BioEssays (BIOESSAYS)

Publications in this journal

• Article: If microbial ecosystem therapy can change your life, what's the problem?

  G. Ettinger, J.P. Burton, G. Reid
  BioEssays 01/2013;
• Article: When a domain is not a domain, and why it is important to properly filter proteins in databases

  Clare-Louise Towse, Valerie Daggett
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  ABSTRACT: Membership in a protein domain database does not a domain make; a feature we realized when generating a consensus view of protein fold space with our consensus domain dictionary (CDD). This dictionary was used to select representative structures for characterization of the protein dynameome: the Dynameomics initiative. Through this endeavor we rejected a surprising 40% of the 1,695 folds in the CDD as being non-autonomous folding units. Although some of this was due to the challenges of grouping similar fold topologies, the dissonance between the cataloguing and structural qualification of protein domains remains surprising. Another potential factor is previously overlooked intrinsic disorder; predictions suggest that 40% of proteins have either local or global disorder. One thing is clear, filtering a structural database and ensuring a consistent definition for protein domains is crucial, and caution is prescribed when generalizations of globular domains are drawn from unfiltered protein domain datasets.
  BioEssays 12/2012; 34(12).
• Article: The thrifty epigenotype: an acquired and heritable predisposition for obesity and diabetes?

  Reinhard Stöger
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  ABSTRACT: Obesity and type 2 diabetes arise from a set of complex gene-environment interactions. Explanations for the heritability of these syndromes and the environmental contribution to disease susceptibility are addressed by the "thrifty genotype" and the "thrifty phenotype" hypotheses. Here, the merits of both models are discussed and elements of them are used to synthesize a "thrifty epigenotype" hypothesis. I propose that: (1) metabolic thrift, the capacity for efficient acquisition, storage and use of energy, is an ancient, complex trait, (2) the environmentally responsive gene network encoding this trait is subject to genetic canalization and thereby has become robust against mutational perturbations, (3) DNA sequence polymorphisms play a minor role in the aetiology of obesity and type 2 diabetes-instead, disease susceptibility is predominantly determined by epigenetic variations, (4) corresponding epigenotypes have the potential to be inherited across generations, and (5) Leptin is a candidate gene for the acquisition of a thrifty epigenotype.
  BioEssays 03/2008; 30(2):156-66.
• Article: Dr Watson's woeful words--and two missed opportunities.

  Adam S Wilkins
  BioEssays 03/2008; 30(2):99-101.
• Article: The gene-centric concept: a new liability?

  Henry H Q Heng
  BioEssays 03/2008; 30(2):196-7.
• Article: Another notch in stem cell biology: Drosophila intestinal stem cells and the specification of cell fates.

  Andrew A Wilson, Darrell N Kotton
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  ABSTRACT: Previous work has suggested that many stem cells can be found in microanatomic niches, where adjacent somatic cells of the niche control the differentiation and proliferation states of their resident stem cells. Recently published work examining intestinal stem cells (ISCs) in the adult Drosophila midgut suggests a new paradigm where some stem cells actively control the cell fate decisions of their daughters. Here, we review recent literature((1)) demonstrating that, in the absence of a detectable stem cell niche, multipotent Drosophila ISCs modulate the Notch signaling pathway in their adjacent daughter cells in order to specify the differentiated lineages of their descendants. These observations made in Drosophila are challenging and advancing our understanding of stem cell biology.
  BioEssays 03/2008; 30(2):107-9.
• Article: Which way does the Wnt blow? Exploring the duality of canonical Wnt signaling on cellular aging.

  Nathan A DeCarolis, Keith A Wharton, Amelia J Eisch
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  ABSTRACT: Critical cellular functions, including stem cell maintenance, fate determination, and cellular behavior, are governed by canonical Wnt signaling, an evolutionarily conserved pathway whose intracellular signal is transduced by beta-catentin. Emerging evidence suggests that canonical Wnt signaling influences cellular aging, indicating that increases in Wnt signaling delay age-related deficits.1 However, recent Science papers suggest that Wnt signaling accelerates the onset of aging.2,3 In an attempt to resolve this paradox and clarify how Wnt signaling affects aging, we provide a selective review of research relevant to Wnt signaling and aging.
  BioEssays 03/2008; 30(2):102-6.
• Article: Neurogenesis in adult CNS: from denial to opportunities and challenges for therapy.

  Luca Colucci-D'Amato, Umberto di Porzio
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  ABSTRACT: The discovery of neurogenesis and neural stem cells (NSC) in the adult CNS has overturned a long-standing and deep-routed "dogma" in neuroscience, established at the beginning of the 20(th) century. This dogma lasted for almost 90 years and died hard when NSC were finally isolated from the adult mouse brain. The scepticism in accepting adult neurogenesis has now turned into a rush to find applications to alleviate or cure the devastating diseases that affect the CNS. Here we highlight a number of methodological, technical and conceptual drawbacks responsible for the historical denial of adult neurogenesis. Furthermore, we discuss old and new issues that need to be faced before NSC or endogenous neurogenesis can safely enter into the doctor's bag for therapies.
  BioEssays 03/2008; 30(2):135-45.
• Source

  Available from: arizona.edu

  Article: Paleogenomics in vertebrates, or the recovery of lost genomes from the mist of time.

  Matthieu Muffato, Hugues Roest Crollius
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  ABSTRACT: Knowledge of the structure of ancestral genomes provides the basis of a new framework to better represent and interpret results from genomic and evolutionary studies. Because these ancestors lived tens of hundreds of million years ago, this knowledge will inevitably take the form of abstract representations, reconstructed on the basis both of experimental evidence collected on extant genomes and of our understanding of evolutionary processes. This is the field of Paleogenomics, a young discipline that is providing an increasingly precise picture of our ancestral vertebrate genomes based on cytogenetic data, genome sequences and new algorithmic developments. Many recent studies have focused on the ancestral placental mammal and teleost fish genomes, although the outlines of even more distant pre-vertebrate ancestors are being reported.
  BioEssays 03/2008; 30(2):122-34.
• Article: Vitamin D discovery outpaces FDA decision making.

  Trevor G Marshall
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  ABSTRACT: The US FDA currently encourages the addition of vitamin D to milk and cereals, with the aim of reducing rickets in children and osteoporosis in adults. However, vitamin D not only regulates the expression of genes associated with calcium homeostasis, but also genes associated with cancers, autoimmune disease, and infection. It does this by controlling the activation of the vitamin D receptor (VDR), a type 1 nuclear receptor and DNA transcription factor. Molecular biology is rapidly coming to an understanding of the multiplicity of roles played by the VDR, but clinical medicine is having difficulty keeping up with the pace of change. For example, the FDA recently proposed a rule change that will encourage high levels of vitamin D to be added to even more foods, so that the manufacturers can claim those foods "reduce the risk of osteoporosis". The FDA docket does not review one single paper detailing the transcriptional activity of vitamin D, even though, on average, one new paper a day is being published on that topic. Nor do they review whether widespread supplementation with vitamin D, an immunomodulatory secosteroid, might predispose the population to immune dysfunction. This BioEssay explores how lifelong supplementation of the food chain with vitamin D might well be contributing to the current epidemics of obesity and chronic disease.
  BioEssays 03/2008; 30(2):173-82.
• Article: Differential pharmacological regulation of drug efflux and pharmacoresistant schizophrenia.

  Mary Bebawy, Manoranjenni Chetty
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  ABSTRACT: Pharmacoresistant schizophrenia is a significant impediment to the successful management of the disease. The expression and function of P-glycoprotein (P-gp) has recently been implicated in this phenomenon. P-gp is a multidrug efflux transporter that prevents drug substrates from crossing the blood-brain barrier (BBB). Although the direct interaction between individual antipsychotic agents and P-gp has been demonstrated, the effect of antipsychotic drug combinations used in disease management on P-gp transport function remains to be elucidated. This could have important clinical implications in some individuals as dosage adjustments based on plasma drug concentration changes may not always be appropriate if drug-drug interactions and the resulting changes in drug concentration in the brain are not considered. This paper introduces the potential impact that combination antipsychotic therapy may have on P-gp function at the BBB and discusses the consequences of this in the prevention and circumvention of unfavourable therapeutic response in schizophrenic disorders.
  BioEssays 03/2008; 30(2):183-8.
• Article: How does noncoding transcription regulate Hox genes?

  Adelheid Lempradl, Leonie Ringrose
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  ABSTRACT: Noncoding RNA has arrived at centre stage in recent years with the discovery of "hidden transcriptomes" in many higher organisms. Over two decades ago, noncoding transcripts were discovered in Drosophila Hox complexes, but their function has remained elusive. Recent studies1-3 have examined the role of these noncoding RNAs in Hox gene regulation, and have generated a fierce debate as to whether the noncoding transcripts are important for silencing or activation. Here we review the evidence, and show that, by taking developmental timing into account, some of these apparently conflicting results can be resolved. We examine current models that explain these data and explore alternative interpretations.
  BioEssays 03/2008; 30(2):110-21.
• Article: cAMP-dependent protein kinase A and the dynamics of epithelial cell surface domains: moving membranes to keep in shape.

  Kacper A Wojtal, Dick Hoekstra, Sven C D van Ijzendoorn
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  ABSTRACT: Cyclic adenosine monophosphate (cAMP) and cAMP-dependent protein kinase A (PKA) are evolutionary conserved molecules with a well-established position in the complex network of signal transduction pathways. cAMP/PKA-mediated signaling pathways are implicated in many biological processes that cooperate in organ development including the motility, survival, proliferation and differentiation of epithelial cells. Cell surface polarity, here defined as the anisotropic organisation of cellular membranes, is a critical parameter for most of these processes. Changes in the activity of cAMP/PKA elicit a variety of effects on intracellular membrane dynamics, including membrane sorting and trafficking. One of the most intriguing aspects of cAMP/PKA signaling is its evolutionary conserved abundance on the one hand and its precise spatial-temporal actions on the other. Here, we review recent developments with regard to the role of cAMP/PKA in the regulation of intracellular membrane trafficking in relation to the dynamics of epithelial surface domains.
  BioEssays 03/2008; 30(2):146-55.
• Source

  Available from: riken.go.jp

  Article: Hagfish (cyclostomata, vertebrata): searching for the ancestral developmental plan of vertebrates.

  Shigeru Kuratani, Kinya G Ota
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  ABSTRACT: The phylogenetic position of the hagfish remains enigmatic. In contrast to molecular data that suggest monophyly of the cyclostomes, several morphological features imply a more ancestral state of this animal compared with the lampreys. To resolve this question requires an understanding of the embryology of the hagfish, especially of the neural crest. The early development of the hagfish has long remained a mystery. We collected a shallow-water-dwelling hagfish, Eptatretus burgeri, set up an aquarium tank designed to resemble its habitat, and successfully obtained several embryos. By observing the histology and expression of genes known to play fundamental roles in the neural crest, we found that the hagfish crest develops as delaminating migratory cells, as in other vertebrates. We conclude that the delaminating neural crest is a vertebrate synapomorphy that seems to have appeared from the beginning of their evolutionary history, before the splitting away of the hagfish lineage.
  BioEssays 03/2008; 30(2):167-72.
• Article: A shifting paradigm: histone deacetylases and transcriptional activation.

  Catharine L Smith
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  ABSTRACT: Transcriptional repression and silencing have been strongly associated with hypoacetylation of histones. Accordingly, histone deacetylases, which remove acetyl groups from histones, have been shown to participate in mechanisms of transcriptional repression. Therefore, current models of the role of acetylation in transcriptional regulation focus on the acetylation status of histones and designate histone acetyltransferases, which add acetyl groups to histones, as transcriptional coactivators and histone deacetylases as corepressors. In recent years, an accumulation of studies have shown that these enzymes also target non-histone proteins and that histone deacetylases have clear roles as coactivators at a variety of genes, some of which are key regulators of cell growth and survival. This review summarizes the evidence for histone deacetylases as coactivators and provides models of coactivation mechanisms, some of which integrate roles of acetylated histones and non-histone proteins in transcription.
  BioEssays 02/2008; 30(1):15-24.
• Article: The 7th UK Evolutionary Developmental Biology Meeting, 7th August 2007.

  Rebecca F Furlong
  BioEssays 02/2008; 30(1):90-1.
• Article: Repressing the neuron within.

  William G Fairbrother, Will Fairbrother, Diane Lipscombe
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  ABSTRACT: A myriad of coordinated signals control cellular differentiation. Reprogramming the cell's proteome drives global changes in cell morphology and function that define cell phenotype. A switch in alternative splicing of many pre-mRNAs encoding neuronal-specific proteins accompanies neuronal differentiation. Three groups recently showed that the global splicing repressor, polypyrimidine track-binding protein (PTB), regulates this switch.1-3 Although a subset of neuronal genes are turned on in both non-neuronal and neuronal cells, restricted expression of PTB in non-neuronal cells diverts their mRNAs to nonsense-mediated decay and prevents protein expression. When the PTB brake is released, the cell splices like a neuron.
  BioEssays 02/2008; 30(1):1-4.
• Source

  Available from: tau.ac.il

  Article: Alternative splicing: current perspectives.

  Eddo Kim, Amir Goren, Gil Ast
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  ABSTRACT: Alternative splicing is a well-characterized mechanism by which multiple transcripts are generated from a single mRNA precursor. By allowing production of several protein isoforms from one pre-mRNA, alternative splicing contributes to proteomic diversity. But what do we know about the origin of this mechanism? Do the same evolutionary forces apply to alternatively and constitutively splice exons? Do similar forces act on all types of alternative splicing? Are the products generated by alternative splicing functional? Why is "improper" recognition of exons and introns allowed by the splicing machinery? In this review, we summarize the current knowledge regarding these issues from an evolutionary perspective.
  BioEssays 02/2008; 30(1):38-47.