bluuebunny/crossref_metadata_2025 huggingface dataset:
Exon‐primed, intron‐crossing (EPIC) loci for five nuclear genes in deep‐sea protobranch bivalves: primer design, PCR protocols and locus utility
Authors: JENNINGS ROBERT M. , ETTER R. J.
Published: June 2011

We describe PCR primers and amplification protocols developed to obtain introns from conserved nuclear genes in deep‐sea protobranch bivalves. Because almost no sequence data for protobranchs are publically available, mollusk and other protostome sequences from GenBank were used to design degenerate primers, making these loci potentially useful in other invertebrate taxa. Amplification and sequencing success varied across the test group of 30 species, and we present five loci spanning this range of outcomes. Intron presence in the targeted regions also varied across genes and species, often within single genera; for instance, the calmodulin and β‐tubulin loci contained introns with high frequency, whereas the triose phosphate isomerase locus never contained an intron. In introns for which we were able to obtain preliminary estimates of polymorphism levels in single species, polymorphism was greater than traditional mitochondrial loci. These markers will greatly increase the ability to assess population structure in the ecologically important protobranchs, and may prove useful in other taxa as well.
Hypolithic communities: important nitrogen sources in Antarctic desert soils
Authors: Cowan D. A. , Sohm J. A. , Makhalanyane T. P. , Capone D. G. , Green T. G. A. , Cary S. C. , Tuffin I. M.
Published: June 2011

Hypolithic microbial communities (i.e. cryptic microbial assemblages found on the undersides of translucent rocks) are major contributors of carbon input into the oligotrophic hyper‐arid desert mineral soils of the Eastern Antarctic Dry Valleys. Here we demonstrate, for the first time, that hypolithic microbial communities possess both the genetic capacity for nitrogen fixation (i.e. the presence of nifH genes) and the ability to catalyse acetylene reduction, an accepted proxy for dinitrogen fixation. An estimate of the total contribution of these communities suggests that hypolithic communities are important contributors to fixed nitrogen budgets in Antarctic desert soils.
State‐dependent changes in astrocyte regulation of extrasynaptic NMDA receptor signalling in neurosecretory neurons
Authors: Fleming Tiffany M. , Scott Victoria , Naskar Krishna , Joe Natalie , Brown Colin H. , Stern Javier E.
Published: June 2011

Non‐technical summary  Glutamate is a critical excitatory neurotransmitter in the modulation of hypothalamic neuronal activity and neurosecretion from the posterior pituitary. Still, the precise mechanisms and modalities by which it acts remain to be fully elucidated. We show that in addition to mediating conventional fast synaptic transmission, glutamate persistently activates extrasynaptic NMDA receptors, providing a tonic excitatory drive to hypothalamic neurosecretory neurons. We also show that this tonic excitatory modality is influenced by the neighbouring astrocytes, and is enhanced in dehydrated rats. Knowledge on alternative modalities by which glutamate influences hypothalamic neuronal function increases our understanding of general brain mechanisms regulating neurosecretion and bodily homeostasis.
Stability Enhancement by Casing Grooves: The Importance of Stall Inception Mechanism and Solidity
Authors: Houghton Tim , Day Ivor
Published: June 2011

This paper concerns the optimization of casing grooves and the important influence of stall inception mechanism on groove performance. Installing casing grooves is a well known technique for improving the stable operating range of a compressor, but the wide-spread use of grooves is restricted by the loss of efficiency and flow capacity. In this paper, laboratory tests are used to examine the conditions under which casing treatment can be used to greatest effect. The use of a single casing groove was investigated in a recently published companion paper. The current work extends this to multiple-groove treatments and considers their performance in relation to stall inception mechanisms. Here it is shown that the stall margin gain from multiple grooves is less than the sum of the gains if the grooves were used individually. By contrast, the loss of efficiency is additive as the number of grooves increases. It is then shown that casing grooves give the greatest stall margin improvement when used in a compressor, that exhibits spike-type stall inception, while modal activity before stall can dramatically reduce the effectiveness of the grooves. This finding highlights the importance of being able to predict which stall inception mechanism might occur in a given compressor before and after grooves are added. Some published prediction techniques are therefore examined, but found wanting. Lastly, it is shown that casing grooves can, in some cases, be used to remove rotor blades and produce a more efficient, stable, and light-weight rotor.
Ramping Up AMPK
Authors: Ray L. Bryan
Published: June 2011

The cellular energy sensor adenosine monophosphate–activated protein kinase also binds and is regulated by adenosine diphosphate.
Distinctive Immunomodulatory and Inflammatory Properties of the Escherichia coli Type II Heat-Labile Enterotoxin LT-IIa and Its B Pentamer following Intradermal Administration
Authors: Mathias-Santos Camila , Rodrigues Juliana F. , Sbrogio-Almeida Maria Elisabete , Connell Terry D. , Ferreira Luís C. S.
Published: June 2011

The type I and type II heat-labile enterotoxins (LT-I and LT-II) are strong mucosal adjuvants when they are coadministered with soluble antigens. Nonetheless, data on the parenteral adjuvant activities of LT-II are still limited. Particularly, no previous study has evaluated the adjuvant effects and induced inflammatory reactions of LT-II holotoxins or their B pentameric subunits after delivery via the intradermal (i.d.) route to mice. In the present report, the adjuvant and local skin inflammatory effects of LT-IIa and its B subunit pentamer (LT-IIaB5) were determined. When coadministered with ovalbumin (OVA), LT-IIa and, to a lesser extent, LT-IIaB5exhibited serum IgG adjuvant effects. In addition, LT-IIa but not LT-IIaB5induced T cell-specific anti-OVA responses, particularly in respect to induction of antigen-specific cytotoxic CD8+T cell responses. LT-IIa and LT-IIaB5induced differential tissue permeability and local inflammatory reactions after i.d. injection. Of particular interest was the reduced or complete lack of local reactions, such as edema and tissue induration, in mice i.d. inoculated with LT-IIa and LT-IIaB5,respectively, compared with mice immunized with LT-I. In conclusion, the present results show that LT-IIa and, to a lesser extent, LT-IIaB5exert adjuvant effects when they are delivered via the i.d. route. In addition, the low inflammatory effects of LT-IIa and LT-IIaB5in comparison to those of LT-I support the usefulness of LT-IIa and LT-IIaB5as parenterally delivered vaccine adjuvants.
Immunization of Teenagers with a Fifth Dose of Reduced DTaP-IPV Induces High Levels of Pertussis Antibodies with a Significant Increase in Opsonophagocytic Activity
Authors: Aase Audun , Herstad Tove Karin , Merino Samuel , Bolstad Merete , Sandbu Synne , Bakke Hilde , Aaberge Ingeborg S.
Published: June 2011

Waning vaccine-induced immunity againstBordetella pertussisis observed among adolescents and adults. A high incidence of pertussis has been reported in this population, which serves as a reservoir forB. pertussis. A fifth dose of reduced antigen of diphtheria-tetanus-acellular-pertussis and inactivated polio vaccine was given as a booster dose to healthy teenagers. The antibody activity againstB. pertussisantigens was measured prior to and 4 to 8 weeks after the booster by different assays: enzyme-linked immunosorbent assays (ELISAs) of IgG and IgA against pertussis toxin (PT) and filamentous hemagglutinin (FHA), IgG against pertactin (PRN), opsonophagocytic activity (OPA), and IgG binding to liveB. pertussis. There was a significant increase in the IgG activity against PT, FHA, and PRN following the booster immunization (P< 0.001). The prebooster sera showed a geometric mean OPA titer of 65.1 and IgG binding to live bacteria at a geometric mean concentration of 164.9 arbitrary units (AU)/ml. Following the fifth dose, the OPA increased to a titer of 360.4, and the IgG concentration against live bacteria increased to 833.4 AU/ml (P< 0.001 for both). The correlation analyses between the different assays suggest that antibodies against FHA and PRN contribute the most to the OPA and IgG binding.
Prevalence and Genetic Relatedness of Methicillin-Susceptible Staphylococcus aureus Isolates Detected by the Xpert MRSA Nasal Assay
Authors: Arbefeville Sophie S. , Zhang Kunyan , Kroeger Jennifer S. , Howard Wanita J. , Diekema Daniel J. , Richter Sandra S.
Published: June 2011

Methicillin-susceptible
Staphylococcus aureus
(MSSA) isolates lacking
mecA
yet testing positive on the Xpert MRSA assay were recovered from culture for 7.7% of 248 Xpert-positive nasal samples. These “false-positive” Xpert results may be attributed to staphylococcal cassette chromosome (SCC) elements without the
mecA
gene. Pulsed-field gel electrophoresis (PFGE) analysis revealed a diverse population of MSSA strains.
Refractory Chronic Pleurisy Caused by Helicobacter equorum-Like Bacterium in a Patient with X-Linked Agammaglobulinemia
Authors: Funato Michinori , Kaneko Hideo , Ohkusu Kiyofumi , Sasai Hideo , Kubota Kazuo , Ohnishi Hidenori , Kato Zenichiro , Fukao Toshiyuki , Kondo Naomi
Published: June 2011

We describe a 35-year-old man with X-linked agammaglobulinemia who had refractory chronic pleurisy caused by a
Helicobacter equorum-
like bacterium. Broad-range bacterial PCR targeting the 16S and 23S rRNA genes and
in situ
hybridization targeting the 16S rRNA gene of
H. equorum
confirmed the presence of this pathogen in a human for the first time.
Quantitation of Candida CFU in Initial Positive Blood Cultures
Authors: Pfeiffer Christopher D. , Samsa Gregory P. , Schell Wiley A. , Reller L. Barth , Perfect John R. , Alexander Barbara D.
Published: June 2011

One potential limitation of DNA-based molecular diagnostic tests for
Candida
bloodstream infection (BSI) is organism burden, which is not sufficiently characterized. We hypothesized that the number of CFU per milliliter (CFU/ml) present in an episode of
Candida
BSI is too low for reliable DNA-based diagnostics. In this study, we determined
Candida
burden in the first positive blood culture and explored factors that affect organism numbers and patient outcomes. We reviewed records of consecutive patients with a positive blood culture for
Candida
in the lysis-centrifugation blood culture system (Isolator, Wampole Laboratories, Cranbury, NJ) from 1987 to 1991. Descriptive statistics and logistic regression analyses were performed. One hundred fifty-two episodes of
Candida
BSI were analyzed. Patient characteristics included adult age (72%), indwelling central venous catheters (83%), recent surgery (29%), neutropenia (24%), transplant (14%), and other immune suppression (21%). Rates of treatment success and 30-day mortality for candidemia were each 51%. The median CFU/ml was 1 (mode 0.1, range 0.1 to >1,000). In the multivariate analysis, pediatric patients were more likely than adults to have high organism burdens (odds ratio [OR], 10.7; 95% confidence interval [95% CI], 4.3 to 26.5). Initial organism density did not affect patient outcome.
Candida
CFU/ml in the first positive blood culture of a BSI episode varies greatly; >50% of cultures had ≤1 CFU/ml, a concentration below the experimental yeast cell threshold for reliable DNA-based diagnostics. DNA-based diagnostics for
Candida
BSI will be challenged by low organism density and the need for sufficient specimen volume; future research on alternate targets is warranted.
Cepheid GeneXpert MTB/RIF Assay for Mycobacterium tuberculosis Detection and Rifampin Resistance Identification in Patients with Substantial Clinical Indications of Tuberculosis and Smear-Negative Microscopy Results
Authors: Ioannidis Panayotis , Papaventsis Dimitrios , Karabela Simona , Nikolaou Stavroula , Panagi Marina , Raftopoulou Ekaterini , Konstantinidou Eythymia , Marinou Ioanna , Kanavaki Sofia
Published: June 2011

The GeneXpert MTB/RIF assay was evaluated with microscopically negative and positive pulmonary and extrapulmonary specimens from patients with substantial clinical indications for tuberculosis. For the pulmonary samples, the sensitivity, specificity, and positive and negative predictive values were 90.6%, 94.3%, 93.5%, and 91.7%, and for the extrapulmonary samples, they were 100%, 91.6%, 50%, and 100%, respectively. For microscopically negative specimens, the respective values were 86.3%, 93%, 79%, and 95.6%. The assay correctly detected rifampin resistance in all but one specimen, which harbored a mixed population. The GeneXpert assay was highly effective for tuberculosis diagnosis and identification of rifampin-resistant strains in smear-negative samples.
Four Independent Molecular Prion Protein Parameters for Discriminating New Cases of C, L, and H Bovine Spongiform Encephalopathy in Cattle
Authors: Langeveld Jan P. M. , Erkens Jo H. F. , Rammel Ines , Jacobs Jorg G. , Davidse Aart , van Zijderveld Fred G. , Bossers Alex , Schildorfer Hermann
Published: June 2011

In anticipation of the emergence of more variants of bovine spongiform encephalopathy (BSE), a semiquantitative display of the following four independent molecular diagnostic prion parameters was designed: N terminus, proteinase K (PK) resistance, glycoprofile, and mixed population. One H BSE case, three L BSE cases, six C BSE cases, and one unusual classical BSE (C BSE) case are reported.
Cooling an acute muscle injury: can basic scientific theory translate into the clinical setting?
Authors: Bleakley C M , Glasgow P , Webb M J
Published: June 2011

Ice is commonly used after acute muscle strains but there are no clinical studies of its effectiveness. By comparison, there are a number of basic scientific studies on animals which show that applying ice after muscle injury has a consistent effect on a number of important cellular and physiological events relating to recovery. Some of these effects may be temperature dependant; most animal studies induce significant reductions in muscle temperature at the injury site. The aim of this short report was to consider the cooling magnitudes likely in human models of muscle injury and to discuss its relevance to the clinical setting. Current best evidence shows that muscle temperature reductions in humans are moderate in comparison to most animal models, limiting direct translation to the clinical setting. Further important clinical questions arise when we consider the heterogenous nature of muscle injury in terms of injury type, depth and insulating adipose thickness. Contrary to current practice, it is unlikely that a ‘panacea’ cooling dose or duration exists in the clinical setting. Clinicians should consider that in extreme circumstances of muscle strain (eg, deep injury with high levels of adipose thickness around the injury site), the clinical effectiveness of cooling may be significantly reduced.
Injury mortality indicators: recommendations from the International Collaborative Effort on Injury Statistics
Authors: Cryer Colin , Fingerhut Lois , Segui-Gomez Maria
Published: June 2011

Background

The International Collaborative Effort (ICE) on Injury Statistics called for an effort ‘to reach consensus on what are the 10 most important indicators of injury incidence that offer the potential for international comparisons and for regional or global monitoring.’

Objectives

To describe the process of developing the ICE indicators and to present the specifications of selected injury mortality indicators, along with comparisons between selected countries for those specified indicators.

Methods

Participants on the ICE list had been asked to send to one of the authors what they considered the most important five indicators of injury incidence. These were synthesised and presented under six themes: mortality indicators (general); mortality indicators (motor vehicle); mortality indicators (other); hospital data-based (overall); hospital data-based (traumatic brain injury (TBI)); long-term disability (overall). Following two work group discussions and after drafting and revising indicator specifications, agreement was reached on mortality indicators and specifications. Specifications for those mortality indicators are presented. Morbidity indicators are still to be agreed.

Results

The mortality indicators proposed were age-adjusted rates of injury death; motor vehicle traffic crash-related death; self-harm/suicide; assault/homicide; and TBI death. The empirical work highlighted difficulties in identifying TBI in countries where mortality data do not capture multiple injuries, prompting us to drop the mortality indicator related to TBI and moving us instead to introduce an indicator to monitor the use of undetermined intent in the classification of injury mortality.

Conclusion

The ICE has reached a consensus on what injury mortality indicators should be used for comparison between countries. Specifications for each of these have been applied successfully to the mortality data of seven countries.
Direct evidence for concurrent morphological and genetic heterogeneity in an invasive ductal carcinoma of triple-negative phenotype
Authors: Patani Neill , Barbashina Violetta , Lambros Maryou B K , Gauthier Arnaud , Mansour Marthe , Mackay Alan , Reis-Filho Jorge S
Published: June 2011

Triple-negative breast cancers account for 12–17% of all invasive breast carcinomas and comprise a heterogeneous group of tumours, with varying histological features and clinical behaviours. Focal apocrine differentiation can be associated with a subset of these lesions. To establish whether morphological diversity is associated with divergent genetic aberrations the genomic profiles of microdissected, morphologically distinct components from an invasive ductal carcinoma of no special type with triple-negative phenotype and a region of apocrine differentiation were determined by high-resolution microarray-based comparative genomic hybridisation and validated by fluorescence in-situ hybridisation. Morphologically distinct components were found to harbour differing genetic aberrations, with the region of apocrine differentiation demonstrating genomic gains and losses on chromosome arms 9p and 9q, respectively, not present in non-apocrine areas. The results provide additional direct evidence of intra-tumour genetic heterogeneity in breast cancer and demonstrate that morphologically distinct regions can be associated with distinct genetic aberrations.
When should conscientious objection be accepted?
Authors: Magelssen Morten
Published: June 2011

This paper makes two main claims: first, that the need to protect health professionals' moral integrity is what grounds the right to conscientious objection in health care; and second, that for a given claim of conscientious objection to be acceptable to society, a certain set of criteria should be fulfilled. The importance of moral integrity for individuals and society, including its special role in health care, is advocated. Criteria for evaluating the acceptability of claims to conscientious objection are outlined. The precise content of the criteria is dictated by the two main interests that are at stake in the dilemma of conscientious objection: the patient's interests and the health professional's moral integrity. Alternative criteria proposed by other authors are challenged. The bold claim is made that conscientious objection should be recognised by society as acceptable whenever the five main criteria of the proposed set are met.
Occupational health impact of the 2009 H1N1 flu pandemic: surveillance of sickness absence
Authors: Torá-Rocamora Isabel , Delclos George L , Martínez José Miguel , Jardí Josefina , Alberti Constança , Manzanera Rafael , Yasui Yutaka , Clèries Ramón , Tobías Aurelio , Benavides Fernando G
Published: June 2011

Objectives

Workplace absences due to illness can disrupt usual operations and increase costs for businesses. This study of sickness absence due to influenza and influenza-related illness presents a unique opportunity to characterise and measure the impact of the 2009 (H1N1) pandemic, by comparing trends during the pandemic to those of previous years, and adding this information to that obtained by traditional epidemiological surveillance systems.

Methods

We compared the numbers of cases of sickness absence due to illness caused by influenza and influenza-related illness in 2007–2009, and in the first 3 months of 2010 in Catalonia (n=811 940) using a time series approach. Trends were examined by economic activity, age and gender. The weekly endemic-epidemic index (EEI) was calculated and its 95% CI obtained with the delta method, with observed and expected cases considered as independent random variables.

Results

Influenza activity peaked earlier in 2009 and yielded more cases than in previous years. Week 46 (in November 2009) had the highest number of new cases resulting in sickness absence (EEI 20.99; 95% CI 9.44 to 46.69). Women and the ‘education, health and other social activities’ sector were the most affected.

Conclusions

Results indicate that the new H1N1 pandemic had a significant impact on business, with shifts in the timing of peak incidence, a doubling in the number of cases, and changes in the distribution of cases by economic activity sector and gender. Traditional epidemiological surveillance systems could benefit from the addition of information based on sickness absence data.
Conflict of interest and FCTC implementation in China
Authors: Wan Xia , Ma Shaojun , Hoek Janet , Yang Jie , Wu Lanyan , Zhou Jiushun , Yang Gonghuan
Published: June 2011

Objective

To critically review the structure of tobacco control policy making in China, examine conflicts of interest within this structure, and consider how these affected the introduction of on-pack warnings.

Methods

Government policy documents and warning labels were obtained and critically reviewed.

Results

Few differences exist between the on-pack warnings formerly used in China and those introduced ostensibly to meet Framework Convention on Tobacco Control (FCTC) obligations. Comparison with tobacco manufactured for export or overseas consumption shows the new Chinese domestic on-pack warnings are demonstrably inferior to those required internationally. The inherent conflict of interest in the Chinese tobacco control agency structure, which must meet commercial and public health objectives, undermined the introduction of new health warnings.

Conclusions

To promote more effective tobacco control policies, the conflict of interest inhibiting the public health function of the State Tobacco Monopoly Administration (STMA) must be removed. Specifically, the public health function must be separated from oversight of commercial production, and packaging must be redesigned with pictorial warnings and messages compliant with Article 11 of the FCTC.
Exempting casinos from the Smoke-free Illinois Act will not bring patrons back: they never left: Figure 1
Authors: Harris Jenine K , Carothers Bobbi J , Luke Douglas A , Silmere Hiie , McBride Timothy D , Pion Martin
Published: June 2011

Objective

The Smoke-free Illinois Act was implemented in January 2008, one month after the beginning of a national recession. In December 2010, the Illinois legislature proposed new legislation that would provide an exemption for casinos from the act until neighbouring states also implement smoke-free casino policies. Lobbyists and gaming commission representatives argued that Illinois casinos were losing patrons to casinos in neighbouring states that allow smoking. This study examined the influence of the act on casino admissions in Illinois and neighbouring states in light of the economy.

Methods

A multilevel model was developed to examine monthly casino admissions from January 2007 to December 2008.

Results

There was no difference in changes in admissions across the four states over time after accounting for the economic downturn.

Conclusions

The Smoke-Free Illinois Act did not have a detectable effect on Illinois casino admissions.
Renal calculi in wild Eurasian otters (Lutra lutra) in England
Authors: Simpson V. R. , Tomlinson A. J. , Molenaar F. M. , Lawson B. , Rogers K. D.
Published: June 2011

Macroscopic renal calculi were seen in 50 of 492 (10.2 per cent) wild Eurasian otters found dead in England from 1988 to 2007. Forty‐eight adults and two subadults were affected. Calculi were present in 15.7 per cent (31 of 197) of adult males and 12.7 per cent (17 of 134) of adult females. There was an increase in prevalence in the study population over time; no calculi were found in 73 otters examined between 1988 and 1996, but in most subsequent years they were observed with increased frequency. Calculi occurred in both kidneys but were more common in the right kidney. They varied greatly in shape and size; larger calculi were mostly seen in the calyces while the smallest ones were commonly found in the renal medulla. Calculi from 45 cases were examined by x‐ray diffraction analysis; in 43 (96 per cent), they were composed solely of ammonium acid urate. Affected otters had heavier adrenal glands relative to their body size than unaffected otters (P<0.001). There was no significant association between body condition index and the presence of calculi (P>0.05). Many otters had fresh bite wounds consistent with intraspecific aggression. The proportion bitten increased over time and this coincided with the increased prevalence of renal calculi.
A NOTE ON A PARTICLE–ANTIPARTICLE INTERACTION
Authors: SIDHARTH B. G.
Published: June 2011

We develop an isospin-like formulation with particles and their antiparticle counterparts. This leads to a new shortlived interaction between them, valid at very high energies and mediated by massive particles. We point out that evidence for this is already suggested by the very recent observations by the CDF collaboration at Fermilab.
ELECTROMAGNETIC AND ISOVECTOR TERMS IN STANDARD RELATIVISTIC MEAN FIELD MODEL
Authors: SULAKSONO A.
Published: June 2011

The effects of auxiliary contribution in forms of electromagnetic tensors and relativistic electromagnetic exchange in local density approximation as well as δ meson and isovector density-dependent nonlinear terms in standard relativistic mean field model constrained by nuclear matter stability criteria in some selected finite nuclei and nuclear matter properties are studied. It is found that in the case of finite nuclei, the electromagnetic tensors play the most dominant part compared to other auxiliary terms. Due to the presence of electromagnetic tensors, the binding energies prediction of the model can be improved quite significantly. However, these terms do not yield demanded effects for rms radii prediction. In the case of nuclear matter properties, the isovector density-dependent nonlinear term plays the most crucial role in providing predictions which are quite compatible with experimental constraints. We have also shown these auxiliary contributions are indeed unable to improve the single particle spectrum results of the model.
USING BINDING PROFILES TO PREDICT BINDING SITES OF TARGET RNAs
Authors: POOLSAP UNYANEE , KATO YUKI , SATO KENGO , AKUTSU TATSUYA
Published: June 2011

Prediction of RNA–RNA interaction is a key to elucidating possible functions of small non-coding RNAs, and a number of computational methods have been proposed to analyze interacting RNA secondary structures. In this article, we focus on predicting binding sites of target RNAs that are expected to interact with regulatory antisense RNAs in a general form of interaction. For this purpose, we propose bistaRNA, a novel method for predicting multiple binding sites of target RNAs. bistaRNA employs binding profiles that represent scores for hybridized structures, leading to reducing the computational cost for interaction prediction. bistaRNA considers an ensemble of equilibrium interacting structures and seeks to maximize expected accuracy using dynamic programming. Experimental results on real interaction data validate good accuracy and fast computation time of bistaRNA as compared with several competitive methods. Moreover, we aim to find new targets given specific antisense RNAs, which provides interesting insights into antisense RNA regulation. bistaRNA is implemented in C++. The program and Supplementary Material are available at .
VERIFICATION OF PHYLOGENETIC INFERENCE PROGRAMS USING METAMORPHIC TESTING
Authors: SADI MD. SHAIK , KUO FEI-CHING , HO JOSHUA W. K. , CHARLESTON MICHAEL A. , CHEN T. Y.
Published: June 2011

Many phylogenetic inference programs are available to infer evolutionary relationships among taxa using aligned sequences of characters, typically DNA or amino acids. These programs are often used to infer the evolutionary history of species. However, in most cases it is impossible to systematically verify the correctness of the tree returned by these programs, as the correct evolutionary history is generally unknown and unknowable. In addition, it is nearly impossible to verify whether any non-trivial tree is correct in accordance to the specification of the often complicated search and scoring algorithms. This difficulty is known as the oracle problem of software testing: there is no oracle that we can use to verify the correctness of the returned tree. This makes it very challenging to test the correctness of any phylogenetic inference programs. Here, we demonstrate how to apply a simple software testing technique, called Metamorphic Testing, to alleviate the oracle problem in testing phylogenetic inference programs. We have used both real and randomly generated test inputs to evaluate the effectiveness of metamorphic testing, and found that metamorphic testing can detect failures effectively in faulty phylogenetic inference programs with both types of test inputs.
APPLICATION OF NANOTECHNOLOGY IN ANTIMICROBIAL COATINGS IN THE WATER INDUSTRY
Authors: DE KWAADSTENIET M. , BOTES M. , CLOETE T. E.
Published: June 2011

Biofouling is a concern in the water industry due to the impact it has on maintainence of system functioning and the cost involved for prevention. Mechanical and chemical methods such as the application of biocides currently used to control biofouling are not always effective. The need for alternative methods for the prevention of biofouling therefore exists. Self-cleaning and antimicrobial surfaces, such as antimicrobial and antifouling coatings, have already shown the potential to control biofouling. A new contribution to this field is the application of nanotechnology in the design and fabrication of coatings. Nanomaterials may prohibit biofouling either by repelling microorganisms through hydrophobic nanostructures or killing of microorganisms in direct contact with surfaces containing nanobiocides. This review focuses on the different approaches and techniques to fabricate antimicrobial polymeric surfaces, the application of specific nanoparticles and nanomaterials, and nanoenabled antimicrobial coatings such as paints.
Efficient and effective misaligned data access handling in a dynamic binary translation system
Authors: Li Jianjun , Wu Chenggang , Hsu Wei-Chung
Published: June 2011

Binary Translation (BT) has been commonly used to migrate application software across Instruction Set Architectures (ISAs). Some architectures, such as X86, allow Misaligned Data Accesses (MDAs), while most modern architectures require natural data alignments. In a binary translation system, where the source ISA allows MDA and the target ISA does not, memory operations must be carefully translated. Naive translation may cause frequent misaligned data access traps to occur at runtime on the target machine and severely slow down the migrated application.

This article evaluates different approaches in handling MDA in a binary translation system including how to identify MDA candidates and how to translate such memory instructions. This article also proposes some new mechanisms to more effectively deal with MDAs. Extensive measurements based on SPEC CPU2000 and CPU2006 benchmarks show that the proposed approaches are more effective than existing methods and getting close to the performance upper bound of MDA handling.
Nav1.5-dependent persistent Na+ influx activates CaMKII in rat ventricular myocytes and N1325S mice
Authors: Yao Lina , Fan Peidong , Jiang Zhan , Viatchenko-Karpinski Serge , Wu Yuzhi , Kornyeyev Dmytro , Hirakawa Ryoko , Budas Grant R. , Rajamani Sridharan , Shryock John C. , Belardinelli Luiz
Published: June 2011

Late Na+ current ( INaL) and Ca2+/calmodulin-dependent protein kinase II (CaMKII) are both increased in the diseased heart. Recently, CaMKII was found to phosphorylate the Na+ channel 1.5 (Nav1.5), resulting in enhanced INaL. Conversely, an increase of INaL would be expected to cause elevation of intracellular Ca2+ and activation of CaMKII. However, a relationship between enhancement of INaL and activation of CaMKII has yet to be demonstrated. We investigated whether Na+ influx via Nav1.5 leads to CaMKII activation and explored the functional significance of this pathway. In neonatal rat ventricular myocytes (NRVM), treatment with the INaL activators anemone toxin II (ATX-II) or veratridine increased CaMKII autophosphorylation and increased phosphorylation of CaMKII substrates phospholamban and ryanodine receptor 2. Knockdown of Nav1.5 (but not Nav1.1 or Nav1.2) prevented ATX-II-induced CaMKII phosphorylation, providing evidence for a specific role of Nav1.5 in CaMKII activation. In support of this view, CaMKII activity was also increased in hearts of transgenic mice overexpressing a gain-of-function Nav1.5 mutant (N1325S). The effects of both ATX-II and the N1325S mutation were reversed by either INaL inhibition (with ranolazine or tetrodotoxin) or CaMKII inhibition (with KN93 or autocamtide 2-related inhibitory peptide). Furthermore, ATX-II treatment also induced CaMKII-Nav1.5 coimmunoprecipitation. The same association between CaMKII and Nav1.5 was also found in N1325S mice, suggesting a direct protein-protein interaction. Pharmacological inhibitions of either CaMKII or INaL also prevented ATX-II-induced cell death in NRVM and reduced the incidence of polymorphic ventricular tachycardia induced by ATX-II in rat perfused hearts. Taken together, these results suggest that a Nav1.5-dependent increase in Na+ influx leads to activation of CaMKII, which in turn phosphorylates Nav1.5, further promoting Na+ influx. Pharmacological inhibition of either CaMKII or Nav1.5 can ameliorate cardiac dysfunction caused by excessive Na+ influx.
Gap junctions favor normal rat kidney epithelial cell adaptation to chronic hypertonicity
Authors: Desforges Bénédicte , Savarin Philippe , Bounedjah Ouissame , Delga Stéphanie , Hamon Loïc , Curmi Patrick A. , Pastré David
Published: June 2011

Upon hypertonic stress most often resulting from high salinity, cells need to balance their osmotic pressure by accumulating neutral osmolytes called compatible osmolytes like betaine, myo-inositol, and taurine. However, the massive uptake of compatible osmolytes is a slow process compared with other defense mechanisms related to oxidative or heat stress. This is especially critical for cycling cells as they have to double their volume while keeping a hospitable intracellular environment for the molecular machineries. Here we propose that clustered cells can accelerate the supply of compatible osmolytes to cycling cells via the transit, mediated by gap junctions, of compatible osmolytes from arrested to cycling cells. Both experimental results in epithelial normal rat kidney cells and theoretical estimations show that gap junctions indeed play a key role in cell adaptation to chronic hypertonicity. These results can provide basis for a better understanding of the functions of gap junctions in osmoregulation not only for the kidney but also for many other epithelia. In addition to this, we suggest that cancer cells that do not communicate via gap junctions poorly cope with hypertonic environments thus explaining the rare occurrence of cancer coming from the kidney medulla.
Hypoxia. Cross talk between oxygen sensing and the cell cycle machinery
Authors: Semenza Gregg L.
Published: June 2011

A fundamental physiological property of mammalian cells is the regulation of proliferation according to O2 availability. Progression through the cell cycle is inhibited under hypoxic conditions in many, but not all, cell types, and this G1 arrest is dependent on hypoxia-inducible factor (HIF) 1α. Components of the hexameric MCM helicase, which binds to replication origins before the onset of DNA synthesis, are present in large excess in mammalian cells relative to origins, suggesting that they may have additional functions. Screens for HIF-1α interacting proteins revealed that MCM7 binds to the amino-terminal PER-SIM-ARNT (PAS) domain of HIF-1α and stimulates prolyl hydroxylation-dependent ubiquitination and degradation of HIF-1α, whereas MCM3 binds to the carboxyl terminus of HIF-1α and enhances asparaginyl hydroxylation-dependent inhibition of HIF-1α transactivation domain function. Thus MCM proteins inhibit HIF activity via two distinct O2-dependent mechanisms. Under prolonged hypoxic conditions, MCM mRNA expression is inhibited in a HIF-1α-dependent manner. Thus HIF and MCM proteins act in a mutually antagonistic manner, providing a novel molecular mechanism for homeostatic regulation of cell proliferation based on the relative levels of these proteins.
Antibody-directed myostatin inhibition enhances muscle mass and function in tumor-bearing mice
Authors: Murphy Kate T. , Chee Annabel , Gleeson Ben G. , Naim Timur , Swiderski Kristy , Koopman René , Lynch Gordon S.
Published: June 2011

Cancer cachexia describes the progressive skeletal muscle wasting and weakness in many cancer patients and accounts for >20% of cancer-related deaths. We tested the hypothesis that antibody-directed myostatin inhibition would attenuate the atrophy and loss of function in muscles of tumor-bearing mice. Twelve-week-old C57BL/6 mice received a subcutaneous injection of saline (control) or Lewis lung carcinoma (LLC) tumor cells. One week later, mice received either once weekly injections of saline (control, n = 12; LLC, n = 9) or a mouse chimera of anti-human myostatin antibody (PF-354, 10 mg·kg−1·wk−1, LLC+PF-354, n = 11) for 5 wk. Injection of LLC cells reduced muscle mass and maximum force of tibialis anterior (TA) muscles by 8–10% ( P < 0.05), but the muscle atrophy and weakness were prevented with PF-354 treatment ( P > 0.05). Maximum specific (normalized) force of diaphragm muscle strips was reduced with LLC injection ( P < 0.05) but was not improved with PF-354 treatment ( P > 0.05). PF-354 enhanced activity of oxidative enzymes in TA and diaphragm muscles of tumor-bearing mice by 118% and 89%, respectively ( P < 0.05). Compared with controls, apoptosis that was not of myofibrillar or satellite cell origin was 140% higher in TA muscle cross sections from saline-treated LLC tumor-bearing mice ( P < 0.05) but was not different in PF-354-treated tumor-bearing mice ( P > 0.05). Antibody-directed myostatin inhibition attenuated the skeletal muscle atrophy and loss of muscle force-producing capacity in a murine model of cancer cachexia, in part by reducing apoptosis. The improvements in limb muscle mass and function highlight the therapeutic potential of antibody-directed myostatin inhibition for cancer cachexia.
Brain IL-6- and PG-dependent actions of IL-1β and lipopolysaccharide in avian fever
Authors: Marais Manette , Maloney Shane K. , Gray David A.
Published: June 2011

There is no persuasive evidence of a correlation between proinflammatory cytokines and avian fever. In this study, for the first time, we use avian cytokines to investigate a role for proinflammatory cytokines in the central component of avian fever. IL-1β and IL-6 injected intracerebroventricularly into Pekin ducks ( n = 8) initiated robust fevers of equal magnitude and duration, although there was a significant difference in the latency to a febrile response. In addition, the IL-1β-induced fever could be abolished with an intracerebroventricular injection of antibodies to avian IL-6 or an oral administration of a PG synthesis inhibitor. Our findings indicate the following sequence of events within the central component of the avian febrile mechanism: IL-1β gives rise to bioactive IL-6, which stimulates an accelerated synthesis of PGs, and these PGs then adjust the sensitivity of warm-sensitive neurons in the avian brain stem to mediate fever. Yet PGE2 was not upregulated in the cerebrospinal fluid of ducks made febrile with LPS. We conclude that IL-1β and IL-6 may well mediate fever by instigating an accelerated synthesis of brain-derived PG, of a class other than PGE2, or that IL-6 serves as one of the terminal mediators of the avian febrile response.
Aging and exercise training reduce testes microvascular Po2and alter vasoconstrictor responsiveness in testicular arterioles
Authors: Dominguez James M. , Davis Robert T. , McCullough Danielle J. , Stabley John N. , Behnke Bradley J.
Published: June 2011

Testicular function and associated testosterone concentration decline with advancing age, and an impaired O2supply may contribute, in part, to this reduction. We hypothesized that there would be a reduced microvascular Po2(Po2m) in the testes from aged rats, and this reduced Po2mwould be associated with impaired vasomotor control in isolated resistance arterioles. In addition, given the positive effect of exercise on microvascular Po2and arteriolar function, we further hypothesized that there would be an enhanced Po2min the testes from aged animals after aerobic exercise training. Testicular Po2mwas measured in vivo via phosphorescence quenching in young and aged sedentary (SED) and exercise-trained (ET; 15 m/min treadmill walking, 15-degree incline, 5 days/wk for 10 wk) male Fischer-344 rats. Vasoconstriction to α-adrenergic [norepinephrine (NE) and phenylephrine (PE)] and myogenic stimuli in testicular arterioles was assessed in vitro. In the SED animals, testicular Po2mwas reduced by ∼50% with old age (aged SED 11.8 ± 1.9 vs. young SED 22.1 ± 1.1 mmHg; P = 0.0001). Contrary to our hypothesis, exercise training did not alter Po2min the aged group and reduced testicular Po2min the young animals, abolishing age-related differences (young ET, 10.0 ± 0.8 vs. aged ET, 10.7 ± 0.9 mmHg; P = 0.37). Vasoconstrictor responsiveness to NE and PE was diminished in aged compared with young (NE: young SED, 58 ± 2 vs. aged SED, 47 ± 2%; P = 0.001) (PE: young SED, 51 ± 3 vs. aged SED, 36 ± 5%; P = 0.008). Exercise training did not alter maximal vasoconstriction to NE in young or aged groups. In summary, advancing age is associated with a reduced testis Po2mand impaired adrenergic vasoconstriction. The diminished testicular microvascular driving pressure of O2and associated vascular dysfunction provides mechanistic insight into the old age-related decrease in testicular function, and a reduced Po2mmay contribute, in part, to reduced fertility markers after exercise training.
Adrenergic control of vascular resistance varies in muscles composed of different fiber types: influence of the vascular endothelium
Authors: Behnke Bradley J. , Armstrong Robert B. , Delp Michael D.
Published: June 2011

The influence of the sympathetic nervous system (SNS) upon vascular resistance is more profound in muscles comprised predominately of low-oxidative type IIB vs. high-oxidative type I fiber types. However, within muscles containing high-oxidative type IIA and IIX fibers, the role of the SNS on vasomotor tone is not well established. The purpose of this study was to examine the influence of sympathetic neural vasoconstrictor tone in muscles composed of different fiber types. In adult male rats, blood flow to the red and white portions of the gastrocnemius (GastRed and GastWhite, respectively) and the soleus muscle was measured pre- and postdenervation. Resistance arterioles from these muscles were removed, and dose responses to α1-phenylephrine or α2-clonidine adrenoreceptor agonists were determined with and without the vascular endothelium. Denervation resulted in a 2.7-fold increase in blood flow to the soleus and GastRed and an 8.7-fold increase in flow to the GastWhite. In isolated arterioles, α2-mediated vasoconstriction was greatest in GastWhite (∼50%) and less in GastRed (∼31%) and soleus (∼17%); differences among arterioles were abolished with the removal of the endothelium. There was greater sensitivity to α1-mediated vasoconstriction in the GastWhite and GastRed vs. the soleus, which was independent of whether the endothelium was present. These data indicate that 1) control of vascular resistance by the SNS in high-oxidative, fast-twitch muscle is intermediate to that of low-oxidative, fast-twitch and high-oxidative, slow-twitch muscles; and 2) the ability of the SNS to control blood flow to low-oxidative type IIB muscle appears to be mediated through postsynaptic α1- and α2-adrenoreceptors on the vascular smooth muscle.
Transpulmonary pyruvate kinetics
Authors: Johnson Matthew L. , Hussien Rajaa , Horning Michael A. , Brooks George A.
Published: June 2011

Shuttling of intermediary metabolites, such as pyruvate, contributes to the dynamic energy and biosynthetic needs of tissues. Tracer kinetic studies offer a powerful tool to measure the metabolism of substrates like pyruvate that are simultaneously taken up from and released into the circulation by organs. However, we understood that during each circulatory passage, the entire cardiac output transits the pulmonary circulation. Therefore, we examined the transpulmonary pyruvate kinetics in an anesthetized rat model during an unstimulated (Con), lactate clamp (LC), and epinephrine infusion (Epi) conditions using a primed-continuous infusion of [U-13C]pyruvate. Compared with Con and Epi stimulation, LC significantly increased mixed central venous ([v̄]) and arterial ([a]) pyruvate concentrations ( P < 0.05). We hypothesized that the lungs, specifically the pulmonary capillary beds are sites of simultaneous production and removal of pyruvate and contributes significantly to whole body carbohydrate intermediary metabolism. Transpulmonary net pyruvate balances were positive during all three conditions, indicating net pyruvate uptake. Net balance was significantly greater during epinephrine stimulation compared with the unstimulated control ( P < 0.05). Tracer-measured pyruvate fractional extraction averaged 42.8 ± 5.8% for all three conditions and was significantly higher during epinephrine stimulation ( P < 0.05) than during either Con or LC conditions, that did not differ from each other. Pyruvate total release (tracer measured uptake − net balance) was significantly higher during epinephrine stimulation (400 ± 100 μg/min) vs. Con (30 ± 20 μg/min) ( P < 0.05). These data are interpreted to mean that significant pyruvate extraction occurs during circulatory transport across lung parenchyma. The extent of pulmonary parenchymal pyruvate extraction predicts high expression of monocarboxylate (lactate/pyruvate) transporters (MCTs) in the tissue. Western blot analysis of whole lung homogenates detected three isoforms, MCT1, MCT2, and MCT4. We conclude that a major site of circulating pyruvate extraction resides with the lungs and that during times of elevated circulating lactate, pyruvate, or epinephrine stimulation, pyruvate extraction is increased.