bluuebunny/crossref_metadata_2025 huggingface dataset:
Oxidized LDL/CD36 interaction induces loss of cell polarity and inhibits macrophage locomotion
Authors: Park Young Mi , Drazba Judith A. , Vasanji Amit , Egelhoff Thomas , Febbraio Maria , Silverstein Roy L.
Published: June 2012

Cell polarization is essential for migration and the exploratory function of leukocytes. However, the mechanism by which cells maintain polarity or how cells revert to the immobilized state by gaining cellular symmetry is not clear. Previously we showed that interaction between oxidized low-density lipoprotein (oxLDL) and CD36 inhibits macrophage migration; in the current study we tested the hypothesis that oxLDL/CD36-induced inhibition of migration is the result of intracellular signals that regulate cell polarity. Live cell imaging of macrophages showed that oxLDL actuated retraction of macrophage front end lamellipodia and induced loss of cell polarity. Cd36 null and macrophages null for Vav, a guanine nucleotide exchange factor (GEF), did not show this effect. These findings were caused by Rac-mediated inhibition of nonmuscle myosin II, a cell polarity determinant. OxLDL induced dephosphorylation of myosin regulatory light chain (MRLC) by increasing the activity of Rac. Six-thioguanine triphosphate (6-thio-GTP), which inhibits Vav-mediated activation of Rac, abrogated the effect of oxLDL. Activation of the Vav-Rac-myosin II pathway by oxidant stress may induce trapping of macrophages at sites of chronic inflammation such as atherosclerotic plaque.
Molecular chaperones and stress-inducible protein-sorting factors coordinate the spatiotemporal distribution of protein aggregates
Authors: Malinovska Liliana , Kroschwald Sonja , Munder Matthias C. , Richter Doris , Alberti Simon
Published: June 2012

Acute stress causes a rapid redistribution of protein quality control components and aggregation-prone proteins to diverse subcellular compartments. How these remarkable changes come about is not well understood. Using a phenotypic reporter for a synthetic yeast prion, we identified two protein-sorting factors of the Hook family, termed Btn2 and Cur1, as key regulators of spatial protein quality control in Saccharomyces cerevisiae. Btn2 and Cur1 are undetectable under normal growth conditions but accumulate in stressed cells due to increased gene expression and reduced proteasomal turnover. Newly synthesized Btn2 can associate with the small heat shock protein Hsp42 to promote the sorting of misfolded proteins to a peripheral protein deposition site. Alternatively, Btn2 can bind to the chaperone Sis1 to facilitate the targeting of misfolded proteins to a juxtanuclear compartment. Protein redistribution by Btn2 is accompanied by a gradual depletion of Sis1 from the cytosol, which is mediated by the sorting factor Cur1. On the basis of these findings, we propose a dynamic model that explains the subcellular distribution of misfolded proteins as a function of the cytosolic concentrations of molecular chaperones and protein-sorting factors. Our model suggests that protein aggregation is not a haphazard process but rather an orchestrated cellular response that adjusts the flux of misfolded proteins to the capacities of the protein quality control system.
Efficacy of Variable Tetraconazole Rates Against Cercospora beticola Isolates with Differing In Vitro Sensitivities to DMI Fungicides
Authors: Bolton Melvin D. , Rivera-Varas Viviana , del Río Mendoza Luis E. , Khan Mohamed F. R. , Secor Gary A.
Published: June 2012

Cercospora leaf spot (CLS) of sugar beet is caused by the fungus Cercospora beticola. CLS management practices include the application of the sterol demethylation inhibitor (DMI) fungicides tetraconazole, difenoconazole, and prothioconazole. Evaluating resistance to DMIs is a major focus for CLS fungicide resistance management. Isolates were collected in 1997 and 1998 (baseline sensitivity to tetraconazole, prothioconazole, or difenoconazole) and 2007 through 2010 from the major sugar-beet-growing regions of Minnesota and North Dakota and assessed for in vitro sensitivity to two or three DMI fungicides. Most (47%) isolates collected in 1997–98 exhibited 50% effective concentration (EC50) values for tetraconazole of <0.01 μg ml–1, whereas no isolates could be found in this EC50 range in 2010. Since 2007, annual median and mean tetraconazole EC50 values have generally been increasing, and the frequency of isolates with EC50 values >0.11 μg ml–1 increased from 2008 to 2010. In contrast, the frequency of isolates with EC50 values for prothioconazole of >1.0 μg ml–1 has been decreasing since 2007. Annual median difenoconazole EC50 values appears to be stable, although annual mean EC50 values generally have been increasing for this fungicide. Although EC50 values are important for gauging fungicide sensitivity trends, a rigorous comparison of the relationship between in vitro EC50 values and loss of fungicide efficacy in planta has not been conducted for C. beticola. To explore this, 12 isolates exhibiting a wide range of tetraconazole EC50 values were inoculated to sugar beet but no tetraconazole was applied. No relationship was found between isolate EC50 value and disease severity. To assess whether EC50 values are related to fungicide efficacy in planta, sugar beet plants were sprayed with various dilutions of Eminent, the commercial formulation of tetraconazole, and subsequently inoculated with isolates that exhibited very low, medium, or high tetraconazole EC50 values. The high EC50 isolate caused significantly more disease than isolates with medium or very low EC50 values at the field application rate and most reduced rates. Because in vitro sensitivity testing is typically carried out with the active ingredient of the commercial fungicide, we investigated whether loss of disease control was the same for tetraconazole as for the commercial product Eminent. The high EC50 isolate caused more disease on plants treated with tetraconazole than Eminent but disease severity was not different between plants inoculated with the very low EC50 isolate.
Characterizing Heterogeneity of Disease Incidence in a Spatial Hierarchy: A Case Study from a Decade of Observations of Fusarium Head Blight of Wheat
Authors: Kriss A. B. , Paul P. A. , Madden L. V.
Published: June 2012

A multilevel analysis of heterogeneity of disease incidence was conducted based on observations of Fusarium head blight (caused by Fusarium graminearum) in Ohio during the 2002–11 growing seasons. Sampling consisted of counting the number of diseased and healthy wheat spikes per 0.3 m of row at 10 sites (about 30 m apart) in a total of 67 to 159 sampled fields in 12 to 32 sampled counties per year. Incidence was then determined as the proportion of diseased spikes at each site. Spatial heterogeneity of incidence among counties, fields within counties, and sites within fields and counties was characterized by fitting a generalized linear mixed model to the data, using a complementary log-log link function, with the assumption that the disease status of spikes was binomially distributed conditional on the effects of county, field, and site. Based on the estimated variance terms, there was highly significant spatial heterogeneity among counties and among fields within counties each year; magnitude of the estimated variances was similar for counties and fields. The lowest level of heterogeneity was among sites within fields, and the site variance was either 0 or not significantly greater than 0 in 3 of the 10 years. Based on the variances, the intracluster correlation of disease status of spikes within sites indicated that spikes from the same site were somewhat more likely to share the same disease status relative to spikes from other sites, fields, or counties. The estimated best linear unbiased predictor (EBLUP) for each county was determined, showing large differences across the state in disease incidence (as represented by the link function of the estimated probability that a spike was diseased) but no consistency between years for the different counties. The effects of geographical location, corn and wheat acreage per county, and environmental conditions on the EBLUP for each county were not significant in the majority of years.
Aversive and Reinforcing Opioid Effects
Authors: Angst Martin S. , Lazzeroni Laura C. , Phillips Nicholas G. , Drover David R. , Tingle Martha , Ray Amrita , Swan Gary E. , Clark J. David
Published: June 2012

Background

The clinical utility of opioids is limited by adverse drug effects including respiratory depression, sedation, nausea, and pruritus. In addition, abuse of prescription opioids is problematic. Gaining a better understanding of the genetic and environmental mechanisms contributing to an individual's susceptibility to adverse opioid effects is essential to identify patients at risk.

Methods

A classic twin study paradigm provided estimates for the genetic and familial (genetic and/or shared environment) contribution to acute adverse and affective opioid responses, all secondary outcomes of a larger dataset. One hundred twenty-one twin pairs were recruited in a single occasion, randomized, double-blind, and placebo-controlled study. The μ-opioid receptor agonist alfentanil and saline placebo were administered as target-controlled infusions under carefully monitored laboratory conditions. Measured outcomes included respiratory depression, sedation, nausea, pruritus, drug liking, and drug disliking. Demographic information was collected, and aspects of mood and sleep were evaluated.

Results

Significant heritability was detected for respiratory depression (30%), nausea (59%), and drug disliking (36%). Significant familial effects were detected for sedation (29%), pruritus (38%), dizziness (32%), and drug liking (26%). Significant covariates included age, sex, race, ethnicity, education, mood, and depression. Covariates affected sedation, pruritus, drug liking and disliking, and dizziness.

Conclusions

This study demonstrates that large-scale efforts to collect quantitative and well-defined opioid response data are not only feasible but also produce data that are suitable for genetic analysis. Genetic, environmental, and demographic factors work together to control adverse and reinforcing opioid responses, but contribute differently to specific responses.
Impact of surrounding tissue on conductance measurement of coronary and peripheral lumen area
Authors: Won Choi Hyo , Jansen Benjamin , Zhang Zhen-Du , Kassab Ghassan S.
Published: June 2012

Parallel conductance (electric current flow through surrounding tissue) is an important determinant of accurate measurements of arterial lumen diameter, using the conductance method. The present study is focused on the role of non-uniform geometrical/electrical configurations of surrounding tissue, which are a primary source of electric current leakage. Computational models were constructed to simulate the conductance catheter measurement with two different excitation electrodes spacings (i.e. 12 and 20 mm for coronary and peripheral sizing, respectively) for different vessel–tissue configurations: (i) blood vessel fully embedded in muscle tissue, (ii) blood vessel superficially embedded in muscle tissue, and (iii) blood vessel superficially embedded in muscle tissue with fat covering half of the arterial vessel (anterior portion). The simulations suggest that the parallel conductance and accuracy of measurement is dependent on the inhomogeneous/anisotropic configuration of surrounding tissue, including the asymmetric dimension and anisotropy in electrical conductivity of surrounding tissue. Specifically, the measurement was shown to be accurate as long as the vessel was superficial, regardless of the considerable total surrounding tissue dimension for coronary or peripheral arteries. Moreover, it was shown that the unfavourable impact of parallel conductance on the accuracy of conductance catheter measurement is decreased by the combination of a lower transverse electrical conductivity of surrounding muscle tissue, a smaller electrode spacing and a larger lumen diameter. The present findings confirm that the conductance catheter technique provides an accurate platform for sizing of clinically relevant (i.e. superficial and diseased) arteries.
Social encounter networks: collective properties and disease transmission
Authors: Danon Leon , House Thomas A. , Read Jonathan M. , Keeling Matt J.
Published: June 2012

A fundamental challenge of modern infectious disease epidemiology is to quantify the networks of social and physical contacts through which transmission can occur. Understanding the collective properties of these interactions is critical for both accurate prediction of the spread of infection and determining optimal control measures. However, even the basic properties of such networks are poorly quantified, forcing predictions to be made based on strong assumptions concerning network structure. Here, we report on the results of a large-scale survey of social encounters mainly conducted in Great Britain. First, we characterize the distribution of contacts, which possesses a lognormal body and a power-law tail with an exponent of −2.45; we provide a plausible mechanistic model that captures this form. Analysis of the high level of local clustering of contacts reveals additional structure within the network, implying that social contacts are degree assortative. Finally, we describe the epidemiological implications of this local network structure: these contradict the usual predictions from networks with heavy-tailed degree distributions and contain public-health messages about control. Our findings help us to determine the types of realistic network structure that should be assumed in future population level studies of infection transmission, leading to better interpretations of epidemiological data and more appropriate policy decisions.
Optical spectral singularities and coherent perfect absorption in a two-layer spherical medium
Authors: Mostafazadeh Ali , Sarisaman Mustafa
Published: June 2012

An optical spectral singularity is a zero-width resonance that corresponds to lasing at threshold gain. Its time-reversal causes coherent perfect absorption of light and forms the theoretical basis of antilasing. In this article, we explore optical spectral singularities of a two-layer spherical medium. In particular, we examine the cases that a gain medium is coated by a thin layer of high-refractive index glass and a spherical glass covered by a layer of gain material. In the former case, the coating reduces the minimum radius required for exciting spectral singularities and gives rise to the formation of clusters of spectral singularities separated by wide spectral gaps. In the latter case, the coating leads to a doubling of the number of spectral singularities.
Moving boundary problems governed by anomalous diffusion
Authors: Vogl Christopher J. , Miksis Michael J. , Davis Stephen H.
Published: June 2012

Anomalous diffusion can be characterized by a mean-squared displacement 〈
x
2
(
t
)〉 that is proportional to
t

α

where
α
≠1. A class of one-dimensional moving boundary problems is investigated that involves one or more regions governed by anomalous diffusion, specifically subdiffusion (
α
<1). A novel numerical method is developed to handle the moving interface as well as the singular history kernel of subdiffusion. Two moving boundary problems are solved: the first involves a subdiffusion region to the one side of an interface and a classical diffusion region to the other. The interface will display non-monotone behaviour. The subdiffusion region will always initially advance until a given time, after which it will always recede. The second problem involves subdiffusion regions to both sides of an interface. The interface here also reverses direction after a given time, with the more subdiffusive region initially advancing and then receding.
Sibling rivalry: training effects, emergence of dominance and incomplete control
Authors: Benhaiem Sarah , Hofer Heribert , Kramer-Schadt Stephanie , Brunner Edgar , East Marion L.
Published: June 2012

Within-brood or -litter dominance provides fitness-related benefits if dominant siblings selfishly skew access to food provided by parents in their favour. Models of facultative siblicide assume that dominants exert complete control over their subordinate sibling's access to food and that control is maintained, irrespective of the subordinate's hunger level. By contrast, a recent functional hypothesis suggests that subordinates should contest access to food when the cost of not doing so is high. Here, we show that within spotted hyena (Crocuta crocuta) twin litters, dominants most effectively skew access to maternal milk in their favour when their aggression prompts a highly submissive response. When hungry, subordinates were less submissive in response to aggression, thereby decreasing lost suckling time and increasing suckling time lost by dominants. In a species where adult females socially dominate adult males, juvenile females were more often dominant than males in mixed-sex litters, and subordinate sisters used more effective counter-tactics against dominant brothers than subordinate brothers against dominant sisters. Our results provide, to our knowledge, the first evidence in a mammal that dominant offspring in twin litters do not exert complete control over their sibling's access to resources (milk), and that sibling dominance relationships are influenced by sibling sex and training effects.
Environmental change exposes beneficial epistatic interactions in a catalytic RNA
Authors: Hayden Eric J. , Wagner Andreas
Published: June 2012

Natural selection drives populations of individuals towards local peaks in a fitness landscape. These peaks are created by the interactions between individual mutations. Fitness landscapes may change as an environment changes. In a previous contribution, we discovered a variant of the
Azoarcus
group I ribozyme that represents a local peak in the RNA fitness landscape. The genotype at this peak is distinguished from the wild-type by four point mutations. We here report ribozyme fitness data derived from constructing all possible combinations of these point mutations. We find that these mutations interact epistatically. Importantly, we show that these epistatic interactions change qualitatively in the three different environments that we studied. We find examples where the relative fitness of a ribozyme can change from neutral or negative in one environment, to positive in another. We also show that the fitness effect of a specific GC–AU base pair switch is dependent on both the environment and the genetic context. Moreover, the mutations that we study improve activity at the cost of decreased structural stability. Environmental change is ubiquitous in nature. Our results suggest that such change can facilitate adaptive evolution by exposing new peaks of a fitness landscape. They highlight a prominent role for genotype–environment interactions in doing so.
Seasonal stress drives predictable changes in inbreeding depression in field-tested captive populations of
Drosophila melanogaster
Authors: Enders Laramy S. , Nunney Leonard
Published: June 2012

Recent meta-analyses conducted across a broad range of taxa have demonstrated a strong linear relationship between the change in magnitude of inbreeding depression under stress and stress level, measured as fitness loss in outbred individuals. This suggests that a general underlying response may link stress and inbreeding depression. However, this relationship is based primarily on laboratory data, and it is unknown whether natural environments with multiple stressors and fluctuating stress levels alter how stress affects inbreeding depression. To test whether the same pattern persists in the field, we investigated the effect of seasonal variation on stress level and inbreeding depression in a 3-year field study measuring the productivity of captive populations of inbred and outbred
Drosophila melanogaster
. We found cold winter temperatures were most stressful and induced the greatest inbreeding depression. Furthermore, these data, collected under natural field conditions, conformed to the same predictive linear relationship seen in
Drosophila
laboratory studies, with inbreeding depression increasing by 0.17 lethal equivalents for every 10 per cent increase in stress level. Our results suggest that under natural conditions stress level is a primary determinant of the magnitude of inbreeding depression and should be considered when assessing extinction vulnerability in small populations.
MUT-16 promotes formation of perinuclear Mutator foci required for RNA silencing in the C. elegans germline
Authors: Phillips Carolyn M. , Montgomery Taiowa A. , Breen Peter C. , Ruvkun Gary
Published: June 2012

RNA silencing can be initiated by endogenous or exogenously delivered siRNAs. In Caenorhabditis elegans, RNA silencing guided by primary siRNAs is inefficient and therefore requires an siRNA amplification step involving RNA-dependent RNA polymerases (RdRPs). Many factors involved in RNA silencing localize to protein- and RNA-rich nuclear pore-associated P granules in the germline, where they are thought to surveil mRNAs as they exit the nucleus. Mutator class genes are required for siRNA-mediated RNA silencing in both germline and somatic cells, but their specific roles and relationship to other siRNA factors are unclear. Here we show that each of the six mutator proteins localizes to punctate foci at the periphery of germline nuclei. The Mutator foci are adjacent to P granules but are not dependent on core P-granule components or other RNAi pathway factors for their formation or stability. The glutamine/asparagine (Q/N)-rich protein MUT-16 is specifically required for the formation of a protein complex containing the mutator proteins, and in its absence, Mutator foci fail to form at the nuclear periphery. The RdRP RRF-1 colocalizes with MUT-16 at Mutator foci, suggesting a role for Mutator foci in siRNA amplification. Furthermore, we demonstrate that genes that yield high levels of siRNAs, indicative of multiple rounds of siRNA amplification, are disproportionally affected in mut-16 mutants compared with genes that yield low levels of siRNAs. We propose that the mutator proteins and RRF-1 constitute an RNA processing compartment required for siRNA amplification and RNA silencing.
Programmed cell death 6, a novel p53‐responsive gene, targets to the nucleus in the apoptotic response to DNA damage
Authors: Suzuki Kazuho , Dashzeveg Nurmaa , Lu Zheng‐Guang , Taira Naoe , Miki Yoshio , Yoshida Kiyotsugu
Published: June 2012

The cellular response to genotoxic stress is multifaceted in nature. Following DNA damage, the tumor suppressor gene p53 activates and plays critical roles in cell cycle arrest, activation of DNA repair and in the event of irreparable damage, induction of apoptosis. The breakdown of apoptosis causes the accumulation of mutant cells. The elucidation of the mechanism for the p53‐dependent apoptosis will be crucial in applying the strategy for cancer patients. However, the mechanism of p53‐dependent apoptosis remains largely unclear. Here, we carried out ChIP followed by massively parallel DNA sequencing assay (ChIP‐seq) to uncover mechanisms of apoptosis. Using ChIP‐seq, we identified PDCD6 as a novel p53‐responsive gene. We determined putative p53‐binding sites that are important for p53 regulation in response to DNA damage in the promoter region of PDCD6. Knockdown of PDCD6 suppressed p53‐dependent apoptosis. We also observed that cytochrome c release and the cleavage of PARP by caspase‐3 were suppressed by depletion of PDCD6. We further observed that PDCD6 localizes in the nucleus in response to DNA damage. We identified the nuclear localization signal of PDCD6 and, importantly, the nuclear accumulation of PDCD6 significantly induced apoptosis after genotoxic stress. Therefore, we conclude that a novel p53‐responsive gene PDCD6 is accumulated in the nucleus and induces apoptosis in response to DNA damage.
Contingent incentives reduce cigarette smoking among pregnant, methadone‐maintained women: results of an initial feasibility and efficacy randomized clinical trial
Authors: Tuten Michelle , Fitzsimons Heather , Chisolm Margaret S. , Nuzzo Paul A. , Jones Hendree E.
Published: June 2012

Aims

This study examined the feasibility and efficacy of behavioral incentives for reducing cigarette smoking among pregnant methadone‐maintained patients.

Design

Participants (n = 102) were assigned randomly to: (i) contingent behavioral incentives (CBI: n = 42); (ii) non‐contingent behavioral incentives (NCBI: n = 28); or (iii) treatment as usual (TAU: n = 32).

Setting

Study procedures were implemented at the Center for Addiction and Pregnancy in Baltimore, MD.

Participants

Study participants were pregnant, methadone‐maintained women enrolled in substance use disorder treatment.

Measurements

Baseline carbon monoxide (CO) levels were calculated for each participant. Subsequently, breath samples were tested three times weekly to measure changes in smoking behavior. CBI participants received incentives for target reductions from baseline: any reduction (week 1); 10% reduction (weeks 2–4), 25% reduction (weeks 5–7), 50% reduction (weeks 8–9), 75% reduction (week 10–11); and abstinence [CO < 4 parts per million (p.p.m.)] (week 12 until delivery). NCBI participants received incentives independent of smoking CO measurement results. TAU participants received no incentives, the standard treatment at the program.

Findings

CBI condition participants submitted significantly lower mean CO values than the NCBI and TAU conditions over the course of the intervention (P < 0.0001). Nearly half (48%) of the CBI participants met the 75% smoking reduction target and one‐third (31%) met the abstinence target at week 12. In contrast, none of the NCBI met either the 75% or abstinence targets. Only 2% of the TAU participants met the 75% reduction and none of the TAU participants met the abstinence targets. These smoking behavior reductions did not yield significant differences in birth outcomes.

Conclusions

Cigarette smoking may be reduced significantly among pregnant, methadone‐maintained women through the use of contingent reinforcement for gradual reductions in breath carbon monoxide levels.
Systematic review: potential preventive effects of statins against oesophageal adenocarcinoma
Authors: Alexandre L. , Clark A. B. , Cheong E. , Lewis M. P. N. , Hart A. R.
Published: June 2012

Background

The incidence of oesophageal adenocarcinoma (OAC) has risen dramatically in recent decades, and its prognosis remains extremely poor. There is emerging evidence that statins may prevent OAC.

Aim

To systematically review both the experimental and epidemiological evidence to determine whether statins reduce the risk of developing OAC.

Methods

Relevant laboratory and epidemiological studies were identified by systematically searching the PUBMED and EMBASE electronic databases for data on statins and oesophageal cancer (OC). The evidence was assessed according to the nine Bradford Hill criteria (BHC) of causality. Pooled effect sizes (ES) were calculated for the risk of OC with prior statin use.

Results

Many of the BHC were supported including: ‘plausible biological mechanisms’, ‘coherence’, ‘strong associations’, ‘consistency’, ‘biological gradient’, ‘analogy’ and ‘temporality’. Three experimental studies reported that statins inhibited proliferation, induced apoptosis and may limit metastatic potential in OAC cell lines. Fixed effects meta‐analysis of two prospective studies in Barrett's oesophagus cohorts, involving 1382 participants, showed an ES of 0.53 (95% CI = 0.36–0.78, P = 0.001, I2 = 0%) for risk of OAC with prior statin use. Meta‐analysis of three prospective studies in general population cohorts, involving 35 214 participants, showed an ES of 0.86 (95% CI = 0.78–0.94, P = 0.001, I2 = 0%) for risk of OC with prior statin use. The most important criterion, ‘experiment’, is as yet unfulfilled as to date there are no clinical trials which investigate this hypothesis.

Conclusion

There is some evidence that statins may protect against the development of OAC, although to be conclusive, data from randomised clinical trials are required.
Pedigrees as a source of information in mtDNA studies of dogs and horses
Authors: Głażewska I. , Prusak B. , Gralak B.
Published: June 2012

The goal of this study was to demonstrate the usefulness of pedigree data in studies of mitochondrial DNA diversity in dogs and horses. Pedigree information allows for precisely choosing animals with distinct haplotypes for analysis, makes it possible to find rare haplotypes present exclusively in single individuals and helps to evaluate haplotype frequencies at the present and in the past. Estimating founder contributions to gene pools enables evaluating the parts of gene pools observed with the help of mtDNA analysis. An important aspect is also the financial benefits: using pedigree data, researchers can save a significant amount of time and money needed for sample collection and laboratory analysis.
Methylthioadenosine phosphorylase inactivation depends on gene deletion in laryngeal squamous cell carcinoma
Authors: Conde Laura , Vilaseca Isabel , Alós Llucia , Bernal‐Sprekelsen Manuel , Cardesa Antonio , Nadal Alfons
Published: June 2012

Conde L, Vilaseca I, Alós L, Bernal‐Sprekelsen M, Cardesa A & Nadal A  (2012) Histopathology Methylthioadenosine phosphorylase inactivation depends on gene deletion in laryngeal squamous cell carcinoma

Aims:  Methylthioadenosine phosphorylase (MTAP) is an essential enzyme for the methionine and adenosine salvage pathway in normal cells, frequently inactivated in many different human cancers. MTAP status could be important for tumour cell sensitivity to adjuvant chemotherapy. To our knowledge, there have been no reports to date on MTAP status in laryngeal carcinoma.

Methods and results:  A series of 31 laryngeal squamous cell carcinomas was investigated for MTAP mRNA expression using reverse transcription and quantitative polymerase chain reaction (qPCR), as well as for MTAP gene deletion and/or promoter hypermethylation using qPCR and methylation‐specific PCR, respectively. Low MTAP mRNA expression was found in 32% of cases, and was associated with MTAP gene deletion (in 70%; P < 0.001) but not with MTAP promoter hypermethylation, indicating that, in this tumour, gene deletion is the main mechanism for MTAP inactivation. Neither low mRNA expression nor gene deletion was associated with any of the clinicopathological parameters investigated.

Conclusion:  Given the significance of MTAP status for cell sensitivity to different chemotherapeutic regimens, our results suggest that determination of MTAP inactivation should be taken into consideration in managing laryngeal squamous cell carcinomas.
In vitro antioxidant and bioactive properties of raw and roasted wattle (Acacia victoriae Bentham) seed extracts
Authors: Ee Kah Y. , Agboola Samson , Rehman Ata , Zhao Jian
Published: June 2012

Protease inhibitors (PIs) from raw wattle (Acacia victoriae) seeds as well as phenolic extracts from raw and roasted wattle seeds were analysed for antioxidant, angiotensin‐converting enzyme (ACE) inhibition, cytotoxicity, antimicrobial, antiparasitic, antitumor and insecticidal activities. Progressive purification of the PIs resulted in increases in their ACE inhibitory activity and cytotoxicity, but decreases in antioxidant activity. Roasting of wattle seed significantly increased the antioxidant activity of the phenolic extracts as did alkaline hydrolysis of wattle seed flour, but the treatment destroyed their ACE inhibitory activity and reduced the level of cytotoxicity. A moderate degree of synergism between the PIs and phenolic extracts of wattle seed was observed for ACE inhibition activity, but not for antioxidant activity or cytotoxicity. Wattle seed PIs exhibited moderate cytotoxicity, but did not possess any significant antibacterial, antifungal, antiparasitic, antitumour or insecticidal activities.
Kinetics investigation of antioxidant capacity and total phenols of low‐temperature steeping Bi Luo Chun green tea
Authors: Liao Wayne C. , Wu Wen H. , Lai Shih T. , Lin Wei J. , Liou Hua‐Chien , Chan Chin‐Feng
Published: June 2012

Traditionally, tea is steeped in boiled water in Taiwan. In this study, Bi Luo Chun (250 μg mL−1) steeped at 4, 22, 30, 40 and 50 °C reached the saturation of 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH) radical scavenging capacity at the time of 15, 8, 2, 0.17 (10 s) and 0.17 min (10 s), respectively. The result indicated that tea steeped in cold water (under 22 °C) still can reach a saturation of antioxidant capacity in 15 min. However, the initial scavenging rate (% min−1) was quick and decreased with time at all steeping temperatures (r: −0.98 to −1.00). Total phenols and the DPPH scavenging capacity of Bi Luo Chun showed excellent correlation with time. However, the plot of DPPH scavenging capacity vs. total phenols was not always correlated. The result indicated that polyphenol infusion at different times may have a different DPPH scavenging capacity.
Quality indicators for in‐hospital management of exacerbation of chronic obstructive pulmonary disease: results of an international Delphi study
Authors: Lodewijckx Cathy , Sermeus Walter , Panella Massimiliano , Deneckere Svin , Leigheb Fabrizio , Troosters Thierry , Boto Paulo Alexandre , Mendes Rita Veloso , Decramer Marc , Vanhaecht Kris
Published: June 2012

lodewijckx c., sermeus w., panella m., deneckere s., leigheb f., troosters t., boto p.a., mendes r.v., decramer m. & vanhaecht k. (2012) Quality indicators for in‐hospital management of exacerbation of chronic obstructive pulmonary disease: results of an international Delphi study. Journal of Advanced Nursing69(2), 348–362. doi: 10.1111/j.1365‐2648.2012.06013.x

Aim.  To report a Delphi study that was conducted to select process and outcome indicators that are relevant to study quality of care and impact of care pathways for patients hospitalized with exacerbation of chronic obstructive pulmonary disease.

Background.  Management of patients hospitalized with exacerbation of chronic obstructive pulmonary disease is suboptimal and outcomes are poor. To evaluate the impact of care pathways properly, relevant indicators need to be selected.

Design.  Delphi study.

Methods.  The study was conducted over 4 months in 2008, with 35 experts out of 15 countries, including 19 medical doctors, 8 nurses and 8 physiotherapists. Participants were asked to rate, for 72 process and 21 outcome indicators, the relevance for follow‐up in care pathways for in‐hospital management of exacerbation of chronic obstructive pulmonary disease. Consensus (agreement by at least 75% of the participants) that an indicator is relevant for follow‐up was sought in two rounds.

Results.  Consensus was reached for 26 of 72 process indicators (36·1%) and 10 of 21 outcome indicators (47·6%). Highest consensus levels were found for the process indicators regarding oxygen therapy (100%), pulmonary rehabilitation (100%) and patient education (94·5–88·6%) and for the outcome indicators concerning understanding of therapy (91·4–85·7%) and self‐management (88·6–88·2%).

Conclusion.  The selected indicators appear to be sensitive for improvement. Therefore, researchers and clinicians that want to study and improve the care for patients hospitalized with exacerbation of chronic obstructive pulmonary disease should primarily focus on these indicators.
Seed dispersal by lizards on a continental‐shelf island: predicting interspecific variation in seed rain based on plant distribution and lizard movement patterns
Authors: Piazzon Martín , Larrinaga Asier R. , Rodríguez‐Pérez Javier , Latorre Lucia , Navarro Luis , Santamaría Luis
Published: June 2012

Aim  We estimated the patterns of seed deposition provided by the eyed lizard, Timon lepidus, and evaluated whether these patterns can be generalized across plant species with different traits (fruit and seed size) and spatial distributions.

Location  Monteagudo Island, Atlantic Islands National Park (north‐western Spain).

Methods  We radio‐tracked seven lizards for 14 days and estimated their home ranges using fixed kernels. We also geo‐referenced all fruit‐bearing individuals of four plant species dispersed by eyed lizards in the study area (Corema album, Osyris alba, Rubus ulmifolius and Tamus communis), measured the passage time of their seeds through the lizard gut, and estimated seed predation in four habitats (bare sand, grassland, shrub and gorse). Seed dispersal kernels were estimated using a combination of these data and were combined with seed predation probability maps to incorporate post‐dispersal seed fate (‘seed survival kernels’).

Results  Median seed gut‐passage times were around 52–98 h, with maximum values up to 250 h. Lizards achieved maximum displacement in their home ranges within 24–48 h. Seed predation was high (80–100% of seeds in 2 months), particularly under Corema shrub and gorse. Seed dispersal kernels showed a common pattern, with two areas of preferential seed deposition, but the importance of these varied among plant species. Interspecific differences among dispersal kernels were strongly reduced by post‐dispersal seed predation; hence, seed survival kernels of the different plant species showed high auto‐ and pairwise‐correlations at small distances (< 50 m). As a result, survival to post‐dispersal seed predation increased with dispersal distance for O. alba and T. communis, but not for C. album.

Main conclusions  Seed dispersal by lizards was determined primarily by the interaction between the dispersers’ home ranges and the position of the fruit‐bearing plants. As a result, seed rain shared a common template, but showed considerable variation among species, determined by their specific spatial context. Seed predation increased the spatial coherence of the seed rain of the different species, but also resulted in contrasting relationships between seed survival and dispersal distance, which may be of importance for the demographic and evolutionary processes of the plants.
Exenatide improves excessive daytime sleepiness and wakefulness in obese patients with type 2 diabetes without obstructive sleep apnoea
Authors: IDRIS ISKANDAR , ABDULLA HAITHAM , TILBROOK SEAN , DEAN ROY , ALI NABEEL
Published: June 2012

We investigate the effects of exenatide on excessive daytime sleepiness (EDS), driving performance and depression score in patients with type 2 diabetes with EDS. Eight obese patients with diabetes but without obstructive sleep apnoea (OSA) participated in a placebo‐controlled single‐blind study during which multiple wakefulness and sleep latency test, Epworth score, driving performance, depression score, fasting glucose and glycated haemoglobin (HbA1c) levels were assessed at baseline, end of placebo and treatment phase at baseline and after 22 weeks of treatment. Mean (±standard error of the mean) age, body mass index (kg m2) and HbA1c [mmol mol−1 (%)] of patients at baseline were 50 ± 4.9 years, 37.6 ± 1.1 and 65 ± 19 (8.06 ± 0.41), respectively. When compared to placebo, exenatide treatment was associated with a decrease in both subjective and objective sleepiness, based on the Epworth score reduction and the sleep latency increase assessed by multiple objective sleepiness and sustained attention (OSLER) tests, respectively. Mean sleep latency time (adjusted for change in HbA1c and weight) were 32.1 ± 1.7, 29.1 ± 1.7 and 37.7 ± 1.7, respectively (P = 0.002). Modelling for covariates suggested that improvement in mean sleep latency time is predicted by changes in weight (P = 0.003), but not by changes in HbA1c (P = 0.054). Epworth sleepiness score was reduced significantly (values for placebo versus exenatide: 11.3 ± 1.2 versus 5.7 ± 1.3; P = 0.003). No significant change was noted in the depression score and driving performance. Exenatide is associated with a significant reduction in objective sleepiness in obese patients with type 2 diabetes without OSA, independent of HbA1c levels. These findings could form a basis for further studies to investigate the pathophysiological mechanisms of sleepiness in obese patients with type 2 diabetes.
Role of dung beetle feeding mechanisms in limiting the suitability of species as hosts for the nematode Spirocerca lupi
Authors: DU TOIT C. A. , HOLTER P. , LUTERMANN H. , SCHOLTZ C. H.
Published: June 2012

Various species of dung beetle serve as intermediate hosts after ingesting the embryonated eggs (11–15 × 30–37 µm) of Spirocerca lupi (Spirurida: Spirocercidae) in dog faeces. The feeding mechanisms of coprophagous dung beetles restrict the size of the food particles they can ingest and hence may determine which species can be efficient vectors for S. lupi. In this study, we aimed to exclude certain dung beetle species as possible hosts of S. lupi based on whether or not they ingested latex beads of known diameters mixed into fresh cattle dung. We found that the majority (11/14) of species tested can potentially serve as intermediate hosts of S. lupi because their mouthparts allow the passage of food particles larger than the minimum size range of the eggs of this parasite.
Rickettsia felis in cat fleas, Ctenocephalides felis parasitizing opossums, San Bernardino County, California
Authors: ABRAMOWICZ K. F. , WEKESA J. W. , NWADIKE C. N. , ZAMBRANO M. L. , KARPATHY S. E. , CECIL D. , BURNS J. , HU R. , EREMEEVA M. E.
Published: June 2012

Los Angeles and Orange Counties are known endemic areas for murine typhus in California; however, no recent reports of flea‐borne rickettsioses are known from adjacent San Bernardino County. Sixty‐five opossums (Didelphis virginiana) were trapped in the suburban residential and industrial zones of the southwestern part of San Bernardino County in 2007. Sixty out of 65 opossums were infested with fleas, primarily cat fleas, Ctenocephalides felis (Bouché, 1835). The flea minimum infection rate with Rickettsia felis was 13.3% in pooled samples and the prevalence was 23.7% in single fleas, with two gltA genotypes detected. In spite of historic records of murine typhus in this area, no evidence for circulation of R. typhi in fleas was found during the present study. Factors contributing to the absence of R. typhi in these cat fleas in contrast to its presence in cat fleas from Orange and Los Angeles Counties are unknown and need to be investigated further in San Bernardino County.
Evidence for roles of the Escherichia coli Hda protein beyond regulatory inactivation of DnaA
Authors: Baxter Jamie C. , Sutton Mark D.
Published: June 2012

The ATP‐bound form of the Escherichia coli DnaA protein binds ‘DnaA boxes’ present in the origin of replication (oriC) and operator sites of several genes, including dnaA, to co‐ordinate their transcription with initiation of replication. The Hda protein, together with the β sliding clamp, stimulates the ATPase activity of DnaA via a process termed regulatory inactivation of DnaA (RIDA), to regulate the activity of DnaA in DNA replication. Here, we used the mutant dnaN159 strain, which expresses the β159 clamp protein, to gain insight into how the actions of Hda are co‐ordinated with replication. Elevated expression of Hda impeded growth of the dnaN159 strain in a Pol II‐ and Pol IV‐dependent manner, suggesting a role for Hda managing the actions of these Pols. In a wild‐type strain, elevated levels of Hda conferred sensitivity to nitrofurazone, and suppressed the frequency of −1 frameshift mutations characteristic of Pol IV, while loss of hda conferred cold sensitivity. Using the dnaN159 strain, we identified 24 novel hda alleles, four of which supported E. coli viability despite their RIDA defect. Taken together, these findings suggest that although one or more Hda functions are essential for cell viability, RIDA may be dispensable.
The role of effective leaf mixing length in the relationship between the δ18O of stem cellulose and source water across a salinity gradient
Authors: ELLSWORTH PATRICIA V. , ELLSWORTH PATRICK Z. , ANDERSON WILLIAM T. , STERNBERG LEONEL S. L.
Published: June 2012

Previous mangrove tree ring studies attempted, unsuccessfully, to relate the δ18O of trunk cellulose (δ18OCELL) to the δ18O of source water (δ18OSW). Here, we tested whether biochemical fractionation associated with one of the oxygen in the cellulose glucose moiety or variation in leaf water oxygen isotope fractionation (ΔLW) can interfere with the δ18OSW signal as it is recorded in the δ18OCELL of mangrove (saltwater) and hammock (freshwater) plants. We selected two transects experiencing a salinity gradient, located in the Florida Keys, USA. The δ18OCELL throughout both transects did not show the pattern expected based on that of the δ18OSW. We found that in one of the transects, biochemical fractionation interfered with the δ18OSW signal, while in the other transect ΔLW differed between mangrove and hammock plants. Observed differences in ΔLW between mangroves and hammocks were caused by a longer effective leaf mixing length (L) of the water pathway in mangrove leaves compared to those of hammock leaves. Changes in L could have caused the δ18OCELL to record not only variations in the δ18OSW but also in ΔLW making it impossible to isolate the δ18OSW signal.
Immunomodulatory Type II Natural Killer T Lymphocytes in Health and Disease
Authors: Rhost S. , Sedimbi S. , Kadri N. , Cardell S. L.
Published: June 2012

Natural killer T (NKT) lymphocytes are αβ T cells activated by lipid‐based ligands presented on the non‐polymorphic CD1d‐molecule. Type I NKT cells that carry an invariant Vα14 (in the mouse) or Vα24 (in humans) T cell receptor α‐chain rearrangement have received significant attention for their involvement in a diversity of immune reactions. Their sister population, CD1d‐restricted type II NKT cells, has been more difficult to study because of the lack of molecular markers that specify these cells. In the last few years, however, significant progress has been made, demonstrating that type II NKT cells have unique functions in immune responses to tumours and infections, in autoimmunity, obesity and graft‐versus‐host disease. Type II NKT cells appear more frequent than type I NKT cells in humans and accumulate in certain diseases such as ulcerative colitis, hepatitis and multiple myeloma. Recently, novel type II NKT cell ligands have been identified, and it is becoming clear that the type II NKT cell population may be oligoclonal. Here, we review the recent progress in the study of type II NKT cells, supporting the view that type II NKT cells may be attractive targets for immunotherapy.
B Cell‐Activating Factor Enhances Interleukin‐6 and Interleukin‐10 Production by ODN‐Activated Human B Cells
Authors: Yehudai D. , Snir A. , Peri R. , Halasz K. , Haj T. , Odeh M. , Kessel A.
Published: June 2012

We aim to investigate the additive value of B cell‐activating factor (BAFF) when added to oligodeoxynucleotides (ODN)‐activated B cells with respect to TLR‐9, CD69, MHC‐II expression, IL‐6 and IL‐10 secretion and B cell cycling. Therefore, B cells from healthy individuals were incubated under the following conditions: (1) B cells with medium, (2) B cells with ODN 0.5 μm, (3) B cells with BAFF 20 μm and (4) B cells with both ODN 0.5 μm and BAFF 20 μm. We found that addition of BAFF did not enhance the expression of TLR‐9, CD69 and MHC‐II in ODN‐activated B cells. Incubation of B cells with BAFF and ODN together leads to a marked elevation of IL‐6 and IL‐10 levels compared to ODN alone. Synthesis and mitosis were higher in B cells stimulated by BAFF than in B cells stimulated by ODN. These findings suggest that both BAFF and TLR‐9 contribute independently to B cell function.