MucR binds multiple target sites in the promoter of its own gene and is a heat-stable protein: Is MucR a H-NS-like protein?

The protein MucR from Brucella spp. is involved in the expression regulation of genes necessary for host interaction and infection. MucR is a member of the Ros/MucR family, which comprises prokaryotic zinc-finger proteins and includes Ros from Agrobacterium tumefaciens and the Ml proteins from Mesorhizobium loti. MucR from Brucella spp. can regulate the expression of virulence genes and repress its own gene expression. Despite the well-known role played by MucR in the repression of its own gene, no target sequence has yet been identified in the mucR promoter gene. In this study, we provide the first evidence that MucR from Brucella abortus binds more than one target site in the promoter region of its own gene, suggesting a molecular mechanism by which this protein represses its own expression. Furthermore, a circular dichroism analysis reveals that MucR is a heat-stable protein. Overall, the results of this study suggest that MucR might resemble a H-NS protein

Does mild COPD affect prognosis in the elderly?

<p>Abstract</p> <p>Background</p> <p>Chronic obstructive pulmonary disease (COPD) affects independence and survival in the general population, but it is unknown to which extent this conclusion applies to elderly people with mild disease. The aim of this study was to verify whether mild COPD, defined according to different classification systems (ATS/ERS, BTS, GOLD) impacts independence and survival in elderly (aged 65 to 74 years) or very elderly (aged 75 years or older) patients.</p> <p>Methods</p> <p>We used data coming from the Respiratory Health in the Elderly (Salute Respiratoria nell'Anziano, SaRA) study and compared the differences between the classification systems with regards to personal capabilities and 5-years survival, focusing on the mild stage of COPD.</p> <p>Results</p> <p>We analyzed data from 1,159 patients (49% women) with a mean age of 73.2 years (SD: 6.1). One third of participants were 75 years or older. Mild COPD, whichever was its definition, was not associated with worse personal capabilities or increased mortality after adjustment for potential confounders in both age groups.</p> <p>Conclusions</p> <p>Mild COPD may not affect survival or personal independence of patients over 65 years of age if the reference group consists of patients with a comparable burden of non respiratory diseases. Comorbidity and age itself likely are main determinants of both outcomes.</p

HPV and Cytology Testing in Women Undergoing 9-Valent HPV Opportunistic Vaccination: A Single-Cohort Follow Up Study

Background: This study evaluates the possible effect of 9-valent (9vHPV) vaccination on the results of HPV and cytological tests in a cohort of adult women. Methods: This study is a retrospective, single-cohort, monocentric study. Sexually active women aged 14–70 years, who underwent 9vHPV vaccination, were enrolled. Dose administration dates, side effects and data on Pap smears and HPV tests performed before and after the first vaccine dose were collected. Subjects were considered “unexposed” to the vaccine for all time intervals before the first dose administration, and “exposed” to the first, second and third vaccine doses in all time intervals following each specific dose. Results: A total of 512 women underwent the first 9vHPV dose administration and were enrolled in the study. Median age at vaccination was 30.5 (14–70). Log-rank tests and Cox regression analyses showed a highly statistically significant (p Conclusions: 9vHPV vaccination may play a role in shortening the clearance time of HPV HR+ or Pap positivity in sexually active adult women

Genetic and epigenetic mutations affect the DNA binding capability of human ZFP57 in transient neonatal diabetes type 1

AbstractIn the mouse, ZFP57 contains three classical Cys2His2 zinc finger domains (ZF) and recognizes the methylated TGCmetCGC target sequence using the first and the second ZFs. In this study, we demonstrate that the human ZFP57 (hZFP57) containing six Cys2His2 ZFs, binds the same methylated sequence through the third and the fourth ZFs, and identify the aminoacids critical for DNA interaction. In addition, we present evidences indicating that hZFP57 mutations and hypomethylation of the TNDM1 ICR both associated with Transient Neonatal Diabetes Mellitus type 1 result in loss of hZFP57 binding to the TNDM1 locus, likely causing PLAGL1 activation

Discriminative and predictive properties of disease-specific and generic health status indexes in elderly COPD patients

<p>Abstract</p> <p>Background</p> <p>The association between bronchial obstruction severity and mortality in Chronic Obstructive Pulmonary Disease (COPD) is well established, but it is unknown whether disease-specific health status measures and multidimensional assessment (MDA) have comparable prognostic value.</p> <p>Methods</p> <p>We analyzed data coming from the Salute Respiratoria nell'Anziano (Respiratory Health in the Elderly – SaRA) study, enrolling elderly people attending outpatient clinics for respiratory and non-respiratory problems. From this population we selected 449 patients with bronchial obstruction (77.3% men, mean age 73.1). We classified patients' health status using tertiles of the Saint George Respiratory Questionnaire (SGRQ) and a MDA including functional (the 6' walking test, WT), cognitive (Mini-Mental State Examination, MMSE) and affective status (Geriatric Depression Scale, GDS). The agreement of the classification methods was calculated using the kappa statistic, and survival associated with group membership was evaluated using survival analysis.</p> <p>Results</p> <p>Pulmonary function, expressed by the FEV1, worsened with increasing SGRQ or MDA scores. Cognitive function was not associated with the SGRQ, while physical performance and mood status were impaired only in the highest tertile of SGRQ. A poor agreement was found between the two classification systems tested (k = 0.194). Compared to people in the first tertile of SGRQ score, those in the second tertile had a sex-adjusted HR of 1.22 (0.75 – 1.98) and those in the third tertile of 2.90 (1.92 – 4.40). The corresponding figures of the MDA were 1.49 (95% CI 1.02 – 2.18) and 2.01 (95% CI: 1.31 – 3.08). After adjustment for severity of obstruction, only a SGRQ in the upper tertile was associated with mortality (HR: 1.86; 95% CI: 1.14 – 3.02).</p> <p>Conclusion</p> <p>In elderly outpatients with mild-moderate COPD, a disease-specific health status index seems to be a better predictor of death compared to a MDA.</p

An integrated computational protocol for the accurate prediction of EPR and PNMR parameters of aminoxyl radicals in solution

Magnetic spectroscopic techniques such as electron paramagnetic resonance (EPR) and paramagnetic NMR (PNMR) are valuable tools for understanding the structure and dynamics of complex systems such as, for example, biomolecules or nanomaterials labeled with suitable free radicals. Unfortunately, such spectra do not give direct access to the radical structure because of the subtle interplay between several different effects not easily separable and evaluable by experimentalists alone. In this respect, computational spectroscopy is becoming an essential and versatile tool for the assignment and interpretation of experimental spectra. In this article, the new integrated computational approaches developed in the recent years in our research group are reviewed. Such approaches have been applied to two widely used spin probes showing that proper account of stereo-electronic, environmental and dynamical effects leads to magnetic properties in remarkable agreement with experimental results. Copyright (C) 2010 John Wiley & Sons, Ltd

Models of Aged Magnesium\u2013Silicate\u2013Hydrate Cements Based on the Lizardite and Talc Crystals: A Periodic DFT-GIPAW Investigation

Classical MD simulations and periodic DFT-GIPAW calculations have been employed to investigate possible structural models of aged magnesium 12silicate 12hydrate (M 12S 12H) cements. Four models were built, two based, respectively, on the lizardite Mg3Si2O5(OH)4 and talc Mg3Si4O10(OH)2 crystals in which we have modified the Mg/Si ratio and distribution of Qn silicon species (n is the number of bridging oxygens for each quaternary silicon atom) according to previous experimental evidence. The other two models were still based on the lizardite and talc crystals, but the original Mg/Si ratios were retained. The latter two models were used to simulate MSH binders containing different proportions of talc- and lizardite-based amorphous phases as proposed in several experimental works. From these initial models, additional structures were generated by adding increasing amounts of water molecules to investigate its effect on the structure and on the 29Si and 25Mg MAS NMR spectra. Our results demonstrate that MSH phases with an Mg/Si ratio close to 1 can be described as a defective talc-based model or as the combination of talc and lizardite amorphous models with the former being the dominant phase. In both cases, the hydrated models provide the best agreement with NMR experiments

Extension of the AMBER force field to cyclic alpha,alpha dialkylated peptides

The popular biomolecular AMBER (ff99SB) force field (FF) has been extended with new parameters for the simulations of peptides containing alpha, alpha dialkylated residues with cyclic side chains. Together with the recent set of nitroxide parameters [E. Stendardo, A. Pedone, P. Cimino, M. C. Menziani, O. Crescenzi and V. Barone, Phys. Chem. Chem. Phys., 2010, 12, 11697] this extension allows treating the TOAC residue (TOAC, 2,2,6,6-tetramethylpiperidine-1-oxyl-4-amino-4-carboxylic acid) widely used as a spin label in protein studies. All the conformational minima of the Ac-Ac6C-NMe (Ac = acetyl, Ac6C = 1-aminocyclohexaneacetic acid, NMe = methylamino) and Ac-TOAC-NMe dipeptides have been examined in terms of geometry and relative energy stability by Quantum Mechanical (QM) computations employing an hybrid density functional (PBE0) for an extended training set of conformers with various folds. A very good agreement between QM and MM (molecular mechanics) data has been obtained in most of the investigated properties, including solvent effects. Finally, the new set of parameters has been validated by comparing the conformational and dynamical behavior of TOAC-labeled polypeptides investigated by means of classical molecular dynamics (MD) simulations with QM data and experimental evidence. The new FF accurately describes the tuning of conformational and dynamical behavior of the Ac-TOAC-NMe dipeptide and double spin-labeled heptapeptide Fmoc-(Aib-Aib-TOAC)(2)-Aib-OMe (Fmoc, fluorenyl-9-methoxycarbonyl; Aib, alpha-aminoisobutyric acid; OMe, methoxy) by solvents with different polarity. In particular, we found that the 3(10) helical structure of heptapeptide is the most stable one in vacuo, with a geometry very similar to the X-ray crystallographic structure, whereas a conformational equilibrium between the 3(10)- and alpha-helical structures is established in aqueous solution, in agreement with EPR data