Estructura cristalina de ADN y su utilización para la identificación de fármacos

Estructura cristalina de ADN y su utilización para la identificación de fármacos. La estructura cristalina que comprende un entrecruzamiento de tres cadenas de ADN está caracterizada porque: pertenece al grupo espacial P4(1)32 y tiene unas dimensiones de celda a=b=c=70,98 ± 0,7°A; todos los nucleótidos que constituyen dichas cadenas de ADN se encuentran emparejados; y dicho entrecruzamiento de tres cadenas de ADN alberga, en una cavidad hidrofóbica, una molécula. La estructura cristalina de la invención es una diana adecuada para el diseño de fármacos anti-ADN con una elevada especificidad.Peer reviewedConsejo Superior de Investigaciones Científicas (España)B1 Patente sin examen previ

Mechanism-controlled thermomechanical treatment of high manganese steels

Austenitic high manganese steels exhibit outstanding mechanical properties, such as high energy absorption, owing to various deformation-mechanisms such as dislocation slip, twinning-induced plasticity (TWIP) and transformation-induced plasticity (TRIP). Here, we show a novel thermomechanical treatment to manufacture a high manganese steel Fe–18Mn-0.3C (wt.-%) with excellent mechanical performance by combining these three deformation-mechanisms. This process of mechanism-controlled rolling resulted in ultra-high tensile strength of the high manganese steel up to 1.6 GPa, simultaneously with uniform elongations up to 15%.A thermomechanical process was developed to establish this combination of properties. Warm rolling was conducted at 200 °C, to suppress TRIP and activate TWIP as deformation mechanism. Thus, a high density of deformation twins and dislocations was introduced to the microstructure, avoiding martensite formation. During a subsequent recovery annealing at 520 °C or 550 °C, the dislocation density was reduced, yet the high density of deformation twins was preserved. The combination of warm rolling and recovery annealing resulted in an ultrafine microstructure with a high density of twins and moderate density of dislocations. The TRIP effect is predominant during plastic deformation at ambient conditions in the highly twinned microstructure. The resulting steel exhibits an ultra-high yield strength and sufficient ductility, favorable properties for lightweight construction in automotive or aerospace industry

Perfringolysin O-induced plasma membrane pores trigger actomyosin remodeling and endoplasmic reticulum redistribution

Clostridium perfringens produces an arsenal of toxins that act together to cause severe infections in humans and livestock animals. Perfringolysin O (PFO) is a cholesterol-dependent pore-forming toxin encoded in the chromosome of virtually all C. perfringens strains and acts in synergy with other toxins to determine the outcome of the infection. However, its individual contribution to the disease is poorly understood. Here, we intoxicated human epithelial and endothelial cells with purified PFO to evaluate the host cytoskeletal responses to PFO-induced damage. We found that, at sub-lytic concentrations, PFO induces a profound reorganization of the actomyosin cytoskeleton culminating into the assembly of well-defined cortical actomyosin structures at sites of plasma membrane (PM) remodeling. The assembly of such structures occurs concomitantly with the loss of the PM integrity and requires pore-formation, calcium influx, and myosin II activity. The recovery from the PM damage occurs simultaneously with the disassembly of cortical structures. PFO also targets the endoplasmic reticulum (ER) by inducing its disruption and vacuolation. ER-enriched vacuoles were detected at the cell cortex within the PFO-induced actomyosin structures. These cellular events suggest the targeting of the endothelium integrity at early stages of C. perfringens infection, in which secreted PFO is at sub-lytic concentrations.This work was financed by FEDER—Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020—Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT - Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior in the framework of the project POCI-01-0145-FEDER-030863 (PTDC/BIA-CEL/30863/2017) and Norte-01-0145-FEDER-000012—Structured program on bioengineered therapies for infectious diseases and tissue regeneration, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (FEDER). Publication Fees were supported by ICBAS, University of Porto. CB and FSM were supported by FCT fellowships (SFRH/BD/112217/2015, SFRH/BPD/94458/2013, respectively). CB was a Fulbright and FLAD fellow. SS received support from FCT Investigator program (COMPETE, POPH, and FCT)

Социальное благополучие как критерий эффективности неоиндустриализации экономики

Неоиндустриализация предполагает экономику, основанную на знаниях и сетях. В отличие от индустриальной экономики, где ключевыми факторами развития являются добыча и переработка сырья, в новой экономике будет доминировать инженерное творчество, дизайн и программирование. Это коренным образом меняет картину социального благополучия, которое выступает, с одной стороны, критерием, с другой - конечным результатом неоиндустриализации экономики

On the origin and pathway of the saline inflow to the Nordic Seas: insights from models

The behaviours of three high-resolution ocean circulation models of the North Atlantic, differing chiefly in their description of the vertical coordinate, are investigated in order to elucidate the routes and mechanisms by which saline water masses of southern origin provide inflows to the Nordic Seas. An existing hypothesis is that Mediterranean Overflow Water (MOW) is carried polewards in an eastern boundary undercurrent, and provides a deep source for these inflows. This study, however, provides an alternative view that the inflows are derived from shallow sources, and are comprised of water masses of western origin, carried by branches of the North Atlantic Current (NAC), and also more saline Eastern North Atlantic Water (ENAW), transported northwards from the Bay of Biscay region via a ‘Shelf Edge Current’ (SEC) flowing around the continental margins. In two of the models, the MOW flows northwards, but reaches only as far as the Porcupine Bank (53°N). In third model, the MOW also invades the Rockall Trough (extending to 60°N). However, none of the models allows the MOW to flow northwards into the Nordic Seas. Instead, they all support the hypothesis of there being shallow pathways, and that the saline inflows to the Nordic Seas result from NAC-derived and ENAW water masses, which meet and partially mix in the Rockall Trough. Volume and salinity transports into the southern Rockall Trough via the SEC are, in the various models, between 25 and 100% of those imported by the NAC, and are also a similarly significant proportion (20–75%) of the transports into the Nordic Seas. Moreover, the highest salinities are carried northwards by the SEC (these being between 0.13 and 0.19 psu more saline at the southern entrance to the Trough than those in the NAC-derived waters). This reveals for the first time the importance of the SEC in carrying saline water masses through the RockallTrough and into the Nordic Seas. Furthermore, the high salinities found on density surfaces appropriate to the MOW in the Nordic Seas are shown to result from the wintertime mixing of the saline near-surface waters advected northwards by the SEC/NAC system. Throughout, we have attempted to demonstrate the extent to which the models agree or disagree with interpretations derived from observations, so that the study also contributes to an ongoing community effort to assess the realism of our current generation of ocean models

Autoantibodies to aS1-Casein Are Induced by Breast-Feeding

Background: The generation of antibodies is impaired in newborns due to an immature immune system and reduced exposure to pathogens due to maternally derived antibodies and placental functions. During nursing, the immune system of newborns is challenged with multiple milk-derived proteins. Amongst them, caseins are the main constituent. In particular, human aS1-casein (CSN1S1) was recently shown to possess immunomodulatory properties. We were thus interested to determine if auto-antibodies to CSN1S1 are induced by breast-feeding and may be sustained into adulthood. Methods: 62 sera of healthy adult individuals who were (n = 37) or were not (n = 25) breast-fed against human CSN1S1 were investigated by a new SD (surface display)-ELISA. For cross-checking, these sera were tested for anti Epstein-Barr virus (EBV) antibodies by a commercial ELISA. Results: IgG-antibodies were predominantly detected in individuals who had been nursed. At a cut-off value of 0.4, the SDELISA identified individuals with a history of having been breast-fed with a sensitivity of 80% and a specificity of 92%. Under these conditions, 35 out of 37 sera from healthy donors, who where breast-fed, reacted positively but only 5 sera of the 25 donors who were not breast-fed. The duration of breast-feeding was of no consequence to the antibody reaction as some healthy donors were only short term breast-fed (5 days minimum until 6 weeks maximum), but exhibited significant serum reaction against human CSN1S1 nonetheless. Conclusion: We postulate that human CSN1S1 is an autoantigen. The antigenicity is orally determined, caused by breastfeeding, and sustained into adulthood

Contacting domains segregate a lipid transporter from a solute transporter in the malarial host–parasite interface

While membrane contact sites between intracellular organelles are abundant, little is known about the contacts between membranes that delimit extracellular junctions within cells, such as intracellular parasites. Here authors demonstrate the segregation of a lipid transporter from a solute transporter in the malarial host-parasite interface

Worms:Pernicious parasites or allies against allergies?

Host-parasite interactio

Engineering and geological features of soils fundamentals buildings and engineering networks of the Dnipro city

The analysis of engineering and geological properties of soils both in the natural state and under the influence of human economic activity is performed in the work. The researches from the point of view of conditions of construction and operation of buildings and constructions of engineering infrastructure of the city of Dnipro are proved. As a result of the analysis of specific geomorphological zones, specific examples of violations of the operation of buildings on subsidence soils, a number of measures are proposed for maintenance and operation of buildings and structures located in areas composed of subsidence soils, on the example of specific areas exposed to past man-made events. An analytical assessment of the ecological catastrophe on the territory of the Topolya 1 railway in 1997 is provided. The paper considers a principled approach to the principles and conditions of operation of buildings and structures on specific subsidence soils of the city of Dnipro.В роботі виконано аналіз інженерно-геологічних властивостей грунтів як в природньому стані, так і під впливом господарської діяльності людини. Доведені дослідження з точки зору умов будівництва і експлуатації будівель та споруд інженерної інфрастуктури міста Дніпро. Внаслідок аналізу конкретних геоморфологічних зон, конкретних прикладів порушень умов експлуатації будівель на просідальних грунтах, пропонується ряд заходів по утриманню і експлуатації будівель і споруд, розташованих на територіях, складених просідальними грунтами, на прикладі конкретних районів, які піддавалися в минулому негативним подіям техногенного характреру. Надається аналітична оцінка екологічної катастрофи на території ж/м "Тополя -1" у 1997 році. В роботі розглядається принциповий підхід до принципів і умов експлуатації будівель і споруд на специфічних просідальних грунтах міста Дніпро