Involution of the mouse mammary gland is associated with an immune cascade and an acute-phase response, involving LBP, CD14 and STAT3

INTRODUCTION: Involution of the mammary gland is a complex process of controlled apoptosis and tissue remodelling. The aim of the project was to identify genes that are specifically involved in this process. METHODS: We used Affymetrix oligonucleotide microarrays to perform a detailed transcript analysis on the mechanism of controlled involution after withdrawal of the pups at day seven of lactation. Some of the results were confirmed by semi-quantitative reverse transcriptase polymerase chain reaction, Western blotting or immunohistochemistry. RESULTS: We identified 145 genes that were specifically upregulated during the first 4 days of involution; of these, 49 encoded immunoglobulin genes. A further 12 genes, including those encoding the signal transducer and activator of transcription 3 (STAT3), the lipopolysaccharide receptor (CD14) and lipopolysaccharide-binding protein (LBP), were involved in the acute-phase response, demonstrating that the expression of acute-phase response genes can occur in the mammary gland itself and not only in the liver. Expression of LBP and CD14 was upregulated, at both the RNA and protein level, immediately after pup withdrawal; CD14 was strongly expressed in the luminal epithelial cells. Other genes identified suggested neutrophil activation early in involution, followed by macrophage activation late in the process. Immunohistochemistry and histological staining confirmed the infiltration of the involuting mammary tissue with neutrophils, plasma cells, macrophages and eosinophils. CONCLUSION: Oligonucleotide microarrays are a useful tool for identifying genes that are involved in the complex developmental process of mammary gland involution. The genes identified are consistent with an immune cascade, with an early acute-phase response that occurs in the mammary gland itself and resembles a wound healing process

QTLs for salt tolerance in three different barley mapping populations 2006

Soil salinity is one of the crucial factors limiting crop production. Progression of salinisation of agriculturally arable land is mainly connected with mismanagement of water in irrigation systems, in particular under arid and semiarid climate conditions and global changes of water flow in the landscape. Selection of salt tolerant genotypes is necessary to ensure yield and to reclaim salt affected soils. The development of molecular marker(s) could facilitate the selection process. Phenotyping of mapping populations under salt stress conditions and calculation of QTLs are suitable instruments to detect markers that are responsible for tolerance/sensitivity. However, a quantitative inherited trait like salt tolerance requires a range of adaptations, with a whole host of genes interacting with each other to produce the visible phenotype

Antagonistic effects of transforming growth factor-beta on vitamin D3 enhancement of osteocalcin and osteopontin transcription: reduced interactions of vitamin D receptor/retinoid X receptor complexes with vitamin E response elements

Osteocalcin and osteopontin are noncollagenous proteins secreted by osteoblasts and regulated by a complex interplay of systemic and locally produced factors, including growth factors and steroid hormones. We investigated the mechanism by which transforming growth factor-beta (TGF beta) inhibits 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3)-enhanced expression of the osteocalcin (OC) and osteopontin (OP) genes. ROS 17/2.8 cells, in which both genes are expressed, were transfected with reporter constructs driven by native (i.e. wild-type) rat OC and mouse OP promoters. TGF beta abrogated the 1,25-(OH)2D3 enhanced transcription of both the OC and OP genes. The inhibitory TGF beta response for each requires vitamin D response element (VDRE) sequences, although there are additional contributions from proximal basal regulatory elements. These transcriptional effects were further investigated for contribution of the trans-activating factors, which interact with OC and OP VDREs, involving the vitamin D receptor (VDR) and retinoid X receptor (RXR). Gel mobility shift assays show that TGF beta significantly reduces induction of the heterodimers VDR/RXR complexes in 1,25-(OH)2D3-treated ROS 17/2.8 cells. However, Western blot and ligand binding analysis reveal that TGF beta does not affect nuclear availability of the VDR. We also show that activator protein-1 activity is up-regulated by TGF beta; thus, activator protein-1 binding sites in the OC promoter may potentially contribute to inhibitory effects of TGF beta on basal transcription. Our studies demonstrate that the inhibitory action of TGF beta on the 1,25-(OH)2D3 enhancement of OC and OP transcription in osteoblastic cells results from modulations of protein-DNA interactions at the OC and OP VDRE, which cannot be accounted for by changes in VDR protein levels. As OC and OP participate in bone turnover, our results provide insight into the contributions of TGF beta and 1,25-(OH)2D3 to VDR-mediated gene regulatory mechanism operative in bone formation and/or resorption events

Towards a collaborative, global infrastructure for biodiversity assessment

Biodiversity data are rapidly becoming available over the Internet in common formats that promote sharing and exchange. Currently, these data are somewhat problematic, primarily with regard to geographic and taxonomic accuracy, for use in ecological research, natural resources management and conservation decision-making. However, web-based georeferencing tools that utilize best practices and gazetteer databases can be employed to improve geographic data. Taxonomic data quality can be improved through web-enabled valid taxon names databases and services, as well as more efficient mechanisms to return systematic research results and taxonomic misidentification rates back to the biodiversity community. Both of these are under construction. A separate but related challenge will be developing web-based visualization and analysis tools for tracking biodiversity change. Our aim was to discuss how such tools, combined with data of enhanced quality, will help transform today's portals to raw biodiversity data into nexuses of collaborative creation and sharing of biodiversity knowledge

Are the Crystal Structures of Enantiopure and Racemic Mandelic Acids Determined by Kinetics or Thermodynamics?

YesMandelic acids are prototypic chiral molecules where the sensitivity of crystallized forms (enantiopure/racemic compound/polymorphs) to both conditions and substituents provides a new insight into the factors that may allow chiral separation by crystallization. The determination of a significant number of single crystal structures allows the analysis of 13 enantiopure and 30 racemic crystal structures of 21 (F/Cl/Br/CH3/CH3O) substituted mandelic acid derivatives. There are some common phenyl packing motifs between some groups of racemic and enantiopure structures, although they show very different hydrogen-bonding motifs. The computed crystal energy landscape of 3-chloromandelic acid, which has at least two enantiopure and three racemic crystal polymorphs, reveals that there are many more possible structures, some of which are predicted to be thermodynamically more favorable as well as slightly denser than the known forms. Simulations of mandelic acid dimers in isolation, water, and toluene do not differentiate between racemic and enantiopure dimers and also suggest that the phenyl ring interactions play a major role in the crystallization mechanism. The observed crystallization behavior of mandelic acids does not correspond to any simple “crystal engineering rules” as there is a range of thermodynamically feasible structures with no distinction between the enantiopure and racemic forms. Nucleation and crystallization appear to be determined by the kinetics of crystal growth with a statistical bias, but the diversity of the mandelic acid crystallization behavior demonstrates that the factors that influence the kinetics of crystal nucleation and growth are not yet adequately understood.EPSRC, Max Planck Society for the Advancement of Sciences, UCL-MPS Impact Ph.D. Fellowship, EU COST Actio

Stochastic excitation of acoustic modes in stars

For more than ten years, solar-like oscillations have been detected and frequencies measured for a growing number of stars with various characteristics (e.g. different evolutionary stages, effective temperatures, gravities, metal abundances ...). Excitation of such oscillations is attributed to turbulent convection and takes place in the uppermost part of the convective envelope. Since the pioneering work of Goldreich & Keely (1977), more sophisticated theoretical models of stochastic excitation were developed, which differ from each other both by the way turbulent convection is modeled and by the assumed sources of excitation. We review here these different models and their underlying approximations and assumptions. We emphasize how the computed mode excitation rates crucially depend on the way turbulent convection is described but also on the stratification and the metal abundance of the upper layers of the star. In turn we will show how the seismic measurements collected so far allow us to infer properties of turbulent convection in stars.Comment: Notes associated with a lecture given during the fall school organized by the CNRS and held in St-Flour (France) 20-24 October 2008 ; 39 pages ; 11 figure

Implementation and Validation of Schapery-Rand Anisotropic Viscoelasticity Model for Super-Pressure Balloons

The thin film used for the NASA Ultra Long Duration Balloons (ULDB) shows con-siderable time-dependent behaviour. Furthermore, experiments on scaled ULDB balloons have revealed that wrinkles are present over a wide range of pressures. A numerical model has been developed describing the nonlinear anisotropic viscoelastic material behaviour by means of a Schapery-type model and this model has been extended to model wrinkling by means of a user-defined subroutine in the finite-element package ABAQUS. After a description of the viscoelastic modelling approach, a lobe of a 48 gore ULDB flat facet balloon is modelled and compared to experimental results. Additionally two test cases of anisotropic wrinkling are presented, one involving a flat membrane and one a cylindrical balloon structure. I

Bloom-Gilman duality of inelastic structure functions in nucleon and nuclei

The Bloom-Gilman local duality of the inelastic structure function of the proton, the deuteron and light complex nuclei is investigated using available experimental data in the squared four-momentum transfer range from 0.3 to 5 (GeV/c)**2. The results of our analysis suggest that the onset of the Bloom-Gilman local duality is anticipated in complex nuclei with respect to the case of the protonand the deuteron. A possible interpretation of this result in terms of a rescaling effect is discussed with particular emphasis to the possibility of reproducing the damping of the nucleon-resonance transitions observed in recent electroproduction data off nuclei.Comment: revised version, to appear in Physical Review

Structural alterations in a type IV pilus subunit protein result in concurrent defects in multicellular behaviour and adherence to host tissue

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72384/1/j.1365-2958.2001.02629.x.pd

Search for a W' boson decaying to a bottom quark and a top quark in pp collisions at sqrt(s) = 7 TeV

Results are presented from a search for a W' boson using a dataset corresponding to 5.0 inverse femtobarns of integrated luminosity collected during 2011 by the CMS experiment at the LHC in pp collisions at sqrt(s)=7 TeV. The W' boson is modeled as a heavy W boson, but different scenarios for the couplings to fermions are considered, involving both left-handed and right-handed chiral projections of the fermions, as well as an arbitrary mixture of the two. The search is performed in the decay channel W' to t b, leading to a final state signature with a single lepton (e, mu), missing transverse energy, and jets, at least one of which is tagged as a b-jet. A W' boson that couples to fermions with the same coupling constant as the W, but to the right-handed rather than left-handed chiral projections, is excluded for masses below 1.85 TeV at the 95% confidence level. For the first time using LHC data, constraints on the W' gauge coupling for a set of left- and right-handed coupling combinations have been placed. These results represent a significant improvement over previously published limits.Comment: Submitted to Physics Letters B. Replaced with version publishe