458 research outputs found

    El retrat d'Alexandre VI Borja com a imatge del poder

    Get PDF
    Català: Anàlisi dels retrats d'Alexandre VI a l'Apartament Borja del Vaticà i al missal de Nadal de la Biblioteca Apostòlica Vaticana com a eines al servei de la construcció d'una imatge sacralitzada del poder espiritual i polític del papa Borja. Models i divergències respecte de la tradició dels retrats pontificis i imperials medievals. English: Analysis of the portraits of Alexander VI in the Borgian Apartments of the Vatican and the Christmas Missal of the Vatican Library as tools for the construction of a sacred and empowered image for the Borgia pope from both the spiritual and the political standpoints. Models and deviations from the tradition of medieval imperial and papal portraits are also discussed. Italiano: Analisi dei ritratti di Alessandro VI nell'appartamento Borgia nel Vaticano e nel messale di Natale della Biblioteca Apostolica Vaticana come strumenti al servizio della costruzione di un'immagine sacralizzata del potere spirituale e politico del papa Borgia. Modelli e divergenze rispetto alla tradizione dei ritratti pontifici e imperiali dell'età medievale

    An Analysis of Cognitive Factors in School-Aged Children with Emotional Disturbance and ADHD Using the WISC-IV

    Get PDF
    Children with Emotional Disturbance and ADHD demonstrate social, emotional, and behavioral symptoms that present many challenges for School Psychologists because of differences between each student’s individual needs. A high level of comorbidity exists for these children with internalizing and externalizing symptoms. Little is known about neurocognitive factors as they relate to ED versus ADHD. The current study examined the cognitive profiles of a total of 58 children with ED versus ADHD, using the Wechsler Intelligence Scale for Children, Fourth Edition (WISC-IV). Index scores that were examined included Verbal Comprehension, Perceptual Reasoning, Working Memory, and Processing Speed. The groups were compared in order to determine overall group mean differences. Further analysis identified proportions of differences between the groups at the 10, 15, 20, and 25 point levels for the following Index level comparisons: VCIWMI, PRI-WMI, PRI-PSI, VCI-PSI, VCI-PRI, WMI-PSI. Results of the study found overall group mean differences between the groups for VCI. Further analysis of Index level comparisons indicated that children with ED demonstrated significance with VCI\u3eWMI and VCI\u3ePSI and PRI\u3eWMI. Children with ADHD demonstrated significance with WMI\u3eVCI, which is the opposite of prior research findings. Limitations of the current study and implications for future research are also discussed

    Growth inhibitory action of distinct sequences derived from the co-chaperone Bag-1L

    Get PDF
    Bag-1L is a multifunctional protein overexpressed in prostate, breast and colon cancer among the others. In this work a region of 68 amino acids has been found to inhibit the growth of 22Rv.1 and LNCaP prostate cancer cell lines but not of the BPH-1 bening prostate cells in colony forming assay and xenograft mouse models by binding to the molecular chaperones GRP75 and GRP78. A shorter sequence of 19 amino acids has been found sufficient for binding the target proteins and inhibit growth

    The Effect of the Protein Matrix on Fluorescence and an Analysis of the Effect of Fusing Residues 62 and 63 in Kindling Proteins

    Get PDF
    In the ground state of the highly conjugated green fluorescent protein (GFP), the chromophore should be planar. However, numerous crystal structures of GFP and GFP-like proteins have been reported with slightly twisted chromophores. We have previously shown that the protein cavity surrounding the chromophore in wild-type GFP is not complementary with a planar chromophore. This study shows that the crystal structure of wild-type GFP is not an anomaly: most of the GFP and GFP-like proteins in the protein databank have a protein matrix that is not complementary with a planar chromophore. When the π-conjugation across the ethylenic bridge of the chromophore is removed the protein matrix will significantly twist the freely rotating chromophore from the relatively planar structures found in the crystal structures. The possible consequences of this non-planar deformation on the photophysics of GFP are discussed. In addition to GFP there are GFP-like proteins that can be reversibly photoswitched between a fluorescent and a nonfluorescent state. Conformational searching and molecular dynamics are used to examine the various kindling proteins with a cleaved chromophore. MD simulations supported that the chromophore does indeed start to move away from its initial trans configuration, and actually completes a full trans/cis isomerization. The nearby His197 residue does not provide a large barrier to the chromophore rotation when it is cleaved from the protein backbone. This implies that the rest of the protein backbone did not provide an obstacle to the isomerization. Fusion of the chromophore back to the protein backbone was also done and conformational analyses showed that the proteins with fused and cleaved chromophores did now show a great deal of change the φ and τ dihedral angles most cases

    The Molecular Chaperone GRP78/BiP in the Development of Chemoresistance: Mechanism and Possible Treatment

    Get PDF
    Treatment of several types of cancer such as lung, breast, prostate, and pancreas has shown notable progresses in the past decades. However, after an initial response, tumors eventually became resistant to chemotherapy. This phenomenon, known as chemoresistance, accounts for the death of most cancer patients. Several studies in patients refractory to therapy have revealed the upregulation of the molecular chaperone GRP78/Binding Protein, BiP (BiP) both at the RNA and protein expression level. Furthermore GRP78/BiP relocates to the cell membrane in malignant but not in benign cells. In this communication we review studies on the role and the mechanism of action of GRP78/BiP during development of chemoresistance in cancer cells. In addition we discuss the possible role of GRP78 as a biomarker and as a target in cancer therapy

    Photophysics and Dihedral Freedom of the Chromophore in Yellow, Blue, and Green Fluorescent Protein

    Get PDF
    Green fluorescent protein (GFP) and GFP-like fluorescent proteins owe their photophysical properties to an autocatalytically formed intrinsic chromophore. According to quantum mechanical calculations, the excited state of chromophore model systems has significant dihedral freedom, which may lead to fluorescence quenching intersystem crossing. Molecular dynamics simulations with freely rotating chromophoric dihedrals were performed on green, yellow, and blue fluorescent proteins in order to model the dihedral freedom available to the chromophore in the excited state. Most current theories suggest that a restriction in the rotational freedom of the fluorescent protein chromophore will lead to an increase in fluorescence brightness and/or quantum yield. According to our calculations, the dihedral freedom of the systems studied (BFP > A5 > YFP > GFP) increases in the inverse order to the quantum yield. In all simulations, the chromophore undergoes a negatively correlated hula twist (also known as a bottom hula twist mechanism)

    Objective Evidence of Gastro-Esophageal Reflux Disease is Rare in Patients with Autoimmune Gastritis.

    Get PDF
    Background and Aims: Patients with autoimmune atrophic gastritis (AAG) often complain of acid reflux symptoms, despite the evidence of hypo-achlorhydria. Rome IV criteria are used to define functional esophageal disorders. Our aim was to characterize gastroesophageal reflux disease (GERD) phenotypes in patients with AAG. Methods: Between 2017-2018, 172 AAG patients were evaluated at Gastro-Oncology outpatient clinic of University of Padua. Of them, 38 patients with reflux symptoms underwent high-resolution manometry (HRM) and multichannel intraluminal impedance-pH monitoring (MII-pH). Seventy-six AAG consecutive patients asymptomatic for gastroesophageal reflux were selected as age and gender matched controls. Serum biomarkers (pepsinogens, gastrin-17 and Helicobacter pylori antibodies), upper endoscopy, histology and clinical data were compared. Results: Out of 38/172 (22%) AAG patients with reflux symptoms, 2/38 had a GERD diagnosis based on abnormal esophageal acid exposure and 6/38 had a major motility disorder (i.e. outflow obstruction). Among the 30/38 patients with normal endoscopic findings, 9/30 had reflux hypersensitivity, 19 functional heartburn, 1 functional globus, 1 functional chest pain according to the Rome IV criteria. Antral atrophy, advanced corpus atrophy and OLGA stage were more frequent in controls than in reflux patients (p=0.01, p=0.031, p=0.01, respectively). No differences were found for serum biomarkers and symptom presentation. Most of the patients received proton pump inhibitors (PPIs) treatment (87%), with a minority (34%) reporting clinical benefit. Conclusions: Reflux symptoms are relatively common in AAG patients, but a firm diagnosis of GERD is rare (5%), whereas most of the patients have a functional disorder. PPI treatment is mostly clinical ineffective and should not be largely indicated

    Patient-Reported Outcomes After Swallowing (SWOARs)-Sparing IMRT in Head and Neck Cancers: Primary Results from a Prospective Study Endorsed by the Head and Neck Study Group (HNSG) of the Italian Association of Radiotherapy and Clinical Oncology (AIRO)

    Get PDF
    Objectives To prospectively investigate changes in M.D. Anderson Dysphagia Inventory (MDADI) scores in patients affected by naso- and oropharynx cancer after definitive radiochemotherapy (ChemoRT) using swallowing organs at risk (SWOARs)-sparing IMRT. Methods MDADI questionnaires were collected at baseline and at 6 and 12 months after treatment. MDADI scores were categorized as follows: >= 80 "optimal," 80-60 "adequate," < 60 "poor" deglutition-related quality of life (QoL) group, and dichotomized as "optimal" vs "adequate/poor" for the analysis. A mean MDADI composite (MDADI-C) change of 10 points was considered as minimal clinically important difference (MCID). Results Sixty-three patients were enrolled of which 47 were considered for the analysis. At baseline, 26 (55%) were "optimal" and 21 (45%) were "adequate/poor." The mean baseline MDADI-C score was 93.6 dropping to 81 at 6 months (p = 0.013) and slightly rising to 85.5 at 12 months (p = 0.321) for the "optimal" group. Indeed, the mean baseline MDADI-C score was 64.3 rising to 77.5 at 6 months (p = 0.006) and stabilizing at 76 at 12 months (p = 0.999) for the "adequate/poor" group. A statistically significant but not clinically relevant worsening of the MDADI-C score was reported for the "optimal" group, whereas both a statistically significant and clinically meaningful improvement of the MDADI-C score were reported for the "adequate/poor" group from before to post-treatment. Conclusion Our results suggest a doubly clinical benefit of dose optimization to SWOARs to minimize the RT sequalae in patients with a baseline "optimal" deglutition-related QoL and to recover from cancer dysphagia in those with a baseline "adequate/poor" deglutition-related QoL

    Autoimmune Atrophic Gastritis: The Role of miRNA in Relation to Helicobacter Pylori Infection

    Get PDF
    IntroductionMicroRNAs (miRNAs) have been proposed as diagnostic markers, biomarkers of neoplastic progression, and possible therapeutic targets in several immune-mediated diseases. We aimed to analyze the expression profile of selected miRNAs (miR21, miR142, miR223, miR155) in patients with autoimmune atrophic gastritis (AAG), patients with non-autoimmune multifocal atrophic gastritis (MAG), and healthy control subjects (HC).Materials and methodsA total of 103 patients with AAG were consecutively recruited for this study among those attending our gastroenterology outpatient clinic. Participating patients were divided into two groups: primary, not Helicobacter pylori (HP)-associated related AAG (n=57, P-AAG) and HP-associated AAG (n=46, HP-AAG); this subgroup included HP-positive patients, patients with previously reported HP infection, and patients harboring antral atrophy, considered as a stigma of HP infection. We also included 20 sex-age-matched MAG patients and 10 HC. Upper endoscopy with gastric biopsies were performed on each AAG and MAG patient. Circulating levels of miR21-5p, miR142-3p, miR223-3p, and miR155-5p were measured by RT-PCR in all groups.ResultsMiR-21 was over-expressed in P-AAG (p=0.02), HP-AAG (p = 0.04), and MAG (p=0.03) compared with HC. By contrast, miR-142 was more expressed in HC than in HP-AAG (p=0.04) and MAG (p=0.03). MiR-155 showed no significant differences among the four subgroups, while, unexpectedly, miR-223 was overexpressed in HC compared to P-AAG (p=0.01), HP-AAG (p=0.003), and MAG (p&lt;0.001), and was higher in P-AAG than in MAG (p=0.05).ConclusionsMiR-21 was over-expressed in patients with gastric precancerous conditions irrespective of etiology, while in the same subgroups miR-142 and miR-223 were under-expressed compared to healthy controls. Controlling miRNAs up- or downregulation could lead to a breakthrough in treating chronic autoimmune diseases and potentially interfere with the progression to cancer
    corecore