bluuebunny/crossref_metadata_2025_split huggingface dataset:
Globally, unrelated protein sequences appear random
Authors: Lavelle Daniel T. , Pearson William R. 
Published: December 2009

AbstractMotivation: To test whether protein folding constraints and secondary structure sequence preferences significantly reduce the space of amino acid words in proteins, we compared the frequencies of four- and five-amino acid word clumps (independent words) in proteins to the frequencies predicted by four random sequence models.Results: While the human proteome has many overrepresented word clumps, these words come from large protein families with biased compositions (e.g. Zn-fingers). In contrast, in a non-redundant sample of Pfam-AB, only 1% of four-amino acid word clumps (4.7% of 5mer words) are 2-fold overrepresented compared with our simplest random model [MC(0)], and 0.1% (4mers) to 0.5% (5mers) are 2-fold overrepresented compared with a window-shuffled random model. Using a false discovery rate q-value analysis, the number of exceptional four- or five-letter words in real proteins is similar to the number found when comparing words from one random model to another. Consensus overrepresented words are not enriched in conserved regions of proteins, but four-letter words are enriched 1.18- to 1.56-fold in α-helical secondary structures (but not β-strands). Five-residue consensus exceptional words are enriched for α-helix 1.43- to 1.61-fold. Protein word preferences in regular secondary structure do not appear to significantly restrict the use of sequence words in unrelated proteins, although the consensus exceptional words have a secondary structure bias for α-helix. Globally, words in protein sequences appear to be under very few constraints; for the most part, they appear to be random.Contact: wrp@virginia.eduSupplementary information: Supplementary data are available at Bioinformatics online.
Geological pattern formation by growth and dissolution in aqueous systems
Authors: Meakin Paul , Jamtveit Bjørn 
Published: November 2009

Progress towards the development of a better understanding of the formation of geological patterns in wet systems due to precipitation and dissolution is reviewed. Emphasis is placed on the formation of terraces, stalactites, stalagmites and other carbonate patterns due to precipitation from flowing supersaturated solutions and the formation of scallops by dissolution in undersaturated turbulent fluids. In addition, the formation of spherulites, dendrites and very large, essentially euhedral, crystals is discussed. In most cases, the formation of very similar patterns as a result of the freezing/melting of ice and the precipitation/dissolution of minerals strongly suggests that complexity associated with aqueous chemistry, interfacial chemistry and biological processes has only a secondary effect on these pattern formation processes.
Amplification of Bisulfite-Converted DNA for Genome-Wide DNA Methylation Profiling: Figure 1.
Authors: Reinders Jon 
Published: December 2009

INTRODUCTIONDNA methylation, in which cytosine is modified to form 5-methylcytosine, is a well-characterized epigenetic modification essential for normal development in plants and mammals. Aberrant DNA methylation patterns have been implicated in disease development, notably cancer. It is therefore important to develop genome-wide DNA methylation profiling technology. In this article, I describe a bisulfite methylation profiling (BiMP) method for assessing DNA methylation patterns. Treatment of DNA with sodium bisulfite converts unmethylated cytosine to uracil, whereas 5-methylcytosine is not converted. During subsequent polymerase chain reaction (PCR) amplification, uracil amplifies as thymine, whereas 5-methylcytosine amplifies as cytosine, thereby creating C-to-T transitions. Although single base detection of DNA methylation patterns provided by bisulfite conversion is clearly advantageous, there are inherent challenges associated with this approach. Successful conversion requires relatively high temperatures (50°C-60°C) and low pH (5.2), both of which may result in a high degree of DNA fragmentation. Also, whole genome amplification methods established for genomic DNA have resulted in poor reproducibility when applied to bisulfite-converted DNA. The protocol described here mitigates these adverse effects and provides bisulfite-converted DNA suitable for genome-wide DNA methylation profiling using array-based analysis platforms.
Isolation of Sea Squirt (Ciona) Gametes, Fertilization, Dechorionation, and Development: Figure 1.
Authors: Christiaen Lionel , Wagner Eileen , Shi Weiyang , Levine Michael 
Published: December 2009

INTRODUCTIONThis protocol is the starting point for most manipulations that are used to study the sea squirt (Ciona) embryo, including in situ hybridization, the microinjection of morpholino oligos, and the electroporation of transgenic DNAs. Ciona eggs and embryos are exquisitely sensitive to even trace amounts of detergent; therefore, it is strongly advised to designate a soap-free workspace for embryo culture. Any solutions that come into contact with embryos should be prepared in absolutely clean glassware with the highest quality water.
ArabidopsisN-MYC DOWNREGULATED-LIKE1, a Positive Regulator of Auxin Transport in a G Protein–Mediated Pathway
Authors: Mudgil Yashwanti , Uhrig Joachm F. , Zhou Jiping , Temple Brenda , Jiang Kun , Jones Alan M. 
Published: December 2009

AbstractRoot architecture results from coordinated cell division and expansion in spatially distinct cells of the root and is established and maintained by gradients of auxin and nutrients such as sugars. Auxin is transported acropetally through the root within the central stele and then, upon reaching the root apex, auxin is transported basipetally through the outer cortical and epidermal cells. The two Gβγ dimers of the Arabidopsis thaliana heterotrimeric G protein complex are differentially localized to the central and cortical tissues of the Arabidopsis roots. A null mutation in either the single β (AGB1) or the two γ (AGG1 and AGG2) subunits confers phenotypes that disrupt the proper architecture of Arabidopsis roots and are consistent with altered auxin transport. Here, we describe an evolutionarily conserved interaction between AGB1/AGG dimers and a protein designated N-MYC DOWNREGULATED-LIKE1 (NDL1). The Arabidopsis genome encodes two homologs of NDL1 (NDL2 and NDL3), which also interact with AGB1/AGG1 and AGB1/AGG2 dimers. We show that NDL proteins act in a signaling pathway that modulates root auxin transport and auxin gradients in part by affecting the levels of at least two auxin transport facilitators. Reduction of NDL family gene expression and overexpression of NDL1 alter root architecture, auxin transport, and auxin maxima. AGB1, auxin, and sugars are required for NDL1 protein stability in regions of the root where auxin gradients are established; thus, the signaling mechanism contains feedback loops.
Feedback Inhibition of Ammonium Uptake by a Phospho-Dependent Allosteric Mechanism inArabidopsis
Authors: Lanquar Viviane , Loqué Dominique , Hörmann Friederike , Yuan Lixing , Bohner Anne , Engelsberger Wolfgang R. , Lalonde Sylvie , Schulze Waltraud X. , von Wirén Nicolaus , Frommer Wolf B. 
Published: December 2009

AbstractThe acquisition of nutrients requires tight regulation to ensure optimal supply while preventing accumulation to toxic levels. Ammonium transporter/methylamine permease/rhesus (AMT/Mep/Rh) transporters are responsible for ammonium acquisition in bacteria, fungi, and plants. The ammonium transporter AMT1;1 from Arabidopsis thaliana uses a novel regulatory mechanism requiring the productive interaction between a trimer of subunits for function. Allosteric regulation is mediated by a cytosolic C-terminal trans-activation domain, which carries a conserved Thr (T460) in a critical position in the hinge region of the C terminus. When expressed in yeast, mutation of T460 leads to inactivation of the trimeric complex. This study shows that phosphorylation of T460 is triggered by ammonium in a time- and concentration-dependent manner. Neither Gln nor l-methionine sulfoximine–induced ammonium accumulation were effective in inducing phosphorylation, suggesting that roots use either the ammonium transporter itself or another extracellular sensor to measure ammonium concentrations in the rhizosphere. Phosphorylation of T460 in response to an increase in external ammonium correlates with inhibition of ammonium uptake into Arabidopsis roots. Thus, phosphorylation appears to function in a feedback loop restricting ammonium uptake. This novel autoregulatory mechanism is capable of tuning uptake capacity over a wide range of supply levels using an extracellular sensory system, potentially mediated by a transceptor (i.e., transporter and receptor).
Clocks in the Green Lineage: Comparative Functional Analysis of the Circadian Architecture of the PicoeukaryoteOstreococcus
Authors: Corellou Florence , Schwartz Christian , Motta Jean-Paul , Djouani-Tahri El Batoul , Sanchez Frédéric , Bouget François-Yves 
Published: December 2009

AbstractBiological rhythms that allow organisms to adapt to the solar cycle are generated by endogenous circadian clocks. In higher plants, many clock components have been identified and cellular rhythmicity is thought to be driven by a complex transcriptional feedback circuitry. In the small genome of the green unicellular alga Ostreococcus tauri, two of the master clock genes Timing of Cab expression1 (TOC1) and Circadian Clock-Associated1 (CCA1) appear to be conserved, but others like Gigantea or Early-Flowering4 are lacking. Stably transformed luciferase reporter lines and tools for gene functional analysis were therefore developed to characterize clock gene function in this simple eukaryotic system. This approach revealed several features that are comparable to those in higher plants, including the circadian regulation of TOC1, CCA1, and the output gene Chlorophyll a/b Binding under constant light, the relative phases of TOC1/CCA1 expression under light/dark cycles, arrhythmic overexpression phenotypes under constant light, the binding of CCA1 to a conserved evening element in the TOC1 promoter, as well as the requirement of the evening element for circadian regulation of TOC1 promoter activity. Functional analysis supports TOC1 playing a central role in the clock, but repression of CCA1 had no effect on clock function in constant light, arguing against a simple TOC1 /CCA1 one-loop clock in Ostreococcus. The emergence of functional genomics in a simple green cell with a small genome may facilitate increased understanding of how complex cellular processes such as the circadian clock have evolved in plants.
Control of Cell Proliferation, Organ Growth, and DNA Damage Response Operate Independently of Dephosphorylation of the Arabidopsis Cdk1 Homolog CDKA;1
Authors: Dissmeyer Nico , Weimer Annika K. , Pusch Stefan , De Schutter Kristof , Kamei Claire Lessa Alvim , Nowack Moritz K. , Novak Bela , Duan Gui-Lan , Zhu Yong-Guan , De Veylder Lieven , Schnittger Arp 
Published: December 2009

Abstract
Entry into mitosis is universally controlled by cyclin-dependent kinases (CDKs). A key regulatory event in metazoans and fission yeast is CDK activation by the removal of inhibitory phosphate groups in the ATP binding pocket catalyzed by Cdc25 phosphatases. In contrast with other multicellular organisms, we show here that in the flowering plant Arabidopsis thaliana, cell cycle control does not depend on sudden changes in the phosphorylation pattern of the PSTAIRE-containing Cdk1 homolog CDKA;1. Consistently, we found that neither mutants in a previously identified CDC25 candidate gene nor plants in which it is overexpressed display cell cycle defects. Inhibitory phosphorylation of CDKs is also the key event in metazoans to arrest cell cycle progression upon DNA damage. However, we show here that the DNA damage checkpoint in Arabidopsis can also operate independently of the phosphorylation of CDKA;1. These observations reveal a surprising degree of divergence in the circuitry of highly conserved core cell cycle regulators in multicellular organisms. Based on biomathematical simulations, we propose a plant-specific model of how progression through the cell cycle could be wired in Arabidopsis.
Structural Basis for Evolution of Product Diversity in Soybean Glutathione Biosynthesis
Authors: Galant Ashley , Arkus Kiani A.J. , Zubieta Chloe , Cahoon Rebecca E. , Jez Joseph M. 
Published: December 2009

AbstractThe redox active peptide glutathione is ubiquitous in nature, but some plants also synthesize glutathione analogs in response to environmental stresses. To understand the evolution of chemical diversity in the closely related enzymes homoglutathione synthetase (hGS) and glutathione synthetase (GS), we determined the structures of soybean (Glycine max) hGS in three states: apoenzyme, bound to γ-glutamylcysteine (γEC), and with hGSH, ADP, and a sulfate ion bound in the active site. Domain movements and rearrangement of active site loops change the structure from an open active site form (apoenzyme and γEC complex) to a closed active site form (hGSH•ADP•SO4 2− complex). The structure of hGS shows that two amino acid differences in an active site loop provide extra space to accommodate the longer β-Ala moiety of hGSH in comparison to the glycinyl group of glutathione. Mutation of either Leu-487 or Pro-488 to an Ala improves catalytic efficiency using Gly, but a double mutation (L487A/P488A) is required to convert the substrate preference of hGS from β-Ala to Gly. These structures, combined with site-directed mutagenesis, reveal the molecular changes that define the substrate preference of hGS, explain the product diversity within evolutionarily related GS-like enzymes, and reinforce the critical role of active site loops in the adaptation and diversification of enzyme function.
The Haematological Malignancy Research Network (HMRN): a new information strategy for population based epidemiology and health service research
Authors: Smith Alexandra , Roman Eve , Howell Debra , Jones Richard , Patmore Russell , Jack Andrew ,   on behalf of the Haematological Malignancy Research Network (members listed in )
Published: December 2009

SummaryThe Haematological Malignancy Research Network (HMRN) was established in 2004 to provide robust generalizable data to inform clinical practice and research. It comprises an ongoing population‐based cohort of patients newly diagnosed by a single integrated haematopathology laboratory in two adjacent UK Cancer Networks (population 3·6 million). With an emphasis on primary‐source data, prognostic factors, sequential treatment/response history, and socio‐demographic details are recorded to clinical trial standards. Data on 8131 patients diagnosed over the 4 years 2004–08 are examined here using the latest World Health Organization classification. HMRN captures all diagnoses (adult and paediatric) and the diagnostic age ranged from 4 weeks to 99 years (median 70·4 years). In line with published estimates, first‐line clinical trial entry varied widely by disease subtype and age, falling from 59·5% in those aged <15 years to 1·9% in those aged over 75 years – underscoring the need for contextual population‐based treatment and response data of the type collected by HMRN. The critical importance of incorporating molecular and prognostic markers into comparative survival analyses is illustrated with reference to diffuse‐large B‐cell lymphoma, acute myeloid leukaemia and myeloma. With respect to aetiology, several descriptive factors are highlighted and discussed, including the unexplained male predominance evident for most subtypes across all ages.
Children and television watching: a qualitative study of New Zealand parents' perceptions and views
Authors: Dorey E. , Roberts V. , Maddison R. , Meagher‐Lundberg P. , Dixon R. , Ni Mhurchu C. 
Published: December 2009

AbstractBackground  Television (TV) viewing is one of the most pervasive sedentary pursuits among children and adolescents. Research studies have shown that higher TV viewing hours are associated with a number of negative effects such as being overweight and obese, attention and behavioural problems, and impaired academic performance. Most interventions to reduce time spent watching TV have been school‐based and little is known about the strategies that families use to control TV watching time.Methods  Six focus groups with Māori, Pacific and non‐Māori non‐Pacific parents were conducted to examine New Zealand parents' perceptions of their children's TV watching. Focus groups explored attitudes towards TV viewing, strategies used to reduce viewing, and opinion on two different electronic monitors that can be used to restrict TV viewing. Focus group discussions were transcribed and a content analysis was conducted.Results  Parents described TV as playing a dominant role in their family's lives, and highlighted several barriers to reducing children's TV viewing, such as parents not willing to reduce their own TV watching, a lack of safe alternatives to TV and the need to use TV as a babysitting tool. Limiting access to TV, making TV viewing a reward and finding alternative activities were current strategies parents employed to limit TV viewing; however, the barriers highlighted by parents make implementing such strategies difficult. Attitudes towards electronic monitor use to reduce TV viewing were mixed, but suggest further investigation of these devices is needed.Conclusions  Electronic devices that restrict the amount and content of TV viewing have some potential to support interventions and merit further investigation. It is imperative for interventions aimed at reducing TV viewing to consider the role TV plays within a family context, ensuring parental perceptions around the benefits and barriers of reducing TV are accounted for.
Health‐related quality of life and financial impact of caring for a child with Thalassaemia Major in the UK
Authors: Clarke S. A. , Skinner R. , Guest J. , Darbyshire P. , Cooper J. , Shah F. , Roberts I. , Eiser C. 
Published: December 2009

AbstractBackground  Thalassaemia Major (TM) is a serious condition characterized by life‐long dependence on blood transfusions and chelation therapy. Our aim was to determine health‐related quality of life (HRQOL) in children with TM living in the UK, and the impact of caring for a child receiving National Health Service treatment on family finances.Methods  This was a cross‐sectional assessment of HRQOL in children (n= 22) with TM aged 8–18 years. Children were recruited from three UK Paediatric Haematology and Bone Marrow Transplant centres. Mothers completed measures of their child's HRQOL [PedsQL™ 4.0 (Measurement Model for the Pediatric Quality of Life Inventory™, James W. Varni PhD, PedMetrics™, Quantifying the Qualitative SM, Copyright 1998–2009)] and behaviour (Strengths and Difficulties questionnaire), and the impact of caring for the child on family finances.Results  Child behaviour was within the normal range but child HRQOL was significantly lower than population norms. Family financial concerns associated with TM were associated with poorer child HRQOL (P= 0.020).Conclusions  Thalassaemia Major poses a considerable challenge to child HRQOL, well documented in areas of the world where TM is prevalent. Despite the availability of National Health Service care and financial benefits our study suggests a similar burden in the UK.
T cell sensitivity and the outcome of viral infection
Authors: Walker L J , Sewell A K , Klenerman P 
Published: December 2009

SummaryThe importance of CD8+ T cells in the control of viral infections is well established. However, what differentiates CD8+ T cell responses in individuals who control infection and those who do not is not well understood. ‘Functional sensitivity’ describes an important quality of the T cell response and is determined in part by the affinity of the T cell receptor for antigen. A more sensitive T cell response is generally believed to be more efficient and associated with better control of viral infection, yet may also drive viral mutation and immune escape. Various in vitro techniques have been used to measure T cell sensitivity; however, rapid ex vivo analysis of this has been made possible by the application of the ‘magic’ tetramer technology. Such tools have potentially important applications in the design and evaluation of vaccines.
Interferon signature gene expression is correlated with autoantibody profiles in patients with incomplete lupus syndromes
Authors: Li Q-Z , Zhou J , Lian Y , Zhang B , Branch V K , Carr-Johnson F , Karp D R , Mohan C , Wakeland E K , Olsen N J 
Published: December 2009

SummaryInterferon (IFN) signature genes have been shown to be expressed highly in peripheral blood of patients with systemic lupus erythematosus (SLE), especially in the presence of active disease. However, the expression of this gene signature in individuals with incomplete forms of lupus and the pathogenic relationship between IFN signature genes and autoantibody production have not been explored fully. In the present study, we examined the gene expression and autoantibody profiles of patients diagnosed with incomplete lupus erythematosus (ILE) to determine correlations of the gene expression signature with autoantibody production. Gene expression analysis was carried out on the 24K Illumina Human Refseq-8 arrays using blood samples from 84 subjects, including patients with SLE (n = 27) or ILE (n = 24), first-degree relatives (FDR) of these patients (n = 22) and non-autoimmune control (NC) individuals (n = 11). Autoantibody expression was measured using standard immunoassays and autoantigen proteomic arrays. Up-regulation of a set of 63 IFN signature genes was seen in 83% of SLE patients and 50% of ILE patients. High levels of IFN gene expression in ILE and SLE showed significant correlations with the expression of a subset of IgG autoantibodies, including chromatin, dsDNA, dsRNA, U1snRNP, Ro/SSA, La/SSB, topoisomerase I and Scl 70, while low IFN levels were correlated with immunoglobulin (Ig)M autoreactivity. These studies suggest that in patients with ILE the IFN gene expression signature may identify a subset of these individuals who are at risk for disease progression. Furthermore, high levels of alpha IFN may promote autoantibody class-switch from IgM to the more pathogenic IgG class.
The therapeutic potential of the filarial nematode-derived immunodulator, ES-62 in inflammatory disease
Authors: Harnett M M , Melendez A J , Harnett W 
Published: December 2009

SummaryThe dramatic recent rise in the incidence of allergic or autoimmune inflammatory diseases in the West has been proposed to reflect the lack of appropriate priming of the immune response by infectious agents such as parasitic worms during childhood. Consistent with this, there is increasing evidence supporting an inverse relationship between worm infection and T helper type 1/17 (Th1/17)-based inflammatory disorders such as rheumatoid arthritis, inflammatory bowel disease, type 1 diabetes and multiple sclerosis. Perhaps more surprisingly, given that such worms often induce strong Th2-type immune responses, there also appears to be an inverse correlation between parasite load and atopy. These findings therefore suggest that the co-evolution of helminths with hosts, which has resulted in the ability of worms to modulate inflammatory responses to promote parasite survival, has also produced the benefit of protecting the host from pathological lesions arising from aggressive proinflammatory responses to infection or, indeed, aberrant inflammatory responses underlying autoimmune and allergic disorders. By focusing upon the properties of the filarial nematode-derived immunomodulatory molecule, ES-62, in this review we shall discuss the potential of exploiting the immunomodulatory products of parasitic worms to identify and develop novel therapeutics for inflammation.