Integrated metabolic flux and omics analysis of leishmania major metabolism

Leishmaniasis is a virulent parasitic infection that causes a significant threat to human health worldwide. The existing drugs are becoming less effective due to the ability of Leishmania spp. to alter its metabolism to adapt to harsh environments. Understanding how this parasite manipulates its metabolism inside the host (e.g. sandfly and human) might underpin new ways to prevent the disease and develop effective treatment strategies. Despite significant advances in omics technologies, biochemistry of parasites still lacks the understanding of molecular components that determine the metabolic behavior under varying conditions. Metabolic network modeling might be of interest to identify physiologically relevant nodes in a metabolic network. The present work proposes a metabolic model iSK570 (an extension of the iAC560 model) with additional reactions for the metabolism of lipids, long chain fatty acids and carbohydrates to study the metabolic behavior of this parasite. Gene Inactivity Moderated by Metabolism and Expression (GIMME) algorithm was used to verify the consistency between model flux predictions and gene expression data. Improved flux distributions were obtained, allowing a more accurate understanding of stage-specific metabolism in of promastigotes and amastigotes.This work was supported by the Initial Training Network, GlycoPar, funded by the FP7 Marie Curie Actions of the European Commission (FP7-PEOPLE-2013-ITN-608295). The authors gratefully express appreciation to SilicoLife Lda for providing required infrastructural facilities related to this work. We also thank Bruno Pereira (systems biologist at SilicoLife) and Hugo Giesteira (programmer at SilicoLife) for scientific and technical assistance during various phases of the project.info:eu-repo/semantics/publishedVersio

Avaliação do grau de exposição de seres humanos da Sub-Região da Cova da Beira ao Agente Zoonótico Leishmania infantum

leishmaniose é uma doença infeciosa causada por protozoários do género Leishmania. Aproximadamente 20 espécies apresentam caráter zoonótico, sendo a transmissão efetuada sobretudo pela picada de insetos flebotomíneos hematófagos, que funcionam como vetores. A bacia do Mediterrâneo é endémica para a espécie L.infantum, responsável por uma das formas mais graves da doença: a leishmaniose visceral. O cão é o principal hospedeiro comprovado. Apesar de endémica no nosso país, é ainda bastante negligenciada e subnotificada. Devido aos escassos dados epidemiológicos relativos a Portugal, mais concretamente à sub-região da Cova da Beira, este estudo tem como principal objetivo avaliar o grau de exposição da população desta região ao agente zoonótico L.infantum. Foi feito o aproveitamento de amostras de sangue e de soro de 229 participantes voluntários no Centro Hospitalar Cova da Beira, para posterior realização do teste de reação em cadeia de polimerase e teste de aglutinação direta, respetivamente. Para cada par de amostras foi também recolhida informação anónima respeitante ao sexo do dador, idade, local de residência e também à posse e/ou contacto com cães e gatos. Os resultados obtidos em ambos os testes foram negativos, não tendo sido detetado nenhum caso de infeção ativa ou sinal de contacto prévio com o parasita. A melhoria das condições de habitação, saneamento, higiene, alimentação e saúde poderão ter um importante papel na capacidade dos hospedeiros em combater a infeção eficazmente. Por outro lado, a melhoria do tratamento e controlo dos doentes com HIV (grupo de maior suscetibilidade para a doença) pode estar também associada a uma queda na incidência da infeção neste grupo, tal como já se vem a verificar noutros países europeus. Por último, o maior controlo da infeção nos animais domésticos por parte da comunidade veterinária poderá estar a influenciar positivamente o bloqueio da dispersão desta endemia. Em suma, apesar de não ser possível extrapolar conclusões com base nesta amostra, este estudo não corrobora a hipótese de que a sub-região da Cova da Beira seja endémica para a L.infantum.Leishmaniasis is an infectious disease caused by protozoa of the genus Leishmania. Approximately 20 of these species are zoonotic, transmission occurring mainly by hematophagous sandflies insect bite, which function as vector. The Mediterranean basin is endemic to L.infantum species, responsible for one of the most severe forms of the disease: visceral leishmaniasis. The dog is the main proven host. Although endemic in our country, human leishmaniasis is still somewhat neglected and underreported. There are few epidemiological data about human population of Portugal, specifically the Cova da Beira region. So, this study aims to evaluate the exposure degree to zoonotic agent L.infantum in the population of this region. Samples of blood and serum of 229 volunteers were collected, at Centro Hospitalar Cova da Beira, for later execution of polymerase chain reaction test and direct agglutination test, respectively. For each pair of samples was also collected anonymous information concerning the sex, age, place of residence of the donor and the possession and/or contact with dogs and cats. The results obtained in both tests were negative and was not detected any case of active infection or any sign of previous contact with L.infantum. The improvement of housing conditions, sanitation, hygiene, nutrition and health state may play an important role in the ability of human hosts to effectively fight the infection. Furthermore, the improved treatment and monitoring of patients with HIV infection (group with an increased susceptibility to the development of visceral leishmaniasis) may also be associated with a decrease in the incidence of infection in this group, as already happened previously in other European countries. Finally, a greater control of the infection in domestic animals by the veterinary community may have positively influenced the blocking of this endemic dispersion. In short, although no conclusions can be extrapolated based on this sample, this study suggests the hypothesis that L.infantum infection is not endemic in the human population of Cova da Beira region

Kinetics of optical properties of colorectal muscle during optical clearing

In this paper, we describe a simple and indirect method to evaluate the kinetics of the optical properties for biological tissues under optical clearing treatments. We use the theoretical formalism in this method to process experimental data obtained from colorectal muscle samples to evaluate and characterize the dehydration and refractive index matching mechanisms

Characterization of Ni-CNTs Nanocomposites Produced by Ball-Milling

This research focuses on the characterization of a metal matrix nanocomposite (MMNC) comprised of a nickel matrix reinforced by carbon nanotubes (CNTs). The aim of this study was to characterize Ni-CNTs nanocomposites produced by powder metallurgy using ball-milling. CNTs were initially untangled using ultrasonication followed by mixture/dispersion with Ni powder by ball-milling for 60, 180, or 300 min. The mixtures were cold-pressed and then pressureless sintered at 950 degrees C for 120 min under vacuum. Their microstructural characterization was mainly performed by optical microscopy (OM), scanning electron microscopy (SEM), and electron backscatter diffraction (EBSD). The mechanical properties were evaluated by Vickers microhardness. The results indicate that combining ultrasonication and ball-milling can successfully produce Ni-CNTs nanocomposites. The ball-milling time has a significant effect on both the CNT dispersion and the final nanocomposite microstructure

Frequency and correlates of picky eating and overeating in school-aged children: a Portuguese population-based study

Using the Achenbach System of Empirically Based Assessment (ASEBA) battery in a non-clinical Portuguese population-based study, we aimed to examine a broad spectrum of emotional and behavioral problems and competencies, including picky eating and overeating behaviors in children and youth. Overall, 2687 children from 6 to 18 years old were evaluated by their parents, teachers and, in the case of children older than 11 years old, by themselves. Picky eating and overeating were assessed using the Child Behavior Checklist (CBCL) and Youth Self Report (YSR). The frequency of picky eating and overeating was 23.1% and 24%, respectively. Picky eaters, compared with over eaters and non-picky/non-over eaters, tended to belong to the younger group of participants, and in turn, over eaters tended to belong to the older group. Overeating was significantly associated with overweight, which also emerged as a predictor of belonging to the overeating group. Both picky eaters and over eaters scored significantly higher on all emotional and behavioral problems and DSM-5-oriented subscales. The results of two independent binary logistic regression analyses indicated that internalizing and externalizing problems, together with the total problems score emerged as a predictor for both groups, including picky eater and overeater school-aged children. In accordance with previous studies, our results also supported the possibility that a broader pattern of potentially non-adaptive emotional and behavioral problems could also be associated with both pickiness and excessive eating.info:eu-repo/semantics/acceptedVersio

Reconstruction of a genome-scale metabolic model for Actinobacillus succinogenes 130Z

Background Actinobacillus succinogenes is a promising bacterial catalyst for the bioproduction of succinic acid from low-cost raw materials. In this work, a genome-scale metabolic model was reconstructed and used to assess the metabolic capabilities of this microorganism under producing conditions. Results The model, iBP722, was reconstructed based on the functional reannotation of the complete genome sequence of A. succinogenes 130Z and manual inspection of metabolic pathways, covering 1072 enzymatic reactions associated with 722 metabolic genes that involve 713 metabolites. The highly curated model was effective in capturing the growth of A. succinogenes on various carbon sources, as well as the SA production under various growth conditions with fair agreement between experimental and predicted data. Calculated flux distributions under different conditions show that a number of metabolic pathways are affected by the activity of some metabolic enzymes at key nodes in metabolism, including the transport mechanism of carbon sources and the ability to fix carbon dioxide. Conclusions The established genome-scale metabolic model can be used for model-driven strain design and medium alteration to improve succinic acid yields.Financially supported by BRIGIT (KBBE-2012-6-311935, FP7 project Contract nr 311935) and by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2013 unit and COMPETE 2020 (POCI-01-0145-FEDER-006684), in addition to the BioTecNorte operation (NORTE-01-0145-FEDER-000004) funded by European Regional Development Fund under the scope of Norte2020 - Programa Operacional Regional do Norte.info:eu-repo/semantics/publishedVersio

EBSD Analysis of Metal Matrix Nanocomposite Microstructure Produced by Powder Metallurgy

The development of metal nanocomposites reinforced by carbon nanotubes (CNTs) remains a focus of the scientific community due to the growing need to produce lightweight advanced materials with unique mechanical properties. However, for the successful production of these nanocomposites, there is a need to consolidate knowledge about how reinforcement influences the matrix microstructure and which are the strengthening mechanisms promoting the best properties. In this context, this investigation focuses on the study of the reinforcement effect on the microstructure of an Ni-CNT nanocomposites produced by powder metallurgy. The microstructural evolution was analysed by electron backscattered diffraction (EBSD). The EBSD results revealed that the dispersion/mixing and pressing processes induce plastic deformation in the as-received powders. The dislocation structures produced in those initial steps are partially eliminated in the sintering process due to the activation of recovery and recrystallization mechanisms. However, the presence of CNTs in the matrix has a significant effect on the dislocation annihilation, thus reducing the recovery of the dislocation structures

Kinetics of optical properties of human colorectal tissues during optical clearing: a comparative study between normal and pathological tissues

To characterize the optical clearing treatments in human colorectal tissues and possibly to differentiate between treatments of normal and pathological tissues, we have used a simple indirect method derived from Mie scattering theory to estimate the kinetics of the reduced scattering coefficient. A complementary method to estimate the kinetics of the scattering coefficient is also used so that the kinetics of the anisotropy factor and of the refractive index are also calculated. Both methods rely only on the thickness and collimated transmittance measurements made during treatment. The results indicate the expected time dependencies for the optical properties of both tissues: an increase in the refractive index and anisotropy factor and a decrease in the scattering coefficients. The similarity in the kinetics obtained for normal and pathological tissues indicates that optical clearing treatments can be applied also in pathological tissues to produce similar effects. The estimated time dependencies using experimental spectral data in the range from 400 to 1000 nm allowed us to compare the kinetics of the optical properties between different wavelengths.info:eu-repo/semantics/publishedVersio

LDPE-Nanoclay films for food packaging with improved barrier properties

This study focuses on the development of low-density polyethylene matrix nanocomposite films for food packaging industry and aims at improving low-density polyethylene oxygen barrier properties while maintaining other relevant characteristics, such as processability, easy post-processing, optical and mechanical properties. low-density polyethylene nanocomposites, with 1 and 2.5 wt.% nanoclay (NC) and also compatibilized with 5 wt.% polyethylene grafted with maleic anhydride (PE-g-MA), were prepared and used to produce blown films. The nanocomposites were characterized in terms of their morphology, thermal, rheological, mechanical, barrier and optical properties, through scanning electron microscopy (SEM), X-ray diffraction (XRD), differential scanning calorimetry (DSC), rheological measurements, tensile tests, water vapor transmission, oxygen permeability tests and spectrophotometry. The results demonstrated good NC dispersion in the polymer matrix and decreased oxygen permeability in the compatibilized nanocomposite films. All the other properties did not significantly change when compared to neat low-density polyethylene. Overall, the film properties were improved with the added nanoclay and PE-g-MA and, have potential for food packaging.Acknowledgements This study was supported by the project "MobFood - Mobilizing scientific and technological knowledge in response to the challenges of the agri-food market", Reference POCI-01- 0247-FEDER-024524