233 research outputs found
Insensitivity of flavoured leptogenesis to low energy CP violation
If the baryon asymmetry of the Universe is produced by leptogenesis, CP
violation is required in the lepton sector. In the seesaw extension of the
Standard Model with three hierarchical right-handed neutrinos, we show that the
baryon asymmetry is insensitive to the PMNS phases: thermal leptogenesis can
work for any value of the observable phases. This result was well-known when
there are no flavour effects in leptogenesis; we show that it remains true when
flavour effects are included.Comment: 4 pages, 1 figure; version accepted for publication, added
explanations, notation clarifie
Adrenomedullin expression in a rat model of acute lung injury induced by hypoxia and LPS
Adrenomedullin
(ADM) is upregulated independently by hypoxia and LPS, two key
factors in the pathogenesis of acute lung injury (ALI). This study
evaluates the expression of ADM in ALI using experimental models
combining both stimuli: an in vivo model of rats treated with LPS and
acute normobaric hypoxia (9% O2) and an in vitro model of rat lung
cell lines cultured with LPS and exposed to hypoxia (1% O2). ADM
expression was analyzed by in situ hybridization, Northern blot,
Western blot, and RIA analyses. In the rat lung, combination of
hypoxia and LPS treatments overcomes ADM induction occurring
after each treatment alone. With in situ techniques, the synergistic
effect of both stimuli mainly correlates with ADM expression in
inflammatory cells within blood vessels and, to a lesser extent, to cells
in the lung parenchyma and bronchiolar epithelial cells. In the in vitro
model, hypoxia and hypoxia LPS treatments caused a similar strong
induction of ADM expression and secretion in epithelial and endothelial
cell lines. In alveolar macrophages, however, LPS-induced
ADM expression and secretion were further increased by the concomitant
exposure to hypoxia, thus paralleling the in vivo response. In
conclusion, ADM expression is highly induced in a variety of key
lung cell types in this rat model of ALI by combination of hypoxia and
LPS, suggesting an essential role for this mediator in this syndrom
Effects of acute hypoxia and lipopolysaccharide on nitric oxide synthase-2 expression in acute lung injury
The potential role of nitric oxide synthase-2 (NOS2) in acute lung
injury (ALI) has gained increasing attention. This study evaluates
the effects of hypoxia, an important feature of ALI, on NOS2 expression
in a rat model of ALI caused by exposure to hypoxia and LPS.
Exposure to hypoxia alone had no effect on the expression of NOS2
in rat lungs. LPS treatment resulted in a significant increase in NOS2
in the lungs, which was further enhanced by concomitant exposure
to hypoxia. Immunohistochemical analysis and in situ hybridization
showed no changes in the expression of NOS2 in lung resident cells
under any conditions. The increase in NOS2 levels is mainly due to
the influx of NOS2-expressing inflammatory cells. By morphologic
analysis, these inflammatory cells were identified as neutrophils,
lymphocytes, and monocytes. In vitro experiments of lung epithelial
and endothelial cell lines showed no detectable expression of NOS2
with any of the treatments. In a macrophage cell line, LPS-induced
NOS2 expression was not affected by the concomitant exposure to
hypoxia. In conclusion, LPS increases NOS2 expression in rat lungs
through the recruitment of NOS2-producing leukocytes. Simultaneous
exposure to LPS and hypoxia results in a greater influx of inflammatory
cells that further enhances NOS2 expression
Adrenomedullin in mammalian embryogenesis
Here are summarized data supporting that adrenomedullin (AM) is a multifunctional factor involved in the complex regulatory mechanisms of mammalian development. During rodent embryogenesis, AM is first expressed in the heart, followed by a broader but also defined spatio-temporal pattern of expression in vascular, neural, and skeletal-forming tissues as well as in the main embryonic internal organs. AM pattern of expression is suggestive of its involvement in the control of embryonic invasion, proliferation, and differentiation processes, probably through autocrine or paracrine modes of action. AM levels in fetoplacental tissues, uterus, maternal and umbilical plasma are highly increased during normal gestation. These findings in addition to other physiological and gene targeting studies support the importance of AM as a vasorelaxant factor implicated in the regulation of maternal vascular adaptation to pregnancy, as well as of fetal and fetoplacental circulations. AM is also present in amniotic fluid and milk, which is suggestive of additional functions in the maturation and immunological protection of the fetus. Altered expression of AM has been found in some gestational pathologies, although it is not yet clear whether this corresponds to causative or compensatory mechanisms. Future studies in regard to the distribution and expression levels of the molecules known to function as AM receptors, together with data on the action of complement factor H (an AM binding protein), may help to better define the roles of AM during embryonic development
On the full Boltzmann equations for Leptogenesis
We consider the full Boltzmann equations for standard and soft leptogenesis,
instead of the usual integrated Boltzmann equations which assume kinetic
equilibrium for all species. Decays and inverse decays may be inefficient for
thermalising the heavy-(s)neutrino distribution function, leading to
significant deviations from kinetic equilibrium. We analyse the impact of using
the full kinetic equations in the case of a previously generated lepton
asymmetry, and find that the washout of this initial asymmetry due to the
interactions of the right-handed neutrino is larger than when calculated via
the integrated equations. We also solve the full Boltzmann equations for soft
leptogenesis, where the lepton asymmetry induced by the soft SUSY-breaking
terms in sneutrino decays is a purely thermal effect, since at T=0 the
asymmetry in leptons cancels the one in sleptons. In this case, we obtain that
in the weak washout regime (K ~< 1) the final lepton asymmetry can change up to
a factor four with respect to previous estimates.Comment: 34 pages, 6 figures, to be published in JCA
Neutrino masses from higher than d=5 effective operators
We discuss the generation of small neutrino masses from effective operators
higher than dimension five, which open new possibilities for low scale see-saw
mechanisms. In order to forbid the radiative generation of neutrino mass by
lower dimensional operators, extra fields are required, which are charged under
a new symmetry. We discuss this mechanism in the framework of a two Higgs
doublet model. We demonstrate that the tree level generation of neutrino mass
from higher dimensional operators often leads to inverse see-saw scenarios in
which small lepton number violating terms are naturally suppressed by the new
physics scale. Furthermore, we systematically discuss tree level
generalizations of the standard see-saw scenarios from higher dimensional
operators. Finally, we point out that higher dimensional operators can also be
generated at the loop level. In this case, we obtain the TeV scale as new
physics scale even with order one couplings.Comment: 22 pages, 3 figures, 2 tables. Some references adde
Full Boltzmann equations for leptogenesis including scattering
We study the evolution of a cosmological baryon asymmetry produced via
leptogenesis by means of the full classical Boltzmann equations, without the
assumption of kinetic equilibrium and including all quantum statistical
factors. Beginning with the full mode equations we derive the usual equations
of motion for the right-handed neutrino number density and integrated lepton
asymmetry, and show explicitly the impact of each assumption on these
quantities. For the first time, we investigate also the effects of scattering
of the right-handed neutrino with the top quark to leading order in the Yukawa
couplings by means of the full Boltzmann equations. We find that in our full
Boltzmann treatment the final lepton asymmetry can be suppressed by as much as
a factor of 1.5 in the weak wash-out regime (K<1), compared to the usual
integrated approach which assumes kinetic equilibrium and neglects quantum
statistics. This suppression is in contrast with the enhancement seen in some
previous studies that considered only decay and inverse decay of the
right-handed neutrino. However, this suppression quickly decreases as we
increase K. In the strong wash-out regime (K>1), the full Boltzmann treatment
and the integrated approach give nearly identical final lepton asymmetries
(within 10 % of each other at K>3). Finally, we show that the opposing effects
of quantum statistics on decays/inverse decays and the scattering processes
tend to reduce the net importance of scattering on leptogenesis in the full
treatment compared to the integrated approach.Comment: 39 pages, 8 figures, typos corrected, replaced to match published
versio
Soft leptogenesis in the inverse seesaw model
We consider leptogenesis induced by soft supersymmetry breaking terms ("soft
leptogenesis"), in the context of the inverse seesaw mechanism. In this model
there are lepton number (L) conserving and L-violating soft
supersymmetry-breaking B-terms involving the singlet sneutrinos which, together
with the -- generically small-- L-violating parameter responsible of the
neutrino mass, give a small mass splitting between the four singlet sneutrino
states of a single generation. In combination with the trilinear soft
supersymmetry breaking terms they also provide new CP violating phases needed
to generate a lepton asymmetry in the singlet sneutrino decays. We obtain that
in this scenario the lepton asymmetry is proportional to the L-conserving soft
supersymmetry-breaking B-term, and it is not suppressed by the L-violating
parameters. Consequently we find that, as in the standard see-saw case, this
mechanism can lead to sucessful leptogenesis only for relatively small value of
the relevant soft bilinear coupling. The right-handed neutrino masses can be
sufficiently low to elude the gravitino problem. Also the corresponding Yukawa
couplings involving the lightest of the right-handed neutrinos are constrained
to be \sum |Y_{1k}|^2\lesssim 10^{-7} which generically implies that the
neutrino mass spectrum has to be strongly hierarchical.Comment: 28 pages, 1 figure; some references added; final version to appear in
JHE
Biological Background of Resistance to Current Standards of Care in Multiple Myeloma
A high priority problem in multiple myeloma (MM) management is the development of resistance to administered therapies, with most myeloma patients facing successively shorter periods of response and relapse. Herewith, we review the current knowledge on the mechanisms of resistance to the standard backbones in MM treatment: proteasome inhibitors (PIs), immunomodulatory agents (IMiDs), and monoclonal antibodies (mAbs). In some cases, strategies to overcome resistance have been discerned, and an effort should be made to evaluate whether resensitization to these agents is feasible in the clinical setting. Additionally, at a time in which we are moving towards precision medicine in MM, it is equally important to identify reliable and accurate biomarkers of sensitivity/refractoriness to these main therapeutic agents with the goal of having more efficacious treatments and, if possible, prevent the development of relapse.Funding: E.M.O. was supported by an Inplant grant fromIDIVALand TP by a grant fromAECC(INVES18043PAĂŤN). E.M.A. and A.D.-T. received a grant from the Regional Council from Castilla y LeĂłn, and P.M. from the Institute for Biomedical Research from Salamanca. This work was supported by funding from Spanish FIS (PI15/00067, PI15/02156 and PI18/01600) and FEDER, AECC (GCB120981SAN), RamĂłn Areces Foundation (FRA16/003); the Regional Council from Castilla y LeĂłn (GRS 1604/A/17, GRS 1880/A/18 and Centro en Red de Medicina Regenerativa y Terapia Celular), and the Institute for Biomedical Research from Salamanca (IBY17/00008)
The role of adrenomedullin as a growth regulatory peptide in the normal and malignant setting
Adrenomedullin (AM ) is a recently
discovered pluripo1ent peptide initially isolated fraro a human adrenal gland tumor (pheochromocytoma).
Adrenomedullin has been shown to have an ancient origin with immunoreactive species fOWld in maromals, birds, reptiles, amphibians, fish , and eemnoderms (s t a r fish ). Given its highly conserved evolutionary expression, AM is thought te playa critica!
!•ole in spedes survival. This peptide has been show lo mediate a variety of physiological fu netlons, of
which iis involvement in growth r egulation wil1 be tbe central focus of this papero In the following text, we will review the cited Iiterature in this area and inelude our own observations regarding AM express10n
in carcinogenesis, embryogenesis, and wound
r epair. Adrenomedullin will be shown to induce both growth promotian or growth suppression depending on the taTget cell examined aud the sUITounding nutritional
environment in which the analysis was done. Its implied role as a mitogen, aogiogenic fador, and apoplosis survival factor will be critiqued and evaluated relative to its impor tance in the cel! proHferation
process. Finally, we will review the a ntimicrobiaJ effect AM has on severa1 human pathogens ( Es•cherichia coli and Candidn albi.cans) and demonstrate its partieipation in the host immune response syslem as a first line defense peptide
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