654 research outputs found
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
The intrinsic charm contribution to the proton spin
The charm quark contribution to the first moment of is
calculated using a heavy mass expansion of the divergence of the singlet axial
current. It is shown to be small.Comment: LATEX, 6 page
Nonlinear porous medium flow with fractional potential pressure
We study a porous medium equation, with nonlocal diffusion effects given by
an inverse fractional Laplacian operator. We pose the problem in n-dimensional
space for all t>0 with bounded and compactly supported initial data, and prove
existence of a weak and bounded solution that propagates with finite speed, a
property that is nor shared by other fractional diffusion models.Comment: 32 pages, Late
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
Measuring the Temperature of Hot Nuclear Fragments
A new thermometer based on fragment momentum fluctuations is presented. This
thermometer exhibited residual contamination from the collective motion of the
fragments along the beam axis. For this reason, the transverse direction has
been explored. Additionally, a mass dependence was observed for this
thermometer. This mass dependence may be the result of the Fermi momentum of
nucleons or the different properties of the fragments (binding energy, spin
etc..) which might be more sensitive to different densities and temperatures of
the exploding fragments. We expect some of these aspects to be smaller for
protons (and/or neutrons); consequently, the proton transverse momentum
fluctuations were used to investigate the temperature dependence of the source
Effects of testosterone administration on threat and escape anticipation in the orbitofrontal cortex.
Recent evidence suggests that the steroid hormone testosterone can decrease the functional coupling between orbitofrontal cortex (OFC) and amygdala. Theoretically this decoupling has been linked to a testosterone-driven increase of goal-directed behaviour in case of threat, but this has never been studied directly. Therefore, we placed twenty-two women in dynamically changing situations of escapable and inescapable threat after a within-subject placebo controlled testosterone administration. Using functional magnetic resonance imaging (fMRI) we provide evidence that testosterone activates the left lateral OFC (LOFC) in preparation of active goal-directed escape and decouples this OFC area from a subcortical threat system including the central-medial amygdala, hypothalamus and periaqueductal gray. This LOFC decoupling was specific to threatening situations, a point that was further emphasized by an absence of such decoupling in a second experiment focused on resting-state connectivity. These results not only confirm that testosterone administration decouples the LOFC from the subcortical threat system, but also show that this is specifically the case in response to acute threat, and ultimately leads to an increase in LOFC activity when the participant prepares a goal-directed action to escape. Together these results for the first time provide a detailed understanding of functional brain alterations induced by testosterone under threat conditions, and corroborate and extend the view that testosterone prepares the brain for goal-directed action in case of threat.FSW – Publicaties zonder aanstelling Universiteit Leide
Asymmetry Dependence of the Nuclear Caloric Curve
A basic feature of the nuclear equation of state is not yet understood: the
dependence of the nuclear caloric curve on the neutron-proton asymmetry.
Predictions of theoretical models differ on the magnitude and even the sign of
this dependence. In this work, the nuclear caloric curve is examined for fully
reconstructed quasi-projectiles around mass A=50. The caloric curve extracted
with the momentum quadrupole fluctuation thermometer shows that the temperature
varies linearly with quasi-projectile asymmetry (N-Z)/A. An increase in
asymmetry of 0.15 units corresponds to a decrease in temperature on the order
of 1 MeV. These results also highlight the importance of a full
quasi-projectile reconstruction in the study of thermodynamic properties of hot
nuclei
Disparate MgII Absorption Statistics towards Quasars and Gamma-Ray Bursts : A Possible Explanation
We examine the recent report by Prochter et al. (2006) that gamma-ray burst
(GRB) sight lines have a much higher incidence of strong MgII absorption than
quasar sight lines. We propose that the discrepancy is due to the different
beam sizes of GRBs and quasars, and that the intervening MgII systems are
clumpy with the dense part of each cloudlet of a similar size as the quasars,
i.e. < 10^16 cm, but bigger than GRBs. We also discuss observational
predictions of our proposed model. Most notably, in some cases the intervening
MgII absorbers in GRB spectra should be seen varying, and quasars with smaller
sizes should show an increased rate of strong MgII absorbers. In fact, our
prediction of variable MgII lines in the GRB spectra has been now confirmed by
Hao et al. (2007), who observed intervening FeII and MgII lines at z=1.48 to be
strongly variable in the multi-epoch spectra of z=4.05 GRB060206.Comment: 12 pages, 2 figures; substantially revised model calculation;
accepted for publication in Astrophysics & Space Science as a Lette
Trib2 suppresses tumor initiation in Notch-driven T-ALL
Trib2 is highly expressed in human T cell acute lymphoblastic leukemia (T-ALL) and is a direct transcriptional target of the oncogenic drivers Notch and TAL1. In human TAL1-driven T-ALL cell lines, Trib2 is proposed to function as an important survival factor, but there is limited information about the role of Trib2 in primary T-ALL. In this study, we investigated the role of Trib2 in the initiation and maintenance of Notch-dependent T-ALL. Trib2 had no effect on the growth and survival of murine T-ALL cell lines in vitro when expression was blocked by shRNAs. To test the function of Trib2 on leukemogenesis in vivo, we generated Trib2 knockout mice. Mice were born at the expected Mendelian frequencies without gross developmental anomalies. Adult mice did not develop pathology or shortened survival, and hematopoiesis, including T cell development, was unperturbed. Using a retroviral model of Notch-induced T-ALL, deletion of Trib2 unexpectedly decreased the latency and increased the penetrance of T-ALL development in vivo. Immunoblotting of primary murine T-ALL cells showed that the absence of Trib2 increased C/EBPα expression, a known regulator of cell proliferation, and did not alter AKT or ERK phosphorylation. Although Trib2 was suggested to be highly expressed in T-ALL, transcriptomic analysis of two independent T-ALL cohorts showed that low Trib2 expression correlated with the TLX1-expressing cortical mature T-ALL subtype, whereas high Trib2 expression correlated with the LYL1-expressing early immature T-ALL subtype. These data indicate that Trib2 has a complex role in the pathogenesis of Notch-driven T-ALL, which may vary between different T-ALL subtypes
- …