bluuebunny/crossref_metadata_2025 huggingface dataset:
Seasonal and diel patterns in the migrations of fishes between a river and a floodplain tributary
Authors: Nunn A. D. , Copp G. H. , Vilizzi L. , Carter M. G.
Published: January 2010

Nunn AD, Copp GH, Vilizzi L, Carter MG. Seasonal and diel patterns in the migrations of fishes between a river and a floodplain tributary. Ecology of Freshwater Fish 2010: 19: 153–162. © 2009 John Wiley & Sons A/S

Abstract –  The population behaviours associated with the migrations of fishes in lowland river ecosystems are amongst the most poorly‐understood dispersal mechanisms of temperate freshwater organisms. This study evaluated the influence of four environmental variables (light levels, river discharge, water temperature and water velocity) on the timing, intensity and direction of fish movements between the River Avon (Hampshire, England) and a small floodplain tributary, Ibsley Brook, over a 12‐month period. Using canonical correspondence analysis (CCA) to identify patterns of movement (by groups of species) and the relative strengths of explanatory variables in the data, the probability of fishes migrating between the river and tributary was determined using Bayesian modelling. The intensity and direction of fish movements between the river and tributary varied temporally, both on a diel and seasonal basis, and there were species‐ and age‐specific patterns in behaviour. Diel movements appeared to be triggered by changes in light intensity and brook water velocity, whereas seasonal movements were mostly driven by changes in river discharge and water temperature, particularly those associated with floods. This study emphasises the importance of connectivity in river systems, as fishes migrated in all conditions, but especially during rapidly‐rising discharge.
RESPONSE SURFACE MODELING OF LISTERIA MONOCYTOGENES INACTIVATION ON LETTUCE TREATED WITH ELECTROLYZED OXIDIZING WATER
Authors: DING TIAN , DONG QING‐LI , RAHMAN S. M. E. , OH DEOG‐HWAN
Published: January 2010

Electrolyzed oxidizing water has been estimated that it has strong bactericidal activity and has been widely used as a disinfectant for inactivating microbial organisms. The combined effects of temperature (15–35C), chlorine concentration of electrolyzed oxidizing water (30–70 ppm) and treatment time (1–5 min) on the reduction of Listeria monocytogenes in lettuce were investigated. Reductions of 1.39–2.79 log10 cfu/g were observed in different combinations of the three factors. Also, a quadratic equation for L. monocytogenes inactivation kinetic was developed by multiple regression analysis using response surface methodology. The predicted values were shown to be significantly in good agreement with experimental values because the adjusted determination coefficient () was 0.9578 and the level of significance was P < 0.0001. Besides, average mean deviation (E%), bias factor (Bf) and accuracy factor (Af), which are validation indicators of the model were 0.0218, 1.0003 and 1.0220, respectively. Thus, predicted model showed a good correlation between the experimental and predicted values, indicating success at providing reliable predictions of L. monocytogenes growth in lettuce.

PRACTICAL APPLICATIONS

Electrolyzed oxidizing water is an important sanitizer, and nowadays it has been widely used in food industry. Lettuce is regarded as a “healthier” food, which is one of the most popular vegetables consumed, whereas many outbreaks caused by L. monocytogenes have been reported until now. According to the model developed in this study, inactivation of L. monocytogenes in lettuce treated with EO water could be predicted by inputting a certain group of environmental factors.
MicroRNAs of the immune system
Authors: Davidson‐Moncada Jan , Papavasiliou F. Nina , Tam Wayne
Published: January 2010

MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression by binding to complementary target mRNAs and either promoting their decay or inhibiting their translation. Most eukaryotic genomes studied encode miRNAs, which are processed from longer noncoding transcripts through pathways conserved from fungi to plants to animals. miRNAs are now understood to be key mediators of developmental transitions in a number of model organisms. With respect to the immune system, miRNAs affect all facets of immune system development, from hematopoiesis to activation in response to infection during both the innate and the adaptive immune response. At the same time, miRNA dysregulation is a central event in the development and pathophysiology of a number of cancers of the immune system. Here we will discuss our current understanding of this general regulatory mechanism, focusing on its involvement in inflammation and in oncogenesis.
New insights into T cell biology and T cell‐directed therapy for autoimmunity, inflammation, and immunosuppression
Authors: Steward‐Tharp Scott M. , Song Yun‐jeong , Siegel Richard M. , O'Shea John J.
Published: January 2010

T cell‐directed therapies have become mainstays in the management of various autoimmune diseases and organ transplantation. The understanding of T cell biology has expanded greatly since the development of most agents currently in use. Here we discuss important recent discoveries pertaining to T helper cell differentiation, lineage commitment, and function. Within this context, we examine existing T cell‐directed therapies, including new agents being evaluated in clinical and preclinical studies. We also use recent findings to speculate on novel targets.
Current perspectives on selective dopamine D3receptor antagonists as pharmacotherapeutics for addictions and related disorders
Authors: Heidbreder Christian A. , Newman Amy H.
Published: January 2010

Repeated exposure to drugs of abuse produces long‐term molecular and neurochemical changes that may explain the core features of addiction, such as the compulsive seeking and taking of the drug, as well as the risk of relapse. A growing number of new molecular and cellular targets of addictive drugs have been identified, and rapid advances are being made in relating those targets to specific behavioral phenotypes in animal models of addiction. In this context, the pattern of expression of the dopamine (DA) D3receptor in the rodent and human brain and changes in this pattern in response to drugs of abuse have contributed primarily to direct research efforts toward the development of selective DA D3receptor antagonists. Growing preclinical evidence indicates that these compounds may actually regulate the motivation to self‐administer drugs and disrupt drug‐associated cue‐induced craving. This report will be divided into three parts. First, preclinical evidence in support of the efficacy of selective DA D3receptor antagonists in animal models of drug addiction will be reviewed. The effects of mixed DA D2/D3receptor antagonists will not be discussed here because most of these compounds have low selectivity at the D3versus D2receptor, and their efficacy profile is related primarily to functional antagonism at D2receptors and possibly interactions with other neurotransmitter systems. Second, major advances in medicinal chemistry for the identification and optimization of selective DA D3receptor antagonists and partial agonists will be analyzed. Third, translational research from preclinical efficacy studies to so‐called proof‐of‐concept studies for drug addiction indications will be discussed.
Non‐Representational Approaches to Body–Landscape Relations
Authors: Macpherson Hannah
Published: January 2010

This short paper offers a critical summary of some of the key themes of non‐representational theory (NRT), with a particular focus on recent approaches to body‐landscape relations and the potential place of disability in these accounts. NRT in British human geography has encouraged an emphasis on the embodied, practiced and habitual qualities of embodied experience. Recent non‐representational work on landscape has developed these agendas to show how landscape may be thought of as a ‘process’ (Rose 2002) or ‘tension’ which potentially ‘animates’ the embodied subject (Rose and Wylie 2006). Here the body and the landscape are understood to be complimentary concepts that are useful to think through together – each in a constant process of ‘becoming’ through the other. This paper reflects on the methodological challenges of researching such non‐representational body‐landscape relations, showing how researchers have drawn on insights of disciplines as diverse as neuroscience and performance studies to address this challenge.
Occurrence and Treatment of ADHD in Adults
Authors: Meyer John S.
Published: January 2010

This study provides positive confirmation that ADD occurs in adults, as well as children, and respond to ATX treatment similar to that seen in children
China's Oil Strategy: “Going Out” to Iran
Authors: Chen Wen‐Sheng
Published: January 2010

China's rapid development has drawn worldwide attention and has been referred to as a “peaceful rise” in recent years. The country's booming economy feeds Beijing's insatiable thirst for sufficient, stable, and secure energy sources. This article argues that Iran's plentiful oil reserves and its capacity to produce and export vast quantities of oil make Tehran a natural partner as China pursues its goal of rising to global‐power status. Furthermore, Iran's location on the “Energy Silk Road” to China is potentially of great significance for Beijing as it seeks to break out of the “Malacca predicament.” This article suggests that China sees an important role for Iran in securing its oil supply and pursuing a “westward oil strategy.” The article also demonstrates that China's energy ties with Iran are constrained and conditioned by Sino‐U.S. cooperation and competition and by the Middle Eastern power structure.
The KATP channel is a molecular sensor of atrophy in skeletal muscle
Authors: Tricarico Domenico , Mele Antonietta , Camerino Giulia Maria , Bottinelli Roberto , Brocca Lorenza , Frigeri Antonio , Svelto Maria , George Jr Alfred L. , Camerino Diana Conte
Published: January 2010

The involvement of ATP‐sensitive K+ (KATP) channels in the atrophy of slow‐twitch (MHC‐I) soleus (SOL) and fast‐twitch (MHC‐IIa) flexor digitorum brevis (FDB) muscles was investigated in vivo in 14‐day‐hindlimb‐unloaded (14‐HU) rats, an animal model of disuse, and in vitro in drug‐induced muscle atrophy. Patch‐clamp and gene expression experiments were performed in combination with measurements of fibre diameters used as an index of atrophy, and with MHC labelling in 14‐HU rats and controls. A down‐regulation of KATP channel subunits Kir6.2, SUR1 and SUR2B with marked atrophy and incomplete phenotype transition were observed in SOL of 14‐HU rats. The observed changes in KATP currents were well correlated with changes in fibre diameters and SUR1 expression, as well as with MHC‐IIa expression. Half of the SOL fibres of 14‐HU rats had reduced diameter and KATP currents and were labelled by MHC‐I antibodies. Non‐atrophic fibres were labelled by MHC‐IIa (22%) antibodies and had enhanced KATP currents, or were labelled by MHC‐I (28%) antibodies but had normal current. FDB was not affected in 14‐HU rats and this is related to the high expression/activity of Kir6.2/SUR1 subunits characterizing this muscle phenotype. The long‐term incubation of the control muscles in vitro with the KATP channel blocker glibenclamide (10−6 m) reduced the KATP currents with atrophy and these effects were prevented by the KATP channel opener diazoxide (10−4 m). The in vivo down‐regulation of SUR1, and possibly of Kir6.2 and SUR2B, or their in vitro pharmacological blockade activates atrophic signalling in skeletal muscle. All these findings suggest a new role for the KATP channel as a molecular sensor of atrophy.
Modeling Blockage of Particles in Conduit Constrictions: Dense Granular-Suspension Flow
Authors: Parry A. J. , Millet O.
Published: January 2010

This paper presents a numerical simulation study of dense granular-suspension flow in a conduit with constriction. An empirical function of solid concentrations and Reynolds number prescribes the force between a particle and the fluid. This simplification reduces the computing load of the fine flow-field details around each particle. In the fluid-momentum equation, a source term distributes the force over the particle volume. The study addresses particle-laden flow at constant liquid-flow rate. Two different algorithms of the interparticle contact show that the bridging phenomenon causing the blockage of the particles persists in the presence of the fluid flow. While the particles are in movement, there are frequent interparticle and particle-wall impacts and vigorous fluctuations of the net reaction force on the wall from the particle phase. There is close correlation between the component of this reaction oriented in the flow direction and the rate of change in the pressure drop across the constricted conduit.
Simulation of multispectral x-ray imaging scenarios by Wien shift optical spectroscopy
Authors: Brydegaard M. , Svanberg S.
Published: January 2010

The acquisition of multispectral x-ray images and the treatment of such data are essential for understanding many devices that we encounter in everyday life. Examples include computerized tomography in hospitals and scanners at airports. X-ray devices remain impractical for undergraduate laboratories because of their considerable cost and the risk of exposure to ionizing radiation. One way to acquire spectral information and thus constituent-discriminating data in x-ray imaging is to alter the spectral contents of the illuminating x-ray source, which can be achieved by changing the x-ray tube voltage and thus energetically displacing the bremsstrahlung. A similar effect occurs in the emission from a black-body radiator in the optical and infrared regions when altering the temperature. We illustrate how to simulate the x-ray scenario with a webcam and an ordinary light bulb. Insight into how chemical and physical information regarding objects can be obtained in multispectral imaging supported by multivariate analysis is gained.
Histone Eviction During Hypoxia
Authors: Gough Nancy R.
Published: January 2010

Histones are removed and then replaced at the promoter of the gene encoding endothelial nitric oxide synthase in response to hypoxia.
Recruiting the Components for Cell Division
Authors: Riddihough Guy
Published: January 2010

Phosphorylation of the chromatin protein histone H2A plays a critical role in chromosome segregation during cell division.
Cocaine Addiction and Histone Methylation
Authors: Stern Peter R.
Published: January 2010

Cocaine suppression of histone methylation in the nucleus accumbens mediates the drug’s ability to enhance reward.
Synaptic Activity of ATM and ATR
Authors: Gough Nancy R.
Published: January 2010

The kinases ATM and ATR associate with synaptic vesicle proteins and influence synaptic plasticity.
A Nod to Autophagy
Authors: Adler Elizabeth M.
Published: January 2010

Bacterial invasion elicits autophagy through Nod1 and Nod2 independently of RIP2 and the NF-κB signaling pathway.
Validation of the INNO-LiPA HBV DR Assay (Version 2) in Monitoring Hepatitis B Virus-Infected Patients Receiving Nucleoside Analog Treatment
Authors: Niesters H. G. M. , Zoulim F. , Pichoud C. , Buti M. , Shapiro F. , D'Heuvaert N. , Celis L. , Doutreloigne J. , Sablon E.
Published: January 2010

Hepatitis B virus (HBV) antiviral drug resistance mutations prevent successful outcome of treatment and lead to worsening of liver disease. Detection of its emergence permits opportune treatment with alternative drugs. Unfortunately, the use of newly approved antivirals, including adefovir dipivoxil, emtricitabine, and telbivudine, is also associated with the development of drug resistance, albeit to a lesser extent than the use of lamivudine. The objectives of this work were to assess the performance characteristics (sensitivity and accuracy) of an updated drug resistance test, the INNO-LiPA HBV DR v2, which includes detection of mutations associated with lamivudine, adefovir, emtricitabine, and telbivudine resistance, and to compare the results with consensus sequencing of serum samples from patients treated with HBV antivirals. Diagnostic sensitivity, defined as detection of a positive amplification line on the line probe assay (LiPA) strip, was 94.8% (95% confidence interval [CI], 89.7 to 97.9) after initial testing, increasing to 96.3% (95% CI, 91.6 to 98.8) after repeat test 1 and to 100% (95% CI, 97.3 to 100.0) after repeat test 2. In diagnostic accuracy determinations, full concordance was observed between sequencing and LiPA for 77.0% of the codons tested (620/805 codons [95% CI, 74.0 to 79.9]), whereas LiPA and sequencing were partially concordant 22% of the time (177/805 codons). In 167 out of 177 cases, LiPA detected a wild-type/mutant mixture whereas sequencing detected only one of the two results. Performance testing of the new LiPA test, the INNO-LiPA HBV DR v2, showed convincing diagnostic sensitivity and accuracy. The ability of the test to detect mixed infections and minority viral populations associated with resistance to the current generation of antivirals, including adefovir, emtricitabine, and telbivudine, makes it a useful tool for HBV therapy monitoring.
Surveillance and Correlation of Antibiotic Prescription and Resistance of Gram-Negative Bacteria in Singaporean Hospitals
Authors: Hsu Li-Yang , Tan Thean-Yen , Tam Vincent H. , Kwa Andrea , Fisher Dale Andrew , Koh Tse-Hsien
Published: January 2010

A surveillance study was performed in four Singapore public hospitals from 2006 to 2008 to determine the correlation between antibiotic prescription and Gram-negative bacterial antimicrobial resistance. Targeted organisms included ceftriaxone- and ciprofloxacin-resistantEscherichia coliandKlebsiella pneumoniae, as well as imipenem-resistantPseudomonas aeruginosaandAcinetobacterspp. Antibiotic prescription data were collated in the WHO anatomical therapeutic chemical (ATC)/defined daily dose (DDD) format, while antibiotic resistance was expressed as incidence density adjusted for total inpatient-days every quarter. Individual trends were determined by linear regression, while possible associations between antibiotic prescription and resistance were evaluated via cross-correlation analysis. Results over 3 years indicated significantly rising incidence densities of ceftriaxone- and ciprofloxacin-resistantE. coliand imipenem-resistantAcinetobacterspp. (blood isolates only). Antimicrobial-resistantKlebsiella pneumoniaerates declined. The prescription rates of piperacillin-tazobactam, ertapenem, meropenem, ciprofloxacin, and levofloxacin increased significantly, while imipenem and moxifloxacin prescription decreased. Cross-correlation analysis demonstrated possible associations between prescription of fluoroquinolones and ciprofloxacin-resistantE. coli(R2= 0.46), fluoroquinolones and ceftriaxone-resistantE. coli(R2= 0.47), and carbapenems and imipenem-resistantAcinetobacterspp. (R2= 0.48), all at zero time lag. Changes in meropenem prescription were associated with a similar trend in imipenem-resistantAcinetobacterblood isolates after a 3-month time lag. No correlation was found between cephalosporin use and resistance. In conclusion, our data demonstrated correlation between prescription of and Gram-negative bacterial resistance to several, but not all, key antimicrobial agents in Singapore hospitals. In areas where Gram-negative bacterial resistance is endemic and prescription of broad-spectrum antimicrobial agents is high, factors other than antimicrobial usage may be equally important in maintaining high resistance rates.
Amodiaquine Dosage and Tolerability for Intermittent Preventive Treatment To Prevent Malaria in Children
Authors: Cairns M. , Cisse B. , Sokhna C. , Cames C. , Simondon K. , Ba E. H. , Trape J.-F. , Gaye O. , Greenwood B. M. , Milligan P. J. M.
Published: January 2010

Sulfadoxine-pyrimethamine with amodiaquine (SP-AQ) is a highly efficacious regimen for intermittent preventive treatment to prevent malaria in children (IPTc), but the amodiaquine component is not always well tolerated. We determined the association between amodiaquine dosage by body weight and mild adverse events (AEs) and investigated whether alternative age-based regimens could improve dosing accuracy and tolerability, using data from two trials of IPTc in Senegal, one in which AQ dose was determined by age and the other in which it was determined by weight category. Both dosage strategies resulted in some children receiving AQ doses above the recommended therapeutic range. The odds of vomiting increased with increasing amodiaquine dosage. In one study, incidence of fever also increased with increasing dosage. Anthropometric data from 1,956 children were used to predict the dosing accuracy of existing and optimal alternative regimens. Logistic regression models describing the probability of AEs by dosage were used to predict the potential reductions in mild AEs for each regimen. Simple amendments to current AQ dosing schedules based on the child's age could substantially increase dosing accuracy and thus improve the tolerability of IPTc using SP-amodiaquine in situations where weighing the child is impractical.
In Vitro
Sensitivities of
Plasmodium falciparum
to Different Antimalarial Drugs in Uganda
Authors: Nsobya Samuel L. , Kiggundu Moses , Nanyunja Sarah , Joloba Moses , Greenhouse Bryan , Rosenthal Philip J.
Published: January 2010

The control of malaria is challenged by resistance of
Plasmodium falciparum
to multiple drugs. New combination regimens are now advocated for the treatment of uncomplicated falciparum malaria, but the extent of resistance to newer agents is incompletely understood. We measured the
in vitro
sensitivity of
P. falciparum
parasites cultured from children enrolled in a drug efficacy trial in Kampala, Uganda, from 2006 to 2008. Sensitivities were measured by comparing levels of histidine-rich protein-2 in parasites incubated with different concentrations of drugs with those in untreated controls. The cultured parasites exhibited a wide range of sensitivities to chloroquine (CQ); monodesethylamodiaquine (MDAQ), the major active metabolite of amodiaquine; and quinine (QN). Mean 50% inhibitory concentration (IC
50
) results were above standard cutoffs for resistance for CQ and MDAQ. Parasites were generally sensitive to dihydroartemisinin (DHA), lumefantrine (LM), and piperaquine (PQ). For CQ, MDAQ, and QN but not the other drugs, activities against individual strains were highly correlated. We also assessed known resistance-mediating polymorphisms in two putative transporters,
pfcrt
and
pfmdr1
. When parasites that were least and most sensitive to each drug were compared, the
pfmdr1
86Y mutation was significantly more common in parasites that were most resistant to CQ and MDAQ, and the
pfmdr1
D1246Y mutation was significantly more common in parasites that were most resistant to MDAQ and QN. In summary, we demonstrated in parasites from Kampala a range of sensitivities to older drugs; correlation of sensitivities to CQ, MDAQ, and QN; and good activity against nearly all strains for DHA, LM, and PQ.
Efficacy of Posaconazole as Treatment and Prophylaxis against
Fusarium solani
Authors: Wiederhold Nathan P. , Najvar Laura K. , Bocanegra Rosie , Graybill John R. , Patterson Thomas F.
Published: January 2010

Invasive fusariosis is a highly aggressive fungal infection associated with high mortality in heavily immunocompromised patients. Although posaconazole is efficacious as salvage therapy against infections caused by
Fusarium
species, concerns remain regarding this agent in the setting of reduced potency. To evaluate the efficacy of posaconazole as treatment or prophylaxis against invasive fusariosis caused by
Fusarium solani
, we utilized a neutropenic murine model of disseminated disease. ICR mice were administered escalating doses of posaconazole (6.25, 12.5, 25, or 50 mg/kg of body weight twice daily [BID]) by oral gavage beginning 2 days prior to inoculation in the prophylaxis studies or beginning 12 h after inoculation as treatment. Therapy was continued until day 9 postinoculation, and animals were monitored off therapy until day 15 for survival. Fungal burden was assessed as CFU in the kidneys. A clear dose-response relationship was observed, as the highest dose of posaconazole (50 mg/kg) was the most effective in prolonging survival and reducing tissue fungal burden both as prophylaxis and as treatment. This dose response was associated with high posaconazole serum concentrations as measured by bioassay. However, the extent of efficacy was also dependent on the infecting inoculum, as greater increases in survival and reductions in fungal burden were observed with the lower inocula tested. In this model high dosages of posaconazole were effective as treatment and prophylaxis against disseminated fusariosis caused by
F. solani
.
Rifampin Combination Therapy for Nonmycobacterial Infections
Authors: Forrest Graeme N. , Tamura Kimberly
Published: January 2010

The increasing emergence of antimicrobial-resistant organisms, especially methicillin-resistant
Staphylococcus
aureus
(MRSA), has resulted in the increased use of rifampin combination therapy. The data supporting rifampin combination therapy in nonmycobacterial infections are limited by a lack of significantly controlled clinical studies. Therefore, its current use is based upon in vitro or in vivo data or retrospective case series, all with major limitations. A prominent observation from this review is that rifampin combination therapy appears to have improved treatment outcomes in cases in which there is a low organism burden, such as biofilm infections, but is less effective when effective surgery to obtain source control is not performed. The clinical data support rifampin combination therapy for the treatment of prosthetic joint infections due to methicillin-sensitive
S. aureus
(MSSA) after extensive debridement and for the treatment of prosthetic heart valve infections due to coagulase-negative staphylococci. Importantly, rifampin-vancomycin combination therapy has not shown any benefit over vancomycin monotherapy against MRSA infections either clinically or experimentally. Rifampin combination therapy with daptomycin, fusidic acid, and linezolid needs further exploration for these severe MRSA infections. Lastly, an assessment of the risk-benefits is needed before the addition of rifampin to other antimicrobials is considered to avoid drug interactions or other drug toxicities.
Reduced Vancomycin Susceptibility inStaphylococcus aureus, Including Vancomycin-Intermediate and Heterogeneous Vancomycin-Intermediate Strains: Resistance Mechanisms, Laboratory Detection, and Clinical Implications
Authors: Howden Benjamin P. , Davies John K. , Johnson Paul D. R. , Stinear Timothy P. , Grayson M. Lindsay
Published: January 2010

The emergence of vancomycin-intermediateStaphylococcus aureus(VISA) and heterogeneous vancomycin-intermediateStaphylococcus aureus(hVISA) over the past decade has provided a challenge to diagnostic microbiologists to detect these strains, clinicians treating patients with infections due to these strains, and researchers attempting to understand the resistance mechanisms. Recent data show that these strains have been detected globally and in many cases are associated with glycopeptide treatment failure; however, more rigorous clinical studies are required to clearly define the contribution of hVISA to glycopeptide treatment outcomes. It is now becoming clear that sequential point mutations in key global regulatory genes contribute to the hVISA and VISA phenotypes, which are associated predominately with cell wall thickening and restricted vancomycin access to its site of activity in the division septum; however, the phenotypic features of these strains can vary because the mutations leading to resistance can vary. Interestingly, changes in the staphylococcal surface and expression ofagrare likely to impact host-pathogen interactions in hVISA and VISA infections. Given the subtleties of vancomycin susceptibility testing againstS. aureus, it is imperative that diagnostic laboratories use well-standardized methods and have a framework for detecting reduced vancomycin susceptibility inS. aureus.
Downregulation of PU.1 Leads to Decreased Expression of Dectin-1 in Alveolar Macrophages during
Pneumocystis
Pneumonia
Authors: Zhang Chen , Wang Shao-Hung , Liao Chung-Ping , Shao Shoujin , Lasbury Mark E. , Durant Pamela J. , Lee Chao-Hung
Published: January 2010

Dectin-1 is an important macrophage phagocytic receptor recognizing fungal β-glucans. In this study, the mRNA levels of the Dectin-1 gene were found to be decreased by 61% in alveolar macrophages (AMs) from
Pneumocystis
-infected mice. The expression of Dectin-1 protein on the surface of these cells was also significantly decreased. By fluorescence
in situ
hybridization, mRNA expression levels of the transcription factor PU.1 were also found to be significantly reduced in AMs from
Pneumocystis
-infected mice. Electrophoretic mobility shift assay showed that PU.1 protein bound Dectin-1 gene promoter. With a luciferase reporter gene driven by the Dectin-1 gene promoter, the expression of the PU.1 gene in NIH 3T3 cells was found to enhance the luciferase activity in a dose-dependent manner. PU.1 expression knockdown by small interfering RNA (siRNA) caused a 63% decrease in Dectin-1 mRNA level and 40% decrease in protein level in AMs. Results of this study indicate that downregulation of PU.1 during
Pneumocystis
pneumonia leads to decreased expression of Dectin-1 in AMs.
Identification of a c-di-GMP-Regulated Polysaccharide Locus Governing Stress Resistance and Biofilm and Rugose Colony Formation in
Vibrio vulnificus
Authors: Guo Yunzhi , Rowe-Magnus Dean A.
Published: January 2010

As an etiological agent of bacterial sepsis and wound infections,
Vibrio vulnificus
is unique among the
Vibrionaceae
. Its continued environmental persistence and transmission are bolstered by its ability to colonize shellfish, form biofilms on various marine biotic surfaces, and generate a morphologically and physiologically distinct rugose (R) variant that yields profuse biofilms. Here, we identify a c-di-GMP-regulated locus (
brp
, for
b
iofilm and
r
ugose
p
olysaccharide) and two transcription factors (BrpR and BrpT) that regulate these physiological responses. Disruption of glycosyltransferases within the locus or either regulator abated the inducing effect of c-di-GMP on biofilm formation, rugosity, and stress resistance. The same lesions, or depletion of intracellular c-di-GMP levels, abrogated these phenotypes in the R variant. The parental and
brp
mutant strains formed only scant monolayers on glass surfaces and oyster shells, and although the R variant formed expansive biofilms, these were of limited depth. Dramatic vertical expansion of the biofilm structure was observed in the parental strain and R variant, but not the
brp
mutants, when intracellular c-di-GMP levels were elevated. Hence, the
brp
-encoded polysaccharide is important for surface colonization and stress resistance in
V. vulnificus
, and its expression may control how the bacteria switch from a planktonic lifestyle to colonizing shellfish to invading human tissue.
Anaplasma marginaleType IV Secretion System Proteins VirB2, VirB7, VirB11, and VirD4 Are Immunogenic Components of a Protective Bacterial Membrane Vaccine
Authors: Sutten Eric L. , Norimine Junzo , Beare Paul A. , Heinzen Robert A. , Lopez Job E. , Morse Kaitlyn , Brayton Kelly A. , Gillespie Joseph J. , Brown Wendy C.
Published: January 2010

Anaplasmaand relatedEhrlichiaspp. are important tick-borne, Gram-negative bacterial pathogens of livestock and humans that cause acute infection and disease and can persist. Immunization of cattle with anAnaplasma marginalefraction enriched in outer membranes (OM) can provide complete protection against disease and persistent infection. Serological responses of OM vaccinees to the OM proteome previously identified over 20 antigenic proteins, including three type IV secretion system (T4SS) proteins, VirB9-1, VirB9-2, and VirB10. Subsequent studies showed that these three proteins also stimulated CD4+T-cell responses in OM vaccinees. The T4SS, composed of a complex of proteins spanning the inner and outer membranes of certain bacteria, is an important virulence factor but is relatively unexplored as a vaccine target. The goal of this study was to determine if additional T4SS proteins are immunogenic for animals immunized with the protective OM fraction ofA. marginale.T4SS proteins expressed byin vitrotranscription and translation were screened for stimulating proliferation of T cells from OM vaccinees, and immunogenic proteins were expressed as recombinant proteins inEscherichia coliand their immunogenicity was verified. VirB2, a putative VirB7, VirB11, and VirD4 were immunogenic for OM vaccinees expressing several common major histocompatibility complex (MHC) class II haplotypes. VirB2 is encoded by multiple genes that share a conserved central region, and epitope mapping revealed T-cell epitopes in this region. The discovery of novel immunogenic T4SS proteins recognized by outbred individuals with common MHC haplotypes further justifies evaluating the T4SS as a potential vaccine candidate for pathogenic bacteria.
Natural Variability of
In Vitro
Adherence to Fibrinogen and Fibronectin Does Not Correlate with
In Vivo
Infectivity of
Staphylococcus aureus
Authors: Ythier Mathilde , Entenza Jose M. , Bille Jacques , Vandenesch François , Bes Michèle , Moreillon Philippe , Sakwinska Olga
Published: January 2010

Adherence to fibrinogen and fibronectin plays a crucial role in
Staphylococcus aureus
experimental endocarditis. Previous genetic studies have shown that infection and carriage isolates do not systematically differ in their virulence-related genes, including genes conferring adherence, such as
clfA
and
fnbA
. We set out to determine the range of adherence phenotypes in carriage isolates of
S. aureus
, to compare the adherence of these isolates to the adherence of infection isolates, and to determine the relationship between adherence and infectivity in a rat model of experimental endocarditis. A total of 133 healthy carriage isolates were screened for
in vitro
adherence to fibrinogen and fibronectin, and 30 isolates were randomly chosen for further investigation. These 30 isolates were compared to 30 infective endocarditis isolates and 30 blood culture isolates. The infectivities of the carriage isolates, which displayed either extremely low or high adherence to fibrinogen and fibronectin, were tested using a rat model of experimental endocarditis. The levels of adherence to both fibrinogen and fibronectin were very similar for isolates from healthy carriers and members of the two groups of infection isolates. All three groups of isolates showed a wide range of adherence to fibrinogen and fibronectin. Moreover, the carriage isolates that showed minimal adherence and the carriage isolates that showed strong adherence had the same infectivity in experimental endocarditis. Adherence was proven to be important for pathogenesis in experimental endocarditis, but even the least adherent carriage strains had the ability to induce infection. We discuss the roles of differential gene expression, human host factors, and gene redundancy in resolving this apparent paradox.
A nurse-led palpitations clinic: a 2-year experience
Authors: Scott P A , Appleford P , Farrell T G , Andrews N P
Published: January 2010

Objective

To investigate the role of a nurse-led clinic in the assessment of patients with palpitations.

Design

Prospective descriptive study.

Setting

Nurse-led palpitations clinic in a UK district general hospital.

Participants

Patients referred from primary care or the emergency department with palpitations.

Methods

Referral letters were screened, and only patients without high-risk features or a documented arrhythmia were diverted to the palpitations clinic. Patients were evaluated using a protocol. All patients had an ECG and ambulatory ECG monitoring and were discussed with a cardiologist.

Results

Over 15 months, 389 patients were seen. The mean time from referral to assessment was 38 days (range 3–142). The most common diagnoses were symptomatic extrasystoles (42%) and sinus rhythm (22%). Significant arrhythmias were diagnosed in 15% (atrial fibrillation/flutter, 8%; supraventricular arrhythmias, 6%). Only 52 (13%) were subsequently referred to a cardiologist, including 20 with high-risk features. These 20 patients waited on average an additional 70 days to be seen by a cardiologist compared with patients who were seen directly by a cardiologist after referral by primary care or the emergency department.

Conclusions

For low-risk patients, a nurse-led palpitations clinic may provide a viable alternative to the traditional cardiology outpatient service. Despite attempts to exclude them, some high-risk patients were seen. This was unforeseen and led to a clinically important delay in their appropriate assessment. Hence, before adopting a nurse-led palpitations service, a rigorous pathway for the early assessment of high-risk patients needs to be agreed.
Vitamin D deficiency and type 2 diabetes
Authors: Ozfirat Zehra , Chowdhury Tahseen A
Published: January 2010

Type 2 diabetes is a major public health problem, accounting for significant premature mortality and morbidity. The growth in prevalence of the condition appears to be closely linked with obesity. Over the last 5 years, a number of large observational studies have suggested an association between the onset of type 2 diabetes and Vitamin D deficiency. Vitamin D has important effects on insulin action, and may impact on a number of pathways which may be of importance in the development of type 2 diabetes. This article reviews the evidence linking Vitamin D deficiency in the pathogenesis of type 2 diabetes, and suggests areas for urgent further research to determine whether Vitamin D replacement has a role in the prevention of type 2 diabetes.
Circadian fluctuations in the efficacy of thrombolysis with streptokinase
Authors: Goldhammer E , Kharash L , Abinader E G
Published: January 2010

This study was designed to investigate possible diurnal fluctuations in the efficacy of thrombolysis with streptokinase and whether they follow the circadian periodicity which has already been well documented for the time of onset of acute myocardial infarction, transient myocardial ischaemia, sudden cardiac death, thrombotic stroke, and for the efficacy of thrombolysis with tissue-type plasminogen and urokinase. A total of 156 consecutive patients treated with streptokinase were studied retrospectively; success or failure of thrombolysis was determined according to accepted clinical and angiographic criteria. A definite time peak for successful thrombolysis could be detected at the late afternoon and early evening hours; between 16.00 and 20.00 h, 30.2% of all successful thrombolysis cases were observed compared with 7.0% between 20.00 and 24.00 (p<0.05) or 10.5% between 00.00 and 04.00 (p<0.05). Between 16.00 and 20.00 h, 75.8% of treated patients had successful thrombolysis compared to 15.2% of failed treatments and 9% equivocal results (p<0.001). Multiple regression analysis showed that the independent factor with the major impact on successful reperfusion was the actual time of thrombolysis (p=0.037), followed by the time delay from pain onset to streptokinase administration (p=0.020), while age and gender had much lesser impact (p=0.328 and 0.215, respectively) and the individual risk factors even less. These findings may have several clinical implications; dose adjustment for the time of day may be required, with higher doses during morning hours, or preference for primary coronary angioplasty in order to avoid the increase in bleeding complications related to higher doses of thrombolytic agents.
Verrucous carcinoma of the female breast
Authors: Munro N A , Smith C , Purushotham A D
Published: January 2010

Verrucous carcinoma is a rare skin malignancy of squamous cell origin. It is characterised by negligible cellular atypia and a low mitotic rate. These are reflected in slow locally invasive behaviour and very infrequent metastatic spread. The tumour is also recognised in oral and anogenital sites. Cutaneous lesions present most commonly on the sole of the foot. We report a unique case occurring in the female breast.
Concordance of primary generalised epilepsy and carbamazepine hypersensitivity in monozygotic twins
Authors: Edwards S G M , Hubbard V , Aylett S , Wren D
Published: January 2010

In this paper we describe the previously unreported phenomenon of a carbamazepine-induced mucocutaneous syndrome in identical twins. These twins had developed primary generalised epilepsy within 2 months of each other.
How cigarette design can affect youth initiation into smoking: Camel cigarettes 1983-93
Authors: Wayne G Ferris , Connolly G N
Published: January 2010

Context: Internal industry documents may shed light on how cigarettes are designed to promote youth smoking.

Objective: To determine changes in the design of Camel cigarettes in the period surrounding the “Smooth Character” advertising campaign and to assess the impact of these changes on youth smoking.

Data sources: Internal documents made available through the document website maintained by RJ Reynolds, manufacturer of Camel cigarettes.

Study selection: Electronic searches using keywords to identify relevant data.

Data extraction: A web based index search of documents targeting “smoothness” or “harshness” and “younger adult smokers” (“YAS”) or “first usual brand younger adult smokers” (“FUBYAS”) in the 10 year period surrounding the introduction of the “Smooth Character” campaign was used to identify Camel related product design research projects. A snowball methodology was used: initial documents were identified by focusing on key words, codes, researchers, committees, meetings, and gaps in overall chronology; a second set of documents was culled from these initial documents, and so on.

Data synthesis: Product design research led to the introduction of redesigned Camel cigarettes targeted to younger adult males coinciding with the “Smooth Character” campaign. Further refinements in Camel cigarettes during the following five year period continued to emphasise the smoothness of the cigarette, utilising additives and blends which reduced throat irritation but increased or retained nicotine impact.

Conclusions: Industry competition for market share among younger adult smokers may have contributed to the reversal of a decline in youth smoking rates during the late 1980s through development of products which were more appealing to youth smokers and which aided in initiation by reducing harshness and irritation.
Cigarette filter ventilation is a defective design because of misleading taste, bigger puffs, and blocked vents
Authors: Kozlowski L T , O'Connor R J
Published: January 2010

Objective: To review tobacco industry documents on filter ventilation in light of published studies and to explore the role of filter ventilation in the design of cigarettes that deliver higher smoke yields to smokers than would be expected from standard machine smoked tests (Federal Trade Commission (FTC), International Organization for Standardization (ISO)).

Data sources: Searched from November 1999 to November 2000 internet databases of industry documents (www.pmdocs.com,www.rjrtdocs.com,www.lorillarddocs.com,www.bw.aalatg.com,www.cdc.gov/tobacco/industrydocs,www.tobaccodocuments.org,www.tobaccopapers.org,www.hlth.gov.bc.ca/Guildford,www.cctc.ca/ncth/Guildford,www.cctc.ca/ncth/Guildford2) for documents related to filter ventilation. Documents found dated from 1955 through 1994.

Study selection: Those documents judged to contain the most relevant information or data on filter ventilation related to cigarette taste and compensatory smoking, while also trying to avoid redundancy from various documents deriving from the same underlying data.

Data synthesis: Filter ventilation is a crucial design feature creating three main problems for lower tar cigarettes as measured by official smoking machine testing. Firstly, it misleadingly makes cigarettes taste lighter and milder, and, therefore, they appear less dangerous to smokers. Secondly, it promotes compensation mainly by facilitating the taking of larger puffs. Thirdly, for very heavily ventilated cigarettes (that is, > 65% filter air dilution), behavioural blocking of vents with lips or fingers is an additional contributor to compensatory smoking. These three effects are found in industry research as well as published research.

Conclusions: Filter ventilation is a dangerous, defective technology that should be abandoned in less hazardous nicotine delivery systems. Health interested groups should test cigarettes in a way that reflects compensatory smoking. Lower tar (vented filter) cigarettes should be actively countermarketed.
Marketing to America's youth: evidence from corporate documents
Authors: Cummings K M , Morley C P , Horan J K , Steger C , Leavell N-R
Published: January 2010

Objective: To evaluate the claim that the tobacco industry does not market its products to youth.

Design: The data for this study come from tobacco industry documents collected from the tobacco industry's document websites, presently linked athttp://www.tobaccoarchives.com. The websites were searched using “request for production” (RFP) codes, specified keyword searches, and serendipitous terms identified in document citations found with RFP and keyword searches.

Results: Industry documents show that the cigarette manufacturers carefully monitored the smoking habits of teenagers over the past several decades. Candid quotes from industry executives refer to youth as a source of sales and as fundamental to the survival of the tobacco industry. The documents reveal that the features of cigarette brands (that is, use of filters, low tar, bland taste, etc), packaging (that is, size, colour and design), and advertising (that is, media placements and themes and imagery) were developed specifically to appeal to new smokers (that is, teenagers). Evidence also indicates that relevant youth oriented marketing documents may have been destroyed and that the language used in some of the more recent documents may have been sanitised to cover up efforts to market to youth.

Conclusions: The tobacco industry's internal documents reveal an undeniable interest in marketing cigarettes to underage smokers. The industry's marketing approaches run counter to and predicate methods for tobacco prevention: (1) keep the price of the product high; (2) keep product placements and advertising away from schools and other areas with a high volume of youth traffic; (3) make cigarette advertising (that is, themes and visual images) unappealing to youth; (4) make product packaging unappealing to youth; and (5) design the product so it is not easy to inhale.