PIF4 enhances DNA binding by CDF2 to co-regulate target gene expression and promote Arabidopsis hypocotyl cell elongation

How specificity is conferred within gene regulatory networks is an important problem in biology. The basic helix–loop–helix PHYTOCHROME-INTERACTING FACTORs (PIFs) and single zinc-finger CYCLING DOF FACTORs (CDFs) mediate growth responses of Arabidopsis to light and temperature. We show that these two classes of transcription factor (TF) act cooperatively. CDF2 and PIF4 are temporally and spatially co-expressed, they interact to form a protein complex and act in the same genetic pathway to promote hypocotyl cell elongation. Furthermore, PIF4 substantially strengthens genome-wide occupancy of CDF2 at a subset of its target genes. One of these, YUCCA8, encodes an auxin biosynthesis enzyme whose transcription is increased by PIF4 and CDF2 to contribute to hypocotyl elongation. The binding sites of PIF4 and CDF2 in YUCCA8 are closely spaced, and in vitro PIF4 enhances binding of CDF2. We propose that this occurs by direct protein interaction and because PIF4 binding alters DNA conformation. Thus, we define mechanisms by which PIF and CDF TFs cooperate to achieve regulatory specificity and promote cell elongation in response to light

Immunohistochemical analysis indicates that the anatomical location of B-cell non-Hodgkin's lymphoma is determined by differentially expressed chemokine receptors, sphingosine-1-phosphate receptors and integrins.

BackgroundThe aim of this study was to elucidate the mechanisms responsible for the location of B-cell non-Hodgkin's lymphoma (B-NHL) at different anatomical sites. We speculated that the malignant B cells in these disorders have the potential for trafficking between blood and secondary lymphoid organs (SLO) or extranodal sites and that their preferential accumulation at different locations is governed by the expression of key molecules that regulate the trafficking of normal lymphocytes.MethodsBiopsy or blood samples from 91 cases of B-NHL affecting SLO (n = 27), ocular adnexae (n = 51) or blood (n = 13) were analysed by immunohistochemistry or flow cytometry for the expression of the following molecules: CCR7, CCL21 and αL (required for the entry of normal lymphocytes into SLO); CXCR4, CXCL12 and α4 (required for entry into extranodal sites); CXCR5, CXCL13 and S1PR2 (required for tissue retention); S1PR1 and S1PR3 (required for egress into the blood). The expression of each of these molecules was then related to anatomical location and histological subtype.ResultsThe expression of motility/adhesion molecules varied widely between individual patient samples and correlated much more strongly with anatomical location than with histological subtype. SLO lymphomas [comprising 10 follicular lymphoma (FL), 8 diffuse large B-cell lymphoma (DLBCL), 4 mantle-cell lymphoma (MCL) and 5 marginal-zone lymphoma (MZL)] were characterised by pronounced over-expression of S1PR2, suggesting that the malignant cells in these lymphomas are actively retained at the site of clonal expansion. In contrast, the malignant B cells in ocular adnexal lymphomas (10 FL, 9 DLBCL, 4 MCL and 28 MZL) expressed a profile of molecules suggesting a dynamic process of trafficking involving not only tissue retention but also egress via S1PR3 and homing back to extranodal sites via CXCR4/CXCL12 and α4. Finally, leukaemic lymphomas (6 FL, 5 MCL and 2 MZL) were characterised by aberrant expression of the egress receptor S1PR1 and low expression of molecules required for tissue entry/retention.ConclusionsIn summary, our study strongly suggests that anatomical location in B-NHL is governed by the differential expression of specific adhesion/motility molecules. This novel observation has important implications for therapeutic strategies that aim to disrupt protective micro-environmental interactions

Correlations in intermediate-energy two-proton removal reactions

We report final-state-exclusive measurements of the light charged fragments in coincidence with 26Ne residual nuclei following the direct two-proton removal from a neutron-rich 28Mg secondary beam. A Dalitz-plot analysis and comparisons with simulations show that a majority of the triple- coincidence events with two protons display phase-space correlations consistent with the (two-body) kinematics of a spatially-correlated pair-removal mechanism. The fraction of such correlated events, 56(12) %, is consistent with the fraction of the calculated cross section, 64 %, arising from spin S = 0 two-proton configurations in the entrance-channel (shell-model) 28Mg ground state wave function. This result promises access to an additional and more specific probe of the spin and spatial correlations of valence nucleon pairs in exotic nuclei produced as fast secondary beams.Comment: accepted for publication in Physical Review Letter

Investigations of three, four, and five-particle exit channels of levels in light nuclei created using a 9C beam

The interactions of a E/A=70-MeV 9C beam with a Be target was used to populate levels in Be, B, and C isotopes which undergo decay into many-particle exit channels. The decay products were detected in the HiRA array and the level energies were identified from their invariant mass. Correlations between the decay products were examined to deduce the nature of the decays, specifically to what extent all the fragments were created in one prompt step or whether the disintegration proceeded in a sequential fashion through long-lived intermediate states. In the latter case, information on the spin of the level was also obtained. Of particular interest is the 5-body decay of the 8C ground state which was found to disintegrate in two steps of two-proton decay passing through the 6Beg.s. intermediate state. The isobaric analog of 8Cg.s. in 8B was also found to undergo two-proton decay to the isobaric analog of 6Beg.s. in 6Li. A 9.69-MeV state in 10C was found to undergo prompt 4-body decay to the 2p+2alpha exit channel. The two protons were found to have a strong enhancementin the diproton region and the relative energies of all four p-alpha pairs were consistent with the 5Lig.s. resonance

Keeping children safe at home: protocol for a case-control study of modifiable risk factors for scalds

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions. BACKGROUND: Scalds are one of the most common forms of thermal injury in young children worldwide. Childhood scald injuries, which mostly occur in the home, result in substantial health service use and considerable morbidity and mortality. There is little research on effective interventions to prevent scald injuries in young children.OBJECTIVES: To determine the relationship between a range of modifiable risk factors for medically attended scalds in children under the age of 5 years.DESIGN: A multicentre case-control study in UK hospitals and minor injury units with parallel home observation to validate parental reported exposures. Cases will be 0-4 years old with a medically attended scald injury which occurred in their home or garden, matched on gender and age with community controls. An additional control group will comprise unmatched hospital controls drawn from children aged 0-4 years attending the same hospitals and minor injury units for other types of injury. Conditional logistic regression will be used for the analysis of cases and matched controls, and unconditional logistic regression for the analysis of cases and unmatched controls to estimate ORs and 95% CI, adjusted and unadjusted for confounding variables.MAIN EXPOSURE MEASURES: Use of safety equipment and safety practices for scald prevention and scald hazards.DISCUSSION: This large case-control study will investigate modifiable risk factors for scalds injuries, adjust for potential confounders and validate measures of exposure. Its findings will enhance the evidence base for prevention of scalds injuries in young children