bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stress‐induced increase in skeletal muscle force requires protein kinase A phosphorylation of the ryanodine receptor
Authors: Andersson Daniel C. , Betzenhauser Matthew J. , Reiken Steven , Umanskaya Alisa , Shiomi Takayuki , Marks Andrew R. 
Published: October 2012

Key points
Under conditions of acute adrenergic stress (i.e. fight or flight response), the contractile force of muscle is enhanced, a phenomenon known as inotropy.
The molecular determinant of the inotropic mechanism is poorly understood but involves potentiated release of calcium within the muscle cell.
Here we report that adrenergic receptor‐dependent phosphorylation of a single amino acid in the calcium release channel (ryanodine receptor 1) mediates the increased calcium and force that is seen in the muscle following acute stress.
These findings further our understanding of the molecular mechanisms of muscular force regulation, and the importance for exercise physiology and muscle weakness (dynopenia).
Abstract  Enhancement of contractile force (inotropy) occurs in skeletal muscle following neuroendocrine release of catecholamines and activation of muscle β‐adrenergic receptors. Despite extensive study, the molecular mechanism underlying the inotropic response in skeletal muscle is not well understood. Here we show that phosphorylation of a single serine residue (S2844) in the sarcoplasmic reticulum (SR) Ca2+ release channel/ryanodine receptor type 1 (RyR1) by protein kinase A (PKA) is critical for skeletal muscle inotropy. Treating fast twitch skeletal muscle from wild‐type mice with the β‐receptor agonist isoproterenol (isoprenaline) increased RyR1 PKA phosphorylation, twitch Ca2+ and force generation. In contrast, the enhanced muscle Ca2+, force and in vivo muscle strength responses following isoproterenol stimulation were abrogated in RyR1‐S2844A mice in which the serine in the PKA site in RyR1 was replaced with alanine. These data suggest that the molecular mechanism underlying skeletal muscle inotropy requires enhanced SR Ca2+ release due to PKA phosphorylation of S2844 in RyR1.
ON and OFF channels in human retinal ganglion cells
Authors: Hashimoto Takao , Katai Satoshi , Saito Yasunori , Kobayashi Fumitoshi , Goto Tetsuya 
Published: October 2012

Key points
The ON and OFF channels are basic functional elements in parallel processing in the visual system in vertebrates including primates, and ON cells excite by positive contrasts, while OFF cells excite by negative contrasts.
We investigated the electrophysiological properties of optic tract fibre activities in neurosurgical patients with Parkinson's disease, focusing on ON‐ and OFF‐type responses to flashlight stimulation.
Most of the multi‐fibre responses at the light on event were excitatory, and excitatory responses at the light off event were observed at a few sites. Analysis of the single‐fiber responses revealed ON fibres and OFF fibres.
All excitatory responses to light on were transient, while all but one excitatory responses to light off were sustained. These different response types are said to contain different modes of visual information.
Our results demonstrate for the first time the ON and OFF channels and their temporal features in visual processing in humans.
Abstract  The ON and OFF channels are basic functional elements in parallel processing in the visual system in vertebrates including primates. We analysed the responses of the optic tract fibre activity in response to switching a flashlight on or off in 25 awake patients with Parkinson's disease who underwent stereotactic surgery targeting the internal globus pallidus. The responses were evoked in a darkened room by a light with a luminance of approximately 4 × 104 cd m−2 at the eye and a wide‐spectrum wavelength. Most of the responses at the light on event were excitatory (38 out of 41 sites, 93%). Thirty‐five sites with increase in activity at the light on event showed reciprocal responses or no responses to light off, and these sites were classified as containing ON fibres. In single‐fibre analysis, all of 14 ON fibres were recorded at the sites of multi‐fibre excitatory responses. Six sites showed multi‐fibre excitatory responses at the light off event; three sites showed sustained reduction in activity at the light on event, and these three sites were classified as containing OFF fibres. In single‐fibre analysis, two OFF fibres were recorded at the sites of multi‐fibre suppressive responses at the light on event, and the other two OFF fibres were recorded at the sites of multi‐fibre excitatory responses at the light on event. We found that all excitatory responses to light on were transient, while all but one excitatory responses to light off were sustained. Reduction in activity tended to be smaller than increase in activity at the light on event. These results demonstrate that the ON and OFF channels, and their transient and sustained features function in visual processing in humans.
Multicriteria optimization for volumetric‐modulated arc therapy by decomposition into a fluence‐based relaxation and a segment weight‐based restriction
Authors: Bokrantz Rasmus 
Published: October 2012

Purpose:To develop a method for inverse volumetric‐modulated arc therapy (VMAT) planning that combines multicriteria optimization (MCO) with direct machine parameter optimization. The ultimate goal is to provide an efficient and intuitive method for generating high quality VMAT plans.Methods:Multicriteria radiation therapy treatment planning amounts to approximating the relevant treatment options by a discrete set of plans, and selecting the combination thereof that strikes the best possible balance between conflicting objectives. This approach is applied to two decompositions of the inverse VMAT planning problem: a fluence‐based relaxation considered at a coarsened gantry angle spacing and under a regularizing penalty on fluence modulation, and a segment weight‐based restriction in a neighborhood of the solution to the relaxed problem. The two considered variable domains are interconnected by direct machine parameter optimization toward reproducing the dose‐volume histogram of the fluence‐based solution.Results:The dose distribution quality of plans generated by the proposed MCO method was assessed by direct comparison with benchmark plans generated by a conventional VMAT planning method. The results for four patient cases (prostate, pancreas, lung, and head and neck) are highly comparable between the MCO plans and the benchmark plans: Discrepancies between studied dose‐volume statistics for organs at risk were—with the exception of the kidneys of the pancreas case—within 1 Gy or 1 percentage point. Target coverage of the MCO plans was comparable with that of the benchmark plans, but with a small tendency toward a shift from conformity to homogeneity.Conclusions:MCO allows tradeoffs between conflicting objectives encountered in VMAT planning to be explored in an interactive manner through search over a continuous representation of the relevant treatment options. Treatment plans selected from such a representation are of comparable dose distribution quality to conventionally optimized VMAT plans.
Visualizing ex vivo radiofrequency and microwave ablation zones using electrode vibration elastography
Authors: DeWall Ryan J. , Varghese Tomy , Brace Chris L. 
Published: October 2012

Purpose:Electrode vibration elastography is a new shear wave imaging technique that can be used to visualize thermal ablation zones. Prior work has shown the ability of electrode vibration elastography to delineate radiofrequency ablations; however, there has been no previous study of delineation of microwave ablations or radiological–pathological correlations using multiple observers.Methods:Radiofrequency and microwave ablations were formed inex vivo bovine liver tissue. Their visualization was compared on shear wave velocity and maximum displacement images. Ablation dimensions were compared to gross pathology. Elastographic imaging and gross pathology overlap and interobserver variability were quantified using similarity measures.Results:Elastographic imaging correlated with gross pathology. Correlation of area estimates was better in radiofrequency than in microwave ablations, with Pearson coefficients of 0.79 and 0.54 on shear wave velocity images and 0.90 and 0.70 on maximum displacement images for radiofrequency and microwave ablations, respectively. The absolute relative difference in area between elastographic imaging and gross pathology was 18.9% and 22.9% on shear wave velocity images and 16.0% and 23.1% on maximum displacement images for radiofrequency and microwave ablations, respectively.Conclusions:Statistically significant radiological–pathological correlation was observed in this study, but correlation coefficients were lower than other modulus imaging techniques, most notably in microwave ablations. Observers provided similar delineations for most thermal ablations. These results suggest that electrode vibration elastography is capable of imaging thermal ablations, but refinement of the technique may be necessary before it can be used to monitor thermal ablation procedures clinically.
Activity of Moxifloxacin, Imipenem, and Ertapenem against Escherichia coli, Enterobacter cloacae, Enterococcus faecalis, and Bacteroides fragilis in Monocultures and Mixed Cultures in an
In Vitro
Pharmacokinetic/Pharmacodynamic Model Simulating Concentrations in the Human Pancreas
Authors: Schubert Sabine , Dalhoff Axel 
Published: October 2012

ABSTRACT

The activities of moxifloxacin, imipenem, and ertapenem against pathogens causing severe necrotizing pancreatitis were studied in an
in vitro
pharmacokinetics/pharmacodynamics (PK/PD) model.
Escherichia coli
,
Enterobacter cloacae
,
Enterococcus faecalis
, and
Bacteroides fragilis
were exposed in monocultures and mixed cultures to concentrations of the three agents comparable to those in the human pancreas. Moxifloxacin was more active than the two carbapenems in monocultures and mixed cultures, reducing the numbers of CFU more drastically and more rapidly.
KPC-4 Is Encoded within a Truncated Tn
4401
in an IncL/M Plasmid, pNE1280, Isolated from Enterobacter cloacae and Serratia marcescens
Authors: Bryant Kendall A. , Van Schooneveld Trevor C. , Thapa Ishwor , Bastola Dhundy , Williams Laurina O. , Safranek Thomas J. , Hinrichs Steven H. , Rupp Mark E. , Fey Paul D. 
Published: October 2012

ABSTRACT

We describe the transfer of
bla
KPC-4
from
Enterobacter cloacae
to
Serratia marcescens
in a single patient. DNA sequencing revealed that KPC-4 was encoded on an IncL/M plasmid, pNE1280, closely related to pCTX-M360. Further analysis found that KPC-4 was encoded within a novel Tn
4401
element (Tn
4401f
) containing a truncated
tnpA
and lacking
tnpR
, IS
Kpn7
left, and Tn
4401
IRL-1, which are conserved in other Tn
4401
transposons. This study highlights the continued evolution of Tn
4401
transposons and movement to multiple plasmid backbones that results in acquisition by multiple species of Gram-negative bacilli.
Complete Sequence of pJIE186-2, a Plasmid Carrying Multiple Virulence Factors from a Sequence Type 131 Escherichia coli O25 Strain
Authors: Zong Zhiyong 
Published: October 2012

ABSTRACT

The complete sequence of a 137-kb plasmid, pJIE186-2, from a sequence type 131 (ST131)
Escherichia coli
strain was determined. pJIE186-2 contained IncF replicons (FIB, FIIA, and FIAΔ), an incomplete conjugative region, and multiple virulence factors (
sitABCD
,
iucABCD-iutA
,
iroCDEN
,
etsABC
,
hlyF
,
iss
,
ompT
, and
vagCD
) but no antimicrobial resistance genes. The host strain also had another plasmid, pJIE186-1, carrying multiple resistance genes. The two plasmids conferred selective advantages for the host strain, contributing to the recent emergence of ST131
E. coli
.
Novel 6′-
N
-Aminoglycoside Acetyltransferase AAC(6′)-Iaj from a Clinical Isolate of Pseudomonas aeruginosa
Authors: Tada Tatsuya , Miyoshi-Akiyama Tohru , Shimada Kayo , Shimojima Masahiro , Kirikae Teruo 
Published: October 2012

ABSTRACT

Pseudomonas aeruginosa
NCGM1588 has a novel chromosomal class 1 integron, In151, which includes the
aac(6′)-Iaj
gene. The encoded protein, AAC(6′)-Iaj, was found to consist of 184 amino acids, with 70% identity to AAC(6′)-Ia.
Escherichia coli
transformed with a plasmid containing the
aac(6′)-Iaj
gene acquired resistance to all aminoglycosides tested except gentamicin. Of note,
aac(6′)-Iaj
contributed to the resistance to arbekacin. Thin-layer chromatography revealed that AAC(6′)-Iaj acetylated all aminoglycosides tested except gentamicin. These findings indicated that AAC(6′)-Iaj is a functional acetyltransferase that modifies the amino groups at the 6′ positions of aminoglycosides and contributes to aminoglycoside resistance of
P. aeruginosa
NCGM1588, including arbekacin.
Structural Insights into the Subclass B3 Metallo-β-Lactamase SMB-1 and the Mode of Inhibition by the Common Metallo-β-Lactamase Inhibitor Mercaptoacetate
Authors: Wachino Jun-ichi , Yamaguchi Yoshihiro , Mori Shigetarou , Kurosaki Hiromasa , Arakawa Yoshichika , Shibayama Keigo 
Published: October 2012

ABSTRACT

A novel subclass B3 metallo-β-lactamase (MBL), SMB-1, recently identified from a
Serratia marcescens
clinical isolate, showed a higher hydrolytic activity against a wide range of β-lactams than did the other subclass B3 MBLs, i.e., BJP-1 and FEZ-1, from environmental bacteria. To identify the mechanism underlying the differences in substrate specificity among the subclass B3 MBLs, we determined the structure of SMB-1, using 1.6-Å diffraction data. Consequently, we found that SMB-1 reserves a space in the active site to accommodate β-lactam, even with a bulky R1 side chain, due to a loss of amino acid residues corresponding to F31 and L226 of BJP-1, which protrude into the active site to prevent β-lactam from binding. The protein also possesses a unique amino acid residue, Q157, which probably plays a role in recognition of β-lactams via the hydrogen bond interaction, which is missing in BJP-1 and FEZ-1, whose

K
m

values for β-lactams are particularly high. In addition, we determined the mercaptoacetate (MCR)-complexed SMB-1 structure and revealed the mode of its inhibition by MCR: the thiolate group bridges to two zinc ions (Zn1 and Zn2). One of the carboxylate oxygen atoms of MCR makes contact with Zn2 and Ser221, and the other makes contact with T223 and a water molecule. Our results demonstrate the possibility that MCR could be a potent inhibitor for subclass B3 MBLs and that the screening technique using MCR as an inhibitor would be effective for detecting subclass B3 MBL producers.
Epidemiology of Vancomycin-Resistant Enterococcus faecalis: a Case-Case-Control Study
Authors: Hayakawa Kayoko , Marchaim Dror , Palla Mohan , Gudur Uma Mahesh , Pulluru Harish , Bathina Pradeep , Alshabani Khaled , Govindavarjhulla Aditya , Mallad Ashwini , Abbadi Deepika Reddy , Chowdary Deepti , Kakarlapudi Hari , Guddati Harish , Das Manoj , Kannekanti Naveen , Vemuri Praveen , Doddamani Rajiv , Mundra Venkat Ram Rakesh , Guddeti Raviteja Reddy , Policherla Rohan , Bai Sarika , Lohithaswa Sharan , Shashidharan Shiva Prasad , Chidurala Sowmya , Diviti Sreelatha , Sukayogula Krishna , Joseph Melwin , Pogue Jason M. , Lephart Paul R. , Martin Emily T. , Rybak Michael J. , Kaye Keith S. 
Published: October 2012

ABSTRACT

Although much is known about vancomycin-resistant (VR)
Enterococcus faecium
, little is known about the epidemiology of VR
Enterococcus faecalis
. The predilection of VR
E. faecalis
to transfer the vancomycin resistance determinant to
Staphylococcus aureus
is much greater than that of VR
E. faecium
. The epidemiology of VR
E. faecalis
has important implications regarding the emergence of vancomycin-resistant
S. aureus
(VRSA); 8 of 13 reported VRSA cases have been from Michigan. A retrospective case-case-control study was conducted at the Detroit Medical Center, located in southeastern Michigan. Unique patients with VR
E. faecalis
infection were matched to patients with strains of vancomycin-susceptible (VS)
E. faecalis
and to uninfected controls at a 1:1:1 ratio. Five hundred thirty-two VR
E. faecalis
cases were identified and were matched to 532 VS
E. faecalis
cases and 532 uninfected controls. The overall mean age of the study cohort (
n
= 1,596) was 63.0 ± 17.4 years, and 747 (46.8%) individuals were male. Independent predictors for the isolation of VR
E. faecalis
(but not VS
E. faecalis
) compared to uninfected controls were an age of ≥65 years, nonhome residence, diabetes mellitus, peripheral vascular disease, exposure to cephalosporins and fluoroquinolones in the prior 3 months, and immunosuppressive status. Invasive procedures and/or surgery, chronic skin ulcers, and indwelling devices were risk factors for both VR
E. faecalis
and VS
E. faecalis
isolation. Cephalosporin and fluoroquinolone exposures were unique, independent predictors for isolation of VR
E. faecalis
. A majority of case patients had VR
E. faecalis
present at the time of admission. Control of VR
E. faecalis
, and ultimately VRSA, will likely require regional efforts focusing on infection prevention and antimicrobial stewardship.
Antifungal Lock Therapy
Authors: Walraven Carla J. , Lee Samuel A. 
Published: October 2012

ABSTRACT

The widespread use of intravascular devices, such as central venous and hemodialysis catheters, in the past 2 decades has paralleled the increasing incidence of catheter-related bloodstream infections (CR-BSIs).
Candida albicans
is the fourth leading cause of hospital-associated BSIs. The propensity of
C. albicans
to form biofilms on these catheters has made these infections difficult to treat due to multiple factors, including increased resistance to antifungal agents. Thus, curing CR-BSIs caused by
Candida
species usually requires catheter removal in addition to systemic antifungal therapy. Alternatively, antimicrobial lock therapy has received significant interest and shown promise as a strategy to treat CR-BSIs due to
Candida
species. The existing
in vitro
, animal, and patient data for treatment of
Candida
-related CR-BSIs are reviewed. The most promising antifungal lock therapy (A
f
LT) strategies include use of amphotericin, ethanol, or echinocandins. Clinical trials are needed to further define the safety and efficacy of A
f
LT.
Rapid Identification of Carbapenemase Types in Enterobacteriaceae and Pseudomonas spp. by Using a Biochemical Test
Authors: Dortet Laurent , Poirel Laurent , Nordmann Patrice 
Published: October 2012

ABSTRACT

A biochemical test (Carba NP test II) was developed to identify carbapenemase production in
Enterobacteriaceae
and
Pseudomonas
spp. and to discriminate between the different types of carbapenemases (classes A, B, and D). It is based on the detection of the acidification resulting from imipenem hydrolysis, coupled with tazobactam and EDTA as inhibitors. This is an easy and reliable technique (100% sensitivity and specificity) for detection of not only carbapenemase activity but also carbapenemase types in
Enterobacteriaceae
and
Pseudomonas aeruginosa
.
Liposome-Mediated Delivery of Iminosugars Enhances Efficacy against Dengue Virus
In Vivo
Authors: Miller Joanna L. , Lachica Ruben , Sayce Andrew C. , Williams James P. , Bapat Manisha , Dwek Raymond , Beatty P. Robert , Harris Eva , Zitzmann Nicole 
Published: October 2012

ABSTRACT

A key challenge faced by promising antiviral drugs, such as iminosugars, is
in vivo
delivery to achieve effective levels of drug without toxicity. Four iminosugars, all deoxynojirimycin (DNJ) derivatives—
N
-butyl DNJ (
N
B-DNJ),
N
-nonyl DNJ,
N
-(9-methoxynonyl) DNJ, and
N
-(6′-[4″-azido-2″-nitrophenylamino]hexyl)-1-DNJ (
N
AP-DNJ)—potently inhibited both the percentage of cells infected with dengue virus and release of infectious virus from primary human monocyte-derived macrophages, demonstrating their efficacy in primary cells. In a lethal antibody-dependent enhancement mouse model of dengue pathogenesis, free
N
B-DNJ significantly enhanced survival and lowered viral load in organs and serum. Liposome-mediated delivery of
N
B-DNJ, in comparison with free
N
B-DNJ, resulted in a 3-log
10
reduction in the dose of drug sufficient to enhance animal survival. The optimizing of the effective dose in this way could liberate the therapeutic potential of many cytotoxic antivirals against both dengue virus and a wide array of other viruses.
Characterization of the Polymyxin B Resistome of Pseudomonas aeruginosa
Authors: Fernández Lucía , Álvarez-Ortega Carolina , Wiegand Irith , Olivares Jorge , Kocíncová Dana , Lam Joseph S. , Martínez José Luis , Hancock Robert E. W. 
Published: October 2012

ABSTRACT

Multidrug resistance in
Pseudomonas aeruginosa
is increasingly becoming a threat for human health. Indeed, some strains are resistant to almost all currently available antibiotics, leaving very limited choices for antimicrobial therapy. In many such cases, polymyxins are the only available option, although as their utilization increases so does the isolation of resistant strains. In this study, we screened a comprehensive PA14 mutant library to identify genes involved in changes of susceptibility to polymyxin B in
P. aeruginosa
. Surprisingly, our screening revealed that the polymyxin B resistome of this microorganism is fairly small. Thus, only one resistant mutant and 17 different susceptibility/intrinsic resistance determinants were identified. Among the susceptible mutants, a significant number carried transposon insertions in lipopolysaccharide (LPS)-related genes. LPS analysis revealed that four of these mutants (
galU
,
lptC
,
wapR
, and
ssg
) had an altered banding profile in SDS-polyacrylamide gels and Western blots, with three of them exhibiting LPS core truncation and lack of O-antigen decoration. Further characterization of these four mutants showed that their increased susceptibility to polymyxin B was partly due to increased basal outer membrane permeability. Additionally, these mutants also lacked the aminoarabinose-substituted lipid A species observed in the wild type upon growth in low magnesium. Overall, our results emphasize the importance of LPS integrity and lipid A modification in resistance to polymyxins in
P. aeruginosa
, highlighting the relevance of characterizing the genes that affect biosynthesis of cell surface structures in this pathogen to follow the evolution of peptide resistance in the clinic.