bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis and characterisation of three-dimensional dendritic ZnO nanorods
Authors: Tian Y. , Lu H. B. , Wu Y. , Li J. C.
Published: November 2009

Intriguing ZnO three-dimensional (3D) dendritic nanorods on silicon substrates have been successfully synthesised by thermal evaporation of pure zinc powder at a relative low temperature of 478°C without any metal catalyst. ZnO dendritic nanostructure exhibits unique shape and it is composed of stems and nanorod branches. It is found that the nanorods are single crystalline wurtzite structures, and each nanorod grows along the [0001] direction. At different growth temperatures, the shapes of ZnO nanostructures can be altered. System analysis reveals that the formation and morphology of ZnO dendritic nanostructures are sensitive to the growth temperature. Finally, room temperature photoluminescence spectrum is also investigated, revealing that the ZnO dendritic nanostructure could find application in UV optoelectronic devices; the nanostructure implies some potential applications for nanoscale functional devices.
Src tyrosine kinase preactivation is associated with platelet hypersensitivity in essential thrombocythemia and polycythemia vera
Authors: Randi Maria Luigia , Brunati Anna Maria , Scapin Margherita , Frasson Martina , Deana Renzo , Magrin Elisa , Fabris Fabrizio , Donella-Deana Arianna
Published: November 2009

Polycythemia vera (PV) and essential thrombocythemia (ET) are chronic myeloproliferative disorders characterized by an increased incidence of thrombo-hemorrhagic complications. The acquired somatic Janus kinase 2 (JAK2) V617F mutation is present in the majority of PV and ET patients. Because aberrant protein Tyr-phosphorylation has been associated with hematopoietic malignancies, the activity of the tyrosine kinases Src and JAK2 was analyzed in resting and thrombin-stimulated platelets from 13 PV and 42 ET patients. JAK2 was found inactive in healthy and pathological resting cells regardless of the V617F mutation. In addition, Src was inactive in all resting platelets, but in the pathological specimens it was present in a preactivated conformation as a consequence of anomalous dephosphorylation of its inhibitory phospho-Tyr527 residue, likely mediated by Src homology-2 domain-containing protein Tyr-phosphatase-2 (SHP-2), whose constitutive activity correlated with its recruitment to Src. Low thrombin concentration triggered a more rapid Src-signaling activation, higher [Ca2+]c increase, and aggregation in pathological platelets compared with controls. Thrombin-induced Src activation preceded JAK2 activation, which occurred simultaneously in normal and pathological platelets. Our results indicate that a constitutive Src kinase preactivation is implicated in platelet hypersensitivity and likely involved, at least partially, in the functional abnormalities of PV and ET platelets.
Targeting EXT1 reveals a crucial role for heparan sulfate in the growth of multiple myeloma
Authors: Reijmers Rogier M. , Groen Richard W. J. , Rozemuller Henk , Kuil Annemieke , de Haan-Kramer Anneke , Csikós Tamás , Martens Anton C. M. , Spaargaren Marcel , Pals Steven T.
Published: November 2009

Expression of the heparan sulfate proteoglycan syndecan-1 is a hallmark of both normal and multiple myeloma (MM) plasma cells. Syndecan-1 could affect plasma cell fate by strengthening integrin-mediated adhesion via its core protein and/or by accommodating and presenting soluble factors via its HS side chains. Here, we show that inducible RNAi-mediated knockdown of syndecan-1 in human MM cells leads to reduced growth rates and a strong increase of apoptosis. Importantly, knockdown of EXT1, a copolymerase critical for HS chain biosynthesis, had similar effects. Using an innovative myeloma xenotransplantation model in Rag-2−/−γc−/− mice, we demonstrate that induction of EXT1 knockdown in vivo dramatically suppresses the growth of bone marrow localized myeloma. Our findings provide direct evidence that the HS chains of syndecan-1 are crucial for the growth and survival of MM cells within the bone marrow environment, and indicate the HS biosynthesis machinery as a potential treatment target in MM.
Annexin A2 tetramer activates human and murine macrophages through TLR4
Authors: Swisher Jennifer F. A. , Burton Nicholas , Bacot Silvia M. , Vogel Stefanie N. , Feldman Gerald M.
Published: November 2009

Annexins are a large family of intracellular phospholipid-binding proteins, yet several extracellular roles have been identified. Specifically, annexin A2, found in a heterotetrameric complex with S100A10, not only serves as a key extracellular binding partner for pathogens and host proteins alike, but also can be shed or secreted. We reported previously that soluble annexin A2 tetramer (A2t) activates human monocyte-derived macrophages (MDM), resulting in secretion of inflammatory mediators and enhanced phagocytosis. Although a receptor for A2t has been cloned from bone marrow stromal cells, data contained in this study demonstrate that it is dispensable for A2t-dependent activation of MDM. Furthermore, A2t activates wild-type murine bone marrow–derived macrophages, whereas macrophages from myeloid differentiation factor 88–deficient mice display a blunted response, suggesting a role for Toll-like receptor (TLR) signaling. Small interfering RNA knockdown of TLR4 in human MDM reduced the response to A2t, blocking antibodies against TLR4 (but not TLR2) blocked activation altogether, and bone marrow–derived macrophages from TLR4−/− mice were refractory to A2t. These data demonstrate that the modulation of macrophage function by A2t is mediated through TLR4, suggesting a previously unknown, but important role for this stress-sensitive protein in the detection of danger to the host, whether from injury or invasion.
Regulating human Th17 cells via differential expression of IL-1 receptor
Authors: Lee Won-Woo , Kang Seong Wook , Choi Jihoon , Lee Seung-Hyun , Shah Kamini , Eynon Elizabeth E. , Flavell Richard A. , Kang Insoo
Published: November 2009

In humans, interleukin-1β (IL-1β) has been suggested as an essential cytokine for developing IL-17– or IL-17A–producing CD4+ T helper 17 (Th17) cells. However, little is known about the relationship of IL-1 receptor expression and Th17 cell differentiation. We report here the presence of 2 distinct CD4+ T-cell populations with and without expression of IL-1RI that correlates with the capacity to produce IL-17 in naive and memory CD4+ T cells of human peripheral blood. IL-1RI+ memory CD4+ T cells had increased gene expression of IL17, RORC, and IRF4 even before T-cell receptor triggering, indicating that the effect of IL-1β is programmed in these cells via IL-1RI. Although CD4+ T cells from umbilical cord blood did not express IL-1RI, the cytokines IL-7, IL-15, and transforming growth factor-β (TGF-β) up-regulated IL-1RI expression on naive CD4+ T cells, suggesting that IL-1RI+ naive CD4+ T cells develop in periphery. Furthermore, IL-17 production from the cytokine-treated naive CD4+ T cells was induced by IL-1β and this induction was blocked by IL-1R antagonist. These results indicate that human Th17 cell differentiation is regulated via differential expression of IL-1RI, which is controlled by IL-7 and IL-15.
The impact on outcome of the addition of all-trans retinoic acid to intensive chemotherapy in younger patients with nonacute promyelocytic acute myeloid leukemia: overall results and results in genotypic subgroups defined by mutations in NPM1, FLT3, and CEBPA
Authors: Burnett Alan K. , Hills Robert K. , Green Claire , Jenkinson Sarah , Koo Kenneth , Patel Yashma , Guy Carol , Gilkes Amanda , Milligan Donald W. , Goldstone Anthony H. , Prentice Archibald G. , Wheatley Keith , Linch David C. , Gale Rosemary E.
Published: November 2009

We investigated the benefit of adding all-trans retinoic acid (ATRA) to chemotherapy for younger patients with nonacute promyelocytic acute myeloid leukemia and high-risk myelodysplastic syndrome, and considered interactions between treatment and molecular markers. Overall, 1075 patients less than 60 years of age were randomized to receive or not receive ATRA in addition to daunorubicin/Ara-C/thioguanine chemotherapy with Ara-C at standard or double standard dose. There were data on FLT3 internal tandem duplications and NPM1 mutations (n = 592), CEBPA mutations (n = 423), and MN1 expression (n = 195). The complete remission rate was 68% with complete remission with incomplete count recovery in an additional 16%; 8-year overall survival was 32%. There was no significant treatment effect for any outcome, with no significant interactions between treatment and demographics, or cytarabine randomization. Importantly, there were no interactions by FLT3/internal tandem duplications, NPM1, or CEBPA mutation. There was a suggestion that ATRA reduced relapse in patients with lower MN1 levels, but no significant effect on overall survival. Results were consistent when restricted to patients with normal karyotype. ATRA has no overall effect on treatment outcomes in this group of patients. The study did not identify any subgroup of patients likely to derive a significant survival benefit from the addition of ATRA to chemotherapy. This study is registered at http://www.controlled-trials.com under ISRCTN17833622.
DG-AMMOS: A New tool to generate 3D conformation of small molecules using D istance G eometry and A utomated M olecular M echanics O ptimization for in silico S creening
Authors: Lagorce David , Pencheva Tania , Villoutreix Bruno O , Miteva Maria A
Published: November 2009

Background

Discovery of new bioactive molecules that could enter drug discovery programs or that could serve as chemical probes is a very complex and costly endeavor. Structure-based and ligand-based in silico screening approaches are nowadays extensively used to complement experimental screening approaches in order to increase the effectiveness of the process and facilitating the screening of thousands or millions of small molecules against a biomolecular target. Both in silico screening methods require as input a suitable chemical compound collection and most often the 3D structure of the small molecules has to be generated since compounds are usually delivered in 1D SMILES, CANSMILES or in 2D SDF formats.

Results

Here, we describe the new open source program DG-AMMOS which allows the generation of the 3D conformation of small molecules using Distance Geometry and their energy minimization via Automated Molecular Mechanics Optimization. The program is validated on the Astex dataset, the ChemBridge Diversity database and on a number of small molecules with known crystal structures extracted from the Cambridge Structural Database. A comparison with the free program Balloon and the well-known commercial program Omega generating the 3D of small molecules is carried out. The results show that the new free program DG-AMMOS is a very efficient 3D structure generator engine.

Conclusion

DG-AMMOS provides fast, automated and reliable access to the generation of 3D conformation of small molecules and facilitates the preparation of a compound collection prior to high-throughput virtual screening computations. The validation of DG-AMMOS on several different datasets proves that generated structures are generally of equal quality or sometimes better than structures obtained by other tested methods.
Cloning, expression in Pichia pastoris, and characterization of a thermostable GH5 mannan endo-1,4-β-mannosidase from Aspergillus niger BK01
Authors: Bien-Cuong Do , Thi-Thu Dang , Berrin Jean-Guy , Haltrich Dietmar , Kim-Anh To , Sigoillot Jean-Claude , Yamabhai Montarop
Published: November 2009

Background

Mannans are key components of lignocellulose present in the hemicellulosic fraction of plant primary cell walls. Mannan endo-1,4-β-mannosidases (1,4-β-D-mannanases) catalyze the random hydrolysis of β-1,4-mannosidic linkages in the main chain of β-mannans. Biodegradation of β-mannans by the action of thermostable mannan endo-1,4-β-mannosidase offers significant technical advantages in biotechnological industrial applications, i.e. delignification of kraft pulps or the pretreatment of lignocellulosic biomass rich in mannan for the production of second generation biofuels, as well as for applications in oil and gas well stimulation, extraction of vegetable oils and coffee beans, and the production of value-added products such as prebiotic manno-oligosaccharides (MOS).

Results

A gene encoding mannan endo-1,4-β-mannosidase or 1,4-β-D-mannan mannanohydrolase (E.C. 3.2.1.78), commonly termed β-mannanase, from Aspergillus niger BK01, which belongs to glycosyl hydrolase family 5 (GH5), was cloned and successfully expressed heterologously (up to 243 μg of active recombinant protein per mL) in Pichia pastoris. The enzyme was secreted by P. pastoris and could be collected from the culture supernatant. The purified enzyme appeared glycosylated as a single band on SDS-PAGE with a molecular mass of approximately 53 kDa. The recombinant β-mannanase is highly thermostable with a half-life time of approximately 56 h at 70°C and pH 4.0. The optimal temperature (10-min assay) and pH value for activity are 80°C and pH 4.5, respectively. The enzyme is not only active towards structurally different mannans but also exhibits low activity towards birchwood xylan. Apparent Km values of the enzyme for konjac glucomannan (low viscosity), locust bean gum galactomannan, carob galactomannan (low viscosity), and 1,4-β-D-mannan (from carob) are 0.6 mg mL-1, 2.0 mg mL-1, 2.2 mg mL-1 and 1.5 mg mL-1, respectively, while the kcat values for these substrates are 215 s-1, 330 s-1, 292 s-1 and 148 s-1, respectively. Judged from the specificity constants kcat/Km, glucomannan is the preferred substrate of the A. niger β -mannanase. Analysis by thin layer chromatography showed that the main product from enzymatic hydrolysis of locust bean gum is mannobiose, with only low amounts of mannotriose and higher manno-oligosaccharides formed.

Conclusion

This study is the first report on the cloning and expression of a thermostable mannan endo-1,4-β-mannosidase from A. niger in Pichia pastoris. The efficient expression and ease of purification will significantly decrease the production costs of this enzyme. Taking advantage of its acidic pH optimum and high thermostability, this recombinant β-mannanase will be valuable in various biotechnological applications.
A combination of indole-3-carbinol and genistein synergistically induces apoptosis in human colon cancer HT-29 cells by inhibiting Akt phosphorylation and progression of autophagy
Authors: Nakamura Yoshitaka , Yogosawa Shingo , Izutani Yasuyuki , Watanabe Hirotsuna , Otsuji Eigo , Sakai Tosiyuki
Published: November 2009

Background

The chemopreventive effects of dietary phytochemicals on malignant tumors have been studied extensively because of a relative lack of toxicity. To achieve desirable effects, however, treatment with a single agent mostly requires high doses. Therefore, studies on effective combinations of phytochemicals at relatively low concentrations might contribute to chemopreventive strategies.

Results

Here we found for the first time that co-treatment with I3C and genistein, derived from cruciferous vegetables and soy, respectively, synergistically suppressed the viability of human colon cancer HT-29 cells at concentrations at which each agent alone was ineffective. The suppression of cell viability was due to the induction of a caspase-dependent apoptosis. Moreover, the combination effectively inhibited phosphorylation of Akt followed by dephosphorylation of caspase-9 or down-regulation of XIAP and survivin, which contribute to the induction of apoptosis. In addition, the co-treatment also enhanced the induction of autophagy mediated by the dephosphorylation of mTOR, one of the downstream targets of Akt, whereas the maturation of autophagosomes was inhibited. These results give rise to the possibility that co-treatment with I3C and genistein induces apoptosis through the simultaneous inhibition of Akt activity and progression of the autophagic process. This possibility was examined using inhibitors of Akt combined with inhibitors of autophagy. The combination effectively induced apoptosis, whereas the Akt inhibitor alone did not.

Conclusion

Although in vivo study is further required to evaluate physiological efficacies and toxicity of the combination treatment, our findings might provide a new insight into the development of novel combination therapies/chemoprevention against malignant tumors using dietary phytochemicals.
Serum estradiol should be monitored not only during the peri-menopausal period but also the post-menopausal period at the time of aromatase inhibitor administration
Authors: Nagao Taeko , Kira Misako , Takahashi Masako , Honda Junko , Hirose Toshiyuki , Tangoku Akira , Zembutsu Hitoshi , Nakamura Yusuke , Sasa Mitsunori
Published: November 2009

Background

Aromatase inhibitor (AI) therapy is being extensively used as postoperative adjuvant therapy in patients with hormone receptor-positive postmenopausal breast cancer. On the other hand, it has been reported that ovarian function was restored when AI was administered to patients who had undergone chemical menopause with chemotherapy or tamoxifen. However, there have been no reports of comprehensive monitoring of estradiol (E2) in breast cancer patients with ordinary menopause who were being administered AI.

Patients and Methods

Beginning in March 2008, regular monitoring of the serum levels of E2, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) was performed for 66 postmenopausal breast cancer patients who had been started on AI therapy. For this study, we chose anastrozole as the AI. The assays of those hormones were outsourced to a commercial clinical laboratory.

Results

In 4 of the 66 patients the serum E2 level was decreased at 3 months but had then increased at 6 months, while in 2 other patients E2 was decreased at both 3 and 6 months but had increased at 9 months.

Conclusion

The results indicate that, in some breast cancer patients with ordinary menopause, E2 rebounds following AI therapy. In the future, E2 monitoring should be performed for a larger number of patients being administered AI therapy.

Trial registration

Our trial registration number is 19-11-1211.
Modulation of experimental autoimmune encephalomyelitis by endogenous Annexin A1
Authors: Paschalidis Nikolaos , Iqbal Asif J , Maione Francesco , Wood Elisabeth G , Perretti Mauro , Flower Rod J , D'Acquisto Fulvio
Published: November 2009

Background

Autoimmune diseases, like multiple sclerosis, are triggered by uncontrolled activation of cells of the immune system against self-antigen present, for instance, in the central nervous system. We have reported novel biological functions for Annexin A1, an effector of endogenous anti-inflammation, to produce positive actions on the adaptive immune system by reducing the threshold of T cell activation. In this study, we investigated the potential modulatory role of Annexin A1 in the development of experimental autoimmune encephalomyelitis, a model of multiple sclerosis.

Methods

Male control C57/BL6 and AnxA1 null mice were immunized subcutaneously with an emulsion consisting of 300 μg of MOG35-55in PBS combined with an equal volume of CFA. Lymph node cells obtained from mice immunized with MOG33-55for 14 days were re-stimulatedin vitrowith MOG33-55(100 μg/ml) for 4 days and the Th1/Th17 cytokine profile measured by ELISA. Spinal cords were processed either to isolate the infiltrated T cells or fixed and stained with haematoxylin and eosin. Statistical analyses were performed using two-tailed, unpaired Student's t tests or ANOVA.

Results

Our results show a direct correlation between Annexin A1 expression and severity of EAE. Analysis of MOG35-55-induced EAE development in Annexin A1 null mice showed decreased signs of the disease compared to wild type mice. This defect was significant at the peak of the disease and accompanied by reduced infiltration of T cells in the spinal cord. Finally, analysis of the T cell recall responsein vitrofollowing stimulation with MOG35-55showed a decrease proliferation of Annexin A1 null T cells, with a significantly reduced Th1/Th17 phenotype, compared to wild type cells.

Conclusion

Together these findings suggest that Annexin A1 null mice have an impaired capacity to develop EAE. Furthermore strategies aiming at reducing Annexin A1 functions or expression in T cells might represent a novel therapeutic approach for multiple sclerosis.
Multiple Myeloma Involving Skin and Pulmonary Parenchyma after Autologous Stem Cell Transplantation
Authors: Yuan Yuan , Wieczorek Rosemary , Green David L , Cook Perry , Ballard Harold , Araten David J
Published: November 2009

Pulmonary involvement and skin involvement are rare complications of plasma cell neoplasms. Here we describe what may be the first reported case of a patient with relapse in both of these sites following autologous peripheral blood stem cell transplantation.
HLA-E gene polymorphism associates with ankylosing spondylitis in Sardinia
Authors: Paladini Fabiana , Belfiore Francesca , Cocco Elisa , Carcassi Carlo , Cauli Alberto , Vacca Alessandra , Fiorillo Maria Teresa , Mathieu Alessandro , Cascino Isabella , Sorrentino Rosa
Published: November 2009

Introduction

Ankylosing spondylitis (AS) is a severe, chronic inflammatory disease strongly associated with HLA-B27. The presence of additional HLA risk factors has been suggested by several studies. The aim of the current study is to assess the occurrence of an additional HLA susceptibility locus in the region between HLA-E and HLA-C in the Sardinian population.

Methods

200 random controls, 120 patients with AS and 175 HLA-B27 positive controls were genotyped for six single nucleotide polymorphisms (SNPs) spanning the HLA region between HLA-E and HLA-C loci previously shown to harbour an additional susceptibility locus for AS. Allele, genotype and haplotype frequencies were compared.

Results

The data confirm our previous finding of a significant increase in patients with AS of allele A at SNP rs1264457 encoding for an Arg at the functional HLA-E polymorphism (Arg128/Gly128). This was due to a remarkable increase in the frequency of genotype A/A in patients vs HLA-B27-matched controls (51% vs 29%; P for trend: 5 × 10-5). Genotype distribution of three other SNPs mapping in genes (GNL1, PRR3 and ABCF-1) close to HLA-E and showing high LD with it, was also significantly skewed. Accordingly, haplotype distribution was also remarkably different. The frequency of the haplotype AAGA, is 42% in random controls, increases to 53% in the HLA-B27-positive controls, and reaches 68% in patients with AS (P values: 2 × 10-11 vs random and 3 × 10-4 vs HLA-B27 controls).

Conclusions

There is a strong association between the presence of a haplotype in genes mapping between HLA-E and HLA-C and AS due to an increase of homozygous markers in patients. The strongest association however, is with the HLA-E functional polymorphism rs1264457. Since HLA-E is the ligand for the NKG2A receptor, these data point to the natural killer (NK) activity as possible player in the pathogenesis of AS.
Dose Intensity in Early-Stage Breast Cancer: A Community Practice Experience
Authors: Bretzel Robert L. , Cameron Ralph , Gustas Marc , Garcia Maria A. , Hoffman Heather K. , Malhotra Rosalind , Miller Karen , Prime Janine , Favret Anne
Published: November 2009

Although nodal status, grade, size, and receptor status play roles in determining breast cancer prognosis, there is increasing evidence that maintaining dose intensity of adjuvant chemotherapy increases disease-free survival rate.
The Sisters Network: A National African American Breast Cancer Survivor Advocacy Organization
Authors: Newman Lisa A. , Jackson Karen E.
Published: November 2009

Founded in 1994 by an African American woman who was diagnosed with breast cancer only a few months earlier, the Sisters Network advocacy organization today has nearly 3,000 members in 35 chapters throughout the country.
Partnering With Payers for Success: Quality Oncology Practice Initiative, Blue Cross Blue Shield of Michigan, and the Michigan Oncology Quality Consortium
Authors: Blayney Douglas W. , Stella Philip J. , Ruane Thomas , Martin Jane , LaVasseur Beth , Leyden Thomas , Malloy Mary
Published: November 2009

More than 16% of the total sites participating nationally in the QOPI survey are in Michigan. A significant component of the growth in QOPI participation in Michigan can be attributed to the involvement and quality improvement efforts of Blue Cross Blue Shield of Michigan.
Quality Oncology Practice Initiative Certification Program: Overview, Measure Scoring Methodology, and Site Assessment Standards
Authors: McNiff Kristen K. , Bonelli Katherine R. , Jacobson Joseph O.
Published: November 2009

More than a decade ago, the Institute of Medicine created the National Cancer Policy Board and identified a need to assess national quality of cancer care, generating a cascade of projects, including ASCO's QOPI.
Minireview: Osteoprotective Action of Estrogens Is Mediated by Osteoclastic Estrogen Receptor-α
Authors: Imai Yuuki , Kondoh Shino , Kouzmenko Alexander , Kato Shigeaki
Published: November 2009

The osteoprotective action of estrogen in women has drawn considerable attention because estrogen deficiency-induced osteoporosis became one of the most widely spread diseases in developed countries. In men, the significance of estrogen action for bone health maintenance is also apparent from the osteoporotic phenotype seen in male patients with genetically impaired estrogen signaling. Severe bone loss and high bone turnover, including typical osteofeatures seen in postmenopausal women, can also be recapitulated in rodents after ovariectomy. However, the expected osteoporotic phenotype is not observed in female mice deficient in estrogen receptor (ER)-α or -β or both, even though the degenerative defects are clearly seen in other estrogen target tissues together with up-regulated levels of circulating testosterone. It has also been reported that estrogens may attenuate bone remodeling by cell autonomous suppressive effects on osteoblastogenesis and osteoclastogenesis. Hence, the effects of estrogens in bone appear to be complex, and the molecular role of bone estrogen receptors in osteoprotective estrogen action remains unclear. Instead, it has been proposed that estrogens indirectly control bone remodeling. For example, the enhanced production of cytokines under estrogen deficiency induces bone resorption through stimulation of osteoclastogenesis. However, the osteoporotic phenotype without systemic defects has been recapitulated in female (but not in male) mice by osteoclast-specific ablation of the ERα, proving that bone cells represent direct targets for estrogen action. An aberrant accumulation of mature osteoclasts in these female mutants indicates that in females, the inhibitory action of estrogens on bone resorption is mediated by the osteoclastic ERα through the shortened lifespan of osteoclasts.
Interspecific and intersexual learning rate differences in four butterfly species
Authors: Kandori Ikuo , Yamaki Takafumi , Okuyama Sei-ichi , Sakamoto Noboru , Yokoi Tomoyuki
Published: November 2009

Learning plays an important role in food acquisition for a wide range of insects and has been demonstrated to be essential during flower foraging in taxa such as bees, parasitoid wasps, butterflies and moths. However, little attention has been focused on differences in floral cue learning abilities among species and sexes. We examined the associative learning of flower colour with nectar in four butterfly species: Idea leuconoe, Argyreus hyperbius, Pieris rapae and Lycaena phlaeas. All butterflies that were trained learned the flower colours associated with food. The flower colour learning rates were significantly higher in I. leuconoe and A. hyperbius than in P. rapae and L. phlaeas. Among the four species examined, the larger and longer-lived species exhibited higher learning rates. Furthermore, female butterflies showed a significantly higher learning rate than males. This study provides the first evidence that learning abilities related to floral cues differ among butterfly species. The adaptive significance of superior learning abilities in the larger and longer-lived butterfly species and in females is discussed.
Photosensitivity to different light intensities in blind and sighted rodents
Authors: Zubidat A. E. , Nelson R. J. , Haim A.
Published: November 2009

Photoperiod is an important cue regulating biological rhythms in mammals, including ‘blind’ subterranean and sighted fossorial rodent species. These species may respond differentially to changes in light quality according to their retinal complexity. The effects of increasing light intensity on daily rhythms of urine excretion and urinary output of 6-sulfatoxymelatonin levels were compared in ‘blind’ mole rats Spalax ehrenbergi and sighted social voles, Microtus socialis. Our results show that the threshold irradiance required to entrain rhythms of voles is three magnitudes greater than that for mole rats. The results suggest that mole rats have an operational photoreceptive pathway with a lower threshold irradiance than voles. Such a low threshold reflects the remarkable capability of this ‘blind’ species to utilize light signals even under challenging light conditions.
Thermal learning in the honeybee,Apis mellifera
Authors: Hammer Tobin J. , Hata Curtis , Nieh James C.
Published: November 2009

Honeybee foragers are exposed to thermal stimuli when collecting food outside and receiving food rewards inside the nest. In both contexts, there is an opportunity for foragers to associate warmth with food rewards. However, honeybee thermal learning is poorly understood. Using an associative learning paradigm (the proboscis extension reflex), we show that honeybees can learn to associate a nectar reward with a heated stimulus applied to the antenna to mimic natural contact with a warm flower or nectar-offering forager. Conditioning with longer inter-trial intervals (ITI) significantly improved learning acquisition. We also trained bees to discriminate between temperatures above (warm) and below (cold) ambient air temperature. Learning acquisition improved by 38% per 10°C increase in absolute stimulus intensity (difference between the rewarded temperature and unrewarded ambient air temperature). However, bees learned positive temperature (warm) significantly better than negative temperature (cold) differences, approximately twice as well for 10°C as compared with a −10°C difference. Thus, thermosensation, a sensory modality that is relatively unexplored in honeybees, could play a role in the acquisition of information from nestmates (social learning) and in foraging decisions influenced by associations between floral temperature and nectar rewards.
The responses of zebrafish (Danio rerio) to high external ammonia and urea transporter inhibition: nitrogen excretion and expression of rhesus glycoproteins and urea transporter proteins
Authors: Braun Marvin H. , Steele Shelby L. , Perry Steve F.
Published: November 2009

While adult zebrafish, Danio rerio, possess ammonia and urea transporters (Rh and UT proteins, respectively) in a number of tissues, they are most heavily concentrated within the gills. UT has a diffuse expression pattern within Na+-K+-ATPase (NKA)-type mitochondrion-rich cells and Rh proteins form a network similar to the arrangement seen in pufferfish gills (Nakada et al., 2007b). Rhag expression appeared to be limited to the pillar cells lining the blood spaces of the lamellae while Rhbg was localized to the outer layer of both the lamellae and the filament, upon the pavement cells. Exposure to high external ammonia (HEA) or phloretin increased tissue levels of ammonia and urea, respectively, in adult and juvenile zebrafish; however, the responses to these stressors were age dependent. HEA increased mRNA levels for a number of Rh proteins in embryos and larvae but did not elicit similar effects in adult gills, which appear to compensate for the unfavourable ammonia excretory gradient by increasing expression of V-type H+-ATPase. Phloretin exposure increased UT mRNA levels in embryos and larvae but was without effect in adult gill tissue. Surprisingly, in both adults and juveniles, HEA increased the mRNA expression of UT and phloretin increased the mRNA expression of Rh proteins. These results imply that, in zebrafish, there may be a tighter link between ammonia and urea excretion than is thought to occur in most teleosts.
Cell kinetics of the marine spongeHalisarca caeruleareveal rapid cell turnover and shedding
Authors: De Goeij J. M. , De Kluijver A. , Van Duyl F. C. , Vacelet J. , Wijffels R. H. , De Goeij A. F. P. M. , Cleutjens J. P. M. , Schutte B.
Published: November 2009

This study reveals the peculiar in vivo cell kinetics and cell turnover of the marine sponge Halisarca caerulea under steady-state conditions. The tropical coral reef sponge shows an extremely high proliferation activity, a short cell cycle duration and massive cell shedding. Cell turnover is predominantly confined to a single cell population, i.e. the choanocytes, and in this process apoptosis only plays a minor role. To our knowledge, such fast cell kinetics under steady-state conditions, with high turnover by shedding in the absence of apoptosis, has not been observed previously in any other multicellular organism. The duration of the cell cycle in vivo resembles that of unicellular organisms in culture. Morphological and histochemical studies demonstrate compartmentalization of choanocytes in the sponge tissue, which corresponds well with its remarkable cellular kinetics. Coral reef cavity sponges, like H. caerulea, inhabit low nutrient tropical waters, forcing these organisms to filter large volumes of water and to capture the few nutrients efficiently. Under these oligotrophic conditions, a high cell turnover may be considered as a very useful strategy, preventing permanent damage to the sponge by environmental stress. Halisarca caerulea maintains its body mass and keeps its food uptake system up to date by constantly renewing its filter system. We conclude that studies on cell kinetics and functional morphology provide new and essential information on the growth characteristics and the regulation of sponge growth in vivo as well as in vitro and the role of choanocytes in tissue homeostasis.
The intestinal response to feeding in seawater gulf toadfish, Opsanus beta, includes elevated base secretion and increased epithelial oxygen consumption
Authors: Taylor J. R. , Grosell M.
Published: November 2009

Intestinal HCO3− secretion is essential to marine teleost fish osmoregulation and comprises a considerable source of base efflux attributable to both serosal HCO3− and endogenous CO2 hydration. The role of intestinal HCO3− secretion in dynamic acid—base balance regulation appears negligible in studies of unfed fish, but evidence of high intestinal fluid [HCO3−] in fed marine teleosts led us to investigate the source of this HCO3− and its potential role in offsetting the postprandial ‘alkaline tide’ commonly associated with digestion. Specifically, we hypothesized that elevated metabolic rate and thus endogenous CO2 production by intestinal tissue as well as increased transepithelial intestinal HCO3− secretion occur post-feeding and offset a postprandial alkaline tide. To test these hypotheses changes in HCO3− secretion and O2 consumption by gulf toadfish (Opsanus beta) isolated intestine were quantified 0, 3, 6, 12, 24 and 48 h post-feeding. Intestinal tissue of unfed fish in general showed high rates of HCO3− secretion (15.5 μmol g−1 h−1) and O2 consumption (8.9 μmol g−1 h−1). Furthermore, postprandial increases in both intestinal HCO3− secretion and O2 consumption (1.6- and 1.9-fold peak increases, respectively) were observed. Elevated intestinal HCO3− secretion rates preceded and outlasted those of O2 consumption, and occurred at a magnitude and duration sufficient to account for the lack of alkaline tide. The dependence of these high rates of postprandial intestinal base secretion on serosal HCO3− indicates transepithelial HCO3− transport increases disproportionately more than endogenous CO2 production. The magnitude of postprandial intestinal HCO3− secretion indicates the intestine certainly is capable of postprandial acid#x02014;base balance regulation.
Fatty acid composition of pectoralis muscle membrane, intramuscular fat stores and adipose tissue of migrant and wintering white-throated sparrows (Zonotrichia albicollis)
Authors: Klaiman J. M. , Price E. R. , Guglielmo C. G.
Published: November 2009

The fatty acid composition of muscle membrane phospholipids and fat stores may affect migration performance in birds. The purpose of this study was to investigate seasonal changes in the fatty acid composition of (1) pectoralis muscle phospholipids, (2) intramuscular triglyceride stores and (3) adipose tissue triglycerides in free-living white-throated sparrows (Zonotrichia albicollis). During migratory seasons there was an increase in the n-6:n-3 ratio of muscle membrane phospholipid fatty acids without a change in the proportion of unsaturated fatty acids. This change was driven mainly by an increase in the proportion of 18:2n-6 and a decrease in the proportion of 22:6n-3. An increase in the proportion of 18:2n-6 was also observed in the intramuscular and adipose tissue triglyceride stores during the migratory seasons. These increases in 18:2n-6 were offset by a decrease in 16:0; resulting in an elevated proportion of unsaturated fatty acids and elevated double bond index in both fat stores of migrants. The elevated levels of 18:2n-6 in migrant fat stores indicates a high dietary component of this fatty acid, as white-throated sparrows feed mainly on tree seeds and some insects during migration and may not have access to a diet high in n-3 fatty acids. We suspect that elevated dietary levels of 18:2n-6 also caused the observed increases in the proportion of this fatty acid in muscle phospholipids. Overall, we conclude that seasonal changes in adipose and muscle fatty acid composition are likely attributable to diet more than other factors such as migratory exercise or mitochondrial density.
Characterization of the sea bass melanocortin 5 receptor: a putative role in hepatic lipid metabolism
Authors: Sánchez E. , Rubio V. C. , Cerdá-Reverter J. M.
Published: November 2009

The melanocortin 5 receptor (MC5R) plays a key role in the regulation of exocrine secretion in mammalian species. This receptor has also been characterized in some fish species but its function is unknown. We report the molecular and pharmacological characterization, as well as the tissue expression pattern, of sea bass MC5R. Cloning of five active alleles showing different levels of sensitivity to endogenous melanocortin and one non-functional allele demonstrate the allelic complexity of the MC5R locus. The sea bass receptor was activated by all the melanocortins tested, with ACTH and desacetyl-MSH and β-MSH showing the lowest efficiency. The acetylation of the MSH isoforms seems to be critical for the effectiveness of the agonist. Agouti-related protein had no effect on basal or agonist-stimulated activation of the receptor. SbMC5R was mainly expressed in the brain but lower expression levels were found in several peripheral tissues, including liver. Progressive fasting did not induce up- or downregulation of hypothalamic MC5R expression, suggesting that central MC5R is not involved in the regulation of food intake in the sea bass. MTII, a sbMC5R agonist, stimulated hepatic lipolysis in vitro, measured as free fatty acid release into the culture medium after melanocortin agonist exposure of liver fragments, suggesting that MC5R is involved in the regulation of hepatic lipid metabolism. Taken together, the data suggest that different allelic combinations may confer differential sensitivity to endogenous melanocortin in tissues where MC5R is expressed and, by extension, in hepatic lipid metabolism.
Ventilatory and cardiovascular actions of centrally and peripherally administered trout pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) in the unanaesthetized trout
Authors: Le Mével J.-C. , Lancien F. , Mimassi N. , Conlon J. M.
Published: November 2009

In mammals, pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) are involved in cardiovascular and respiratory regulation. Several studies have demonstrated the presence of PACAP, VIP and their receptors in various tissues of teleost fish, including the brain, but little is known about their respiratory and cardiovascular effects. The present study was undertaken to compare the central and peripheral actions of graded doses (25-100 pmol) of trout PACAP and trout VIP on ventilatory and cardiovascular variables in the unanaesthetized rainbow trout. Compared with vehicle, only intracerebroventricular injection of PACAP significantly (P<0.05) elevated the ventilation frequency and the ventilation amplitude, but both peptides significantly increased the total ventilation (). However, the maximum hyperventilatory effect of PACAP was approximately 2.5-fold higher than the effect of VIP at the 100 pmol dose (PACAP, =+5407±921 arbitrary units, a.u.; VIP, =+2056±874 a.u.; means ± s.e.m.). When injected centrally, only PACAP produced a significant increase in mean dorsal aortic blood pressure (PDA) (100 pmol: +21%) but neither peptide affected heart rate (fH). Intra-arterial injections of either PACAP or VIP were without effect on the ventilatory variables. PACAP was without significant action on PDA and fH while VIP significantly elevated PDA (100 pmol: +36%) without changing fH. In conclusion, the selective central hyperventilatory actions of exogenously administered trout PACAP, and to a lesser extent VIP, suggest that the endogenous peptides may be implicated in important neuroregulatory functions related to the central control of ventilation in trout.
Playing the Admissions Game: Student Reactions to Increasing College Competition
Authors: Bound John , Hershbein Brad , Long Bridget Terry
Published: November 2009

Gaining entrance to a four-year college or university, particularly a selective institution, has become increasingly competitive over the last several decades. We document this phenomenon and show how it has varied across different parts of the student ability distribution and across regions, with the most pronounced increases in competition being found among higher-ability students and in the Northeast. Additionally, we explore how the college preparatory behavior of high school seniors has changed in response to the growth in competition. We also discuss the theoretical implications of increased competition on longer-term measures of learning and achievement and attempt to test them empirically; the evidence and related literature, while limited, suggests little long-term benefit.
Mortality Inequality
Authors: Peltzman Sam
Published: November 2009

The paper describes how changes in the inequality of lifetimes have contributed to changes in the social distribution of welfare. I address the following questions: How can we measure inequality of lifetimes? How has this kind of inequality changed over time? How is this inequality related to increased longevity? How do these trends differ across and within countries? Unequal longevity was once a major source of social inequality, perhaps even more important in some sense than income inequality, for a long time. But over the last century, this inequality has declined drastically in high-income countries and is now comparatively trivial.
Field Experiments in Class Size from the Early Twentieth Century
Authors: Rockoff Jonah
Published: November 2009

A vast majority of adults believe that class size reductions are a good way to improve the quality of public schools. Reviews of the research literature, on the other hand, have provided mixed messages on the degree to which class size matters for student achievement. Here I will discuss a substantial, but overlooked, body of experimental work on class size that developed prior to World War II. These field experiments did not have the benefit of modern econometrics, and only a few were done on a reasonably large scale. However, they often used careful empirical designs, and the collective magnitude of this body of work is considerable. Moreover, this research produced little evidence to suggest that students learn more in smaller classes, which stands in contrast to some, though not all, of the most recent work by economists. In this essay, I provide an overview of the scope and breadth of the field experiments in class size conducted prior to World War II, the motivations behind them, and how their experimental designs were crafted to deal with perceived sources of bias. I discuss how one might interpret the findings of these early experimental results alongside more recent research.
The Evolution of Medical Spending Risk
Authors: Gruber Jonathan , Levy Helen
Published: November 2009

How has the economic risk of health spending changed over time for U.S. households? We describe trends in aggregate health spending in the United States and how private insurance markets and public insurance programs have changed over time. We then present evidence from Consumer Expenditure Survey microdata on how the distribution of household spending on health—that is, out-of-pocket payments for medical care plus the household's share of health insurance premiums—has changed over time. This distribution has shifted up over time—households spend more on medical care and insurance than they used to—but for the purposes of measuring change in risk, it is not the mean but the dispersion of this distribution that is of interest. We consider two measures of dispersion that serve as proxies for household risk: the standard deviation of the distribution of household health spending and the ratio of the 90th percentile of spending to the median (the so-called “90/50 gap”). We find, surprisingly, that neither has increased despite the rapid rise in aggregate health spending. This conclusion holds true for broad subgroups of the population (for example, the nonelderly as a group) but not for some narrowly-defined subgroups (for example, low-income families with children). We next consider how much risk households should face, from the perspective of economic efficiency. Household risk may not have changed much over the past several decades, but do we have any evidence that this level represents either too much or too little risk? Finally, we discuss implications for public policy—in particular, for current debates over expanding health insurance coverage to the uninsured.
Job Loss and the Fraying of the Implicit Employment Contract
Authors: Hallock Kevin F.
Published: November 2009

Most workers have one employment contract that is explicit and another one that is implicit. The explicit employment contract specifies working hours, compensation, and job tasks. The implicit contract involves expectations about the extent to which the employment relationship is likely to continue over time. Will the firms will seek to avoid mass layoffs unless or until absolutely necessary? Will firms cushion the wages and compensation of employees to some extent from broad swings in the economy? Will employees show some degree of loyalty to the firm? This paper will argue that, along a number of dimensions, the nature of the worker–firm employment relationship may have changed substantially in recent years—a group of changes that as a whole have negatively affected the lives of workers and produced modest, if any, benefits for firms. If employers have become less involved with cushioning the blow of unemployment and avoiding layoffs where possible, then public policy might have a role to play in spreading the burden of a down labor market so that the burden is not borne so heavily by those who lose their jobs entirely.
Aesthetic surgery and regulatory risk for doctors
Authors: Slack Mr Robert
Published: November 2009

The regulatory framework, in which all doctors work, is governed by the General Medical Council (GMC) in the United Kingdom. This article highlights areas of risk by reference to GMC publications and rulings, which can lead to doctors working in aesthetic surgery, coming under their scrutiny, and how best to avoid that event.