bluuebunny/crossref_metadata_2025 huggingface dataset:
Malignancies and survival patterns in the National Cancer Institute inherited bone marrow failure syndromes cohort study
Authors: Alter Blanche P. , Giri Neelam , Savage Sharon A. , Peters June A. , Loud Jennifer T. , Leathwood Lisa , Carr Ann G. , Greene Mark H. , Rosenberg Philip S.
Published: May 2010

Fanconi anaemia (FA), dyskeratosis congenita (DC), Diamond‐Blackfan anaemia (DBA), and Shwachman‐Diamond syndrome (SDS) comprise major inherited bone marrow failure syndromes (IBMFS). Adverse events include severe bone marrow failure (BMF), myelodysplastic syndrome (MDS), acute myeloid leukaemia (AML), and solid tumours (ST). The natural history of FA is well characterised; hazard rates in the other syndromes have not yet been quantified. An open cohort was established at the National Cancer Institute (NCI) in 2002. Patients enrolled prior to December, 2007 were followed up to December, 2008. Diagnoses were confirmed with standard tests. Age‐associated risks of adverse events were calculated. Most patients in each syndrome survived to young adulthood. Patients with FA had earlier onset of cancers, need for stem cell transplant, and death; followed by DC; DBA and SDS were mildest. While FA and DC patients had markedly increased risks of cancer, AML and MDS, there were no cases of leukaemia in DBA or SDS patients. The NCI cohort provides the first direct quantitative comparison of timing and magnitude of cancer risk in the IBMFS. The findings demonstrate that both FA and DC are major cancer susceptibility syndromes. The IBMFS, historically considered paediatric disorders, have important management implications for physicians treating adult patients.
Loss of insulin‐mediated microvascular perfusion in skeletal muscle is associated with the development of insulin resistance
Authors: St‐Pierre P. , Genders A. J. , Keske M. A. , Richards S. M. , Rattigan S.
Published: May 2010

Aim: The aetiology of the development of type 2 diabetes remains unresolved. In the present study, we assessed whether an impairment of insulin‐mediated microvascular perfusion occurs early in the onset of insulin resistance.

Materials and methods: Hooded Wistar rats were fed either a normal diet (ND) or a high‐fat diet (HFD) for 4 weeks. Anaesthetized animals were subjected to an isoglycaemic hyperinsulinaemic clamp (3 or 10 mU/min/kg × 2 h), and measurements were made of glucose infusion rate (GIR), hindleg glucose uptake, muscle glucose uptake by 2‐deoxy‐d‐glucose (R′g), glucose appearance (Ra), glucose disappearance (Rd), femoral blood flow (FBF) and hindleg 1‐methylxanthine disappearance (1‐MXD, an index of microvascular perfusion).

Results: Compared with ND‐fed animal, HFD feeding led to a mild increase in fasting plasma glucose and plasma insulin, without an increase in total body weight. During the clamps, HFD rats showed an impairment of insulin‐mediated action on GIR, hindleg glucose uptake, R′g, Ra, Rd and FBF, with a greater loss of insulin responsiveness at 3 mU/min/kg than at 10 mU/min/kg. The HFD also impaired insulin‐mediated microvascular perfusion as assessed by 1‐MXD. Interestingly, 1‐MXD was the only measurement that remained unresponsive to the higher dose of 10 mU/min/kg insulin.

Conclusions: We conclude that the early stage of insulin resistance is characterized by an impairment of the insulin‐mediated microvascular responses in skeletal muscle. This is likely to cause greater whole body insulin resistance by limiting the delivery of hormones and nutrients to muscle.
Maternal blood glucose in diabetic pregnancies and cognitive performance in offspring in young adulthood: a Danish cohort study
Authors: Nielsen G. L. , Andersen E. , Lundbye‐Christensen S.
Published: May 2010

Diabet. Med. 27, 786–790 (2010)

Aims  Maternal diabetes is a known risk factor for perinatal complications, but there are little data on consequences for long‐term intellectual outcome in offspring. We assess cognitive performance in military conscripts according to maternal blood glucose levels during pregnancy.

Methods  We identified a cohort of 60 Danish male offspring of insulin‐treated diabetic mothers born between 1976 and 1984 and followed this cohort to military conscription. From medical records, we extracted data on all available values of maternal blood glucose categorized as fasting and non‐fasting and by day in pregnancy, together with maternal White class, smoking habits and socio‐economic status. The main outcome was cognitive performance at conscription measured with a validated intelligence test. The association between maternal blood glucose level and cognitive performance was assessed by multivariate linear regression and a fitted fractional polynomial.

Results  Median fasting blood glucose values in the second half of pregnancy was negatively associated with cognitive scores at conscription [adjusted coefficient –1.7; 95% confidence interval (CI) –3.0; –0.4]. Restriction to only first‐born sibling slightly strengthened the association (coefficient –1.9; 95% CI –3.3; –0.5), but after exclusion of two pregnancies with the blood glucose > 10 mmol/l the association became insignificant (coefficient –0.6; 95% CI –2.6; 1.4).

Conclusions  Maternal blood glucose level during diabetic pregnancy is negatively associated with cognitive performance in offspring at military conscription. In pregnancies with fasting blood glucose levels below 10 mmol/l, the association is weak and considered to be without clinical relevance.
Sphingosine kinase 1 is critically involved in nitric oxide‐mediated human endothelial cell migration and tube formation
Authors: Schwalm Stephanie , Pfeilschifter Josef , Huwiler Andrea
Published: May 2010

Background and purpose: Sphingosine kinases (SKs) convert sphingosine to sphingosine 1‐phosphate (S1P), which is a bioactive lipid that regulates a variety of cellular processes including proliferation, differentiation and migration.

Experimental approach: We used the human endothelial cell line EA.hy926 to investigate the effect of nitric oxide (NO) donors on SK‐1 expression, and on cell migration and tube formation.

Key results: We showed that exposure of EA.hy926 cells to Deta‐NO (125–1000 µM) resulted in a time‐ and concentration‐dependent up‐regulation of SK‐1 mRNA and protein expression, and activity with a first significant effect at 250 µM of Deta‐NO. The increased SK‐1 mRNA expression resulted from an enhanced SK‐1 promoter activity. A similar effect was also seen with various other NO donors. In mechanistic terms, the NO‐triggered effect occurred independently of cGMP, but involved the classical mitogen‐activated protein kinase cascade because the MEK inhibitor U0126 abolished the NO‐induced SK‐1 expression. The effect of NO was also markedly reduced by the thiol‐reducing agentN‐acetylcysteine, suggesting a redox‐dependent mechanism. Functionally, Deta‐NO triggered an increase in the migration of endothelial cells in an adapted Boyden chamber assay, and also increased endothelial tube formation in a Matrigel assay. These responses were both abolished in cells depleted of SK‐1.

Conclusions and implications: These data show that NO donors up‐regulate specifically SK‐1 expression and activity in human endothelial cells, and SK‐1 in turn critically contributes to the migratory capability and tube formation of endothelial cells. Thus, SK‐1 may be considered an attractive novel target to interfere with pathological processes involving angiogenesis.
Endocannabinoid‐like N‐arachidonoyl serine is a novel pro‐angiogenic mediator
Authors: Zhang X , Maor Y , Wang JF , Kunos G , Groopman JE
Published: May 2010

BACKGROUND AND PURPOSE N‐arachidonoyl serine (ARA‐S) is a recently identified endocannabinoid‐like lipid with weak affinity for the fully characterized cannabinoid receptors (CB1 and CB2) and the transient receptor potential vanilloid receptor 1 (TRPV‐1). ARA‐S induces vasodilatation and shows vasoprotective potential via activation of key signalling pathways in endothelial cells. Based on these findings, the effect of ARA‐S on endothelial functions was further studied.

EXPERIMENTAL APPROACH Primary human dermal microvascular endothelial cells (HMVEC) were used to investigate effects of ARA‐S (0‐10 µM) on certain endothelial functions, using cell proliferation, migration and wound repair models in vitro, and angiogenesis assays in vitro and ex vivo. Selective CB receptor antagonists and specific siRNAs were deployed to block individual CB receptors.

KEY RESULTS We found that ARA‐S stimulated angiogenesis and endothelial wound healing through induction of vascular endothelial growth factor C and its cognate receptor expression in primary HMVEC. Moreover, knock‐down of G protein‐coupled receptor 55 (GPR55) partly inhibited ARA‐S‐induced signal transduction and endothelial functions.

CONCLUSIONS AND IMPLICATIONS Our results indicate that ARA‐S is a pro‐angiogenic factor in addition to a vessel dilator. The GPR55 receptor may serve as one target of ARA‐S.
Male Mutation Bias and Possible Long‐Term Effects of Human Activities
Authors: COTTON SAMUEL , WEDEKIND CLAUS
Published: May 2010

Abstract:  The ability of a population to adapt to changing environments depends critically on the amount and kind of genetic variability it possesses. Mutations are an important source of new genetic variability and may lead to new adaptations, especially if the population size is large. Mutation rates are extremely variable between and within species, and males usually have higher mutation rates as a result of elevated rates of male germ cell division. This male bias affects the overall mutation rate. We examined the factors that influence male mutation bias, and focused on the effects of classical life‐history parameters, such as the average age at reproduction and elevated rates of sperm production in response to sexual selection and sperm competition. We argue that human‐induced changes in age at reproduction or in sexual selection will affect male mutation biases and hence overall mutation rates. Depending on the effective population size, these changes are likely to influence the long‐term persistence of a population.
Distribution and Use of Income from Bushmeat in a Rural Village, Central Gabon
Authors: COAD L. , ABERNETHY K. , BALMFORD A. , MANICA A. , AIREY L. , MILNER‐GULLAND E. J.
Published: May 2010

Abstract:  Bushmeat hunting is an activity integral to rural forest communities that provides a high proportion of household incomes and protein requirements. An improved understanding of the relationship between bushmeat hunting and household wealth is vital to assess the potential effects of future policy interventions to regulate an increasingly unsustainable bushmeat trade. We investigated the relationship between hunting offtake and household wealth, gender differences in spending patterns, and the use of hunting incomes in two rural forest communities, Central Gabon, from 2003 to 2005. Households in which members hunted (hunting households) were significantly wealthier than households in which no one hunted (nonhunting households), but within hunting households offtakes were not correlated with household wealth. This suggests there are access barriers to becoming a hunter and that hunting offtakes may not be the main driver of wealth accumulation. Over half of the money spent by men in the village shop was on alcohol and cigarettes, and the amount and proportion of income spent on these items increased substantially with increases in individual hunting offtake. By contrast, the majority of purchases made by women were of food, but their food purchases decreased actually and proportionally with increased household hunting offtake. This suggests that the availability of bushmeat as a food source decreases spending on food, whereas hunting income may be spent in part on items that do not contribute significantly to household food security. Conservation interventions that aim to reduce the commercial bushmeat trade need to account for likely shifts in individual spending that may ensue and the secondary effects on household economies.
Impact of a Community‐Based Payment for Environmental Services Intervention on Forest Use in Menabe, Madagascar
Authors: SOMMERVILLE MATTHEW , MILNER‐GULLAND E.J. , RAHAJAHARISON MICHAEL , JONES JULIA P.G.
Published: May 2010

Abstract:  Despite the growing interest in conservation approaches that include payments for environmental services (PES), few evaluations of the influence of such interventions on behaviors of individuals have been conducted. We used self‐reported changes in six legal and illegal forest‐use behaviors to investigate the way in which a PES for biodiversity conservation intervention in Menabe, Madagascar, influenced behavior. Individuals (n =864) from eight intervention communities and five control communities answered questions on their forest‐use behaviors before and after the intervention began, as well as on their reasons for changing and their attitudes to various institutions. The payments had little impact on individuals’ reported decisions to change behaviors, but it had a strong impact on individuals’ attitudes. Payments appeared to legitimize monitoring of behaviors by the implementing nongovernmental organization (NGO), but did not act as a behavioral driver in their own right. Although there were no clear differences between changes in behaviors in the intervention and control communities, the intervention did influence motivations for change. Fear of local forest associations and the implementing NGO were strong motivators for changing behavior in communities with the PES intervention, whereas fear of the national government was the main reason given for change in control communities. Behavioral changes were most stable where fear of local organizations motivated the change. Our results highlight the interactions between different incentives people face when making behavioral decisions and the importance of considering the full range of incentives when designing community‐based PES interventions.
16S rRNA GENE HETEROGENEITY IN THE FILAMENTOUS MARINE CYANOBACTERIAL GENUSLYNGBYA1
Authors: Engene Niclas , Cameron Coates R. , Gerwick William H.
Published: May 2010

The SSU (16S) rRNA gene was used to investigate the phylogeny of the cyanobacterial genusLyngbyaas well as examined for its capacity to discriminate between different marine species ofLyngbya. We show thatLyngbyaforms a polyphyletic genus composed of a marine lineage and a halophilic/brackish/freshwater lineage. In addition, we found morphological and genetic evidence thatLyngbyaspp. often grow in association with other microorganisms, in particular smaller filamentous cyanobacteria such asOscillatoria, and propose that these associated microorganisms have led to extensive phylogenetic confusion in identification ofLyngbyaspp. At the species level, the phylogenetic diversity obtained from the comparison of 16S rRNA genes exceeded morphological diversity inLyngbya. However, the expectation that this improved phylogeny would be useful to species and subspecies identification was eliminated by the fact that phylogenetic species did not correlate in any respect with the species obtained from current taxonomic systems. In addition, phylogenetic identification was adversely affected by the presence of multiple gene copies within individualLyngbyacolonies. Analysis of clonalLyngbyacultures and multiple displacement amplified (MDA) single‐cell genomes revealed thatLyngbyagenomes contain two 16S rRNA gene copies, and that these typically are of variable sequence. Furthermore, intragenomic and interspecies 16S rRNA gene heterogeneity was approximately of the same magnitude. Hence, the intragenomic heterogeneity of the 16S rRNA gene overestimates the microdiversity of different strains and does not accurately reflect speciation within cyanobacteria, including the genusLyngbya.
Variation in mate recognition specificities among fourCallosobruchusseed beetles
Authors: Shimomura Kenji , Mimura Takanori , Ishikawa Susumu , Yajima Shunsuke , Ohsawa Kanju
Published: May 2010

Differentiation of mate recognition systems is one of the important steps for speciation in animals. For some insects, a contact sex pheromone present on the cuticular surface is indispensable in discriminating reproductive partners. InCallosobruchusspecies (Coleoptera: Chrysomelidae: Bruchinae), contact sex pheromones have been found in two species,Callosobruchus chinensis(L.) andCallosobruchus maculatus(Fabricius). It was suggested, however, that these two species lacked the ability to discriminate their conspecific and/or heterosexual partners. To elucidate this inconsistency, we verified the existence of contact sex pheromones from two other species,Callosobruchus rhodesianus(Pic) andCallosobruchus analis(Fabricius). As a result, unlikeC. chinensisandC. maculatus, the males ofC. rhodesianusandC. analiswere able to discriminate their heterosexual partners. Comparing cross‐copulation behavior, i.e., copulation behavior between two species, against these four species indicated that the mate recognition specificities were quite different. Males ofC. rhodesianusandC. analishad highly species‐specific mating behavior, whereas males ofC. chinensisandC. maculatuswere much less specific. These results indicate that variation in mate recognition can arise even among congeneric species living in a sympatric environment, and this variation might have arisen during species differentiation. Based on our results in combination with previous reports on interspecific competition, we suggest that the observed asymmetric cross‐copulation behavior might be, at least partially, an adaptation for surviving interspecific competition.
Titanium hydride and hydrogen concentration in acid‐etched commercially pure titanium and titanium alloy implants: a comparative analysis of five implant systems
Authors: Szmukler‐Moncler S. , Bischof M. , Nedir R. , Ermrich M.
Published: May 2010

Objectives: Acid etching is a popular method to texture the surface of dental implants. During etching, the titanium oxide protective layer is dissolved and small native hydrogen ions diffuse into the unprotected implant surface. They enrich the implant surface with hydrogen and precipitate into titanium hydride (TiH). The aim of this study was to measure the concentration of TiH at the implant surface and the total concentration of Hydrogen at five commercially available implant systems, made of either commercially pure (cp) titanium or titanium alloy.

Material and methods: X‐Ray diffraction (XRD) was conducted on each implant system to determine the compounds present at the implant surface. Following a TiH2/Ti calibration curve, the concentration of TiH was determined. Concentration of hydrogen in the implants was measured by the inert gas fusion thermal conductivity/infrared detection method.

Results: XRD data showed that TiH was present on all cp titanium implants but not on the alloyed implants. TiH concentration varied between 5% and 37%. Hydrogen concentration varied between 43 and 108 ppm, no difference in uptake was found between the cp titanium and alloyed implants. Low solubility of hydrogen in α‐titanium is responsible for precipitation into TiH. Stronger etching conditions led to higher concentration of TiH2‐x.

Conclusion: High solubility of hydrogen in the β‐phase of the alloy is preventing hydrogen from precipitating into TiH. All implants, even those lacking TiH at the surface, were enriched with hydrogen. In all implants, hydrogen concentration was within the normative limit of 130 ppm.

To cite this article:
 Szmukler‐Moncler S, Bischof M, Nedir R, Ermrich M. Titanium hydride and hydrogen concentration in acid‐etched commercially pure titanium and titanium alloy implants: a comparative analysis of five implant systems. Clin. Oral Impl. Res. 21, 2010; 944–950. doi: 10.1111/j.1600‐0501.2009.01938.x
Does indomethacin for closure of patent ductus arteriosus affect cerebral function?
Authors: Flisberg A , Kjellmer I , Löfhede J , Löfgren N , Rosa‐Zurera M , Lindecrantz K , Thordstein M
Published: May 2010

Objective:  To study whether indomethacin used in conventional dose for closure of patent ductus arteriosus affects cerebral function measured by Electroencephalograms (EEG) evaluated by quantitative measures.

Study design:  Seven premature neonates with haemodynamically significant persistent ductus arteriosus were recruited. EEG were recorded before, during and after an intravenous infusion of 0.2 mg/kg indomethacin over 10 min. The EEG was analysed by two methods with different degrees of complexity for the amount of low‐activity periods (LAP, “suppressions”) as an indicator of affection of cerebral function.

Results:  Neither of the two methods identified any change in the amount of LAPs in the EEG as compared to before the indomethacin infusion.

Conclusion:  Indomethacin in conventional dose for closure of patent ductus arteriosus does not affect cerebral function as evaluated by quantitative EEG.
Breastfeeding is associated with the production of type I interferon in infants infected with influenza virus
Authors: Melendi Guillermina A , Coviello Silvina , Bhat Niranjan , Zea‐Hernandez Johanna , Ferolla Fausto M , Polack Fernando P
Published: May 2010

Background:  Breast milk‐mediated protection against respiratory viruses is well established. However, protective mechanisms are unclear. Type I interferons (IFN) mediate host defence against respiratory viruses, particularly influenza virus. The relationship among type I IFN, respiratory viral infections and breastfeeding has not been explored.

Methods:  Type I IFN responses were studied by ELISA and real time PCR in nasal secretions of infants experiencing their first respiratory infection. Modulation of IFN by breastfeeding and other variables affecting severity during viral infection was explored.

Results:  One hundred and twenty infants were positive by RT‐PCR for influenza virus (n = 24), human metapneumovirus (hMPV) (n = 30) or respiratory syncytial virus (RSV) (n = 66). Type I IFNs were detected more frequently in infants infected with influenza virus than in those infected with RSV or hMPV. Breastfeeding promoted higher rates and levels of type I IFN only in infants infected with influenza virus. No effect on IFN production was observed for age, gender or smoking.

Conclusion:  Our study confirms that type I IFN production is detected more frequently in infants infected with influenza virus. Importantly, higher rates and levels of type I IFN in these infants are associated with breastfeeding. These observations suggest that breast milk can protect against respiratory viruses by activating innate antiviral mechanisms in the host.
Analyzing Factors Affecting U.S. Food Price Inflation
Authors: Baek Jungho , Koo Won W.
Published: May 2010

Since the summer of 2007, U.S. food price inflation has increased dramatically. Given public anxiety over fast‐rising food prices, this study attempts to analyze the effects of market factors—prices of energy and agricultural commodities and exchange rate—on U.S. food prices using a cointegration analysis. Results show that the agricultural commodity price and exchange rate play the key roles in determining the short‐ and long‐run movement of U.S. food prices. It is also found that in recent years, energy price has been a significant factor affecting U.S. food prices in the long run, but has little effect in the short run. This implies the strong linkage between energy and agricultural markets in the long run over the recent years.

Depuis l’été 2007, l’inflation des prix des aliments aux États‐Unis a augmenté considérablement. En raison de l’anxiété que la hausse rapide des prix des aliments suscite au sein de la population, nous avons tenté d’évaluer, à l’aide d’une analyse de co‐intégration, les répercussions de certains facteurs de marché– le prix de l’énergie, le prix des produits agricoles primaires et le taux change – sur les prix des aliments aux États‐Unis. Les résultats ont montré que les prix des produits agricoles primaires et le taux de change jouent un rôle important dans la détermination des tendances à court et à long terme des prix des aliments aux États‐Unis. Nous avons également constaté que, au cours des dernières années, le prix de l’énergie a eu une forte influence sur les prix des aliments aux États‐Unis à long terme, mais peu d’influence à court terme. Cette observation montre l’étroit lien à long terme des marchés de l’énergie et des produits agricoles au cours des dernières années.
Preclinical studies with IRX‐2 and thymosin α1 in combination therapy
Authors: Naylor Paul H. , Hadden John W.
Published: May 2010

Thymosin α1 (Tα1) is a 28 amino acid biologically active protein with pleiotropic immune enhancing activity. IRX‐2 is a primary cell‐derived biologic containing multiple cytokines that enhance dendritic cell maturation, promote T‐cell growth and differentiation, and inhibit tumor‐mediated apoptosis of T cells. IRX‐2 is being developed as an immunotherapeutic agent as a novel T‐cell adjuvant platform for vaccines as well. Based on their biological activities, thymosin α1 and IRX‐2 were predicted to exhibit synergistic effects when evaluated in animal and human studies. In animal studies, the combination of IRX‐2 and Tα1 (IRX‐3) increased T‐cell numbers compared to either alone during recovery from hydrocortisone mediated reduction. IRX‐3 further enhanced reduction in tumor burden following chemotherapy compared to IRX‐2. Based on these studies, IRX‐3 is predicted to be especially important in a setting where reversal of immune suppression due to the presence of tumor, irradiation, and/or chemotherapy is likely to be an important factor in cytokine activity.
Thymosin β4 regulates migration of colon cancer cells by a pathway involving interaction with Ku80
Authors: Cierniewski Czeslaw S. , Papiewska‐Pajak Izabela , Malinowski Mariusz , Sacewicz‐Hofman Izabela , Wiktorska Magdalena , Kryczka Jakub , Wysocki Tomasz , Niewiarowska Jolanta , Bednarek Radoslaw
Published: May 2010

Aberrant expression of thymosin β4 (Tβ4) has recently been found to be associated with colorectal carcinoma (CRC) progression evidently due to an increase of the motility and invasion of tumor cells and the induction of a proangiogenic phenotype of endothelial cells. Both mechanisms depend upon matrix‐degrading proteases, particularly plasmin and matrix metalloproteinases (MMPs) that are responsible for extensive tissue remodeling. Cleavage of ECM macromolecules weakens the structural integrity of tissues and exposes cryptic domains of extracellular components, which elicit biological responses distinct from intact molecules. Interestingly, signaling via integrins (αVβ3, α5β1) in CRC cells (HT29, CX1.1) is induced by Tβ4 and VEGF‐A only when they grow in 3D fibrin gels but not in 2D ones. The cells growing in 3D fibrin gels release upon Tβ4 significant amounts of active MMPs (MMP‐2, MMP‐9, and MMP‐7) that cause extensive proteolysis in their close vicinity. As evidenced by a variety of approaches (transfection experiments, coimmunoprecipitation, gene silencing with siRNA), we found that this involves interaction of Tβ4 with Ku80, which has recently been described by us to mediate Tβ4 intracellular activity.
Impact of Changes in Sugar Exudate Created by Biological Damage to Tomato Plants on the Persistence of Escherichia coli O157:H7
Authors: Aruscavage Daniel , Phelan P. Larry , Lee Ken , LeJeune Jeffrey T.
Published: May 2010

ABSTRACT:  The survival of enteric pathogens on vegetable leaves improves due to presence of phytopathogens. Phytopathogen damage alters the microenvironment on the leaf surface. The objective of this study was to identify differences in sugar concentrations in tomato leaves damaged by biotropic plant pathogens and determine if these differences affect Escherichia coli O157:H7 survival. E. coli O157:H7 survived better on tomato plants damaged by Xanthomonas campestris than on healthy plants (P = 0.012). The most common sugars and sugar alcohols in the damaged leaf exudate were glucose, fructose, inositol, and sucrose. The abundance of sucrose and inositol differed between the healthy and infected plants (P < 0.05). In this study, it was found that phytopathogen damaged plants increased sugar availability on the leaf surface for E. coli O157:H7 to proliferate. Keeping plants free from biological damage can limit the amount of leaching of sugars that could allow human pathogens to proliferate. There is the possibility of increasing food safety of vegetable products by limiting phytopathogenic damage to plants.
Antihypertensive Effect of Salt‐Free Soy Sauce, a New Fermented Seasoning, in Spontaneously Hypertensive Rats
Authors: Matsui Toshiro , Zhu Xiao‐Lin , Shiraishi Koso , Ueki Tatsuro , Noda Yoshiharu , Matsumoto Kiyoshi
Published: May 2010

ABSTRACT:  In this study, we focused on the antihypertensive effect of newly fermented salt‐free soy sauce (SFS) in spontaneously hypertensive rats (SHRs). A 13‐wk oral administration of SFS was performed daily in 8‐ to 21‐wk‐old SHRs with a dose of 200 mg/kg of body weight/d. The systolic (SBP) and diastolic (DBP) blood pressures were measured for each week during the experimental period. As a result, a significant (P < 0.01) BP lowering effect was observed from the 5th d to the end of the experiment in the SFS group compared with the control group (ΔSBP21‐wk: 27 mmHg, ΔDBP21‐wk: 20 mmHg). In contrast to such substantial effect by SFS intake, angiotensin I‐converting enzyme activities in blood and local organs as well as pharmaceutical parameters such as serum Na+ or K+ level did not show any significant difference between in both SFS and control groups. Vasoconstriction experiment using thoracic aorta rings from 21‐wk SHRs provided an interesting result that the rings from the SFS group evoked a >2‐fold higher increase in the angiotensin II‐stimulated constrictive response compared with the rings from the control group (P = 0.012), which suggested that the SFS‐intake would be effective in possessing a higher vessel tone.

Practical Application: In this study, we investigated the antihypertensive effect of newly fermented SFS in SHRs. As a result of 13‐wk SFS‐administration, we found a significant antihypertensive effect of the SFS. This finding strongly demonstrates that the developed SFS would be greatly beneficial for health and useful for health‐related industries.
Broccoli‐Derived By‐Products—A Promising Source of Bioactive Ingredients
Authors: Domínguez‐Perles Raúl , Martínez‐Ballesta Maria Carmen , Carvajal Micaela , García‐Viguera Cristina , Moreno Diego A.
Published: May 2010

ABSTRACT: The regular dietary intake of broccoli on a weekly basis has been related to better health, but industrial use of broccoli by‐products (crop remains) is negligible. Adding value to broccoli by‐products in a country such as Spain, one of the main broccoli producers for the EU, is of scientific and economic interest. The present article is focused on the bioactive compounds (glucosinolates, phenolic acids, and flavonoids) and nutrients (vitamin C, minerals, and trace elements), as well as the in vitro radical‐scavenging capacity (DPPH· test), of the broccoli products (harvest remains) resulting from greenhouse cultivation using 80 mM NaCl treatment, representative of the currently available irrigation water in the production areas of Murcia (SE Spain). The bioactive compounds and nutrient contents varied according to the cultivar, organ (leaves or stalks), and the saline stress (80 mM NaCl), in the cultivars Marathon, Nubia, and Viola. Cultivar Nubia was not affected dramatically by 80 mM NaCl and the contents of phytochemicals and nutrients in the by‐products of Nubia fell within the range of health‐promoting levels of edible commercial parts (inflorescences or flower heads). Therefore, adding value to broccoli agrowaste by obtaining bioactive ingredients and nutrients could benefit the food and drug industry.

Practical Application: Many by‐products of the agrifood industry may be useful as sources of nutrients and potentially functional ingredients, giving the opportunity to obtain added‐value products. Previous studies have been focused on edible florets, but in this case we are interested in adding value to broccoli by‐products that represent a real problem in the production sites because no intended use for this material has been envisaged. Therefore, the aim of this study was to add value to the broccoli‐derived by‐products, since recycling all this agrowaste to obtain bioactive ingredients for industry can boost profits and reduce costs and environmental problems.
Basal Cell Carcinoma: What’s New Under the Sun
Authors: Dessinioti Clio , Antoniou Christina , Katsambas Andreas , Stratigos Alexander J.
Published: May 2010

Basal cell carcinoma (BCC) is the most common skin cancer in white populations with an increasing incidence worldwide, thereby imposing an important public health problem. Its etiology is still unclear, but existing data indicate that the risk for BCC development is of multifactorial origin and results from the interplay of both constitutional and environmental factors. Yet, UV radiation (UVR) is believed to be the predominant causative risk factor in the pathogenesis of BCC. For years, BCC and squamous cell carcinoma (SCC) have been grouped together as “nonmelanoma skin cancer.” However, it seems that there are considerable biologic differences between BCC and SCC, and thus each type of epithelial cancer should be addressed separately. The present review provides an overview of the intriguing etiologic link of BCC with UVR and attempts a comprehensive review of recent epidemiologic and molecular evidence that supports this association.
Hydrological Controls and Freshening in Meromictic Soap Lake, Washington, 1939‐20021
Authors: Kallis Jahn , Bodensteiner Leo , Gabriel Anthony
Published: May 2010

Kallis, Jahn, Leo Bodensteiner, and Anthony Gabriel, 2010. Hydrological Controls and Freshening in Meromictic Soap Lake, Washington, 1939‐2002. Journal of the American Water Resources Association (JAWRA) 46(4): 744‐756. DOI: 10.1111/j.1752‐1688.2010.00446.x

Abstract:  The chemically stratified layer of naturally formed meromictic lakes exhibits unusual and often extreme physical and chemical conditions that have resulted in the evolution of uniquely adapted species. The Columbia Basin Irrigation Project appears to have had a marked effect on the hydrology of Soap Lake, a meromictic lake in the Grand Coulee of central Washington. The relation of hydrology to salinity was assessed by analyzing water budgets before and after the introduction of the irrigation project. Before irrigation, water gains were balanced by losses; after irrigation began groundwater gains approximately doubled. To manage lake levels and reduce groundwater influx, wells were installed to intercept groundwater. Although the hydrological cycle has been restored to pre‐irrigation conditions, the meromictic character of the lake continues to change. Interception wells remove 10 to 16 Mm3 of groundwater annually, but influx continues based on change in the monimolimnion. From 1958 to 2003 the chemocline descended 1.1 m and the volume of the monimolimnion from 698,000 m3 to 114,000 m3. Annual loss of volume is occurring at a rate of 1.9% since 1958. Although groundwater interception wells are maintaining the volume of the entire lake, the recession of the chemocline indicates that conditions that have maintained meromixis at Soap Lake are currently not in equilibrium.
The effects of immunosuppressive drugs on CD4+CD25+ regulatory T cells: a systematic review of clinical and basic research
Authors: Zhang Chuntao , Shan Juan , Feng Li , Lu Jun , Xiao Zheng , Luo Lei , Li Chengwen , Guo Yingjia , Li Youping
Published: May 2010

Objective To review the effects of different immunosuppressive drugs on proliferation and function of regulatory T cells (Tregs).

Methods We searched MEDLINE, Embase (from inception to September 2009), and the Cochrane Library (Issue 4, 2009) for clinical and basic research about the effects of various immunosuppressive drugs on Tregs. Data were extracted and methodological quality was assessed by two independent reviewers. Outcome measures for clinical research included blood Tregs levels, acute rejection episodes, and graft function. Outcomes for basic research included percentage of Tregs proliferation, function, Tregs phenotype, and evidence for possible mechanisms. We analyzed data qualitatively.

Results Forty‐two studies, including 19 clinical trials and 23 basic studies, were included. The immunosuppressive drugs studied were calcineurin inhibitors (CNIs), Rapa, anti‐metabolism drugs, IL‐2 receptor‐blocking antibodies, T‐cell depleting antibodies, and co‐stimulation blockade antibodies. Most of the studies were on Rapa and CNIs. Eight basic studies on Rapa and CNIs showed that Rapa could promote the proliferation and function of Tregs, while CNIs could not. Five clinical trials involving a total of 158 patients showed that patients taking Rapa had higher blood concentration of Tregs than patients taking CNIs, but no difference was found in graft function (6–42 months follow‐up).

Conclusion There is substantial evidence that Rapa favors Tregs survival and function. However, the higher numbers of blood Tregs in patients treated with Rapa do not show any association with better graft function. Larger clinical studies with longer follow‐up are needed to more thoroughly assess the efficacy of immunosuppressive drugs on Tregs, and reveal whether a relationship exists between Tregs and graft function.
Structural Modifications in Chemically Polymerized Glass Networks and their Effects
Authors: Yoldas Bulent E.
Published: May 2010

The network morphology of oxides and glasses formed by chemical polymerization is subject to considerable structural manipulations. The structural variations are introduced by the chemical reactions of metal organic compounds that construct and shape the underlying oxide networks in these sol–gel systems. In addition, significant nonstoichiometry may be introduced during the thermal removal of structural hydroxyl and organic groups that frame the oxide networks. Resultant nonequilibrium states persist at very high temperatures and affect thermoplastic and photonic properties of these materials. Among the strongly affected properties are sintering and melting temperatures, molten state viscosity, and emergence of photoluminescence. In this article, the genesis and nature of the structural variations in the chemically polymerized glass networks and exploratory experiments showing their effect on the thermoplastic and photonic properties are presented.
Size Scaling of Tensile Failure Stress in a Float Soda–Lime–Silicate Glass
Authors: Wereszczak Andrew A. , Kirkland Timothy P. , Ragan Meredith E. , Strong Kevin T. , Lin Hua‐Tay , Patel Parimal
Published: May 2010

The (tensile) strength–size scaling of a float soda–lime–silicate glass was studied using biaxial flexure and Hertzian ring crack initiation testing. The examined Weibull effective areas spanned ∼0.4–48,000 mm2. Both the air and tin sides were tested. The air side was stronger than the tin side as others have observed; however, the differences in their characteristic strengths decreased with a decreasing effective area, and their strengths converged for effective areas smaller than ∼100 mm2. The failure stress at the smallest effective area examined for the tin side was ∼500% greater than that at the largest effective area, while that difference was ∼250% for the air side. A Weibull modulus change at ∼100 mm2 suggests different strength‐limiting flaw types were dominant below and above this effective area. These results reinforce the importance of the interpretation and use of the tensile strength of glass in context to how much of its area is being subjected to tensile stress.
The Adiponectin-Mitochondria Connection
Authors: Adler Elizabeth M.
Published: May 2010

Adiponectin signaling through AdipoR1 plays a crucial role in regulating muscle mitochondrial function.
Gag Mutations Can Impact Virological Response to Dual-Boosted Protease Inhibitor Combinations in Antiretroviral-Naïve HIV-Infected Patients
Authors: Larrouy Lucile , Chazallon C. , Landman R. , Capitant C. , Peytavin G. , Collin G. , Charpentier C. , Storto A. , Pialoux G. , Katlama C. , Girard P. M. , Yeni P. , Aboulker J. P. , Brun-Vezinet F. , Descamps D.
Published: May 2010

ANRS 127 was a randomized pilot trial involving naïve patients receiving two dual-boosted protease inhibitor (PI) combinations. Virological response, defined as a plasma HIV RNA level of <50 copies/ml at week 16, occurred in only 41% patients. Low baseline plasma HIV RNA level was the only significant predictor of virological response. The purpose of this study was to investigate the impact on virological response of pretherapy mutations in cleavage sites ofgag,gag-pol, and thegag-polframeshift region. The wholegaggene and protease-coding region were amplified and sequenced at baseline and at week 16 for 48 patients still on the allocated regimen at week 16. No major PI resistance-associated mutations were detected either at baseline or in the 26 patients who did not achieve virological response at week 16. Baseline cleavage site substitutions in the product of thegagopen reading frame at positions 128 (p17/p24) (P= 0.04) and 449 (p1/p6gag) (P= 0.01) were significantly more frequent in those patients not achieving virological response. Conversely, baseline cleavage site mutation at position 437 (TFP/p6pol) was associated with virological response (P= 0.04). In multivariate analysis adjusted for baseline viral load, these 3 substitutions remained independently associated with virological response. We demonstrated here,in vivo, an impact of baseline polymorphicgagmutations on virological response in naïve patients receiving a combination of two protease inhibitors. However, it was not possible to link the substitutions selected under PI selective pressure with virological failure.
Antimicrobial Resistance among Respiratory Pathogens in Spain: Latest Data and Changes over 11 Years (1996-1997 to 2006-2007)
Authors: Pérez-Trallero Emilio , Martín-Herrero Jose E. , Mazón Ana , García-Delafuente Celia , Robles Purificación , Iriarte Victor , Dal-Ré Rafael , García-de-Lomas Juan
Published: May 2010

A nationwide multicenter susceptibility surveillance study (Susceptibility to the Antimicrobials Used in the Community in España [SAUCE] project), SAUCE-4, including 2,559
Streptococcus pneumoniae
, 2,287
Streptococcus pyogenes
, and 2,736
Haemophilus influenzae
isolates was carried out from May 2006 to June 2007 in 34 Spanish hospitals. Then, the results from SAUCE-4 were compared to those from all three previous SAUCE studies carried out in 1996-1997, 1998-1999, and 2001-2002 to assess the temporal trends in resistance and the phenotypes of resistance over the 11-year period. In SAUCE-4, on the basis of the CLSI breakpoints, penicillin (parenteral, nonmeningitis breakpoint) and cefotaxime were the antimicrobials that were the most active against
S. pneumoniae
(99.8% and 99.6%, respectively). Only 0.9% of isolates had a penicillin MIC of ≥2 μg/ml. In
S. pyogenes
, nonsusceptibility to erythromycin was observed in 19.4% of isolates. Among the
H. influenzae
isolates, a β-lactamase-positive prevalence of 15.7% was found. A statistically significant temporal decreasing trend over the 11-year period was observed for nonsusceptibility (from 60.0% to 22.9%) and resistance (from 36.5% to 0.9%) to penicillin and for the proportion of erythromycin-resistant isolates of
S. pneumoniae
of the macrolide-lincosamide-streptogramin B (MLS
B
) phenotype (from 98.4% to 81.3%). A similar trend was observed for the prevalence of ampicillin resistance (from 37.6% to 16.1%), β-lactamase production (from 25.7% to 15.7%), and β-lactamase-negative ampicillin resistance (BLNAR) in
H. influenzae
(from 13.5% to 0.7%). Among erythromycin-resistant isolates of
S. pyogenes
, a significant increasing trend in the prevalence of MLS
B
was observed (from 7.0% to 35.5%). SAUCE-4 confirms a generalized decline in the resistance of the main respiratory pathogens to the antimicrobials as well as a shift in their resistance phenotypes.
Novel Protease Inhibitors (PIs) Containing Macrocyclic Components and 3(
R
),3a(
S
),6a(
R
)-
bis
-Tetrahydrofuranylurethane That Are Potent against Multi-PI-Resistant HIV-1 Variants
In Vitro
Authors: Tojo Yasushi , Koh Yasuhiro , Amano Masayuki , Aoki Manabu , Das Debananda , Kulkarni Sarang , Anderson David D. , Ghosh Arun K. , Mitsuya Hiroaki
Published: May 2010

Natural products with macrocyclic structural features often display intriguing biological properties. Molecular design incorporating macrocycles may lead to molecules with unique protein-ligand interactions. We generated novel human immunodeficiency virus type 1 (HIV-1) protease inhibitors (PIs) containing a macrocycle and
bis
-tetrahydrofuranylurethane. Four such compounds exerted potent activity against HIV-1
LAI
and had 50% effective concentrations (EC
50
s) of as low as 0.002 μM with minimal cytotoxicity. GRL-216 and GRL-286 blocked the replication of HIV-1
NL4-3
variants selected by up to 5 μM saquinavir, ritonavir, nelfinavir, lopinavir, or atazanavir; they had EC
50
s of 0.020 to 0.046 μM and potent activities against six multi-PI-resistant clinical HIV-1 (HIV

mPI
r

) variants with EC
50
s of 0.027 to 0.089 μM. GRL-216 and -286 also blocked HIV-1 protease dimerization as efficiently as darunavir. When HIV-1
NL4-3
was selected by GRL-216, it replicated progressively more poorly and failed to replicate in the presence of >0.26 μM GRL-216, suggesting that the emergence of GRL-216-resistant HIV-1 variants is substantially delayed. At passage 50 with GRL-216 (the HIV isolate selected with GRL-216 at up to 0.16 μM [HIV
216-0.16 μM
]), HIV-1
NL4-3
containing the L10I, L24I, M46L, V82I, and I84V mutations remained relatively sensitive to PIs, including darunavir, with the EC
50
s being 3- to 8-fold-greater than the EC
50
of each drug for HIV-1
NL4-3
. Interestingly, HIV
216-0.16 μM
had 10-fold increased sensitivity to tipranavir. Analysis of the protein-ligand X-ray structures of GRL-216 revealed that the macrocycle occupied a greater volume of the binding cavity of protease and formed greater van der Waals interactions with V82 and I84 than darunavir. The present data warrant the further development of GRL-216 as a potential antiviral agent for treating individuals harboring wild-type and/or HIV

mPI
r

.
Identification of
Anaplasma marginale
Proteins Specifically Upregulated during Colonization of the Tick Vector
Authors: Ramabu Solomon S. , Ueti Massaro W. , Brayton Kelly A. , Baszler Timothy V. , Palmer Guy H.
Published: May 2010

The transition between infection of the mammalian host and colonization of an arthropod vector is required for the ongoing transmission of a broad array of pathogens, from viruses to protozoa. Understanding how this transition is mediated provides opportunities to disrupt transmission through either chemotherapy or immunization. We used an unbiased proteomic screen to identify
Anaplasma marginale
proteins specifically upregulated in the tick compared to the mammalian host. Comparative mass spectrometric analysis of proteins separated by two-dimensional gel electrophoresis of uninfected and infected ISE6 cells and infected mammalian cells identified 15 proteins exclusively expressed or upregulated in tick cells. All 15 had originally been annotated as hypothetical proteins. We confirmed quantitative upregulation and expression
in situ
within the midgut epithelial and salivary gland acinar cells of vector ticks during successful transmission. The results support the hypothesis that
A. marginale
gene expression is regulated by the specific host environment and, in a broader context, that the core genome evolved in the arthropod vector with differential regulation, allowing adaptation to mammalian hosts. Furthermore, the confirmation of the
in situ
expression of candidates identified in ISE6 cell lines indicates that this approach may be widely applicable to bacteria in the genera
Anaplasma
and
Ehrlichia
, removing a major technical impediment to the identification of new targets for vaccine and chemotherapeutic blocking of transmission.