Evaluation of the growth-inhibitory effect of trifluralin analogues on in vitro cultured Babesia bovis parasites

Bovine babesiosis, caused by Babesia bovis, is a global tick borne hemoprotozoan parasite disease characterized by fever, anemia, weight losses and ultimately death. Several babesicidal drugs that have been in use in cattle for years have proven to be only partially effective and the development of alternative chemotherapeutics that are highly specific and have low toxicity against babesiosis is needed. Trifluralin derivatives specifically bind alpha-tubulin in plants and protozoa parasites causing growth inhibition. A set of 12 trifluralin analogues (TFLA) has previously been shown to be inhibitory for the growth of Leishmania species. The conservation of several key amino acids involved in the trifluralin binding site of alpha-tubulin among Leishmania sp. and B. bovis provides rationale for testing these compounds also as babesiacides. The previously tested Leishmania inhibitory, TFLA 1-12 minus TFLA 5, in addition to three novel TFLA (termed TFLA 13-15), were tested against in vitro cultured B. bovis parasites. While all of the TFLA tested in the study showed inhibition of B. bovis growth in vitro TFLA 7, TFLA 10 and TFLA 13, were the most effective inhibitors with estimated IC50 (μM) at 72h of 8.5±0.3; 9.2±0.2; 8.9±0.7, respectively for the biologically attenuated cloned B. bovis Mo7 strain, and 13.6±1.5; 18.7±1.6; 10.6±1.9, respectively for the virulent B. bovis T3Bo strain. The differences found between the two strains were not statistically significant. Importantly, these drugs displayed low levels of toxicity for the host erythrocytes and bovine renal arterial endothelial cells at the doses tested. The demonstrated ability of trifluralin analogues to inhibit in vitro growth of B. bovis parasites combined with their low toxicity for host cells suggests that these compounds may be further developed as novel alternatives for the treatment of bovine babesiosis.publishersversionpublishe

Slow pyrolysis of cork granules under nitrogen atmosphere: by-products characterization and their potential valorization

ABSTRACT: Cork granules (Quercus suber L.) were slowly pyrolyzed at temperatures between 400-700 degrees C and under N-2 flow. While preserving its structure, some cells of the cork biochar became interconnected, allowing such carbon residue to be used as templates for manufacturing ceria redox materials. The pyrolytic char morphology was similar to that of the natural precursor. The produced cork biochar belonged to Class 1 (C > 60%) and possessed a high heating value of 32 MJ kg(-1). Other pyrolysis-derived compounds were identified and quantified through GC-FID and GC-MS analyses. The yield of gases released during cork pyrolysis was strongly dependent on the temperature used due to the thermal decomposition reactions involved in the degradation of cork. In particular, rising pyrolysis temperature from 500 to 700 T resulted in reducing the total hydrocarbon gases from 74 to 24 vol%. On the other hand, the yield of H-2 increased from 0 to 58% by increasing the pyrolysis temperature from 400 to 700 T. Due to the presence of suberin in cork, the composition and yield of bio-oil could be regulated by the pyrolysis temperature. Cork bio-oil was found to consist of long-chain hydrocarbons (from C11 to C24). The bio-oil resulting from the slow pyrolysis of cork residues is suitable as an appropriate feedstock for producing aliphatic-rich pyrolytic biofuels or as a source of olefms. Overall, the findings of this study suggest that Quercus suber L. could be a promising feedstock for biochar and biofuel production through the pyrolytic route and could contribute to the environmental and economic sustainability of the cork production industry.info:eu-repo/semantics/publishedVersio

Changes in bone Pb accumulation: Cause and effect of altered bone turnover

Notice: this is the author’s version of a work that was accepted for publication in Bone. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Bone, [Vol 64 (2014 Jul)] DOI 10.1016/j.bone.2014.04.021"This paper assesses the magnitude of Pb uptake in cortical and trabecular bones in healthy animals and animals with altered balance in bone turnover, and the impact of exposure to Pb on serum markers of bone formation and resorption. The results reported herein provide physiological evidence that Pb distributes differently in central compartments in Pb metabolism, such as cortical and trabecular bone, in healthy animals and animals with altered balance in bone turnover, and that exposure to Pb does have an impact on bone resorption resulting in OC-dependent osteopenia. These findings show that Pb may play a role in the etiology of osteoporosis and that its concentration in bones varies as a result of altered bone turnover characteristic of this disease, a long standing question in the field. In addition, data collected in this study are consistent with previous observations of increased half-life of Pb in bone at higher exposures. This evidence is relevant for the necessary revision of current physiologically based kinetic models for Pb in humans.

Morfologias urbanas e espaços públicos na Metrópole de Lisboa: uma aproximação instrumental e metodológica no quadro de uma investigação

O texto que aqui se apresenta resulta de uma pesquisa em curso cuja a temática central se desenvolve em torno dos espaços públicos e do protagonismo urbano. Apresenta-se um quadro instrumental e metodológico, que se encontra em fase experimental de aplicação. Uma das hipóteses de pesquisa, apoiada no respectivo trabalho de observação empírica, tende a ilustrar o eventual protagonismo da Metrópole de Lisboa através da manifestação ou emergência de factores conducentes a uma determinada qualidade social e urbana do espaço em observação. Partindo-se da hipótese que existem determinadas áreas emblemáticas das transformações sociais e territoriais e condicionantes da configuração metropolitana, procurou-se estruturar um quadro metodológico que facilitasse a utilização e articulação do material empírico resultante da análise de espaços públicos concretos da Metrópole de Lisboa, olhada através de diferentes lentes analíticas: a escala metropolitana, a escala urbana e a escala local. A matriz analítica centrada no espaço público enquanto base para o estudo do protagonismo urbano (nas perspectivas urbanística, política e sociocultural) assenta em quatro dimensões analíticas. Procura-se uma nova síntese do urbano na qual o espaço público é simultaneamente objecto de análise e vertente analítica privilegiada para a concretização dos planos analíticos que enquadram o estudo do protagonismo urbano em espaço público.FCT - Fundação para a Ciência e a TecnologiaCâmara Municipal de Lisboa – CulturaMinistério da Cultur

Demographic connectivity of sardine in the Bay of Biscay and Iberian coast region

Demographic connectivity in sardine populatio

Clinical Epidemiology of Buruli ulcer from Benin (2005-2013): effect of time-delay to diagnosis on clinical forms and severe phenotypes

Buruli Ulcer (BU) is a neglected infectious disease caused by Mycobacterium ulcerans that is responsible for severe necrotizing cutaneous lesions that may be associated with bone involvement. Clinical presentations of BU lesions are classically classified as papules, nodules, plaques and edematous infiltration, ulcer or osteomyelitis. Within these different clinical forms, lesions can be further classified as severe forms based on focality (multiple lesions), lesions' size (>15 cm diameter) or WHO Category (WHO Category 3 lesions). There are studies reporting an association between delay in seeking medical care and the development of ulcerative forms of BU or osteomyelitis, but the effect of time-delay on the emergence of lesions classified as severe has not been addressed. To address both issues, and in a cohort of laboratory-confirmed BU cases, 476 patients from a medical center in Allada, Benin, were studied. In this laboratory-confirmed cohort, we validated previous observations, demonstrating that time-delay is statistically related to the clinical form of BU. Indeed, for non-ulcerated forms (nodule, edema, and plaque) the median time-delay was 32.5 days (IQR 30.0-67.5), while for ulcerated forms it was 60 days (IQR 20.0-120.0) (p = 0.009), and for bone lesions, 365 days (IQR 228.0-548.0). On the other hand, we show here that time-delay is not associated with the more severe phenotypes of BU, such as multi-focal lesions (median 90 days; IQR 56-217.5; p = 0.09), larger lesions (diameter >15 cm) (median 60 days; IQR 30-120; p = 0.92) or category 3 WHO classification (median 60 days; IQR 30-150; p = 0.20), when compared with unifocal (median 60 days; IQR 30-90), small lesions (diameter =15 cm) (median 60 days; IQR 30-90), or WHO category 1+2 lesions (median 60 days; IQR 30-90), respectively. Our results demonstrate that after an initial period of progression towards ulceration or bone involvement, BU lesions become stable regarding size and focal/multi-focal progression. Therefore, in future studies on BU epidemiology, severe clinical forms should be systematically considered as distinct phenotypes of the same disease and thus subjected to specific risk factor investigation.The research leading to these results received funding from the Health Services of the Fundacao Calouste Gulbenkian under the grant Proc. No94776 LJ; from the Fundacao para a Ciecia e Tecnologia (FCT), cofunded by Programa Operacional Regional do Norte (ON.2-O Novo Norte); from the Quadro de Referencia Estrategico Nacional (QREN) through the Fundo Europeu de Desenvolvimento Regional (FEDER) and from the Projeto Estrategico - LA 26 - 2013-2014 (PEst-C/SAU/LA0026/2013). A. G. Fraga received an individual FCT fellowship (SFRH/BPD/68547/2010) and J. Menino received an individual QREN fellowship (UMINHO/BPD/14/2014). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

The complete sequence of a 9000 bp fragment of the right arm of Saccharomyces cerevisiae chromosome VII contains four previously unknown open reading frames

We report the sequence of a 9000 bp fragment from the right arm of Saccharomyces cerevisiae chromosome VII. Analysis of the sequence revealed four complete previously unknown open reading frames, which were named G7587, G7589, G7591 and G7594 following standard rules for provisional nomenclature. Outstanding features of some of these proteins were the homology of the putative protein coded by G7589 with proteins involved in transcription regulation and the transmembrane domains predicted in the putative protein coded by G7591

What Darwin did not see : Pleistocene fossil assemblages on a highenergy coast at Ponta das Bicudas, Santiago, Cape Verde Islands

Two distinct Pleistocene assemblages from SE Santiago Island are comparable to modern analogues elsewhere in the Cape Verde Islands. A low-diversity Siderastrea radians assemblage lived atop basalt knobs surrounded by sand on a slope below a cliff. A Millepora alcicornis–Megabalanus azoricus assemblage occupied the cliff. The latter was a typical rocky-shore assemblage from a high-energy setting belowthe tidal zone.Bioerosion structures in basalt produced by Circolites kotoncensis and Gastrochaenolites isp. also occur there. Despite extensive studies on local limestone deposits in 1832 and 1836, lack of exposure prevented Darwin from seeing these fossils.Funding for fieldwork on Santiago Island in June 2011 was provided under grant CGL2010-15372-BTE from the Spanish Ministry of Science and Innovation to project leader Eduardo Mayoral (University of Huelva). Financial support to A. Santos came from the Spanish Ministry of Science and Technology (Juan de la Cierva subprogram, Ref: JCI-2008-2431). Additional support by the Junta de Andalucia (Spanish government) to the Research Group RNM276 is also acknowledged. Partial funding to J. Ledesma-Vazquez on this project came from the Programma Integral de Fortalecimiento Institucional 2010. We thank Christopher K. Pham, Department of Oceanography and Fisheries, University of the Azores, Portugal, for help with identification of the fossil barnacles and Ricardo Ramalho, Institut fur Geophysik, Westphalishe-Wilhelms Universitat, Germany, for discussions about bioerosion by sea urchins on basalt surfaces

Genome of the Avirulent Human-Infective Trypanosome—Trypanosoma rangeli

Background: Trypanosoma rangeli is a hemoflagellate protozoan parasite infecting humans and other wild and domestic mammals across Central and South America. It does not cause human disease, but it can be mistaken for the etiologic agent of Chagas disease, Trypanosoma cruzi. We have sequenced the T. rangeli genome to provide new tools for elucidating the distinct and intriguing biology of this species and the key pathways related to interaction with its arthropod and mammalian hosts.  Methodology/Principal Findings: The T. rangeli haploid genome is ,24 Mb in length, and is the smallest and least repetitive trypanosomatid genome sequenced thus far. This parasite genome has shorter subtelomeric sequences compared to those of T. cruzi and T. brucei; displays intraspecific karyotype variability and lacks minichromosomes. Of the predicted 7,613 protein coding sequences, functional annotations could be determined for 2,415, while 5,043 are hypothetical proteins, some with evidence of protein expression. 7,101 genes (93%) are shared with other trypanosomatids that infect humans. An ortholog of the dcl2 gene involved in the T. brucei RNAi pathway was found in T. rangeli, but the RNAi machinery is non-functional since the other genes in this pathway are pseudogenized. T. rangeli is highly susceptible to oxidative stress, a phenotype that may be explained by a smaller number of anti-oxidant defense enzymes and heatshock proteins.  Conclusions/Significance: Phylogenetic comparison of nuclear and mitochondrial genes indicates that T. rangeli and T. cruzi are equidistant from T. brucei. In addition to revealing new aspects of trypanosome co-evolution within the vertebrate and invertebrate hosts, comparative genomic analysis with pathogenic trypanosomatids provides valuable new information that can be further explored with the aim of developing better diagnostic tools and/or therapeutic targets