Magnetic micellar nanovehicles: prospects of multifunctional hybrid systems for precision theranostics

Hybrid nanoarchitectures such as magnetic polymeric micelles (MPMs) are among the most promising nanotechnology-enabled materials for biomedical applications combining the benefits of polymeric micelles and magnetic nanoparticles within a single bioinstructive system. MPMs are formed by the self-assembly of polymer amphiphiles above the critical micelle concentration, generating a colloidal structure with a hydrophobic core and a hydrophilic shell incorporating magnetic particles (MNPs) in one of the segments. MPMs have been investigated most prominently as contrast agents for magnetic resonance imaging (MRI), as heat generators in hyperthermia treatments, and as magnetic-susceptible nanocarriers for the delivery and release of therapeutic agents. The versatility of MPMs constitutes a powerful route to ultrasensitive, precise, and multifunctional diagnostic and therapeutic vehicles for the treatment of a wide range of pathologies. Although MPMs have been significantly explored for MRI and cancer therapy, MPMs are multipurpose functional units, widening their applicability into less expected fields of research such as bioengineering and regenerative medicine. Herein, we aim to review published reports of the last five years about MPMs concerning their structure and fabrication methods as well as their current and foreseen expectations for advanced biomedical applications.This research was funded by European Research Council, Consolidator Grant, grant number 772817. European Union’s Horizon 2020 Research and Innovation programme, grant number 810850. Fundação para a Ciência e a Tecnologia, grant number SFRD/BD/144816/2019

Anaerobic biodegradability of meat-processing wastes: effect of physical, chemical and enzymatic pre-treatments

Methane is produced during the anaerobic degradation of greaves and rinds, two by-products of pig slaughter and meat-processing industry. However, although values of 914±37 and 664±35 m3 CH4 ton-1 waste (wet weight) respectively were obtained, the degradation rate in batch assays was slow and lasted between 25 and 30 days. Therefore, in order to assess the potential increase in the biodegradation rate and biodegradability of these substrates, physical (temperature), chemical (alkali) and enzymatic (lipase) pre-treatments were tested. Partial hydrolysis was achieved for all the conditions applied but the efficiency was higher in alkaline and enzymatic treatments. These conditions produced hydrolysates with higher soluble+colloidal COD, long-chain fatty acids and ammonia concentrations, comparatively with the other treatments applied. Enzymatic hydrolysis increased 14% the methane production potential of the rinds, and this increase was even higher (80%) when rinds were thermally treated before addition of the enzyme. With all other pre-treatments, anaerobic biodegradability of both wastes was not improved comparatively to the raw materials. Alkaline conditions induced a severe decreased (89%) of rinds’ biodegradability. Enzymatic pre-treatment appears to be a promising strategy for increasing methane production from meat-processing wastes

Biochemical Methane Potential of raw and pre-treated meat-processing wastes

Raw and pre-treated greaves and rinds, two meat-processing wastes, were assessed for biochemical methane potential (BMP). Combinations of temperature (25, 55, 70 and 120°C), NaOH (0.3 g g-1 waste volatile solids) and lipase from Candida rugosa (10 U g-1 fat) were applied to promote wastes hydrolysis, and the effect on BMP was evaluated. COD solubilisation was higher (66% for greaves; 55% for rinds) when greaves were pre-treated with NaOH at 55°C and lipase was added to rinds after autoclaving. Maximum fat hydrolysis (52-54%) resulted from NaOH addition, at 55°C for greaves and 25°C for rinds. BMP of raw greaves and rinds was 707±46 and 756±56 L CH4 (at standard temperature and pressure) kg-1 VS, respectively. BMP of rinds improved 25% by exposure to 70ºC; all other strategies tested had no positive effect on BMP of both wastes, and anaerobic biodegradability was even reduced by the combined action of base and temperature.The authors thank Cristiana Goncalves for her help with the enzymatic pre-treatments. The financial support from Portuguese Innovation Agency (ADI), through the project FatValue (QREN no. 3491), is gratefully acknowledged. Professor Giovana Tommaso thanks the EMUNDUS15 - Erasmus Mundus External Cooperation Window (Lot15) that provided financial support for her stay in the University of Minho, Portugal

Magnetic stimulation drives macrophage polarization in cell to–cell communication with IL-1β primed tendon cells

Inflammation is part of the natural healing response, but it has been simultaneously associated with tendon disorders, as persistent inflammatory events contribute to physiological changes that compromise tendon functions. The cellular interactions within a niche are extremely important for healing. While human tendon cells (hTDCs) are responsible for the maintenance of tendon matrix and turnover, macrophages regulate healing switching their functional phenotype to environmental stimuli. Thus, insights on the hTDCs and macrophages interactions can provide fundamental contributions on tendon repair mechanisms and on the inflammatory inputs in tendon disorders. We explored the crosstalk between macrophages and hTDCs using co-culture approaches in which hTDCs were previously stimulated with IL-1β. The potential modulatory effect of the pulsed electromagnetic field (PEMF) in macrophage-hTDCs communication was also investigated using the magnetic parameters identified in a previous work. The PEMF influences a macrophage pro-regenerative phenotype and favors the synthesis of anti-inflammatory mediators. These outcomes observed in cell contact co-cultures may be mediated by FAK signaling. The impact of the PEMF overcomes the effect of IL-1β-treated-hTDCs, supporting PEMF immunomodulatory actions on macrophages. This work highlights the relevance of intercellular communication in tendon healing and the beneficial role of the PEMF in guiding inflammatory responses toward regenerative strategies.This research was funded by the ERC CoG grant MagTendon (No. 772817), FCT Project Mag TT PTDC/CTM-CTM/29930/2017, and project NORTE-01-0145-FEDER-000021 supported by Norte Portugal Regional Operational Programme (NORTE 2020). A. Vinhas is funded by Fundação para a Ciência e Tecnologia (FCT)-doctoral grant PD/BD/128089/2016

Crystallization and preliminary structure determination of the membrane-bound complex cytochrome c nitrite reductase from Desulfovibrio vulgaris Hildenborough

The cytochrome c nitrite reductase (cNiR) isolated from Desulfovibrio vulgaris Hildenborough is a membrane-bound complex formed of NrfA and NrfH subunits. The catalytic subunit NrfA is a soluble pentahaem cytochrome c that forms a physiological dimer of about 120 kDa. The electron-donor subunit NrfH is a membrane-anchored tetrahaem cytochrome c of about 18 kDa molecular weight and belongs to the NapC/NirT family of quinol dehydrogenases, for which no structures are known. Crystals of the native cNiR membrane complex, solubilized with dodecylmaltoside detergent (DDM), were obtained using PEG 4K as precipitant. Anomalous diffraction data were measured at the Swiss Light Source to 2.3 Å resolution. Crystals belong to the orthorhombic space group P212121, with unit-cell parameters a = 79.5, b = 256.7, c = 578.2 Å. Molecular-replacement and MAD methods were combined to solve the structure. The data presented reveal that D. vulgaris cNiR contains one NrfH subunit per NrfA dimer.publishe

Antibodies to Toxoplasma gondii and Leishmania spp. in domestic cats from Luanda, Angola

Toxoplasma gondii and Leishmania spp. are zoonotic protozoa of importance to animal and public health. The present study aimed to assess for the first time the seroprevalence of these zoonotic parasites in a domestic feline population living in Luanda, Angola. One hundred and two cats were sampled at a veterinary medical centre, from May 2014 to February 2016. The age of the cats ranged from 2.5 to 143 months (median: 12 months; interquartile range: 7.5–24). Serum samples were tested for immunoglobulin (Ig) G antibodies to T. gondii at two-fold dilutions of 1:20 to 1:2560 with a modified agglutination test (MAT) commercial kit. The direct agglutination test (DAT) for titration of IgG antibodies specific to Leishmania spp. used a standard freeze-dried antigen at a concentration of 5 × 10 7 promastigotes per milliliter, following a predefined protocol. Two-fold dilution series ranging from 1:25 to 1:800 were tested, with a cut-off titre of 100 chosen for seropositivity. Four out of 102 cats (3.9%; 95% confidence interval [CI]: 1.1–9.7) had antibodies to T. gondii: one had a titer of 20, one a titer of 160, and two had a titer ≥ 2560. No cat (0.0%; CI: 0.0–3.5) was found seropositive for Leishmania spp. A statistically significant difference was found between T. gondii seroprevalence and Leishmania spp. seroprevalence (p = 0.043). The odds of a cat being seropositive to T. gondii increased by an average factor of 1.58 for each 1-year increase in age (p = 0.003). The sampled cats were well-cared animals and may not represent the overall feline population of Angola at the national and city levels. The fact that only 12 out of the 102 sampled cats ate or had access to raw or undercooked meat and/or viscera may have reduced the likelihood of finding seropositive results. Under these circumstances, additional studies, including a larger number of cats, are necessary for a more comprehensive assessment of the zoonotic risk posed by these animals in Angola.The authors would like to express their gratitude to Hugo Vilhena for his logistic support. This work was sponsored by the Foundation for Science and Technology (FCT), Ministry of Education and Science, Portugal, under the Projects UID/CVT/00772/2013 and UID/CVT/ 0772/2016.info:eu-repo/semantics/publishedVersio

First report of canine ocular thelaziosis by Thelazia callipaeda in Portugal

BACKGROUND: Thelazia callipaeda eyeworms are transmitted by the non-biting insect vector Phortica variegata in Europe and infest the conjunctiva(s) of several mammalians, including dogs and humans. Infested hosts might remain asymptomatic or display clinical manifestations characterized by variable degrees of severity. METHODS: From July to November 2011, nine dogs were detected with eyeworms at two veterinary clinics in Chaves and Bragança (North of Portugal). Nematodes collected from dogs were morphologically and molecularly characterized at species level. RESULTS: Nematodes were identified as T. callipaeda. The number of worms collected from each dog ranged from three to 76 (average = 17.9 ± 26.8) and was not associated with the severity of clinical signs. Ocular discharge and conjunctivitis were observed in all dogs and ocular pruritus occurred in six of them. Polymerase chain reaction and sequencing of a portion of target cytochrome c oxidase subunit 1 gene further identified all nematodes as haplotype 1. CONCLUSIONS: This is the first report of T. callipaeda and associated ocular disease in dogs from Portugal, suggesting that thelaziosis should be included in the differential diagnosis of canine ocular affections. The risk of the infestation spreading from Spain and France to Portugal, through domestic dogs or wild mammals, is realistic

The Gammaherpesvirus m2 Protein Manipulates the Fyn/Vav Pathway through a Multidocking Mechanism of Assembly

To establish latent infections in B-cells, gammaherpesviruses express proteins in the infected B-cells of the host that spuriously activate signalling pathways located downstream of the B-cell receptor. One such protein is M2, a murine gammaherpesvirus 68-encoded molecule that activates the Vav1/Rac1 pathway via the formation of trimolecular complexes with Scr family members. Previous reports have shown that the formation of this heteromolecular complex involves interactions between a proline rich region of M2 and the Vav1 and Fyn SH3 domains. Here, we show that the optimal association of these proteins requires a second structural motif encompassing two tyrosine residues (Tyr120 and 129). These residues are inducibly phosphorylated by Fyn in non-hematopoietic cells and constitutively phosphorylated in B-cells. We also demonstrate that the phosphorylation of Tyr120 creates specific docking sites for the SH2 domains of both Vav1 and Fyn, a condition sine qua non for the optimal association of these two signalling proteins in vivo. Interestingly, signaling experiments indicate that the expression of M2 in B-cells promotes the tyrosine phosphorylation of Vav1 and additional signaling proteins, a biological process that requires the integrity of both the M2 phosphotyrosine and proline rich region motifs. By infecting mice with viruses mutated in the m2 locus, we show that the integrity of each of these two M2 docking motifs is essential for the early steps of murine gammaherpesvirus-68 latency. Taken together, these results indicate that the M2 phosphotyrosine motif and the previously described M2 proline rich region work in a concerted manner to manipulate the signaling machinery of the host B-cell

Back to the past: the individual and its role in creativity in organisations

O objetivo deste texto é realçar o papel do indivíduo na criatividade nas organizações. Esse papel tem sido estranhamente remetido para um plano secundário, à medida que as modernas visões da criatividade a definem, sobretudo, com relação ao contexto em que ocorre. De fato, na perspectiva atual, a criatividade não pode ser entendida sem se considerarem os contextos funcional, relacional e organizacional nos quais está inserido o trabalhador. Tais são as considerações da maior parte dos autores que escreve sobre o tópico, como sejam Amabile (1996), Csikszentmihalyi (1996), ou, mais recentemente, Glăveanu (2010a, 2010b). Essa corrente dominante, com origem no interacionismo psico-social, tem ainda influenciado o desenvolvimento teórico de outros conceitos em psicologia, sociologia, e, na sequência, nas ciências sociais e humanas, e na gestão. Essa supremacia no que concerne a criatividade, tem conduzido os autores a olvidar o papel do indivíduo no processo e no resultado criativos, chegando a retirar-lhe a responsabilidade e o protagonismo pela geração e produção de ideias. Desse modo, no presente texto, recuperam-se os argumentos em favor da centralidade da pessoa na criatividade, defendendo-se que esta tem uma existência isolada de influências externas, e que, como tal, devem relembrar-se as bases individuais da criatividadeThe goal of the current text is to highlight the role of the individual in creativity in organisations. This role has been strangely disregarded in recent years, as modern accounts of creativity have been emphasising the idea that creativity is only defined in context. This main stream argues that creativity is a process that essentially occurs within a functional, relational, and organisational context in which workers are inserted. Key authors defending such a position include the likes of Amabile (1996), Csikszentmihalyi (1996), and, more recently, Glăveanu (2010a, 2010b). This is a vision rooted in the psychosocial interactionist perspective, which has also had a considerable impact in other areas in psychology, sociology, management and other social and human sciences. This supremacy, with regards to creativity, has led many to forget the role of the individual person in the creative process and output, removing their responsibility and protagonism for generating and producing ideas. Hence, the current text intends to bring back to discussion the individual bases of creativity, that people can have an existence isolated from external influences, further defending that the concept can and should be defined out of context, rather than in contextinfo:eu-repo/semantics/publishedVersio