TEMPRANILLO is a regulator of juvenility in plants

Many plants are incapable of flowering in inductive daylengths during the early juvenile vegetative phase (JVP). Arabidopsis mutants with reduced expression of TEMPRANILLO (TEM), a repressor of FLOWERING LOCUS T (FT) had a shorter JVP than wild-type plants. Reciprocal changes in mRNA expression of TEM and FT were observed in both Arabidopsis and antirrhinum, which correlated with the length of the JVP. FT expression was induced just prior to the end of the JVP and levels of TEM1 mRNA declined rapidly at the time when FT mRNA levels were shown to increase. TEM orthologs were isolated from antirrhinum (AmTEM) and olive (OeTEM) and were expressed most highly during their juvenile phase. AmTEM functionally complemented AtTEM1 in the tem1 mutant and over-expression of AmTEM prolonged the JVP through repression of FT and CONSTANS (CO). We propose that TEM may have a general role in regulating JVP in herbaceous and woody species

Cancer incidence in British Indians and British whites in Leicester, 2001–2006

BACKGROUND: Incidence rates for many cancers are lower in India than in Britain and it is therefore of interest to compare rates in British Indians to British whites, as well as to rates in India. We present estimates for Leicester, which has the largest population of Indian origin in Britain, and also has virtually complete, self-assigned, ethnicity data. METHODS: We obtained data on all cancer registrations from 2001 to 2006 for Leicester with ethnicity data obtained by linkage to the Hospital Episode Statistics database. Age-standardised incidence rates were calculated for British Indians and British whites as well as incidence rate ratios, adjusted for age and income. RESULTS: Incidence rate ratios for British Indians compared with British whites were significantly less than 1.0 for all cancers combined (0.65) and for cancer of the breast (0.72), prostate (0.76), colon (0.46), lung (0.30), kidney (0.36), stomach (0.54), bladder (0.48) and oesophagus (0.64), but higher than 1.0 for liver cancer (1.95). CONCLUSION: These results are likely to be the most accurate estimate of cancer incidence in British Indians to date and confirm that cancer incidence in British Indians is lower than in British whites in Leicester, particularly for cancer of the breast, prostate, colon and lung (and other smoking-related cancers), but much higher than in India

Novel Coronin7 interactions with Cdc42 and N-WASP regulate actin organization and Golgi morphology

YesThe contribution of the actin cytoskeleton to the unique architecture of the Golgi complex is manifold. An important player in this process is Coronin7 (CRN7), a Golgi-resident protein that stabilizes F-actin assembly at the trans-Golgi network (TGN) thereby facilitating anterograde trafficking. Here, we establish that CRN7-mediated association of F-actin with the Golgi apparatus is distinctly modulated via the small Rho GTPase Cdc42 and N-WASP. We identify N-WASP as a novel interaction partner of CRN7 and demonstrate that CRN7 restricts spurious F-actin reorganizations by repressing N-WASP ‘hyperactivity’ upon constitutive Cdc42 activation. Loss of CRN7 leads to increased cellular F-actin content and causes a concomitant disruption of the Golgi structure. CRN7 harbours a Cdc42- and Rac-interactive binding (CRIB) motif in its tandem β-propellers and binds selectively to GDP-bound Cdc42N17 mutant. We speculate that CRN7 can act as a cofactor for active Cdc42 generation. Mutation of CRIB motif residues that abrogate Cdc42 binding to CRN7 also fail to rescue the cellular defects in fibroblasts derived from CRN7 KO mice. Cdc42N17 overexpression partially rescued the KO phenotypes whereas N-WASP overexpression failed to do so. We conclude that CRN7 spatiotemporally influences F-actin organization and Golgi integrity in a Cdc42- and N-WASP-dependent manner.This work was supported by SFB 670 and DFG NO 113/22. K.B. was supported by a fellowship from the NRW International Graduate School “From Embryo to Old Age: the Cell Biology and Genetics of Health and Disease” (IGSDHD), Cologne

Exploring differential item functioning in the Western Ontario and McMaster Universities osteoarthritis index (WOMAC)

Background: The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) is a widely used patient reported outcome in osteoarthritis. An important, but frequently overlooked, aspect of validating health outcome measures is to establish if items exhibit differential item functioning (DIF). That is, if respondents have the same underlying level of an attribute, does the item give the same score in different subgroups or is it biased towards one subgroup or another. The aim of the study was to explore DIF in the Likert format WOMAC for the first time in a UK osteoarthritis population with respect to demographic, social, clinical and psychological factors. Methods: The sample comprised a community sample of 763 people with osteoarthritis who participated in the Somerset and Avon Survey of Health. The WOMAC was explored for DIF by gender, age, social deprivation, social class, employment status, distress, body mass index and clinical factors. Ordinal regression models were used to identify DIF items. Results: After adjusting for age, two items were identified for the physical functioning subscale as having DIF with age identified as the DIF factor for 2 items, gender for 1 item and body mass index for 1 item. For the WOMAC pain subscale, for people with hip osteoarthritis one item was identified with age-related DIF. The impact of the DIF items rarely had a significant effect on the conclusions of group comparisons. Conclusions: Overall, the WOMAC performed well with only a small number of DIF items identified. However, as DIF items were identified in for the WOMAC physical functioning subscale it would be advisable to analyse data taking into account the possible impact of the DIF items when weight, gender or especially age effects, are the focus of interest in UK-based osteoarthritis studies. Similarly for the WOMAC pain subscale in people with hip osteoarthritis it would be worthwhile to analyse data taking into account the possible impact of the DIF item when age comparisons are of primary interest

Anemia and growth failure among HIV-infected children in India: a retrospective analysis

<p>Abstract</p> <p>Background</p> <p>Anemia and poor nutrition have been previously described as independent risk factors for death among HIV-infected children. We sought to describe nutritional status, anemia burden and HIV disease correlates among infected children in India.</p> <p>Methods</p> <p>We analyzed retrospective data from 248 HIV-infected children aged 1–12 years attending three outpatient clinics in South India (2004–2006). Standard WHO definitions were used for anemia, HIV staging and growth parameters. Statistical analysis included chi square, t tests, univariate and multivariate logistic regression analyses.</p> <p>Results</p> <p>The overall prevalence of anemia (defined as hemoglobin < 11 gm/dL) was 66%, and 8% had severe anemia (Hb < 7 gm/dL). The proportion of underweight and stunted children in the population was 55% and 46% respectively. Independent risk factors of anemia by multivariate analysis included the pre-school age group (age younger than 6 years) (OR: 2.87; 95% CI: 1.45, 5.70; p < 0.01), rural residence (OR: 12.04; 95% CI: 5.64, 26.00; p < 0.01), advanced HIV disease stage (OR: 6.95; 95% CI: 3.06, 15.79; p < 0.01) and presence of stunting (Height-for-age Z Score < -2) (OR: 3.24; 95% CI: 1.65, 6.35; p < 0.01). Use of iron/multivitamin supplementation was protective against risk of anemia (OR: 0.44; 95% CI: 0.22, 0.90; p = 0.03). Pulmonary tuberculosis was an independent risk factor in multivariate analysis (OR: 3.36; 95% CI: 1.43, 7.89; p < 0.01) when correlated variables such as HIV disease stage and severe immunodeficiency, and nutritional supplement use were not included. Use of antiretroviral therapy (ART) was associated with a reduced risk of anemia (OR: 0.29; 95% CI: 0.16, 0.53; p < 0.01). No significant association was found between anemia and gender, cotrimoxazole, or ART type (zidovudine versus stavudine).</p> <p>Conclusion</p> <p>The high prevalence and strong interrelationship of anemia and poor nutrition among HIV-infected children in India, particularly those living in rural areas underscores the need for incorporating targeted nutritional interventions during national scale up of care, support and treatment among HIV-infected children.</p

Genomic Sequencing and Comparative Analysis of Epstein-Barr Virus Genome Isolated from Primary Nasopharyngeal Carcinoma Biopsy

Whether certain Epstein-Barr virus (EBV) strains are associated with pathogenesis of nasopharyngeal carcinoma (NPC) is still an unresolved question. In the present study, EBV genome contained in a primary NPC tumor biopsy was amplified by Polymerase Chain Reaction (PCR), and sequenced using next-generation (Illumina) and conventional dideoxy-DNA sequencing. The EBV genome, designated HKNPC1 (Genbank accession number JQ009376) is a type 1 EBV of approximately 171.5 kb. The virus appears to be a uniform strain in line with accepted monoclonal nature of EBV in NPC but is heterogeneous at 172 nucleotide positions. Phylogenetic analysis with the four published EBV strains, B95-8, AG876, GD1, and GD2, indicated HKNPC1 was more closely related to the Chinese NPC patient-derived strains, GD1 and GD2. HKNPC1 contains 1,589 single nucleotide variations (SNVs) and 132 insertions or deletions (indels) in comparison to the reference EBV sequence (accession number NC007605). When compared to AG876, a strain derived from Ghanaian Burkitt's lymphoma, we found 322 SNVs, of which 76 were non-synonymous SNVs and were shared amongst the Chinese GD1, GD2 and HKNPC1 isolates. We observed 88 non-synonymous SNVs shared only by HKNPC1 and GD2, the only other NPC tumor-derived strain reported thus far. Non-synonymous SNVs were mainly found in the latent, tegument and glycoprotein genes. The same point mutations were found in glycoprotein (BLLF1 and BALF4) genes of GD1, GD2 and HKNPC1 strains and might affect cell type specific binding. Variations in LMP1 and EBNA3B epitopes and mutations in Cp (11404 C>T) and Qp (50134 G>C) found in GD1, GD2 and HKNPC1 could potentially affect CD8+ T cell recognition and latent gene expression pattern in NPC, respectively. In conclusion, we showed that whole genome sequencing of EBV in NPC may facilitate discovery of previously unknown variations of pathogenic significance

RSF Governs Silent Chromatin Formation via Histone H2Av Replacement

Human remodeling and spacing factor (RSF) consists of a heterodimer of Rsf-1 and hSNF2H, a counterpart of Drosophila ISWI. RSF possesses not only chromatin remodeling activity but also chromatin assembly activity in vitro. While no other single factor can execute the same activities as RSF, the biological significance of RSF remained unknown. To investigate the in vivo function of RSF, we generated a mutant allele of Drosophila Rsf-1 (dRsf-1). The dRsf-1 mutant behaved as a dominant suppressor of position effect variegation. In dRsf-1 mutant, the levels of histone H3K9 dimethylation and histone H2A variant H2Av were significantly reduced in an euchromatic region juxtaposed with heterochromatin. Furthermore, using both genetic and biochemical approaches, we demonstrate that dRsf-1 interacts with H2Av and the H2Av-exchanging machinery Tip60 complex. These results suggest that RSF contributes to histone H2Av replacement in the pathway of silent chromatin formation

A Deubiquitylating Complex Required for Neosynthesis of a Yeast Mitochondrial ATP Synthase Subunit

The ubiquitin system is known to be involved in maintaining the integrity of mitochondria, but little is known about the role of deubiquitylating (DUB) enzymes in such functions. Budding yeast cells deleted for UBP13 and its close homolog UBP9 displayed a high incidence of petite colonies and slow respiratory growth at 37°C. Both Ubp9 and Ubp13 interacted directly with Duf1 (DUB-associated factor 1), a WD40 motif-containing protein. Duf1 activates the DUB activity of recombinant Ubp9 and Ubp13 in vitro and deletion of DUF1 resulted in the same respiratory phenotype as the deletion of both UBP9 and UBP13. We show that the mitochondrial defects of these mutants resulted from a strong decrease at 37°C in the de novo biosynthesis of Atp9, a membrane-bound component of ATP synthase encoded by mitochondrial DNA. The defect appears at the level of ATP9 mRNA translation, while its maturation remained unchanged in the mutants. This study describes a new role of the ubiquitin system in mitochondrial biogenesis

Characterization of Epstein-Barr Virus miRNAome in Nasopharyngeal Carcinoma by Deep Sequencing

Virus-encoded microRNAs (miRNAs) have been shown to regulate a variety of biological processes involved in viral infection and viral-associated pathogenesis. Epstein-Barr virus (EBV) is a herpesvirus implicated in nasopharyngeal carcinoma (NPC) and other human malignancies. EBV-encoded miRNAs were among the first group of viral miRNAs identified. To understand the roles of EBV miRNAs in the pathogenesis of NPC, we utilized deep sequencing technology to characterize the EBV miRNA transcriptome in clinical NPC tissues. We obtained more than 110,000 sequence reads in NPC samples and identified 44 EBV BART miRNAs, including four new mature miRNAs derived from previously identified BART miRNA precursor hairpins. Further analysis revealed extensive sequence variations (isomiRs) of EBV miRNAs, including terminal isomiRs at both the 5′ and 3′ ends and nucleotide variants. Analysis of EBV genomic sequences indicated that the majority of EBV miRNA nucleotide variants resulted from post-transcriptional modifications. Read counts of individual EBV miRNA in NPC tissue spanned from a few reads to approximately 18,000 reads, confirming the wide expression range of EBV miRNAs. Several EBV miRNAs were expressed at levels similar to highly abundant human miRNAs. Sequence analysis revealed that most of the highly abundant EBV miRNAs share their seed sequences (nucleotides 2–7) with human miRNAs, suggesting that seed sequence content may be an important factor underlying the differential accumulation of BART miRNAs. Interestingly, many of these human miRNAs have been found to be dysregulated in human malignancies, including NPC. These observations not only provide a potential linkage between EBV miRNAs and human malignancy but also suggest a highly coordinated mechanism through which EBV miRNAs may mimic or compete with human miRNAs to affect cellular functions