Mobilie Banking adoption: a novel in the portuguese context

Dissertação apresentada como requisito parcial para obtenção do grau de Mestre em Estatística e Gestão de Informação

Novel FGFR1 Mutations in Kallmann Syndrome and Normosmic Idiopathic Hypogonadotropic Hypogonadism: Evidence for the Involvement of an Alternatively Spliced Isoform

OBJECTIVE: To determine the prevalence of fibroblast growth factor receptor 1 (FGFR1) mutations and their predicted functional consequences in patients with idiopathic hypogonadotropic hypogonadism (IHH). DESIGN: Cross-sectional study. SETTING: Multicentric. PATIENT(S): Fifty unrelated patients with IHH (21 with Kallmann syndrome and 29 with normosmic IHH). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Patients were screened for mutations in FGFR1. The functional consequences of mutations were predicted by in silico structural and conservation analysis. RESULT(S): Heterozygous FGFR1 mutations were identified in six (12%) kindreds. These consisted of frameshift mutations (p.Pro33-Alafs*17 and p.Tyr654*) and missense mutations in the signal peptide (p.Trp4Cys), in the D1 extracellular domain (p.Ser96Cys) and in the cytoplasmic tyrosine kinase domain (p.Met719Val). A missense mutation was identified in the alternatively spliced exon 8A (p.Ala353Thr) that exclusively affects the D3 extracellular domain of FGFR1 isoform IIIb. Structure-based and sequence-based prediction methods and the absence of these variants in 200 normal controls were all consistent with a critical role for the mutations in the activity of the receptor. Oligogenic inheritance (FGFR1/CHD7/PROKR2) was found in one patient. CONCLUSION(S): Two FGFR1 isoforms, IIIb and IIIc, result from alternative splicing of exons 8A and 8B, respectively. Loss-of-function of isoform IIIc is a cause of IHH, whereas isoform IIIb is thought to be redundant. Ours is the first report of normosmic IHH associated with a mutation in the alternatively spliced exon 8A and suggests that this disorder can be caused by defects in either of the two alternatively spliced FGFR1 isoforms.

Mitchell-Riley Syndrome: A Novel Mutation in RFX6 Gene

A novel RFX6 homozygous missense mutation was identified in an infant with Mitchell-Riley syndrome. The most common features of Mitchell-Riley syndrome were present, including severe neonatal diabetes associated with annular pancreas, intestinal malrotation, gallbladder agenesis, cholestatic disease, chronic diarrhea, and severe intrauterine growth restriction. Perijejunal tissue similar to pancreatic tissue was found in the submucosa, a finding that has not been previously reported in this syndrome. This case associating RFX6 mutation with structural and functional pancreatic abnormalities reinforces the RFX6 gene role in pancreas development and β-cell function, adding information to the existent mutation databases.

The two-component system of a novel copper resistant operon of Marinobacter hydrocarbonoclasticus

Dissertation for the Master’s Degree in Structural and Functional Biochemistry

Regulation of the rice gene OsRMC under salt stress: identification and functional characterization of novel transcription factors

Dissertation presented to obtain the Ph.D degree in Biology

Novel insights into plant vascular development: disclosing a mechanism to maintain thermospermine homeostasis in the xylem

Dissertation presented to obtain the Ph.D degree in Biology

Novel insights into the action of antimicrobial agents against human pathogens

Dissertation presented to obtain the Ph.D degree in Biochemistry

Feasibility study of the immunogenicity and safety of a novel DTPw/Hib (PRP-T) Brazilian combination compared to a licensed vaccine in healthy children at 2, 4, and 6 months of age

Vaccination of infants with conjugated Haemophilus influenzae type b (Hib) vaccines has been proven to reduce Hib meningitis by 95% and pneumoniae by 20%. The routine use of Hib vaccine is facilitated by the introduction of combination vaccines into the EPI (Expanded Plan of Immunization). The objective of this study was to compare the immunogenicity and reactogenicity of an extemporaneously mixed DTPw/Hib (diphtheria-tetanus-whole cell pertussis) combination, using the technology of two Brazilian manufacturers, against a licensed DTPw/Hib European combination in 108 infants vaccinated at 2, 4 and 6 months according to the local national schedule. The Brazilian combination was highly immunogenic with Hib seroprotection rates (anti-PRP > 0.15 mg /ml of 98% after 2 doses and 100% after 3). Also for tetanus and pertussis the new Brazilian combination was as immunogenic as the European counterpart, except the diphtheria seroprotection rates and titers were lower. There was also no clinically relevant difference in reactogenicity. If these feasibility results are confirmed, the Brazilian DTPw/Hib combination should help to boost the uptake of Hib vaccination in Brazil.

Novel functions of the cohesin accessory factor dPDS5 uncover a new meiotic checkpoint

Dissertation presented to obtain the Ph.D degree in Biology.

Development of novel benzimidazole- based COX Inhibitors new synthetic strategies and screening of heterocyclic structures

Dissertação para obtenção do Grau de Doutor em Química, especialidade Química Orgânica

Dynamics and kinetics of natural killer cell cytotoxicity in human malaria as evaluated by a novel stepwise cytotoxicity assay

Malaria causes important functional alterations of the immune system, but several of them are poorly defined. To evaluate thoroughly the natural killer cell cytotoxicity in patients with malaria, we developed a technique capable to assess both the dynamics and the kinetics of the process. For the kinetics assay, human peripheral blood mononuclear cells were previously incubated with K562 cells and kept in agarose medium, while for the dynamics assay both cells were maintained in suspension. NK activity from patients with vivax malaria presented a kinetics profile faster than those with falciparum malaria. NK cytotoxicity positively correlated with parasitemia in falciparum malaria. The dynamics of NK cytotoxicity of healthy individuals was elevated at the beginning of the process and then significantly decreased. In contrast, malaria patients presented successive peaks of NK activity. Our results confirmed the occurrence of alteration in NK cell function during malaria, and added new data about the NK cytotoxicity process.

Undrestanding postoperative cognitive dysfunction: novel insights

ABSTRACT: Background: Sleep is integral to biological function and sleep disruption can result in both physiological and psychological dysfunction. The acute cognitive consequences of sleep loss has been an active field of recent investigation, evidence suggests that sleep disruption in critically ill older adults can result in acute decrements in cognitive functioning. Surgery activates the innate immune system, inducing neuroinflammatory changes that interfere with cognition. The fact that patients with sleep disorders have an increased likelihood of exhibiting postoperative delirium encourages us to investigate the contribution of perioperative SF to the neuroinflammatory and cognitive responses of surgery. Methods: The effects of 24h sleep fragmentation (SF) and surgery were explored on adult C57BL/6J male mice. SF procedure started at 7 am with the home-cages being placed on a large platform orbital shaker cycled every 120 seconds (30 sec on/90 sec off). This procedure lasted for 24h. Stabilized tibia fracture was performed either before or after the 24h SF procedure. Separate cohorts of mice were tested for systemic and hippocampal inflammation and cognition. Results: Twenty-four hours of SF induced non-hippocampal memory dysfunction and increase in systemic IL-6. SF and surgery caused hippocampal-dependent memory impairment, although memory impairment was not exacerbated by combining SF with surgery. One day after either SF or surgery there was a significant increase in IL6 mRNA and TNF-alpha mRNA. These increments were more pronounced when either pre or post operative SF was combined with surgery. Conclusions: We show that while SF and surgery can independently produce significant memory impairment, perioperative SF significantly increased hippocampal inflammation without further cognitive impairment. The dissociation between neuroinflammation and cognitive decline may relate to our use of a sole memory paradigm that does not capture other aspects of cognition, especially learning.

Study of novel energy metabolism pathways in anaerobic bacteria

Energy conservation in chemotrophic anaerobic bacteria is achieved by two possible processes, substrate level phosphorylation (SLP) and electron transfer phosphorylation (ETP). This second mechanism, also known as respiration, involves chemiosmotic coupling. However, a third mechanism for energy coupling was recently proposed: the flavin-based electron bifurcation (FBEB). (...)

Chagas disease as a mechanistic model for testing a novel hypothesis

The association between depression and cardiovascular disease is well documented. Nevertheless, the process through which they are linked remains unknown, as does the direction of this relationship. Studies have suggested both that depression is a risk factor for heart disease and that heart disease is a risk factor for depression. A number of studies have established that a relationship exists between depression and inflammation, with alterations in the levels of inflammatory markers (IL-1, IL-6, TNF-alpha and others). Depressive symptoms have also been identified in many diseases characterized by inflammatory processes e.g. rheumatoid arthritis, bronchial asthma, diabetes, tuberculosis and cardiovascular diseases. In this brief viewpoint, we explain and propose how to use Chagas disease, a disorder characterized by inflammatory processes and leading to cardiovascular and autonomic problems, as a model for studying the directionality of the relationship between heart disease and depression.

Phage display as a tool for development of novel therapeutics for breast cancer

Phage display technology is a powerful platform for the generation of highly specific human monoclonal antibodies (Abs) with potential use in clinical applications. Moreover, this technique has also proven to be a reliable approach in identifying and validating new cancer-related targets. For scientific or medical applications, different types of Ab libraries can be constructed. The use of Fab Immune libraries allows the production of high quality and affinity antigen-specific Abs. In this work, two immune human phage display IgG Fab libraries were generated from the Ab repertoire of 16 breast cancer patients, in order to obtain a tool for the development of new therapeutic Abs for breast cancer, a condition that has great impact worldwide. The generated libraries are estimated to contain more than 108 independent clones and a diversity over 90%. Libraries validation was pursued by selection against BSA, a foreign and highly immunogenic protein, and HER2, a well established cancer target. Preliminary results suggested that phage pools with affinity for these antigens were selected and enriched. Individual clones were isolated, however, it was not possible to obtain enough data to further characterize them. Selection against the DLL1 protein was also performed, once it is a known ligand of the Notch pathway, whose deregulation is associated to breast cancer, making it an interesting target for the generation of function-blocking Abs. Selection resulted in the isolation of a clone with low affinity and Fab expression levels. The validation process was not completed and further effort will have to be put in this task in the future. Although immune libraries concept implies limited applicability, the library reported here has a wide range of use possibilities, since it was not restrained to a single antigen but instead thought to be used against any breast cancer associated target, thus being a valuable tool.