Analysis of the interaction of calcitriol with the disulfide isomerase ERp57

Calcitriol, the active form of vitamin D3, can regulate the gene expression through the binding to the nuclear receptor VDR, but it can also display nongenomic actions, acting through a membrane- associated receptor, which has been discovered as the disul de isomerase ERp57. The aim of our research is to identify the binding sites for calcitriol in ERp57 and to analyze their interaction. We rst studied the interaction through bioinformatics and uorimetric analyses. Subsequently, we focused on two protein mutants containing the predicted interaction domains with calcitriol: abb’- ERp57, containing the rst three domains, and a’-ERp57, the fourth domain only. To consolidate the achievements we used the calorimetric approach to the whole protein and its mutants. Our results allow us to hypothesize that the interaction with the a’ domain contributes to a greater extent than the other potential binding sites to the dissociation constant, calculated as a Kd of about 10−9 M

Interdisciplinary Knowledge for Conservation of Ruins: Stratigraphic Investigations of San Giovanni Battista Church (Sardinia, Italy)

The debate over how best to preserve and reuse ruins continues apace among academics around the world, remaining a still unresolved issue. In modern ages, different approaches have defined several solutions for rehabilitating these complex architectures. However, these do not appropriately consider their role of chrono-typological and material benchmark for the whole understanding of the fabric and consequent basis for their future sustainable enhancement. In particular, this is even more discussed in Sardinia where the high presence of ruined structures as well as the lack of documentary sources and funding has led mostly towards non-intervention policies. For these reasons, the present research contributes to this debate proposing an interdisciplinary methodology of knowledge specifically designed for buildings in a state of ruin. It involves different scientific areas: 3D survey with laser scanning technologies, archaeological graphic restitutions, stratigraphic surveys and classification of masonries types and diagnostic laboratory tests on materials (mortars, plasters, stones). The study highlights the valuable archaeological and documentary relevance of ruins for the understanding of their history, building technologies, materials and a state of conservation. It contributes to the definition of a design project, and to the identification of the typological and dimensional features referred to a specific context, also useful tool for dating coeval minor architectures, difficult to date. The investigation plan is here tested on the rural church of Saint Giovanni Battista (Bortigali, Sardinia, Italy), dating back to the XIII-XIV century and actually in a state of ruin. The case study is particularly representative of the complexity related to the investigation of Sardinian rural churches characterized by the lack of archival sources and an interesting variety of masonries types due to their different chronologies, even if it makes the buildings themselves the only available document for the comprehension of their constructive phases. The illustrated knowledge plan also provides a substantial contribution for the definition of possible actions for the conservation, re-functionalization and valorisation of these ruins

Defence heritage in a state of ruin: the archaeometric study of della Fava castle in Sardinia (Italy)

Defence heritage has always had a dominating presence in the landscape. It speaks of the passing of time in various countries, and it is a witness to a complex system of relationships between fortified architecture and documenting local materials and techniques. Innumerable researches have been carried out to study these ruined structures frequently without evaluating their valuable chronological role of ‘benchmark’ in the landscape. In Sardinia these studies, principally related to the dating, history and evolution of this heritage, are complicated by the lack of documented sources and by the small number of castles and ruins still available. The present research contributes to more insight in this field, reflecting on the study of medieval fortified heritage, which is in a state of ruin in north-east of Sardinia (12th–13th centuries), and it proposes an interdisciplinary protocol of research for this architecture. The object is the investigation of the ‘della fava’ castle (Posada), which represents one of the most important defensive architectural systems on the coast. Its structures have been studied in depth through a series of archaeometric analyses, based on surveys, typological, architectural and construction techniques, as well as petro-mineralogical inspection, with the purpose of reconstructing dimensional, material and constructive aspects of the traditional masonry techniques. This article allows to achieve two different aims: (1) to understand how a structure is made and consequently to define the correct conservation and design project; and (2) to identify typological and dimensional constants that referred to a specific geological context and period; these constants can be a useful tool for comparing and dating coeval structures, such as ‘minor architecture’, that are difficult to date

Safety and Efficacy of Surgery for Metastatic Tumor to the Pancreas: A Single-Center Experience

Pancreatic metastases from other neoplasms are rare. The role of surgery for this clinical entity is unclear. The aim of this study was to investigate the role of resection in patients with pancreatic secondary lesions. We observed 44 patients with pancreatic metastases from other tumors. Renal cell carcinoma was the most common primary tumor (n = 19, 43.2%). Thirty-seven patients underwent surgery, and pancreatic resection with curative intent was feasible in 35 cases. Fifteen patients (43.2%) experienced major postoperative complications (Clavien-Dindo > 2), and postoperative mortality rate was 5.4%. The median overall survival and disease-free survival were 38 (range 0–186) and 11 (range 0–186) months, respectively. Overall survival and disease-free survival were significantly longer for pancreatic metastases from renal cell carcinoma when compared to other primary tumors. Multivariate analysis confirmed a pathological diagnosis of metastasis from RCC as an independent prognostic factor for overall survival (OR 2.48; 95% CI, 1.00–6.14; p = 0.05). In conclusion, radical resection of metastases to the pancreas is feasible and safe, and may confer a survival benefit for selected patients. There is a clear benefit of metastasectomy in terms of patient survival for metastases from renal cell carcinoma, while for those with other primary tumors, surgery seems to be mainly palliative

Actividad antifúngica y antiadhesiva de tensioactivos derivados de arginina frente a levaduras del género candida

Una de las características del reino Fungi es su capacidad de colonizar superficies inertes o tejidos vivos a través de su adhesión y la formación de comunidades, simples o mixtas, embebidas en una matriz de exopolisacárido, llamadas biofilms. Las terapias antimicrobianas a menudo no logran controlar este tipo de comunidades, develando la necesidad de diseñar nuevos compuestos antifúngicos que puedan utilizarse tanto sobre bienes como sobre superficies, de manera de inhibir o demorar su colonización. El objetivo del presente trabajo es el estudio de la actividad antifúngica y antiadhesiva de tensioactivos catiónicos derivados de aminoácidos frente a levaduras del género Candida. Con este fin, se realizó la síntesis de alquilamidas derivadas de arginina (Bz-Arg-NHC10 y Bz-Arg-NHC12) utilizando papaína adsorbida sobre poliamida como biocatalizador, con rendimientos del 98% y 85% respectivamente. La purificación de los productos se llevó a cabo por cromatografía de intercambio catiónico, empleando mezclas acuoso-etanólicas de bajo impacto ambiental. Ambos compuestos demostraron actividad antifúngica frente a C. albicans y C. tropicalis. El análisis de las cinéticas de muerte de las levaduras en presencia de los compuestos reveló una reducción de entre uno y cinco órdenes de magnitud del número de microorganismos viables luego de las primeras horas de incubación. Por otro lado, el pre-tratamiento de microplacas de poliestireno con los tensioactivos mostró su efectividad para inhibir la adherencia de las levaduras a esta superficie, registrándose reducciones de la adhesión de entre el 25 y el 83%. En este sentido, Bz-Arg-NHC12 mostró un mayor efecto antiadhesivo, siendo C. tropicalis más sensible al efecto de los surfactantesFil: Mylek, Silvina. Universidad Nacional de La PlataFil: Grillo, Patricia. Universidad Nacional de La PlataFil: Morcelle, Susana. Universidad Nacional de La PlataFil: Fait, María Elisa. Universidad Nacional de La Plat

Dataset from fundus images for the study of diabetic retinopathy.

This article presents a database containing 757 color fun dus images acquired at the Department of Ophthalmology of the Hospital de Clínicas, Facultad de Ciencias Médicas (FCM), Universidad Nacional de Asunción (UNA), Paraguay. Firstly, the retinal images were acquired with a clinical procedure presented in this paper. The acquisition of the retinographies was made through the Visucam 500 camera of the Zeiss brand. Next, two expert ophthalmologists have classified the dataset. These data can help physicians and researchers in the detection of cases of Non-Proliferative Diabetic Retinopa thy (NPDR) and Proliferative Diabetic Retinopathy (PDR), in their different stages. The dataset generated will be useful for ophthalmologists and researchers to work on automatic detection algorithms for Diabetic Retinopathy (DR).CONACYT - Consejo Nacional de Ciencia y TecnologíaPROCIENCI

Involvement of GTA protein NC2β in Neuroblastoma pathogenesis suggests that it physiologically participates in the regulation of cell proliferation

<p>Abstract</p> <p>Background</p> <p>The General Transcription Apparatus (GTA) comprises more than one hundred proteins, including RNA Polymerases, GTFs, TAFs, Mediator, and cofactors such as heterodimeric NC2. This complexity contrasts with the simple mechanical role that these proteins are believed to perform and suggests a still uncharacterized participation to important biological functions, such as the control of cell proliferation.</p> <p>Results</p> <p>To verify our hypothesis, we analyzed the involvement in Neuroblastoma (NB) pathogenesis of GTA genes localized at 1p, one of NB critical regions: through RT-PCR of fifty eight NB biopsies, we demonstrated the statistically significant reduction of the mRNA for NC2β (localized at 1p22.1) in 74% of samples (p = 0.0039). Transcripts from TAF13 and TAF12 (mapping at 1p13.3 and 1p35.3, respectively) were also reduced, whereas we didn't detect any quantitative alteration of the mRNAs from GTF2B and NC2α (localized at 1p22-p21 and 11q13.3, respectively). We confirmed these data by comparing tumour and constitutional DNA: most NB samples with diminished levels of NC2β mRNA had also genomic deletions at the corresponding locus.</p> <p>Conclusion</p> <p>Our data show that NC2β is specifically involved in NB pathogenesis and may be considered a new NB biomarker: accordingly, we suggest that NC2β, and possibly other GTA members, are physiologically involved in the control of cell proliferation. Finally, our studies unearth complex selective mechanisms within NB cells.</p