bluuebunny/crossref_metadata_2025 huggingface dataset:
α1 adrenoceptor activation by norepinephrine inhibits LPS‐induced cardiomyocyte TNF‐α production via modulating ERK1/2 and NF‐κB pathway
Authors: Yu Xiaohui , Jia Baoyin , Wang Faqiang , Lv Xiuxiu , Peng Xuemei , Wang Yiyang , Li Hongmei , Wang Yanping , Lu Daxiang , Wang Huadong
Published: December 2013

Cardiomyocyte tumour necrosis factor α (TNF‐α) production contributes to myocardial depression during sepsis. This study was designed to observe the effect of norepinephrine (NE) on lipopolysaccharide (LPS)‐induced cardiomyocyte TNF‐α expression and to further investigate the underlying mechanisms in neonatal rat cardiomyocytes and endotoxaemic mice. In cultured neonatal rat cardiomyocytes, NE inhibited LPS‐induced TNF‐α production in a dose‐dependent manner. α1‐ adrenoceptor (AR) antagonist (prazosin), but neither β1‐ nor β2‐AR antagonist, abrogated the inhibitory effect of NE on LPS‐stimulated TNF‐α production. Furthermore, phenylephrine (PE), an α1‐AR agonist, also suppressed LPS‐induced TNF‐α production. NE inhibited p38 phosphorylation and NF‐κB activation, but enhanced extracellular signal‐regulated kinase 1/2 (ERK1/2) phosphorylation and c‐Fos expression in LPS‐treated cardiomyocytes, all of which were reversed by prazosin pre‐treatment. To determine whether ERK1/2 regulates c‐Fos expression, p38 phosphorylation, NF‐κB activation and TNF‐α production, cardiomyocytes were also treated with U0126, a selective ERK1/2 inhibitor. Treatment with U0126 reversed the effects of NE on c‐Fos expression, p38 mitogen‐activated protein kinase (MAPK) phosphorylation and TNF‐α production, but not NF‐κB activation in LPS‐challenged cardiomyocytes. In addition, pre‐treatment with SB202190, a p38 MAPK inhibitor, partly inhibited LPS‐induced TNF‐α production in cardiomyocytes. In endotoxaemic mice, PE promoted myocardial ERK1/2 phosphorylation and c‐Fos expression, inhibited p38 phosphorylation and IκBα degradation, reduced myocardial TNF‐α production and prevented LPS‐provoked cardiac dysfunction. Altogether, these findings indicate that activation of α1‐AR by NE suppresses LPS‐induced cardiomyocyte TNF‐α expression and improves cardiac dysfunction during endotoxaemia via promoting myocardial ERK phosphorylation and suppressing NF‐κB activation.
‘Thinking Before Acting’ or ‘Acting Before Thinking’: Antecedents of Individual Action Propensity in Work Situations
Authors: Vera Dusya , Crossan Mary , Rerup Claus , Werner Steve
Published: December 2013

We introduce the concept of ‘individual action propensity’ to examine the approach of individuals towards solving situations for which they lack knowledge and/or experience about what to do. We focus on a naturally contrasting pair of responses: ‘thinking before acting’ or ‘acting before thinking’, and associate low action propensity with thinking one's way into understanding how to act, and high action propensity with acting one's way into understanding such situations. We build on regulatory mode theory – with its dimensions of locomotion and assessment and the trade‐off between speed and accuracy – to examine individual characteristics as predictors of individual action propensity. We find that individual action propensity is associated with being a woman, having fewer years of formal education, not relying on help‐seeking behaviours, and having a positive attitude towards spontaneity. Our findings shed light on why individuals take action, or not, and provide implications for research on organizational action propensity.
Optimal Capital Taxation in a Neoclassical Growth Model
Authors: LU CHIA‐HUI , CHEN BEEN‐LON
Published: December 2013

This paper studies the optimal factor tax incidence in a neoclassical growth model with a given share of government expenditure in output. In the Ramsey planner's optimization, the effect of next period's capital on government expenditure equals the given share of the marginal product of capital. Capital accumulation reduces the discounted net marginal product of next period's capital by way of increasing government expenditure. In order to internalize the distortion, it is optimal to tax capital income in the long run.
Tax Uniformity: A Commitment Device for Restraining Opportunistic Behavior
Authors: DEWIT GERDA , LEAHY DERMOT
Published: December 2013

We show that uniform and differentiated tax systems diverge in their propensity to generate distortionary opportunistic behavior. First, when firms choose investment before the government can commit to its taxes, the tax scheme creates strategic incentives for firms to distort their investment. Second, a system of differentiated taxes has a greater propensity to foster strategic distortions in investment than a uniform tax regime. While the paper makes these points in a set‐up in which polluting firms face an emission tax and invest in abatement, the main message is shown to hold for a wide class of tax policy games.
The Role of Ego Networks in Manufacturing Joint Venture Formations
Authors: Carnovale Steven , Yeniyurt Sengun
Published: December 2013

This article develops a network theory–based framework of manufacturing joint venture formations and provides an empirical test in the context of the automotive industry. Hypotheses are developed regarding the implications of the network structure for a firm's partner selection in manufacturing joint ventures. The roles of network theory constructs such as ego network size, ego network density, and ego network betweenness centrality on new manufacturing joint venture formations are explored using a dynamic framework. A comprehensive time series panel dataset with 3,247,124 observations containing the joint venture information of 1,158 automotive firms collectively engaging in 589 manufacturing joint ventures over 19 years is utilized to test the hypotheses. Results provide strong empirical support for the role of network structure in equity‐based partnership formation. Specifically, ego network size and ego network betweenness centrality of both the focal manufacturer and potential partner have significant effects on new manufacturing joint venture formations. Findings regarding the role of ego network density are mixed.
Understanding the Role of Government and Buyers in Supplier Energy Efficiency Initiatives
Authors: Wu Zhaohui , Ellram Lisa M. , Schuchard Ryan
Published: December 2013

In environmental management, companies must respond to myriad needs and pressures from stakeholders such as buyers, regulators, communities, andNGOs. While researchers recognize that these stakeholder entities have different saliency and influences over a focal firm, the influences from multiple stakeholders are often aggregated as a single factor, overlooking differences among them. Stakeholders may have competing demands: A buyer may consider only potential environment‐cost trade‐offs, while the government balances the environment, increased cost‐competitive manufacturing and job creation. Such demands compete for the same resources within the supplier's organization, forcing suppliers to satisfice and compromise. This study qualitatively examines Chinese suppliers' responses to requests to adopt energy efficiency (EE) initiatives in their production plants by two of their most critical stakeholders: buyers and the government. We identify three categories ofEEinitiatives implemented by the suppliers and find that their implementations are contingent on their ownership characteristics and value alignment with these two stakeholders. Further, we find that suppliers interpret buyers' motives regardingEEin the context of buyer–supplier relationships and environmental positioning of the buyers' products. These findings are articulated in a set of propositions that are introduced based on our analysis of these case study data.
Cloning and Activity Analysis of Promoter of RanGTPase Gene from Shrimp, Marsupenaeus japonicus
Authors: Han Fang , Wang Zhi‐Yong
Published: December 2013

RanGTPases, one superfamily of small G protein family, have been demonstrated to be involved in the innate immune system and they are up‐regulated after pathogen infection. However, the regulation mechanism of RanGTPases remains unclear. In this study, the 5′ flanking region of shrimp RanGTPase gene was cloned and sequenced. To detect the activity of the promoter, pIZΔIE/EGFP was modified from pIZ/V5‐His by replacing the OPIE2 promoter with this promoter and inserting enhanced green fluorescence protein (EGFP) gene downstream. The promoter can drive the expression of reporter EGFP gene in Hi5 insect cells, indicating the promoter has activity. These results extend our previous findings and provide insights into the molecular regulation of RanGTPase gene expression, which will be helpful for shrimp viral disease control.
Replacement of Fish Meal with Soybean Meal, Alone or in Combination with Distiller's Dried Grains with Solubles in Practical Diets for Pacific White Shrimp, Litopenaeus vannamei, Grown in a Clear‐Water Culture System
Authors: Cummins Vaun C. , Webster Carl D. , Thompson Kenneth R. , Velasquez Alejandro
Published: December 2013

The objective of this study was to evaluate inclusion of distiller's dried grains with solubles (DDGS) as partial replacement of commercial, solvent‐extracted soybean meal (SBM) in fish meal‐free diets for Pacific white shrimp, Litopenaeus vannamei. Aquaria connected to a recirculating biofiltration system were utilized to evaluate growth, survival, and feed conversion of shrimp during the 8‐wk feeding trial. Each 110‐L aquarium was stocked with 15 shrimp (mean individual weight 0.99 g) and fed one of five diets: a diet containing 20% fish meal (FM), which served as the control (Diet 1); a diet containing 0% FM and 52.5% SBM (Diet 2); and diets containing 0% FM and either 10, 20, or 30% DDGS as partial replacement of SBM (Diets 3, 4, and 5, respectively). Shrimp were fed according to a pre‐determined feeding chart five times daily (0730, 1030, 1330, 1630, and 1930 h) and there were three replicates per dietary treatment. The results from the feeding trial demonstrated that final weight, weight gain (g), and percentage weight gain were significantly higher (P < 0.05) for shrimp fed Diet 1 (10.96 g, 10.01 g, and 1051%, respectively) compared to shrimp fed diets containing DDGS; however, shrimp fed diets containing DDGS had similar (P > 0.05) final weight, weight gain (g), and percentage weight gain as shrimp fed a diet containing 0% FM and 52.5% SBM (Diet 2). Feed conversion ratio (FCR) of shrimp fed Diet 1 (2.84) was significantly lower (P < 0.05) compared to shrimp fed any other diet. Survival (%) was not different (P > 0.05) among treatments and averaged 77.3% for the study. This study demonstrated that practical shrimp diets containing no FM had an adverse impact on growth performance of white shrimp when grown in a clear‐water system and that further research is needed to refine diet formulations when culturing shrimp in these systems when attempting to feed a diet without FM.
Possible Roles of Farnesoic Acid O‐Methyltransferase in Regulation of Molting in the Shrimp, Penaeus Chinensis
Authors: Li Zhaoxia , Xu Xiaofei , Wang Jinye , Wang Chunde
Published: December 2013

Methyl farnesoate (MF) is the crustacean homolog of the insect juvenile hormone and is believed to regulate physiological processes such as molting and reproduction in crustaceans. Farnesoic acid (FA) O‐methyltransferase (FAMeT) is an important enzyme in conversion of FA to MF and may thus play key roles in regulation of growth in crustaceans. In this study, we cloned a full‐length PcFAMeT cDNA sequence consisting of 1319 bp (Genbank: JQ315119) with an open reading frame (ORF) of 840 bp that encodes 280 amino acids from the shrimp, Penaeus chinensis. Comparison of the amino acid sequence revealed that PcFAMeT had an overall similarity of 81.07–96.07% with other penaeid shrimp FAMeT. Quantitative real‐time polymerase chain reaction (PCR) analysis showed that PcFAMeT transcript has a wide tissue distribution pattern in P. chinensis and the highest expression of the transcripts occurred in muscle tissue. Stage‐specific expression profile revealed that the highest expression of FAMeT occurred at the intermolt stage which implied that the conversion of FA to MF may be involved in the onset of molting processes.
Extracellular Ubiquitin Increases Expression of Angiogenic Molecules and Stimulates Angiogenesis in Cardiac Microvascular Endothelial Cells
Authors: Steagall Rebecca J. , Daniels Christopher R. , Dalal Suman , Joyner William L. , Singh Mahipal , Singh Krishna
Published: December 2013

Extracellular Ub is an immune modulator that plays a role in suppression of inflammation, organ injury, myocyte apoptosis, and fibrosis. The purpose of this study was to investigate the effects of extracellular Ub on the process of cardiac angiogenesis. CMECs and aortic tissue were isolated from rats to measure changes in angiogenic protein levels and to assess angiogenic responses to extracellular Ub. In CMECs, extracellular Ub increased protein levels of VEGF‐A and MMP‐2, known angiogenesis regulators. CMECs demonstrated enhanced rearrangement of fibrillar actin and migration in response to Ub treatment. Ub‐treated CMECs demonstrated an increase in tube network formation which was inhibited by the CXCR4 receptor antagonist, AMD3100. Methylated Ub, unable to form polyubiquitin chains, enhanced tube network formation. Aortic ring sprouting assays demonstrated that Ub increases microvessel sprouting in the Matrigel. The results of our study suggest a novel role for extracellular Ub in cardiac angiogenesis, providing evidence that extracellular Ub, at least in part acting via the CXCR4 receptor, has the potential to facilitate the process of angiogenesis in myocardial endothelial cells.
The multifunctional role of the pallilysin‐associated Treponema pallidum protein, Tp0750, in promoting fibrinolysis and extracellular matrix component degradation
Authors: Houston Simon , Russell Shannon , Hof Rebecca , Roberts Alanna K. , Cullen Paul , Irvine Kyle , Smith Derek S. , Borchers Christoph H. , Tonkin Michelle L. , Boulanger Martin J. , Cameron Caroline E.
Published: December 2013

The mechanisms that facilitate dissemination of the highly invasive spirochaete, Treponema pallidum, are incompletely understood. Previous studies showed the treponemal metalloprotease pallilysin (Tp0751) possesses fibrin clot degradation capability, suggesting a role in treponemal dissemination. In the current study we report characterization of the functionally linked protein Tp0750. Structural modelling predicts Tp0750 contains a von Willebrand factor type A (vWFA) domain, a protein‐protein interaction domain commonly observed in extracellular matrix (ECM)‐binding proteins. We report Tp0750 is a serine protease that degrades the major clot components fibrinogen and fibronectin. We also demonstrate Tp0750 cleaves a matrix metalloprotease (MMP) peptide substrate that is targeted by several MMPs, enzymes central to ECM remodelling. Through proteomic analyses we show Tp0750 binds the endothelial fibrinolytic receptor, annexin A2, in a specific and dose‐dependent manner. These results suggest Tp0750 constitutes a multifunctional protein that is able to (1) degrade infection‐limiting clots by both inhibiting clot formation through degradation of host coagulation cascade proteins and promoting clot dissolution by complexing with host proteins involved in the fibrinolytic cascade and (2) facilitate ECM degradation via MMP‐like proteolysis of host components. We propose that through these activities Tp0750 functions in concert with pallilysin to enable T. pallidum dissemination.
Genomic resources for breeding crops with enhanced abiotic stress tolerance
Authors: Bansal Kailash C. , Lenka Sangram K. , Mondal Tapan K.
Published: December 2013

To meet the challenges of climate change, exploring natural diversity in the existing plant genetic resource pool as well as creation of new mutants through chemical mutagenesis and molecular biology is needed for developing climate‐resilient elite genotypes. Ever‐increasing area under existing abiotic stresses as well as emerging abiotic stress factors and their combinations have further added to the problems of the current crop improvement programmes. However, with the advancement in modern techniques such as next‐generation sequencing technologies, it is now possible to generate on a whole‐genome scale, genomic resources for crop species at a much faster pace with considerably less efforts and money. The genomic resources thus generated will be useful for various plant breeding applications such as marker‐assisted breeding for gene introgression, mapping QTLs or identifying new or rare alleles associated with a particular trait. In this article, we discuss various aspects of generation of genomic resources and their utilization for developing abiotic stress‐tolerant crops to ensure sustainable agricultural production and food security in the backdrop of rapid climate change.
Dynamic Calibration of a Coaxial Thermocouples for Short Duration Transient Measurements
Authors: Kumar Rakesh , Sahoo Niranjan
Published: December 2013

Coaxial thermocouple sensors are suitable for measuring highly transient surface heat fluxes because the response times of these sensors are very small (∼0.1 ms). These robust sensors have the flexibility of mounting them directly on the surface of any geometry. So, they have been routinely used in ground-based impulse facilities as temperature sensors where rapid changes in heat loads are expected on aerodynamic models. Subsequently, the surface heat fluxes are predicted from the transient temperatures by appropriate one-dimensional heat conduction modeling for semi-infinite body. In this backdrop, the purpose of this work is to design and fabricate K-type coaxial thermocouples in-house and calibrate them under similar nature of heat loads by using simple laboratory instruments. Here, two methods of dynamic calibration of coaxial thermocouples have been discussed, where the known step loads are applied through radiation and conduction modes of heat transfer. Using appropriate one dimensional heat conduction modeling, the surface heat fluxes are predicted from the measured temperature histories and subsequently compared with the input heat loads. The recovery of surface heat flux from laser based calibration experiment under-predicts by 4% from its true input heat load. Similarly, recovery of surface heat flux from the conduction mode calibration experiments under-predicts 6% from its true input value. Further, finite-element based numerical study is performed on the coaxial thermocouple model to obtain surface temperatures with same heat loads as used in the experiments. The recovery of surface temperatures from finite element simulation is achieved within an accuracy of ±0.3% from the experiment.
Effect of 5 MeV proton radiation on DC performance and reliability of circular-shaped AlGaN/GaN high electron mobility transistors
Authors: Xi Yuyin , Hsieh Yueh-Ling , Hwang Ya-Hsi , Li Shun , Ren Fan , Pearton Stephen J. , Patrick Erin , Law Mark E. , Yang Gwangseok , Kim Hong-Yeol , Kim Jihyun , Baca Albert G. , Allerman Andrew A. , Sanchez Carlos A.
Published: December 2013

The authors report an investigation of the effect of different doses of 5 MeV proton irradiation on circular-shaped AlGaN/GaN high electron mobility transistors. The degradation of saturation drain current (IDSS) was minimal up to an irradiation dose of 2 × 1013 cm−2. By comparison, a dose of 2 × 1014 cm−2 dose produced a 12.5% reduction of IDSS and 9.2% increase of sheet resistance. In addition, the threshold voltage showed larger positive shifts for 2×1014 cm−2 dose compared to 2×1013 cm−2, and both of these doses produced showed larger shifts for smaller gate to drain distances. Increases of 39.8% and 47.1%, respectively, in the breakdown voltage for 6 and 10 μm drain to gate distances (LGD) was observed and was attributed to the creation of a virtual gate at the AlGaN/GaN interface due to the irradiation, which reduced the peak electric field at the drain side of the gate edge.
Direct evidence for interface state annealing in the negative bias temperature instability response
Authors: Nguyen Duc D. , Kouhestani Camron , Kambour Kenneth E. , Devine Roderick A. B.
Published: December 2013

Using a rapid data acquisition methodology, the authors examine the time dependent recovery of the “permanent” component of charge build-up due to the negative bias temperature instability in Si based p-channel field effect transistors in inversion and n-channel devices in accumulation. The authors find clear evidence for recovery of the charge associated with interface states for elevated temperatures (≥150 °C) and for extended times (trecover ∼ 20 000 s). Recovery appears to begin at shorter times for p-channel devices than for n-channel. An explanation is advanced both for the mechanism of interface state annealing and for the difference observed between p and n channel devices.
Advanced Manufacturing Policies and Paradigms for Innovation
Authors: Bonvillian William B.
Published: December 2013

U.S. innovation is heavy on early-stage R&D; it requires additional focus on manufacturing stages.
Single-Cell Metabolomics: Analytical and Biological Perspectives
Authors: Zenobi R.
Published: December 2013

There is currently much interest in broad molecular profiling of single cells; a cell’s metabolome—its full complement of small-molecule metabolites—is a direct indicator of phenotypic diversity of single cells and a nearly immediate readout of how cells react to environmental influences. However, the metabolome is very difficult to measure at the single-cell level because of rapid metabolic dynamics, the structural diversity of the molecules, and the inability to amplify or tag small-molecule metabolites. Measurement techniques including mass spectrometry, capillary electrophoresis, and, to a lesser extent, optical spectroscopy and fluorescence detection have led to impressive advances in single-cell metabolomics. Even though none of these methodologies can currently measure the metabolome of a single cell completely, rapidly, and nondestructively, progress has been sufficient such that the field is witnessing a shift from feasibility studies to investigations that yield new biological insight. Particularly interesting fields of application are cancer biology, stem cell research, and monitoring of xenobiotics and drugs in tissue sections at the single-cell level.
Precision Spectroscopy of Polarized Molecules in an Ion Trap
Authors: Loh H. , Cossel K. C. , Grau M. C. , Ni K.-K. , Meyer E. R. , Bohn J. L. , Ye J. , Cornell E. A.
Published: December 2013

Toward a New Physics

The search for physics beyond the Standard Model is carried out at accelerator facilities such as the Large Hadron Collider but also on a smaller scale in atomic and molecular physics experiments. One of the signatures of this “new physics” would be a nonvanishing electric dipole moment of the electron, but experiments designed to look for it need to distinguish between the signal and many potential artifacts.

Loh
et al.

(p.
1220
) introduce a method based on the spectroscopy of polarized molecular ions that avoids some of the sources of systematic error.
How Fisheries Affect Evolution
Authors: Belgrano Andrea , Fowler Charles W.
Published: December 2013

Commercial fishing alters the genetic traits of fish stocks.
Placing Climate Change

Sea Change (Tionndadh na Mara)
Elinor Gallant and Ruth Little, curators

Royal Botanic Garden Edinburgh. Through 26 January 2014. www.rbge.org.uk/whats-on/event-details/3091
Authors: Dixon Deborah
Published: December 2013

Collaborating with scientists, artists explore the links between people and place in the Scottish isles in the context of climate change.
Assembly of a Neural Circuit
Authors: Hong Weizhe
Published: December 2013

Differential expression of cell-surface molecules instruct the precise assembly of a neural circuit.
Evolution of Vertebrate Transcriptional Regulator Binding
Authors: Schmidt Dominic
Published: December 2013

Comparative evolutionary analysis of transcriptional regulator binding across several vertebrate species reveals intricate regulatory genome evolution.
Elusive Denisovans Sighted in Oldest Human DNA
Authors: Gibbons Ann
Published: December 2013

Traces of DNA from the Denisovans, a shadowy species thought to have lived in Asia, turn up in a surprising place: in a proto-Neandertal from Spain.
A Painful Cure for Ailing Academy
Authors: Stone Richard
Published: December 2013

In recent weeks, the Russian Academy of Sciences has faced a forced merger, the appointment of a new overlord with no background in science, and now, a painful downsizing: At least 30% of the academy's roughly 55,000 researchers are expected to be laid off in 2014.
Faulty Brain Connections in Dyslexia?
Authors: Underwood Emily
Published: December 2013

A scientific fight is brewing around the cause of dyslexia, a learning disability that affects reading and other language-processing skills.
From Toxins to Treatments
Authors: Kupferschmidt Kai
Published: December 2013

Researchers are hoping to find lifesaving drugs in the deadly venoms from snakes and other animals.
LIFE SCIENCE TECHNOLOGIES Living Large: Scaling Up Cell Culture
Authors: Dove Alan
Published: December 2013

Traditional laboratory biology is a small-scale operation; tissue culture dishes are seldom much larger than the experimenter's hand, volume measurements are in milliliters, and a protein purification that yields a few micrograms is a success. With burgeoning interest in translational research, structural biology, and regenerative medicine, many scientists are starting to think bigger. Whether trying to purify grams of protein for crystallography or testing the feasibility of turning a novel gene product into a new drug, these researchers soon find themselves pondering the complications of larger-scale cell culture.
The Majority of a Collection of U.S. Endocarditis Enterococcus faecalis Isolates Obtained from 1974 to 2004 Lack Capsular Genes and Belong to Diverse, Non-Hospital-Associated Lineages
Authors: Chowdhury Shahreen A. , Nallapareddy Sreedhar R. , Arias Cesar A. , Murray Barbara E.
Published: December 2013

Eighty-one endocarditis-derived
Enterococcus faecalis
isolates that were collected from individual patients in the United States between 1974 and 2004 were sequence typed and analyzed for the presence of various genes, including some previously associated with virulence. Overall, using our previously described trilocus sequence typing (TLST), 44 different sequence types (STs) were found within this collection; 26 isolates were singletons (a unique TLST sequence type [ST
T
]), some ST
T
s contained multiple isolates (up to 6 isolates), and 16% of the isolates (13 isolates) could be grouped by additional sequence typing into clonal cluster 21 (CC21). Of note, only four isolates (7%) of the 56 whose multilocus sequence types were determined were found to belong to one of the previously described hospital-associated clonal clusters CC2 and CC9, and only 15% and 37% of all isolates had high-level resistance to gentamicin and streptomycin, respectively, including 10% that were resistant to both. We also found that 64% of the isolates lacked the genes for production of capsule polysaccharide, which has been proposed to enhance the pathogenic potential of the hospital-associated clonal clusters. In summary, while our collection is not a random sample of cases of
E. faecalis
endocarditis, these results indicate that nonencapsulated strains belonging to non-hospital-associated lineages were predominant among endocarditis
E. faecalis
isolates recovered during this time period.
H3 Stalk-Based Chimeric Hemagglutinin Influenza Virus Constructs Protect Mice from H7N9 Challenge
Authors: Krammer Florian , Margine Irina , Hai Rong , Flood Alexander , Hirsh Ariana , Tsvetnitsky Vadim , Chen Dexiang , Palese Peter
Published: December 2013

The recent outbreak of H7N9 influenza virus infections in humans in China has raised concerns about the pandemic potential of this strain. Here, we test the efficacy of H3 stalk-based chimeric hemagglutinin universal influenza virus vaccine constructs to protect against H7N9 challenge in mice. Chimeric hemagglutinin constructs protected from viral challenge in the context of different administration routes as well as with a generic oil-in-water adjuvant similar to formulations licensed for use in humans.
High-Multiplicity HIV-1 Infection and Neutralizing Antibody Evasion Mediated by the Macrophage-T Cell Virological Synapse
Authors: Duncan Christopher J. A. , Williams James P. , Schiffner Torben , Gärtner Kathleen , Ochsenbauer Christina , Kappes John , Russell Rebecca A. , Frater John , Sattentau Quentin J.
Published: December 2013

Macrophage infection is considered to play an important role in HIV-1 pathogenesis and persistence. Using a primary cell-based coculture model, we show that monocyte-derived macrophages (MDM) efficiently transmit a high-multiplicity HIV-1 infection to autologous CD4+T cells through a viral envelope glycoprotein (Env) receptor- and actin-dependent virological synapse (VS), facilitated by interactions between ICAM-1 and LFA-1. Virological synapse (VS)-mediated transmission by MDM results in high levels of T cell HIV-1 integration and is 1 to 2 orders of magnitude more efficient than cell-free infection. This mode of cell-to-cell transmission is broadly susceptible to the activity of CD4 binding site (CD4bs) and glycan or glycopeptide epitope-specific broadly neutralizing monoclonal antibodies (bNMAbs) but shows resistance to bNMAbs targeting the Env gp41 subunit membrane-proximal external region (MPER). These data define for the first time the structure and function of the macrophage-to-T cell VS and have important implications for bNMAb activity in HIV-1 prophylaxis and therapy.

IMPORTANCEThe ability of HIV-1 to move directly between contacting immune cells allows efficient viral dissemination with the potential to evade antibody attack. Here, we show that HIV-1 spreads from infected macrophages to T cells via a structure called a virological synapse that maintains extended contact between the two cell types, allowing transfer of multiple infectious events to the T cell. This process allows the virus to avoid neutralization by a class of antibody targeting the gp41 subunit of the envelope glycoproteins. These results have implications for viral spreadin vivoand the specificities of neutralizing antibody elicited by antibody-based vaccines.
Leiomyosarcoma of the maxilla in a 24-year-old man who initially presented with odontalgia, and suffered from tumour mismanagement
Authors: Taghipour Zahir Shokouh , Sharahjin Naser Sefidrokh
Published: December 2013

Leiomyosarcoma is an uncommon malignant soft tissue tumour originating from smooth muscle cells. It generally occurs in the female genital tract, especially in the uterus, gastrointestinal tract, retroperitoneum and rarely in the head and neck. Here we report a case of leiomyosarcoma in a 24-year-old man with a 6-month history of toothache and extraction of three right upper molar teeth, that was complicated by fistula tract formation and facial swelling. Imaging studies demonstrated tumoural lesions involving the right maxillary sinus, nasal cavity, hard palate and orbit. The histopathological and immunohistochemical studies confirmed that it was leiomyosarcoma.
Successful medical management of aNocardia farcinicamultiloculated pontine abscess
Authors: Chow Felicia C , Marson Alexander , Liu Catherine
Published: December 2013

A 60-year-old man on chronic corticosteroids developed diplopia, gait instability and facial weakness. Brain MRI revealed a multiloculated pontine lesion. Cerebrospinal fluid (CSF) analysis demonstrated a neutrophil-predominant pleocytosis with elevated protein and low glucose. CSF cultures were negative, as was an extensive infectious diseases evaluation. Neurosurgical intervention was deferred in favour of empiric antimicrobial therapy due to the lesion's inaccessible location. After discontinuation of therapy, the patient reported a severe headache. A subsequent MRI demonstrated intraventricular pus. CSF culture grewNocardia farcinica.The patient received parenteral therapy followed by oral trimethoprim-sulfamethoxazole. At 9 months, he is symptom free. This case illustrates the importance of includingNocardiain the differential diagnosis of brainstem abscesses, especially in immunocompromised patients. The availability of antimicrobial agents with excellentNocardiaactivity and CSF penetration may enable treatment of brainstem abscesses for which surgical intervention has traditionally been considered necessary with medical management alone.
Successful pregnancy in a woman with arthrogryposis multiplex congenita
Authors: Castro Jorge , Abreu-Silva João , Godinho Cristina , Valente Francisco
Published: December 2013

Arthrogryposis multiplex congenita refers to a clinical condition or syndrome characterised by multiple congenital contractures that affect two or more different areas of the body. Of the cases reported so far, an important percentage had to be terminated before pregnancy term, predominantly by caesarean section. We describe a 36 year-old woman who wanted to conceive. A multidisciplinary approach was set from the preconceptional period and special attention was given to respiratory function, potential anaesthetic difficulties and thromboembolic risks. She delivered by caesarean section at 38 weeks. This case emphasises the possibility of achieving a term delivery in these patients and points out the importance of a multidisciplinary team, specially of obstetricians and anaesthesiologists.
Management of children in the deployed intensive care unit at Camp Bastion, Afghanistan
Authors: Inwald David P , Arul G S , Montgomery M , Henning J , McNicholas J , Bree S
Published: December 2013

Background

The deployed Intensive Therapy Unit (ITU) in the British military field hospital in Camp Bastion, Afghanistan, admits both adults and children. The purpose of this paper is to review the paediatric workload in the deployed ITU and to describe how the unit copes with the challenge of looking after critically injured and ill children.

Methods

Retrospective review of patients <16 years of age admitted to the ITU in the British military field hospital in Camp Bastion, Afghanistan, over a 1-year period from April 2011 to April 2012.

Results

112/811 (14%) admissions to the ITU were paediatric (median age 8 years, IQR 6–12, range 1–16). 80/112 were trauma admissions, 13 were burns, four were non-trauma admissions and 15 were readmissions. Mechanism of injury in trauma was blunt in 12, blast (improvised explosive device) in 45, blast (indirect fire) in seven and gunshot wound in 16. Median length of stay was 0.92 days (IQR 0.45–2.65). 82/112 admissions (73%) were mechanically ventilated, 16/112 (14%) required inotropic support. 12/112 (11%) died before unit discharge. Trauma scoring was available in 65 of the 80 trauma admissions. Eight had Injury Severity Score or New Injury Severity Score >60, none of whom survived. However, of the 16 patients with predicted mortality >50% by Trauma Injury Severity Score, seven survived. Seven cases required specialist advice and were discussed with the Birmingham Children's Hospital paediatric intensive care retrieval service. The mechanisms by which the Defence Medical Services support children admitted to the deployed adult ITU are described, including staff training in clinical, ethical and child protection issues, equipment, guidelines and clinical governance and rapid access to specialist advice in the UK.

Conclusions

With appropriate support, it is possible to provide intensive care to children in a deployed military ITU.
Plant growth dynamics and root morphology of little-known species of Chenopodium from contrasted Andean habitats
Authors: Alvarez-Flores Ricardo , Winkel Thierry , Degueldre David , Del Castillo Carmen , Joffre Richard
Published: December 2013

Plant morphology determines the access to soil resources, a feature crucial for early growth in annual species. Plant growth and root traits in little-known species of Andean chenopods were compared with the hypothesis that plants from low-resource habitats show traits that enhance resource capture. Three cultivated Chenopodium populations (two populations of the tetraploid Chenopodium quinoa Willd., one population of the diploid Chenopodium pallidicaule Aellen) and one population of their wild tetraploid relative Chenopodium hircinum Schrad. were grown in pots under nonlimiting conditions over nine weeks of early vegetative growth. All populations followed the same sequence of biomass allocation and showed similar maximal values of shoot and root relative growth rates (RGR). Population differences in plant biomass, net assimilation rate, total root length, and specific root length were associated with seed mass ranking and species ploidy level. Chenopodium quinoa produced less branched stems and maintained high root RGR for a longer time than the other two species, and the C. quinoa population from low-resource habitat showed a faster main root growth. These results show that C. pallidicaule developed a plant growth syndrome adapted to cold, high-altitude habitats, while C. quinoa from low-resource habitats showed an improved capacity to explore soil at depth in early growth stages.
Sex-biased parasitism in Richardson’s ground squirrels (Urocitellusrichardsonii) depends on the parasite examined
Authors: Waterman J.M. , Macklin G.F. , Enright C.
Published: December 2013

Sex-biased parasitism is found in many species, but the skew to one sex or the other varies and is most likely due to differences in host and parasite behaviour and the intensity of sexual selection. We examined sex-biased parasitism in Richardson’s ground squirrels (Urocitellus richardsonii (Sabine, 1822)) and hypothesized that males would be more heavily parasitized than females, as they are larger, have larger home ranges, and display high aggression and fighting during the short mating season, suggesting that they may trade off investment in immunity for higher investment in reproduction. Squirrels were caught during the mating season and examined for endoparasites and ectoparasites. Body mass, condition, and immune measures were recorded. Males had higher nematode prevalence and abundance, whereas females had higher flea prevalence. Males also had lower lymphocytes than females, as well as higher neutrophil to lymphocyte ratios. Females had higher eosinophils and they were in poorer body condition than males. The higher endoparasite loads in males suggests that they may be trading off immunity, whereas higher flea prevalence in females may be due to differences in sociality between the sexes. Our study demonstrates the importance of examining multiple parasite types to understand the factors influencing sex-biased parasitism.
COMPARATIVE STUDY OF THE BEHAVIOR OF BATHOPHENANTHROLINE IN THE RESTRICTED GEOMETRY OF LANGMUIR–BLODGETT FILM WITH TWO DIFFERENT FATTY ACIDS
Authors: NATH JAYASREE , DEB SUBRATA , CHAKRABARTI ADRITA , PAL AJITESH , NATH RANENDU KUMAR
Published: December 2013

This communication reports the successful fabrication and the comparative study of Langmuir and Langmuir–Blodgett (LB) films of nonamphiphilic phenanthrene derivative, 1, 10 phenanthroline (bathophenanthroline) (BATH), when incorporated to a long chain fatty acid viz. heptadecanoic acid and stearic acid. Measurements of compressibility modulus from the surface pressure versus area per molecule isotherm indicate that the mixed film of BATH and SA is harder than that with HA. The plot of area per molecule versus mole fraction is the indication of some repulsive interactions between binary components of the mixed monolayer which facilitates the formation of aggregates. UV–Vis absorption spectroscopy and steady-state fluorescence spectroscopy confirms the formation of microcrystalline aggregates in the mixed LB films. Scanning electron microscopic study supports this observation. The dependence of various LB parameters in the mixed films such as mole fraction, number of layers and surface pressure of lifting have also been investigated in the light of electronic absorption spectroscopy.
Evaluating Predictors within a Present-Value Framework
Authors: Yun Jhe
Published: December 2013

I impose functional-form restrictions on the time-series processes of expected returns and expected dividend growth rates to better estimate them in a small sample. The approach helps to aggregate information contained in the entire history of prices, dividend growth, and additional predictors without parameter proliferation. I find that both expected returns and expected dividend growth rates are substantially time-varying, positively correlated with each other, and covary with several macroeconomic variables. The estimated expectations of returns and dividend growth rates are strong predictors of realized returns and dividend growth rates, respectively, both in-sample and out-of-sample. Book-to-Market Ratio, Stock Variance, Consumption-Wealth-Income Ratio, and BAA-rated Corporate Bond Yield significantly improve the return and dividend forecasts of my present-value model.
Mitochondrial 8-oxoguanine glycosylase decreases mitochondrial fragmentation and improves mitochondrial function in H9C2 cells under oxidative stress conditions
Authors: Torres-Gonzalez Moises , Gawlowski Thomas , Kocalis Heidi , Scott Brian T. , Dillmann Wolfgang H.
Published: December 2013

The mitochondrial DNA base modification 8-hydroxy 2′-deoxyguanine (8-OHdG) is one of the most common DNA lesions induced by reactive oxygen species (ROS) and is considered an index of DNA damage. High levels of mitochondrial 8-OHdG have been correlated with increased mutation, deletion, and loss of mitochondrial (mt) DNA, as well as apoptosis. 8-Oxoguanosine DNA glycosylase-1 (OGG1) recognizes and removes 8-OHdG to prevent further DNA damage. We evaluated the effects of OGG1 on mtDNA damage, mitochondrial function, and apoptotic events induced by oxidative stress using H9C2 cardiac cells treated with menadione and transduced with either Adv-Ogg1 or Adv-Control (empty vector). The levels of mtDNA 8-OHdG and the presence of apurinic/apyrimidinic (AP) sites were decreased by 30% and 35%, respectively, in Adv-Ogg1 transduced cells ( P < 0.0001 and P < 0.005, respectively). In addition, the expression of base excision repair (BER) pathway members APE1 and DNA polymerase γ was upregulated by Adv-Ogg1 transduction. Cells overexpressing Ogg1 had increased membrane potential ( P < 0.05) and decreased mitochondrial fragmentation ( P < 0.005). The mtDNA content was found to be higher in cells with increased OGG1 ( P < 0.005). The protein levels of fission and apoptotic factors such as DRP1, FIS1, cytoplasmic cytochrome c, activated caspase-3, and activated caspase-9 were lower in Adv-Ogg1 transduced cells. These observations suggest that Ogg1 overexpression may be an important mechanism to protect cardiac cells against oxidative stress damage.
Functional properties of human ferroportin, a cellular iron exporter reactive also with cobalt and zinc
Authors: Mitchell Colin J. , Shawki Ali , Ganz Tomas , Nemeth Elizabeta , Mackenzie Bryan
Published: December 2013

Iron homeostasis is achieved by regulating the intestinal absorption of the metal and its recycling by macrophages. Iron export from enterocytes or macrophages to blood plasma is thought to be mediated by ferroportin under the control of hepcidin. Although ferroportin was identified over a decade ago, little is understood about how it works. We expressed in Xenopus oocytes a human ferroportin-enhanced green fluorescent protein fusion protein and observed using confocal microscopy its exclusive plasma-membrane localization. As a first step in its characterization, we established an assay to detect functional expression of ferroportin by microinjecting oocytes with 55Fe and measuring efflux. Ferroportin expression increased the first-order rate constants describing 55Fe efflux up to 300-fold over control. Ferroportin-mediated 55Fe efflux was saturable, temperature-dependent (activation energy, Ea ≈ 17 kcal/mol), maximal at extracellular pH ≈ 7.5, and inactivated at extracellular pH < 6.0. We estimated that ferroportin reacts with iron at its intracellular aspect with apparent affinity constant < 10−7 M. Ferroportin expression also stimulated efflux of 65Zn and 57Co but not of 64Cu, 109Cd, or 54Mn. Hepcidin treatment of oocytes inhibited efflux of 55Fe, 65Zn, and 57Co. Whereas hepcidin administration in mice resulted in a marked hypoferremia within 4 h, we observed no effect on serum zinc levels in those same animals. We conclude that ferroportin is an iron-preferring cellular metal-efflux transporter with a narrow substrate profile that includes cobalt and zinc. Whereas hepcidin strongly regulated serum iron levels in the mouse, we found no evidence that ferroportin plays an important role in zinc homeostasis.
Absence of lateral gastrocnemius activity and differential motor unit behavior in soleus and medial gastrocnemius during standing balance
Authors: Héroux Martin E. , Dakin Christopher J. , Luu Billy L. , Inglis John Timothy , Blouin Jean-Sébastien
Published: December 2013

In a standing position, the vertical projection of the center of mass passes in front of the ankle, which requires active plantar-flexor torque from the triceps surae to maintain balance. We recorded motor unit (MU) activity in the medial (MG) and lateral (LG) gastrocnemius muscle and the soleus (SOL) in standing balance and voluntary isometric contractions to understand the effect of functional requirements and descending drive from different neural sources on motoneuron behavior. Single MU activity was recorded in seven subjects with wire electrodes in the triceps surae. Two 3-min standing balance trials and several ramp-and-hold contractions were performed. Lateral gastrocnemius MU activity was rarely observed in standing. The lowest thresholds for LG MUs in ramp contractions were 20–35 times higher than SOL and MG MUs ( P < 0.001). Compared with MUs from the SOL, MG MUs were intermittently active ( P < 0.001), had higher recruitment thresholds ( P = 0.022), and greater firing rate variability ( P < 0.001); this difference in firing rate variability was present in standing balance and isometric contractions. In SOL and MG MUs, both recruitment of new MUs ( R2 = 0.59–0.79, P < 0.01) and MU firing rates ( R2 = 0.05–0.40, P < 0.05) were associated with anterior-posterior and medio-lateral torque in standing. Our results suggest that the two heads of the gastrocnemius may operate in different ankle ranges with the larger MG being of primary importance when standing, likely due to its fascicle orientation. These differences in MU discharge behavior were independent of the type of descending neural drive, which points to a muscle-specific optimization of triceps surae motoneurons.