73 research outputs found
Disruption of the Cdc42/Par6/aPKC or Dlg/Scrib/Lgl polarity complex promotes epithelial proliferation via overlapping mechanisms
The establishment and maintenance of apical-basal polarity is a defining characteristic and essential feature of functioning epithelia. Apical-basal polarity (ABP) proteins are also tumor suppressors that are targeted for disruption by oncogenic viruses and are commonly mutated in human carcinomas. Disruption of these ABP proteins is an early event in cancer development that results in increased proliferation and epithelial disorganization through means not fully characterized. Using the proliferating Drosophila melanogaster wing disc epithelium, we demonstrate that disruption of the junctional vs. basal polarity complexes results in increased epithelial proliferation via distinct downstream signaling pathways. Disruption of the basal polarity complex results in JNK-dependent proliferation, while disruption of the junctional complex primarily results in p38-dependent proliferation. Surprisingly, the Rho-Rok-Myosin contractility apparatus appears to play opposite roles in the regulation of the proliferative phenotype based on which polarity complex is disrupted. In contrast, non-autonomous Tumor Necrosis Factor (TNF) signaling appears to suppress the proliferation that results from apical-basal polarity disruption, regardless of which complex is disrupted. Finally we demonstrate that disruption of the junctional polarity complex activates JNK via the Rho-Rok-Myosin contractility apparatus independent of the cortical actin regulator, Moesin
New results on solar neutrino fluxes from 192 days of Borexino data
We report the direct measurement of the ^7Be solar neutrino signal rate
performed with the Borexino detector at the Laboratori Nazionali del Gran
Sasso. The interaction rate of the 0.862 MeV ^7Be neutrinos is
49+-3(stat)+-4(syst) counts/(day * 100ton). The hypothesis of no oscillation
for ^7Be solar neutrinos is inconsistent with our measurement at the 4sigma
level. Our result is the first direct measurement of the survival probability
for solar nu_e in the transition region between matter-enhanced and
vacuum-driven oscillations. The measurement improves the experimental
determination of the flux of ^7Be, pp, and CNO solar nu_e, and the limit on the
magnetic moment of neutrinos
New limits on nucleon decays into invisible channels with the BOREXINO Counting Test Facility
The results of background measurements with the second version of the
BOREXINO Counting Test Facility (CTF-II), installed in the Gran Sasso
Underground Laboratory, were used to obtain limits on the instability of
nucleons, bounded in nuclei, for decays into invisible channels ():
disappearance, decays to neutrinos, etc. The approach consisted of a search for
decays of unstable nuclides resulting from and decays of parents
C, C and O nuclei in the liquid scintillator and the water
shield of the CTF. Due to the extremely low background and the large mass (4.2
ton) of the CTF detector, the most stringent (or competitive) up-to-date
experimental bounds have been established: y, y, y and y, all at 90% C.L.Comment: 22 pages, 3 figures,submitted to Phys.Lett.
The Borexino detector at the Laboratori Nazionali del Gran Sasso
Borexino, a large volume detector for low energy neutrino spectroscopy, is
currently running underground at the Laboratori Nazionali del Gran Sasso,
Italy. The main goal of the experiment is the real-time measurement of sub MeV
solar neutrinos, and particularly of the mono energetic (862 keV) Be7 electron
capture neutrinos, via neutrino-electron scattering in an ultra-pure liquid
scintillator. This paper is mostly devoted to the description of the detector
structure, the photomultipliers, the electronics, and the trigger and
calibration systems. The real performance of the detector, which always meets,
and sometimes exceeds, design expectations, is also shown. Some important
aspects of the Borexino project, i.e. the fluid handling plants, the
purification techniques and the filling procedures, are not covered in this
paper and are, or will be, published elsewhere (see Introduction and
Bibliography).Comment: 37 pages, 43 figures, to be submitted to NI
Study of neutrino electromagnetic properties with the prototype of the Borexino detector
Abstract The results of background measurements with the prototype of the Borexino detector (CTF) have been used to obtain an upper bound on the neutrino magnetic moment, µ ν . The new upper limit for µ ν from pp and 7 Be solar neutrinos is (5.5 × 10 −10 )µ B (90% c.l.) in the Standard Solar Model scenario. This is the first limit on µ ν obtained using sub-MeV neutrinos. The sensitivity of the prototype to the neutrino charge radius and the neutrino radiative decay are also presented
Genetic differentiation of Artemia franciscana (Kellogg, 1906) in Kenyan coastal saltworks
The nature of genetic divergence between the Artemia population native to San Francisco Bay, (SFB) USA and those from the introductions of SFB material in the Kenyan coast two decades ago were investigated using the mitochondrial DNA (mtDNA) and heat shock protein 70 (Hsp70) gene molecular markers. The DNA was extracted from 80 single Artemia cysts using the Chelex protocol. The 1,500 bp fragment of the 12S - 16S region of the mtDNA and a 1,935 bp fragment of the Hsp70 gene were amplified through Polymerase Chain Reaction (PCR) followed by Restriction Fragment Length Polymorphism (RFLP) digestion using appropriate endonucleases. The mtDNA analysis indicated higher haplotype diversity (0.76 ± 0.07) in Artemia from Fundisha saltworks while the rest of the samples were monomorphic. A private haplotype (AAABBA) in Fundisha samples confirmed a molecular evidence of a systematic genetic differentiation albeit in an insignificant manner (P > 0.05). There was molecular evidence of coexistence of SFB and GSL Artemia strains in Fundisha saltworks. The monomorphic DNA fingerprint in Kensalt Artemia cysts was probably caused by non-sequential Artemia culture system and limited mtDNA fragment size analysed. The Hsp70 gene RFLP fingerprint did not show any unique gene signatures in the Kenyan Artemia samples suggesting that other factors other than Hsp70 were involved in their superior thermotolerance. Further genetical studies based on the larger mtDNA fragment using robust genetic markers are recommended. Ecological studies of the heat shock protein family and the stress response would be more relevant than the qualitative RFLP technique
Economic consequences of investing in anti-HCV antiviral treatment from the Italian NHS perspective : a real-world-based analysis of PITER data
OBJECTIVE:
We estimated the cost consequence of Italian National Health System (NHS) investment in direct-acting antiviral (DAA) therapy according to hepatitis C virus (HCV) treatment access policies in Italy.
METHODS:
A multistate, 20-year time horizon Markov model of HCV liver disease progression was developed. Fibrosis stage, age and genotype distributions were derived from the Italian Platform for the Study of Viral Hepatitis Therapies (PITER) cohort. The treatment efficacy, disease progression probabilities and direct costs in each health state were obtained from the literature. The break-even point in time (BPT) was defined as the period of time required for the cumulative costs saved to recover the Italian NHS investment in DAA treatment. Three different PITER enrolment periods, which covered the full DAA access evolution in Italy, were considered.
RESULTS:
The disease stages of 2657 patients who consecutively underwent DAA therapy from January 2015 to December 2017 at 30 PITER clinical centres were standardized for 1000 patients. The investment in DAAs was considered to equal €25 million, €15 million, and €9 million in 2015, 2016, and 2017, respectively. For patients treated in 2015, the BPT was not achieved, because of the disease severity of the treated patients and high DAA prices. For 2016 and 2017, the estimated BPTs were 6.6 and 6.2 years, respectively. The total cost savings after 20 years were €50.13 and €55.50 million for 1000 patients treated in 2016 and 2017, respectively.
CONCLUSIONS:
This study may be a useful tool for public decision makers to understand how HCV clinical and epidemiological profiles influence the economic burden of HCV
L'Italia come modello per l'Europa e per il mondo nelle politiche sanitarie per il trattamento dell'epatite cronica da HCV
The World Health Organization foresees the
elimination of HCV infection by 2030. In light of this and the curre
nt, nearly worldwide, restriction in direct-acting agents
(DAA) accessibility due to their high price, we aimed to evaluate
the cost-effectiveness of two alternative DAA treatment
policies: Policy 1 (universal): treat all patients, regardless of the fibrosis stage; Policy 2 (prioritized): treat only priori
tized
patients and delay treatment of the
remaining patients until reaching stage F3. T
he model was based on patient’s data
from the PITER cohort. We demonstrated that extending HC
V treatment of patients in any fibrosis stage improves health
outcomes and is cost-effective
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