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Integration of statistics and food process engineering: Assessing the uncertainty of thermal processing and shelf-life estimations
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Uncovering the neuroprotective mechanisms of curcumin on transthyretin amyloidosis
Transthyretin (TTR) amyloidoses (ATTR amyloidosis) are diseases associated with transthyretin (TTR) misfolding, aggregation and extracellular deposition in tissues as amyloid. Clinical manifestations of the disease are variable and include mainly polyneuropathy and/or cardiomyopathy. The reasons why TTR forms aggregates and amyloid are related with amino acid substitutions in the protein due to mutations, or with environmental alterations associated with aging, that make the protein more unstable and prone to aggregation. According to this model, several therapeutic approaches have been proposed for the diseases that range from stabilization of TTR, using chemical chaperones, to clearance of the aggregated protein deposited in tissues in the form of oligomers or small aggregates, by the action of disruptors or by activation of the immune system. Interestingly, different studies revealed that curcumin presents anti-amyloid properties, targeting multiple steps in the ATTR amyloidogenic cascade. The effects of curcumin on ATTR amyloidosis will be reviewed and discussed in the current work in order to contribute to knowledge of the molecular mechanisms involved in TTR amyloidosis and propose more efficient drugs for therapy.This research was funded by the European Regional Development Fund (FEDER) through the Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, grant number Norte-01-0145-FEDER-000008—Porto Neurosciences and Neurologic Disease Research Initiative at I3S. Nelson Ferreira was a recipient of a Postdoctoral Fellowship R171-2014-591 from Lundbeck foundation and by Lundbeck Foundation grant R248-2016-2518 for Danish Research Institute of Translational Neuroscience—DANDRITE, Nordic-EMBL Partnership for Molecular Medicine, Aarhus University, Denmark
Membrane Type 1 Matrix Metalloproteinase Regulates Monocyte Migration and Collagen Destruction in Tuberculosis
Tuberculosis (TB) remains a global pandemic and drug resistance is rising. Multicellular granuloma formation is the pathological hallmark of Mycobacterium tuberculosis infection. The membrane type 1 matrix metalloproteinase (MT1-MMP or MMP-14) is a collagenase that is key in leukocyte migration and collagen destruction. In patients with TB, induced sputum MT1-MMP mRNA levels were increased 5.1-fold compared with matched controls and correlated positively with extent of lung infiltration on chest radiographs (r = 0.483; p < 0.05). M. tuberculosis infection of primary human monocytes increased MT1-MMP surface expression 31.7-fold and gene expression 24.5-fold. M. tuberculosis-infected monocytes degraded collagen matrix in an MT1-MMP-dependent manner, and MT1-MMP neutralization decreased collagen degradation by 73%. In human TB granulomas, MT1-MMP immunoreactivity was observed in macrophages throughout the granuloma. Monocyte-monocyte networks caused a 17.5-fold increase in MT1-MMP surface expression dependent on p38 MAPK and G protein-coupled receptor-dependent signaling. Monocytes migrating toward agarose beads impregnated with conditioned media from M. tuberculosis-infected monocytes expressed MT1-MMP. Neutralization of MT1-MMP activity decreased this M. tuberculosis network-dependent monocyte migration by 44%. Taken together, we demonstrate that MT1-MMP is central to two key elements of TB pathogenesis, causing collagen degradation and regulating monocyte migration
Surviving in a second language: survival processing effect in memory of bilinguals
Human memory likely evolved to serve adaptive functions, that is, to help maximise our chances of survival and reproduction. One demonstration of such adaptiveness is the increased retention of information processed in survival contexts, the so-called Survival Processing Effect (SPE). This study examined this effect in a native (L1) and in a second language (L2). This comparison is relevant to explore if emotionality is involved in the SPE, as emotional activation seems to be larger in L1 than in L2. Following the original survival processing procedure, participants rated the relevance of information to the survival and moving scenarios and performed a recognition (Experiment 1) or a free recall (Experiment 2) task in L1 or L2. In both experiments, the SPE was replicated in L1 but not in L2. The absence of the effect when emotional activation is less likely suggests that emotionality might play a role in the survival processing effect; nevertheless, additional studies are needed to further investigate this hypothesis.info:eu-repo/semantics/acceptedVersio
High Efficacy of Two Artemisinin-Based Combinations (Artesunate + Amodiaquine and Artemether + Lumefantrine) in Caala, Central Angola.
In April 2004, 137 children 6-59 months of age with uncomplicated Plasmodium falciparum (Pf) malaria (Caala, Central Angola) were randomized to receive either artemether-lumefantrine (Coartem) or artesunate + amodiaquine (ASAQ). After 28 days of follow-up, there were 2/61 (3.2%) recurrent parasitemias in the Coartem group and 4/64 (6.2%) in the ASAQ group (P = 0.72), all classified as re-infections after PCR genotyping (cure rate = 100% [95%CI: 94-100] in both groups). Only one patient (ASAQ group) had gametocytes on day 28 versus five (Coartem) and three (ASAQ) at baseline. Compared with baseline, anemia was significantly improved after 28 days of follow-up in both groups (Coartem: from 54.1% to 13.4%; ASAQ: from 53.1% to 15.9%). Our findings are in favor of a high efficacy of both combinations in Caala. Now that Coartem has been chosen as the new first-line anti-malarial, the challenge is to insure that this drug is available and adequately used
Citoplastos receptores produzidos por diferentes técnicas de enucleação na transferência nuclear em bovinos.
Uma das etapas mais críticas do procedimento de transferência nuclear (TN) é a remoção da cromatina do oócito para a produção de citoplastos. O objetivo deste trabalho foi estudar o efeito de diferentes ambientes citoplasmáticos obtidos a partir de três técnicas de enucleação (convencional, assistida quimicamente e induzida quimicamente) sobre o remodelamento nuclear e desenvolvimento embrionário, avaliando-se o perfil de expressão dos genes XIST, G6PD e HSPA1A em embriões bovinos. Para isso, quatro experimentos foram delineados. No primeiro experimento, verificou-se que o processo de enucleação pode ser iniciado a partir de 1,0 h de tratamento com demecolcina nas duas técnicas de enucleação química. A dinâmica nuclear e de microtúbulos de oócitos ativados tratados com demecolcina foi avaliada em um segundo experimento, e oócitos tratados apresentaram redução da densidade dos microtúbulos, porém, essas estruturas não desapareceram completamente na maioria dos oócitos. No experimento III, a demecolcina não apresentou efeitos significativos na atividade do fator promotor de maturação (MPF) e da proteína cinase ativada por mitógeno (MAPK) quando utilizada na concentração 0,05μg/mL. No último experimento, a demecolcina não prejudicou o desenvolvimento embrionário e também não alterou o perfil de expressão dos genes XIST, G6PD e HSPA1A em embriões reconstituídos com células embrionárias; porém, quando foram avaliados os níveis de transcritos desses genes em embriões reconstituídos com células somáticas, observou-se maior expressão relativa do XIST e do G6PD em embriões oriundos da técnica de enucleação assistida quimicamente em comparação aos embriões produzidos pela técnica convencional. Portanto, conclui-se que a enucleação química não altera a reprogramação nuclear nem o desenvolvimento embrionário quando são utilizadas células doadoras embrionárias no procedimento de TN. Ainda, a técnica de enucleação assistida quimicamente promove incrementos na expressão dos genes XIST e G6PD quando são utilizadas células somáticas, mostrando que o uso da demecolcina é uma importante ferramenta no procedimento de transferência nuclear.Sob co-orientação Dra. Simone Cristina Méo Niciura
Para ler a América Latina: Tad Szulc, As relações Interamericanas e a política externa dos Estados Unidos (1955-1965)
This research examines Tad Szulc's writings and performance (1926-2001) in inter-American post-war relations. He was an American intellectual relevant to inter-American relations in the second half of the twentieth century. He was a press professional linked to The New York Times. He made an itinerant journalistic coverage that crossed America writing on key issues of politics at the time: development; nationalism and communism. He spoke with heads of state, bureaucrats and intellectuals, and worked closely with state and private initiatives across the continent, including governments, large corporations and intelligence services. His journalistic work and books published between September 1955 and May 1965. He examines the sociopolitical analyzes that the journalist formulated of the region and the foreign policy of the United States, his trajectory with private institutions, administrations and government agencies in the States United States and Latin America. In that period, Szulc wrote more than one thousand five hundred articles, articles, reviews and travel reports and launched five books on Latin America. These publications are the central sources of research. In addition to these, this work examines a roll of periodicals, diplomatic dispatches, intelligence reports, official speeches and memoir books. This research investigates the role of the United States's international correspondence for inter-American post-war relations. It mobilizes recurrent
interpretations for this question that emphasize the correspondents as: interpreters of Latin American reality; critics of internal and external politics; tentacles of US political, military, and economic power; agents of Latin American governments and interests. The thesis argues
that all these roles are simultaneous and that the correspondent is a mediator with his own interests
Spondylodiscitis associated with recurrent Serratia bacteremia due to a transjugular intrahepatic portosystemic shunt (TIPS): a case report
We report a case of spondylodiscitis caused by multiresistant Serratia marcescens in a cirrhotic patient who had several Serratia bacteremias after the placement of a transjugular intrahepatic portosystemic shunt (TIPS) device. We concluded that an endovascular stent that can not be removed makes management of recurrent bacteremia difficult. Furthermore, back pain due to bacteremia is indicative of spondylodiscitis. Serratia marcescens can be an aggressive pathogen, causing spinal infection
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