RelA/NF-kappaB recruitment on the bax gene promoter antagonizes p73-dependent apoptosis in costimulated T cells

The balance between antiapoptotic and proapoptotic proteins of the Bcl-2 family is critical in determining the fate of T cells in response to death stimuli. Proapoptotic genes, such as bax, are generally regulated by the p53 family of transcription factors, whereas NF-kappaB subunits can activate the transcription of antiapoptotic Bcl-2 members. Here, we show that CD28 activation protects memory T cells from irradiation-induced apoptosis by both upregulating bcl-xL and inhibiting bax gene expression. We found that p73, but not p53, binds to and trans-activates the bax gene promoter in irradiated T cells. The activation of RelA/NF-kappaB subunit in CD28 costimulated T cells and its binding onto the bax gene promoter results in suppression of bax transcription and decrease in both p73 and RNA polymerase II recruitment in vivo. RelA recruitment on the bax gene promoter is also accompanied by the lost of p300 binding and the parallel appearance of histone deacetylase-1-containing complexes. These findings identify RelA/NF-kappaB as a critical regulator of T-cell survival by affecting the balance of Bcl-2 family members

Krill oil, vitamin D and Lactobacillus reuteri cooperate to reduce gut inflammation

Current research into original therapies to treat intestinal inflammation is focusing on no-drug therapies. KLD is a mixture of krill oil (KO), probiotic Lactobacillus reuteri (LR), and vitamin D (VitD3). The aim of this study was to assess in vitro and in vivo the potential cooperative effects of KLD in reducing gut inflammation. Colorectal adenocarcinoma cell lines, CACO2 and HT29, and C57BL/6 mice were used for in vitro and in vivo analyses, respectively. Cells were exposed to cytomix (interferon gamma + tumour necrosis factor alpha (TNF-a)) to induce inflammation or co-exposed to cytomix and KO, LR and VitD3 alone or to cytomix and KLD. Animals were treated for 7 days with dextran sodium sulphate (DSS) to induce colitis or with DSS and KLD. In vitro assays: F-actin expression was analysed by immunofluorescence; scratch test and trans-epithelial electric resistance test were performed to measure wound healing; adhesion/invasion assays of adhesive and invasive Escherichia coli (AIEC) bacteria were made; mRNA expression of TNF-α, interleukin (IL)-8 and vitamin D receptor (VDR) was detected by quantitative PCR. In vivo assays: body weight, clinical score, histological score and large intestine weight and length were estimated; mRNA expression of TNF-α, IL-1ß, IL-6, IL-10 by quantitative PCR; VDR expression was detected by quantitative PCR and immunohistochemistry. In vitro: KLD restores epithelial cell-cell adhesion and mucosal healing during inflammation, while decreases the adhesiveness and invasiveness of AIEC bacteria and TNF-α and IL-8 mRNA expression and increases VDR expression. In vivo: KLD significantly improves body weight, clinical score, histological score and large intestine length of mice with DSS-induced colitis and reduces TNF-α, IL-1ß and IL-6 mRNA levels, while increases IL-10 mRNA and VDR levels. KLD has significant effects on the intestinal mucosa, strongly decreasing inflammation, increasing epithelial restitution and reducing pathogenicity of harmful commensal bacteria

Prospects for the Search for a Standard Model Higgs Boson in ATLAS using Vector Boson Fusion

The potential for the discovery of a Standard Model Higgs boson in the mass range m_H < 2 m_Z in the vector boson fusion mode has been studied for the ATLAS experiment at the LHC. The characteristic signatures of additional jets in the forward regions of the detector and of low jet activity in the central region allow for an efficient background rejection. Analyses for the H -> WW and H -> tau tau decay modes have been performed using a realistic simulation of the expected detector performance. The results obtained demonstrate the large discovery potential in the H -> WW decay channel and the sensitivity to Higgs boson decays into tau-pairs in the low-mass region around 120 GeV.Comment: 20 pages, 13 ps figures, uses EPJ style fil

Nanocarriers for neuromuscular diseases

Overview of the results obtained so far in the frame of a research on suitable nanocarriers for treating myotonic dystroph

p53-Mediated downregulation of H ferritin promoter transcriptional efficiency via NF-Y

The tumor suppressor protein p53 triggers many of the cellular responses to DNA damage by regulating the transcription of a series of downstream target genes. p53 acts on the promoter of the target genes by interacting with the trimeric transcription factor NF-Y. H ferritin promoter activity is tightly dependent on a multiprotein complex called Bbf; on this complex NF-Y plays a major role. The aim of this work was to study the modulation of H ferritin expression levels by p53. CAT reporter assays indicate that: (i) p53 overexpression strongly downregulates the transcriptional efficiency driven by an H ferritin promoter construct containing only the NF-Y recognition sequence and that the phenomenon is reverted by p53 siRNA; (ii) the p53 C-terminal region is sufficient to elicitate this regulation and that a correct C-terminal acetylation is also required. The H ferritin promoter displays no p53-binding sites; chromatin immunoprecipitation assays indicate that p53 is recruited on this promoter by NF-Y. The p53–NF-Y interaction does not alter the NF-Y DNA-binding ability as indicated by electrophoretic mobility shift assay (EMSA) analysis. These results demonstrate that the gene coding for the H ferritin protein belongs to the family of p53-regulated genes, therefore adding a new level of complexity to the regulation of the H ferritin transcription and delineate a role for this protein in a series of cellular events triggered by p53 activation

A GaN MMIC stacked doherty power amplifier for space applications

This paper presents the design and the experimental results of a Monolithic Microwave Integrated Circuit Power Am-plifier in which the transistor-stacking approach is used within the Doherty architecture in order to maximize the achievable performance. In particular, the Stacked cell is realized by dividing the common source transistor in two smaller devices leading to a very compact and symmetric structure, whereas the Doherty approach is exploited to fulfil high efficiency at back-off. The chip has been manufactured on a 100 nm gate length GaN high electron mobility technology, growth on Silicon substrate and targeting the satellite downlink Ka-band. The two-stage amplifier was designed to meet the power requirements while satisfying the thermal constraints for use in space applications. In the frequency range from 17.3 GHz to 20.3 GHz, measurement results have shown a linear gain of about 25 dB with a peak power of 38dBm and a power added efficiency larger than 35%

Efficacy of the treatment of developmental language disorder: A systematic review

Background. Language disorder is the most frequent developmental disorder in childhood and it has a significant negative impact on children’s development. The goal of the present review was to systematically analyze the effectiveness of interventions in children with developmental language disorder (DLD) from an evidence-based perspective. Methods. We considered systematic reviews, meta-analyses of randomized controlled trials (RCTs), control group cohort studies on any type of intervention aimed at improving children’s skills in the phono-articulatory, phonological, semantic-lexical, and morpho-syntactic fields in preschool and primary school children (up to eight years of age) that were diagnosed with DLD.We identified 27 full-length studies, 26 RCT and one review. Results. Early intensive intervention in three- and four-year-old children has a positive effect on phonological expressive and receptive skills and acquisitions are maintained in the medium term. Less evidence is available on the treatment of expressive vocabulary (and no evidence on receptive vocabulary). Intervention on morphological and syntactic skills has effective results on expressive (but not receptive) skills; however, a number of inconsistent results have also been reported. Only one study reports a positive effect of treatment on inferential narrative skills. Limited evidence is also available on the treatment of meta-phonological skills. More studies investigated the effectiveness of interventions on general language skills, which now appears as a promising area of investigation, even though results are not all consistent. Conclusions. The effectiveness of interventions over expressive and receptive phonological skills, morpho-syntactic skills, as well as inferential skills in narrative context underscores the importance that these trainings be implemented in children with DLD

The Higgs Working Group: Summary Report (2001)

Report of the Higgs working group for the Workshop `Physics at TeV Colliders', Les Houches, France, 21 May - 1 June 2001. It contains 7 separate sections: A. Theoretical Developments B. Higgs Searches at the Tevatron C. Experimental Observation of an invisible Higgs Boson at LHC D. Search for the Standard Model Higgs Boson using Vector Boson Fusion at the LHC E. Study of the MSSM channel $A/H \to \tau \tau$ at the LHC F. Searching for Higgs Bosons in $t\bar t H$ Production G. Studies of Charged Higgs Boson Signals for the Tevatron and the LHCComment: 120 pages, latex, many figures, proceedings of the Workshop `Physics at TeV Colliders', Les Houches, France, 21 May - 1 June 2001, full Author list included in paper. Typos corrected, author list and acknowledgements completed. Convernors: D. Cavalli, A. Djouadi, K. Jakobs, A. Nikitenko, M. Spira, C.E.M. Wagner, W.-M. Ya

The Dietary Intake of Polyphenols Is Associated with a Lower Risk of Severe Lumbar Spinal Stenosis: A Case-Control Analysis from the PREFACE Study

Polyphenols are naturally occurring compounds endowed with antioxidant and anti-inflammatory properties. We sought to examine the association of dietary polyphenols with the risk of severe lumbar spinal stenosis (LSS), a condition possibly characterized by a high inflammatory component. A case-control study included 156 patients with LSS and indication to surgery and 312 controls, matched (1:2) for sex, age (±6 months), and physical activity. The polyphenol intake was calculated by matching food consumption data from a 188-item food frequency questionnaire with the Phenol-Explorer database regarding the polyphenol content of each reported food. In a multivariable-adjusted logistic regression analysis including lifestyles, sociodemographic factors, and the Mediterranean Diet Score, a 1-standard deviation (SD) increase in dietary polyphenols intake was associated with lower odds of LSS (Odds ratio [OR] = 0.65; 95% CI: 0.47–0.89). Analyses of different polyphenol classes showed that a per 1-SD in the consumption of flavonoids and stilbenes was related to lower LSS risk (OR = 0.57; 95% CI: 0.42–0.78; OR = 0.40; 95% CI: 0.27–0.61, respectively). Further adjustment for the total dietary antioxidant capacity did not modify the strength of these associations. A diet rich in polyphenols is independently associated with a lower risk of severe LSS, possibly through mechanisms that include the anti-inflammatory potential of these bioactive compounds

Prenatal muscle development in a mouse model for the secondary dystroglycanopathies

The defective glycosylation of α-dystroglycan is associated with a group of muscular dystrophies that are collectively referred to as the secondary dystroglycanopathies. Mutations in the gene encoding fukutin-related protein (FKRP) are one of the most common causes of secondary dystroglycanopathy in the UK and are associated with a wide spectrum of disease. Whilst central nervous system involvement has a prenatal onset, no studies have addressed prenatal muscle development in any of the mouse models for this group of diseases. In view of the pivotal role of α-dystroglycan in early basement membrane formation, we sought to determine if the muscle formation was altered in a mouse model of FKRP-related dystrophy