Regulation of NFKB through the nuclear processing of p105 (NFKB1) in Epstein-Barr Virus immortalized B cell lines.

Transcription factors of the NF-κB/Rel family are retained in the cytoplasm as inactive complexes through association with IκB inhibitory proteins. Several NF-κB activators induce the proteolysis of IκB proteins, which results in the nuclear translocation and DNA binding of NF-κB complexes. Here, we report a novel mechanism of NF-κB regulation mediated by p105 (NF-κB1) precursor of p50 directly at the nuclear level. In Epstein- Barr virus-immortalized B cells, p105 was found in the nucleus, where it was complexed with p65. In concomitance with NF-κB activation, mitomycin C induced the processing of p105 to p50 in the nucleus, while it did not affect the steady-state protein levels of IκBα and p105 in the cytoplasm. Differently, phorbol 12-myristate 13-acetate induced a significant proteolysis of both IκBα and p105 in the cytoplasm, while it did not affect the protein level of p105 in the nucleus. These results suggest that in Epstein-Barr virus-positive B cell lines the nuclear processing of p105 can contribute to NF-κB activation in response to specific signaling molecules, such as DNA-damaging agents

Abdominal pain and hypertension in the third trimester of pregnancy. Is pre-eclampsia the only explanation?

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Vitamin D deficiency: A new risk factor for type 2 diabetes?

Recent compelling evidence suggests a role of vitamin D deficiency in the pathogenesis of insulin resistance and insulin secretion derangements, with a consequent possible interference with type 2 diabetes mellitus. The mechanism of this link is incompletely understood. In fact, vitamin D deficiency is usually detected in obesity in which insulin resistance is also a common finding. The coexistence of insulin resistance and vitamin D deficiency has generated several hypotheses. Some cross-sectional and prospective studies have suggested that vitamin D deficiency may play a role in worsening insulin resistance; others have identified obesity as a risk factor predisposing individuals to exhibit both vitamin D deficiency and insulin resistance. The available data from intervention studies are largely confounded, and inadequate considerations of seasonal effects on 25(OH)D concentrations are also a common design flaw in many studies. On the contrary, there is strong evidence that obesity might cause both vitamin D deficiency and insulin resistance, leaving open the possibility that vitamin D and diabetes are not related at all. Although it might seem premature to draw firm conclusions on the role of vitamin D supplementation in reducing insulin resistance and preventing type 2 diabetes, this manuscript will review the circumstances leading to vitamin D deficiency and how such a deficiency can eventually independently affect insulin sensitivity. © 2012 S. Karger AG, Basel

Report of a case of discoid lupus erythematosus localised to the oral cavity: immunofluorescence findings.

Discoid Lupus Erythematosus (DLE) is a chronic disease with a typical cutaneous involvement. This pathology rarely involves mucosa: oral cavity is interested in 20% of DLE patients. We describe a case of oral DLE in a 50-year-old woman with an anamnesis for autoimmune disorders. This study shows the helpful role of immunofluorescence in the diagnosis of autoimmune diseases. The first diagnostic step was the clinical observation of the oral mucosa: the lesion area was erythematous, athrophic and hyperkeratotic. The patient then underwent laboratory examination. We utilized human epithelial cells (Hep-2010) for Indirect Immuno-Fluorescence (IIF). Moreover, the biopsy site for Direct Immuno-Fluorescence (DIF) and histopathological analysis was the untreated oral lesion. IIF detected an increase of Anti-Nuclear Antibody (ANA) and positivity for SSA-RO. By DIF, we observed IgG/IgA/fibrinogen along basal layer. Multiple biopsies reported signs of chronic basal damage. Steroid systemic therapy induced a considerable lesion regression. We suggest the use of immunofluorescence with the integration of further data to improve diagnosis of rare diseases and to establish a suitable therapy

Effect of Vitamin D Supplementation on Obesity-Induced Insulin Resistance: A Double-Blind, Randomized, Placebo-Controlled Trial

Objective: The aim was to investigate whether vitamin D supplementation, combined with a hypocaloric diet, could have an independent effect on insulin sensitivity in subjects with both overweight and hypovitaminosis D. Changes from baseline in anthropometric parameters, body composition, glucose tolerance, and insulin secretion were considered as secondary outcomes. Methods: Eighteen volunteers who were nondiabetic and vitamin D deficient and had BMI > 25 kg/m2 were randomized (1:1) in a double-blind manner to a hypocaloric diet + either oral cholecalciferol at 25,000 IU/wk or placebo for 3 months. Hyperinsulinemic-euglycemic clamp to measure insulin sensitivity was performed at baseline and after intervention. Results: Body weight in both groups decreased significantly (−7.5% in the vitamin D group and −10% in the placebo group; P < 0.05 for both), with no between-group differences. Serum 25-hydroxyvitamin D levels in the vitamin D group increased considerably (from 36.7 ± 13.2 nmol/L to 74.8 ± 18.7 nmol/L; P < 0.001). Insulin sensitivity in the vitamin D group improved (from 4.6 ± 2.0 to 6.9 ± 3.3 mg·kg−1·min−1; P < 0.001), whereas no changes were observed in the placebo group (from 4.9 ± 1.1 to 5.1 ± 0.3 mg·kg−1·min−1; P = 0.84). Conclusions: Cholecalciferol supplementation, combined with a weight loss program, significantly improves insulin sensitivity in healthy subjects with obesity and might represent a personalized approach for insulin-resistant subjects with obesity

Biliverdin Protects against Liver Ischemia Reperfusion Injury in Swine

Ischemia reperfusion injury (IRI) in organ transplantation remains a serious and unsolved problem. Organs that undergo significant damage during IRI, function less well immediately after reperfusion and tend to have more problems at later times when rejection can occur. Biliverdin has emerged as an agent that potently suppress IRI in rodent models. Since the use of biliverdin is being developed as a potential therapeutic modality for humans, we tested the efficacy for its effects on IRI of the liver in swine, an accepted and relevant pre-clinical animal model. Administration of biliverdin resulted in rapid appearance of bilirubin in the serum and significantly suppressed IRI-induced liver dysfunction as measured by multiple parameters including urea and ammonia clearance, neutrophil infiltration and tissue histopathology including hepatocyte cell death. Taken together, our findings, in a large animal model, provide strong support for the continued evaluation of biliverdin as a potential therapeutic in the clinical setting of transplantation of the liver and perhaps other organs

Substrate-based atom waveguide using guided two-color evanescent light fields

We propose a dipole-force linear waveguide which confines neutral atoms up to lambda/2 above a microfabricated single-mode dielectric optical guide. The optical guide carries far blue-detuned light in the horizontally-polarized TE mode and far red-detuned light in the vertically-polarized TM mode, with both modes close to optical cut-off. A trapping minimum in the transverse plane is formed above the optical guide due to the differing evanescent decay lengths of the two modes. This design allows manufacture of mechanically stable atom-optical elements on a substrate. We calculate the full vector bound modes for an arbitrary guide shape using two-dimensional non-uniform finite elements in the frequency-domain, allowing us to optimize atom waveguide properties. We find that a rectangular optical guide of 0.8um by 0.2um carrying 6mW of total laser power (detuning +-15nm about the D2 line) gives a trap depth of 200uK for cesium atoms (m_F = 0), transverse oscillation frequencies of f_x = 40kHz and f_y = 160kHz, collection area ~ 1um^2 and coherence time of 9ms. We discuss the effects of non-zero m_F, surface interactions, heating rate, the substrate refractive index, and the limits on waveguide bending radius.Comment: 12 pages, 4 figures, revtex, submitted to Phys. Rev. A Replaced: final version accepted by PRA v.61 Feb 2000. (2 paragraphs added

Intra-islet insulin synthesis defects are associated with endoplasmic reticulum stress and loss of beta cell identity in human diabetes

Aims/hypothesis: Endoplasmic reticulum (ER) stress and beta cell dedifferentiation both play leading roles in impaired insulin secretion in overt type 2 diabetes. Whether and how these factors are related in the natural history of the disease remains, however, unclear. Methods: In this study, we analysed pancreas biopsies from a cohort of metabolically characterised living donors to identify defects in in situ insulin synthesis and intra-islet expression of ER stress and beta cell phenotype markers. Results: We provide evidence that in situ altered insulin processing is closely connected to in vivo worsening of beta cell function. Further, activation of ER stress genes reflects the alteration of insulin processing in situ. Using a combination of 17 different markers, we characterised individual pancreatic islets from normal glucose tolerant, impaired glucose tolerant and type 2 diabetic participants and reconstructed disease progression. Conclusions/interpretation: Our study suggests that increased beta cell workload is accompanied by a progressive increase in ER stress with defects in insulin synthesis and loss of beta cell identity. Graphical abstract: [Figure not available: see fulltext.

Understanding the Role of Designed Solid Acid Sites in the Low-Temperature Production of ϵ-Caprolactam

Modern society is placing increasing demands on commodity chemicals, driven by the ever‐growing global population and the desire for improved standards of living. As the polymer industry grows, a sustainable route to ϵ‐caprolactam, the precursor to the recyclable nylon‐6 polymer, is becoming increasingly important. To this end, we have designed and characterized a recyclable SAPO catalyst using a range of characterization techniques, to achieve near quantitative yields of ϵ‐caprolactam from cyclohexanone oxime. The catalytic process operates under significantly less energetically demanding conditions than other widely practiced industrial processes

Study of the internal quantum efficiency of FBK sensors with optimized entrance windows

Single-photon detection of X-rays in the energy range of 250 eV to 1 keV is difficult for hybrid detectors because of the low quantum efficiency and low signal-to-noise ratio. The low quantum efficiency is caused by the absorption of soft X-rays in the entrance window of the silicon sensors. The entrance window consists of an insensitive layer on the surface and a highly doped layer, which is typically from a few hundred nanometers to a couple of micrometers thick and is comparable to the absorption depth of soft X-ray photons (e.g. the attenuation length of 250 eV X-ray photons is ∼100 nm in silicon). The low signal-to-noise ratio is mainly caused by the small signal amplitude (e.g. ca. 70 electrons for 250 eV X-ray photons in silicon) with respect to the electronic noise. To improve the quantum efficiency, the entrance window must be optimized by minimizing the absorption of soft X-rays in the insensitive layer, and reducing charge recombination at the Si-SiO2 interface and in the highly doped region. Low gain avalanche diodes (LGADs) with a multiplication factor between 5 and 10 increase the signal amplitude and therefore improve the signal-to-noise ratio for soft X-rays, enabling single-photon detection down to 250 eV. Combining LGAD technology with an optimized entrance window technology can thus allow hybrid detectors to become a useful tool also for soft X-ray detection. In this work we present the optimization of the entrance window by studying the internal quantum efficiency of eight different process technology variations. The sensors are characterized using light emitting diodes with a wavelength of 405 nm. At this wavelength, the light has an absorption depth of 125 nm, equivalent to that of 276 eV X-rays. The best variation achieves an internal quantum efficiency of 0.992 for 405 nm UV light. Based on this study, further optimization of the quantum efficiency for soft X-rays detection is planned