THE PRINCIPLE OF INTEGRITY AND THE FRAGMENTATION OF PUBLIC PROCUREMENT

Objective: Through this work, a study on the integrity of the human being and the fractionation of public procurement has been carried out.Methods: As part of the study, the authors reviewed scientific works on the subject.Results: After analyzing the contracting law 30225, its regulations and other aspects that are part of the contractual procedure, certain factors have been determined that intervene in the actions of the agents in charge of public contracting, such as: i) normative disparity; ii) incapacity of those in charge of the selection processes; and iii) acts of corruption, which put at risk the denaturalization of the norms, generating the splitting of a contract.Conclusions: The splitting of a contracting procedure corresponds more to a subjective decision where the official or servant in charge of the contracting process has the power to discern the good from the bad. The bad decision that entails an illicit conduct will generate liability

Alpha-catenin-Dependent Recruitment of the Centrosomal Protein CAP350 to Adherens Junctions Allows Epithelial Cells to Acquire a Columnar Shape

Epithelial morphogenesis involves a dramatic reorganisation of the microtubule cytoskeleton. How this complex process is controlled at the molecular level is still largely unknown. Here, we report that the centrosomal microtubule (MT)-binding protein CAP350 localises at adherens junctions in epithelial cells. By two-hybrid screening, we identified a direct interaction of CAP350 with the adhesion protein α-catenin that was further confirmed by co-immunoprecipitation experiments. Block of epithelial cadherin (E-cadherin)-mediated cell-cell adhesion or α-catenin depletion prevented CAP350 localisation at cell-cell junctions. Knocking down junction-located CAP350 inhibited the establishment of an apico-basal array of microtubules and impaired the acquisition of columnar shape in Madin-Darby canine kidney II (MDCKII) cells grown as polarised epithelia. Furthermore, MDCKII cystogenesis was also defective in junctional CAP350-depleted cells. CAP350-depleted MDCKII cysts were smaller and contained either multiple lumens or no lumen. Membrane polarity was not affected, but cortical microtubule bundles did not properly form. Our results indicate that CAP350 may act as an adaptor between adherens junctions and microtubules, thus regulating epithelial differentiation and contributing to the definition of cell architecture. We also uncover a central role of α-catenin in global cytoskeleton remodelling, in which it acts not only on actin but also on MT reorganisation during epithelial morphogenesis.This work was supported by Ministerio de Economia y Competitividad, Spain (BFU2012-36717 and CSD2009-00016 to RMR and BFU2011-22916 to JRM) and by Junta de Andalucia (CVI-7256 and CTS-2071), and by a funding GenHomme Network 02490-6088 to Hybrigenics and the Institut Curie. MA and AZ were supported by MEC–FPI Grants.Peer Reviewe

Solvent-assisted in situ synthesis of cysteamine-capped silver nanoparticles

Silver nanoparticles offer a huge potential for biomedical applications owing to their exceptional properties and small size. Specifically, cysteamine-capped silver nanoparticles could form the basis for new anticancer therapies combining the cytotoxic effect of the silver core with the inherent antitumor activity of cysteamine, which inhibit cancer cell proliferation and suppress invasion and metastasis. In addition, the capability of the cysteamine coating monolayer to couple a variety of active principles and targeting (bio)molecules of interest proves key to the tailoring of this platform in order to exploit the pathophysiology of specific tumor types. Nevertheless, the chain length and conformational flexibility of cysteamine, together with its ability to attach to the surface of silver nanoparticles via both the thiol and the amine group, have made the in situ synthesis of these particles an especially challenging task. Herein we report a solvent-assisted in situ synthesis method that solves this problem. The obtained nanoparticles have been fully characterized by UV–visible absorption spectroscopy, Fourier transform infrared spectroscopy, transmission electron microscopy, electron diffraction measurement, high resolution transmission electron microscopy, scanning transmission electron microscopy, energy dispersive x-ray spectroscopy nanoanalysis, and dynamic light scattering measurement. Our synthesis method achieves extremely high yield and surface coating ratio, and colloidal stability over a wide range of pH values including physiological pH. Additionally, we have demonstrated that cysteamine-capped nanoparticles obtained by this method can be conjugated to an antibody for active targeting of the epidermal growth factor receptor, which plays an important role in the pathogenesis and progression of a wide variety of tumors, and induce cell death in human squamous carcinoma cells. We believe this method can be readily extended to combinations of noble metals and longer chain primary, secondary, ternary or even quaternary aminethiolsEspaña, Junta de Andalucía P10- FQM-6615España, Ministerio de Economia y Competitividad CTP2016-80206-

Increased intrinsic stiffness and mineralization in femurs of adult rats after high intensity treadmill running training

Physical activity plays a tremendous role in determining bone mechanical behavior, which is superimposed to gravidity. OBJECTIVE: Compare the geometric and material responses of the rat femur to a high intensity treadmill running training of a relatively short duration, as assessed by 3-point mechanical test. METHODS: Mature male rats (180.0±30 g) were assigned (7 rats/group) to no exercise (NE) or treadmill exercise (EX). After preconditioning period, the running speed was set at 45 cm.seg−1 during 2 wks, frequency 5 d/wk, 2-hour sessions/day. Body weight and weight of the crural quadriceps were registered at euthanasia. The right femur was mechanically tested through 3-point bending. The left femur was ashed to estimate bone mineral content. Geometric and material bone properties were estimated directly or calculated by appropriate equations. RESULTS: Final body weight was 14% reduced in EX rats, while the crural quadriceps was 47% increased. Yield and fracture loads, and structural stiffness were significantly higher in the EX rats, as were the apparent elastic modulus, the bone mineral content and the degree of mineralization. Geometric properties were not affected. CONCLUSIONS: High intensity treadmill running training increases bone strength and stiffness by increasing material stiffness and mineralization, without affecting geometric bone parameters

Dysfunction of the unfolded protein response increases neurodegeneration in aged rat hippocampus following proteasome inhibition

Dysfunctions of the ubiquitin proteasome system (UPS) have been proposed to be involved in the aetiology and/or progression of several age-related neurodegenerative disorders. However, the mechanisms linking proteasome dysfunction to cell degeneration are poorly understood. We examined in young and aged rat hippocampus the activation of the unfolded protein response (UPR) under cellular stress induced by proteasome inhibition. Lactacystin injection blocked proteasome activity in young and aged animals in a similar extent and increased the amount of ubiquitinated proteins. Young animals activated the three UPR arms, IRE1α, ATF6α and PERK, whereas aged rats failed to induce the IRE1α and ATF6α pathways. In consequence, aged animals did not induce the expression of pro-survival factors (chaperones, Bcl-XL and Bcl-2), displayed a more sustained expression of proapoptotic markers (CHOP, Bax, Bak and JKN), an increased caspase-3 processing. At the cellular level, proteasome inhibition induced neuronal damage in young and aged animals as assayed using Fluorojade-B staining. However, degenerating neurons were evident as soon as 24 h postinjection in aged rats, but it was delayed up to 3 days in young animals. Our findings show evidence supporting age-related dysfunctions in the UPR activation as a potential mechanism linking protein accumulation to cell degeneration. An imbalance between pro-survival and pro-apoptotic proteins, because of noncanonical activation of the UPR in aged rats, would increase the susceptibility to cell degeneration. These findings add a new molecular vision that might be relevant in the aetiology of several age-related neurodegenerative disorders

Lipopolysacharide-induced neuroinflammation leads to the accumulation of ubiquitinated proteins and increases susceptibility to neurodegeneration induced by proteasome inhibition in rat hippocampus

BACKGROUND: Neuroinflammation and protein accumulation are characteristic hallmarks of both normal aging and age-related neurodegenerative diseases. However, the relationship between these factors in neurodegenerative processes is poorly understood. We have previously shown that proteasome inhibition produced higher neurodegeneration in aged than in young rats, suggesting that other additional age-related events could be involved in neurodegeneration. We evaluated the role of lipopolysaccharide (LPS)-induced neuroinflammation as a potential synergic risk factor for hippocampal neurodegeneration induced by proteasome inhibition. METHODS: Young male Wistar rats were injected with 1 μL of saline or LPS (5 mg/mL) into the hippocampus to evaluate the effect of LPS-induced neuroinflammation on protein homeostasis. The synergic effect of LPS and proteasome inhibition was analyzed in young rats that first received 1 μL of LPS and 24 h later 1 μL (5 mg/mL) of the proteasome inhibitor lactacystin. Animals were sacrificed at different times post-injection and hippocampi isolated and processed for gene expression analysis by real-time polymerase chain reaction; protein expression analysis by western blots; proteasome activity by fluorescence spectroscopy; immunofluorescence analysis by confocal microscopy; and degeneration assay by Fluoro-Jade B staining. RESULTS: LPS injection produced the accumulation of ubiquitinated proteins in hippocampal neurons, increased expression of the E2 ubiquitin-conjugating enzyme UB2L6, decreased proteasome activity and increased immunoproteasome content. However, LPS injection was not sufficient to produce neurodegeneration. The combination of neuroinflammation and proteasome inhibition leads to higher neuronal accumulation of ubiquitinated proteins, predominant expression of pro-apoptotic markers and increased neurodegeneration, when compared with LPS or lactacystin (LT) injection alone. CONCLUSIONS: Our results identify neuroinflammation as a risk factor that increases susceptibility to neurodegeneration induced by proteasome inhibition. These results highlight the modulation of neuroinflammation as a mechanism for neuronal protection that could be relevant in situations where both factors are present, such as aging and neurodegenerative diseases

Rapidly progressive conjunctival melanoma

Hombre de 73 años que presenta una lesión nodular pigmentada a nivel inferonasal de su conjuntiva bulbar. El estudio histopatológico mostró una proliferación neoplásica melanocítica caracterizada por una proliferación vascular en la base de la lesión con células invasivas de melanoma positivas para Melan-A. El paciente fue sometido a una escisión y una esclerotomia superficial. No se evidenciaron signos de recurrencia después de 12 meses de seguimiento. Sin embargo, es necesario realizer un seguimiento a más largo para mayor seguridad.A 73-year-old male presented with a pigmented nodular lesion in the inferonasal bulbar conjunctiva. Histopathological examination revealed a neoplastic melanocytic proliferation. This was characterized by vessel proliferation within the base of the lesion and invasive melanoma cells, positive for Melan-A. The patient underwent a dry “no touch” excision and a superficial sclerectomy. There were no signs of recurrence after 12 months of follow-up. However, it is necessary to perform a longer follow-up for greater security

VALORES HEMATOLÓGICOS Y BIOQUÍMICA RENAL REFERENCIALES DE VENADOS COLA BLANCA (Odocoileus virginianus peruvianus) EN CAUTIVERIO.

The objective of the present study was to determine the normal hematological values and renal biochemistry of the adult white-tailed deer (Odocoileus virginianus) reared in captivity. Blood samples were collected in 25 animals. The deers were anesthetized with two chemical methods of restraint (ketamina 7 mg/kg; ketamina 4 mg/kg and xilacina 1 mg/ kg) without significant difference between both methods in relation to hematological and biochemistry values. In the erythrocytic series, the number of red cells was 10.12 x 106/μl, hemoglobin was 9.5 g/dl, hematocrit was 28.9%, and the erythocytic indexes were VCM = 28.8 fL, HCM = 9.6 pg, CHCM = 33.2 g/dl, without differences due to sex. The number of leukocytes was statistical different (p<0.05) between females (4018 x 103/μl) and males (3059 x 103/μl), but the differential count was similar between sexes (neutrophils: 55.5%, lymphocytes: 39.8%, monocytes: 0.1%, eosinophils: 4.6%). In the renal biochemistry, the mean values for urea and creatinine were 47 mg/dl and 2.1 mg/dl respectively.El objetivo del presente estudio fue determinar el perfil hematológico y bioquímica renal normal del Venado Cola Blanca (Odocoileus virginianus), adulto (1 a 6 años), criado en cautiverio. Se colectaron 25 muestras de sangre de tres zoológicos o zoocriaderos de la zona de Lima. Los animales fueron previamente sedados con dos métodos químicos de contención (ketamina 10 mg/kg y ketamina 4 mg/kg con Xilacina 1 mg/kg), sin que hubiera diferencia significativa entre ambos con relación a los valores hematológicos y bioquímicos. En la serie eritrocítica, el número de glóbulos rojos fue de 10.12 x 106/μl, hemoglobina de 9.5 g/dl, hematocrito de 28.9%, y los índices eritrocíticos fueron de: VCM = 28.8 fL, HCM = 9.6 pg, CHCM = 33.2 g/dl, sin encontrar diferencia entre sexos. En la serie leucocítica, el número de leucocitos fue estadísticamente diferente (p<0.05) entre hembras (4.018 x 103/μl) y machos (3059 x 103/μl), pero sin diferencias en el recuento diferencial (neutrófilos: 55.5%, linfocitos: 39.8%, monocitos: 0.1%, eosinófilos: 4.6%). En la bioquímica renal, el valor de urea fue 47 mg/dl y la creatinina fue de 2.1 mg/dl

GENYOi005-A: An induced pluripotent stem cells (iPSCs) line generated from a patient with Familial Platelet Disorder with associated Myeloid Malignancy (FPDMM) carrying a p.Thr196Ala variant

Familial Platelet Disorder with associated Myeloid Malignancy (FPDMM) is a rare platelet disorder caused by mutations in RUNX1. We generated an iPSC line (GENYOi005-A) from a FPDMM patient with a non-previously reported variant p.Thr196Ala. Non-integrative Sendai viruses expressing the Yamanaka reprogramming factors were used to reprogram peripheral blood mononuclear cells from this FPDMM patient. Characterization of GENYOi005-A included genetic analysis of RUNX1 locus, Short Tandem Repeats profiling, alkaline phosphatase enzymatic activity, expression of pluripotency-associated factors and differentiation studies in vitro and in vivo. This iPSC line will provide a powerful tool to study developmental alterations of FPDMM patientsThis work was supported by the Ramon y Cajal (RYC-2015-18382) to PJR founded by the Ministry of Economy and Competitiveness; the Instituto de Salud Carlos III-FEDER (CP12/03175 and CPII17/00032) to V.R-M., (PI17/01311) to M.L.L and J.R., (PI17/01966; Fundación Mutua Madrileña AP172142019; Premio Lopez Borrasca SETH 2019; GRS2061/A/19) to J.M.B. and (CPII15/00018 and PI16/01340) to PJR; by the Chair "Doctors Galera-Requena in cancer stem cell research" (CMC-CTS963) to J.A.M. and C.G-L