1,717 research outputs found
NEMO regulates a cell death switch in TNF signaling by inhibiting recruitment of RIPK3 to the cell death-inducing complex II
Incontinentia Pigmenti (IP) is a rare X-linked disease characterized by early male lethality and multiple abnormalities in heterozygous females. IP is caused by NF-ÎșB essential modulator (NEMO) mutations. The current mechanistic model suggests that NEMO functions as a crucial component mediating the recruitment of the IÎșB-kinase (IKK) complex to tumor necrosis factor receptor 1 (TNF-R1), thus allowing activation of the pro-survival NF-ÎșB response. However, recent studies have suggested that gene activation and cell death inhibition are two independent activities of NEMO. Here we describe that cells expressing the IP-associated NEMO-A323P mutant had completely abrogated TNF-induced NF-ÎșB activation, but retained partial antiapoptotic activity and exhibited high sensitivity to death by necroptosis. We found that robust caspase activation in NEMO-deficient cells is concomitant with RIPK3 recruitment to the apoptosis-mediating complex. In contrast, cells expressing the ubiquitin-binding mutant NEMO-A323P did not recruit RIPK3 to complex II, an event that prevented caspase activation. Hence NEMO, independently from NF-ÎșB activation, represents per se a key component in the structural and functional dynamics of the different TNF-R1-induced complexes. Alteration of this process may result in differing cellular outcomes and, consequently, also pathological effects in IP patients with different NEMO mutations
A Geological Itinerary Through the Southern Apennine Thrust-Belt (BasilicataâSouthern Italy)
Open access via Springer Compact AgreementPeer reviewedPublisher PD
Serological markers for prediction of response to anti-tumor necrosis factor treatment in Crohn's disease
peer reviewedOBJECTIVES: The use of monoclonal anti-tumor necrosis factor (TNF) antibodies (infliximab, Remicade) is a new therapeutic approach for severe refractory luminal or fistulizing, Crohn's disease (CD). However, up to 30% of patients do not respond to this treatment. So far, no parameters predictive of response to anti-TNT have been identified. Our aim was to determine whether serological markers ASCA (anti-Saccharomyces cerevisiae antibodies) or pANCA (perinuclear antineutrophil cytoplasmic antibodies) could identify Crohn's patients likely to benefit from anti-TNF therapy. METHODS: Serum samples of 279 CID patients were analyzed for ASCA and pANCA before anti-TNF therapy. A blinded physician determined clinical response at week 4 (refractory luminal CD) or week 10 (fistulizing CD) after the first infusion of infliximab (5 mg/kg). RESULTS: Overall, there was no relationship between ASCA or pANCA and response to therapy. However, lower response rates were observed for patients with refractory intestinal disease carrying the pANCA+/ASCA- combination, although this lacked significance (p = 0.067). CONCLUSIONS: In this cohort of infliximab-treated patients, neither ASCA nor pANCA could predict response to treatment. However, the combination pANCA+/ASCA- might warrant further investigation for its value in predicting nonresponse in patients with refractory luminal disease
Comparison of Different Methods of Automated Landform Classification at the Drainage Basin Scale: Examples from the Southern Italy
In this work, we tested the reliability of two different methods of
automated landform classification (ACL) in three geological domains of the
southern Italian chain with contrasting morphological features. ACL maps
deriving from the TPI-based (topographic position index) algorithm are strictly
dependent to the search input parameters and they are not able to fully capture
landforms of different size. Geomorphons-based classification has shown a
higher potential and can represent a powerful method of ACL, although it
should be improved with the introduction of additional DEM-based parameters
for the extraction of landform classe
Tools for Semi-automated Landform Classification: A Comparison in the Basilicata Region (Southern Italy)
Recent advances in spatial methods of digital elevation model
(DEMs) analysis have addressed many research topics on the assessment of
morphometric parameters of the landscape. Development of computer algorithms for calculating the geomorphometric properties of the Earthâs surface has
allowed for expanding of some methods in the semi-automatic recognition and
classification of landscape features. In such a way, several papers have been
produced, documenting the applicability of the landform classification based on
map algebra. The Topographic Position Index (TPI) is one of the most widely
used parameters for semi-automated landform classification using GIS software.
The aim was to apply the TPI classes for landform classification in the Basilicata
Region (Southern Italy). The Basilicata Region is characterized by an extremely
heterogeneous landscape and geological features. The automated landform
extraction, starting from two different resolution DEMs at 20 and 5 m-grids, has
been carried out by using three different GIS software: Arcview, Arcmap, and
SAGA. Comparison of the landform maps resulting from each software at a
different scale has been realized, furnishing at the end the best landform map and
consequently a discussion over which is the best software implementation of the
TPI method
Measurement of the CKM angle Îł from a combination of B±âDh± analyses
A combination of three LHCb measurements of the CKM angle Îł is presented. The decays B±âD K± and
B±âDϱ are used, where D denotes an admixture of D0 and D0 mesons, decaying into K+Kâ, Ï+Ïâ, K±Ïâ, K±ÏâϱÏâ, K0SÏ+Ïâ, or K0S K+Kâ ïŹnal states. All measurements use a dataset corresponding to 1.0 fbâ1 of integrated luminosity. Combining results from B±âD K± decays alone a best-ïŹt value of
Îł =72.0⊠is found, and conïŹdence intervals are set
Îł â [56.4,86.7]⊠at 68% CL,
Îł â [42.6,99.6]⊠at 95% CL.
The best-ïŹt value of Îł found from a combination of results from B±âDϱ decays alone, is Îł =18.9âŠ,
and the conïŹdence intervals
Îł â [7.4,99.2]⊠âȘ [167.9,176.4]⊠at 68% CL
are set, without constraint at 95% CL. The combination of results from B± â D K± and B± â Dϱ
decays gives a best-ïŹt value of Îł =72.6⊠and the conïŹdence intervals
Îł â [55.4,82.3]⊠at 68% CL,
Îł â [40.2,92.7]⊠at 95% CL
are set. All values are expressed modulo 180âŠ, and are obtained taking into account the effect of D0âD0
mixing
Measurement of the relative rate of prompt Ïc0, Ïc1 and Ïc2 production at âs=7TeV
Prompt production of charmonium Ïc0, Ïc1 and Ïc2 mesons is studied using proton-proton collisions at the LHC at a centre-of-mass energy of âs=7TeV. The Ïc mesons are identified through their decay to J/ÏÎł, with J/ÏâÎŒ+muâ using photons that converted in the detector. A data sample, corresponding to an integrated luminosity of 1.0fbâ1 collected by the LHCb detector, is used to measure the relative prompt production rate of Ïc1 and Ïc2 in the rapidity range 2.0<y<4.5 as a function of the J/Ï transverse momentum from 3 to 20 GeV/c. First evidence for Ïc0 meson production at a hadron collider is also presented
Study of B0(s)âK0Sh+hâČâ decays with first observation of B0sâK0SK±Ïâ and B0sâK0SÏ+Ïâ
A search for charmless three-body decays of B 0 and B0s mesons with a K0S meson in the final state is performed using the pp collision data, corresponding to an integrated luminosity of 1.0 fbâ1, collected at a centre-of-mass energy of 7 TeV recorded by the LHCb experiment. Branching fractions of the B0(s)âK0Sh+hâČâ decay modes (h (âČ) = Ï, K), relative to the well measured B0âK0SÏ+Ïâ decay, are obtained. First observation of the decay modes B0sâK0SK±Ïâ and B0sâK0SÏ+Ïâ and confirmation of the decay B0âK0SK±Ïâ are reported. The following relative branching fraction measurements or limits are obtained B(B0âK0SK±Ïâ)B(B0âK0SÏ+Ïâ)=0.128±0.017(stat.)±0.009(syst.), B(B0âK0SK+Kâ)B(B0âK0SÏ+Ïâ)=0.385±0.031(stat.)±0.023(syst.), B(B0sâK0SÏ+Ïâ)B(B0âK0SÏ+Ïâ)=0.29±0.06(stat.)±0.03(syst.)±0.02(fs/fd), B(B0sâK0SK±Ïâ)B(B0âK0SÏ+Ïâ)=1.48±0.12(stat.)±0.08(syst.)±0.12(fs/fd)B(B0sâK0SK+Kâ)B(B0âK0SÏ+Ïâ)â[0.004;0.068]at90%CL
Model-independent search for CP violation in D0âKâK+ÏâÏ+ and D0âÏâÏ+Ï+Ïâ decays
A search for CP violation in the phase-space structures of D0 and View the MathML source decays to the final states KâK+ÏâÏ+ and ÏâÏ+Ï+Ïâ is presented. The search is carried out with a data set corresponding to an integrated luminosity of 1.0 fbâ1 collected in 2011 by the LHCb experiment in pp collisions at a centre-of-mass energy of 7 TeV. For the KâK+ÏâÏ+ final state, the four-body phase space is divided into 32 bins, each bin with approximately 1800 decays. The p-value under the hypothesis of no CP violation is 9.1%, and in no bin is a CP asymmetry greater than 6.5% observed. The phase space of the ÏâÏ+Ï+Ïâ final state is partitioned into 128 bins, each bin with approximately 2500 decays. The p-value under the hypothesis of no CP violation is 41%, and in no bin is a CP asymmetry greater than 5.5% observed. All results are consistent with the hypothesis of no CP violation at the current sensitivity
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