bluuebunny/crossref_metadata_2025 huggingface dataset:
Measuring Chromatin Interaction Dynamics on the Second Time Scale at Single-Copy Genes
Authors: Poorey Kunal , Viswanathan Ramya , Carver Melissa N. , Karpova Tatiana S. , Cirimotich Shana M. , McNally James G. , Bekiranov Stefan , Auble David T.
Published: October 2013

Capturing Binding Location and Speed

Transcription factor–binding sites in chromatin can be mapped by the chromatin immunoprecipitation (ChIP) assay, which analyzes formaldehyde-fixed chromatin fragments obtained from cells. However, the standard ChIP assay does not provide information about how stable the inter-actions are. Other approaches, including live-cell imaging, can reveal aspects of the dynamic behavior of transcription factors but are limited either in location precision or time resolution.

Poorey
et al.

(p.
369
, published online 3 October) developed a model to explain how the ChIP signal relates to formaldehyde cross-linking time, and they developed a method to measure chromatin site–specific binding dynamics with high temporal resolution.
Whole-Genome Sequences of 94 Environmental Isolates of Bacillus cereus
Sensu Lato
Authors: Van der Auwera Géraldine A. , Feldgarden Michael , Kolter Roberto , Mahillon Jacques
Published: October 2013

Bacillus cereus
sensu lato
is a species complex that includes the anthrax pathogen
Bacillus anthracis
and other bacterial species of medical, industrial, and ecological importance. Their phenotypes of interest are typically linked to large plasmids that are closely related to the anthrax plasmids pXO1 and pXO2. Here, we present the draft genome sequences of 94 isolates of
B. cereus
sensu lato
, which were chosen for their plasmid content and environmental origins.
Identification of a Novel Strain of Human Papillomavirus from Children with Diarrhea in China
Authors: Yu Jie-mei , Ao Yuan-yun , Zhao Guoyan , Li Li-li , Wang David , Duan Zhao-jun
Published: October 2013

A highly divergent human papillomavirus (HPV) strain, HPV-L55, was identified in fecal samples from children hospitalized with diarrhea in China. The L1 gene of HPV-L55 shares <75% identity with previously reported HPVs, indicating that this virus represents a novel type of HPV. Phylogenetic analysis classified this virus as a member of the gammapapillomaviruses.
Full-Genome Sequence of a Reassortant H1N1 Swine Influenza Virus Isolated from Pigs in Italy
Authors: Chiapponi Chiara , Baioni Laura , Luppi Andrea , Moreno Ana , Castellan Alberto , Foni Emanuela
Published: October 2013

In this study, the full-genome sequence of a novel reassortant H1N1 swine influenza virus (SIV) is reported. The isolate has a hemagglutinin (HA) gene of the pandemic H1N1 influenza virus, but it carries the seven genome segments of the avian-origin H1N1 SIV currently circulating in European pig farms.
Genome Sequence of Streptococcus parauberis Strain KCTC11980, Isolated from Diseased
Paralichthys olivaceus
Authors: Park Myoung Ae , Kwon Mun Gyeong , Hwang Jee Youn , Jung Sung Hee , Kim Dong-Wook , Park Jin-Young , Kim Ji-Sun , Na Yun-Jeong , Kim Min-Young , Kim Dae-Soo , Chae Sung-Hwa , Seo Jung Soo
Published: October 2013

Streptococcus parauberis
is a coccoid, nonmotile, alpha-hemolytic, Gram-positive bacterium of the
Streptococcaceae
family.
Streptococcus parauberis
strain KCTC11980 was isolated from the kidney of a diseased olive flounder collected from an aquaculture farm on Jeju Island in 2010. The 2.12-Mb genome sequence consists of 44 large contigs in 16 scaffolds and contains 2,214 predicted protein-coding genes, with a G+C content of 35.4%.
Draft Genome Sequence of Vibrio coralliilyticus Strain OCN008, Isolated from Kāne‘ohe Bay, Hawai‘i
Authors: Ushijima Blake , Videau Patrick , Aeby Greta S. , Callahan Sean M.
Published: October 2013

Vibrio coralliilyticus
is a Gram-negative bacterium found in seawater and is associated with diseased marine organisms. Strains of
V. coralliilyticus
have been shown to infect coral from multiple genera. We report the draft genome sequence of
V. coralliilyticus
strain OCN008, the third
V. coralliilyticus
genome to be sequenced.
Whole-Genome Sequence of the Clinical Strain Corynebacterium argentoratense DSM 44202, Isolated from a Human Throat Specimen
Authors: Bomholt Christina , Glaub Alina , Gravermann Kerstin , Albersmeier Andreas , Brinkrolf Karina , Rückert Christian , Tauch Andreas
Published: October 2013

Corynebacterium argentoratense
is part of the human skin microbiota and is occasionally detected in the upper respiratory tract of patients suffering from tonsillitis. The complete DNA sequence of the type strain DSM 44202 comprises 2,031,902 bp, yielding the smallest genome sequenced thus far for a corynebacterium associated with humans.
Draft Genome Sequence of a Neisseria meningitidis Serogroup C Isolate of Sequence Type 11 Linked to an Outbreak among Men Who Have Sex with Men
Authors: Veyrier Frédéric J. , Hong Eva , Deghmane Ala-Eddine , Taha Muhamed-Kheir
Published: October 2013

Meningococcal disease occurs as sporadic cases in developed countries, with the occasional emergence of new clones of
Neisseria meningitidis
. Here, we report the genome sequence of
N. meningitidis
strain LNP27256, an isolate of sequence type 11 linked to a recent outbreak among men who have sex with men in Europe.
Genome Sequence of the Quorum-Sensing-Signal-Producing Nonpathogen Agrobacterium tumefaciens Strain P4
Authors: Mondy Samuel , Lalouche Ouaghlis , Dessaux Yves , Faure Denis
Published: October 2013

Agrobacterium tumefaciens
P4 is a quorum-sensing-signal-producing bacterium that has been isolated from the tobacco rhizosphere. This strain belongs to genomospecies 1 of the
A. tumefaciens
complex; it is avirulent on various putative host plants, devoid of the Ti plasmid, and contains a
luxI
homolog on the At plasmid.
Draft Genome Sequence of Pasteurella multocida A:3 Strain 671/90
Authors: Lainson Frederick A. , Dagleish Mark P. , Fontaine Michael C. , Bayne Colin , Hodgson J. Christopher
Published: October 2013

Pasteurella multocida
serogroup A is commonly isolated from nasal swabs of clinically healthy calves and also from diseased lung tissue in bovine pneumonia. Here, we report the draft genome sequence of the virulent strain
P. multocida
671/90, which has been characterized previously in experimental infections of calves and mice.
Acute right ventricular myocarditis presenting with chest pain and syncope
Authors: Mancio Jennifer , Bettencourt Nuno , Oliveira Marco , Pires-Morais Gustavo , Ribeiro Vasco Gama
Published: October 2013

Myocarditis is assumed to involve both ventricles equally. Right ventricular predominant involvement is rarely described. A case of acute viral right ventricular myocarditis presenting with chest pain and syncope, grade 3 atrioventricular block, right ventricular dilatation and free wall hypokinesia is reported. Cardiac MRI showed late enhancement of the right ventricular free wall without involvement of the left ventricle. Anti-Coxsackie A9 virus neutralising IgM-type antibodies titre was elevated. This case emphasises that manifestations of myocarditis can be limited to the right ventricle and should be considered in the differential diagnosis of right ventricular enlargement.
Adolescent idiopathic scoliosis in Down's syndrome
Authors: Cozon Caroline Louise
Published: October 2013

Adolescent idiopathic scoliosis in Down's syndrome individuals has previously been reported in the context of institutionalised individuals and is of an iatrogenic nature, resulting from previous thoracotomy for congenital heart defects. We report the case of a male, non-institutionalised Down's syndrome individual, with no history of previous thoracic surgery and we follow the natural history of the condition, with particular reference to height velocity and curve progression velocity throughout puberty and successful treatment with a Boston thoracolumbosacral orthosis.
Acute post-traumatic endophthalmitis secondary toPropionibacterium acnes
Authors: Shailaja S , Kamath Yogish , Hazarika Manali , Vishwanath Shashidhar
Published: October 2013

Propionibacterium acneshas rarely been reported as the causative organism in acute endophthalmitis following penetrating ocular trauma. We report a 53-year-old man, who presented with best corrected vision of counting fingers at 2 m, <N36, in the right eye and clinical features suggestive of endophthalmitis following penetrating trauma with a tree branch 2 days earlier. Conjunctival swab, aqueous and vitreous tap were sent for aerobic, anaerobic and fungal culture. The patient was treated with intravitreal ceftazidime, vancomycin along with topical antibiotics and steroids. An aqueous anaerobic culture was positive forP acnes. At the fifth month follow-up, the best corrected vision had improved to 20/20, N6. Thus, a good visual outcome was achieved, following appropriate treatment of a rather unusual causative organism.
Bibliographic review of research publications on access to and use of medicines in low-income and middle-income countries in the Eastern Mediterranean Region: identifying the research gaps
Authors: Rashidian Arash , Jahanmehr Nader , Jabbour Samer , Zaidi Shehla , Soleymani Fatemeh , Bigdeli Maryam
Published: October 2013

Objectives

We assessed the situation of academic publications on access to and use of medicines (ATM) in low-income and middle-income countries (LMICs) of the Eastern Mediterranean Region (EMR). We aimed to inform priority setting for research on ATM in the region.

Design

Bibliographic review of published studies.

Setting

LMICs in EMR.

Inclusion criteria

Publications on ATM issues originating from or focusing on EMR LMICs covering the period 2000–2011. Publications involving multinational studies were included if at least one eligible country had been included in the study.

Information sources and data extraction

We conducted comprehensive searches of the PubMed, Social Science Citation Index and Science Citation Index. We used the WHO ATM framework for data extraction and synthesis. We analysed the data according to the ATM issues, health system levels, year of publication and the countries of origin or focus of the studies.

Results

151 articles met the inclusion criteria. Most articles (77%) originated from LMICs in EMR, suggesting that the majority of evidence on ATM in the region is home-grown. Over 60% of articles were from Iran, Pakistan, Jordan and Lebanon (in order of volume), while we found no studies assessing ATM in Somalia, Djibouti and South Sudan, all low-income countries. Most studies focused on the rational use of medicines, while affordability and financing received limited attention. There was a steady growth over time in the number of ATM publications in the region (r=0.87).

Conclusions

There is a growing trend, over the years, of more studies from the region appearing in international journals. There is a need for further research on the financing and affordability aspects of ATM in the region. Cross-border issues and the roles of non-health sectors in access to medicines in the region have not been explored widely.
A pragmatic randomised controlled trial of ‘PhysioDirect’ telephone assessment and advice services for patients with musculoskeletal problems: economic evaluation
Authors: Hollinghurst Sandra , Coast Joanna , Busby John , Bishop Annette , Foster Nadine E , Franchini Angelo , Grove Sean , Hall Jeanette , Hopper Cherida , Kaur Surinder , Montgomery Alan A , Salisbury Chris
Published: October 2013

Objectives

To compare the cost-effectiveness of PhysioDirect with usual physiotherapy care for patients with musculoskeletal problems.

Design

(1) Cost-consequences comparing cost to the National Health Service (NHS), to patients, and the value of lost productivity with a range of outcomes. (2) Cost-utility analysis comparing cost to the NHS with Quality-Adjusted Life Years (QALYs).

Setting

Four physiotherapy services in England.

Participants

Adults (18+) referred by their general practitioner or self-referred for physiotherapy.

Interventions

PhysioDirect involved telephone assessment and advice followed by face-to-face care if needed. Usual care patients were placed on a waiting list for face-to-face care.

Primary and secondary outcomes

Primary clinical outcome: physical component summary from the SF-36v2 at 6 months. Also included in the cost-consequences: Measure Yourself Medical Outcomes Profile; a Global Improvement Score; response to treatment; patient satisfaction; waiting time. Outcome for the cost-utility analysis: QALYs.

Results

2249 patients took part (1506 PhysioDirect; 743 usual care). (1) Cost-consequences: there was no evidence of a difference between the two groups in the cost of physiotherapy, other NHS services, personal costs or value of time off work. Outcomes were also similar. (2) Cost-utility analysis based on complete cases (n=1272). Total NHS costs, including the cost of physiotherapy were higher in the PhysioDirect group by £19.30 (95% CI −£37.60 to £76.19) and there was a QALY gain of 0.007 (95% CI −0.003 to 0.016). The incremental cost-effectiveness ratio was £2889 and the net monetary benefit at λ=£20 000 was £117 (95% CI −£86 to £310).

Conclusions

PhysioDirect may be a cost-effective alternative to usual physiotherapy care, though only with careful management of staff time. Physiotherapists providing the service must be more fully occupied than was possible under trial conditions: consideration should be given to the scale of operation, opening times of the service and flexibility in the methods used to contact patients.
Six questions about training that every practice manager should ask
Authors: Grosdidier Sheila
Published: October 2013

The costs might be easier to quantify than the benefits, but staff training is essential and undoubtable reaps rewards, says Sheila Grosdidier, who gives advice on a structured approach.
Recognising avian notifiable diseases 2. Newcastle disease
Authors: Irvine Richard M.
Published: October 2013

Newcastle disease, in common with avian influenza, is a highly infectious transboundary avian notifiable disease that is subject to internationally recognised definitions, as described by the World Organisation for Animal Health (OIE) and legislation for the purposes of maintaining poultry health, trade and disease control. This article, the second in a three‐part series on avian notifiable diseases, discusses the biology of Newcastle disease virus, as well as the statutory definitions and epidemiology of disease. In addition, it describes key clinical and pathological features of Newcastle disease in different poultry hosts. Avian influenza was similarly described in Part 1 of this series, which was published in the September issue of In Practice (vol 35, pp 426‐437). Part 3 will be published in the November/December issue of In Practice and will discuss the investigation of poultry health problems with reference to avian notifiable diseases and differential diagnoses.
Alpha2‐adrenoceptor agonists in small animal practice 1. Why they do what they do
Authors: Flaherty Derek
Published: October 2013

Alpha2‐adrenoceptor agonists are widely used for premedication, sedation and, more recently, provision of analgesia in small animal practice. However, although these drugs may offer significant benefits over alternative agents, they also have a number of side effects that must be appreciated. This, the first in a series of two articles, explains how the pharmacology of these drugs leads to both the desirable and adverse effects observed with these agents. The second article, which will be published in a forthcoming issue of In Practice, will describe the most appropriate way to use alpha2‐adrenoceptor agonists to optimise their clinical effects.
FRAGMENTATION FUNCTIONS OF GLUON SPLITTING INTO CHARMED HADRONS IN THE RECOMBINATION MODEL
Authors: PENG RU , LI HANLIN
Published: October 2013

In the framework of the recombination model we determine the shower parton distributions (SPDs) with the fragmentation functions (FFs) for mesons and then predict the fragmentation functions for baryons. We get the fragmentation functions of gluon splitting into charmed hadrons. We show the relationship of fragmentation functions for mesons and baryons and find that they are not independent if the hadronization of the shower partons is taken into account.
ON SUPERMULTIPLET TWISTING AND SPIN-STATISTICS
Authors: HÜBSCH T.
Published: October 2013

Twisting of off-shell supermultiplets in models with (1+1)-dimensional spacetime has been discovered in 1984, and was shown to be a generic feature of off-shell representations in worldline supersymmetry two decades later. It is shown herein that in all supersymmetric models with spacetime of four or more dimensions, this off-shell supermultiplet twisting, if nontrivial, necessarily maps regular (non-ghost) supermultiplets to ghost supermultiplets. This feature is shown to be ubiquitous in all fully off-shell supersymmetric models with (BV/BRST-treated) constraints.
THE LARGE HADRON COLLIDER 2008–2013
Authors: MYERS STEPHEN
Published: October 2013

The Large Hadron Collider (LHC) was first suggested (in a documented way) in 1983 (S. Myers and W. Schnell, Preliminary performance estimates for a LEP proton collider, LEP Note 440, April 1983) as a possible future hadron collider to be installed in the 27 km "LEP" tunnel. More than 30 years later the collider has been operated successfully with beam for three years with spectacular performance and has discovered the long-sought-after Higgs boson. The LHC is the world's largest and most energetic particle collider. It took many years to plan and build this large complex machine which promises exciting, new physics results for many years to come.

I describe the LHC design objectives, review some of the more relevant beam effects, define the major accelerator components and parameters, and finally give an overview of the commissioning and operational performance since the initial turn on of the collider. The latter will include the major accident which took place in September 2008 and the subsequent repair and redesign of the faulty components.

The first attempt to circulate beam in the LHC in September 2008 were initially very successful. However, after only nine days of preliminary beam commissioning, on 19 September 2008, disaster struck: the last octant was being ramped up in preparation for high energy operation when a magnet interconnect failed and the enormous energy stored in the superconducting magnets was released in an uncontrolled way and damaged around 600 m of the LHC installed equipment. The next 14 months were crucial for the machine. A crash programme for the repair of the damaged sector was initiated as well as in depth studies to understand the cause of the failure and make design changes which would ensure that such an accident could never reoccur in the future.

In this paper, the story of the four years of the intensive activity since the accident is described starting with the repair of the damaged area and followed by the three very successful years of beam operation.
OCTONION AND CONSERVATION LAWS FOR DYONS
Authors: CHANYAL B. C. , BISHT P. S. , NEGI O. P. S.
Published: October 2013

Starting with the usual definitions of octonions and split octonions in terms of Zorn vector matrix realization, we have made an attempt to write the continuity equation and other wave equations of dyons in split octonions. Accordingly, we have investigated the work energy theorem or "Poynting Theorem," Maxwell stress tensor and Lorentz invariant for generalized fields of dyons in split octonion electrodynamics. Our theory of dyons in split octonion formulations is discussed in term of simple and compact notations. This theory reproduces the dynamic of electric (magnetic) in the absence of magnetic (electric) charges.
Rates in the strong invariance principle for ergodic automorphisms of the torus
Authors: Dedecker Jérôme , Merlevède Florence , Pène Françoise
Published: October 2013

Let T be an ergodic automorphism of the d-dimensional torus 𝕋d. In the spirit of Le Borgne, we give conditions on the Fourier coefficients of a function f from 𝕋dto ℝ under which the partial sums f ◦ T + f ◦ T2+ ⋯ + f ◦ Tnsatisfy a strong invariance principle. Next, reinforcing the condition on the Fourier coefficients in a natural way, we obtain explicit rates of convergence in the strong invariance principle, up to n1/4log n.
Portfolio optimization under the stochastic elasticity of variance
Authors: Yang Sung-Jin , Lee Min-Ku , Kim Jeong-Hoon
Published: October 2013

Based on the observation that the elasticity of variance of risky assets is randomly varying around a constant, we take an underlying asset model in which the averaged constant elasticity of variance is perturbed by a small fast fluctuating process and study the Merton type portfolio optimization problem using dynamic programming as well as asymptotic expansions. The Hamilton–Jacobi–Bellman equation for each of the power and exponential utility functions leads to an optimal trading strategy as a perturbation around the well known one. We reveal the impact of both the constant elasticity of variance upon the Merton investment optimal control under the Black–Scholes model and the stochastic elasticity of variance upon the investment optimal control under the constant elasticity of variance model. The concavity of the investment policy with respect to the excess return is characteristic of a market economy with the constant or stochastic elasticity of variance.
Study of a PEM Fuel Cell Fed with Unclean Hydrogen and Oxygen From Air
Authors: Vazquez Gerardo , Cruz Sergio , Davila Jose Angel , Radilla Juan , Cardoso Judith
Published: October 2013

The performance of a PEMFC fed with H2 +1% CO in the anodic side and oxygen from air in the cathodic compartment has been investigated. The oxidation of H2 in the presence of CO has been performed using a nanostructured core-shell material (Au@Pt/C). By using anodic stripping voltammetry, the onset potential of CO-desorption on Au@Pt/C has been determined and compared with that obtained on Pt/C. CO oxidation starts 30 mV less positive on Au@Pt/C than on Pt/C; this indicates that the bond strength between CO-Pt is weaker on Au@Pt/C than in Pt/C. The PEMFC performance using hydrogen polluted with 1% of CO (10psi) in the anodic side and oxygen from air (10psi) in the cathodic compartment presents a maximum power density of 49 mW/cm2 when Au@Pt/C is used as catalyst; this value is larger than the 46 mW/cm2 achieved with Pt/C under same operating conditions.
Quantumchemical Calculations of the Structural Stability of β–Cyclodextrin/Dopamine and β–Cyclodextrin/Ascorbic Acid Systems
Authors: Cuan Angeles , Velasco Axel , Palomar-Pardavé Manuel , Ramírez-Silva Maria Teresa , Romero-Romo Mario A. , Cortés-Romero Carlos Martin , Corona-Avendaño Silvia
Published: October 2013

A theoretical study of the complex formation and stability between β-cyclodextrin/dopamine (βCD/DA) and β-cyclodextrin/ascorbic acid (βCD/AA) was performed by means of quantum chemical calculations using Density Functional Theory (DFT). The B3LYP functional and the 6-31G (d) basis set were used for calculations under the so called all electrons scheme. The mechanistic considerations for interactions in both chemical systems were evaluated assuming entrance of either DA or AA into the ring of the guest molecule (βCD). According to our results, the most preferred orientations of βCD/DA system was obtained either when the DA catechol group or the amino group entered to the βCD ring, while for the βCD/AA system the most likely interaction occurred when AA functional groups, alcohol or lactone, entered to the βCD ring. Geometry, molecular energy and some electronic properties were obtained from calculations that led to determine the conformer’s structural stability. The effect of acidic media was studied by setting pH values lower than 4.1 in which amino group of DA is protonated and carboxylic group of AA keeps its proton bonded. Vibrational frequencies for each reactant molecule as well as for complex system were calculated to ensure that obtained values corresponded to structures with minimal energy. The calculated IR spectra of conformers were analyzed to characterize the interaction between the host-guest complexes by means of its coupled vibrational frequencies. Theoretical UV spectra were calculated to verify the maximum UV absorption corresponding to fully protonated DA (H3DA+) and AA (H2AA) species when located within the βCD ring and is compared with reported experimental data. The zero point energy values and enthalpy and Gibb’s free energy were calculated and discussed.
Quantification of As(III) by Swasv on Glassy Carbon Electrode Codeposit Copper with Presence of β-Ciclodextrin
Authors: López-Vargas Erika , Galán-Vidal Carlos Andrés , Rodríguez-Ávila José Antonio , Álvarez-Romero Giaan Arturo , Mendoza-Huizar Luis Humberto
Published: October 2013

Nowadays, the ability to detect arsenic in drinking water is a very important subject because of arsenic’s toxicity. In this sense, it is necessary to have economical and portable detection methodologies in order to control water quality, mainly in remote communities without access to expensive equipment such as atomic absorption. Currently, electrochemical methods are a low cost alternative which can be used outside the laboratory; however, these techniques use toxic or precious metals as working electrodes. The main interference in the quantification of arsenic is the Cu(II) because an intermetallic compound is formed with arsenic. In this paper we explore the co-deposition of Cu on a glassy carbon electrode to quantify As(III) in H2SO4 as a supporting electrolyte. The methodology reported a detection limit of 5.2 μg L-1, helpful to following the official guidelines. Zn2+, Fe2+, Pb2+, Hg2+ and Cl- are not significant interferences in quantification.
Electrical Properties of (CeO2)0.9(MO)0.1 (M=Ca or Mg) Solid Electrolyte System
Authors: Montalvo-Lozano R A , Padmasree K P , Fuentes A F , Montemayor S M
Published: October 2013

Electrical conductivity studies of alkaline earth oxides doped ceria Ce0.9M0.1O2-
δ, (where M=Ca and Mg) is reported in this work. The samples were prepared at room temperature by mechanical milling. X-ray diffraction patterns confirm the cubic fluorite structure. Scanning electron micrographs of MgO doped sample shows the presence of the segregation of Mg2+ which results a negative effect on the electric properties of the MgO doped sample. Frequency dependence of ac conductivity (σac) of these oxide ion conductors showed a remarkably different behavior from that of the cation ones. As temperature increases above 350°C, ac conductivity σac in the low frequency range was strongly influenced by space charge polarization at grain boundary and the high frequency plateau agreed with the bulk conductivity of the system. Bulk and grain boundary conductivity studies show that CaO doped ceria exhibit better electrical properties compared to MgO doped sample.
Improvement of Hexavalent Chromium Reduction Applying Boron Doped Diamond as Cathode Material
Authors: Velazquez-Peña Sarai , Linares-Hernández Ivonne , Lugo-Lugo Violeta , Martínez-Miranda Verónica , Barrera-Díaz Carlos , Almazán Sánchez Perla Tatiana
Published: October 2013

The goal of this work is to optimize the electrochemical reduction of hexavalent chromium using synthetic solutions employing doped diamond electrodes (BDD) as a cathode material. The rate of Cr(VI) reduction was measured as a function of treatment conditions, the sludge generated in the process was characterized by SEM, EDS and XPS to provide insight into the mechanism of the reduction on the cathode material proposed. Also cyclic voltammetry was used to confirm the cathodic Cr(VI) reduction is taking place.
Intravenous fish oil lipid emulsion promotes a shift toward anti-inflammatory proresolving lipid mediators
Authors: Kalish Brian T. , Le Hau D. , Fitzgerald Jonathan M. , Wang Samantha , Seamon Kyle , Gura Kathleen M. , Gronert Karsten , Puder Mark
Published: October 2013

Parenteral nutrition (PN)-associated liver disease (PNALD) is a life-threatening complication of the administration of PN. The development of PNALD may be partly due to the composition of the lipid emulsion administered with PN: soybean oil-based lipid emulsions (SOLE) are associated with liver disease, while fish oil-based lipid emulsions (FOLE) are associated with prevention and improvement of liver disease. The objective of this study was to determine how the choice of lipid emulsion modified the production of bioactive lipid mediators (LMs). We utilized a mouse model of steatosis to study the differential effect of FOLE and SOLE. We subsequently validated these results in serum samples from a small cohort of human infants transitioning from SOLE to FOLE. In mice, FOLE was associated with production of anti-inflammatory, proresolving LMs; SOLE was associated with increased production of inflammatory LMs. In human infants, the transition from SOLE to FOLE was associated with a shift toward a proresolving lipidome. Together, these results demonstrate that the composition of the lipid emulsion directly modifies inflammatory homeostasis.
Reduced hepatic mitochondrial respiration following acute high-fat diet is prevented by PGC-1α overexpression
Authors: Morris E. Matthew , Jackman Matthew R. , Meers Grace M. E. , Johnson Ginger C. , Lopez Jordan L. , MacLean Paul S. , Thyfault John P.
Published: October 2013

Changes in substrate utilization and reduced mitochondrial respiratory capacity following exposure to energy-dense, high-fat diets (HFD) are putatively key components in the development of obesity-related metabolic disease. We examined the effect of a 3-day HFD on isolated liver mitochondrial respiration and whole body energy utilization in obesity-prone (OP) rats. We also examined if hepatic overexpression of peroxisomal proliferator-activated receptor-γ coactivator-1α (PGC-1α), a master regulator of mitochondrial respiratory capacity and biogenesis, would modify liver and whole body responses to the HFD. Acute, 3-day HFD (45% kcal) in OP rats resulted in increased daily energy intake, energy balance, weight gain, and adiposity, without an increase in liver triglyceride (triacylglycerol) accumulation. HFD-fed OP rats also displayed decreased whole body substrate switching from the dark to the light cycle, which was paired with reductions in hepatic mitochondrial respiration of multiple substrates in multiple respiratory states. Hepatic PGC-1α overexpression was observed to protect whole body substrate switching, as well as maintain mitochondrial respiration, following the acute HFD. Additionally, liver PGC-1α overexpression did not alter whole body dietary fatty acid oxidation but resulted in greater storage of dietary free fatty acids in liver lipid, primarily as triacylglycerol. Together, these data demonstrate that a short-term HFD can result in a decrease in metabolic flexibility and hepatic mitochondrial respiratory capacity in OP rats that is completely prevented by hepatic overexpression of PGC-1α.
Ezrin regulates the expression of Mrp2/Abcc2 and Mdr1/Abcb1 along the rat small intestinal tract
Authors: Nakano Takafumi , Sekine Shuichi , Ito Kousei , Horie Toshiharu
Published: October 2013

Multidrug resistance-associated protein 2 (MRP2)/ATP-binding cassette protein C2 (ABCC2) and multidrug resistance protein 1 (MDR1)/ABCB1 are well-known efflux transporters located on the brush border membrane of the small intestinal epithelia, where they limit the absorption of a broad range of substrates. The expression patterns of MRP2/ABCC2 and MDR1/ABCB1 along the small intestinal tract are tightly regulated. Several reports have demonstrated the participation of ERM (ezrin/radixin/moesin) proteins in the posttranslational modulation of MRP2/ABCC2 and MDR1/ABCB1, especially with regard to their membrane localization. The present study focused on the in vivo expression profiles of MRP2/ABCC2, MDR1/ABCB1, ezrin, and phosphorylated ezrin to further elucidate the relationship between the efflux transporters and the ERM proteins. The current results showed good correlation between the phosphorylation status of ezrin and Mrp2/Abcc2 expression along the gastrointestinal tract of rats and between the expression profiles of both ezrin and Mdr1/Abcb1 in the small intestine. We also demonstrated the involvement of conventional protein kinase C isoforms in the regulation of ezrin phosphorylation. Furthermore, experiments conducted with wild-type (WT) ezrin and a T567A (Ala substituted Thr) dephosphorylated mutant showed a decrease in membrane surface-localized and total expressed MRP2/ABCC2 in T567A-expressing vs. WT ezrin-expressing Caco-2 cells. In contrast, T567A- and WT-expressing cells both showed an increase in membrane surface-localized and total expressed MDR1/ABCB1. These findings suggest that the phosphorylation status and the expression profile of ezrin differentially direct MRP2/ABCC2 and MDR1/ABCB1 expression, respectively, along the small intestinal tract.
Activation of upper airway muscles during breathing and swallowing
Authors: Fregosi Ralph F. , Ludlow Christy L.
Published: October 2013

The upper airway is a complex muscular tube that is used by the respiratory and digestive systems. The upper airway is invested with several small and anatomically peculiar muscles. The muscle fiber orientations and their nervous innervation are both extremely complex, and how the activity of the muscles is initiated and adjusted during complex behaviors is poorly understood. The bulk of the evidence suggests that the entire assembly of tongue and laryngeal muscles operate together but differently during breathing and swallowing, like a ballet rather than a solo performance. Here we review the functional anatomy of the tongue and laryngeal muscles, and their neural innervation. We also consider how muscular activity is altered as respiratory drive changes, and briefly address upper airway muscle control during swallowing.
A selective 5-HT1areceptor agonist improves respiration in a mouse model of Rett syndrome
Authors: Levitt Erica S. , Hunnicutt Barbara J. , Knopp Sharon J. , Williams John T. , Bissonnette John M.
Published: October 2013

Rett syndrome is a neurological disorder caused by loss of function mutations in the gene that encodes the DNA binding protein methyl-CpG-binding protein 2 (Mecp2). A prominent feature of the syndrome is disturbances in respiration characterized by frequent apnea and an irregular interbreath cycle. 8-Hydroxy-2-dipropylaminotetralin has been shown to positively modulate these disturbances (Abdala AP, Dutschmann M, Bissonnette JM, Paton JF, Proc Natl Acad Sci U S A 107: 18208–18213, 2010), but the mode of action is not understood. Here we show that the selective 5-HT1abiased agonist 3-chloro-4-fluorophenyl-(4-fluoro-4-{[(5-methylpyrimidin-2-ylmethyl)-amino]-methyl}-piperidin-1-yl)-methanone (F15599) decreases apnea and corrects irregularity in both heterozygous Mecp2-deficient female and in Mecp2 null male mice. In whole cell voltage-clamp recordings from dorsal raphe neurons, F15599 potently induced an outward current, which was blocked by barium, reversed at the potassium equilibrium potential, and was antagonized by the 5-HT1aantagonist WAY100135. This is consistent with somatodendritic 5-HT1areceptor-mediated activation of G protein-coupled inwardly rectifying potassium channels (GIRK). In contrast, F15599 did not activate 5-HT1b/dreceptors that mediate inhibition of glutamate release from terminals in the nucleus accumbens by a presynaptic mechanism. Thus F15599 activated somatodendritic 5-HT1aautoreceptors, but not axonal 5-HT1b/dreceptors. In unanesthetized Mecp2-deficient heterozygous female mice, F15599 reduced apnea in a dose-dependent manner with maximal effect of 74.5 ± 6.9% at 0.1 mg/kg and improved breath irrregularity. Similarly, in Mecp2 null male mice, apnea was reduced by 62 ± 6.6% at 0.25 mg/kg, and breathing became regular. The results indicate respiration is improved with a 5-HT1aagonist that activates GIRK channels without affecting neurotransmitter release.
Prognostic and Predictive Blood-Based Biomarkers in Patients with Advanced Pancreatic Cancer: Results from CALGB80303 (Alliance)
Authors: Nixon Andrew B. , Pang Herbert , Starr Mark D. , Friedman Paula N. , Bertagnolli Monica M. , Kindler Hedy L. , Goldberg Richard M. , Venook Alan P. , Hurwitz Herbert I. ,   for the Alliance for Clinical Trials In Oncology
Published: October 2013

Purpose: CALGB80303 was a phase III trial of 602 patients with locally advanced or metastatic pancreatic cancer comparing gemcitabine/bevacizumab versus gemcitabine/placebo. The study found no benefit in any outcome from the addition of bevacizumab to gemcitabine. Blood samples were collected and multiple angiogenic factors were evaluated and then correlated with clinical outcome in general (prognostic markers) and with benefit specifically from bevacizumab treatment (predictive markers).

Experimental Design: Plasma samples were analyzed via a novel multiplex ELISA platform for 31 factors related to tumor growth, angiogenesis, and inflammation. Baseline values for these factors were correlated with overall survival (OS) using univariate Cox proportional hazard regression models and multivariable Cox regression models with leave-one-out cross validation. Predictive markers were identified using a treatment by marker interaction term in the Cox model.

Results: Baseline plasma was available from 328 patients. Univariate prognostic markers for OS were identified including: Ang2, CRP, ICAM-1, IGFBP-1, TSP-2 (all P < 0.001). These prognostic factors were found to be highly significant, even after adjustment for known clinical factors. Additional modeling approaches yielded prognostic signatures from multivariable Cox regression. The gemcitabine/bevacizumab signature consisted of IGFBP-1, interleukin-6, PDGF-AA, PDGF-BB, TSP-2; whereas the gemcitabine/placebo signature consisted of CRP, IGFBP-1, PAI-1, PDGF-AA, P-selectin (both P < 0.0001). Finally, three potential predictive markers of bevacizumab efficacy were identified: VEGF-D (P < 0.01), SDF1 (P < 0.05), and Ang2 (P < 0.05).

Conclusion: This study identified strong prognostic markers for pancreatic cancer patients. Predictive marker analysis indicated that plasma levels of VEGF-D, Ang2, and SDF1 significantly predicted for benefit or lack of benefit from bevacizumab in this population. Clin Cancer Res; 19(24); 6957–66. ©2013 AACR.
BH3 Profiling Discriminates Response to Cytarabine-Based Treatment of Acute Myelogenous Leukemia
Authors: Pierceall William E. , Kornblau Steven M. , Carlson Nicole E. , Huang Xuelin , Blake Noel , Lena Ryan , Elashoff Michael , Konopleva Marina , Cardone Michael H. , Andreeff Michael
Published: October 2013

As acute myelogenous leukemia (AML) patient response to cytarabine-based standard-of-care treatment is variable, stratification into subgroups by biomarker-predicted response may lead to improved clinical outcomes. Here, we assess cell mitochondrial depolarization to proapoptotic signaling BH3-only peptides as a surrogate for the function of Bcl-2 family proteins to address clinical response to cytarabine-based therapy in patients with AML (N = 62). Peripheral blood mononuclear cell (PBMC) or bone marrow aspirate specimens were obtained from newly diagnosed patients with AML, viably preserved, and assayed by flow cytometry following BH3 profile assay with individual BH3 peptides. Mann–Whitney analysis indicates biomarker correlation with response to induction therapy: Notably, BIM priming was highly significant (P = 2 × 10−6) with a compelling sensitivity/specificity profile [area under curve (AUC) = 0.83; 95% confidence interval (CI), 0.73–0.94; P = 2 × 10−10]. Multivariate analysis indicates improved profiles for BIM readout + patient age (AUC = 0.89; 95% CI, 0.81–0.97) and BIM + patient age + cytogenetic status (AUC = 0.91; 95% CI, 0.83–0.98). When patients were stratified by cytogenetic status, BIM readout was significant for both intermediate (P = 0.0017; AUC = 0.88; 95% CI, 0.71–1.04) and unfavorable (P = 0.023; AUC = 0.79; 95% CI, 0.58–1.00) risk groups, demonstrating predictive power independent of cytogenetics. Additional analyses of secondary clinical endpoints displayed correlation between overall survival (P = 0.037) and event-free survival (P = 0.044) when patients were stratified into tertiles by BIM peptide response. Taken together, these results highlight the potential utility of BH3 profiling in personalized diagnostics of AML by offering actionable information for patient management decisions. Mol Cancer Ther; 12(12); 2940–9. ©2013 AACR.
A Proangiogenic Signature Is Revealed in FGF-Mediated Bevacizumab-Resistant Head and Neck Squamous Cell Carcinoma
Authors: Gyanchandani Rekha , Ortega Alves Marcus V. , Myers Jeffrey N. , Kim Seungwon
Published: October 2013

Resistance to antiangiogenic therapies is a critical problem that has limited the utility of antiangiogenic agents in clinical settings. However, the molecular mechanisms underlying this resistance have yet to be fully elucidated. In this study, we established a novel xenograft model of acquired resistance to bevacizumab. To identify molecular changes initiated by the tumor cells, we performed human-specific microarray analysis on bevacizumab-sensitive and -resistant tumors. Efficiency analysis identified 150 genes upregulated and 31 genes downregulated in the resistant tumors. Among angiogenesis-related genes, we found upregulation of fibroblast growth factor-2 (FGF2) and fibroblast growth factor receptor-3 (FGFR3) in the resistant tumors. Inhibition of the FGFR in the resistant tumors led to the restoration of sensitivity to bevacizumab. Furthermore, increased FGF2 production in the resistant cells was found to be mediated by overexpression of upstream genes phospholipase C (PLCg2), frizzled receptor-4 (FZD4), chemokine [C-X3-C motif] (CX3CL1), and chemokine [C-C motif] ligand 5 (CCL5) via extracellular signal-regulated kinase (ERK). In summary, our work has identified an upregulation of a proangiogenic signature in bevacizumab-refractory HNSCC tumors that converges on ERK signaling to upregulate FGF2, which then mediates evasion of anti-VEGF therapy. These findings provide a new strategy on how to enhance the therapeutic efficacy of antiangiogenic therapy.

Implications: Novel xenograft model leads to the discovery of FGF as a promising therapeutic target in overcoming the resistance of antiangiogenic therapy in HNSCC. Mol Cancer Res; 11(12); 1585–96. ©2013 AACR.
Molecular Background of Urate Transporter Genes in Patients with Exercise-Induced Acute Kidney Injury
Authors: Kaito Hiroshi , Ishimori Shingo , Nozu Kandai , Shima Yuko , Nakanishi Koichi , Yoshikawa Norishige , Iijima Kazumoto
Published: October 2013

Background/Aims: Exercise-induced acute renal failure [exercise-induced acute kidney injury (EI-AKI)] is defined as AKI due to heavy anaerobic exercise. Although hypouricemia is known to be a risk factor for the onset of EI-AKI, a direct causal link between EI-AKI and serum uric acid has not been established. This study aimed to analyze urate transporter genes in patients with EI-AKI and its molecular mechanism. Methods: Genomic DNA and total RNA were isolated from peripheral blood leukocytes of patients with a history of EI-AKI. Mutations were analyzed by PCR and a direct sequencing method. We first analyzed the SLC22A12 gene, and then the SLC2A9 gene if no mutations were found in SLC22A12. Results: Seventeen patients were enrolled in this study and 16 had mutations: 15 in SLC22A12 and 1 in SLC2A9. Fourteen (82.4%) patients showed hypouricemia, and all of the patients with hypouricemia had either homozygous or compound heterozygous mutations in SLC22A12 or SLC2A9, which confirmed that all of them had renal hypouricemia. Two patients had heterozygous mutations of SLC22A12, and they were not accompanied by hypouricemia. One patient was found to have no mutations in SLC22A12 or SLC2A9. Conclusion: We were able to determine the genetic background of urate transporter genes in patients with EI-AKI. Decreased function of urate transporters, rather than decreased serum uric acid levels, may be of great importance for the onset of EI-AKI.
Disruption of the ATE1 and SLC12A1 Genes by Balanced Translocation in a Boy with Non-Syndromic Hearing Loss
Authors: Vona B. , Neuner C. , El Hajj N. , Schneider E. , Farcas R. , Beyer V. , Zechner U. , Keilmann A. , Poot M. , Bartsch O. , Nanda I. , Haaf T.
Published: October 2013

We report on a boy with non-syndromic hearing loss and an apparently balanced translocation t(10;15)(q26.13;q21.1). The same translocation was found in the normally hearing brother, father and paternal grandfather; however, this does not exclude its involvement in disease pathogenesis, for example, by unmasking a second mutation. Breakpoint analysis via FISH with BAC clones and long-range PCR products revealed a disruption of the arginyltransferase 1 (ATE1) gene on translocation chromosome 10 and the solute carrier family 12, member 1 gene (SLC12A1) on translocation chromosome 15. SNP array analysis revealed neither loss nor gain of chromosomal regions in the affected child, and a targeted gene enrichment panel consisting of 130 known deafness genes was negative for pathogenic mutations. The expression patterns in zebrafish and humans did not provide evidence for ear-specific functions of the ATE1 and SLC12A1 genes. Sanger sequencing of the 2 genes in the boy and 180 GJB2 mutation-negative hearing-impaired individuals did not detect homozygous or compound heterozygous pathogenic mutations. Our study demonstrates the many difficulties in unraveling the molecular causes of a heterogeneous phenotype. We cannot directly implicate disruption of ATE1 and/or SLC12A1 to the abnormal hearing phenotype; however, mutations in these genes may have a role in polygenic or multifactorial forms of hearing impairment. On the other hand, it is conceivable that our patient carries a disease-causing mutation in a so far unidentified deafness gene. Evidently, disruption of ATE1 and/or SLC12A1 gene function alone does not have adverse effects.
Tenosynovial Giant Cell Tumor Arising on the Scapular Region
Authors: Fukuda Asako , Ueno Takashi , Takayama Ryoko , Ansai Shin-ichi , Futagami Ayako , Kawana Seiji
Published: October 2013

Tenosynovial giant cell tumor (TSGCT) is a benign soft tissue tumor arising from the synovial membrane that composes the lining of joints, tendons and bursae. TSGCT is a common tumor occurring in the hands and fingers, and also consecutively in the knees, ankles, feet and hips. It is rarely found in the scapular region. To the best of our knowledge, only 2 cases arising on the upper back have been reported. This report presents the case of a 44-year-old Japanese female with a TSGCT arising on her right scapular region.