bluuebunny/crossref_metadata_2025 huggingface dataset:
EXA1, a GYF domain protein, is responsible for loss‐of‐susceptibility to plantago asiatica mosaic virus in Arabidopsis thaliana
Authors: Hashimoto Masayoshi , Neriya Yutaro , Keima Takuya , Iwabuchi Nozomu , Koinuma Hiroaki , Hagiwara‐Komoda Yuka , Ishikawa Kazuya , Himeno Misako , Maejima Kensaku , Yamaji Yasuyuki , Namba Shigetou
Published: July 2016

One of the plant host resistance machineries to viruses is attributed to recessive alleles of genes encoding critical host factors for virus infection. This type of resistance, also referred to as recessive resistance, is useful for revealing plant–virus interactions and for breeding antivirus resistance in crop plants. Therefore, it is important to identify a novel host factor responsible for robust recessive resistance to plant viruses. Here, we identified a mutant from an ethylmethane sulfonate (EMS)‐mutagenized Arabidopsis population which confers resistance to plantago asiatica mosaic virus (PlAMV, genus Potexvirus). Based on map‐based cloning and single nucleotide polymorphism analysis, we identified a premature termination codon in a functionally unknown gene containing a GYF domain, which binds to proline‐rich sequences in eukaryotes. Complementation analyses and robust resistance to PlAMV in a T‐DNA mutant demonstrated that this gene, named Essential for poteXvirus Accumulation 1 (EXA1), is indispensable for PlAMV infection. EXA1 contains a GYF domain and a conserved motif for interaction with eukaryotic translation initiation factor 4E (eIF4E), and is highly conserved among monocot and dicot species. Analysis using qRT‐PCR and immunoblotting revealed that EXA1 was expressed in all tissues, and was not transcriptionally responsive to PlAMV infection in Arabidopsis plants. Moreover, accumulation of PlAMV and a PlAMV‐derived replicon was drastically diminished in the initially infected cells by the EXA1 deficiency. Accumulation of two other potexviruses also decreased in exa1‐1 mutant plants. Our results provided a functional annotation to GYF domain‐containing proteins by revealing the function of the highly conserved EXA1 gene in plant–virus interactions.
The role of the store‐operated calcium entry channel Orai1 in cultured rat hippocampal synapse formation and plasticity
Authors: Korkotian Eduard , Oni‐Biton Efrat , Segal Menahem
Published: July 2016

Key points

The role of non‐synaptic calcium entry in the formation and functions of dendritic spines was studied in dissociated cultured rat hippocampal neurons.

Orai1, a store‐operated calcium channel, is found in dendritic spines.

Orai1 co‐localizes in dendritic spines with STIM2 under conditions of lower [Ca2+]o.

Orai1 channels are associated with the formation of new dendritic spines in response to elevated [Ca2+]o.

Lack of Orai1, either by transfection with a dominant negative construct or with small interfering RNA to Orai1, results in retarded dendritic spines, an increase in density of filopodia, lower synaptic connectivity and the ability to undergo plastic changes.

These results highlight a novel role for Orai1 in synapse formation, maturation and plasticity.

The possible role of store operated calcium entry (SOCE) through the Orai1 channel in the formation and functions of dendritic spines was studied in cultured hippocampal neurons. In calcium store‐depleted neurons, a transient elevation of extracellular calcium concentration ([Ca2+]o) caused a rise in [Ca2+]ithat was mediated by activation of the SOCE. The store depletion resulted in an increase in stromal interacting molecule 2 (an endoplasmic calcium sensor) association with Orai1 in dendritic spines. The response to the rise in [Ca2+]owas larger in spines endowed with a cluster of Orai1 molecules than in spines devoid of Orai1. Transfection of neurons with a dominant negative Orai1 resulted in retarded maturation of dendritic spines, a reduction in synaptic connectivity with afferent neurons and a reduction in the ability to undergo morphological changes following induction of chemical long‐term potentiation. Similarly, small interfering RNA (siRNA)‐treated neurons had fewer mature dendritic spines, and lower rates of mEPSCs compared to scrambled control siRNA‐treated neurons. Thus, influx of calcium through Orai1 channels facilitates the maturation of dendritic spines and the formation of functional synapses in central neurons.
Adsorption of Papain on solid substrates of different hydrophobicity
Authors: Lachmanová Štěpánka , Kolivoška Viliam , Pospíšil Lubomír , Fanelli Nicolangelo , Hromadová Magdaléna
Published: July 2016

Adsorption properties of protein Papain at the solid|liquid (0.1 M KCl) interfaces of different hydrophobicity [highly oriented pyrolytic graphite (HOPG), bare gold, CH3, OH, and COOH-terminated self-assembled monolayers on gold] were studied by a combined quartz crystal microbalance and atomic force microscopy techniques. It was found that Papain forms an incomplete monolayer at hydrophobic interfaces (HOPG and CH3-terminated substrate), whereas on more hydrophilic ones, a complete monolayer formation was always observed with either the onset of the formation of a second layer (bare gold substrate) or adsorption in a multilayer fashion, possibly a bilayer formation (OH-terminated substrate). The surface concentration and compact monolayer film thickness was much lower on the COOH-terminated substrate compared to other surfaces studied. This result was explained by partial dissociation of the interfacial COOH groups leading to additional electrostatic interactions between the positively charged protein domains and negatively charged carboxylate anions, as well as to local pH changes promoting protein denaturation.
Release from masking for small spatial separations: Effects of age and hearing loss
Authors: Srinivasan Nirmal Kumar , Jakien Kasey M. , Gallun Frederick J.
Published: July 2016

Spatially separating target and masking speech can result in substantial spatial release from masking (SRM) for normal-hearing listeners. In this study, SRM was examined at eight spatial configurations of azimuth angle: maskers co-located with the target (0°) or symmetrically separated by 2°, 4°, 6°, 8°, 10°, 15°, or 30°. Results revealed that different listening groups (young normal-hearing, older normal-hearing, and older hearing-impaired) required different minimum amounts of spatial separation between target and maskers to achieve SRM. The results also indicated that aging was the contributing factor predicting SRM at smaller separations, whereas hearing loss was the contributing factor at larger separations.
Beam diffraction effects in sound transmission of a fluid-embedded viscoelastic plate at normal incidence
Authors: Aanes Magne , Lohne Kjetil Daae , Lunde Per , Vestrheim Magne
Published: July 2016

The characteristics of a sound beam transmitted through a fluid-embedded viscoelastic plate at normal incidence can deviate significantly from those of a plane-wave. Phenomena such as frequency shift, signal amplification or reduction, and changed beam properties, are observed for resonance peaks associated with specific leaky Lamb modes. When interpreting measurements using plane-wave theory, such deviations will influence the measurement of material parameters and plate thickness. The finite-element-based models used in this study describe the signal chain from the electrical voltage excitation at the piezoelectric transducer terminals to the sound pressure propagated through the plate and fluid to the position at which it is measured by a hydrophone. The measured phenomena are described at a quantitative level.
Rest–Activity Patterns in Older Adults with Heart Failure and Healthy Older Adults
Authors: Liebzeit Daniel , Phelan Cynthia , Moon Chooza , Brown Roger , Bratzke Lisa
Published: July 2016

The purpose of this investigation is to examine differences in rest-activity patterns and sleep characteristics in older adults with heart failure (HF) and healthy older adults. The sample included older adults with HF (n = 20) and a reference group of healthy older adults (n = 20). Traditional cosinor analysis was used to assess three parameters of rest–activity from wrist actigraphy data: amplitude (range of activity), mesor (mean activity), and acrophase (time of peak activity). Traditional sleep characteristics were also determined from actigraphy data: total sleep time (TST), sleep latency (SL), sleep efficiency (SE), and wake after sleep onset (WASO). The HF group demonstrated significantly lower mesor and amplitude than the reference group (p < .01). The HF group had significantly greater TST (p < .01), but the groups had similar SE, SL, and WASO. Despite similar sleep characteristics to healthy older adults, overall rest–activity patterns were significantly dampened in those with HF.
Microscale spatial heterogeneity of protein structural transitions in fibrin matrices
Authors: Fleissner Frederik , Bonn Mischa , Parekh Sapun H.
Published: July 2016

Mechanical loading of fibrin biomaterials induces spatial heterogeneity in protein molecular structure on the microscale.
Active micromachines: Microfluidics powered by mesoscale turbulence
Authors: Thampi Sumesh P. , Doostmohammadi Amin , Shendruk Tyler N. , Golestanian Ramin , Yeomans Julia M.
Published: July 2016

An ordered array of symmetric rotors immersed in active turbulence can turn persistently.
Versatile microwave-driven trapped ion spin system for quantum information processing
Authors: Piltz Christian , Sriarunothai Theeraphot , Ivanov Svetoslav S. , Wölk Sabine , Wunderlich Christof
Published: July 2016

A quantum register with flexible coupling topology is used to efficiently implement a quantum Fourier transform.
Bimolecular complementation affinity purification (BiCAP) reveals dimer-specific protein interactions for ERBB2 dimers
Authors: Croucher David R. , Iconomou Mary , Hastings Jordan F. , Kennedy Sean P. , Han Jeremy Z. R. , Shearer Robert F. , McKenna Jessie , Wan Adrian , Lau Joseph , Aparicio Samuel , Saunders Darren N.
Published: July 2016

The BiCAP method reveals protein partner–specific signaling with implications for breast cancer.
Releasing glutamate to stabilize HIF-1α
Authors: Wong Wei
Published: July 2016

Glutamate released by triple-negative breast cancer cells prevents the degradation of HIF-1α under normal oxygen conditions.
Neuroepigenetics of prenatal nicotine exposure
Authors: Ferrarelli Leslie K.
Published: July 2016

Altered histone methylation in neurons is induced by prenatal nicotine exposure and underlies the long-term behavioral and cognitive effects.
Another mTOR complex?
Authors: Gough Nancy R.
Published: July 2016

Astrocytes have a distinct mTOR complex containing GIT1 and lacking Rictor and Raptor.
Administration of Zinc Chelators Improves Survival of Mice Infected with Aspergillus fumigatus both in Monotherapy and in Combination with Caspofungin
Authors: Laskaris Paris , Atrouni Ahmad , Calera José Antonio , d'Enfert Christophe , Munier-Lehmann Hélène , Cavaillon Jean-Marc , Latgé Jean-Paul , Ibrahim-Granet Oumaïma
Published: July 2016

Aspergillus fumigatus
can infect immunocompromised patients, leading to high mortality rates due to the lack of reliable treatment options. This pathogen requires uptake of zinc from host tissues in order to successfully grow and cause virulence. Reducing the availability of that micronutrient could help treat
A. fumigatus
infections. In this study, we examined the
in vitro
effects of seven chelators using a bioluminescent strain of
A. fumigatus
. 1,10-Phenanthroline and
N
,
N
,
N
′,
N
′-tetrakis(2-pyridylmethyl)ethane-1,2-diamine (TPEN) proved to be the chelators most effective at inhibiting fungal growth. Intraperitoneal administration of either phenanthroline or TPEN resulted in a significant improvement in survival and decrease of weight loss and fungal burden for immunosuppressed mice intranasally infected with
A. fumigatus
.
In vitro
both chelators had an indifferent effect when employed in combination with caspofungin. The use of TPEN in combination with caspofungin also significantly increased survival compared to that when using these drugs individually. Our results suggest that zinc chelation may be a valid strategy for dealing with
A. fumigatus
infections and that both phenanthroline and TPEN could potentially be used either independently or in combination with caspofungin, indicating that their use in combination with other antifungal treatments might also be applicable.
Screening a Commercial Library of Pharmacologically Active Small Molecules against Staphylococcus aureus Biofilms
Authors: Torres Nelson S. , Abercrombie Johnathan J. , Srinivasan Anand , Lopez-Ribot Jose L. , Ramasubramanian Anand K. , Leung Kai P.
Published: July 2016

It is now well established that bacterial infections are often associated with biofilm phenotypes that demonstrate increased resistance to common antimicrobials. Further, due to the collective attrition of new antibiotic development programs by the pharmaceutical industries, drug repurposing is an attractive alternative. In this work, we screened 1,280 existing commercially available drugs in the Prestwick Chemical Library, some with previously unknown antimicrobial activity, against
Staphylococcus aureus
, one of the commonly encountered causative pathogens of burn and wound infections. From the primary screen of the entire Prestwick Chemical Library at a fixed concentration of 10 μM, 104 drugs were found to be effective against planktonic
S. aureus
strains, and not surprisingly, these were mostly antimicrobials and antiseptics. The activity of 18 selected repurposing candidates, that is, drugs that show antimicrobial activity that are not already considered antimicrobials, observed in the primary screen was confirmed in dose-response experiments. Finally, a subset of nine of these drug candidates was tested against preformed biofilms of
S. aureus
. We found that three of these drugs, niclosamide, carmofur, and auranofin, possessed antimicrobial activity against preformed biofilms, making them attractive candidates for repurposing as novel antibiofilm therapies.
Role of ABC and Solute Carrier Transporters in the Placental Transport of Lamivudine
Authors: Ceckova Martina , Reznicek Josef , Ptackova Zuzana , Cerveny Lukas , Müller Fabian , Kacerovsky Marian , Fromm Martin F. , Glazier Jocelyn D. , Staud Frantisek
Published: July 2016

Lamivudine is one of the antiretroviral drugs of choice for the prevention of mother-to-child transmission (MTCT) in HIV-positive women. In this study, we investigated the relevance of drug efflux transporters P-glycoprotein (P-gp) (MDR1 [ABCB1]), BCRP (ABCG2), MRP2 (ABCC2), and MATE1 (SLC47A1) for the transmembrane transport and transplacental transfer of lamivudine. We employedin vitroaccumulation and transport experiments on MDCK cells overexpressing drug efflux transporters,in situ-perfused rat term placenta, and vesicular uptake in microvillous plasma membrane (MVM) vesicles isolated from human term placenta. MATE1 significantly accelerated lamivudine transport in MATE1-expressing MDCK cells, whereas no transporter-driven efflux of lamivudine was observed in MDCK-MDR1, MDCK-MRP2, and MDCK-BCRP monolayers. MATE1-mediated efflux of lamivudine appeared to be a low-affinity process (apparentKmof 4.21 mM andVmaxof 5.18 nmol/mg protein/min in MDCK-MATE1 cells). Consistent within vitrotransport studies, the transplacental clearance of lamivudine was not affected by P-gp, BCRP, or MRP2. However, lamivudine transfer across dually perfused rat placenta and the uptake of lamivudine into human placental MVM vesicles revealed pH dependency, indicating possible involvement of MATE1 in the fetal-to-maternal efflux of the drug. To conclude, placental transport of lamivudine does not seem to be affected by P-gp, MRP2, or BCRP, but a pH-dependent mechanism mediates transport of lamivudine in the fetal-to-maternal direction. We suggest that MATE1 might be, at least partly, responsible for this transport.
Molecular Epidemiology of a Vancomycin-Intermediate Heteroresistant Staphylococcus epidermidis Outbreak in a Neonatal Intensive Care Unit
Authors: Chong Jasmine , Quach Caroline , Blanchard Ana C. , Poliquin Philippe Guillaume , Golding George R. , Laferrière Céline , Lévesque Simon
Published: July 2016

Coagulase-negative staphylococci (CoNS) have become the leading cause of bloodstream infections (BSIs) in intensive care units (ICUs), particularly in premature neonates. Vancomycin-intermediate heteroresistant CoNS (hVICoNS) have been identified as sources of BSIs worldwide, and their potential to emerge as significant pathogens in the neonatal ICU (NICU) remains uncertain. This study describes the molecular epidemiology of an outbreak of vancomycin-heteroresistant (hV)
Staphylococcus epidermidis
central-line-associated BSI (CLABSI) in a single tertiary care NICU and compares it to a second tertiary care NICU that had not been associated with an outbreak. Between November 2009 and April 2014, 119
S. epidermidis
CLABSIs were identified in two tertiary care NICUs in Quebec, Canada. Decreased vancomycin susceptibility was identified in about 88% of all collected strains using Etest methods. However, discrepancies were found according to the Etest and population analysis profiling–area under the concentration-time curve (PAP-AUC) methods used. All strains were susceptible to linezolid, and a few isolates were nonsusceptible to daptomycin. Great genetic diversity was observed within the collection, with 31 pulsed-field gel electrophoresis (PFGE) patterns identified. The outbreak strains were all determined to be heteroresistant to vancomycin and were polyclonal. The study identified two major clones, PFGE patterns E and G, which were found in both NICUs across the 5-year study period. This suggests the persistence of highly successful clones that are well adapted to the hospital environment. hV
S. epidermidis
seems more common than currently realized in the NICU, and certain hV
S. epidermidis
clones can become endemic to the NICU. The reservoirs for these clones remain unknown at this time, and identification of the reservoirs is needed to better understand the impact of hV
S. epidermidis
in the NICU and to inform infection prevention strategies. In addition, there is a need to investigate and validate hV determination protocols for different species of CoNS.
Efficacy of Solithromycin (CEM-101) for Experimental Otitis Media Caused by Nontypeable Haemophilus influenzae and Streptococcus pneumoniae
Authors: Figueira M. , Fernandes P. , Pelton S. I.
Published: July 2016

Solithromycin (CEM-101) is a “fourth-generation” macrolide, as it has three binding site and is acid stable. The three binding sites confer activity against bacteria resistant to the older macrolides and ketolides, including multidrug-resistant
Streptococcus pneumoniae
and nontypeable
Haemophilus influenzae
(NTHi). The objective of this study was to evaluate solithromycin pharmacokinetics (PK), middle ear fluid (MEF) concentrations, and microbiologic efficacy in a chinchilla model of experimental otitis media (EOM) due to strains of
S. pneumoniae
or NTHi. Plasma PK (maximum concentration of drug in serum [
C
max
] and area under the concentration-time curve from 0 to 24 h [AUC
0–24
]) and middle ear fluid (MEF) concentrations were determined. Isolates with specified antimicrobial susceptibility patterns were inoculated directly into the middle ear (ME). Plasma and MEF were collected for PK and MEF cultures performed to determine efficacy. Solithromycin administered at 150 mg/kg of body weight/day resulted in
C
max
and AUC
0–24
values of 2.2 μg/ml and 27.4 μg · h/ml in plasma and 1.7 μg/ml and 28.2 μg · h/ml in extracellular MEF on day 1. By day 3,
C
max
and AUC
0–24
values had increased to 4.5 μg/ml and 54 μg · h/ml in plasma and 4.8 μg/ml and 98.6 μg · h/ml in extracellular MEF. For NTHi EOM, three isolates with MIC/minimal bactericidal concentration (MBC) ratios of 0.5/1 μg/ml (isolate BCH1), 2/2 μg/ml (isolate BMC1247C), and 4/4 μg/ml (isolate BMC1213C) were selected. The MEF of >85% of animals infected with BCH1 and BMC1247C was sterilized. For NTHi BMC1213, >85% of MEF cultures remained positive. For
S. pneumoniae
EOM, 3 isolates with MIC/MBC ratios of 0.06/0.125 μg/ml (
S. pneumoniae
331), 0.125/1 μg/ml (
S. pneumoniae
CP-645 [MLS
B
phenotype]), and 0.5/2 μg/ml (CP-712 [
mefA
subclass
mefA
resistance]) were selected. Solithromycin sterilized MEF in 100% of animals infected with
S. pneumoniae
331 and
S. pneumoniae
CP-645. ME infection persisted in 60% of animals infected with CP-712. In a model of EOM, solithromycin sterilized MEF in >85% of animals challenged with NTHi with an MIC of ≤2 μg/ml and 100% of ME infected with
S. pneumoniae
with an MIC of ≤0.125 μg/ml.
Impact of Time to Appropriate Therapy on Mortality in Patients with Vancomycin-Intermediate Staphylococcus aureus Infection
Authors: Burnham Jason P. , Burnham Carey-Ann D. , Warren David K. , Kollef Marin H.
Published: July 2016

Despite the increasing incidence of vancomycin-intermediate
Staphylococcus aureus
(VISA) infections, few studies have examined the impact of delay in receipt of appropriate antimicrobial therapy on outcomes in VISA patients. We examined the effects of timing of appropriate antimicrobial therapy in a cohort of patients with sterile-site methicillin-resistant
S. aureus
(MRSA) and VISA infections. In this single-center, retrospective cohort study, we identified all patients with MRSA or VISA sterile-site infections from June 2009 to February 2015. Clinical outcomes were compared according to MRSA/VISA classification, demographics, comorbidities, and antimicrobial treatment. Thirty-day all-cause mortality was modeled with Kaplan-Meier curves. Multivariate logistic regression analysis (MVLRA) was used to determine odds ratios for mortality. We identified 354 patients with MRSA (
n
= 267) or VISA (
n
= 87) sterile-site infection. Fifty-five patients (15.5%) were nonsurvivors. Factors associated with mortality in MVLRA included pneumonia, unknown source of infection, acute physiology and chronic health evaluation (APACHE) II score, solid-organ malignancy, and admission from skilled care facilities. Time to appropriate antimicrobial therapy was not significantly associated with outcome. Presence of a VISA infection compared to that of a non-VISA
S. aureus
infection did not result in excess mortality. Linezolid use was a risk for mortality in patients with APACHE II scores of ≥14. Our results suggest that empirical vancomycin use in patients with VISA infections does not result in excess mortality. Future studies should (i) include larger numbers of patients with VISA infections to confirm the findings presented here and (ii) determine the optimal antibiotic therapy for critically ill patients with MRSA and VISA infections.
mcr-1.2
, a New
mcr
Variant Carried on a Transferable Plasmid from a Colistin-Resistant KPC Carbapenemase-Producing Klebsiella pneumoniae Strain of Sequence Type 512
Authors: Di Pilato Vincenzo , Arena Fabio , Tascini Carlo , Cannatelli Antonio , Henrici De Angelis Lucia , Fortunato Simona , Giani Tommaso , Menichetti Francesco , Rossolini Gian Maria
Published: July 2016

A novel
mcr
variant, named
mcr-1.2
, encoding a Gln
3
-to-Leu functional variant of MCR-1, was detected in a KPC-3-producing ST512
Klebsiella pneumoniae
isolate collected in Italy from a surveillance rectal swab from a leukemic child. The
mcr-1.2
gene was carried on a transferable IncX4 plasmid whose structure was very similar to that of
mcr-1
-bearing plasmids previously found in
Escherichia coli
and
K. pneumoniae
strains from geographically distant sites (Estonia, China, and South Africa).
Novel
acsF
Gene Primers Revealed a Diverse Phototrophic Bacterial Population, Including Gemmatimonadetes, in Lake Taihu (China)
Authors: Huang Yili , Zeng Yanhua , Lu Hang , Feng Hao , Zeng Yonghui , Koblížek Michal
Published: July 2016

Anoxygenic phototrophs represent an environmentally important and phylogenetically diverse group of organisms. They harvest light using bacteriochlorophyll-containing reaction centers. Recently, a novel phototrophic bacterium,
Gemmatimonas phototrophica
, belonging to a rarely studied phylum,
Gemmatimonadetes
, was isolated from a freshwater lake in the Gobi Desert. To obtain more information about the environmental distribution of phototrophic
Gemmatimonadetes
, we collected microbial samples from the water column, upper sediment, and deeper anoxic sediment of Lake Taihu, China. MiSeq sequencing of the 16S rRNA,
pufM
, and
bchY
genes was carried out to assess the diversity of local phototrophic communities. In addition, we designed new degenerate primers of aerobic cyclase gene
acsF
, which serves as a convenient marker for both phototrophic
Gemmatimonadetes
and phototrophic
Proteobacteria
. Our results showed that most of the phototrophic species in Lake Taihu belong to
Alpha
- and
Betaproteobacteria
. Sequences of green sulfur and green nonsulfur bacteria (phototrophic
Chlorobi
and
Chloroflexi
, respectively) were found in the sediment. Using the newly designed primers, we identified a diverse community of phototrophic
Gemmatimonadetes
forming 30 operational taxonomic units. These species represented 10.5 and 17.3% of the
acsF
reads in the upper semiaerobic sediment and anoxic sediment, whereas their abundance in the water column was <1%.

IMPORTANCE
Photosynthesis is one of the most fundamental biological processes on Earth. Recently, the presence of photosynthetic reaction centers has been reported from a rarely studied bacterial phylum,
Gemmatimonadetes
, but almost nothing is known about the diversity and environmental distribution of these organisms. The newly designed
acsF
primers were used to identify phototrophic
Gemmatimonadetes
from planktonic and sediment samples collected in Lake Taihu, China. The
Gemmatimonadetes
sequences were found mostly in the upper sediments, documenting the preference of
Gemmatimonadetes
for semiaerobic conditions. Our results also show that the phototrophic
Gemmatimonadetes
present in Lake Taihu were relatively diverse, encompassing 30 operational taxonomic units.
North-Seeking Magnetotactic Gammaproteobacteria in the Southern Hemisphere
Authors: Leão Pedro , Teixeira Lia C. R. S. , Cypriano Jefferson , Farina Marcos , Abreu Fernanda , Bazylinski Dennis A. , Lins Ulysses
Published: July 2016

Magnetotactic bacteria (MTB) comprise a phylogenetically diverse group of prokaryotes capable of orienting and navigating along magnetic field lines. Under oxic conditions, MTB in natural environments in the Northern Hemisphere generally display north-seeking (NS) polarity, swimming parallel to the Earth's magnetic field lines, while those in the Southern Hemisphere generally swim antiparallel to magnetic field lines (south-seeking [SS] polarity). Here, we report a population of an uncultured, monotrichously flagellated, and vibrioid MTB collected from a brackish lagoon in Brazil in the Southern Hemisphere that consistently exhibits NS polarity. Cells of this organism were mainly located below the oxic-anoxic interface (OAI), suggesting it is capable of some type of anaerobic metabolism. Magnetosome crystalline habit and composition were consistent with elongated prismatic magnetite (Fe
3
O
4
) particles. Phylogenetic analysis based on 16S rRNA gene sequencing indicated that this organism belongs to a distinct clade of the
Gammaproteobacteria
class. The presence of NS MTB in the Southern Hemisphere and the previously reported finding of SS MTB in the Northern Hemisphere reinforce the idea that magnetotaxis is more complex than we currently understand and may be modulated by factors other than O
2
concentration and redox gradients in sediments and water columns.

IMPORTANCE
Magnetotaxis is a navigational mechanism used by magnetotactic bacteria to move along geomagnetic field lines and find an optimal position in chemically stratified sediments. For that, magnetotactic bacteria swim parallel to the geomagnetic field lines under oxic conditions in the Northern Hemisphere, whereas those in the Southern Hemisphere swim antiparallel to magnetic field lines. A population of uncultured vibrioid magnetotactic bacteria was discovered in a brackish lagoon in the Southern Hemisphere that consistently swim northward, i.e., the opposite of the overwhelming majority of other Southern Hemisphere magnetotactic bacteria. This finding supports the idea that magnetotaxis is more complex than previously thought.
Infant Mouse Model for the Study of Shedding and Transmission during Streptococcus pneumoniae Monoinfection
Authors: Zafar M. Ammar , Kono Masamitsu , Wang Yang , Zangari Tonia , Weiser Jeffrey N.
Published: July 2016

One of the least understood aspects of the bacteriumStreptococcus pneumoniae(pneumococcus) is its transmission from host to host, the critical first step in both the carrier state and the disease state. To date, transmission models have depended on influenza A virus coinfection, which greatly enhances pneumococcal shedding to levels that allow acquisition by a new host. Here, we describe an infant mouse model that can be utilized to study pneumococcal colonization, shedding, and transmission during bacterial monoinfection. Using this model, we demonstrated that the level of bacterial shedding is highest in pups infected intranasally at age 4 days and peaks over the first 4 days postchallenge. Shedding results differed among isolates of five different pneumococcal types. Colonization density was found to be a major factor in the level of pneumococcal shedding and required expression of capsule. Transmission within a litter occurred when there was a high ratio of colonized “index” pups to uncolonized “contact” pups. Transmission was observed for each of the well-colonizing pneumococcal isolates, with the rate of transmission proportional to the level of shedding. This model can be used to examine bacterial and host factors that contribute to pneumococcal transmission without the effects of viral coinfection.
Evidence for Escherichia coli Diguanylate Cyclase DgcZ Interlinking Surface Sensing and Adhesion via Multiple Regulatory Routes
Authors: Lacanna Egidio , Bigosch Colette , Kaever Volkhard , Boehm Alex , Becker Anke
Published: July 2016

DgcZ is the main cyclic dimeric GMP (c-di-GMP)-producing diguanylate cyclase (DGC) controlling biosynthesis of the exopolysaccharide poly-β-1,6-
N
-acetylglucosamine (poly-GlcNAc or PGA), which is essential for surface attachment of
Escherichia coli
. Although the complex regulation of DgcZ has previously been investigated, its primary role and the physiological conditions under which the protein is active are not fully understood. Transcription of
dgcZ
is regulated by the two-component system CpxAR activated by the lipoprotein NlpE in response to surface sensing. Here, we show that the negative effect of a
cpxR
mutation and the positive effect of
nlpE
overexpression on biofilm formation both depend on DgcZ. Coimmunoprecipitation data suggest several potential interaction partners of DgcZ. Interaction with FrdB, a subunit of the fumarate reductase complex (FRD) involved in anaerobic respiration and in control of flagellum assembly, was further supported by a bacterial-two-hybrid assay. Furthermore, the FRD complex was required for the increase in DgcZ-mediated biofilm formation upon induction of oxidative stress by addition of paraquat. A DgcZ-mVENUS fusion protein was found to localize at one bacterial cell pole in response to alkaline pH and carbon starvation. Based on our data and previous knowledge, an integrative role of DgcZ in regulation of surface attachment is proposed. We speculate that both DgcZ-stimulated PGA biosynthesis and interaction of DgcZ with the FRD complex contribute to impeding bacterial escape from the surface.

IMPORTANCE
Bacterial cells can grow by clonal expansion to surface-associated biofilms that are ubiquitous in the environment but also constitute a pervasive problem related to bacterial infections. Cyclic dimeric GMP (c-di-GMP) is a widespread bacterial second messenger involved in regulation of motility and biofilm formation, and plays a primary role in bacterial surface attachment.
E. coli
possesses a plethora of c-di-GMP-producing diguanylate cyclases, including DgcZ. Our study expands the knowledge on the role of DgcZ in regulation of surface attachment and suggests that it interconnects surface sensing and adhesion via multiple routes.
Iron Homeostasis in Mycobacterium tuberculosis: Mechanistic Insights into Siderophore-Mediated Iron Uptake
Authors: Sritharan Manjula
Published: July 2016

Mycobacterium tuberculosis
requires iron for normal growth but faces a limitation of the metal ion due to its low solubility at biological pH and the withholding of iron by the mammalian host. The pathogen expresses the Fe
3+
-specific siderophores mycobactin and carboxymycobactin to chelate the metal ion from insoluble iron and the host proteins transferrin, lactoferrin, and ferritin. Siderophore-mediated iron uptake is essential for the survival of
M. tuberculosis
, as knockout mutants, which were defective in siderophore synthesis or uptake, failed to survive in low-iron medium and inside macrophages. But as excess iron is toxic due to its catalytic role in the generation of free radicals, regulation of iron uptake is necessary to maintain optimal levels of intracellular iron. The focus of this review is to present a comprehensive overview of iron homeostasis in
M. tuberculosis
that is discussed in the context of mycobactin biosynthesis, transport of iron across the mycobacterial cell envelope, and storage of excess iron. The clinical significance of the serum iron status and the expression of the iron-regulated protein HupB in tuberculosis (TB) patients is presented here, highlighting the potential of HupB as a marker, notably in extrapulmonary TB cases.
Dynamic weakening and amorphization in serpentinite during laboratory earthquakes
Authors: Brantut Nicolas , Passelègue François X. , Deldicque Damien , Rouzaud Jean-Noël , Schubnel Alexandre
Published: July 2016

The mechanical properties of serpentinites are key factors in our understanding of the dynamics of earthquake ruptures in subduction zones, especially intermediate-depth earthquakes. Here, we performed shear rupture experiments on natural antigorite serpentinite, which showed that friction reaches near-zero values during spontaneous dynamic rupture propagation. Rapid coseismic slip (>1 m/s), although it occurs over short distances (<1 mm), induces significant overheating of microscale asperities along the sliding surface, sufficient to produce surface amorphization and likely some melting. Antigorite dehydration occurs in the fault walls, which leaves a partially amorphized material. The water generated potentially contributes to the production of a low-viscosity pressurized melt, explaining the near-zero dynamic friction levels observed in some events. The rapid and dramatic dynamic weakening in serpentinite might be a key process facilitating the propagation of earthquakes at intermediate depths in subduction zones.
Electroacupuncture Improves Cognitive Deficits and Activates Ppar-γ in a Rat Model of Alzheimer's Disease
Authors: Zhang Min , Xv Gui-Hua , Wang Wei-Xin , Meng Di-Juan , Ji Yan
Published: July 2016

Background

Alzheimer's disease (AD) is an age-associated neurodegenerative disorder that is associated with a progressive impairment of cognition. Acupuncture has protective effects, although the molecular mechanisms are largely unknown. The activation of peroxisome proliferator activated receptor γ (PPAR-γ) has an impact on the pathogenesis of AD.

Objective

To test the hypothesis that electroacupuncture (EA) confers therapeutic benefits through activation of PPAR-γ in a rat model of AD.

Methods

80 male Sprague-Dawley rats were randomly divided into four groups (n=20 each): Control (healthy control group), Sham (sham-operated group), AD (untreated AD model group), and AD+EA (AD model group treated with EA). The AD model was induced in the latter two groups by injection of amyloid-β (Aβ)1-40 into the hippocampal CA1 area bilaterally. EA was administered at GV20 and BL23 six times per week for 4 weeks. The rats’ behaviour was examined using the Morris water maze test, and protein expression of Aβ, hyperphosphorylated tau protein (p-Tau), PPAR-γ, and hyperphosphorylated p38 mitogen activated protein kinase (p38MAPK) in the hippocampal CA1 region was examined by immunohistochemistry and Western blotting.

Results

EA significantly improved cognitive deficits and reduced Aβ and p-Tau Ser404 protein concentrations in the hippocampal CA1 region. AD decreased PPAR-γ and increased p-p38MAPK, while EA significantly upregulated PPAR-γ expression and significantly downregulated p-p38MAPK expression.

Conclusions

Acupuncture at GV20 and BL23 might have a beneficial effect on rats with AD via activation of PPAR-γ and inhibition of p-p38MAPK expression.
Acupuncture for the Treatment of Trigger Finger in Adults: A Prospective Case Series
Authors: Inoue Motohiro , Nakajima Miwa , Hojo Tatsuya , Itoi Megumi , Kitakoji Hiroshi
Published: July 2016

Objective

To determine the effect of acupuncture performed at the synovial and ligamentous tendon sheath (A1 pulley site) on pain during snapping and the severity of the snapping phenomenon in patients with trigger finger.

Methods

In this observational study, changes in the patients’ condition were compared before and after acupuncture treatment. Acupuncture was performed on 19 fingers of 15 patients. Acupuncture needles were inserted into the radial and ulnar sides of the flexor tendon at the A1 pulley of the affected finger. Treatment was performed daily up to a maximum of five times. Before and after each treatment, pain during snapping and the severity of snapping were evaluated using a visual analogue scale (VAS).

Results

VAS scores for pain and snapping severity were significantly improved immediately after the first treatment (p<0.001). Pain during snapping, assessed before each treatment, improved over time, reaching statistical significance from the second treatment onwards (p<0.001); similarly, a significant improvement in the severity of snapping was observed, also from the second treatment (p<0.001). Patients with clinically significant improvements (≥50%) in pain and snapping severity had a significantly shorter duration of the disorder than those with <50% improvement (p<0.05).

Conclusions

Acupuncture at the impaired A1 pulley site may be an effective treatment for trigger finger. We postulate that acupuncture may reduce inflammation/swelling of the synovial membrane of the tendon sheath, which predominates when the disorder is of short duration. Further research is required to confirm the efficacy/effectiveness of acupuncture for trigger finger and its mechanisms of action.
Uterine incarceration in a primigravid retroverted bicornuate uterus
Authors: Sadath Haleema , Carpenter Robert , Adam Karolina
Published: July 2016

Uterine incarceration is a rare complication that usually occurs after the first trimester of pregnancy. It leads to increased maternal and/or fetal morbidity and mortality. Risk factors include retroversion of uterus and other pelvic abnormalities. Clinical presentation includes severe abdominal and pelvic pain symptoms. Patients can present with concurrent urinary symptoms due to increasing distortion of adjacent structures from the enlarging uterus. A high clinical suspicion of uterine incarceration is confirmed with ultrasound. More advanced imaging such as MRI can be used as an adjunct to ultrasound imaging. Progression from expectant management to intervention is recommended as soon as possible to prevent complications such as uterine rupture and fetal demise. In subsequent pregnancies, close monitoring with serial ultrasounds is warranted to monitor for recurrence of incarceration which has been reported in a few rare cases.
Treatment of opioid use disorder in an innovative community-based setting after multiple treatment attempts in a woman with untreated HIV
Authors: Voon Pauline , Joe Ronald , Fairgrieve Christopher , Ahamad Keith
Published: July 2016

Opioid use disorder is associated with significant health and social harms. Various evidence-based interventions have proven successful in mitigating these harms, including harm reduction strategies and pharmacological treatment such as methadone. We present a case of a 35-year-old HIV-positive woman who was off antiretroviral therapy due to untreated opioid use disorder, and had a history of frequently self-discharging from hospital against medical advice. During the most recent hospital admission, the patient was transferred to an innovative community-based clinical support residence that supported harm reduction. Initially, she received methadone to only manage the withdrawal symptoms rather than for long-term maintenance therapy. However, with gradual dose increases to treat cravings and withdrawal, she ultimately discontinued all drug use and reinitiated antiretroviral therapy. This case highlights that patients whose goal is not abstinence can be successfully treated for acute medical illnesses and comorbid substance use disorders using harm reduction approaches, including appropriate dosing of pharmacotherapy.
Does a hospital admission in old age denote the beginning of life with a compromised health-related quality of life? A longitudinal study of men and women aged 65 years and above participating in the Stockholm Public Health Cohort
Authors: Karampampa Korinna , Frumento Paolo , Ahlbom Anders , Modig Karin
Published: July 2016

Objectives

The objective of this study was to analyse how hospitalisation after the age of 60 affected individuals' health-related quality of life (HRQoL). The main hypothesis was that a hospital admission in old age can be seen as a proxy of ill health and possibly as a health divider, separating life into a healthy and an unhealthy part. The extent to which this is true depends on which disease individuals face and how functional ability and HRQoL are affected.

Settings

This was a longitudinal study, based on an older cohort of individuals who participated in the Stockholm Public Health Cohort (SPHC) survey in 2006; the survey took place in Stockholm, Sweden. Information regarding hospitalisations and deaths, which is available through Swedish administrative registers, was linked to the survey from the National Patient Register and Cause of Death Register.

Participants

2101 individuals, 65+ years old at inclusion, with no previous hospitalisations at baseline (2006), were followed for 4 years until 2010 (end of follow-up).

Primary and secondary outcome measures

HRQoL was assessed through a utility index derived from the EuroQol 5D questionnaire, at baseline and at 2010. The change in HRQoL after admission(s) to the hospital was estimated as the difference between the 2010 and 2006 levels using linear regression, also considering several covariates.

Results

A single hospitalisation did not reduce individuals' HRQoL, either for men or women. On the other hand, multiple any-cause hospitalisations reduced HRQoL between 3.2% and 6.5%. When looking into hospitalisations for specific causes, such as hip fractures, a decrease in HRQoL was observed as well; however, conclusions regarding this were impeded by the small sample size.

Conclusions

Hospital admissions in old age may indicate a shift from a healthy life to a life of compromised health when considering their frequency and cause over a period of time.
Protocol to describe the analysis of text-based communication in medical records for patients discharged from intensive care to hospital ward
Authors: Parsons Leigh Jeanna , Brown Kyla , Buchner Denise , Stelfox Henry T
Published: July 2016

Introduction

Effective communication during hospital transitions of patient care is fundamental to ensuring patient safety and continuity of quality care. This study will describe text-based communication included in patient medical records before, during and after patient transfer from the intensive care unit (ICU) to a hospital ward (n=10 days) by documenting (1) the structure and focus of physician progress notes within and between medical specialties, (2) the organisation of subjective and objective information, including the location and accessibility of patient data and whether/how this changes during the hospital stay and (3) missing, illegible and erroneous information.

Methods

This study is part of a larger mixed methods prospective observational study of ICU to hospital ward transfer practices in 10 ICUs across Canada. Medical records will be collected and photocopied for each consenting patient for a period of up to 10 consecutive days, including the final 2 days in the ICU, the day of transfer and the first 7 days on the ward (n=10 days). Textual analysis of medical record data will be completed by 2 independent reviewers to describe communication between stakeholders involved in ICU transfer.

Ethics and dissemination

Research ethics board approval has been obtained at all study sites, including the coordinating study centre (which covers 4 Calgary-based sites; UofC REB 13-0021) and 6 additional study sites (UofA Pro00050646; UBC PHC Hi4-01667; Sunnybrook 336-2014; QCH 20140345-01H; Sherbrooke 14-172; Laval 2015-2171). Findings from this study will inform the development of an evidence-based tool that will be used to systematically analyse the series of notes in a patient's medical record.
Promoting the role of patients in improving hand hygiene compliance amongst health care workers
Authors: Ahmed Awaji Maryam , Al-Surimi Khaled
Published: July 2016

Hand hygiene is one of the fundamental measures necessary for reducing healthcare-associated infections. The adherence of health care workers to safe hand hygiene practices is low worldwide, despite evidence showing compliance with hand hygiene guidelines decreases infection rate. This project focuses on the role of patients in promoting healthcare workers' compliance with hand hygiene practices. Several plan-do-study-act (PDSA) cycles were conducted to test interventions which aimed to empower patients and increase staff members' adherence to hand hygiene practices. The initial findings presented on the run chart demonstrate that compliance among healthcare workers increased with the interventions; there was an increase of 15% compliance during the 10 days of project testing. We will need to collect more data to show continued and sustained improvement. Patients can play an important role in promoting safe care and hand hygiene practices.
Preventing violence-related injuries in England and Wales: a panel study examining the impact of on-trade and off-trade alcohol prices
Authors: Page Nicholas , Sivarajasingam Vaseekaran , Matthews Kent , Heravi Saeed , Morgan Peter , Shepherd Jonathan
Published: July 2016

Objective

To examine the influence of real on-trade and off-trade alcohol prices and socioeconomic and environmental factors on rates of violence-related emergency department (ED) attendances in England and Wales over an 8-year period.

Methods

Anonymised injury data which included attendance date, age and gender of patients aged over 18 years who reported injury in violence were collected from a structured sample of 100 EDs across England and Wales between 1 January 2005 and 31 December 2012. Alcohol prices and socioeconomic measures were obtained from the UK Office for National Statistics. Panel techniques were used to derive a statistical model.

Results

Real on-trade (β=−0.661, p<0.01) and off-trade (β=−0.277, p<0.05) alcohol prices were negatively related with rates of violence-related ED attendance among the adult population of England and Wales, after accounting for the effects of regional poverty, income inequality, youth spending power and seasonal effects. It is estimated that over 6000 fewer violence-related ED attendances per year in England and Wales would result from a 1% increase in both on-trade and off-trade alcohol prices above inflation. Of the variables studied, changes in regional poverty and income inequality had the greatest effect on violence-related ED attendances in England and Wales.

Conclusions

Small increases in the price of alcohol, above inflation, in both markets, would substantially reduce the number of patients attending EDs for treatment of violence-related injuries in England and Wales. Reforming the current alcohol taxation system may be more effective at reducing violence-related injury than minimum unit pricing.