Molecular dissection of the nuclear pore complex in relation to nuclear export pathways

The nuclear pore complex (NPC) is the gateway to and from the genome. The work presented in this thesis is the result of the investigations towards understanding some of the key questions affecting NPC biology: How is the NPC built up? Can we dissect different modes of transport at the level of the NPC? Does the NPC play a role in the development of cancer? Several findings presented in this thesis have contributed to the current knowledge of the biology of the Nuclear Pore Complex. Structurally, the hierarchy towards incorporation to the NPC of the cytoplasmic components Nup88, Nup214 and Nup 358 and their relevance to nuclear transport has been established. Concerning nuclear transport itself, a supporting role in CRM1-mediated export has been assigned to Nup358 and an explanation to the weak nature of the interaction of CRM1 and its NES-containing cargoes been elucidated. This work has amplified as well the concept of nuclear translocation by creating a distinction in transport pathways that, instead of been exclusively dependent on the receptor-NPC and the receptor-cargo interactions, consider the characteristics of the cargo itself. In fact , while showing cargos that can be exported by CRM1 independently of Nup214, we present first in vivo evidence of the implication of Nup214 in a NPC gating mechanism for the CRM1-dependent export of preribosomes Furthermore, this result excludes any implication of the strong CRM1 binding Nup214 FG-domain in this mechanism and in other suggested models of CRM1 export. Finally, this thesis has provided information concerning the localization and stability of the aberrant product Nup214-ABL that may be of great value for the development of alternative therapies of leukemic diseasesUBL - phd migration 201

Salmonella Shedding in Slaughter Pigs and the Use of Esterified Formic Acid in the Drinking Water as a Potential Abattoir-Based Mitigation Measure

Pigs shedding Salmonella at slaughter are considered a source of carcass contamination and human infection. To assess this potential risk, the proportion of Salmonella shedders that arrive for slaughter was evaluated in a population of 1068 pigs from 24 farms. Shedding was present in 27.3% of the pigs, and the monophasic variant of Salmonella Typhimurium, an emerging zoonotic serotype, was the most prevalent (46.9%). Antimicrobial resistance (AMR) in Salmonella isolates was common, but few isolates showed AMR to antimicrobials of critical importance for humans such as third-generation cephalosporins (5%), colistin (0%), or carbapenems (0%). However, AMR to tigecycline was moderately high (15%). The efficacy of an esterified formic acid in the lairage drinking water (3 kg formic acid/1000 L) was also assessed as a potential abattoir-based strategy to reduce Salmonella shedding. It was able to reduce the proportion of shedders (60.7% in the control group (CG) vs. 44.3% in the treatment group (TG); p < 0.01). After considering clustering and confounding factors, the odds of shedding Salmonella in the CG were 2.75 (95% CI = 1.80–4.21) times higher than those of the TG, suggesting a potential efficacy of reduction in shedding as high as 63.6%. This strategy may contribute to mitigating the burden of abattoir environmental contamination

Reflections on the future business model of European banks and the supervisory approach

Relevant forces are reshaping the banking sector and redefining banks’ business models. On the one hand, banks have been facing structural difficulties, such as a prolonged low interest rate environment and the costs of excess capacity. In addition, banks need to deal with more recently developing challenges, like the digital transformation, the entrance of new competitors in the banking sector and the climate change. A demanding regulatory environment and the impact of the COVID-19 pandemic further aggravate the situation. As a result, European banks are not being able to produce enough returns to cover their cost of capital, making it necessary to urgently face these challenges. To that purpose, banks may adopt different strategies, some of them complementary, among which the following can be highlighted: the reduction of overcapacity, consolidation, diversification or specialisation and the exploitation of the value of long-term relations with clients, as well as taking advantage of the opportunities stemming from digitalization and sustainable finance. Supervisors will need to stay abreast of the changes in the banking environment and closely monitor the adaptation processes. This article is intended to serve as a basis for discussion, given that several of the issues raised are controversial and uncertain under the current fast changing environment

Reflections on the future business model of European banks and the supervisory approach

Importantes factores están reconfigurando el sector bancario y redefiniendo los modelos de negocio de las entidades. Las entidades han venido afrontando dificultades estructurales, como un entorno de bajos tipos de interés prolongado o el exceso de capacidad instalada. A esto se añaden otros retos más recientes, como la transformación digital, los nuevos competidores en el mercado bancario y el cambio climático. Adicionalmente, un entorno regulatorio exigente y el impacto del COVID-19 suponen una presión añadida. Como resultado, los bancos europeos no están siendo capaces de producir resultados que cubran el coste del capital, lo que hace necesario afrontar con urgencia estos retos. Para ello, existen distintas estrategias posibles, algunas de ellas complementarias, entre las que se pueden destacar: la reducción de la capacidad instalada, la consolidación bancaria, la diversificación o especialización y la explotación del valor de la banca relacional, así como el aprovechamiento de las oportunidades derivadas de la digitalización y las finanzas sostenibles. El supervisor deberá estar al nivel de los cambios que se produzcan en el entorno bancario y seguir de cerca los procesos de adaptación. El propósito de este artículo es servir de base para el debate, dada la controversia existente y la incertidumbre que rodea a algunas de estas cuestiones en un entorno como el actual, que cambia con rapidez

Modeling of a stand-alone solar photovoltaic water pumping system for irrigation

Solar photovoltaic water pumping systems have been research topics in recent decades. The purpose was to develop much more profitable and efficient systems to meet the needs of pumping water for livestock and irrigation. This paper describes the design of a stand-alone photovoltaic water pumping system. A Boost converter is used to apply the Maximum Power Point Tracking (MPPT) algorithm. Similarly, a three-phase voltage source converter (VSC) is used to supply the asynchronous motor. The installation must provide a continuous water flow during the irrigation interval. It has been verified that in adverse weather conditions (cloud transits or partly cloudy) it is necessary to incorporate a decentralized-hybrid energy storage system (based on batteries or ultracapacitors), or excessively oversize the standalone photovoltaic system, to supply the water pump. The model has been simulated in Matlab-Simulink. In this way, different simulations have been developed to verify the basic characteristics of the proposed system. The results of the simulated model and the conclusions obtained are also presented in this paper

Pitfalls in spontaneous in vitro transformation of human mesenchymal stem cells

Spontaneous in vitro transformation of human primary cells was, and continues to be, a scarcely described phenomenon. Only the description of the generation of the HaCAT cell line [1] is a canonical example, worldwide accepted. More recent examples included the emergence of tumorogenic populations upon in vitro culture of fetal human mesenchymal stem cells (hMSC), induced by GM-CSF and IL-4, [2] and bone marrow hMSC [3]. Other examples have also been reported after very long-term in vitro culture of telomerized hMSCTerT [4]. In this scenario, our previous results [5-7] were only a new observation to be added to this list. Only very recently similar results have been published [8], reporting spontaneous malignant transformation in 46 % of bone marrow–derived hMSC long-term cultures (5–106 weeks). However, other authors reported opposite results.S

Gene expression profiling and its use in adenocarcinomas of unknown primary origin: A case report

Carcinomas of unknown primary origin account for 3-5% of all malignancies. The current literature suggests that metastatic dissemination is able to occur in the absence of primary tumor growth. In metastatic disease that is difficult to diagnose, the origin usually remains unknown even after an exhaustive evaluation of immunohistochemistry (IHC) markers. In the current study, a 49-year-old male presented with lymph nodes metastases of unknown origin. The exci- sional biopsy of an inguinal node revealed an adenocarcinoma growth pattern, but the IHC could not determine the primary origin. A gene profiling test was performed to complete the diagnosis and a salivary gland adenocarcinoma was diagnosed with 90% probability. Subsequently, the patient underwent appropriate chemotherapy for salivary gland adenocarcinoma, and exhibited an improved partial response. The present case study highlights the importance of an accurate diagnosis of the primary tumor and the use of all the current tools available in order to provide patients with the best treatment possibl

Exploring analytical proteomics platforms toward the definition of human cardiac stem cells receptome

Human cardiac stem cells (hCSC) express a portfolio of plasma membrane receptors that are involved in the regulatory auto/paracrine feedback loop mechanism of activation of these cells, and consequently contribute to myocardial regeneration. In order to attain a comprehensive description of hCSC receptome and overcoming the inability demonstrated by other technologies applied in receptor identification, mainly due to the transmembrane nature, high hydrophobic character and relative low concentration of these proteins, we have exploited and improved a proteomics workflow. This approach was based on the enrichment of hCSC plasma membrane fraction and addition of prefractionation steps prior to MS analysis. More than 100 plasma membrane receptors were identified. The data reported herein constitute a valuable source of information to further understand cardiac stem cells activation mechanisms and the subsequent cardiac repair process. All MS data have been deposited in the ProteomeXchange with identifier PXD001117 (http://proteomecentral.proteomexchange.org/dataset/PXD001117).Authors acknowledge FP7 EU project CARE-MI (HEALTH-2009_242038) and the Portuguese Foundation for Science and Technology (PTDC/BBBBIO/1414) for financial support. PGA is a recipient of the FCT fellowship SFRH/BPD/86513/2012. MALDI-TOF/TOF analyses were performed at the Mass Spectrometry Unit (UniMS), ITQB/iBET, Oeiras, Portugal. The data deposition to the ProteomeXchange Consortium was supported by PRIDETeam, EBI.S