, and mortality significantly differed between the CEA and noncultured epithelial autograft groups. Mortality and other clinical parameters did not differ between the sheet‐type and spray‐type CEA groups. Allograft application (odds ratio, 4.44; p < 0.01) significantly influenced CEA application. The CEA group showed significantly higher survival rates (p = 0.05). Cultured epithelial autografting had a hazard ratio of 0.55 (p = 0.02) and 0.59 (p = 0.05) according to the uni‐ and multivariate Cox regression analysis, respectively. In conclusion, early and aggressive allograft application is required to facilitate CEA application. Furthermore, the use of CEAs was associated with a lower mortality, but this result should be interpreted with caution as the groups were not randomized.
Repowering of a Combined Cycle Plant
Authors: Walder Karen A. , D’Alessio Steven 
Published: March 2015

Demand for power in the United States is projected to increase between 2 and 4 percent per year for the next 10 years based on various studies. At the same time, the rise in environmental regulatory restrictions has made it increasingly difficult and expensive for utilities to meet these growing power demands with traditional power sources.
During the 1960’s and 70’s hundreds of gas turbine electric generating units were installed in the United States. Many are now approaching the end of their useful economic lives owing to increased maintenance and fuel costs. With the major advances in both fuel efficiency and exhaust gas emission quality power producers are looking toward the repowering of existing plants with modern gas turbines such as the FT8. (Day and Koehler, 1988)
This paper describes the design of Turbo Power and Marine Systems’ (Turbo Power) FT8® repowering package for the present FT4 powered plant at Public Service Electric and Gas Company’s (PSE&G) Burlington Generating Station. Given the objectives of minimum design effort and minimum field construction time, the retrofit package provides an optimal blending of existing FT4 and standard FT8 equipment. Performance, impact on operation, reliability, and availability of the FT8 industrial gas turbine were also important considerations in the retrofit design.
Characterization of a Novel Small Molecule That Potentiates β-Lactam Activity against Gram-Positive and Gram-Negative Pathogens
Authors: Nair Dhanalakshmi R. , Monteiro João M. , Memmi Guido , Thanassi Jane , Pucci Michael , Schwartzman Joseph , Pinho Mariana G. , Cheung Ambrose L. 
Published: March 2015

ABSTRACT

In a loss-of-viability screen using small molecules against methicillin-resistant
Staphylococcus aureus
(MRSA) strain USA300 with a sub-MIC of a β-lactam, we found a small molecule, designated DNAC-1, which potentiated the effect of oxacillin (i.e., the MIC of oxacillin decreased from 64 to 0.25 μg/ml). Fluorescence microscopy indicated a disruption in the membrane structures within 15 min of exposure to DNAC-1 at 2× MIC. This permeabilization was accompanied by a rapid loss of membrane potential, as monitored by use of the DiOC
2
(3,3′-diethyloxacarbocyanine iodide) dye. Macromolecular analysis showed the inhibition of staphylococcal cell wall synthesis by DNAC-1. Transmission electron microscopy of treated MRSA USA300 cells revealed a slightly thicker cell wall, together with mesosome-like projections into the cytosol. The exposure of USA300 cells to DNAC-1 was associated with the mislocalization of FtsZ accompanied by the localization of penicillin-binding protein 2 (PBP2) and PBP4 away from the septum, as well as mild activation of the
vraRS
-mediated cell wall stress response. However, DNAC-1 does not have any generalized toxicity toward mammalian host cells. DNAC-1 in combination with ceftriaxone is also effective against an assortment of Gram-negative pathogens. Using a murine subcutaneous coinjection model with 10
8
CFU of USA300 as a challenge inoculum, DNAC-1 alone or DNAC-1 with a sub-MIC of oxacillin resulted in a 6-log reduction in bacterial load and decreased abscess formation compared to the untreated control. We propose that DNAC-1, by exerting a bimodal effect on the cell membrane and cell wall, is a viable candidate in the development of combination therapy against many common bacterial pathogens.
Activities of
N
,
N
′-Diarylurea MMV665852 Analogs against Schistosoma mansoni
Authors: Cowan Noemi , Dätwyler Philipp , Ernst Beat , Wang Chunkai , Vennerstrom Jonathan L. , Spangenberg Thomas , Keiser Jennifer 
Published: March 2015

ABSTRACT

There is an unmet need to discover and develop novel antischistosomal drugs. As exemplified by MMV665852,
N
,
N
′-diarylureas have recently emerged as a promising antischistosomal chemotype. In this study, we evaluated the structure-activity relationships of 46 commercially available analogs of MMV665852 on newly transformed schistosomula (NTS) and adult
Schistosoma mansoni
worms
in vitro
. Active compounds were evaluated with a cytotoxicity assay,
in silico
calculations, metabolic stability studies, and an
in vivo
assay with mice harboring adult
S. mansoni
worms. Of the 46 compounds tested at 33.3 μM, 13 and 14 compounds killed NTS and adult worms, respectively, within 72 h. Nine compounds had 90% inhibitory concentrations (IC
90
s) of ≤10 μM against adult worms, with selectivity indexes of ≥2.8. Their physicochemical properties and permeation through an artificial membrane indicated good to moderate intestinal absorption. Their metabolic stabilities ranged from low to high. Despite satisfactory
in vitro
results and
in silico
predictions, only one compound resulted in a statistically significant worm burden reduction (66%) after administration of a single oral dose of 400 mg/kg of body weight to
S. mansoni
-infected mice. Worm burden reductions of 0 to 43% were observed for the remaining eight compounds tested. In conclusion, several analogs of the
N
,
N
′-diarylurea MMV665852 had high efficacy against
S. mansoni
in vitro
and favorable physicochemical properties for permeation through the intestinal wall. To counteract the low efficacy observed in the mouse model, further investigations should focus on identifying compounds with improved solubility and pharmacokinetic properties.
Simian-Tropic HIV as a Model To Study Drug Resistance against Integrase Inhibitors
Authors: Wares Melissa , Hassounah Said , Mesplède Thibault , Sandstrom Paul A. , Wainberg Mark A. 
Published: March 2015

ABSTRACT

Drug resistance represents a key aspect of human immunodeficiency virus (HIV) treatment failure. It is important to develop nonhuman primate models for studying issues of drug resistance and the persistence and transmission of drug-resistant viruses. However, relatively little work has been conducted using either simian immunodeficiency virus (SIV) or SIV/HIV recombinant viruses for studying resistance against integrase strand transfer inhibitors (INSTIs). Here, we used a T-cell-tropic SIV/HIV recombinant virus in which the capsid and
vif
regions of HIV-1 were replaced with their SIV counterparts (simian-tropic HIV-1 [stHIV-1]
(SCA,SVIF)
) to study the impact of a number of drug resistance substitutions in the integrase coding region at positions E92Q, G118R, E138K, Y143R, S153Y, N155H, and R263K on drug resistance, viral infectivity, and viral replication capacity. Our results show that each of these substitutions exerted effects that were similar to their effects in HIV-1. Substitutions associated with primary resistance against dolutegravir were more detrimental to stHIV-1
(SCA,SVIF)
infectiousness than were resistance substitutions associated with raltegravir and elvitegravir, consistent with data that have been reported for HIV-1. These findings support the role of stHIV-1
(SCA,SVIF)
as a useful model with which to evaluate the role of INSTI resistance substitutions on viral persistence, transmissibility, and pathogenesis in a nonhuman primate model.
Biofilm Formation and Quorum-Sensing-Molecule Production by Clinical Isolates of Serratia liquefaciens
Authors: Remuzgo-Martínez Sara , Lázaro-Díez María , Mayer Celia , Aranzamendi-Zaldumbide Maitane , Padilla Daniel , Calvo Jorge , Marco Francesc , Martínez-Martínez Luis , Icardo José Manuel , Otero Ana , Ramos-Vivas José 
Published: March 2015

ABSTRACT

Serratia
spp. are opportunistic human pathogens responsible for an increasing number of nosocomial infections. However, little is known about the virulence factors and regulatory circuits that may enhance the establishment and long-term survival of
Serratia liquefaciens
in the hospital environment. In this study, two reporter strains,
Chromobacterium violaceum
CV026 and VIR24, and high-resolution triple-quadrupole liquid chromatography–mass spectrometry (LC-MS) were used to detect and to quantify
N
-acyl-homoserine lactone (AHL) quorum-sensing signals in 20
S. liquefaciens
strains isolated from clinical samples. Only four of the strains produced sufficient amounts of AHLs to activate the sensors. Investigation of two of the positive strains by high-performance liquid chromatography (HPLC)-MS confirmed the presence of significant amounts of short-acyl-chain AHLs (
N
-butyryl-
l
-homoserine lactone [C
4
-HSL] and
N
-hexanoyl-
l
-homoserine lactone [C
6
-HSL]) in both strains, which exhibited a complex and strain-specific signal profile that included minor amounts of other short-acyl-chain AHLs (
N
-octanoyl-
l
-homoserine lactone [C
8
-HSL] and
N
-3-oxohexanoyl-
l
-homoserine lactone [OC
6
-HSL]) and long-acyl-chain (C
10
, C
12
, and C
14
) AHLs. No correlation between biofilm formation and the production of large amounts of AHLs could be established. Fimbria-like structures were observed by transmission electron microscopy, and the presence of the type 1 fimbrial adhesin gene
fimH
in all strains was confirmed by PCR. The ability of
S. liquefaciens
to adhere to abiotic surfaces and to form biofilms likely contributes to its persistence in the hospital environment, increasing the probability of causing nosocomial infections. Therefore, a better understanding of the adherence properties of this species will provide greater insights into the diseases it causes.
Analysis of the Candida albicans Phosphoproteome
Authors: Willger S. D. , Liu Z. , Olarte R. A. , Adamo M. E. , Stajich J. E. , Myers L. C. , Kettenbach A. N. , Hogan D. A. 
Published: March 2015

ABSTRACT

Candida albicans
is an important human fungal pathogen in both immunocompetent and immunocompromised individuals.
C. albicans
regulation has been studied in many contexts, including morphological transitions, mating competence, biofilm formation, stress resistance, and cell wall synthesis. Analysis of kinase- and phosphatase-deficient mutants has made it clear that protein phosphorylation plays an important role in the regulation of these pathways. In this study, to further our understanding of phosphorylation in
C. albicans
regulation, we performed a deep analysis of the phosphoproteome in
C. albicans
. We identified 19,590 unique peptides that corresponded to 15,906 unique phosphosites on 2,896 proteins. The ratios of serine, threonine, and tyrosine phosphosites were 80.01%, 18.11%, and 1.81%, respectively. The majority of proteins (2,111) contained at least two detected phosphorylation sites. Consistent with findings in other fungi, cytoskeletal proteins were among the most highly phosphorylated proteins, and there were differences in Gene Ontology (GO) terms for proteins with serine and threonine versus tyrosine phosphorylation sites. This large-scale analysis identified phosphosites in protein components of Mediator, an important transcriptional coregulatory protein complex. A targeted analysis of the phosphosites in Mediator complex proteins confirmed the large-scale studies, and further
in vitro
assays identified a subset of these phosphorylations that were catalyzed by Cdk8 (Ssn3), a kinase within the Mediator complex. These data represent the deepest single analysis of a fungal phosphoproteome and lay the groundwork for future analyses of the
C. albicans
phosphoproteome and specific phosphoproteins.
Structure and Dynamics of the Native HIV-1 Env Trimer
Authors: Munro James B. , Mothes Walther 
Published: March 2015

ABSTRACT
HIV-1/AIDS remains one of the worst pandemics in human history. Despite tremendous efforts, no effective vaccine has been found. Recent reports give new insights into the structure and dynamics of the HIV-1 Env trimer and renew hopes that a better understanding of Env will translate into new vaccine candidates and more-effective antiretroviral therapies.