bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tissue-Specific Expression Patterns of Arabidopsis NF-Y Transcription Factors Suggest Potential for Extensive Combinatorial Complexity
Authors: Siefers Nicholas , Dang Kristen K. , Kumimoto Roderick W. , Bynum William Edwards , Tayrose Gregory , Holt Ben F. 
Published: November 2008

AbstractAll aspects of plant and animal development are controlled by complex networks of transcription factors. Transcription factors are essential for converting signaling inputs, such as changes in daylength, into complex gene regulatory outputs. While some transcription factors control gene expression by binding to cis-regulatory elements as individual subunits, others function in a combinatorial fashion. How individual subunits of combinatorial transcription factors are spatially and temporally deployed (e.g. expression-level, posttranslational modifications and subcellular localization) has profound effects on their control of gene expression. In the model plant Arabidopsis (Arabidopsis thaliana), we have identified 36 Nuclear Factor Y (NF-Y) transcription factor subunits (10 NF-YA, 13 NF-YB, and 13 NF-YC subunits) that can theoretically combine to form 1,690 unique complexes. Individual plant subunits have functions in flowering time, embryo maturation, and meristem development, but how they combine to control these processes is unknown. To assist in the process of defining unique NF-Y complexes, we have created promoter:β-glucuronidase fusion lines for all 36 Arabidopsis genes. Here, we show NF-Y expression patterns inferred from these promoter:β-glucuronidase lines for roots, light- versus dark-grown seedlings, rosettes, and flowers. Additionally, we review the phylogenetic relationships and examine protein alignments for each NF-Y subunit family. The results are discussed with a special emphasis on potential roles for NF-Y subunits in photoperiod-controlled flowering time.
Molecular background of α‐fetoprotein in liver cancer cells as revealed by global RNA expression analysis
Authors: Saito Shigeru , Ojima Hidenori , Ichikawa Hitoshi , Hirohashi Setsuo , Kondo Tadashi 
Published: November 2008

α‐Fetoprotein (AFP) is considered to be a diagnostic and prognostic biomarker in hepatocellular carcinoma (HCC). However, the role of AFP in the development of HCC is presently obscure. We hypothesized that a certain set of genes is expressed in a manner coordinate with AFP, and that these genes essentially contribute to the malignant characteristics of AFP‐producing HCC. To address this hypothesis, we carried out global mRNA expression analysis of 21 liver cancer cell lines that produce varying levels of AFP. We identified 213 genes whose mRNA expression levels were significantly correlated with that of AFP (P < 0.0001). These included liver‐specific transcription factors for AFP and other albumin family genes. Eighteen HCC‐associated genes and 11 genes associated with malignancies other than HCC showed significant correlations with AFP production levels. Genes involved in lipid catabolism, blood coagulation, iron metabolism, angiogenesis, and the Wnt and mitogen‐activated protein kinase pathways were also identified. Text data mining revealed that participation in the transcription factor network could explain the connection between 78 of the identified genes. Glypican 3, which is a component of the Wnt pathway and contributes to HCC development, had the fifth highest correlation coefficient with AFP. Reactivity to specific antibodies confirmed the significant correlation between AFP and glypican 3 expression in HCC tissues. These observations suggest that AFP‐producing liver cancer cells may have a unique molecular background consisting of cancer‐associated genes. From this genome‐wide association study, novel aspects of the molecular background of AFP were revealed, and thus may lead to the identification of novel biomarker candidates. (Cancer Sci 2008; 99: 2402–2409)
A genome‐screen experiment to detect quantitative trait loci affecting resistance to facial eczema disease in sheep
Authors: Phua S. H. , Dodds K. G. , Morris C. A. , Henry H. M. , Beattie A. E. , Garmonsway H. G. , Towers N. R. , Crawford A. M. 
Published: November 2008

SummaryFacial eczema (FE) is a secondary photosensitization disease arising from liver cirrhosis caused by the mycotoxin sporidesmin. The disease affects sheep, cattle, deer and goats, and costs the New Zealand sheep industry alone an estimated NZ$63M annually. A long‐term sustainable solution to this century‐old FE problem is to breed for disease‐resistant animals by marker‐assisted selection. As a step towards finding a diagnostic DNA test for FE sensitivity, we have conducted a genome‐scan experiment to screen for quantitative trait loci (QTL) affecting this trait in Romney sheep. Four F1 sires, obtained from reciprocal matings of FE resistant and susceptible selection‐line animals, were used to generate four outcross families. The resulting half‐sib progeny were artificially challenged with sporidesmin to phenotype their FE traits measured in terms of their serum levels of liver‐specific enzymes, namely gamma‐glutamyl transferase and glutamate dehydrogenase. In a primary screen using selective genotyping on extreme progeny of each family, a total of 244 DNA markers uniformly distributed over all 26 ovine autosomes (with an autosomal genome coverage of 79–91%) were tested for linkage to the FE traits. Data were analysed using Haley–Knott regression. The primary screen detected one significant and one suggestive QTL on chromosomes 3 and 8 respectively. Both the significant and suggestive QTL were followed up in a secondary screen where all progeny were genotyped and analysed; the QTL on chromosome 3 was significant in this analysis.
Novel polymorphisms in the bovine β‐lactoglobulin gene and their effects on β‐lactoglobulin protein concentration in milk
Authors: Ganai N. A. , Bovenhuis H. , Van Arendonk J. A. M. , Visker M. H. P. W. 
Published: November 2008

SummaryThe aim of our study was to detect new polymorphisms in the bovine β‐lactoglobulin (β‐LG) gene with significant effects on β‐LG protein concentration. Genomic DNA samples from 22 proven bulls were screened for polymorphisms in the coding and promoter regions of the β‐LG gene. In total, 50 polymorphisms were detected. Two single nucleotide polymorphisms (SNPs) (g.1772G>A and g.3054C>T) lead to amino acid changes and are the causal genetic polymorphisms of β‐LG protein variants A and B. Forty‐two polymorphisms were in complete linkage disequilibrium (LD) with β‐LG protein variants A and B. Any of these 42 polymorphisms can be involved in the differential expression of the respective A and B alleles of the β‐LG gene. The eight polymorphisms not in complete LD with β‐LG protein variants A and B and the two polymorphisms causing the amino acid changes were genotyped in a set of 208 cows: 106 animals homozygous for β‐LG protein variant A and 102 animals homozygous for β‐LG protein variant B. Of these eight polymorphisms, six SNPs segregated only within the cows homozygous for β‐LG protein variant A and two SNPs segregated only within the cows homozygous for β‐LG protein variant B. One of the eight polymorphisms had a significant effect on β‐LG protein concentration. This SNP, g.‐731G>A, segregated only within the 106 cows homozygous for β‐LG protein variant A. Within these cows, adjusted relative β‐LG protein concentration was reduced by 1.22% (w/w) in animals homozygous g.‐731AA compared with animals homozygous g.‐731GG.
How well are general practice trainees prepared for paediatric prescribing?
Authors: Isa N. M. , Taylor Michael W. , Helms Peter J. , McLay James S. 
Published: November 2008

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Children make up a significant proportion of a general practitioner's (GP's) prescribing workload.• The realisation that children cannot be assumed to be little adults and may require specialized prescribing and therapeutic knowledge is relatively recent.• Off‐label medicines, which have been associated with an increased frequency of adverse drug reactions, are commonly prescribed by GPs to children. WHAT THIS STUDY ADDS • The majority of GP trainees believe that their undergraduate and postgraduate training in paediatric therapeutics is insufficient for their coming requirements in primary care.• Approximately one‐third of GP trainees do not undertake any paediatrics training prior to starting work as a GP.• Off‐label and unlicensed prescribing are the most poorly covered areas of paediatric therapeutics in universities/university hospitals.• Those trainees who do undergo paediatric training during their vocational years report increased paediatric prescribing confidence.AIMS AND METHODOLOGY We invited 232 General Practice Trainees to complete an on‐line questionnaire to assess how they rated their training for the task of paediatric prescribing and therapeutics in the community.RESULTS Of the 166 (71%) respondents who completed the questionnaire, 26.5% recalled specific teaching about paediatric prescribing and 59.6% covering one or more relevant topic during their undergraduate years. Undertaking a paediatric post during vocational training was associated with greater prescribing confidence (P < 0.001); however, 35% of respondents were not intending to undertake such a post.CONCLUSION This study suggests that many GP trainees perceive their paediatric prescribing training as inadequate.
Screening and treatment for heritable thrombophilia in pregnancy failure: inconsistencies among UK early pregnancy units
Authors: Norrie Gillian , Farquharson Roy G. , Greaves Mike 
Published: November 2008

SummaryThe significance of heritable thrombophilia in pregnancy failure is controversial. We surveyed all UK Early Pregnancy Units and 70% responded. The majority test routinely for heritable thrombophilias; 80%, 76% and 88% undertook at least one screening test in late miscarriage, recurrent miscarriage and placental abruption, respectively. The range of thrombophilias sought is inconsistent: testing for proteins C and S deficiency and F5 R506Q (factor V Leiden) is most prevalent. Detection of heritable thrombophilia frequently leads to administration of antithrombotics in subsequent pregnancies. Thus, thrombophilia testing and use of antithrombotics are widespread in the UK despite controversies regarding the role of heritable thrombophilia in the pathogenesis of pregnancy complications, and the lack of robust evidence for the efficacy of antithrombotic therapy.
Short stature: increased in children with severe learning disability
Authors: Abdullah N. , Drummond P. , Gray N. , Al‐Khalidi O. , Barry R. , Cheetham T. 
Published: November 2008

AbstractIntroduction  ‘Health for all children’ recommends that children should be screened for growth disorders at school entry with a 0.4th centile ‘cut‐off’. Following the diagnosis of growth hormone deficiency in four children attending local special schools, our aim was to compare the height distribution of children attending special schools with mainstream schools.Methods  Children at two local special schools were measured using a Leicester height measurer and values converted to standard deviation scores (SDS). Children were categorized according to whether there were known factors that could affect height. The data were compared with those collected from local mainstream schools.Results  In total, 242 children were registered at the two special schools and 192 children were measured. The mean height SDS of children in mainstream school (n = 2301) was similar to national standards at −0.09 (SD 1.02). The mean height SDS distribution of the 192 children in special schools (age range 3.2–18.4 years; median age 11.3 years) was −0.73; 95%CI −0.9 to −0.5. In those with no established diagnosis to explain altered growth (n = 120) this was −0.613; 95%CI −0.8 to −0.4. Both pre‐pubertal (n = 37) and pubertal (n = 83) children were short and eight (6.7%) had a height less than the 0.4th centile.Conclusions  Children attending special school with severe or profound learning disability were shorter than those attending mainstream school. This is still the case following the exclusion of children with a known cause for abnormal growth. This underlines the importance of each child being assessed by professionals with a refined knowledge of normal and abnormal growth.
Screening for faecal contamination in primary schools in Crete, Greece
Authors: Kyriacou A. , Drakopoulou S. , Georgaki I. , Fountoulakis M. , Mitsou E. , Lasaridi K. E. , Manios Y. , Manios T. 
Published: November 2008

AbstractBackground  Hygienic conditions in primary schools are a major concern for both governmental organizations and families. Particularly, the occurrence of faecal indicators on children's hands and various school surfaces has been associated with increased risk of diarrhoeal diseases. The presence of faecal streptococci on environmental surfaces and children's hands and the possible correlation with socio‐economic factors were examined.Methods  Overall, 1956 samples from hands and 1470 samples from surfaces were collected from 20 primary schools in Heraklion, Crete, Greece.Results  Faecal streptococci were found at 52.9% of children's hands and at 16.7% of other surfaces. Children, who had parents with the highest education level (>12 years), had the lowest percentage (48.8%) of faecal contamination on their hands. Furthermore, boys exhibited higher levels of hands contamination compared with girls. Among the environmental surfaces examined, the school canteen reception was the most contaminated area.Conclusion  High faecal contamination was detected in primary schools in the examined region. Children's hands were highly infected (52.9%), while boys exhibited higher levels of contamination. The educational level of parents correlated well with the contamination of children's hands.
A comparison of father–infant interaction between primary and non‐primary care giving fathers
Authors: Lewis S. N. , West A. F. , Stein A. , Malmberg L.‐E. , Bethell K. , Barnes J. , Sylva K. , Leach P. ,   The Families, Children and Child Care (FCCC) project team
Published: November 2008

AbstractBackground  This study examined the socio‐demographic characteristics and attitudes of primary care giving fathers and non‐primary care giving fathers and the quality of their interaction with their infants.Method  Two groups of fathers of 11.9‐month old infants were compared – 25 primary care giving fathers (20 h per week or more of sole infant care) and 75 non‐primary care giving fathers – with regard to socio‐demographic characteristics, attitudinal differences and father–infant interaction during play and mealtimes. The quality of father–child interaction in relation to the total number of hours of primary care provided by fathers was also examined.Results  Primary care giving fathers had lower occupational status and earned a smaller proportion of the family income but did not differ in educational level or attitudes compared with non‐primary care giving fathers. There were no differences between the partners of the two groups of fathers on any variables, and their infants did not differ in temperament. Primary care giving fathers and their infants exhibited more positive emotional tone during play than non‐primary care giving fathers, although fathers did not differ in responsivity. There were no differences between the groups during mealtimes. There was a positive association between total number of child care hours provided by all fathers and infant positive emotional tone.Conclusions  Primary and non‐primary care giving fathers were similar in many respects, but primary care giving fathers and their infants were happier during play. This suggests a possible link between the involvement of fathers in the care of their children and their children's emotional state. The finding of a trend towards increased paternal happiness with increased hours of child care suggests that there may also be a gain for fathers who are more involved in the care of their infants. Further research is needed to determine whether these differences ultimately have an effect on children's development.
Proinsulin peptide immunotherapy in type 1 diabetes: report of a first-in-man Phase I safety study
Authors: Thrower S L , James L , Hall W , Green K M , Arif S , Allen J S , Van-Krinks C , Lozanoska-Ochser B , Marquesini L , Brown S , Wong F S , Dayan C M , Peakman M 
Published: November 2008

Summary
Immunotherapeutic strategies under consideration for type 1 diabetes include modification of the autoimmune response through antigen-specific routes. Administration of short peptides representing T cell epitopes targeted by patients with the disease represents one approach. This study evaluated safety and mechanistic outcomes during first-in-man intradermal administration of a human leucocyte antigen-DR4 (HLA-DR4)-restricted peptide epitope of proinsulin (C19-A3). This randomized, open-label study assessed two major theoretical risks of peptide immunotherapy, namely induction of allergic hypersensitivity and exacerbation of the proinflammatory autoimmune response, using clinical assessment and mechanistic assays in vitro. Patients with long-standing type 1 diabetes and HLA-DRB1*0401 genotype received 30 µg (n = 18) or 300 µg (n = 18) of peptide in three equal doses at 0, 1 and 2 months or no intervention (n = 12). Proinsulin peptide immunotherapy in the dosing regimen used is well tolerated and free from risk of systemic hypersensitivity and induction/reactivation of proinsulin-specific, proinflammatory T cells. Peptide-specific T cells secreting the immune suppressive cytokine interleukin (IL)-10 were observed at month 3 in four of 18 patients in the low-dose group (versus one of 12 in the control group; P = not significant). Mean IL-10 response to peptide in the low-dose group increased between 0 and 3 months (P = 0·05 after stimulation with 5 µM peptide in vitro) and then declined to baseline levels between 3 and 6 months (P = 0·01 at 10 µM peptide in vitro). These studies pave the way for future investigations in new-onset patients designed to examine whether proinsulin peptide immunotherapy has beneficial effects on markers of T cell autoimmunity and preservation of β cell mass.
Effects of tropism and virulence ofLeishmaniaparasites on cytokine production by infected human monocytes
Authors: Meddeb-Garnaoui A , Zrelli H , Dellagi K 
Published: November 2008

SummaryThe nature of early interactions between Leishmania and macrophages which determine the outcome of infection can be related directly to parasite biological properties. Here we compared the capacity of L. major (Lm) strains, reported to be high (LmHV) and low virulent and (LmLV) in the mouse model and L. infantum (Li) strains, dermotropic (LiD) and viscerotropic (LiV), to infect and modulate cytokine production in human peripheral blood derived monocytes. Monocytes were infected with metacyclic promastigotes for 24, 48 and 72 h. Parasite burden was significantly higher in Lm- than in Li-infected monocytes. LmHV and LiD induced a significantly higher parasite burden than LmLV and LiV respectively. Cytokine production was evaluated in monocytes infected for 24 h. Contrary to interleukin (IL)-12p70, monocyte chemotactic protein-1 and transforming growth factor-β production was increased significantly in infected monocytes with no differences between strains. Lm isolates induced significantly higher quantities of tumour necrosis factor (TNF)-α than Li isolates. Low levels of IL-10 were induced by all Leishmania strains and, interestingly, co-stimulation with lipopolysaccharide (LPS) was accompanied by a dramatic increase in IL-10 production by infected monocytes. In conclusion, Lm isolates displaying different levels of virulence in mice exhibited significant differences in parasite burden but similar abilities to modulate cytokine production in human monocytes. Li strains showed weaker infectivity and TNF-α inducing-capacity compared with Lm strains. The dramatic increase of IL-10 production in infected monocytes co-stimulated by LPS may play a role in disease progression considering the presence of LPS during bacterial superinfections observed during human leishmaniasis.
Spatiotemporal fire occurrence in Borneo over a period of 10 years
Authors: LANGNER ANDREAS , SIEGERT FLORIAN 
Published: November 2008

AbstractSouth‐east Asia's tropical rainforests are experiencing the highest rate of deforestation worldwide and fire is one of the most important drivers of forest loss and subsequent carbon dioxide emissions. In this study, we analyzed all fire events in Borneo recorded by satellites over a period of 10 years. About 16.2 Mha, which corresponds to 21% of the land surface, have been affected by fire at least once and 6% more than one time. During El Niño conditions, which cause prolonged droughts in the region, the fire‐affected area was on average three times larger than during normal weather conditions. Similarly, fires in forests affected 0.3 Mha in normal years and 1 Mha during El Niño years. Carbon rich peat swamp forest ecosystems were most severely affected. There is a pronounced difference in fire occurrence between different countries and provinces in Borneo although ecosystem and land use are very similar across the island. Compared with Sarawak, Sabah (Malaysia) and Brunei the relative annual fire‐affected area in Kalimantan, the Indonesian part of Borneo, was on average five times larger. During El Niño conditions the fire‐affected area increased only in Kalimantan and not in Brunei and the Malaysia. A similar pattern was observed in National Parks. This suggests, that El Niño related droughts are not the only cause of increased fire occurrence and do not necessarily lead to a higher number of fire events. These results improve our understanding of existing fire regimes and drivers of fire in SE Asian tropical ecosystems and may help to better protect the remaining rainforests.
The role of dendritic cells in the mechanism of action of a peptide that ameliorates lupus in murine models
Authors: Sela Uri , Sharabi Amir , Dayan Molly , Hershkoviz Rami , Mozes Edna 
Published: November 2008

SummarySystemic lupus erythematosus (SLE) is characterized in its early stages by the expansion of autoreactive T cells that trigger B‐cell activation with subsequent multi‐organ injury. Dendritic cells (DCs) in lupus were found to display an aberrant phenotype with higher expression of the maturation markers major histocompatibility complex (MHC) class II, CD80 and CD86, as well as higher production of proinflammatory cytokines including interleukin‐12 (IL‐12), resulting in an increased ability to activate T cells. A peptide (hCDR1) based on the complementarity determining region‐1 of an anti‐DNA antibody ameliorated SLE in both induced and spontaneous lupus models by downregulating T‐cell functions. Our objectives were to determine whether DCs play a role in promoting the beneficial effects of hCDR1. We showed here that treatment with hCDR1 lowered the expression levels of MHC class II, CD80 and CD86 on DCs. The latter effect was associated with downregulation of messenger RNA expression and secretion of IL‐12, a cytokine that upregulated T‐cell proliferation and interferon‐γ (IFN‐γ) secretion. Moreover, DCs derived from hCDR1‐treated mice downregulated proliferation and IFN‐γ secretion by T cells from untreated mice. Upregulation of transforming growth factor‐β (TGF‐β) secretion by T cells, following treatment with hCDR1, resulted in downregulation of IFN‐γ production and contributed to the phenotypic changes and magnitude of IL‐12 secretion by DCs. The ameliorating effects of hCDR1 are therefore mediated at least partially by the upregulated secretion of TGF‐β by T cells that contribute to the induction of DCs with immature phenotype and suppressed functions. The resulting DCs further downregulate autoreactive T‐cell functions.