Identification of a Cross-reactive Epitope Widely Present in Lipopolysaccharide from Enterobacteria and Recognized by the Cross-protective Monoclonal Antibody WN1 222-5

Septic shock due to infections with Gram-negative bacteria is a severe disease with a high mortality rate. We report the identification of the antigenic determinants of an epitope that is present in enterobacterial lipopolysaccharide (LPS) and recognized by a cross-reactive monoclonal antibody (mAb WN1 222-5) regarded as a potential means of treatment. Using whole LPS and a panel of neoglycoconjugates containing purified LPS oligosaccharides obtained from Escherichia coli core types R1, R2, R3, and R4, Salmonella enterica, and the mutant strain E. coli J-5, we showed that mAb WN1 222-5 binds to the distal part of the inner core region and recognizes the structural element R1-alpha-d-Glcp-(1-->3)-[l-alpha-d-Hepp-(1-->7)]-l-alpha-d-Hepp 4P-(1-->3)-R2 (where R1 represents additional sugars of the outer core and R2 represents additional sugars of the inner core), which is common to LPS from all E. coli, Salmonella, and Shigella. WN1 222-5 binds poorly to molecules that lack the side chain heptose or lack phosphate at the branched heptose. Also molecules that are substituted with GlcpN at the side chain heptose are poorly bound. Thus, the side chain heptose and the 4-phosphate on the branched heptose are main determinants of the epitope. We have determined the binding kinetics and affinities (KD values) of the monovalent interaction of E. coli core oligosaccharides with WN1 222-5 by surface plasmon resonance and isothermal titration microcalorimetry. Affinity constants (KD values) determined by SPR were in the range of 3.6 x 10-5 to 3.2 x 10-8 m, with the highest affinity being observed for the core oligosaccharide from E. coli F576 (R2 core type) and the lowest KD values for those from E. coli J-5. Affinities of E. coli R1, R3, and R4 oligosaccharides were 5-10-fold lower, and values from the E. coli J-5 mutant were 29-fold lower than the R2 core oligosaccharide. Thus, the outer core sugars had a positive effect on binding

Gap modification of atomically thin boron nitride by phonon mediated interactions

A theory is presented for the modification of bandgaps in atomically thin boron nitride (BN) by attractive interactions mediated through phonons in a polarizable substrate, or in the BN plane. Gap equations are solved, and gap enhancements are found to range up to 70% for dimensionless electron-phonon coupling \lambda=1, indicating that a proportion of the measured BN bandgap may have a phonon origin

A dietary supplement to reduce side effects of oral isotretinoin therapy in acne patients.

AIM: The purpose of the study was to analyze the potential capacity of a dietary supplement, based on gamma linolenic acid, vitamin E, vitamin C, beta-carotene, coenzyme Q10 and Vitis Vitifera, to reduce side effects, in particular the dry skin, erythema and desquamation, due to treatment with oral isotretinoin, and evaluate the ability of the product to increase adherence to therapy in patients with acne. METHODS: Forty-eight patients with nodular acne (32 females and 16 males) were randomly divided into 2 groups: 24 receveid isotretinoin therapy (20-30 mg/day) for 6 months associated to dietary supplement (twice a day), while the other 24 patients received only isotretinoin (20-30 mg/day) for 6 months. For all patients the degree of acne severity, through GAGS (Global Acne Grading System), the sebum production by Sebutape, the hydration by Corneometer and the erythema by Mexameter, were measured. We have also evaluated the adherence to treatment, asking to patients how many days a week they follow the therapy. RERSULTS: Patients treated with dietary supplement had lower side effects, with a less degree of erythema and dryness, and greater degree of hydration; a greater adherence to therapy was also reported. CONCLUSION: Thanks to antioxidant and moisturizing properties, the dietary supplement containing gamma linolenic acid, vitamin E, vitamin C, betacarotene, coenzyme Q10 and Vitis Vitifera, can be considered a useful supplement in the treatment and prevention of dry skin associated with the use of oral isotretinoin

Evidence of silicene in honeycomb structures of silicon on Ag(111)

In the search for evidence of silicene, a two-dimensional honeycomb lattice of silicon, it is important to obtain a complete picture for the evolution of Si structures on Ag(111), which is believed to be the most suitable substrate for growth of silicene so far. In this work we report the finding and evolution of several monolayer superstructures of silicon on Ag(111) depending on the coverage and temperature. Combined with first-principles calculations, the detailed structures of these phases have been illuminated. These structure were found to share common building blocks of silicon rings, and they evolve from a fragment of silicene to a complete monolayer silicene and multilayer silicene. Our results elucidate how silicene formes on Ag(111) surface and provide methods to synthesize high-quality and large-scale silicene.Comment: 6 pages, 4 figure

Che-1 activates XIAP expression in response to DNA damage

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A New Family of Jumonji C Domain-Containing KDM Inhibitors Inspired by Natural Product Purpurogallin

Aberrant epigenetic modifications are involved in cancer development. Jumonji C domain-containing histone lysine demethylases (KDMs) are found mainly up-regulated in breast, prostate, and colon cancer. Currently, growing interest is focusing on the identification and development of new inhibitors able to block the activity of KDMs and thus reduce tumor progression. KDM4A is known to play a role in several cellular physiological processes, and was recently found overexpressed in a number of pathological states, including cancer. In this work, starting from the structure of purpurogallin 9aa, previously identified as a natural KDM4A inhibitor, we synthesized two main sets of compound derivatives in order to improve their inhibitory activity against KDM4A in vitro and in cells, as well as their antitumor action. Based on the hypothetical biogenesis of the 5-oxo-5H-benzo[7]annulene skeleton of the natural product purpurogallin (Salfeld, 1960; Horner et al., 1961; Dürckheimer and Paulus, 1985; Tanaka et al., 2002; Yanase et al., 2005) the pyrogallol and catechol units were first combined with structural modifications at different positions of the aryl ring using enzyme-mediated oxidative conditions, generating a series of benzotropolone analogs. Two of the synthetic analogs of purpurogallin, 9ac and 9bc, showed an efficient inhibition (50 and 80%) of KDM4A in enzymatic assays and in cells by increasing levels of its specific targets, H3K9me3/2 and H3K36me3. However, these two compounds/derivatives did not induce cell death. We then synthesized a further set of analogs of these two compounds with greater structural diversification. The most potent of these analogs, 9bf, displayed the highest KDM4A inhibitory enzymatic activity in vitro (IC50 of 10.1 and 24.37 μM) in colon cancer cells, and the strongest antitumor action in several solid and hematological human cancer cell lines with no toxic effect in normal cells. Our findings suggest that further development of this compound and its derivatives may lead to the identification of new therapeutic antitumor agents acting through inhibition of KDM4A

Application of Managing Cancer and Living Meaningfully (CALM) in Advanced Cancer Patients: An Italian Pilot Study.

Depression and anxiety occur in 25–30% of advanced cancer patients, as conditions arising from a final pathway of distress determined by the interaction of multiple factors. Within the psychotherapeutic intervention developed to address these conditions, Managing Cancer and Living Meaningfully (CALM) is an individual meaning and supportive-expressive intervention for patients with advanced cancer. In preliminary pilot studies,CALM was found to decrease depression and anxiety, and improve spirituality and attachment, while in a randomized clinical trial, CALM reduced depression and improved end-of-life preparation. We conducted a pilot study of CALM using a mixed method approach, in order to: (i) understand the possible application of CALM in a different cultural context (i.e., Italy) and examine the patients’ subjective perception of CALM; and (ii) preliminarily explore, as already done in other countries (i.e., Germany), the possible effects of CALM on a series of psychosocial outcomes