bluuebunny/crossref_metadata_2025 huggingface dataset:
Mast cell lines HMC‐1 and LAD2 in comparison with mature human skin mast cells – drastically reduced levels of tryptase and chymase in mast cell lines
Authors: Guhl Sven , Babina Magda , Neou Angelos , Zuberbier Torsten , Artuc Metin
Published: June 2010

Please cite this paper as: Mast cell lines HMC‐1 and LAD2 in comparison with mature human skin mast cells – drastically reduced levels of tryptase and chymase in mast cell lines. Experimental Dermatology 2010; 19: 845–847.

Abstract:  To circumvent the costly isolation procedure associated with tissue mast cells (MC), two human MC lines, i.e. HMC‐1 and LAD2, are frequently employed, but their relation to mature MC is unknown. Here, we quantitatively assessed their expression of MC markers in direct comparison to skin MC (sMC). sMC expressed all lineage markers at highest and HMC‐1 cells at lowest levels. LAD2 cells expressed comparable high‐affinity IgE receptor α (FcεRIα) and FcεRIγ but less FcεRIβ than sMC and displayed slightly reduced, but robust FcεRI‐mediated histamine release. Only minor differences were found for total histamine content and c‐Kit expression. Huge, and to this level unexpected, differences were found for MC tryptase and chymase, with sMC >>> LAD2 > HMC‐1. Taken together, HMC‐1 cells represent very immature malignantly transformed MC, whereas LAD2 cells can be considered intermediately differentiated. Because of the minute levels of MC proteases, MC lines can serve as surrogates of tissue MC to a limited degree only.
Azelaic acid modulates the inflammatory response in normal human keratinocytes through PPARγ activation
Authors: Mastrofrancesco Arianna , Ottaviani Monica , Aspite Nicaela , Cardinali Giorgia , Izzo Enzo , Graupe Klaus , Zouboulis Christos C , Camera Emanuela , Picardo Mauro
Published: June 2010

Please cite this paper as: Azelaic acid modulates the inflammatory response in normal human keratinocytes through PPARγ activation. Experimental Dermatology 2010; 19: 813–820.

Abstract:  Azelaic acid (AzA), a nine‐carbon dicarboxylic acid, is an agent for the topical treatment of acne. It has also been shown to be effective in rosacea; however, the mechanism of action has not been clarified. Because inflammation is a common feature of both conditions, we investigated the effects of azelaic acid on the inflammatory response of normal human keratinocytes to ultraviolet B light, which is a photosensitizer agent in rosacea. AzA, at 20 mm, a concentration achievable following topical application of a 15% gel, suppresses ultraviolet B light‐induced interleukins‐1β, ‐6 and tumor necrosis factor‐α mRNA expression and protein secretion. Mechanistically, azelaic acid significantly reduced the ultraviolet B light‐induced nuclear translocation of nuclear factor kB p65 subunit and the phosphorylation of the p38 mitogen and stress‐activated protein kinase. Moreover, as peroxisome proliferators–activated receptor γ, (PPARγ) which has a crucial role in the control of inflammation, is activated by fatty acids and products of lipid peroxidation, we further investigated the effect of azelaic acid on the expression of this nuclear receptor. AzA induced peroxisome proliferators–activated receptor‐γ mRNA and its transcriptional activity. The PPARγ antagonist GW9662 abrogated the inhibitory effects of AzA on the UVB‐induced pro‐inflammatory cytokines release and on the cell proliferation. Our study provides new insights into the molecular mechanisms of the activity of azelaic acid and lands additional evidences for its therapeutic effects on inflammatory skin diseases, such as rosacea.
Population density, growth and reproduction of arapaima in an Amazonian river‐floodplain
Authors: Arantes C. C. , Castello L. , Stewart D. J. , Cetra M. , Queiroz H. L.
Published: June 2010

Arantes CC, Castello L, Stewart DJ, Cetra M, Queiroz HL. Population density, growth and reproduction of arapaima in an Amazonian river‐floodplain. Ecology of Freshwater Fish 2010: 19: 455–465. © 2010 John Wiley & Sons A/S

Abstract – Compensatory density effects are key features of fish population dynamics that remain poorly understood in tropical river‐floodplains. We investigated possible compensatory growth and reproductive processes for a river‐floodplain population ofArapaimasp., an extinction‐prone fish species of South America. Body growth was studied through analysis of ring patterns on the scales, and size and age at sexual maturity was studied through analysis of female gonads. Growth and maturity were compared for unmanaged conditions with relatively low population density (in 1990s) versus managed conditions with markedly higher density (in 2005–2006); between 1999 and 2005–2006, abundance increased 7.3 fold. Results contradict theoretical expectations for slower growth and delayed reproduction at higher population density. Total lengths of arapaima at low population density were significantly shorter for age classes 1–5 compared with lengths of those age classes at high population density (ancova,P < 0.0001 for both slopes and intercepts). Total length at 50% maturity (L50) only declined about 4% with increasing density (e.g., 164 cm at low density vs. 157 cm at high density). Apparent faster growth at high density and only a slight change in size at maturity resulted in fishes spawning at an earlier age with high density conditions (age 3 vs. age 4–5). We hypothesise that these patterns reflect compliance with minimum size limits of catch during the high density (managed) situation, where there was no harvest of immature fishes. Compliance with minimum size limits, thus, may have led to faster average body growth rate and earlier reproduction, which has greatly promoted population recovery.
Effects of littoral habitat complexity and sunfish composition on fish production
Authors: Carey M. P. , Maloney K. O. , Chipps S. R. , Wahl D. H.
Published: June 2010

Carey MP, Maloney KO, Chipps SR, Wahl DH. Effects of littoral habitat complexity and sunfish composition on fish production. Ecology of Freshwater Fish 2010: 19: 466–476. © 2010 John Wiley & Sons A/S

Abstract – Habitat complexity is a key driver of food web dynamics because physical structure dictates resource availability to a community. Changes in fish diversity can also alter trophic interactions and energy pathways in food webs. Few studies have examined the direct, indirect, and interactive effects of biodiversity and habitat complexity on fish production. We explored the effects of habitat complexity (simulated vegetation), sunfish diversity (intra‐ vs. inter‐specific sunfish), and their interaction using a mesocosm experiment. Total fish production was examined across two levels of habitat complexity (low: 161 strands m−2and high: 714 strands m−2) and two sunfish diversity treatments: bluegill only (Lepomis macrochirus) and bluegill, redear sunfish (Lepomis microlophus), and green sunfish (Lepomis cyanellus) combination. We also measured changes in total phosphorus, phytoplankton, periphyton, and invertebrates to explain patterns in fish production. Bluegill and total fish production were unaffected by the sunfish treatments. Habitat complexity had a large influence on food web structure by shifting primary productivity from pelagic to a more littoral pathway in the high habitat treatments. Periphyton was higher with dense vegetation, leading to reductions in total phosphorus, phytoplankton, cladoceran abundance and fish biomass. In tanks with low vegetation, bluegill exhibited increased growth. Habitat complexity can alter energy flow through food webs ultimately influencing higher trophic levels. The lack of an effect of sunfish diversity on fish production does not imply that conserving biodiversity is unimportant; rather, we suggest that understanding the context in which biodiversity is important to food web dynamics is critical to conservation planning.
Aquatic exercise improves the monocyte pro‐ and anti‐inflammatory cytokine production balance in fibromyalgia patients
Authors: Ortega E. , Bote M. E. , Giraldo E. , García J. J.
Published: June 2010

Current hypotheses of the etiology of fibromyalgia (FM) include inflammatory disorders. We evaluated the effect of a pool‐aquatic exercise program (8 months, two weekly 60‐min sessions) on the inflammatory cytokine production by isolated monocytes, and on the serum concentration of C‐reactive protein (CRP), in a group of female FM patients. Monocytes from FM patients released more IL‐1β, TNFα, IL‐6, and IL‐10 than those from an age‐matched control group of healthy women (HW). This inflammatory disorder in FM women was also manifested by high circulating concentrations of CRP. Increased IL‐6 with a concomitant decreased TNFα spontaneous release was found after 4 months (midway through) of the exercise program. At the end of the program (8 months), monocytes from FM patients showed diminished spontaneous production of pro‐/anti‐inflammatory cytokines, with a similar spontaneous release of IL‐1β and IL‐6 to that of HW, but a lower production of TNFα and higher of IL‐10. Lipopolysaccharide‐induced production of IL‐1β, TNFα, IL‐6, and IL‐10 also decreased at the end of the exercise program, although IL‐10 remained higher than HW. The anti‐inflammatory effect of the exercise program was also corroborated by a decrease in the circulating CRP concentration. Exercise also improved the health‐related quality of life of FM patients.
Detection of meticillin‐resistant staphylococcus aureus (MRSA) colonization in newborn infants using real‐time polymerase chain reaction (PCR)
Authors: Francis ST , Rawal S , Roberts H , Riley P , Planche T , Kennea NL
Published: June 2010

Objective:  Meticillin‐resistant staphylococcus aureus (MRSA) colonization on neonatal units is a common and important clinical problem. Effectiveness of polymerase chain reaction (PCR) for detecting MRSA nasal colonization of infants was evaluated and compared to culture‐based methods. The effect of skin decolonization in affected infants was studied.

Methods:  Paired nasal swabs were collected from infants in our neonatal unit over a 12‐month period (September 2007–2008). Colonization with MRSA was determined with a commercially available PCR method and compared to culture.

Results:  A total of 696 paired nasal swabs were taken. Three infants were colonized at the beginning and were included. There were positive PCRs in 12 infants. Five infants cultured MRSA from a nasal swab at the same time. No infants were culture‐positive when PCR was negative (sensitivity 100%, specificity 99% compared to culture). PCR results were available within 24 h. Five infants were PCR+ and isolated meticillin‐sensitive Staphylococcus aureus. This organism gave a false‐positive PCR result. Two infants transferred in on broad‐spectrum antibiotics were PCR+ and negative by culture. Decolonization led to negative nasal PCR and culture in 4/5 infants to discharge.

Conclusions: PCR methods are sensitive and specific for detection of MRSA colonization in newborn infants of all gestations with results 1–2 days before culture.
Oxidative markers in children with severe obesity following low‐calorie diets supplemented with mandarin juice
Authors: Codoñer‐Franch Pilar , López‐Jaén Ana Belén , De La Mano‐Hernández Agustín , Sentandreu Enrique , Simó‐Jordá Raquel , Valls‐Bellés Victoria
Published: June 2010

Aim:  To evaluate the effect of supplementing a hypocaloric diet with mandarin juice, a food with a high content of antioxidants (vitamin C, flavonoids and carotenoids), on biomarkers of oxidant/antioxidant status of severe obese children.

Methods:  Forty obese children were randomized into two groups pair‐wise in a 4‐week controlled intervention study. Both groups followed a hypocaloric diet. One group received additionally a supplementation of 500 mL of 100% mandarin juice daily. Clinical data, anthropometry, dietary intake and fasting blood samples were collected at baseline and after the intervention. Lipid peroxidation was assessed by circulating levels of malondialdehyde, and protein oxidation was determined by the concentration of plasma carbonyl groups. The antioxidant defence was evaluated by red cell‐reduced glutathione and plasma levels of α‐tocopherol and vitamin C.

Results:  The supplemented group experienced a decrease in the levels of malondialdehyde (−9.6%, p = 0.014) and carbonyl groups (−36.1%, p = 0.006) and an increase in antioxidants (α‐tocopherol +16.1%, p = 0.006, glutathione +36.1%, p < 0.0001, and vitamin C + 94.6%, p < 0.0001).

Conclusion:  The mandarin juice consumption with a reduced calorie diet positively affects the antioxidant defence and produces a decrease in biomarkers of oxidative stress in obese children.
Cracked Teeth: A Review of the Literature
Authors: LUBISICH ERINNE B. , HILTON THOMAS J. , FERRACANE JACK
Published: June 2010

Although cracked teeth are a common problem for patients and dentists, there is a dearth of evidence‐based guidelines on how to prevent, diagnose, and treat cracks in teeth. The purpose of this article is to review the literature to establish what evidence exists regarding the risk factors for cracked teeth and their prevention, diagnosis, and treatment.

(J Esthet Restor Dent 22:158–167, 2010)
Importance of the gating segment in the substrate‐recognition loop of pyranose 2‐oxidase
Authors: Spadiut Oliver , Tan Tien‐Chye , Pisanelli Ines , Haltrich Dietmar , Divne Christina
Published: June 2010

Pyranose 2‐oxidase from Trametes multicolor is a 270 kDa homotetrameric enzyme that participates in lignocellulose degradation by wood‐rotting fungi and oxidizes a variety of aldopyranoses present in lignocellulose to 2‐ketoaldoses. The active site in pyranose 2‐oxidase is gated by a highly conserved, conformationally degenerate loop (residues 450–461), with a conformer ensemble that can accommodate efficient binding of both electron‐donor substrate (sugar) and electron‐acceptor substrate (oxygen or quinone compounds) relevant to the sequential reductive and oxidative half‐reactions, respectively. To investigate the importance of individual residues in this loop, a systematic mutagenesis approach was used, including alanine‐scanning, site‐saturation and deletion mutagenesis, and selected variants were characterized by biochemical and crystal‐structure analyses. We show that the gating segment (454FSY456) of this loop is particularly important for substrate specificity, discrimination of sugar substrates, turnover half‐life and resistance to thermal unfolding, and that three conserved residues (Asp452, Phe454 and Tyr456) are essentially intolerant to substitution. We furthermore propose that the gating segment is of specific importance for the oxidative half‐reaction of pyranose 2‐oxidase when oxygen is the electron acceptor. Although the position and orientation of the slow substrate 2‐deoxy‐2‐fluoro‐glucose when bound in the active site of pyranose 2‐oxidase variants is identical to that observed earlier, the substrate‐recognition loop in F454N and Y456W displays a high degree of conformational disorder. The present study also lends support to the hypothesis that 1,4‐benzoquinone is a physiologically relevant alternative electron acceptor in the oxidative half‐reaction.
Effect of soil and physiographic factors on ecological plant groups in the eastern Elborz mountain rangeland of Iran
Authors: Tatian Mohammadreza , Arzani Hossein , Reihan Majid Karimpour , Bahmanyar Mohammad Ali , Jalilvand Hamid
Published: June 2010

To investigate the cause of differences among ecological plant groups in the east of the Elborz mountain rangeland, the role of edaphical and topographical characteristics was considered. Two ordination techniques, detrended correspondence analysis (DCA) and canonical correspondence analysis (CCA), were used. The values of slope, aspect, altitude and lithology information were provided by Geographic Information System (GIS), and geomorphological land units were determined by intersection of overlaid data layers. Plant sampling was undertaken within nine land units with similar lithology and altitude but which differed in slope and aspect, using 30 randomly selected 1 m2plots per land unit. Soil samples were taken from two depths (0–20 and 20–50 cm) in each plot. Organic matter, bulk density, texture, calcium carbonate, total nitrogen and available phosphorus and potassium contents were determined. The results indicated that plant species have different responses to edaphical and topographical parameters. The invader species group had a balanced amount of influence from all soil components and topographic factors, whereas the native grasses were located in productive soils, which typically have a low grazing intensity, such as the north facing slopes. Coniferous bushy trees, cushion plants and some shrub plant groups were found on steep slopes with alkaline soils. The broad‐leaved bushy trees plant group was abundant in fine texture soils on low and humid slopes.
The evolution of M*/MBH between z = 2 and z = 0
Authors: Trakhtenbrot Benny , Netzer Hagai
Published: June 2010

We propose a novel method to estimate M*/MBH, the ratio of stellar mass (M*) to black hole mass (MBH) at various redshifts using two recent observational results: the correlation between the bolometric luminosity of active galactic nuclei (AGN) and the star formation rate (SFR) in their host galaxies, and the correlation between SFR and M* in star-forming (SF) galaxies. Our analysis is based on MBH and Lbol measurements in two large samples of type I AGN at z≃ 1 and 2, and the measurements of M*/MBH in 0.05 < z < 0.2 red galaxies. We find that M*/MBH depends on MBH at all redshifts. At z≃ 2, M*/MBH∼ 280 and ∼40 for MBH= 108 and MBH= 109M⊙, respectively. M*/MBH grows by a factor of ∼4–8 from z≃ 2 to 0 with extreme cases that are as large as 10–20. The evolution is steeper than reported in other studies, probably because we treat only AGN in SF hosts. We caution that estimates of M*/MBH evolution which ignore the dependence of this ratio on MBH can lead to erroneous conclusions.
Tracing the history of recent bulge star formation in Active Galactic Nuclei
Authors: Liu Xin
Published: June 2010

We examine the relation between black hole accretion and bulge star formation as a function of look-back time (τ) in 20541 obscured active galactic nuclei (AGNs; with redshifts and bolometric luminosities ) optically selected from the Sloan Digital Sky Survey (SDSS). To quantify the most recently formed stars with ages less than typical AGN lifetimes, we estimate the differentiated specific star formation rate (SSFRτ) based on population synthesis analysis. The Eddington ratio (λ) is inferred using [Oiii]λ5007 luminosity and stellar velocity dispersion as proxies for and black hole mass, respectively. We find that when τ < τ0, SDSS AGNs follow a power law λ∝ SSFR1.0−1.1τ; the relation flattens out when τ > τ0. The threshold time-scale τ0 is ∼0.1 (∼1) Gyr in young (old) bulges. The scatter in the power laws is dominated by observational uncertainties. These results may provide useful constraints on models explaining the correlations between AGN activity and bulge star formation.
Financial Literacy 501
Authors: CUDE BRENDA J.
Published: June 2010

The articles in this special issue of The Journal of Consumer Affairs focus on financial literacy. The scope of the content spans conceptualization and measurement as well as factors influencing financial literacy and its impact. This editorial prelude suggests one way that educators might use this issue as well as a previous (Summer 2008) special issue of the journal that also focused on financial literacy.
Expectations of Inflation: The Role of Demographic Variables, Expectation Formation, and Financial Literacy
Authors: BRUINE de BRUIN WÄNDI , VANDERKLAAUW WILBERT , DOWNS JULIE S. , FISCHHOFF BARUCH , TOPA GIORGIO , ARMANTIER OLIVIER
Published: June 2010

When financial decisions have consequences beyond the immediate future, individuals' economic success may depend on their ability to forecast the rate of inflation. Higher inflation expectations have been reported by individuals who are female, poorer, single and less educated. Our results suggest that these demographic differences in inflation expectations may be partially explained by variations in expectation formation and financial literacy. Specifically, higher inflation expectations were reported by individuals who focused more on how to cover their future expenses and on prices they pay (rather than on the US inflation rate) and by individuals with lower financial literacy.
Exploring QSARs for Inhibitory Activity of Non‐peptide HIV‐1 Protease Inhibitors by GA‐PLS and GA‐SVM
Authors: Deeb Omar , Goodarzi Mohammad
Published: June 2010

The support vector machine (SVM) and partial least square (PLS) methods were used to develop quantitative structure activity relationship (QSAR) models to predict the inhibitory activity of non‐peptide HIV‐1 protease inhibitors. Genetic algorithm (GA) was employed to select variables that lead to the best‐fitted models. A comparison between the obtained results using SVM with those of PLS revealed that the SVM model is much better than that of PLS. The root mean square errors of the training set and the test set for SVM model were calculated to be 0.2027, 0.2751, and the coefficients of determination (R2) are 0.9800, 0.9355 respectively. Furthermore, the obtained statistical parameter of leave‐one‐out cross‐validation test (Q2) on SVM model was 0.9672, which proves the reliability of this model. The results suggest that TE2, Ui, GATS5e, Mor13e, ATS7m, Ss, Mor27e, and RDF035e are the main independent factors contributing to the inhibitory activities of the studied compounds.
The Remarkable Stability of Chimeric, Sialic Acid‐derived α/δ‐Peptides in Human Blood Plasma
Authors: Saludes Jonel P. , Natarajan Arutselvan , DeNardo Sally J. , Gervay‐Hague Jacquelyn
Published: June 2010

Peptides are labile toward proteolytic enzymes, and structural modifications are often required to prolong their metabolic half‐life and increase resistance. One modification is the incorporation of non‐α‐amino acids into the peptide to deter recognition by hydrolytic enzymes. We previously reported the synthesis of chimeric α/δ‐peptides from glutamic acids (Glu) and the sialic acid derivative Neu2en. Conformational analyses revealed these constructs adopt secondary structures in water and may serve as conformational surrogates of polysialic acid. Polysialic acid is a tumor‐associated polysaccharide and is correlated with cancer metastasis. Soluble polysialic acid is rapidly cleared from the blood limiting its potential for vaccine development. One motivation in developing structural surrogates of polysialic acid was to create constructs with increased bioavailability. Here, we report plasma stability profiles of Glu/Neu2en α/δ‐peptides. DOTA was conjugated at the peptide N‐termini by solid phase peptide synthesis, radiolabeled with 111In, incubated in human blood plasma at 37 °C, and their degradation patterns monitored by cellulose acetate electrophoresis and radioactivity counting. Results indicate that these peptides exhibit a long half‐life that is two‐ to three‐orders of magnitude higher than natural α‐peptides. These findings provide a viable platform for the synthesis of plasma stable, sialic acid‐derived peptides that may find pharmaceutical application.
Inhibition of HIV‐1 Replication by Isoxazolidine and Isoxazole Sulfonamides
Authors: Loh Belinda , Vozzolo Luciano , Mok B. James , Lee Chien Chi , Fitzmaurice Richard J. , Caddick Stephen , Fassati Ariberto
Published: June 2010

Targeting host factors is a complementary strategy for the development of new antiviral drugs. We screened a library of isoxazolidine and isoxazole sulfonamides and found four compounds that inhibited HIV‐1 infection in human CD4+ lymphocytic T cells with no toxicity at IC90 concentrations. Structure‐activity relationship showed that benzyl sulfonamides and a halo‐substituted aromatic ring on the heterocycle scaffold were critical for antiretroviral activity. The size and position of the incorporated halogen had a marked effect on the antiretroviral activity. The sulfonamide derivatives had no significant effect on HIV‐1 entry, reverse transcription and integration but impaired a step necessary for activation of viral gene expression. This step was Tat‐independent, strongly suggesting that the target is a cell factor. A virus partially resistant to the least potent compounds could be selected but could not be propagated in the long term, consistent with the possibility that HIV‐1 may be less likely to develop resistance against drugs targeting some host factors. Here, we provide evidence that novel synthetic methods can be applied to develop small molecules with antiretroviral activity that target host factors important for HIV‐1 replication.
The Use of Biochemical and Biophysical Tools for Triage of High‐Throughput Screening Hits – A Case Study with Escherichia coli Phosphopantetheine Adenylyltransferase
Authors: Miller J. Richard , Thanabal Venkataraman , Melnick Michael M. , Lall Manjinder , Donovan Charles , Sarver Ronald W. , Lee Doh‐Yeel , Ohren Jeff , Emerson Don
Published: June 2010

High‐throughput screening is utilized by pharmaceutical researchers and, increasingly, academic investigators to identify agents that act upon enzymes, receptors, and cellular processes. Screening hits include molecules that specifically bind the target and a greater number of non‐specific compounds. It is necessary to ‘triage’ these hits to identify the subset worthy of further exploration. As part of our antibacterial drug discovery effort, we applied a suite of biochemical and biophysical tools to accelerate the triage process. We describe application of these tools to a series of 9‐oxo‐4,9‐dihydropyrazolo[5,1‐b]quinazoline‐2‐carboxylic acids (PQ) hits from a screen of Escherichia coli phosphopantetheine adenylyltransferase (PPAT). Initial confirmation of specific binding to phosphopantetheine adenylyltransferase was obtained using biochemical and biophysical tools, including a novel orthogonal assay, isothermal titration calorimetry, and saturation transfer difference NMR. To identify the phosphopantetheine adenylyltransferase sub‐site bound by these inhibitors, two techniques were utilized: steady‐state enzyme kinetics and a novel 19F NMR method in which fluorine‐containing fragments that bind the ATP and/or phosphopantetheine sites serve as competitive reporter probes. These data are consistent with PQs binding the ATP sub‐site. In addition to identification of a series of PPAT inhibitors, the described hit triage process is broadly applicable to other enzyme targets in which milligram quantities of purified target protein are available.
Effects of temperature and hydric environment on survival of the Panamanian Golden Frog infected with a pathogenic chytrid fungus
Authors: BUSTAMANTE Heidi M. , LIVO Lauren J. , CAREY Cynthia
Published: June 2010

Considerable controversy exists concerning whether or not climate changes (particularly global warming) are causing outbreaks of a lethal amphibian pathogen, the chytrid fungus Batrachochytrium dendrobatidis (Longcore, Pessier & D.K. Nichols 1999). In the present study, groups of Panamanian golden frogs (Atelopus zeteki Dunn, 1993), a critically endangered amphibian thought to be nearly extinct in Panama, were exposed to varying dosages of zoospores of Batrachochytrium dendrobatidis, temperatures and hydric environments in order to learn whether this species is susceptible to this pathogen and, if so, how environmental factors affect survival. This pathogen proved to be highly lethal for A. zeteki. Frogs exposed to a dosage of 100 Bd zoospores survived significantly (P < 0.0001) longer than those that had been exposed to 104 or 106 zoospores. Exposed frogs housed at 23 °C survived significantly (P < 0.0001) longer than those that were housed at 17 °C. Exposed frogs held in dry conditions survived significantly longer than those in wet conditions (P < 0.0001). As a laboratory study, these results do not directly test hypotheses about the relation between climate change and the decline of these frogs in the field, but they inform the discussion about how environmental conditions can have an impact on the interaction between a susceptible amphibian and this pathogen. These data do not support the contention that rising global temperatures are necessary to cause the death of amphibians infected with this pathogen because the pathogen was equally lethal at 17 as at 23 °C, and frogs at the warmer temperature lived significantly longer than those at the cooler one.
Climate change induced range shifts of Galliformes in China
Authors: LI Renqiang , TIAN Huidong , LI Xinhai
Published: June 2010

Climate change will cause range shifts of many species in the future. Galliformes might be particularly vulnerable to climate change, as they have low dispersal ability. Little is known about their possible responses to the future climate. We used a generalized additive model to predict the current and future ranges of all 63 Galliformes in China, based on a comprehensive species occurrence database and a combination of climate variables. Other environmental variables (e.g. elevation and human footprint index) were also considered, as well as the latitude and longitude of the occurrences. Principal component analysis was conducted to illustrate the association between environmental variables and Galliformes distributions. Using the Special Report on Emissions Scenarios (SRES) A2 climate change scenario for 2071–2100, we projected that 29 species would have range shifts over 50%, including 13 endemic species. Galliformes at higher elevation face greater range shifts. Northward shifts are greater than those in other directions. We suggest conservationists pay special attention to the 29 Galliformes that face extensive range shifts, especially the endemic species among them.
Effect of ENSO‐driven precipitation on population irruptions of the Yangtze vole Microtus fortis calamorum in the Dongting Lake region of China
Authors: ZHANG Zhibin , XU Lei , GUO Cong , WANG Yong , GUO Yongwang
Published: June 2010

The Yangtze vole (Microtus fortis Buechner, 1889) is a small herbivore species that inhabits lake beaches in the Dongting Lake region along the Yangtze River in Southern China. Its population shows strong oscillations during the wet season due to summer precipitation‐induced immigration away from the lake into adjacent rice fields. The effect of El Niño‐Southern Oscillation‐driven precipitation on population abundance and growth of the vole species is not fully understood. We undertook an analysis of the combined data of 4 time series covering 1981–2006 from 4 different sites and a separate analysis on a single time series (1981–2006) from one site. Our results demonstrate that a dual effect of El Niño‐Southern Oscillation‐driven precipitation on the population abundance of voles is time‐dependent: precipitation in the current year has a positive effect, whereas precipitation in the previous year has a negative effect. The dual effect of precipitation on vole population is well explained by the unique interactions among vole population, precipitation water level and the lake beach habitat around Dongting Lake. We found that drier than average weather of the previous year benefited voles because their breeding habitats, lake beaches, were exposed for long stretches of time. Wet weather was found to increase the number of voles inhabiting rice fields because as the water level of the lake rose they were forced from beaches into surrounding rice fields. Summer precipitation in the Dongting Lake region was found to be positively associated with the sea surface temperature (SST) of the eastern tropical Pacific Ocean of the previous year and winter SST and spring SST of the current year. Annual rates of increase in the vole population of the reconstructed time series are negatively associated with the vole abundance and autumn precipitation of the previous year and winter precipitation of the current years. These results suggest that both extrinsic and density‐dependent intrinsic factors may affect population dynamics of the Yangtze voles.
Multi‐scale approach to understanding climate effects on offspring size at birth and date of birth in a reptile
Authors: CADBY Chloé D. , WHILE Geoffrey M. , HOBDAY Alistair J. , ULLER Tobias , WAPSTRA Erik
Published: June 2010

Climate change is already impacting species around the world. Although most focus has been on the effect of temperature, changes in climatic variables other than temperature are also expected to drive biological change. Current models suggest that ectotherms, such as reptiles, will be strongly affected by climate change; however, data from natural populations are rare. Here, we use extensive data from 2 populations of a viviparous lizard (Niveoscincus ocellatus Gray, 1845) at the climatic extreme of the species distribution. We examine the effects of climate at a local, a regional and a global scale (thus, integrating a suite of variables at different spatial and temporal scales) on 2 key life history traits: offspring date of birth and size at birth. Overall, our results show that across 9 years of study, local temperature had strong effects on the offspring date of birth but not on the size at birth. Therefore, a rapid increase in local temperature throughout the species range (as predicted under global warming scenarios) is likely to affect phenological processes with potential concomitant effects on offspring fitness and survival.
Tissue engineering of skin and cornea
Authors: Paquet Claudie , Larouche Danielle , Bisson Francis , Proulx Stéphanie , Simard‐Bisson Carolyne , Gaudreault Manon , Robitaille Hubert , Carrier Patrick , Martel Israël , Duranceau Louise , Auger François A. , Fradette Julie , Guérin Sylvain L. , Germain Lucie
Published: June 2010

Human beings are greatly preoccupied with the unavoidable nature of aging. While the biological processes of senescence and aging are the subjects of intense investigations, the molecular mechanisms linking aging with disease and death are yet to be elucidated. Tissue engineering offers new models to study the various processes associated with aging. Using keratin 19 as a stem cell marker, our studies have revealed that stem cells are preserved in human skin reconstructed by tissue engineering and that the number of epithelial stem cells varies according to the donor's age. As with skin, human corneas can also be engineered in vitro. Among the epithelial cells used for reconstructing skin and corneas, significant age‐dependent variations in the expression of the transcription factor Sp1 were observed. Culturing skin epithelial cells with a feeder layer extended their life span in culture, likely by preventing Sp1 degradation in epithelial cells, therefore demonstrating the pivotal role played by this transcription factor in cell proliferation. Finally, using the human tissue‐engineered skin as a model, we linked Hsp27 activation with skin differentiation.
Exogenous mammalian extracellular HSP70 reduces endotoxin manifestations at the cellular and organism levels
Authors: Rozhkova Elena , Yurinskaya Marina , Zatsepina Olga , Garbuz David , Karpov Vadim , Surkov Sergei , Murashev Arkady , Ostrov Vladimir , Margulis Boris , Evgen’ev Mikhail , Vinokurov Maxim
Published: June 2010

In this study, we checked whether HSP70 preparations of different origins are able to protect model animals (rats) from endotoxic shock and modify the response of myeloid cells to lipopolysaccharide (LPS) challenge. It was shown that HSP70 preparations can effectively protect organisms from endotoxic shock by strongly decreasing mortality and restoring both homeostasis and various hemodynamic characteristics. At the cellular level, HSP70 preparations significantly inhibit LPS‐induced reactive oxygen species production in various myeloid cells and decrease NO expression in macrophages, which is enhanced after LPS priming. In parallel, HSP70 preconditioning partially normalizes neutrophil apoptosis, which is disturbed as a result of LPS stimulation. These results suggest that the antiseptic actions of HSP70 preparations are probably realized at the level of receptor membrane complexes of myeloid cells, which represent the major target of LPS action. Taken together, our findings show that extracellular mammalian HSP70 may play an important role in innate immunity modulation and stimulation of endogenous protective mechanisms, both at the cellular and organism levels, which make this protein a promising base for the development of efficient antiseptic drugs.
Molecular bridging of aging and cancer
Authors: Cheung Caroline T. , Kaul Sunil C. , Wadhwa Renu
Published: June 2010

Collaborator of ARF (CARF) was first cloned as an ARF partner in yeast two‐hybrid screens. It enhances ARF‐dependent and ‐independent p53 functions, which are central to the control of cell growth and tumor suppression in human cells. CARF interacts with ARF, p53, and MDM2 proteins, and in turn gets regulated by MDM2‐mediated degradation, suggesting a self‐regulatory loop. CARF is upregulated during replicative, oncogenic, and stress‐induced senescence. Overexpression of CARF induced premature senescence in normal human fibroblasts that was mediated by upregulation of p53‐p21CIP1/WAF1 and p16INK4a– pRB pathways. Knockdown of CARF resulted in mitotic arrest leading to excessive chromosomal condensation, aneuploidy, and apoptosis, suggesting that CARF is essential for cell survival. Most recently, we have found that CARF causes bidirectional regulation of p53 and pRB pathways, either arresting or promoting growth, and thus, it could be a potential threshold link between aging and cancer.
Introduction to Aging, Cancer, and Age‐related Diseases
Authors: Perry Daniel P.
Published: June 2010

A rising tide of chronic age‐dependent diseases, co‐morbidities, and geriatric syndromes—a veritable Silver Tsunami—will soon present serious challenges for North America, Europe, Japan, and other industrialized nations. Meanwhile, a growing number of scientists, led by biogerontologists, maintain that the key to blunting the societal impact of large‐scale decline and disability among older populations lies with better understanding and potential manipulation of biological mechanisms of aging itself. Well‐characterized interventions that slow aging and extend health and vigor in animal models may be forerunners of technologies that preserve additional years of healthy productive life in humans. What will it take to validate these momentous insights from biogerontology and their potential applications for human populations? What are the points of resistance for key opinion leaders and policy makers? And how can biogerontologists make common cause with those outside the discipline to inform larger and more politically powerful audiences?
Protection from aging by small chaperones
Authors: Morrow Geneviève , Kim Hyun‐Ju , Le Pécheur Marie , Kaul Sunil C. , Wadhwa Renu , Tanguay Robert M.
Published: June 2010

Aging is a complex process accompanied by a decreased capacity of cells to cope with random molecular damages. Damaged proteins can form aggregates and have cytotoxic properties, a feature of many age‐associated diseases. Small Hsps are chaperones involved in the refolding and/or disposal of protein aggregates. In Drosophila melanogaster, the mitochondrial DmHsp22 is preferentially upregulated during aging. Its over‐expression results in an extension of lifespan (>30%) and an increased resistance to stress. Although DmHsp22 has a chaperone‐like activity in vitro, additional mechanisms by which it may extend lifespan in vivo are unknown. Genome‐wide transcriptional analysis and comparative mitochondrial proteomic analysis by MALDI‐TOF were performed to unveil differences in long‐lived DmHsp22 over‐expressing flies. Flies over‐expressing DmHsp22 display an upregulation of genes normally downregulated with age and involved in energy production and protein biosynthesis. Interestingly, DmHsp22 over‐expression extended lifespan of normal fibroblasts by slowing the aging process. However, its expression also increased the malignant properties of human transformed cells. The delicate balance between beneficial and noxious effects of this small chaperone are discussed.
Chaperonopathies of senescence and the scrambling of interactions between the chaperoning and the immune systems
Authors: Macario Alberto J. L. , Cappello Francesco , Zummo Giovanni , Conway de Macario Everly
Published: June 2010

Aging entails progressive deterioration of molecules and supramolecular structures, including Hsp chaperones and their complexes, paralleled by functional decline. Recent research has changed our views on Hsp chaperones. They work inside and outside cells in many locations, alone or forming teams, interacting with cells, receptors, and molecules that are not chaperones, in roles that are not typically attributed to chaperones, such as protein folding. Hsp chaperones form a physiological system with a variety of functions and interactions with other systems, for example, the immune system. We propose that chaperone malfunctioning due to structural damage or gene dysregulation during aging has an impact on the immune system, creating the conditions for an overall malfunction of both systems. Pathological chaperones cannot interact with the immune system as normal ones do, and this leads to an overall readjustment of the interactions that is apparent during senescence and is likely to cause many of its manifestations.
Transcriptome analysis and tumor suppressor requirements of STAT5‐induced senescence
Authors: Mallette Frédérick A. , Moiseeva Olga , Calabrese Viviane , Mao Botum , Gaumont‐Leclerc Marie‐France , Ferbeyre Gerardo
Published: June 2010

Although it is acknowledged that senescent cells accumulate with age, the molecular mechanisms leading to cell senescence as a function of age remain to be identified. In cell culture models, it has been clearly shown that senescence involves the activation of a DNA damage response secondary to short telomeres or oncogene expression. Oncogenes are altered versions of genes coding for proteins that mediate signals from extracellular factors such as cytokines, growth factors, and hormones. In particular, we show here that constitutive activation of the JAK/STAT5 signaling pathway induces senescence in both mouse and human normal cells. The process involves activation of the p53 and Rb tumor suppressor pathways and mitochondrial dysfunction. Gene expression analysis of STAT5‐induced senescence revealed changes in the expression of genes coding for cytokines, proteins in cytokine signaling pathways, and several metabolic enzymes. We discuss a model called senescence‐induced senescence, in which cytokines secreted by senescent cells can propagate the process as a function of age.
Major heat shock protein Hsp72 controls oncogene‐induced senescence
Authors: Sherman Michael
Published: June 2010

Various heat shock proteins, including Hsp72, are strongly upregulated in cancers, but their significance for tumor emergence and growth is poorly understood. Here we review recent data from several labs to indicate that Hsps, including Hsp72, are critical for growth of transformed but not normal cells. By manipulating expression and activity of Hsp72 and several oncogenes, it was shown that Hsp72 suppresses oncogene‐induced senescence, thus allowing proliferation of cancer cells. Importantly, Hsp72 is able to suppress both p53‐dependent and p53‐independent senescence pathways. We propose that targeting Hsp72 may be a promising approach toward development of novel cancer therapies.
Antioxidant and Antibacterial Activities on Foodborne Pathogens of Artocarpus heterophyllus Lam. (Moraceae) Leaves Extracts
Authors: Loizzo M.R. , Tundis R. , Chandrika U.G. , Abeysekera A.M. , Menichini F. , Frega N.G.
Published: June 2010

Abstract:  Total water extract, ethyl acetate, and aqueous fractions from the leaves of Artocarpus heterophyllus were evaluated for phenolic content, antioxidant, and antibacterial activities against some foodborne pathogens such as E. coli, Listeria monocytogenes, Salmonella typhimurium, Salmonella enterica, Bacillus cereus, Enterococcus faecalis, and Staphylococcus aureus. The minimum inhibitory concentration (MICs) of extract and fractions determined by the agar dilution method were ranged from 221.9 μg/mL for ethyl acetate fraction to 488.1 μg/mL for total extract. In the agar diffusion method the diameters of inhibition were 12.2 for the total extract, 10.7 and 11.5 for ethyl acetate and aqueous fractions, respectively. A. heterophyllus showed significant antioxidant activity tested in different in vitro systems (DPPH, ABTS, FRAP, and Fe2+ chelating activity assay). In particular, in DPPH assay A. heterophyllus total extract exhibited a strong antiradical activity with an IC50 value of 73.5 μg/mL while aqueous fraction exerted the highest activity in FRAP assay (IC50 value of 72.0 μg/mL). The total phenols content by Folin–Ciocalteau method was determined with the purpose of testing its relationship with the antioxidant and antibacterial activities.

Practical Application:  The appearance of food is one of the major determinants of its appeal to consumers and consequently, sales of the product. Microbial contamination and lipid oxidation are the main factors that determine food quality loss and shelf‐life reduction. Therefore, preventing microbial contamination and delaying lipid oxidation are highly relevant to food processors. The growth of microorganisms in food products may cause spoilage or foodborne diseases. Oxidative processes in food products lead to the degradation of lipids and proteins which, in turn, contribute to the deterioration in flavor, texture, and color of the products. A. heterophyllus leaves extracts demonstrated interesting biological properties that suggest its use as a new potential source of natural antioxidant and antimicrobial agent.
Meta‐analysis: Perioperative regional liver chemotherapy for improving survival and preventing liver metastases in patients with colorectal carcinoma
Authors: TANG Jie Ting , WANG Ji Lin , FANG Jing Yuan
Published: June 2010

OBJECTIVE:  To evaluate the effect of prophylactic regional liver chemotherapy during the perioperative period on improving survival and preventing liver metastases in patients with colorectal cancer (CRC).

METHODS:  A comprehensive retrieval of the relevant literature was performed by searching major biomedical database, mainly from Medline and Embase. Studies reported in the selected literature were categorized into two subgroups according to the type of therapy: a perioperative hepatic artery infusion subgroup and a perioperative portal vein infusion subgroup. Mortality and liver metastasis were analyzed using a fixed‐effects model. Statistical analysis was performed using Review Manager software.

RESULTS:  The results of this meta‐analysis illustrated that survival and the rate of liver metastasis in patients receiving perioperative hepatic artery infusion (HAI) chemotherapy were significantly better than for those receiving surgery alone (pooled relative risk 0.46 [95% CI: 0.31–0.69] and 0.44 [95% CI: 0.28–0.68], respectively, P= 0.0002), while survival and the rate of liver metastasis in patients receiving perioperative portal vein infusion (PVI) chemotherapy were not significantly different from those receiving surgery alone (pooled relative risk 0.98 [95% CI: 0.89–1.09], P= 0.73 and 0.86 [95% CI: 0.72–1.02], respectively. P= 0.08).

CONCLUSION:  As a method of regional liver chemotherapy, HAI might be able to improve survival and reduce the rate of liver metastasis in patients with advanced CRC.