Neuropathology of central nervous system involvement in TTR amyloidosis

Hereditary transthyretin amyloidosis (ATTRv) is a systemic disease caused by the accumulation of misfolded transthyretin (TTR). It usually presents with an adult-onset progressive axonal peripheral neuropathy and cardiomyopathy. In the central nervous system (CNS), variant TTR is produced by the choroid plexus and accumulates in the leptomeninges. CNS symptoms have been increasingly recognized in this population, including transient focal neurological episodes and stroke, particularly in patients with the V30M mutation and longstanding disease. The prevalence, pathophysiology, and progression of CNS involvement remain to be clarified. The present work explores if there is a recognizable sequence of CNS TTR deposition in ATTRv. We studied the topographical and severity distribution of TTR deposition in 16 patients with ATTRv, aged 27–69 years and with a mean disease duration of 10.9 years (range: 3–29). Our results suggest that CNS pathological involvement in V30M ATTRv occurs early in the disease course, probably starting in pre-symptomatic phases, and follows a distinct sequence. Leptomeninges and subarachnoid meningeal vessels are affected earlier, then followed by perforating cortical vessels and subpial deposition, and finally by deposition in the subependymal and basal ganglia vessels near the ependymal lining. Brainstem and spinal cord show early and severe involvement, with amyloid subpial deposition already seen in initial stages. Despite massive superficial amyloid deposition, no parenchymal deposition outside subpial or subependymal regions was found. Additionally, vascular lesions or superficial cortical siderosis were not frequent. Future studies with more patients from different populations and TTR mutations will be important to confirm these findings. Defining stages of TTR pathology in the CNS may be useful to better understand pathogenic mechanisms leading to symptoms and to interpret neuroimaging biomarkers.Unit for Multidisciplinary Research in Biomedicine (UMIB) is funded by the Foundation for Science and Technology (FCT) Portugal (Grant Numbers UIDB/00215/2020, and UIDP/00215/2020). We acknowledge Portuguese Brain Bank for tissue samples supply. The authors thank José Ferreira for the help in editing the manuscript figures

Combining experiments and in silico modeling to infer the role of adhesion and proliferation on the collective dynamics of cells

The collective dynamics of cells on surfaces and interfaces poses technological and theoretical challenges in the study of morphogenesis, tissue engineering, and cancer. Different mechanisms are at play, including, cellâ cell adhesion, cell motility, and proliferation. However, the relative importance of each one is elusive. Here, experiments with a culture of glioblastoma multiforme cells on a substrate are combined with in silico modeling to infer the rate of each mechanism. By parametrizing these rates, the time-dependence of the spatial correlation observed experimentally is reproduced. The obtained results suggest a reduction in cellâ cell adhesion with the density of cells. The reason for such reduction and possible implications for the collective dynamics of cancer cells are discussed.e Portuguese Foundation for Science and Technology (FCT) under Contracts no. PTDC/FIS-MAC/28146/2017 (LISBOA-01-0145-FEDER-028146), UIDB/00618/2020, and UIDP/00618/2020. F.R.M. also acknowledges FCT for her contract under the Transitional Rule DL 57/2016 (CTTI-57/18-I3BS(5)

Equine infectious anemia affects the athletic performance of equines from the Brazilian Pantanal region.

The objective of this work was to evaluate the effects of equine infectious anemia (EIA) on the physical performance of equines from the Brazilian Pantanal region. A total of 16 males were evaluated, divided into two groups: 8 seronegative (G1) and 8 seropositive (G2) for EIA. Two graded exercise tests were carried out before (T1) and after (T2) 42 days of training. Heart rate, lactate concentration, distance covered, and hematocrit level were recorded. In both tests, G1 covered a greater distance. In T2, G2 had lower hematocrit levels and lower speeds reached at different lactate concentrations and heart rates. The athletic performance of the evaluated equines is affected by equine infectious anemia. O objetivo deste trabalho foi avaliar o efeito da anemia infecciosa equina (AIE) no desempenho físico de equinos da região do Pantanal brasileiro. Foram avaliados 16 machos, divididos em dois grupos: 8 soronegativos (G1) e 8 soropositivos (G2) para AIE. Dois testes de esforço progressivo foram realizados, antes (T1) e após (T2) 42 dias de treinamento. Foram registrados frequência cardíaca, concentração de lactato, distância percorrida e níveis de hematócrito. Em ambos os testes, o G1 percorreu uma distância maior. No T2, o G2 apresentou menores níveis de hematócrito e menor velocidade obtida a diferentes concentrações de lactato e frequências cardíacas. O desempenho atlético dos equídeos avaliados é afetado pela anemia infecciosa equina

The implementation of radiation technology program in Portugal

The development of ionizing radiation pplications for Industrial purposes in Portugal began near of 1982 with the support of IAEA. The main steps to put forward prior to the implementation were the sitting and the design study in order to build up the facility. Subsequently, the main parameters to be achieved were the construction, the commissioning, the operation, the maintenance and the foreseen decommission. Once a quality system for the gamma facility was established, the following stage is to develop, validate and control the terilization/disinfection process. The research activities carried out in the UTR have been closely related with the main applications of this technology namely, the sterilization of medical devices and pharmaceuticals and other products’ decontamination. Recently, a research Cobalt-60 equipment was upgraded and a LINAC was implemented in order to sustain the R&D. Fundamental and development research is ngoing in order to understand the irradiation mechanisms of action and to apply the technology with safety and quality patterns.The first author would like to thank Gulbenkian Foundation in Portugal and NIC2010 the financial support for the opportunity to participate at NAARRI International Conference

A selective p53 activator and anticancer agent to improve colorectal cancer therapy

Impairment of the p53 pathway is a critical event in cancer. Therefore, reestablishing p53 activity has become one of the most appealing anticancer therapeutic strategies. Here, we disclose the p53-activating anticancer drug (3S)-6,7-bis(hydroxymethyl)-5-methyl-3-phenyl-1H,3H-pyrrolo[1,2-c]thiazole (MANIO). MANIO demonstrates a notable selectivity to the p53 pathway, activating wild-type (WT)p53 and restoring WT-like function to mutant (mut)p53 in human cancer cells. MANIO directly binds to the WT/mutp53 DNA-binding domain, enhancing the protein thermal stability, DNA-binding ability, and transcriptional activity. The high efficacy of MANIO as an anticancer agent toward cancers harboring WT/mutp53 is further demonstrated in patient-derived cells and xenograft mouse models of colorectal cancer (CRC), with no signs of undesirable side effects. MANIO synergizes with conventional chemotherapeutic drugs, and in vitro and in vivo studies predict its adequate drug-likeness and pharmacokinetic properties for a clinical candidate. As a single agent or in combination, MANIO will advance anticancer-targeted therapy, particularly benefiting CRC patients harboring distinct p53 status.We thank PT national funds (FCT/MCTES , Fundação para a Ciência e a Tecnologia , and Ministério da Ciência, Tecnologia e Ensino Superior ) through grants UIDB/50006/2020 , UID/BIO/04469/2019 , UIDB/04539/2020 , and UIDP/04539/2020 ( CIBB ); BioTecNorte operation ( NORTE-01-0145-FEDER-000004 ) and Porto Neurosciences and Neurologic Disease Research Initiative at I3S ( Norte-01-0145-FEDER-000008 ) funded by the European Regional Development Fund under the scope of Norte2020 - Programa Operacional Regional do Norte ; Masaryk University ( Project MUNI/A/1127/2019 ) and Ministry of Education, Youth and Sports of the Czech Republic (project nos. LQ1605 and LM2018125 ); FCT financial support through the fellowships SFRH/BD/119144/2016 (H.R.) and SFRH/BD/117949/2016 (L.R.); Fondazione AIRC ( IG#18985 , A.I.); and the Programa Operacional Potencial Humano (POCH), specifically the BiotechHealth Programme (Doctoral Programme on Cellular and Molecular Biotechnology Applied to Health Sciences , PD/00016/2012 ). We thank Dario Rizzotto for assistance in preparing the libraries for RNA sequencing. Funding: This work was supported by PT National Funds (FCT/MCTES, Fundação para a Ciência e Tecnologia , and Ministério da Ciência, Tecnologia e Ensino Superior ) via the projects UIDB/50006/2020 ( LAQV/REQUIMTE ), UIDB/00313/2020 , and UIDP/00313/2020 , co-funded by COMPETE2020-UE

Avaliação de cultivares de bananeiras no recôncavo sul da Bahia.

A Bahia é na atualidade o primeiro estado produtor nacional de bananas, com 17% da produção, somando 1.429.010 toneladas de cachos, seguido por São Paulo com 1.238.087 toneladas (IBGE, 2005 -2007). O Estado foi reconhecido pelo Ministério da Agricultura, Pecuária e Abastecimento (Mapa) como área livre da Sigatoka-negra, a mais temida doença das bananeiras na atualidade. A EBDA, visando assegurar o agronegócio da bananicultura no Estado, implantou 12 ?Unidades de Avaliação de Genótipos de Bananeira? resistentes a esta doença, nas principais regiões produtoras, dentre as quais, a região do Recôncavo Sul da Bahia.Uma das mais graves doenças da bananeira é a Sigatoka-negra, causada pelo fungo Micosphaerella fijiensis, Morelet, forma perfeita da fase Paracercospora fijiensis (Morelet) Deighton, que ataca as folhas da planta, ocasionando perdas em rendimentos de 50 a 100% a depender das condições edafoclimáticas e da cultivar. Além disso, a comercialização dos produtos oriundos das regiões onde a doença já foi detectada é proibida, visando impedir a disseminação do patógeno.No Brasil, as variedades tradicionalmente cultivadas são suscetíveis à Sigatoka-negra. Uma das estratégias para a solução desse problema é a criação de variedades resistentes mediante o melhoramento genético. A etapa final do melhoramento constitui-se na avaliação dos genótipos em áreas de produção (Silva, et al 2000). As principais características consideradas em trabalhos de tal natureza são: resistência à doença, ciclo da cultura, altura da planta, peso do cacho, número e comprimento de fruto (Moreira & Saes, 1984; Silva et al.2000). A avaliação de novas cultivares junto aos agricultores, em quadras demonstrativas, pode facilitar a sua adoção (Silveira et al., 1999).pdf 141

Influence of Clinical Status and Parasite Load on Erythropoiesis and Leucopoiesis in Dogs Naturally Infected with Leishmania (Leishmania) chagasi

Background: The bone marrow is considered to be an important storage of parasites in Leishmania-infected dogs, although little is known about cellular genesis in this organ during canine visceral leishmaniasis (CVL). Methodology/Principal Findings: The aim of the present study was to evaluate changes in erythropoiesis and leucopoiesis in bone marrow aspirates from dogs naturally infected with Leishmania chagasi and presenting different clinical statuses and bone marrow parasite densities. The evolution of CVL from asymptomatic to symptomatic status was accompanied by increasing parasite density in the bone marrow. The impact of bone marrow parasite density on cellularity was similar in dogs at different clinical stages, with animals in the high parasite density group. Erythroid and eosinophilic hypoplasia, proliferation of neutrophilic precursor cells and significant increases in lymphocytes and plasma cell numbers were the major alterations observed. Differential bone marrow cell counts revealed increases in the myeloid:erythroid ratio associated to increased numbers of granulopoietic cells in the different clinical groups compared with non-infected dogs. Conclusions: Analysis of the data obtained indicated that the assessment of bone marrow constitutes an additional and useful tool by which to elaborate a prognosis for CVL

Distinct mRNA and protein interactomes highlight functional differentiation of major eIF4F-like complexes from Trypanosoma brucei

Gene expression in pathogenic protozoans of the family Trypanosomatidae has several novel features, including multiple eIF4F-like complexes involved in protein synthesis. The eukaryotic eIF4F complex, formed mainly by eIF4E and eIF4G subunits, is responsible for the canonical selection of mRNAs required for the initiation of mRNA translation. The best-known complexes implicated in translation in trypanosomatids are based on two related pairs of eIF4E and eIF4G subunits (EIF4E3/EIF4G4 and EIF4E4/EIF4G3), whose functional distinctions remain to be fully described. Here, to define interactomes associated with both complexes in Trypanosoma brucei procyclic forms, we performed parallel immunoprecipitation experiments followed by identification of proteins co-precipitated with the four tagged eIF4E and eIF4G subunits. A number of different protein partners, including RNA binding proteins and helicases, specifically co-precipitate with each complex. Highlights with the EIF4E4/EIF4G3 pair include RBP23, PABP1, EIF4AI and the CRK1 kinase. Co-precipitated partners with the EIF4E3/EIF4G4 pair are more diverse and include DRBD2, PABP2 and different zinc-finger proteins and RNA helicases. EIF4E3/EIF4G4 are essential for viability and to better define their role, we further investigated their phenotypes after knockdown. Depletion of either EIF4E3/EIF4G4 mRNAs lead to aberrant morphology with a more direct impact on events associated with cytokinesis. We also sought to identify those mRNAs differentially associated with each complex through CLIP-seq with the two eIF4E subunits. Predominant among EIF4E4-bound transcripts are those encoding ribosomal proteins, absent from those found with EIF4E3, which are generally more diverse. RNAi mediated depletion of EIF4E4, which does not affect proliferation, does not lead to changes in mRNAs or proteins associated with EIF4E3, confirming a lack of redundancy and distinct roles for the two complexes

Levantamento de reconhecimento de baixa e média intensidade dos solos do Estado de Pernambuco.

Os estudos de solos foram desenvolvidos em nível de reconhecimento de baixa e média intensidade, escala 1:100.000, cobrindo toda superfície do Estado de Pernambuco, com aproximadamente 98.938 km2. Os trabalhos foram realizados por meio da parceria entre o Centro Nacional de Pesquisa de Solos (CNPS) - Escritório Regional de Pesquisa e Desenvolvimento Nordeste (ERP/NE) e o Governo do Estado de Pernambuco. O objetivo principal do levantamento de solos foi gerar dados para dar suporte à elaboração do Zoneamento Agroecológico do Estado. A metodologia utilizada seguiu as normas do Serviço Nacional de Levantamento e Conservação de Solos (SNLCS), atual Centro Nacional de Pesquisa de Solos. Os resultados dos estudos mostram que os solos de maior expressão, ocupando cerca de 61% da área, pertencem às classes dos Podzólicos (25%), Solos Litólicos (20%) e, Planossolos e Solonetz Solodizados (16%). Ocupam cerca 23% da área, os solos das classes dos Latossolos (9%), Brunos Não Cálcicos (9%) e Areias Quartzosas (5%). Perfazem cerca de 7% da área, os solos das classes dos Regossolos (5%) e Solos Aluviais (2%). Cerca de 4% da área é ocupada por solos diversos, incluindo os Cambissolos, Gleissolos, Podzóis, Vertissolos, Solos Indiscriminados de Mangues, Brunizéns, Terra Roxa Estruturada e Plintossolos. Os tipos de terrenos, principalmente afloramentos de rocha, ocupam uma superfície ao redor de 3% da área. Cerca de 2% da superfície do Estado correspondem às águas internas.bitstream/item/69954/1/Boletim-de-Pesquisa-Final-11.pdf; bitstream/item/216858/1/Mapa-de-reconhecimento-de-baixa-e-media-intensidade-de-solos-do-estado-de-Pernambuco.pd