796 research outputs found
Triad3a induces the degradation of early necrosome to limit RipK1-dependent cytokine production and necroptosis.
Understanding the molecular signaling in programmed cell death is vital to a practical understanding of inflammation and immune cell function. Here we identify a previously unrecognized mechanism that functions to downregulate the necrosome, a central signaling complex involved in inflammation and necroptosis. We show that RipK1 associates with RipK3 in an early necrosome, independent of RipK3 phosphorylation and MLKL-induced necroptotic death. We find that formation of the early necrosome activates K48-ubiquitin-dependent proteasomal degradation of RipK1, Caspase-8, and other necrosomal proteins. Our results reveal that the E3-ubiquitin ligase Triad3a promotes this negative feedback loop independently of typical RipK1 ubiquitin editing enzymes, cIAPs, A20, or CYLD. Finally, we show that Triad3a-dependent necrosomal degradation limits necroptosis and production of inflammatory cytokines. These results reveal a new mechanism of shutting off necrosome signaling and may pave the way to new strategies for therapeutic manipulation of inflammatory responses
Dynamical Patterns of Cattle Trade Movements
Despite their importance for the spread of zoonotic diseases, our
understanding of the dynamical aspects characterizing the movements of farmed
animal populations remains limited as these systems are traditionally studied
as static objects and through simplified approximations. By leveraging on the
network science approach, here we are able for the first time to fully analyze
the longitudinal dataset of Italian cattle movements that reports the mobility
of individual animals among farms on a daily basis. The complexity and
inter-relations between topology, function and dynamical nature of the system
are characterized at different spatial and time resolutions, in order to
uncover patterns and vulnerabilities fundamental for the definition of targeted
prevention and control measures for zoonotic diseases. Results show how the
stationarity of statistical distributions coexists with a strong and
non-trivial evolutionary dynamics at the node and link levels, on all
timescales. Traditional static views of the displacement network hide important
patterns of structural changes affecting nodes' centrality and farms' spreading
potential, thus limiting the efficiency of interventions based on partial
longitudinal information. By fully taking into account the longitudinal
dimension, we propose a novel definition of dynamical motifs that is able to
uncover the presence of a temporal arrow describing the evolution of the system
and the causality patterns of its displacements, shedding light on mechanisms
that may play a crucial role in the definition of preventive actions
Dynamical Patterns of Cattle Trade Movements
Despite their importance for the spread of zoonotic diseases, our
understanding of the dynamical aspects characterizing the movements of farmed
animal populations remains limited as these systems are traditionally studied
as static objects and through simplified approximations. By leveraging on the
network science approach, here we are able for the first time to fully analyze
the longitudinal dataset of Italian cattle movements that reports the mobility
of individual animals among farms on a daily basis. The complexity and
inter-relations between topology, function and dynamical nature of the system
are characterized at different spatial and time resolutions, in order to
uncover patterns and vulnerabilities fundamental for the definition of targeted
prevention and control measures for zoonotic diseases. Results show how the
stationarity of statistical distributions coexists with a strong and
non-trivial evolutionary dynamics at the node and link levels, on all
timescales. Traditional static views of the displacement network hide important
patterns of structural changes affecting nodes' centrality and farms' spreading
potential, thus limiting the efficiency of interventions based on partial
longitudinal information. By fully taking into account the longitudinal
dimension, we propose a novel definition of dynamical motifs that is able to
uncover the presence of a temporal arrow describing the evolution of the system
and the causality patterns of its displacements, shedding light on mechanisms
that may play a crucial role in the definition of preventive actions
Expression of Human Beta-Defensins in Children with Chronic Inflammatory Bowel Disease
Background: Human beta-defensins (hBDs) are antimicrobial peptides known to play a major role in intestinal innate host defence. Altered mucosal expression of hBDs has been suggested to be implicated in chronic inflammatory bowel disease pathogenesis. However, little is known about expression of these peptides in children. Methods: Intestinal biopsies were obtained from the duodenum (n = 88), terminal ileum (n = 90) and ascending colon (n = 105) of children with Crohnâs disease (n = 26), ulcerative colitis (n = 11) and healthy controls (n = 16). Quantitative realtime (RT) PCR was performed and absolute mRNA copy numbers analyzed for hBD1-3 as well as inflammatory cytokines IL-8 and TNF-alpha. Results: Significant induction of hBD2 and hBD3 was observed in the inflamed terminal ileum and ascending colon of IBD children. In the ascending colon induction of hBD2 was found to be significantly lower in children with Crohnâs disease compared to ulcerative colitis. A strong correlation was found between inducible defensins hBD2 and 3 and the inflammatory cytokines IL-8 and TNF-alpha, both in the terminal ileum and ascending colon. Conclusion: Our study demonstrates distinct changes in hBD expression throughout the intestinal tract of children with IBD
A search for the decay modes B+/- to h+/- tau l
We present a search for the lepton flavor violating decay modes B+/- to h+/-
tau l (h= K,pi; l= e,mu) using the BaBar data sample, which corresponds to 472
million BBbar pairs. The search uses events where one B meson is fully
reconstructed in one of several hadronic final states. Using the momenta of the
reconstructed B, h, and l candidates, we are able to fully determine the tau
four-momentum. The resulting tau candidate mass is our main discriminant
against combinatorial background. We see no evidence for B+/- to h+/- tau l
decays and set a 90% confidence level upper limit on each branching fraction at
the level of a few times 10^-5.Comment: 15 pages, 7 figures, submitted to Phys. Rev.
Observation and study of baryonic B decays: B -> D(*) p pbar, D(*) p pbar pi, and D(*) p pbar pi pi
We present a study of ten B-meson decays to a D(*), a proton-antiproton pair,
and a system of up to two pions using BaBar's data set of 455x10^6 BBbar pairs.
Four of the modes (B0bar -> D0 p anti-p, B0bar -> D*0 p anti-p, B0bar -> D+ p
anti-p pi-, B0bar -> D*+ p anti-p pi-) are studied with improved statistics
compared to previous measurements; six of the modes (B- -> D0 p anti-p pi-, B-
-> D*0 p anti-p pi-, B0bar -> D0 p anti-p pi- pi+, B0bar -> D*0 p anti-p pi-
pi+, B- -> D+ p anti-p pi- pi-, B- -> D*+ p anti-p pi- pi-) are first
observations. The branching fractions for 3- and 5-body decays are suppressed
compared to 4-body decays. Kinematic distributions for 3-body decays show
non-overlapping threshold enhancements in m(p anti-p) and m(D(*)0 p) in the
Dalitz plots. For 4-body decays, m(p pi-) mass projections show a narrow peak
with mass and full width of (1497.4 +- 3.0 +- 0.9) MeV/c2, and (47 +- 12 +- 4)
MeV/c2, respectively, where the first (second) errors are statistical
(systematic). For 5-body decays, mass projections are similar to phase space
expectations. All results are preliminary.Comment: 28 pages, 90 postscript figures, submitted to LP0
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A Search for Dark Higgs Bosons
Recent astrophysical and terrestrial experiments have motivated the proposal
of a dark sector with GeV-scale gauge boson force carriers and new Higgs
bosons. We present a search for a dark Higgs boson using 516 fb-1 of data
collected with the BABAR detector. We do not observe a significant signal and
we set 90% confidence level upper limits on the product of the Standard
Model-dark sector mixing angle and the dark sector coupling constant.Comment: 7 pages, 5 postscript figures, published version with improved plots
for b/w printin
Search for rare quark-annihilation decays, B --> Ds(*) Phi
We report on searches for B- --> Ds- Phi and B- --> Ds*- Phi. In the context
of the Standard Model, these decays are expected to be highly suppressed since
they proceed through annihilation of the b and u-bar quarks in the B- meson.
Our results are based on 234 million Upsilon(4S) --> B Bbar decays collected
with the BABAR detector at SLAC. We find no evidence for these decays, and we
set Bayesian 90% confidence level upper limits on the branching fractions BF(B-
--> Ds- Phi) Ds*- Phi)<1.2x10^(-5). These results
are consistent with Standard Model expectations.Comment: 8 pages, 3 postscript figues, submitted to Phys. Rev. D (Rapid
Communications
Evidence for the h_b(1P) meson in the decay Upsilon(3S) --> pi0 h_b(1P)
Using a sample of 122 million Upsilon(3S) events recorded with the BaBar
detector at the PEP-II asymmetric-energy e+e- collider at SLAC, we search for
the spin-singlet partner of the P-wave chi_{bJ}(1P) states in the
sequential decay Upsilon(3S) --> pi0 h_b(1P), h_b(1P) --> gamma eta_b(1S). We
observe an excess of events above background in the distribution of the recoil
mass against the pi0 at mass 9902 +/- 4(stat.) +/- 2(syst.) MeV/c^2. The width
of the observed signal is consistent with experimental resolution, and its
significance is 3.1sigma, including systematic uncertainties. We obtain the
value (4.3 +/- 1.1(stat.) +/- 0.9(syst.)) x 10^{-4} for the product branching
fraction BF(Upsilon(3S)-->pi0 h_b) x BF(h_b-->gamma eta_b).Comment: 8 pages, 4 postscript figures, submitted to Phys. Rev. D (Rapid
Communications
A Third Measure-Metastable State in the Dynamics of Spontaneous Shape Change in Healthy Human's White Cells
Human polymorphonuclear leucocytes, PMN, are highly motile cells with average 12-15 ”m diameters and prominent, loboid nuclei. They are produced in the bone marrow, are essential for host defense, and are the most populous of white blood cell types. PMN also participate in acute and chronic inflammatory processes, in the regulation of the immune response, in angiogenesis, and interact with tumors. To accommodate these varied functions, their behavior is adaptive, but still definable in terms of a set of behavioral states. PMN morphodynamics have generally involved a non-equilibrium stationary, spheroid Idling state that transitions to an activated, ellipsoid translocating state in response to chemical signals. These two behavioral shape-states, spheroid and ellipsoid, are generally recognized as making up the vocabulary of a healthy PMN. A third, ârandomâ state has occasionally been reported as associated with disease states. I have observed this third, Treadmilling state, in PMN from healthy subjects, the cells demonstrating metastable dynamical behaviors known to anticipate phase transitions in mathematical, physical, and biological systems. For this study, human PMN were microscopically imaged and analyzed as single living cells. I used a microscope with a novel high aperture, cardioid annular condenser with better than 100 nanometer resolution of simultaneous, mixed dark field and intrinsic fluorescent images to record shape changes in 189 living PMNs. Relative radial roundness, R(t), served as a computable order parameter. Comparison of R(t) series of 10 cells in the Idling and 10 in the Treadmilling state reveals the robustness of the ârandomâ appearing Treadmilling state, and the emergence of behaviors observed in the neighborhood of global state transitions, including increased correlation length and variance (divergence), sudden jumps, mixed phases, bimodality, power spectral scaling and temporal slowing. Wavelet transformation of an R(t) series of an Idling to Treadmilling state change, demonstrated behaviors concomitant with the observed transition
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