bluuebunny/crossref_metadata_2025 huggingface dataset:
Pbx-dependent regulation oflbxgene expression in developing zebrafish embryos
Authors: Lukowski Chris M. , Drummond Danna Lynne , Waskiewicz Andrew J.
Published: December 2011

Ladybird (Lbx) homeodomain transcription factors function in neural and muscle development—roles conserved from Drosophila to vertebrates. Lbx expression in mice specifies neural cell types, including dorsally located interneurons and association neurons, within the neural tube. Little, however, is known about the regulation of vertebrate lbx family genes. Here we describe the expression pattern of three zebrafish ladybird genes via mRNA in situ hybridization. Zebrafish lbx genes are expressed in distinct but overlapping regions within the developing neural tube, with strong expression within the hindbrain and spinal cord. The Hox family of transcription factors, in cooperation with cofactors such as Pbx and Meis, regulate hindbrain segmentation during embryogenesis. We have identified a novel regulatory interaction in which lbx1 genes are strongly downregulated in Pbx-depleted embryos. Further, we have produced a transgenic zebrafish line expressing dTomato and EGFP under the control of an lbx1b enhancer—a useful tool to acertain neuron location, migration, and morphology. Using this transgenic strain, we have identified a minimal neural lbx1b enhancer that contains key regulatory elements for expression of this transcription factor.
Development and characterization of microsatellite markers from tropical forage Stylosanthes species and analysis of genetic variability and cross-species transferability
Authors: Chandra Amaresh , Tiwari K.K. , Nagaich D. , Dubey N. , Kumar S. , Roy A.K.
Published: December 2011

A limited number of functional molecular markers has slowed the desired genetic improvement of Stylosanthes species. Hence, in an attempt to develop simple sequence repeat (SSR) markers, genomic libraries from Stylosanthes seabrana B.L. Maass & ’t Mannetje (2n = 2x = 20) using 5′ anchored degenerate microsatellite primers were constructed. Of the 76 new microsatellites, 21 functional primer pairs were designed. Because of the small number of primer pairs designed, 428 expressed sequence tag (EST) sequences from seven Stylosanthes species were also examined for SSR detection. Approximately 10% of sequences delivered functional primer pairs, and after redundancy elimination, 57 microsatellite repeats were selected. Tetranucleotides followed by trinucleotides were the major repeated sequences in Stylosanthes ESTs. In total, a robust set of 21 genomic–SSR (gSSR) and 20 EST–SSR (eSSR) markers were developed. These markers were analyzed for intraspecific diversity within 20 S. seabrana accessions and for their cross-species transferability. Mean expected (He) and observed (Ho) heterozygosity values with gSSR markers were 0.64 and 0.372, respectively, whereas with eSSR markers these were 0.297 and 0.214, respectively. Dendrograms having moderate bootstrap value (23%–94%) were able to distinguish all accessions of S. seabrana with gSSR markers, whereas eSSR markers showed 100% similarities between few accessions. The set of 21 gSSRs, from S. seabrana, and 20 eSSRs, from selected Stylosanthes species, with their high cross-species transferability (45% with gSSRs, 86% with eSSRs) will facilitate genetic improvement of Stylosanthes species globally.
Characterizing the citrus cultivar Carrizo genome through 454 shotgun sequencing
Authors: Belknap William R. , Wang Yi , Huo Naxin , Wu Jiajie , Rockhold David R. , Gu Yong Q. , Stover Ed
Published: December 2011

The citrus cultivar Carrizo is the single most important rootstock to the US citrus industry and has resistance or tolerance to a number of major citrus diseases, including citrus tristeza virus, foot rot, and Huanglongbing (HLB, citrus greening). A Carrizo genomic sequence database providing approximately 3.5× genome coverage (haploid genome size approximately 367 Mb) was populated through 454 GS FLX shotgun sequencing. Analysis of the repetitive DNA fraction indicated a total interspersed repeat fraction of 36.5%. Assembly and characterization of abundant citrus Ty3/gypsy elements revealed a novel type of element containing open reading frames encoding a viral RNA-silencing suppressor protein (RNA binding protein, rbp) and a plant cytokinin riboside 5′-monophosphate phosphoribohydrolase-related protein (LONELY GUY, log). Similar gypsy elements were identified in the Populus trichocarpa genome. Gene-coding region analysis indicated that 24.4% of the nonrepetitive reads contained genic regions. The depth of genome coverage was sufficient to allow accurate assembly of constituent genes, including a putative phloem-expressed gene. The development of the Carrizo database ( http://citrus.pw.usda.gov/ ) will contribute to characterization of agronomically significant loci and provide a publicly available genomic resource to the citrus research community.
Effects of predator exposure on Hsp70 expression and survival in tadpoles of the Common Frog (Rana temporaria)
Authors: Sørensen Jesper Givskov , Loeschcke Volker , Merilä Juha , Laurila Anssi
Published: December 2011

Predator-induced changes in prey behavior and morphology are widespread, but little is known about physiological and cellular-level responses in prey in response to predation risk. We investigated whether predator (larvae of the dragonfly Aeshna Fabricius, 1775) presence elevated the expression level of heat-shock protein 70 (Hsp70)—a commonly found response to stress—in tadpoles of the Common Frog ( Rana temporaria L., 1758). In another experiment, we tested the survival of tadpoles in the presence of a free-ranging predator. Prior to this encounter, the tadpoles were exposed to either an Hsp-inducing environmental stress in the form of heat (31 °C) or to predator cues from a caged predator. We found no evidence for increased Hsp70 expression in tadpoles either in the presence of fed or starved predators. We did not find any effects of prior exposure to neither heat nor predator presence on survival at the end of experiment. Our results do not point to either Hsp70-mediated effect of predator-induced responses or to beneficial effects of the stress response on survival under predation risk.
BIG RIP AND LITTLE RIP SOLUTIONS IN SCALAR MODEL WITH KINETIC AND GAUSS–BONNET COUPLINGS
Authors: GRANDA L. N. , LOAIZA E.
Published: December 2011

Late time cosmological solutions for scalar field model with kinetic and Gauss–Bonnet couplings are considered. The quintom scenario is realized with and without Big Rip singularity. We find that under specific choice of the Gauss–Bonnet coupling, the model considerably simplifies, giving rise to solutions where the kinetic term is proportional to the square of the Hubble parameter. This allows to reconstruct the model for a suitable cosmological evolution. We considered a solution that matches the observed behavior of the equation of state, while Big Rip singularity may be present or absent, depending on the parameters of the solution. Evolutionary scenarios known as Little Rip, have also been considered.
Synthesis and thermal behavior of unsubstituted [30]trithia-2,3,5,10,12,13,15,20,22,23,25,30- dodecaazahexaphyrin
Authors: Trukhina Olga N. , Zhabanov Yuri A. , Krasnov Aleksander V. , Danilova Elena A. , Islyaikin Mikhail K.
Published: December 2011

The parent compound of the trithiadodecaazahexaphyrins has been prepared for the first time. Its thermal stability has been found to be the highest reported to date among the porphyrinoid family.
Does sex (female versus male) influence the impact of class attendance on examination performance?
Authors: Cortright Ronald N. , Lujan Heidi L. , Cox Julie H. , DiCarlo Stephen E.
Published: December 2011

The “conventional wisdom” is that grades are related to class attendance, i.e., students who attend classes more frequently obtain better grades and class attendance dramatically contributes to enhanced learning. However, the influence of sex (female vs. male) on this relationship is understudied. Furthermore, there have been several studies examining the impact of attendance on course grades that challenge the conventional wisdom. To address these issues, we determined the effect of class attendance on examination scores for female and male students enrolled in our undergraduate exercise physiology class of 51 students (20 female students and 31 male students). The experiment was designed not to interfere with the normal conduct of the course. Attendance was recorded in each class, and, although regular attendance was encouraged, it was not required and did not factor into the final grades. The final grade reflected the average days of attendance for female students only. Specifically, female students earning a grade above the class average attended 89 ± 4% of the classes; however, female students earning a grade below the class average attended only 64 ± 6% of the classes. In sharp contrast, there was no difference in the number of classes attended for male students earning grades above or below the class average (84 ± 3% vs. 79 ± 5%). Accordingly, some male students were absent frequently but scored above the class average, whereas other male students attended many classes but scored below the class average. Thus, the influence of regular attendance on examination performance is more important for female students than male students.
Cooperative interaction between reactive oxygen species and Ca2+signals contributes to angiotensin II-induced hypertrophy in adult rat cardiomyocytes
Authors: Gul Rukhsana , Shawl Asif Iqbal , Kim Suhn-Hee , Kim Uh-Hyun
Published: December 2011

Reactive oxygen species (ROS) and Ca2+signals are closely associated with the pathogenesis of cardiac hypertrophy. However, the cause and effect of the two signals in cardiac hypertrophy remain to be clarified. We extend our recent report by investigating a potential interaction between ROS and Ca2+signals utilizing in vitro and in vivo angiotensin II (ANG II)-induced cardiac hypertrophy models. ANG II-induced initial Ca2+transients mediated by inositol trisphosphate (IP3) triggered initial ROS production in adult rat cardiomyocytes. The ROS generated by activation of the NAD(P)H oxidase complex via Rac1 in concert with Ca2+activates ADP-ribosyl cyclase to generate cyclic ADP-ribose (cADPR). This messenger-mediated Ca2+signal further augments ROS production, since 2,2′-dihydroxyazobenzene, an ADP-ribosyl cyclase inhibitor, or 8-Br-cADPR, an antagonistic analog of cADPR, abolished further ROS production. Data from short hairpin RNA (shRNA)-mediated knockdown of Akt1 and p47phoxdemonstrated that Akt1 is the upstream key molecule responsible for the initiation of Ca2+signal that activates p47phoxto generate ROS in cardiomyocytes. Nuclear translocation of nuclear factor of activated T-cell in cardiomyocytes was significantly suppressed by treatment with NAD(P)H oxidase inhibitors as well as by shRNA against Akt1 and p47phox. Our results suggest that in cardiomyocytes Ca2+and ROS messengers generated by ANG II amplify the initial signals in a cooperative manner, thereby leading to cardiac hypertrophy.
Activation of endothelial TRPV4 channels mediates flow-induced dilation in human coronary arterioles: role of Ca2+ entry and mitochondrial ROS signaling
Authors: Bubolz Aaron H. , Mendoza Suelhem A. , Zheng Xiaodong , Zinkevich Natalya S. , Li Rongshan , Gutterman David D. , Zhang David X.
Published: December 2011

In human coronary arterioles (HCAs) from patients with coronary artery disease, flow-induced dilation is mediated by a unique mechanism involving the release of H2O2 from the mitochondria of endothelial cells (ECs). How flow activates ECs to elicit the mitochondrial release of H2O2 remains unclear. Here, we examined the role of the transient receptor potential vanilloid type 4 (TRPV4) channel, a mechanosensitive Ca2+-permeable cation channel, in mediating ROS formation and flow-induced dilation in HCAs. Using RT-PCR, Western blot analysis, and immunohistochemical analysis, we detected the mRNA and protein expression of TRPV4 channels in ECs of HCAs and cultured human coronary artery ECs (HCAECs). In HCAECs, 4α-phorbol-12,13-didecanoate (4α-PDD), a selective TRPV4 agonist, markedly increased (via Ca2+ influx) intracellular Ca2+ concentration. In isolated HCAs, activation of TRPV4 channels by 4α-PDD resulted in a potent concentration-dependent dilation, and the dilation was inhibited by removal of the endothelium and by catalase, a H2O2-metabolizing enzyme. Fluorescence ROS assays showed that 4α-PDD increased the production of mitochondrial superoxide in HCAECs. 4α-PDD also enhanced the production of H2O2 and superoxide in HCAs. Finally, we found that flow-induced dilation of HCAs was markedly inhibited by different TRPV4 antagonists and TRPV4-specific small interfering RNA. In conclusion, the endothelial TRPV4 channel is critically involved in flow-mediated dilation of HCAs. TRPV4-mediated Ca2+ entry may be an important signaling event leading to the flow-induced release of mitochondrial ROS in HCAs. Elucidation of this novel TRPV4-ROS pathway may improve our understanding of the pathogenesis of coronary artery disease and/or other cardiovascular disorders.
Sympathetic nerve stimulation induces local endothelial Ca2+ signals to oppose vasoconstriction of mouse mesenteric arteries
Authors: Nausch Lydia W. M. , Bonev Adrian D. , Heppner Thomas J. , Tallini Yvonne , Kotlikoff Michael I. , Nelson Mark T.
Published: December 2011

It is generally accepted that the endothelium regulates vascular tone independent of the activity of the sympathetic nervous system. Here, we tested the hypothesis that the activation of sympathetic nerves engages the endothelium to oppose vasoconstriction. Local inositol 1,4,5-trisphosphate (IP3)-mediated Ca2+ signals (“pulsars”) in or near endothelial projections to vascular smooth muscle (VSM) were measured in an en face mouse mesenteric artery preparation. Electrical field stimulation of sympathetic nerves induced an increase in endothelial cell (EC) Ca2+ pulsars, recruiting new pulsar sites without affecting activity at existing sites. This increase in Ca2+ pulsars was blocked by bath application of the α-adrenergic receptor antagonist prazosin or by TTX but was unaffected by directly picospritzing the α-adrenergic receptor agonist phenylephrine onto the vascular endothelium, indicating that nerve-derived norepinephrine acted through α-adrenergic receptors on smooth muscle cells. Moreover, EC Ca2+ signaling was not blocked by inhibitors of purinergic receptors, ryanodine receptors, or voltage-dependent Ca2+ channels, suggesting a role for IP3, rather than Ca2+, in VSM-to-endothelium communication. Block of intermediate-conductance Ca2+-sensitive K+ channels, which have been shown to colocalize with IP3 receptors in endothelial projections to VSM, enhanced nerve-evoked constriction. Collectively, our results support the concept of a transcellular negative feedback module whereby sympathetic nerve stimulation elevates EC Ca2+ signals to oppose vasoconstriction.
Altered clock gene expression and vascular smooth muscle diurnal contractile variations in type 2 diabeticdb/dbmice
Authors: Su Wen , Xie Zhongwen , Guo Zhenheng , Duncan Marilyn J. , Lutshumba Jenny , Gong Ming C.
Published: December 2011

This study was designed to determine whether the 24-h rhythms of clock gene expression and vascular smooth muscle (VSM) contractile responses are altered in type 2 diabetic db/db mice. Control and db/db mice were euthanized at 6-h intervals throughout the day. The aorta, mesenteric arteries, heart, kidney, and brain were isolated. Clock and target gene mRNA levels were determined by either real-time PCR or in situ hybridization. Isometric contractions were measured in isolated aortic helical strips, and pressor responses to an intravenous injection of vasoconstrictors were determined in vivo using radiotelemetry. We found that the 24-h mRNA rhythms of the following genes were suppressed in db/db mice compared with control mice: the clock genes period homolog 1/2 ( Per1/2) and cryptochrome 1/2 ( Cry1/2) and their target genes D site albumin promoter-binding protein ( Dbp) and peroxisome proliferator-activated receptor-γ ( Pparg) in the aorta and mesenteric arteries; Dbp in the heart; Per1, nuclear receptor subfamily 1, group D, member 1 ( Rev-erba), and Dbp in the kidney; and Per1 in the suprachiasmatic nucleus. The 24-h contractile variations in response to phenylephrine (α1-agonist), ANG II, and high K+were significantly altered in the aortas from db/db mice compared with control mice. The diurnal variations of the in vivo pressor responses to phenylephrine and ANG II were lost in db/db mice. Moreover, the 24-h mRNA rhythms of the contraction-related proteins Rho kinase 1/2, PKC-potentiated phosphatase inhibitory protein of 17 kDa, calponin-3, tropomyosin-1/2, and smooth muscle protein 22-α were suppressed in db/db mice compared with control mice. Together, our data demonstrated that the 24-h rhythms of clock gene mRNA, mRNA levels of several contraction-related proteins, and VSM contraction were disrupted in db/db mice, which may contribute to the disruption of their blood pressure circadian rhythm.
Cardiovascular regulation during long-duration spaceflights to the International Space Station
Authors: Hughson R. L. , Shoemaker J. K. , Blaber A. P. , Arbeille P. , Greaves D. K. , Pereira-Junior P. P. , Xu D.
Published: December 2011

Early evidence from long-duration flights indicates general cardiovascular deconditioning, including reduced arterial baroreflex gain. The current study investigated the spontaneous baroreflex and markers of cardiovascular control in six male astronauts living for 2–6 mo on the International Space Station. Measurements were made from the finger arterial pressure waves during spontaneous breathing (SB) in the supine posture pre- and postflight and during SB and paced breathing (PB, 0.1 Hz) in a seated posture pre- and postflight, as well as early and late in the missions. There were no changes in preflight measurements of heart rate (HR), blood pressure (BP), or spontaneous baroreflex compared with in-flight measurements. There were, however, increases in the estimate of left ventricular ejection time index and a late in-flight increase in cardiac output (CO). The high-frequency component of RR interval spectral power, arterial pulse pressure, and stroke volume were reduced in-flight. Postflight there was a small increase compared with preflight in HR (60.0 ± 9.4 vs. 54.9 ± 9.6 beats/min in the seated posture, P < 0.05) and CO (5.6 ± 0.8 vs. 5.0 ± 1.0 l/min, P < 0.01). Arterial baroreflex response slope was not changed during spaceflight, while a 34% reduction from preflight in baroreflex slope during postflight PB was significant (7.1 ± 2.4 vs. 13.4 ± 6.8 ms/mmHg), but a smaller average reduction (25%) during SB (8.0 ± 2.1 vs. 13.6 ± 7.4 ms/mmHg) was not significant. Overall, these data show no change in markers of cardiovascular stability during long-duration spaceflight and only relatively small changes postflight at rest in the seated position. The current program routine of countermeasures on the International Space Station provided sufficient stimulus to maintain cardiovascular stability under resting conditions during long-duration spaceflight.
The Levenberg‐Marquardt‐Type Methods for a Kind of Vertical Complementarity Problem
Authors: Du Shou-qiang , Gao Yan
Published: December 2011

Two kinds of the Levenberg‐Marquardt‐type methods for the solution of vertical
complementarity problem are introduced. The methods are based on a nonsmooth equation
reformulation of the vertical complementarity problem for its solution. Local and
global convergence results and some remarks about the two kinds of the Levenberg‐Marquardt‐type methods are also given. Finally, numerical experiments are reported.
Seismic Expression of Polygonal Faults and Its Impact on Fluid Flow Migration for Gas Hydrates Formation in Deep Water of the South China Sea
Authors: Chen Duanxin , Wu Shiguo , Wang Xiujuan , Lv Fuliang
Published: December 2011

Polygonal faults were identified from three-dimensional (3D) seismic data in the middle-late Miocene marine sequences of the South China Sea. Polygonal faults in the study area are normal faults with fault lengths ranging from 100 to 1500 m, fault spaces ranging from 40 to 800 m, and throws ranging from 10 to 40 m. Gas hydrate was inferred from the seismic polarity, the reflection strength, and the temperature-pressure equilibrium computation results. Gas hydrates located in the sediments above the polygonal faults layer. Polygonal faults can act as pathways for the migration of fluid flow, which can supply hydrocarbons for the formation of gas hydrates.
Facilitated Cross‐Bridge Interactions with Thin Filaments by Familial Hypertrophic Cardiomyopathy Mutations in α‐Tropomyosin
Authors: Wang Fang , Brunet Nicolas M. , Grubich Justin R. , Bienkiewicz Ewa A. , Asbury Thomas M. , Compton Lisa A. , Mihajlović Goran , Miller Victor F. , Chase P. Bryant
Published: December 2011

Familial hypertrophic cardiomyopathy (FHC) is a disease of cardiac sarcomeres. To identify molecular mechanisms underlying FHC pathology, functional and structural differences in three FHC‐related mutations in recombinant α‐Tm (V95A, D175N, and E180G) were characterized using both conventional and modified in vitro motility assays and circular dichroism spectroscopy. Mutant Tm′s exhibited reduced α‐helical structure and increased unordered structure. When thin filaments were fully occupied by regulatory proteins, little or no motion was detected at pCa 9, and maximum speed (pCa 5) was similar for all tropomyosins. Ca2+‐responsiveness of filament sliding speed was increased either by increased pCa50 (V95A), reduced cooperativity n (D175N), or both (E180G). When temperature was increased, thin filaments with E180G exhibited dysregulation at temperatures ~10°C lower, and much closer to body temperature, than WT. When HMM density was reduced, thin filaments with D175N required fewer motors to initiate sliding or achieve maximum sliding speed.
Physiology and Pathophysiology of CLC‐1: Mechanisms of a Chloride Channel Disease, Myotonia
Authors: Tang Chih-Yung , Chen Tsung-Yu
Published: December 2011

The CLC‐1 chloride channel, a member of the CLC‐channel/transporter family, plays important roles for the physiological functions of skeletal muscles. The opening of this chloride channel is voltage dependent and is also regulated by protons and chloride ions. Mutations of the gene encoding CLC‐1 result in a genetic disease, myotonia congenita, which can be inherited as an autosmal dominant (Thomsen type) or an autosomal recessive (Becker type) pattern. These mutations are scattered throughout the entire protein sequence, and no clear relationship exists between the inheritance pattern of the mutation and the location of the mutation in the channel protein. The inheritance pattern of some but not all myotonia mutants can be explained by a working hypothesis that these mutations may exert a “dominant negative” effect on the gating function of the channel. However, other mutations may be due to different pathophysiological mechanisms, such as the defect of protein trafficking to membranes. Thus, the underlying mechanisms of myotonia are likely to be quite diverse, and elucidating the pathophysiology of myotonia mutations will require the understanding of multiple molecular/cellular mechanisms of CLC‐1 channels in skeletal muscles, including molecular operation, protein synthesis, and membrane trafficking mechanisms.
The Immune Response to Tumors as a Tool toward Immunotherapy
Authors: Pandolfi F. , Cianci R. , Pagliari D. , Casciano F. , Bagalà C. , Astone A. , Landolfi R. , Barone C.
Published: December 2011

Until recently cancer medical therapy was limited to chemotherapy that could not differentiate cancer cells from normal cells. More recently with the remarkable mushroom of immunology, newer tools became available, resulting in the novel possibility to attack cancer with the specificity of the immune system. Herein we will review some of the recent achievement of immunotherapy in such aggressive cancers as melanoma, prostatic cancer, colorectal carcinoma, and hematologic malignancies. Immunotherapy of tumors has developed several techniques: immune cell transfer, vaccines, immunobiological molecules such as monoclonal antibodies that improve the immune responses to tumors. This can be achieved by blocking pathways limiting the immune response, such as CTLA-4 or Tregs. Immunotherapy may also use cytokines especially proinflammatory cytokines to enhance the activity of cytotoxic T cells (CTLs) derived from tumor infiltrating lymphocytes (TILs). The role of newly discovered cytokines remains to be investigated. Alternatively, an other mechanism consists in enhancing the expression of TAAs on tumor cells. Finally, monoclonal antibodies may be used to target oncogenes.
Global Breast Cancer: The Lessons to Bring Home
Authors: Formenti Silvia C. , Arslan Alan A. , Love Susan M.
Published: December 2011

Breast cancer is the most common cancer affecting women globally. This paper discusses the current progress in breast cancer in Western countries and focuses on important differences of this disease in low- and middle-income countries (LMCs). It introduces several arguments for applying caution before globalizing some of the US-adopted practices in the screening and management of the disease. Finally, it suggests that studies of breast cancer in LMCs might offer important insights for a more effective management of the problem both in developing as well as developed countries.
Factors Influencing Colorectal Cancer Screening Participation
Authors: Gimeno García Antonio Z.
Published: December 2011

Colorectal cancer (CRC) is a major health problem worldwide. Although population-based CRC screening is strongly recommended in average-risk population, compliance rates are still far from the desirable rates. High levels of screening uptake are necessary for the success of any screening program. Therefore, the investigation of factors influencing participation is crucial prior to design and launches a population-based organized screening campaign. Several studies have identified screening behaviour factors related to potential participants, providers, or health care system. These influencing factors can also be classified in non-modifiable (i.e., demographic factors, education, health insurance, or income) and modifiable factors (i.e., knowledge about CRC and screening, patient and provider attitudes or structural barriers for screening). Modifiable determinants are of great interest as they are plausible targets for interventions. Interventions at different levels (patient, providers or health care system) have been tested across the studies with different results. This paper analyzes factors related to CRC screening behaviour and potential interventions designed to improve screening uptake.
Alternative Splicing in Oncogenic Kinases: From Physiological Functions to Cancer
Authors: Druillennec Sabine , Dorard Coralie , Eychène Alain
Published: December 2011

Among the 518 protein kinases encoded by the human kinome, several of them act as oncoproteins in human cancers. Like other eukaryotic genes, oncogenes encoding protein kinases are frequently subjected to alternative splicing in coding as well as noncoding sequences. In the present paper, we will illustrate how alternative splicing can significantly impact on the physiological functions of oncogenic protein kinases, as demonstrated by mouse genetic model studies. This includes examples of membrane-bound tyrosine kinases receptors (FGFR2, Ret, TrkB, ErbB4, and VEGFR) as well as cytosolic protein kinases (B-Raf). We will further discuss how regular alternative splicing events of these kinases are in some instances implicated in oncogenic processes during tumor progression (FGFR, TrkB, ErbB2, Abl, and AuroraA). Finally, we will present typical examples of aberrant splicing responsible for the deregulation of oncogenic kinases activity in cancers (AuroraB, Jak2, Kit, Met, and Ron).
DNA Methylation of Phosphatase and Actin Regulator 3 Detects Colorectal Cancer in Stool and Complements FIT
Authors: Bosch Linda J.W. , Oort Frank A. , Neerincx Maarten , Khalid-de Bakker Carolina A.J. , sive Droste Jochim S. Terhaar , Melotte Veerle , Jonkers Daisy M.A.E. , Masclee Ad A.M. , Mongera Sandra , Grooteclaes Madeleine , Louwagie Joost , van Criekinge Wim , Coupé Veerle M.H. , Mulder Chris J. , van Engeland Manon , Carvalho Beatriz , Meijer Gerrit A.
Published: December 2011

Using a bioinformatics-based strategy, we set out to identify hypermethylated genes that could serve as biomarkers for early detection of colorectal cancer (CRC) in stool. In addition, the complementary value to a Fecal Immunochemical Test (FIT) was evaluated. Candidate genes were selected by applying cluster alignment and computational analysis of promoter regions to microarray-expression data of colorectal adenomas and carcinomas. DNA methylation was measured by quantitative methylation-specific PCR on 34 normal colon mucosa, 71 advanced adenoma, and 64 CRC tissues. The performance as biomarker was tested in whole stool samples from in total 193 subjects, including 19 with advanced adenoma and 66 with CRC. For a large proportion of these series, methylation data for GATA4 and OSMR were available for comparison. The complementary value to FIT was measured in stool subsamples from 92 subjects including 44 with advanced adenoma or CRC. Phosphatase and Actin Regulator 3 (PHACTR3) was identified as a novel hypermethylated gene showing more than 70-fold increased DNA methylation levels in advanced neoplasia compared with normal colon mucosa. In a stool training set, PHACTR3 methylation showed a sensitivity of 55% (95% CI: 33–75) for CRC and a specificity of 95% (95% CI: 87–98). In a stool validation set, sensitivity reached 66% (95% CI: 50–79) for CRC and 32% (95% CI: 14–57) for advanced adenomas at a specificity of 100% (95% CI: 86–100). Adding PHACTR3 methylation to FIT increased sensitivity for CRC up to 15%. PHACTR3 is a new hypermethylated gene in CRC with a good performance in stool DNA testing and has complementary value to FIT. Cancer Prev Res; 5(3); 464–72. ©2011 AACR.
Oral Contraceptives Decrease the Prevalence of Ovarian Cancer in the Hen
Authors: Treviño Lindsey S. , Buckles Elizabeth L. , Johnson Patricia A.
Published: December 2011

Ovarian cancer is the leading cause of reproductive cancer death in U.S. women. This high mortality rate is due to the lack of early detection methods and ineffectiveness of therapy for advanced disease. Until more effective screening methods and therapies are developed, chemoprevention strategies are warranted. The hen has a high spontaneous prevalence of ovarian cancer and has been used as a model for studying ovarian cancer chemoprevention. In this study, we used the hen to determine the effect of progestin alone, estrogen alone, or progestin and estrogen in combination (as found in oral contraceptives) on ovarian cancer prevalence. We found that treatment with progestin alone and in combination with estrogen decreased the prevalence of ovarian cancer. A significant risk reduction of 91% was observed in the group treated with progestin alone (risk ratio = 0.0909; 95% CI: 0.0117–0.704) and an 81% reduction was observed in the group treated with progestin plus estrogen (risk ratio = 0.1916; 95% CI = 0.043–0.864). Egg production was also significantly reduced in these treatment groups compared with control. We found no effect of progestin, either alone or in combination with estrogen, on apoptosis or proliferation in the ovary, indicating that this is not the likely mechanism responsible for the protective effect of progestin in the hen. Our results support the use of oral contraceptives to prevent ovarian cancer and suggest that ovulation is related to the risk of ovarian cancer in hens and that other factors, such as hormones, more than likely modify this risk. Cancer Prev Res; 5(2); 343–9. ©2011 AACR.
Association of Hypo- and Hyperkalemia with Disease Progression and Mortality in Males with Chronic Kidney Disease: The Role of Race
Authors: Hayes John , Kalantar-Zadeh Kamyar , Lu Jun L. , Turban Sharon , Anderson John E. , Kovesdy Csaba P.
Published: December 2011

Background/Aims: Abnormal serum potassium is associated with higher mortality in dialysis patients, but its impact on outcomes in predialysis chronic kidney disease (CKD) is less clear. Furthermore, blacks with normal kidney function have lower urinary potassium excretion, but it is unclear if such differences have a bearing on race-associated outcomes in CKD. Methods: We studied predialysis mortality and slopes of estimated glomerular filtration rate, eGFR) associated with serum potassium in 1,227 males with CKD. Mortality was examined in time-dependent Cox models, and slopes of eGFR in linear mixed effects models with adjustments for case mix and laboratory values. Results: Both hypo- and hyperkalemia were associated with mortality overall and in 933 white patients, but in 294 blacks hypokalemia was a stronger death predictor. Hypokalemia was associated with loss of kidney function independent of race: a 1 mEq/l lower potassium was associated with an adjusted difference in slopes of eGFR of -0.13 ml/min/1.73 m2/year (95% CI: -0.20 to -0.07), p < 0.001. Conclusion: Hypo- and hyperkalemia are associated with higher mortality in CKD patients. Blacks appear to better tolerate higher potassium than whites. Hypokalemia is associated with faster CKD progression independent of race. Hyperkalemia management may warrant race-specific consideration, and hypokalemia correction may slow CKD progression. This is a work of the US Government and is not subject to copyright protection in the USA. Foreign copyrights may apply. Published by S. Karger AG, Basel
Anticoagulation of Diethyl Citrate and Its Comparison with Sodium Citrate in an Animal Model
Authors: Chen Zhao , Chen Bin , Yao Xiu-Qiong , Gui Bao-Song , Ou Yan , Ouyang Jian-Ming
Published: December 2011

Aims: To improve the side effects caused by sodium citrate (Na3Cit), the anticoagulant effects of diethyl citrate (Et2Cit) were investigated. Methods: The in vitro anticoagulant effects and dissociation capacity of the chelate of Et2Cit with calcium ions were compared with those of Na3Cit in rabbits. Results: The activated coagulation time test showed that blood clotting time exceeded 1,200 s when the concentrations of Et2Cit and Na3Cit were greater than 87.2 and 8.72 mmol/l, respectively. The concentrations of free calcium ions in blood c(Ca2+) were reduced when Et2Cit was injected into the rabbits. Conclusions: Et2Cit reduces the concentration of ionized Ca2+ in blood and has anticoagulant effects. The dissociation of the chelate of Et2Cit with Ca2+ was faster than that of Na3Cit with Ca2+ within 10 min after injection. The recovery speed of blood calcium concentration with Et2Cit was more rapid than that with Na3Cit. The findings show that Et2Cit prevents hypocalcemia.
Projected Prevalence of Inadequate Nutrient Intakes in Europe
Authors: Roman Viñas Blanca , Ribas Barba Lourdes , Ngo Joy , Gurinovic Mirjana , Novakovic Romana , Cavelaars Adriënne , de Groot Lisette C.P.G.M. , van’t Veer Pieter , Matthys Christophe , Serra Majem Lluís
Published: December 2011

Background: The purpose of this study was to analyze the prevalence of nutrient intake inadequacy in Europe, applying the Nordic Nutritional Recommendations in the context of the EURRECA Network of Excellence. Methods: Nutrient data was obtained from the European Nutrition and Health Report II. Those nutritional surveys using a validated food frequency questionnaire or diet history and a food diary/ register with at least 7 days of registers or with an adjustment for intraindividual variability were included. The nutrients analyzed were: vitamin C, vitamin D, vitamin B12, folic acid, calcium, iron, zinc, selenium, copper, and iodine. The estimated average requirement cut point was applied to estimate inadequacy. The Nordic and Institute of Medicine nutrient recommendations were used as references. Results: The mean prevalence of inadequacy was below 11% for zinc, iron, and vitamin B12 (only in the elderly), and it was 11–20% for copper in adults and the elderly and for vitamin B12 in adults and vitamin C in the elderly. The prevalence was above 20% for vitamin D, folic acid, calcium, selenium, and iodine in adults and the elderly and for vitamin C in adults. Conclusions: Vitamin C, vitamin D, folic acid, calcium, selenium, and iodine were the nutrients showing a higher prevalence of inadequate intakes in Europe.
Pathology Associated with a Human Case of Rabies in the United Kingdom Caused by European Bat Lyssavirus Type-2
Authors: Johnson N. , Brookes S.M. , Healy D.M. , Spencer Y. , Hicks D. , Nunez A. , Wells G. , Fooks A.R.
Published: December 2011

Human infection with the rabies-related virus European bat lyssavirus type-2 (EBLV-2) has only been reported on two occasions. Here we report the pathology observed within spinal cord and visceral tissues associated with EBLV-2 infection for the first time. Neuronal labelling with an anti-rabies nucleocapsid monoclonal antibody was observed and appeared indistinguishable from the labelling reported from human infection with rabies virus.
22q11.2 Distal Deletion Syndrome: Description of a New Case with Truncus Arteriosus Type 2 and Review
Authors: Garavelli L. , Rosato S. , Wischmeijer A. , Gelmini C. , Esposito A. , Mazzanti L. , Franchi F. , De Crescenzo A. , Palumbo O. , Carella M. , Riccio A.
Published: December 2011

22q11.2 deletion syndrome is mainly characterized by conotruncal congenital heart defects, velopharyngeal insufficiency, hypocalcemia and a characteristic craniofacial appearance. The etiology in the majority of patients is a 3-Mb recurrent deletion in region 22q11.2. Nevertheless, recently some cases of infrequent deletions with various sizes have been reported with a different phenotype. We report on a patient with congenital heart disease (truncus arteriosus type 2) in whom a de novo 1.3-Mb 22q11.2 deletion was detected by array comparative genomic hybridization. The deletion described corresponds to an atypical and distal deletion which spans low copy repeat (LCR) 4 and is associated with breakpoint sites that do not correspond to known LCRs of 22q11.2. We examine the clinical phenotype of our case and compare our findings with those published in the literature. The most prevalent clinical features in this type of deletion are a history of prematurity, pre-natal and post-natal growth retardation, slight facial dysmorphic features, microcephaly and developmental delay, with a speech defect in particular. These are clearly different from those found in the classic 22q11.2 deletion syndrome, and we believe that the main differential diagnosis should be with Silver-Russel syndrome. In our case we observe the cardiac phenotype with truncus arteriosus communis usually seen in the classic 22q11.2 deletion syndrome, and so far associated with the TBX1 gene. Significantly, however, TBX1 is not included in our patient’s deletion. The possible roles of a position effect or other genes are discussed.
Factors Associated with Fluoride Concentrations in Whole and Parotid Ductal Saliva
Authors: Fukushima R. , Pessan J.P. , Sampaio F.C. , Buzalaf M.A.R.
Published: December 2011

Background/Aims: There are still uncertainties regarding the use of whole and parotid ductal saliva as indicators of chronic exposure to fluoride. This study evaluated the effect of water fluoride concentration, age, gender, geographical area and localization (urban/rural) on fluoride concentrations in whole and ductal saliva. Methods: Subjects (n = 300) aged 3–7, 14–20, 30–40 and 50–60 years, from five communities (A–E) with different fluoride concentrations in the drinking water, participated in the study. Two samples of drinking water and parotid and whole saliva were collected for each subject and were analyzed for fluoride using appropriate electrode techniques. Results: Mean water F concentrations (±SE, mg/l, n = 60) were 0.09 ± 0.01, 0.15 ± 0.01, 0.66 ± 0.01, 0.72 ± 0.02, and 1.68 ± 0.08 for A–E, respectively. Mean F concentrations (±SE, mg/l, n = 15) ranged between 0.014 ± 0.002 (A, 3–7 years) and 0.297 ± 0.057 (D, 14–20 years) for whole saliva and 0.009 ± 0.001 (C, 30–40 years) and 0.284 ± 0.038 (E, 50–60 years) for parotid saliva. Results of multivariate linear regression analysis showed that geographical area and water fluoride concentration exerted the strongest influence in whole and ductal saliva F concentrations, respectively. Conclusion: Therefore, parotid ductal saliva seems to be a more appropriate biomarker of fluoride exposure, and factors like age and localization should also be considered when using this biomarker.
Orchiectomy Attenuates Kidney Fibrosis after Ureteral Obstruction by Reduction of Oxidative Stress in Mice
Authors: Cho Min Hyun , Jung Kyong-Jin , Jang Hee-Seong , Kim Jee In , Park Kwon Moo
Published: December 2011

Background/Aims: Men are generally more prone to chronic kidney disease and progression to end-stage renal disease than women. However, the underlying mechanisms remain unclear. In this study, we investigated the role of reactive oxygen species and testosterone in the progression of renal fibrosis in mice with unilateral ureteral obstruction (UUO). Methods: Mice were subjected to either orchiectomy or sham operation 14 days before either UUO or sham surgery. Harvesting of the kidney was performed 7 days after the UUO surgery to measure the production of reactive oxygen species and expression of antioxidants such as catalase, copper-zinc superoxide dismutase, and manganese superoxide dismutase, as well as fibrosis markers including α-smooth muscle actin (α-SMA) and collagen. Results: UUO resulted in increased expression of α-SMA and collagen deposition in the kidneys of both female and male mice. These increases were significantly greater in males than females. Orchiectomy significantly reduced increases in α-SMA expression and collagen deposition when compared with intact male. UUO increased the production of hydrogen peroxide and lipid peroxidation along with the decreases in expression of manganese superoxide dismutase, copper-zinc superoxide dismutase, and catalase. These changes induced by UUO were significantly attenuated by orchiectomy. Conclusion: Males are more susceptible to UUO-induced kidney fibrosis compared with females, and the higher susceptibility of males is obviated by orchiectomy along with reduction in oxidative stress.
Scribes et enquêteurs Note sur le personnel judiciaire en Égypte aux quatre premiers siècles de l’hégire
Authors: Tillier Mathieu
Published: December 2011

Abstract

This article undertakes first a reconstruction of lists of legal scribes (kātibs) and investigators (ṣāḥibsal-masāʾil) active in Fusṭāṭ between the 1st/early 8th and the 4th/10th century. Identification of these people allows a better understanding of the recruitment of Egyptian judiciary staff. Their reputations as scholars, as well as their ethnical, geographical and tribal origins, show that legal careers were limited by social barriers for a long time. Up until the 3rd/9th century, the office of scribe was mostly held bymawālī—high-ranking clients could possibly aspire to the office of investigator—, whereasqāḍīs were recruited among Arabs. The partitioning of the judiciary reveals a complex social hierarchy beyond the mere distinction between Arabs and non-Arabs. The results of this study also allow a re-evaluation of the Abbasid revolution’s impact on Egyptian society.
A Symposium on the American Civil War and Slavery
Authors: Edwards Steve
Published: December 2011

Abstract

On the occasion of the 150th anniversary of the beginning of the American Civil War, Historical Materialism has brought together some of the most significant Marxist scholars working in this area to debate the issues. This text introduces some of the questions raised by the Civil War and Southern slavery for Marxists and introduces the essays that follow.
History and the Philosophy of Art
Authors: Carroll Noël
Published: December 2011

Abstract

In this essay I trace the role of history in the philosophy of art from the early twentieth century to the present, beginning with the rejection of history by formalists like Clive Bell. I then attempt to show how the arguments of people like Morris Weitz and Arthur Danto led to a re-appreciation of history by philosophers of art such as Richard Wollheim, Jerrold Levinson, Robert Stecker and others.
Four Species of Reflexivity and History of Economics in Economic Policy Science
Authors: Schliesser Eric
Published: December 2011

Abstract

This paper argues that history of economics has a fruitful, underappreciated role to play in the development of economics, especially when understood as a policy science. This goes against the grain of the last half century during which economics, which has undergone a formal revolution, has distanced itself from its ‘literary’ past and practices precisely with the aim to be a more successful policy science.

The paper motivates the thesis by identifying and distinguishing four kinds of reflexivity in economics. The main thesis of this paper is that because these forms of reflexivity are not eliminable, the history of economics must play a constitutive role in economics (and graduate education within economics). An assumption that I clarify in this paper is that the history of economics ought to be part of the subject matter studied by economics when they are interested in policy science. Even if one does not accept the conclusion, the fourfold classification of reflexivity might hold independent interest.

The paper is divided in two parts. First, by reflecting on the writings of George Stigler, Paul Samuelson, George and Milton Friedman, I offer a stylized historical introduction to and conceptualization of the themes of this paper. In particular, I identify various historically influential arguments and strategies that reduced the role of history of economics within the economics discipline. In it I also canvass six arguments that try to capture the cost to economics (understood as a science) for sidelining the history of economics from within the discipline. A sub-text of the introduction is that for contingent reasons, post World War II economics evolved into a policy science. Second, by drawing on the work of Kenneth Boulding, in particular, George Soros, Thomas Merton, Gordon Tullock, I distinguish between four species of reflexivity. These are used to then strengthen the argument for the constitutive role of the history of economics within the economics profession. In particular, I argue that so-called Kuhn-losses are especially pernicious when faced with policy choices under so-called Knightian uncertainty.
Seven Mystical Poems on the Hebrew Vowels as Interpreted by Yosef Giqaṭilla and Mordekhay Dato
Authors: Martini Annett
Published: December 2011

Abstract

One of the most original facets of Yosef Giqaṭilla’s mystical concept is his approach to the symbolical meaning of the Hebrew vowels. Throughout his life, he wrote several treatises about this subject, which deal with the Hebrew vowels as fundamental elements within Creation and the structure of the cosmos. About three hundred years later, the Italian kabbalist Mordekhay Dato wrote a commentary on the Secrets of the Vowels which actually is an interpretation of the poems written by Giqaṭilla in order to condense his theses about the Hebrew vowels. The present paper explores the following questions: (1) From where did Dato derive the seven poems, which, on the one hand, are part of Giqaṭilla’s discussion about the vowels, but on the other, have been transmitted separately? (2) Did Dato know their original context? (3) In what way does his interpretation of these verses differ from Giqaṭilla’s?