bluuebunny/crossref_metadata_2025_split huggingface dataset:
Defining the neurocircuitry of exercise hyperpnoea
Authors: Paterson David J. 
Published: August 2013

AbstractOne hundred years ago in this journal, Krogh and Lindhard published a seminal paper highlighting the importance of the brain in the control of breathing during exercise. This symposium report reviews the historical developments that have taken place since 1913, and attempts to place the detailed neurocircuitry thought to underpin exercise hyperpnoea into context by focusing on key structures that might form the command network. With the advent of enhanced neuroimaging and functional neurosurgical techniques, a unique window of opportunity has recently arisen to target potential circuits in humans. Animal studies have identified a priori sites of interest in mid‐brain structures, in particular the subthalamic locomotor region (subthalamic nucleus, STN) and the periaqueductal grey (PAG), which have now been recorded from in humans during exercise. When all data are viewed in an integrative manner, the PAG, in particular the lateral PAG, and aspects of the dorsal lateral PAG, appear to be key communicating circuitry for ‘central command’. Moreover, the PAG also fulfils many requirements of a command centre. It has functional connectivity to higher centres (dorsal lateral prefrontal cortex) and the basal ganglia (in particular, the STN), and receives a sensory input from contracting muscle, but, importantly, it sends efferent information to brainstem nuclei involved in cardiorespiratory control.
Fast direct estimation of the blood input function and myocardial time activity curve from dynamic SPECT projections via reduction in spatial and temporal dimensions
Authors: Zan Yunlong , Boutchko Rostyslav , Huang Qiu , Li Biao , Chen Kewei , Gullberg Grant T. 
Published: August 2013

Purpose:Reconstruction of parametric images from dynamic single photon emission computed tomography (SPECT) data acquired with slow rotating cameras is a challenge because the estimation of the time–activity curves (TACs) may involve fitting data to an inconsistent underdetermined system of equations. This work presents a novel algorithm for the estimation of the blood input function and myocardial TAC with high accuracy and high efficiency directly from these projections.Methods:In the proposed dynamic reconstruction method, the information from the segmentation of functional regions from the static reconstructed image was used as a prior to construct a sparse matrix, through which the spatial distribution of the radioactive tracer was represented. Then the temporal distribution of the radioactive tracer was modeled by nonuniform B‐spline basis functions which were determined according to a new selection rule. With reduction in both the spatial and temporal dimensions of the reconstructed image, the blood input function and myocardial TAC were estimated using the 4D maximum likelihood expectation maximization algorithm. The method was validated using data from both digital phantom simulations and an experimental rat study.Results:Compared with the conventional dynamic SPECT reconstruction method without the reduction in spatial dimensions, the proposed method provides more accurate TACs with less computation time in both phantom simulation studies and a rat experimental study.Conclusions:The proposed method is promising in both providing more accurate time–activity curves and reducing the computation time, which makes it practical for small animal studies using clinical systems with slow rotating cameras.
SbcCD-Mediated Processing of Covalent Gyrase-DNA Complex in Escherichia coli
Authors: Aedo Sandra , Tse-Dinh Yuk-Ching 
Published: August 2013

ABSTRACT

Quinolones trap the covalent gyrase-DNA complex in
Escherichia coli
, leading to cell death. Processing activities for trapped covalent complex have not been characterized. A mutant strain lacking SbcCD nuclease activity was examined for both accumulation of gyrase-DNA complex and viability after quinolone treatment. Higher complex levels were found in Δ
sbcCD
cells than in wild-type cells after incubation with nalidixic acid and ciprofloxacin. However, SbcCD activity protected cells against the bactericidal action of nalidixic acid but not ciprofloxacin.
Antimicrobial Peptide GL13K Is Effective in Reducing Biofilms of Pseudomonas aeruginosa
Authors: Hirt Helmut , Gorr Sven-Ulrik 
Published: August 2013

ABSTRACT

Human parotid secretory protein (PSP; BPIF2A) is predicted to be structurally similar to bactericidal/permeability-increasing protein and lipopolysaccharide (LPS)-binding protein. Based on the locations of known antimicrobial peptides in the latter two proteins, potential active peptides in the PSP sequence were identified. One such peptide, GL13NH
2
(PSP residues 141 to 153) was shown previously to interfere with LPS binding and agglutinate bacteria without bactericidal activity. By introducing three additional positively charged lysine residues, the peptide was converted to the novel bactericidal cationic peptide GL13K (MIC for
Pseudomonas aeruginosa
, 8 μg/ml [5.6 μM]). We investigated the antibiofilm activity of GL13K against static, monospecies biofilms of
P. aeruginosa
PAO1. Two-hour exposure of a 24-h biofilm to 64 μg/ml (44.8 μM) GL13K reduced biofilm bacteria by 10
2
, and 100 μg/ml (70 μM) GL13K reduced bacteria by 10
3
. Similar results could be achieved on 48-h-old biofilms. Lower concentrations of GL13K (32 μg/ml [22.4 μM]) were successful in reducing biofilm cell numbers in combination with tobramycin. This combination treatment also achieved total eradication of the biofilm in a majority (67.5%) of tested samples. An alanine scan of GL13K revealed the importance of the leucine residue in position six of the peptide sequence, where replacement led to a loss of antibiofilm activity, whereas the impact of replacing charged residues was less pronounced. Bacterial metalloproteases were found to partially inactivate GL13K but not a
d
amino acid version of the peptide.
Bioluminescence-Based Neuraminidase Inhibition Assay for Monitoring Influenza Virus Drug Susceptibility in Clinical Specimens
Authors: Marjuki Henju , Mishin Vasiliy P. , Sleeman Katrina , Okomo-Adhiambo Margaret , Sheu Tiffany G. , Guo Lizheng , Xu Xiyan , Gubareva Larisa V. 
Published: August 2013

ABSTRACT

The QFlu prototype bioluminescence-based neuraminidase (NA) inhibition (NI) assay kit was designed to detect NA inhibitor (NAI)-resistant influenza viruses at point of care. Here, we evaluated its suitability for drug susceptibility assessment at a surveillance laboratory. A comprehensive panel of reference viruses (
n
= 14) and a set of 90 seasonal influenza virus A and B isolates were included for testing with oseltamivir and/or zanamivir in the QFlu assay using the manufacturer-recommended protocol and a modified version attuned to surveillance requirements. The 50% inhibitory concentrations (IC
50
s) generated were compared with those of NI assays currently used for monitoring influenza drug susceptibility, the fluorescent (FL) and chemiluminescent (CL) assays. To provide proof of principle, clinical specimens (
n
= 235) confirmed by real-time reverse transcription (RT)-PCR to contain influenza virus A(H1N1)pdm09 and prescreened for the oseltamivir resistance marker H275Y using pyrosequencing were subsequently tested in the QFlu assay. All three NI assays were able to discriminate the reference NA variants and their matching wild-type viruses based on the difference in their IC
50
s. Unless the antigenic types were first identified, certain NA variants (e.g., H3N2 with E119V) could be detected among seasonal viruses using the FL assays only. Notably, the QFlu assay identified oseltamivir-resistant A(H1N1)pdm09 viruses carrying the H275Y marker directly in clinical specimens, which is not feasible with the other two phenotypic assays, which required prior virus culturing in cells. Furthermore, The QFlu assay allows detection of the influenza virus A and B isolates carrying established and potential NA inhibitor resistance markers and may become a useful tool for monitoring drug resistance in clinical specimens.
Population Pharmacokinetics of Colistin Methanesulfonate in Rats: Achieving Sustained Lung Concentrations of Colistin for Targeting Respiratory Infections
Authors: W. S. Yapa Shalini , Li Jian , Porter Christopher J. H. , Nation Roger L. , Patel Kashyap , McIntosh Michelle P. 
Published: August 2013

ABSTRACT

Colistin methanesulfonate (CMS), the inactive prodrug of colistin, is administered by inhalation for the management of respiratory infections. However, limited pharmacokinetic data are available for CMS and colistin following pulmonary delivery. This study investigates the pharmacokinetics of CMS and colistin following intravenous (i.v.) and intratracheal (i.t.) administration in rats and determines the targeting advantage after direct delivery into the lungs. In addition to plasma, bronchoalveolar lavage (BAL) fluid was collected to quantify drug concentrations in lung epithelial lining fluid (ELF). The resulting data were analyzed using a population modeling approach in S-ADAPT. A three-compartment model described the disposition of both compounds in plasma following i.v. administration. The estimated mean clearance from the central compartment was 0.122 liters/h for CMS and 0.0657 liters/h for colistin. Conversion of CMS to colistin from all three compartments was required to fit the plasma data. The fraction of the i.v. dose converted to colistin in the systemic circulation was 0.0255. Two BAL fluid compartments were required to reflect drug kinetics in the ELF after i.t. dosing. A slow conversion of CMS (mean conversion time [MCT
CMS
] = 3.48 h) in the lungs contributed to high and sustained concentrations of colistin in ELF. The fraction of the CMS dose converted to colistin in ELF (
f
m,ELF =
0.226) was higher than the corresponding fractional conversion in plasma after i.v. administration. In conclusion, pulmonary administration of CMS achieves high and sustained exposures of colistin in lungs for targeting respiratory infections.
Rapid Emergence of Resistance to Linezolid and Mutator Phenotypes in Staphylococcus aureus Isolates from an Adult Cystic Fibrosis Patient
Authors: Tazi Asmaa , Chapron Jeanne , Touak Gerald , Longo Magalie , Hubert Dominique , Collobert Gislène , Dusser Daniel , Poyart Claire , Morand Philippe C. 
Published: August 2013

ABSTRACT

Linezolid has emerged as an important therapeutic option for the treatment of
Staphylococcus aureus
in patients with cystic fibrosis. We report the rapid emergence, upon treatment with linezolid, of linezolid-resistant
S. aureus
clinical isolates through the accumulation of resistance-associated 23S rRNA mutations, together with acquisition of an altered mutator phenotype.
Requirement and Redundancy of the Src Family Kinases Fyn and Lyn in Perforin-Dependent Killing of Cryptococcus neoformans by NK Cells
Authors: Oykhman Paul , Timm-McCann Martina , Xiang Richard F. , Islam Anowara , Li Shu Shun , Stack Danuta , Huston Shaunna M. , Ma Ling Ling , Mody Christopher H. 
Published: August 2013

ABSTRACTNatural killer (NK) cells directly recognize and kill fungi, such as the pathogenic fungusCryptococcus neoformans, via cytolytic mechanisms. However, the precise signaling pathways governing this NK cell microbicidal activity and the implications for fungal recognition are still unknown. Previously, it was reported that NK cell anticryptococcal activity is mediated through a conserved phosphatidylinositol 3-kinase–extracellular signal-regulated kinase 1/2 (PI3K-ERK1/2) pathway. Using YT (a human NK-like cell line) and primary human NK cells, we sought to identify the upstream, receptor-proximal signaling elements that led to fungal cytolysis. We demonstrate that Src family kinases were activated in response toC. neoformans. Furthermore, pharmacologic inhibition with an Src kinase inhibitor blockedC. neoformans-induced downstream activation of PI3K and ERK1/2 and abrogated cryptococcal killing. At the same time, the inhibitor disrupted the polarization of perforin-containing granules toward the NK cell-cryptococcal synapse but had no effect on conjugate formation between the organism and the NK cell. Finally, small interfering RNA (siRNA) double (but not single) knockdown of two Src family kinases, Fyn and Lyn, blocked cryptococcal killing. Together these data demonstrate a mechanism whereby the Src family kinases, Fyn and Lyn, redundantly mediate anticryptococcal activity through the activation of PI3K and ERK1/2, which in turn facilitates killing by inducing the polarization of perforin-containing granules to the NK cell-cryptococcal synapse.
An Exploratory Review of the Electroacupuncture Literature: Clinical Applications and Endorphin Mechanisms
Authors: Mayor David 
Published: August 2013

Electroacupuncture (EA) is widely used in clinical practice and research, as well as in experimental investigations into the mechanisms of acupuncture. This study explores publication trends in clinical and experimental studies of EA (1975–2011) for pain and non-pain research; EA use for different clinical conditions (1974–2012); and the relation of EA research, including stimulation frequency, to opioid peptide mechanisms. Appropriate PubMed ‘all fields’ searches were conducted, identified studies were classified using PubMed filters and manually, and data extracted into tables. A total of 2916 clinical studies were located, of which 19% involved EA. Additionally, 3344 animal studies were located, of which 48% involved EA. The publication rate of EA studies per year has risen over time, but the percentage of studies of pain has fallen from 60% to 25%. The conditions most commonly treated with EA are musculoskeletal, neurological, obstetric and gastrointestinal, along with intraoperative and postoperative analgesia. EA studies, particularly with low frequency stimulation, are more likely to support the role of endogenous opioid mechanisms than manual acupuncture studies, and opioid release is more likely in the central nervous system than the circulation. EA is increasingly used in clinical and especially experimental research, particularly for non-pain conditions. Acupuncture does release endogenous opioids, but this probably depends on ‘dosage’, with the evidence more consistent and convincing for EA than for manual acupuncture. Different frequencies of EA appear to activate different endogenous opioid mechanisms.
Effectiveness of an educational video on concussion knowledge in minor league hockey players: a cluster randomised controlled trial
Authors: Cusimano Michael D , Chipman Mary , Donnelly Peter , Hutchison Michael G 
Published: August 2013

BackgroundWith the heightened awareness of concussions in all sports, the development and implementation of effective prevention strategies are necessary. Education has been advocated as an effective injury prevention intervention.PurposeTo examine the effectiveness of the ‘Smart Hockey: More Safety, More Fun’ video on knowledge transfer among minor league hockey players.Study DesignCluster-randomised controlled trial.MethodsA total of 267 participants from two age divisions and competitive levels were assigned to either avideoorno-videogroup. The video was shown (or not shown) to the entire team as a result of random assignment. To evaluate the effectiveness of the educational video, questionnaires specific to concussion knowledge and players’ attitudes and behaviours were completed.ResultsThere was a significant increase in the players’ concussion knowledge scores immediately following exposure to the video (F(1,103)=27.00, p<0.001). However, concussion knowledge at 2 months was not significantly different between thevideoandno-videogroups, after controlling for prior knowledge level, age and competitive level (F(1,115)=0.41, p=0.523). Similarly, players’ attitudes and behaviour scores at 2 months did not differ between groups (F(1,115)=0.41, p=0.507).ConclusionsWe were able to show that a single viewing of an educational video in hockey could immediately improve knowledge about concussion but that this effect was transient and lost at 2-month follow-up. Future prevention endeavours in hockey and other sports should attempt to incorporate strategies and modalities to enhance knowledge retention.
Complementary Populations of Human Adipose CD34+ Progenitor Cells Promote Growth, Angiogenesis, and Metastasis of Breast Cancer
Authors: Orecchioni Stefania , Gregato Giuliana , Martin-Padura Ines , Reggiani Francesca , Braidotti Paola , Mancuso Patrizia , Calleri Angelica , Quarna Jessica , Marighetti Paola , Aldeni Chiara , Pruneri Giancarlo , Martella Stefano , Manconi Andrea , Petit Jean-Yves , Rietjens Mario , Bertolini Francesco 
Published: August 2013

AbstractObesity is associated with an increased frequency, morbidity, and mortality of several types of neoplastic diseases, including postmenopausal breast cancer. We found that human adipose tissue contains two populations of progenitors with cooperative roles in breast cancer. CD45−CD34+CD31+CD13−CCRL2+ endothelial cells can generate mature endothelial cells and capillaries. Their cancer-promoting effect in the breast was limited in the absence of CD45−CD34+CD31−CD13+CD140b+ mesenchymal progenitors/adipose stromal cells (ASC), which generated pericytes and were more efficient than endothelial cells in promoting local tumor growth. Both endothelial cells and ASCs induced epithelial-to-mesenchymal transition (EMT) gene expression in luminal breast cancer cells. Endothelial cells (but not ASCs) migrated to lymph nodes and to contralateral nascent breast cancer lesions where they generated new vessels. In vitro and in vivo, endothelial cells were more efficient than ASCs in promoting tumor migration and in inducing metastases. Granulocyte colony-stimulating factor (G-CSF) effectively mobilized endothelial cells (but not ASCs), and the addition of chemotherapy and/or of CXCR4 inhibitors did not increase endothelial cell or ASC blood mobilization. Our findings suggest that adipose tissue progenitor cells cooperate in driving progression and metastatic spread of breast cancer. Cancer Res; 73(19); 5880–91. ©2013 AACR.
Combination of Antibody That Inhibits Ligand-Independent HER3 Dimerization and a p110α Inhibitor Potently Blocks PI3K Signaling and Growth of HER2+ Breast Cancers
Authors: Garrett Joan T. , Sutton Cammie R. , Kurupi Richard , Bialucha Carl Uli , Ettenberg Seth A. , Collins Scott D. , Sheng Qing , Wallweber Jerry , DeFazio-Eli Lisa , Arteaga Carlos L. 
Published: August 2013

Abstract
We examined the effects of LJM716, an HER3 (ERBB3) neutralizing antibody that inhibits ligand-induced and ligand-independent HER3 dimerization, as a single agent and in combination with BYL719, an ATP competitive p110α-specific inhibitor, against HER2-overexpressing breast and gastric cancers. Treatment with LJM716 reduced HER2-HER3 and HER3-p85 dimers, P-HER3 and P-AKT, both in vitro and in vivo. Treatment with LJM716 alone markedly reduced growth of BT474 xenografts. The combination of LJM716/lapatinib/trastuzumab significantly improved survival of mice with BT474 xenografts compared with lapatinib/trastuzumab (P = 0.0012). LJM716 and BYL719 synergistically inhibited growth in a panel of HER2+ and PIK3CA mutant cell lines. The combination also inhibited P-AKT in HER2-overexpressing breast cancer cells and growth of HER2+ NCI-N87 gastric cancer xenografts more potently than LJM716 or BYL719 alone. Trastuzumab-resistant HER2+/PIK3CA mutant MDA453 xenografts regressed completely after 3 weeks of therapy with LJM716 and BYL719, whereas either single agent inhibited growth only partially. Finally, mice with BT474 xenografts treated with trastuzumab/LJM716, trastuzumab/BYL719, LJM716/BYL719, or trastuzumab/LJM716/BYL719 exhibited similar rates of tumor regression after 3 weeks of treatment. Thirty weeks after treatment discontinuation, 14% of mice were treated with trastuzumab/LJM716/BYL719, whereas &gt;80% in all other treatment groups were sacrificed due to a recurrent large tumor burden (P = 0.0066). These data suggest that dual blockade of the HER2 signaling network with an HER3 antibody that inhibits HER2-HER3 dimers in combination with a p110α-specific inhibitor in the absence of a direct HER2 antagonist is an effective treatment approach against HER2-overexpressing cancers. Cancer Res; 73(19); 6013–23. ©2013 AACR.
Age at Diagnosis May Trump Family History in DrivingBRCATesting in a Population of Breast Cancer Patients
Authors: Vig Hetal S. , McCarthy Anne Marie , Liao Kaijun , Demeter Mirar Bristol , Fredericks Tracey , Armstrong Katrina 
Published: August 2013

AbstractBackground: Standard BRCA genetic testing criteria include young age of diagnosis, family history, and Jewish ancestry. The purpose of this study was to assess the effect of these criteria on BRCA test utilization in breast cancer patients.Methods: Breast cancer patients aged 18 to 64 years living in Pennsylvania in 2007 completed a survey on family history of breast and ovarian cancer and BRCA testing (N = 2,213). Multivariate logistic regression was used to estimate odds of BRCA testing by patient characteristics, and predicted probabilities of testing were calculated for several clinical scenarios.Results: Young age at diagnosis (&lt;50 years) was strongly associated with BRCA testing, with women diagnosed before age 50 years having nearly five times the odds of receiving BRCA testing compared to women diagnosed at age 50 or older (OR = 4.81; 95% CI, 3.85–6.00; P &lt; 0.001). Despite a similar BRCA mutation prevalence estimate (8–10%), a young Jewish patient &lt;50 years with no family history had markedly higher predicted probability of testing (63%) compared with an older, non-Jewish breast cancer patient with more than one first-degree relative (43%).Conclusion: Age at diagnosis, Jewish ancestry, and both maternal and paternal family history are strongly predictive of BRCA testing. However, among women diagnosed at age 50 or older, family history may be an underused criterion that may benefit from targeted intervention.Impact: Robust methods specific to ascertaining detailed family history, such as through electronic medical records, are needed to accurately identify patients for BRCA testing. Cancer Epidemiol Biomarkers Prev; 22(10); 1778–85. ©2013 AACR.