bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of the phosphorylation targets of symbiotic receptor‐like kinases using a high‐throughput multiplexed assay for kinase specificity
Authors: Jayaraman Dhileepkumar , Richards Alicia L. , Westphall Michael S. , Coon Joshua J. , Ané Jean‐Michel 
Published: March 2017

SummaryDetecting the phosphorylation substrates of multiple kinases in a single experiment is a challenge, and new techniques are being developed to overcome this challenge. Here, we used a multiplexed assay for kinase specificity (MAKS) to identify the substrates directly and to map the phosphorylation site(s) of plant symbiotic receptor‐like kinases. The symbiotic receptor‐like kinases nodulation receptor‐like kinase (NORK) and lysin motif domain‐containing receptor‐like kinase 3 (LYK3) are indispensable for the establishment of root nodule symbiosis. Although some interacting proteins have been identified for these symbiotic receptor‐like kinases, very little is known about their phosphorylation substrates. Using this high‐throughput approach, we identified several other potential phosphorylation targets for both these symbiotic receptor‐like kinases. In particular, we also discovered the phosphorylation of LYK3 by NORK itself, which was also confirmed by pairwise kinase assays. Motif analysis of potential targets for these kinases revealed that the acidic motif xxxsDxxx was common to both of them. In summary, this high‐throughput technique catalogs the potential phosphorylation substrates of multiple kinases in a single efficient experiment, the biological characterization of which should provide a better understanding of phosphorylation signaling cascade in symbiosis.
Using direct antiglobulin test results to reduce unnecessary cold agglutinin testing
Authors: Wilen Craig B. , Booth Garrett S. , Grossman Brenda J. , Lane William J. , Szklarski Penny C. , Jackups Ronald 
Published: March 2017

BACKGROUNDCold agglutinin disease (CAD) is a rare autoimmune hemolytic anemia mediated by autoantibodies that preferentially react at 4°C. Laboratory testing for cold‐reactive autoantibodies is laborious and may not be ordered judiciously, particularly in patients with a negative direct antiglobulin test (DAT). We sought to determine whether a negative DAT using anti‐human complement (anti‐C3) rules out elevated cold agglutinin (CA) titers and the diagnosis of CAD.STUDY DESIGN AND METHODSWe performed a retrospective study of patients with a CA test performed at three major academic medical centers: Barnes‐Jewish Hospital (2003‐2014), Vanderbilt University Medical Center (2007‐2009), and Massachusetts General Hospital (2009‐2014).RESULTSThis study included 801 patients, of whom 51% (n = 410) had a DAT within the 7 days before CA testing. A total of 98% of patients with a negative DAT using anti‐C3 had a negative CA titer (<64). Only five subjects had a negative DAT using anti‐C3 and an elevated CA titer.CONCLUSIONSOverutilization of CA testing could be reduced by establishing laboratory acceptance criteria based on a positive DAT using anti‐C3. Such acceptance criteria would have reduced CA testing by 68% for those with an available DAT result.
Estimation of consistent wet period characteristics for further improvement of water resources studies
Authors: Tarawneh Zeyad 
Published: March 2017

AbstractThis study presents an analysis of consistent wet periods for further improvement of water resources studies. While previous studies have focused on characterizing dry periods, this study uses tree‐ring reconstructed precipitation to detect the occurrence of wet periods of magnitude larger than what can be achieved from the analysis of the historical precipitation records. Tree‐ring reconstructed precipitation for Madaba region in Jordan that began in 1743 was used. The analysis of the historical precipitation indicated the occurrence of short wet periods (1–4 years). The analysis of the 239 years of the reconstructed precipitation indicated the occurrence of long wet periods (7 years), and wet period magnitude of 551 mm, that is 20% larger than the observed from the analysis of historical precipitation. Furthermore, this study presents theoretical formulation that can be used to estimate the expected number of wet events of desired length that could emerge during the operation period of surface resources.
Electrochemical recovery of hydrogen from coal acid mine drainage for the enhancement of sulphate reduction using grass cellulose as carbon source
Authors: Mulopo Jean 
Published: March 2017

AbstractThis paper investigates the generation of hydrogen at the cathode in an electrolytic cell treating acid mine drainage (AMD) and the effect of the generated hydrogen on the biological removal of sulphate using grass cellulose. The performance of the bioreactors was assessed by means of sulphate reduction, chemical oxygen demand (COD), and volatile fatty acid (VFA) utilization. To this end, two batch reactors, A, B were operated similarly with the exception of the addition of hydrogen. Reactor A received no hydrogen to act as a control, while reactor B received hydrogen for the experimental duration. Further experiments were conducted to investigate the feasibility of sulphide oxidation to elemental sulphur using air. The results show that during sulphide oxidation, the sulphate concentration decreased from 364 to 183 mg/L, a decrease of 50% and the concentration of sulphide decreased from 163 to 70 mg/L, a decrease of 57%.
The Effect of Hypnosis on Anxiety in Patients With Cancer: A Meta‐Analysis
Authors: Chen Pei‐Ying , Liu Ying‐Mei , Chen Mei‐Ling 
Published: March 2017

ABSTRACTBackgroundAnxiety is a common form of psychological distress in patients with cancer. One recognized nonpharmacological intervention to reduce anxiety for various populations is hypnotherapy or hypnosis. However, its effect in reducing anxiety in cancer patients has not been systematically evaluated.AimThis meta‐analysis was designed to synthesize the immediate and sustained effects of hypnosis on anxiety of cancer patients and to identify moderators for these hypnosis effects.MethodsQualified studies including randomized controlled trials (RCT) and pre‐post design studies were identified by searching seven electronic databases: Scopus, Medline Ovidsp, PubMed, PsycInfo–Ovid, Academic Search Premier, CINAHL Plus with FT‐EBSCO, and SDOL. Effect size (Hedges’ g) was computed for each study. Random‐effect modeling was used to combine effect sizes across studies. All statistical analyses were conducted with Comprehensive Meta‐Analysis, version 2 (Biostat, Inc., Englewood, NJ, USA).ResultsOur meta‐analysis of 20 studies found that hypnosis had a significant immediate effect on anxiety in cancer patients (Hedges’ g: 0.70–1.41, p < .01) and the effect was sustained (Hedges’ g: 0.61–2.77, p < .01). The adjusted mean effect size (determined by Duvan and Tweedie's trim‐and‐fill method) was 0.46. RCTs had a significantly higher effect size than non‐RCT studies. Higher mean effect sizes were also found with pediatric study samples, hematological malignancy, studies on procedure‐related stressors, and with mixed‐gender samples. Hypnosis delivered by a therapist was significantly more effective than self‐hypnosis.Linking Evidence to ActionHypnosis can reduce anxiety of cancer patients, especially for pediatric cancer patients who experience procedure‐related stress. We recommend therapist‐delivered hypnosis should be preferred until more effective self‐hypnosis strategies are developed.
Rehabilitation programs after the implantation of transfemoral osseointegrated fixations for bone-anchored prostheses: a systematic review protocol
Authors: Vertriest Sofie , Pather Shanthan , Sondergeld Peter , Ramis Mary-Anne , Frossard Laurent 
Published: March 2017

Review question:The primary objective of this scoping review is to characterize rehabilitation programs for individuals with transfemoral amputation following the implantation of screw-type or press-fit osseointegrated fixations for bone-anchored prostheses.The secondary objective of this review is to describe partial weight bearing exercises including static and dynamic exercises as well as use of walking aids in each rehabilitation program for screw-type and press-fit fixations.The third objective of this review is to compare key rehabilitation parameters for various partial weight bearing exercises (e.g. type of training prosthesis, loading time and progression, monitoring of loading, loading direction, instructions given to patients and the use of loading regulators) within each program for screw-type and press-fit fixations (intra-variability) and between programs for screw-type and press-fit fixations (inter-variability).The specific review questions areWhat are the intra-variabilities within rehabilitation programs corresponding to the differences in rehabilitation parameters within programs for each screw-type (Q1) and press-fit (Q2) fixations?What are the inter-variabilities between rehabilitation programs corresponding to the differences in rehabilitation parameters between programs for screw-type and press-fit fixations (Q3)?
Solving the quantum many-body problem with artificial neural networks
Authors: Carleo Giuseppe , Troyer Matthias 
Published: March 2017

Machine learning and quantum physics
Elucidating the behavior of quantum interacting systems of many particles remains one of the biggest challenges in physics. Traditional numerical methods often work well, but some of the most interesting problems leave them stumped. Carleo and Troyer harnessed the power of machine learning to develop a variational approach to the quantum many-body problem (see the Perspective by Hush). The method performed at least as well as state-of-the-art approaches, setting a benchmark for a prototypical two-dimensional problem. With further development, it may well prove a valuable piece in the quantum toolbox.

Science
, this issue p.
602
; see also p.
580
On the deep-mantle origin of the Deccan Traps
Authors: Glišović Petar , Forte Alessandro M. 
Published: March 2017

Double trouble for the Deccan Traps
The continental flood basalts in India known as the Deccan Traps formed from a massive outpouring of lava around the time that dinosaurs went extinct. The event dramatically reshaped the landscape and altered the climate. Glišović and Forte used time-reversed convection modeling to reconstruct the origin of this giant magmatic event. They found that two different deep mantle hotspots joined forces about 65 million years ago to produce one of the largest volcanic features on Earth.

Science
, this issue p.
613
Structural Alteration of OmpR as a Source of Ertapenem Resistance in a CTX-M-15-Producing Escherichia coli O25b:H4 Sequence Type 131 Clinical Isolate
Authors: Dupont Hervé , Choinier Pascaline , Roche David , Adiba Sandine , Sookdeb Megan , Branger Catherine , Denamur Erick , Mammeri Hedi 
Published: March 2017

ABSTRACT

In this study, an ertapenem-nonsusceptible
Escherichia coli
isolate was investigated to determine the genetic basis for its carbapenem resistance phenotype. This clinical strain was recovered from a patient that received, 1 year previously, ertapenem to treat a cholangitis due to a carbapenem-susceptible extended-spectrum-β-lactamase (ESBL)-producing
E. coli
isolate. Whole-genome sequencing of these strains was performed using Illumina and single-molecule real-time sequencing technologies. It revealed that they belonged to the ST131 clonal group, had the predicted O25b:H4 serotype, and produced the CTX-M-15 and TEM-1 β-lactamases. One nucleotide substitution was identified between these strains. It affected the
ompR
gene, which codes for a regulatory protein involved in the control of OmpC/OmpF porin expression, creating a Gly-63-Val substitution. The role of OmpR alteration was confirmed by a complementation experiment that fully restored the susceptibility to ertapenem of the clinical isolate. A modeling study showed that the Gly-63-Val change displaced the histidine-kinase phosphorylation site. SDS-PAGE analysis revealed that the ertapenem-nonsusceptible
E. coli
strain had a decreased expression of OmpC/OmpF porins. No significant defect in the growth rate or in the resistance to
Dictyostelium discoideum
amoeba phagocytosis was found in the ertapenem-nonsusceptible
E. coli
isolate compared to its susceptible parental strain. Our report demonstrates for the first time that ertapenem resistance may emerge clinically from ESBL-producing
E. coli
due to mutations that modulate the OmpR activity.
High Prevalence and Predominance of the
aph(2″)-If
Gene Conferring Aminoglycoside Resistance in Campylobacter
Authors: Yao Hong , Liu Dejun , Wang Yang , Zhang Qijing , Shen Zhangqi 
Published: March 2017

ABSTRACT

Campylobacter
is a major foodborne pathogen, and previous studies revealed that
Campylobacter
isolates from food-producing animals are increasingly resistant to gentamicin in China. The molecular epidemiology and genetic mechanisms responsible for gentamicin resistance in China have not been well understood. In this study, 607
Campylobacter
isolates of chicken and swine origins collected in 2014 were analyzed, revealing that 15.6% (25/160) of the
Campylobacter jejuni
isolates and 79.9% (357/447) of the
Campylobacter coli
isolates were resistant to gentamicin. PCR detection of the gentamicin resistance genes indicated that
aph(2″)-If
was more prevalent than the previously identified
aacA/aphD
gene and has become the dominant gentamicin resistance determinant in
Campylobacter
. Transformation and whole-genome sequencing as well as long-range PCR discovered that
aph(2″)-If
was located on a chromosomal segment inserted between two conserved genes, Cj0299 and
panB
. Cloning of
aph(2″)-If
into gentamicin-susceptible
C. jejuni
NCTC 11168 confirmed its function in conferring high-level resistance to gentamicin and kanamycin. Molecular typing by pulsed-field gel electrophoresis suggested that both regional expansion of a particular clone and horizontal transmission were involved in the dissemination of the
aph(2″)-If
gene in
Campylobacter
. To our knowledge, this is the first report describing the high prevalence of a chromosomally encoded
aph(2″)-If
gene in
Campylobacter
. The high prevalence and predominance of this gene might be driven by the use of aminoglycoside antibiotics in food animal production in China and potentially compromise the usefulness of gentamicin as a therapeutic agent for
Campylobacter
-associated systemic infection.
Pharmacokinetics and Pharmacodynamics of Minocycline against Acinetobacter baumannii in a Neutropenic Murine Pneumonia Model
Authors: Zhou Jian , Ledesma Kimberly R. , Chang Kai-Tai , Abodakpi Henrietta , Gao Song , Tam Vincent H. 
Published: March 2017

ABSTRACT

Multidrug-resistant (MDR)
Acinetobacter baumannii
is increasingly more prevalent in nosocomial infections. Although
in vitro
susceptibility of
A. baumannii
to minocycline is promising, the
in vivo
efficacy of minocycline has not been well established. In this study, the
in vivo
activity of minocycline was evaluated in a neutropenic murine pneumonia model. Specifically, we investigated the relationship between minocycline exposure and bactericidal activity using five
A. baumannii
isolates with a broad range of susceptibility (MIC ranged from 0.25 mg/liter to 16 mg/liter). The pharmacokinetics of minocycline (single dose of 25 mg/kg of body weight, 50 mg/kg, 100 mg/kg, and a humanized regimen, given intraperitoneally) in serum and epithelial lining fluid (ELF) were characterized. Dose linearity was observed for doses up to 50 mg/kg and pulmonary penetration ratios (area under the concentration-time curve in ELF from 0 to 24 h [AUC
ELF,0–24
]/area under the concentration time curve in serum from 0 to 24 h [AUC
serum,0–24
]) ranged from 2.5 to 2.8. Pharmacokinetic-pharmacodynamics (PK-PD) index values in ELF for various dose regimens against different
A. baumannii
isolates were calculated. The maximum efficacy at 24 h was approximately 1.5-log-unit reduction of pulmonary bacterial burdens from baseline. The AUC/MIC ratio was the PK-PD index most closely correlating to the bacterial burden (
r
2
= 0.81). The required AUC
ELF,0–24
/MIC for maintaining stasis and achieving 1-log-unit reduction were 140 and 410, respectively. These findings could guide the treatment of infections caused by
A. baumannii
using minocycline in the future. Additional studies to examine resistance development during therapy are warranted.
Impact of High-Level Daptomycin Resistance in the Streptococcus mitis Group on Virulence and Survivability during Daptomycin Treatment in Experimental Infective Endocarditis
Authors: Garcia-de-la-Maria C. , Xiong Y. Q. , Pericas J. M. , Armero Y. , Moreno A. , Mishra N. N. , Rybak M. J. , Tran T. T. , Arias C. A. , Sullam P. M. , Bayer A. S. , Miro J. M. 
Published: March 2017

ABSTRACT

Among the viridans group streptococci, the
Streptococcus mitis
group is the most common cause of infective endocarditis. These bacteria have a propensity to be β-lactam resistant, as well as to rapidly develop high-level and durable resistance to daptomycin (DAP). We compared a parental, daptomycin-susceptible (DAP
s
)
S. mitis/S. oralis
strain and its daptomycin-resistant (DAP
r
) variant in a model of experimental endocarditis in terms of (i) their relative fitness in multiple target organs in this model (vegetations, kidneys, spleen) when animals were challenged individually and in a coinfection strategy and (ii) their survivability during therapy with daptomycin-gentamicin (an
in vitro
combination synergistic against the parental strain). The DAP
r
variant was initially isolated from the cardiac vegetations of animals with experimental endocarditis caused by the parental DAP
s
strain following treatment with daptomycin. The parental strain and the DAP
r
variant were comparably virulent when animals were individually challenged. In contrast, in the coinfection model without daptomycin therapy, at both the 10
6
- and 10
7
-CFU/ml challenge inocula, the parental strain outcompeted the DAP
r
variant in all target organs, especially the kidneys and spleen. When the animals in the coinfection model of endocarditis were treated with DAP-gentamicin, the DAP
s
strain was completely eliminated, while the DAP
r
variant persisted in all target tissues. These data underscore that the acquisition of DAP
r
in
S. mitis/S. oralis
does come at an intrinsic fitness cost, although this resistance phenotype is completely protective against therapy with a potentially synergistic DAP regimen.
Praziquantel for Schistosomiasis: Single-Drug Metabolism Revisited, Mode of Action, and Resistance
Authors: Vale Nuno , Gouveia Maria João , Rinaldi Gabriel , Brindley Paul J. , Gärtner Fátima , Correia da Costa José M. 
Published: March 2017

ABSTRACT
Schistosomiasis, a major neglected tropical disease, affects more than 250 million people worldwide. Treatment of schistosomiasis has relied on the anthelmintic drug praziquantel (PZQ) for more than a generation. PZQ is the drug of choice for the treatment of schistosomiasis; it is effective against all major forms of schistosomiasis, although it is less active against juvenile than mature parasites. A pyrazino-isoquinoline derivative, PZQ is not considered to be toxic and generally causes few or transient, mild side effects. Increasingly, mass drug administration targeting populations in sub-Saharan Africa where schistosomiasis is endemic has led to the appearance of reduced efficacy of PZQ, which portends the selection of drug-resistant forms of these pathogens. The synthesis of improved derivatives of PZQ is attracting attention, e.g., in the (i) synthesis of drug analogues, (ii) rational design of pharmacophores, and (iii) discovery of new compounds from large-scale screening programs. This article reviews reports from the 1970s to the present on the metabolism and mechanism of action of PZQ and its derivatives against schistosomes.
Prophylaxis with Isavuconazole or Posaconazole Protects Immunosuppressed Mice from Pulmonary Mucormycosis
Authors: Gebremariam Teclegiorgis , Alkhazraji Sondus , Baldin Clara , Kovanda Laura , Wiederhold Nathan P. , Ibrahim Ashraf S. 
Published: March 2017

ABSTRACT

We assessed prophylactic or continuous therapy of isavuconazole, posaconazole, or voriconazole in treating pulmonary murine mucormycosis. In the prophylaxis studies, only isavuconazole treatment resulted in significantly improved survival and lowered tissue fungal burden of immunosuppressed mice infected with
Rhizopus delemar.
In the continuous treatment studies, isavuconazole and posaconazole, but not voriconazole, equally prolonged survival time and lowered tissue fungal burden compared to placebo-treated mice. These results support the use of isavuconazole and posaconazole in prophylaxis treatment.
Clinical Response of Tedizolid versus Linezolid in Acute Bacterial Skin and Skin Structure Infections by Severity Measure Using a Pooled Analysis from Two Phase 3 Double-Blind Trials
Authors: Sandison Taylor , De Anda Carisa , Fang Edward , Das Anita F. , Prokocimer Philippe 
Published: March 2017

ABSTRACT
Tedizolid phosphate is approved for the treatment of acute bacterial skin and skin structure infections (ABSSSI). In a pooled analysis of 1,333 ABSSSI patients from the ESTABLISH clinical trials, treatment with tedizolid or linezolid demonstrated similar early and posttherapy clinical responses in nonsevere and severe disease, irrespective of the parameters used to measure ABSSSI severity. Shorter 6-day treatment of ABSSSI, including those that were severe, with tedizolid phosphate demonstrated efficacy comparable to that of 10-day treatment with linezolid. (The ESTABLISH studies discussed in this paper have been registered at ClinicalTrials.gov under identifiers NCT01170221 and NCT01421511.)
Contributions of both ATP-Binding Cassette Transporter and Cyp51A Proteins Are Essential for Azole Resistance in Aspergillus fumigatus
Authors: Paul Sanjoy , Diekema Daniel , Moye-Rowley W. Scott 
Published: March 2017

ABSTRACT

While azole drugs targeting the biosynthesis of ergosterol are effective antifungal agents, their extensive use has led to the development of resistant organisms. Infections involving azole-resistant forms of the filamentous fungus
Aspergillus fumigatus
are often associated with genetic changes in the
cyp51A
gene encoding the lanosterol α14 demethylase target enzyme. Both a sequence duplication in the
cyp51A
promoter (TR34) and a substitution mutation in the coding sequence (L98H) are required for the full expression of azole resistance. A mechanism commonly observed in pathogenic yeast such as
Candida albicans
involves gain-of-function mutations in transcriptional regulatory proteins that induce expression of genes encoding ATP-binding cassette (ABC) transporters. We and others have found that an ABC transporter protein called Cdr1B (here referred to as AbcG1) is required for wild-type azole resistance in
A. fumigatus
. Here, we test the genetic relationship between the TR34 L98H allele of
cyp51A
and an
abcG1
null mutation. Loss of AbcG1 from a TR34 L98H
cyp51A
-containing strain caused a large decrease in the azole resistance of the resulting double-mutant strain. We also generated antibodies that enabled the detection of both the wild-type and L98H forms of the Cyp51A protein. The introduction of the L98H lesion into the
cyp51A
gene led to a decreased production of immunoreactive enzyme, suggesting that this mutant protein is unstable. Our data confirm the importance of AbcG1 function during azole resistance even in a strongly drug-resistant background.