bluuebunny/crossref_metadata_2025_split huggingface dataset:
Wnt signaling in caudal dysgenesis and diabetic embryopathy
Authors: Pavlinkova Gabriela , Salbaum J. Michael , Kappen Claudia 
Published: October 2008

AbstractBACKGROUND:Congenital defects are a major complication of diabetic pregnancy, and the leading cause of infant death in the first year of life. Caudal dysgenesis, occurring up to 200‐fold more frequently in children born to diabetic mothers, is a hallmark of diabetic pregnancy. Given that there is also an at least threefold higher risk for heart defects and NTDs, it is important to identify the underlying molecular mechanisms for aberrant embryonic development.METHODS:We have investigated gene expression in a transgenic mouse model of caudal dysgenesis, and in a pharmacological model using situ hybridization and quantitative real‐time PCR.RESULTS:We identified altered expression of several molecules that control developmental processes and embryonic growth.CONCLUSIONS:The results from our models point towards major implication of altered Wnt signaling in the pathogenesis of developmental anomalies associated with embryonic exposure to maternal diabetes. Birth Defects Research (Part A) 82:710–719, 2008. © 2008 Wiley‐Liss, Inc.
Inhibition of methylation and changes in gene expression in relation to neural tube defects
Authors: van der Linden Ivon J. M. , Heil Sandra G. , van Egmont Petersen Michael , van Straaten Henny W. , Heijer Martin den , Blom Henk J. 
Published: October 2008

AbstractBACKGROUND:An impaired DNA methylation has been suggested to underlie the complex etiology of neural tube defects (NTDs). Previously, we have demonstrated that inhibition of methylation by periodate oxidized adenosine (Adox) results in a widening of the anterior neuropore (ANP) in our in vitro chick embryo model. Since DNA methylation is the chief regulator of gene expression, we hypothesize that inhibition of methylation by Adox in our in vitro chick embryo model will affect the expression of genes that may be involved in neurulation. In the present study, we therefore examined differential gene expression between Adox‐treated and control chick embryos, using the Affymetrix Genechip Chicken Genome Array.METHODS:Chick embryos of 4/5 somites were cultured in vitro with saline (control) or Adox and cranial parts were excised. Gene expression profiling was determined using the Affymetrix Genechip Chicken Genome Array on RNA isolated from two pools of Adox‐treated cranial parts (n = 12) and two pools of saline‐treated cranial parts (n = 12). Microarray data were validated by QPCR analysis.RESULTS:In the Adox‐treated chick embryos, 45 probesets were up‐regulated (fold ≥ 2.0, p < 0.05) and 32 probesets were down‐regulated (fold ≤ 0.5, p < 0.05). Of the 15 genes selected for QPCR analysis, the up‐regulation of phosphoserine phosphatase (PSPH), unc‐51‐like kinase 1 (ULK1), and chemokine (C‐X‐C motif) ligand 12/stromal cell‐derived factor 1 (CXCL12/SDF‐1) was confirmed.CONCLUSIONS:Inhibition of methylation by Adox affects gene expression in our in vitro chick embryo model. Further research will focus on the gene‐specific methylation patterns of PSPH, ULK1, and CXCL12/SDF‐1 and the role of the products of these genes in neurulation. Birth Defects Research (Part A) 82:676–683, 2008. © 2008 Wiley‐Liss, Inc.
A butterfly eye's view of birds
Authors: Frentiu Francesca D. , Briscoe Adriana D. 
Published: October 2008

AbstractThe striking color patterns of butterflies and birds have long interested biologists. But how these animals see color is less well understood. Opsins are the protein components of the visual pigments of the eye. Color vision has evolved in butterflies through opsin gene duplications, through positive selection at individual opsin loci, and by the use of filtering pigments. By contrast, birds have retained the same opsin complement present in early‐jawed vertebrates, and their visual system has diversified primarily through tuning of the short‐wavelength‐sensitive photoreceptors, rather than by opsin duplication or the use of filtering elements. Butterflies and birds have evolved photoreceptors that might use some of the same amino acid sites for generating similar spectral phenotypes across ∼540 million years of evolution, when rhabdomeric and ciliary‐type opsins radiated during the early Cambrian period. Considering the similarities between the two taxa, it is surprising that the eyes of birds are not more diverse. Additional taxonomic sampling of birds may help clarify this mystery. BioEssays 30:1151–1162, 2008. © 2008 Wiley Periodicals, Inc.
Constraints on the evolution of asexual reproduction
Authors: Engelstädter Jan 
Published: October 2008

AbstractSexual reproduction is almost ubiquitous among multicellular organisms even though it entails severe fitness costs. To resolve this apparent paradox, an extensive body of research has been devoted to identifying the selective advantages of recombination that counteract these costs. Yet, how easy is it to make the transition to asexual reproduction once sexual reproduction has been established for a long time? The present review approaches this question by considering factors that impede the evolution of parthenogenesis in animals. Most importantly, eggs need a diploid chromosome set in most species in order to develop normally. Next, eggs may need to be activated by sperm, and sperm may also contribute centrioles and other paternal factors to the zygote. Depending on how diploidy is achieved mechanistically, further problems may arise in offspring that stem from ‘inbreeding depression’ or inappropriate sex determination systems. Finally, genomic imprinting is another well‐known barrier to the evolution of asexuality in mammals. Studies on species with occasional, deficient parthenogenesis indicate that the relative importance of these constraints may vary widely. The intimate evolutionary relations between haplodiploidy and parthenogenesis as well as implications for the clade selection hypothesis of the maintenance of sexual reproduction are also discussed. BioEssays 30:1138–1150, 2008. © 2008 Wiley Periodicals, Inc.
Network modeling of signal transduction: establishing the global view
Authors: Kestler Hans A. , Wawra Christian , Kracher Barbara , Kühl Michael 
Published: October 2008

AbstractEmbryonic development and adult tissue homeostasis are controlled through activation of intracellular signal transduction pathways by extracellular growth factors. In the past, signal transduction has largely been regarded as a linear process. However, more recent data from large‐scale and high‐throughput experiments indicate that there is extensive cross‐talk between individual signaling cascades leading to the notion of a signaling network. The behavior of such complex networks cannot be predicted by simple intuitive approaches but requires sophisticated models and computational simulations. The purpose of such models is to generate experimentally testable hypotheses and to find explanations for unexpected experimental results. Here, we discuss the need for, and the future impact of, mathematical models for exploring signal transduction in different biological contexts such as for example development. BioEssays 30:1110–1125, 2008. © 2008 Wiley Periodicals, Inc.
Edited GluR2, a gatekeeper for motor neurone survival?
Authors: Buckingham S.D. , Kwak S. , Jones A.K. , Blackshaw S.E. , Sattelle D.B. 
Published: October 2008

AbstractAmyotrophic lateral sclerosis (ALS) is a progressive degenerative disorder of motor neurones. Although the genetic basis of familial forms of ALS has been well explored, the molecular basis of sporadic ALS is less well understood. Recent evidence has linked sporadic ALS with the failure to edit key residues in ionotropic glutamate receptors, resulting in excessive influx of calcium ions into motor neurones which in turn triggers cell death. Here we suggest that edited AMPA glutamate (GluR2) receptor subunits serve as gatekeepers for motor neurone survival. BioEssays 30:1185–1192, 2008. © 2008 Wiley Periodicals, Inc.
The brave new era of human genetic testing
Authors: Bandelt Hans‐Jürgen , Yao Yong‐Gang , Richards Martin B. , Salas Antonio 
Published: October 2008

AbstractThe commercialization of ‘big science’ is in full swing, leading to situations in which the ethical principles of academia are beginning to be compromised. This is exemplified by the profitable business of genetic ancestry testing. The goals of this sort of ‘big science’ are not necessarily in any way novel, however. In particular, large genotyping projects have a certain start‐up time when their design is frozen in, so that the projects often lag behind the development of genetic knowledge. On the other hand, extremely provisional knowledge about potential disease markers is being rapidly turned into questionable ‘tests’, purporting to determine risk factors for complex disorders, by private companies that are eager to get their share of a profitable market of the future. The flow of money generated by such concerns looks likely to erode traditional research operations and small‐scale projects, which risk becoming pebbles on the ‘big science’ landscape. BioEssays 30:1246–1251, 2008. © 2008 Wiley Periodicals, Inc.
Avoiding bad genes: oxidatively damaged DNA in germ line and mate choice
Authors: Velando Alberto , Torres Roxana , Alonso‐Alvarez Carlos 
Published: October 2008

AbstractAugust Weismann proposed that genetic changes in somatic cells cannot pass to germ cells and hence to next generations. Nevertheless, evidence is accumulating that some environmental effects can promote heritable changes in the DNA of germ cells, which implies that some somatic influence on germ line is possible. This influence is mostly detrimental and related to the presence of oxidative stress, which induces mutations and epigenetic changes. This effect should be stronger in males due to the particular characteristics of sperm. Here, we propose the hypothesis that females are able to avoid males with oxidatively damaged DNA in the germ line by using oxidative‐dependent (pre‐ and post‐mating) signals. This new hypothesis may shed light on unsolved questions in evolutionary biology, such as the benefits of polyandry, the lek paradox, or the role of sexual selection on the evolution of aging. BioEssays 30:1212–1219, 2008. © 2008 Wiley Periodicals, Inc.
The biphasic behavior of incoherent feed‐forward loops in biomolecular regulatory networks
Authors: Kim Dongsan , Kwon Yung‐Keun , Cho Kwang‐Hyun 
Published: October 2008

AbstractAn incoherent feed‐forward loop (FFL) is one of the most‐frequently observed motifs in biomolecular regulatory networks. It has been thought that the incoherent FFL is designed simply to induce a transient response shaped by a ‘fast activation and delayed inhibition’. We find that the dynamics of various incoherent FFLs can be further classified into two types: time‐dependent biphasic responses and dose‐dependent biphasic responses. Why do the structurally identical incoherent FFLs play such different dynamical roles? Through computational studies, we show that the dynamics of the two types of incoherent FFLs are mutually exclusive. Following from further computational results and experimental observations, we hypothesize that incoherent FFLs have been optimally designed to achieve distinct biological function arising from different cellular contexts. Additional Supporting Information may be found in the online version of the article. BioEssays 30:1204–1211, 2008. © 2008 Wiley Periodicals, Inc.
Ensuring the fidelity of recombination in mammalian chromosomes
Authors: Waldman Alan S. 
Published: October 2008

AbstractMammalian cells frequently depend on homologous recombination (HR) to repair DNA damage accurately and to help rescue stalled or collapsed replication forks. The essence of HR is an exchange of nucleotides between identical or nearly identical sequences. Although HR fulfills important biological roles, recombination between inappropriate sequence partners can lead to translocations or other deleterious rearrangements and such events must be avoided. For example, the recombination machinery must follow stringent rules to preclude recombination between the many repetitive elements in a mammalian genome that share significant but imperfect homology. This paper takes a conceptual approach in addressing the homology requirements for recombination in mammalian genomes as well as the general strategy used by cells to reject recombination between similar but imperfectly matched sequences. A mechanism of heteroduplex rejection that involves the unwinding of recombination intermediates that may form between mismatched sequences is discussed. BioEssays 30:1163–1171, 2008. © 2008 Wiley Periodicals, Inc.
The discovery of polyribosomes
Authors: Noll Hans 
Published: October 2008

AbstractBy the early 1960s, evidence had accumulated that proteins were synthesized from special RNA copies of genes, named “messenger RNAs” (mRNAs), not directly from the stable RNAs found in the ribosomes of the cytoplasm. Yet, precisely how the protein chains were assembled along the RNA and, in particular, the relationship between the mRNAs and the ribosomes during protein synthesis, was obscure. In this account, I discuss how my laboratory found that multiple ribosomes traverse each mRNA, yielding the structures known as polysomes. This work led on to the first physical determination of the coding ratio, new insights into how protein chains are initiated, and an early suggestion that chloroplasts and mitochondria in eukaryotic cells might ultimately have been derived from symbiotic bacteria. BioEssays 30:1220–1234, 2008. © 2008 Wiley Periodicals, Inc.
One thousand and one ways of making functionally similar transcriptional enhancers
Authors: Veitia Reiner A. 
Published: October 2008

AbstractExpression of most genes is regulated by the interaction of multiple transcription factors with cis‐regulatory sequences. Many studies have focused on how changes in promoters and enhancers alter gene expression and phenotype. Recently, Hare et al., using elegant wet and computational approaches uncovered a series of enhancers driving the expression of the even‐skipped gene in scavenger flies (Sepsidae).1 Despite the strong sequence divergence between the enhancers in sepsids and drosophilids, they lead to remarkably similar patterns of gene expression in transgenic Drosophila embryos. This can be explained by the existence of intra‐enhancer compensatory mutations and the presence of overlapping/near binding sites for activators and repressors. BioEssays 30:1052–1057, 2008. © 2008 Wiley Periodicals, Inc.
Simultaneous quantification of a non‐nucleoside reverse transcriptase inhibitor efavirenz, a nucleoside reverse transcriptase inhibitor emtricitabine and a nucleotide reverse transcriptase inhibitor tenofovir in plasma by liquid chromatography positive ion electrospray tandem mass spectrometry
Authors: Nirogi Ramakrishna , Bhyrapuneni Gopinadh , Kandikere Vishwottam , Mudigonda Koteshwara , Komarneni Prashanth , Aleti Raghupathi , Mukkanti K. 
Published: October 2008

AbstractA high‐performance liquid chromatography/positive ion electrospray tandem mass spectrometry method for the simultaneous quantification of efavirenz, emtricitabine and tenofovir was developed and validated with 100 µL human plasma. Following solid‐phase extraction, the analytes were separated using a gradient mobile phase on a reverse‐phase column and analyzed by MS/MS in the multiple reaction monitoring mode using the respective [M + H]+ ions, m/z 316 to 168 for efavirenz, m/z 248–130 for emtricitabine and m/z 288–176 for tenofovir, m/z 482–258 for rosuvastatin (IS), m/z 260–116 for propranolol (IS). The method exhibited a 100‐fold linear dynamic range for all the three analytes in human plasma (20–2000, 2–200 and 20–2000 ng/mL for efavirenz, emtricitabine and tenofovir respectively). The lower limit of quantification was 2 ng/mL for emtricitabine and 20 ng/mL for both efavirenz and tenofovir with a relative standard deviation of less than 11%. Acceptable precision and accuracy were obtained for concentrations over the standard curve range. The total chromatographic run time of 4 min for each sample made it possible to analyze more than 250 human plasma samples per day. The method is precise and sensitive enough for its intended purpose. The method is also successfully applied to quantify efavirenz, emtricitabine and tenofovir concentrations in a rodent pharmacokinetic study. Copyright © 2008 John Wiley & Sons, Ltd.
Clopidogrel: review of bioanalytical methods, pharmacokinetics/pharmacodynamics, and update on recent trends in drug–drug interaction studies
Authors: Mullangi Ramesh , Srinivas Nuggehally R. 
Published: October 2008

AbstractClopidogrel, owing to its excellent inhibitory property of platelet aggregation, is used to reduce the cardiovascular risks in patients with multiple co‐morbid conditions such as stroke, myocardial infarction and atherosclerosis. The current review focuses distinctly on three aspects: (a) an in‐depth coverage on the bioanalytical methods for the quantification of clopidogrel and its inactive carboxylic acid metabolite as well as the active metabolite in pre‐clinical and clinical samples; (b) an overview of the pharmacokinetic/pharmacodynamic aspects of clopidogrel; and (c) enumerating the key findings from drug–drug interaction studies of clopidogrel with various co‐substrates such as lanzoprazole, fluvastatin, atorvastatin, pravastatin, digoxin, ketoconazole, donezepil and theophylline. Copyright © 2008 John Wiley & Sons, Ltd.
A Polylinker Approach to Reductive Loop Swaps in Modular Polyketide Synthases
Authors: Kellenberger Laurenz , Galloway Ian S. , Sauter Guido , Böhm Günter , Hanefeld Ulf , Cortés Jesús , Staunton James , Leadlay Peter F. 
Published: October 2008

AbstractMultiple versions of the DEBS 1‐TE gene, which encodes a truncated bimodular polyketide synthase (PKS) derived from the erythromycin‐producing PKS, were created by replacing the DNA encoding the ketoreductase (KR) domain in the second extension module by either of two synthetic oligonucleotide linkers. This made available a total of nine unique restriction sites for engineering. The DNA for donor “reductive loops,” which are sets of contiguous domains comprising either KR or KR and dehydratase (DH), or KR, DH and enoylreductase (ER) domains, was cloned from selected modules of five natural PKS multienzymes and spliced into module 2 of DEBS 1‐TE using alternative polylinker sites. The resulting hybrid PKSs were tested for triketide production in vivo. Most of the hybrid multienzymes were active, vindicating the treatment of the reductive loop as a single structural unit, but yields were dependent on the restriction sites used. Further, different donor reductive loops worked optimally with different splice sites. For those reductive loops comprising DH, ER and KR domains, premature TE‐catalysed release of partially reduced intermediates was sometimes seen, which provided further insight into the overall stereochemistry of reduction in those modules. Analysis of loops containing KR only, which should generate stereocentres at both C‐2 and C‐3, revealed that the 3‐hydroxy configuration (but not the 2‐methyl configuration) could be altered by appropriate choice of a donor loop. The successful swapping of reductive loops provides an interesting parallel to a recently suggested pathway for the natural evolution of modular PKSs by recombination.
Enantioselective plasma protein binding of propafenone: Mechanism, drug interaction, and species difference
Authors: Hong Yanjun , Tang Yihong , Zeng Su 
Published: October 2008

AbstractThe interaction of propafenone (PPF) enantiomers with human plasma, human serum albumin (HSA), α1‐acid glycoprotein (AGP), as well as with plasma from rat, rabbit, and cow was investigated using indirect chiral high performance liquid chromatography (HPLC) and ultrafiltration techniques. The stronger binding of the S‐PPF found in human plasma was due to AGP. Two classes of binding sites in AGP were identified: one with high‐affinity and small binding capacity (K1(S) = 7.65 × 106 M−1, n1(S) = 0.50; K1(R) = 2.81 × 106 M−1, n1(R) = 0.46), which revealed stereoselectivity; the other with low‐affinity and high‐binding capacity (n2(S) K2(S) = 9.95 × 103 M−1; n2(R) K2(R) = 9.74 × 103 M−1). The binding to HSA was found to be weak and not enantioselective (nKS = 2.08 × 103 M−1, nKR = 2.05 × 103 M−1). The interaction between enantiomers observed in human plasma was confirmed as a competitive type interacting at the high‐affinity site in AGP. The binding mode of both enantiomers with AGP was mainly hydrophobic bond. PPF enantiomers had higher‐binding affinity for the F‐S variant of human AGP. Drug‐drug binding interaction studies showed that verapamil, diazepam, nifedipine, furosemide, nitrendipine, and nimodipine did not affect the binding of PPF enantiomers except quinidine and aprindine at the therapeutic concentration. Comparative studies indicated considerable species‐dependent binding stereoselectivity between plasma of the four species investigated. Chirality, 2009. © 2008 Wiley‐Liss, Inc.
Disparate effects of different mutations in plakoglobin on cell mechanical behavior
Authors: Huang Hayden , Asimaki Angeliki , Lo Denise , McKenna William , Saffitz Jeffrey 
Published: October 2008

AbstractMutations in genes encoding desmosomal proteins have been implicated in the pathogenesis of heart and skin diseases. This has led to the hypothesis that defective cell‐cell adhesion is the underlying cause of injury in tissues that repeatedly bear high mechanical loads. In this study, we examined the effects of two different mutations in plakoglobin on cell migration, stiffness, and adhesion. One is a C‐terminal mutation causing Naxos disease, a recessive syndrome of arrhythmogenic right ventricular cardiomyopathy (ARVC) and abnormal skin and hair. The other is an N‐terminal mutation causing dominant inheritance of ARVC without cutaneous abnormalities. To assess the effects of plakoglobin mutations on a broad range of cell mechanical behavior, we characterized a model system consisting of stably transfected HEK cells which are particularly well suited for analyses of cell migration and adhesion. Both mutations increased the speed of wound healing which appeared to be related to increased cell motility rather than increased cell proliferation. However, the C‐terminal mutation led to dramatically decreased cell‐cell adhesion, whereas the N‐terminal mutation caused a decrease in cell stiffness. These results indicate that different mutations in plakoglobin have markedly disparate effects on cell mechanical behavior, suggesting complex biomechanical roles for this protein. Cell Motil. Cytoskeleton 2008. © 2008 Wiley‐Liss, Inc.
A tropomyosin 1 induced defect in cytokinesis can be rescued by elevated expression of cofilin
Authors: Thoms Julie A. I. , Loch Heather M. , Bamburg James R. , Gunning Peter W. , Weinberger Ron P. 
Published: October 2008

AbstractCytokinesis in eukaryotic cells is mediated by the contractile ring, an actomyosin‐based structure which provides the force required to separate daughter cells. Isoforms of the actin‐binding protein tropomyosin are also localised to the contractile ring in both fission yeast and human astrocytes. Although tropomyosin is required for cytokinesis in yeast, its precise role in the contractile ring is unknown. In this study we find that increased expression of a single tropomyosin isoform, tropomyosin 1, in U373MG astrocytoma cells leads to multinucleated cells and mitotic spindle defects. Furthermore, cells expressing increased levels of tropomyosin 1 usually fail to complete cytokinesis and this is accompanied by reduced accumulation of actin depolymerising factor/cofilin in the contractile ring. Adenovirus mediated expression of cofilin is able to relieve the tropomyosin 1 induced effects on cytokinesis. We conclude that tropomyosin 1 and cofilin play antagonistic roles within the contractile ring and that the balance between tropomyosin 1 and cofilin expression is important for cytokinesis. Cell Motil. Cytoskeleton 2008. © 2008 Wiley‐Liss, Inc.