H-Ferritin Is Essential for Macrophages' Capacity to Store or Detoxify Exogenously Added Iron

Macrophages are central cells both in the immune response and in iron homeostasis. Iron is both essential and potentially toxic. Therefore, iron acquisition, transport, storage, and release are tightly regulated, by several important proteins. Cytosolic ferritin is an iron storage protein composed of 24 subunits of either the L- or the H-type chains. H-ferritin differs from L-ferritin in the capacity to oxidize Fe2+ to Fe3+. In this work, we investigated the role played by H-ferritin in the macrophages' ability to respond to immune stimuli and to deal with exogenously added iron. We used mice with a conditional deletion of the H-ferritin gene in the myeloid lineage to obtain bone marrow-derived macrophages. These macrophages had normal viability and gene expression under basal culture conditions. However, when treated with interferon-gamma and lipopolysaccharide they had a lower activation of Nitric Oxide Synthase 2. Furthermore, H-ferritin-deficient macrophages had a higher sensitivity to iron-induced toxicity. This sensitivity was associated with a lower intracellular iron accumulation but a higher production of reactive oxygen species. These data indicate that H-ferritin modulates macrophage response to immune stimuli and that it plays an essential role in protection against iron-induced oxidative stress and cell death.Tis work was fnanced by FEDER - Fundo Europeu de Desenvolvimento Regional funds through the COMPETE2020 - Operacional Programme for Competitiveness and Internationalization (POCI), Portugal 2020, and by Portuguese funds through FCT - Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior in the framework of the project PTDC/IMI-MIC/1683/2014 (POCI-01-0145-FEDER-016590). PFO and MGA acknowledge FCT for the Investigador FCT 2015. We thank the valuable collaboration of the following i3S Scientifc Platforms: Cell Culture and Genotyping Core Facility (CCGen), [Histology and Electron Microscopy Service (HEMS), and BioSciences Screening], member of the PPBI (PPBI-POCI-01-0145-FEDER-022122)], Animal Facility, and Flow Cytometry Unit (TraCy). We acknowledge Lukas Kuhn (Swiss Institute for Experimental Cancer Research, Lausanne, Switzerland) for kindly providing the frst breeding pairs of Fth1−/− mice. Te authors also acknowledge Marisa Castro, from Departamento de Biologia Molecular from ICBAS, Clara Bento, from i3S, and Edgar Pinto from LAQV – REQUIMTE for technical assistance at diferent stages of the project

Dirofilaria immitis antigenemia and microfilaremia in Iberian wolves and red foxes from Portugal

Background: Dirofilaria immitis is a parasitic nematode endemic in the Mediterranean countries, which causes cardiopulmonary dirofilariosis in wild and domestic animals. Despite being recognized hosts of D. immitis, wild carnivores such as wolves and foxes are frequently disregarded when considering a potential role in the transmission of these zoonotic nematodes. In Portugal, studies available regarding D. immitis circulation are scarce, likely underestimating its relevance. To add knowledge on this, we sought to assess Iberian wolves (Canis lupus signatus) and red foxes (Vulpes vulpes) from northern Portugal for D. immitis antigenemia and microfilaremia. Methods: Blood samples from 42 Iberian wolves and 19 red foxes were collected, during 2010–2012, in Peneda-Gerês National Park. Antigenemia was searched for by rapid antigen detection test kits (Uranotest Dirofilaria ®). Microfilaremia was assessed by polymerase chain reaction (PCR). Nucleic acids were extracted from blood using QIAamp® DNA Mini Kit (Qiagen), and DNA was screened for the presence of microfilaria using a conventional PCR targeting the 5.8S-internal transcribed spacer 2–28S regions, followed by bidirectional sequencing, Basic Local Alignment Search Tool analysis and phylogenetic analysis. Results: Three red foxes had antigenemia, with an occurrence of 15.8% (95% confidence interval [CI] 3.4–39.6), while showing no evidence for the presence of microfilaremia. No wolf samples presented evidence for D. immitis antigenemia. Nevertheless, two wolves were positive for D. immitis microfilaremia (4.8%; 95% CI 0.6–16.2%) as revealed by PCR and confirmed by bidirectional sequencing. Conclusions: Although Dirofilaria microfilaremia in wolves does not necessarily correlate to an endangerment of the infected animal's health, positive individuals can act as a reservoir for further infection if the intermediate mosquito hosts are present. To the best of our knowledge, one single study had reported that wolves were suitable Dirofilaria hosts, but microfilaremia have never been reported. Graphical Abstract: [Figure not available: see fulltext.] © 2022, The Author(s).Funding text 1: Publication of this paper has been sponsored by Elanco Animal Health in the framework of the 17th CVBD®World Forum Symposium.; Funding text 2: This work was supported by national funds, through Fundação para a Ciência e a Tecnologia (FCT, Portuguese Foundation for Science and Technology), under projects UIDB/04750/2020 and LA/P/0064/2020; and projects UIDB/CVT/00772/2020 and LA/P/0059/2020, also funded by FCT

Qualidade de vida de pacientes submetidos à cirurgia bariátrica: estudo transversal

Purpose: Analyze factors that influenced the quality of life (QoL) of patients after bariatric surgery. Methods: A cross-sectional study was carried out, involving 307 adult bariatric surgery patients between 2012 and 2014. Data was obtained from the electronic patient records and telephone interviews. To assess the QoL, the World Health Organization Quality of Life-Bref (WHOQOL-bref) was used. A simple linear regression model was constructed, adjusted by sociodemographic variables, with p<0.05. Results: The domains with the worst scores were the physical (mean=58.45; SD±10.42) and environmental (mean=65.19; SD±11.36). The best domains were the social (mean=76.51; SD±15.71) and psychological (mean=68.70; SD±15.71). In the linear regression model, it was observed that time since the surgery was inversely associated with the physical health domain. For each month post-bariatric surgery, the patient’s average score dropped by 2.66 points, adjusted by sex and age. Conclusions: Time since the surgery could be an important determinant of the physical domain score of quality of life. Identifying the quality of life after bariatric surgery and influential factors is fundamental to prepare these patients for the changes deriving from the weight loss.Objetivo: Analizar los factores que influyeron en la calidad de vida (CV) de los pacientes después de la cirugía bariátrica. Métodos: Se llevó a cabo un estudio transversal en el que participaron 307 pacientes adultos con cirugía bariátrica entre 2012 y 2014. Se han obtenido los datos de los registros electrónicos de los pacientes y de sus entrevistas telefónicas. Después se construyó un modelo de regresión lineal simple, ajustado por variables sociodemográficas, con p <0.05. Para evaluar la CV, se utilizó la Calidad de Vida Breve de la Organización Mundial de la Salud (WHOQOL-bref). Resultados: Los dominios con las peores puntuaciones fueron el físico (media = 58,45; SD ± 10,42) y ambiental (media = 65,19; SD ± 11,36). Los mejores dominios fueron el social (media = 76.51; SD ± 15.71) y psicológico (media = 68.70; SD ± 15.71). En el modelo de regresión lineal, se observó que el tiempo desde la cirugía se asoció inversamente con el dominio de la salud física. Por cada mes posterior a la cirugía bariátrica, el puntaje promedio del paciente se redujo en 2.66 puntos, ajustado por sexo y edad. Conclusión: El tiempo transcurrido desde la cirugía puede ser un determinante importante de la puntuación del dominio físico de la calidad de vida. Identificar la calidad de vida después de la cirugía bariátrica y los factores influyentes es fundamental para preparar a estos pacientes para los cambios derivados de la pérdida de peso.Objetivo: Analisar os fatores que influenciaram a qualidade de vida (QV) dos pacientes após a cirurgia bariátrica. Método: Realizado um estudo transversal envolvendo 307 pacientes adultos submetidos à cirurgia bariátrica, no período de 2012 a 2014. Os dados foram obtidos por meio de prontuário eletrônico e entrevistas telefônicas. Para avaliar a QV, foi utilizada a World Health Organization Quality of Life-bref (WHOQOL-bref). Um modelo de regressão linear simples foi construído, ajustado por variáveis sociodemográficas, com p <0,05.Resultados: Os domínios com os piores escores foram físico (média = 58,45; DP ± 10,42) e ambiental (média = 65,19; DP ± 11,36). Os melhores domínios foram o social (média = 76,51; DP ± 15,71) e o psicológico (média = 68,70; DP ± 15,71). No modelo de regressão linear, observou-se que o tempo desde a cirurgia foi inversamente associado ao domínio saúde física. Para cada mês pós-cirurgia bariátrica, a pontuação média do paciente caiu em 2,66 pontos, ajustada por sexo e idade. Conclusão: O tempo desde a cirurgia pode ser um importante determinante do escore do domínio físico de QV. Identificar a QV após a cirurgia bariátrica e fatores que a influenciam é fundamental para preparar esses pacientes para as mudanças decorrentes da perda de peso

Optical properties of multi-layer type II InP/GaAs quantum dots studied by surface photovoltage spectroscopy

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)We present a low-temperature (73 K) study of the optical properties of multi-layer type II InP/GaAs self-assembled quantum dots by means of surface photovoltage (SPV) spectroscopy, taking advantage of its high sensitivity and contactless nature. The samples contain 10 periods of InP quantum dot planes separated by 5 nm GaAs spacers. The SPV amplitude spectra reveal two major broad peaks, situated at low and high energies, respectively. These features are analyzed taking into account the type II character of the structure, the quantum coupling effects, the spectral behavior of the SPV phase, and the photoluminescence spectra. As a result they have been attributed to optical transitions in the quantum dots and the wetting layers, respectively. The main mechanism for carrier separation in the SPV generation process is clarified via the analysis of the SPV phase spectra. The influence of the substrate absorption on the SPV spectra is discussed in details. (C) 2011 American Institute of Physics. [doi:10.1063/1.3638705]1106Bulgarian National Science Fund [D01-463/12.7.06]Alexander von Humboldt FoundationCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Bulgarian National Science Fund [D01-463/12.7.06

Understanding Phase Transitions with Local Optima Networks: Number Partitioning as a Case Study

Phase transitions play an important role in understanding search difficulty in combinatorial optimisation. However, previous attempts have not revealed a clear link between fitness landscape properties and the phase transition. We explore whether the global landscape structure of the number partitioning problem changes with the phase transition. Using the local optima network model, we analyse a number of instances before, during, and after the phase transition. We compute relevant network and neutrality metrics; and importantly, identify and visualise the funnel structure with an approach (monotonic sequences) inspired by theoretical chemistry. While most metrics remain oblivious to the phase transition, our results reveal that the funnel structure clearly changes. Easy instances feature a single or a small number of dominant funnels leading to global optima; hard instances have a large number of suboptimal funnels attracting the search. Our study brings new insights and tools to the study of phase transitions in combinatorial optimisation

Heterogeneities in leishmania infantum infection : using skin parasite burdens to identify highly infectious dogs

Background: The relationships between heterogeneities in host infection and infectiousness (transmission to arthropod vectors) can provide important insights for disease management. Here, we quantify heterogeneities in Leishmania infantum parasite numbers in reservoir and non-reservoir host populations, and relate this to their infectiousness during natural infection. Tissue parasite number was evaluated as a potential surrogate marker of host transmission potential. Methods: Parasite numbers were measured by qPCR in bone marrow and ear skin biopsies of 82 dogs and 34 crab-eating foxes collected during a longitudinal study in Amazon Brazil, for which previous data was available on infectiousness (by xenodiagnosis) and severity of infection. Results: Parasite numbers were highly aggregated both between samples and between individuals. In dogs, total parasite abundance and relative numbers in ear skin compared to bone marrow increased with the duration and severity of infection. Infectiousness to the sandfly vector was associated with high parasite numbers; parasite number in skin was the best predictor of being infectious. Crab-eating foxes, which typically present asymptomatic infection and are non-infectious, had parasite numbers comparable to those of non-infectious dogs. Conclusions: Skin parasite number provides an indirect marker of infectiousness, and could allow targeted control particularly of highly infectious dogs

MSH3 polymorphisms and protein levels affect CAG repeat instability in huntington's disease mice

Expansions of trinucleotide CAG/CTG repeats in somatic tissues are thought to contribute to ongoing disease progression through an affected individual's life with Huntington's disease or myotonic dystrophy. Broad ranges of repeat instability arise between individuals with expanded repeats, suggesting the existence of modifiers of repeat instability. Mice with expanded CAG/CTG repeats show variable levels of instability depending upon mouse strain. However, to date the genetic modifiers underlying these differences have not been identified. We show that in liver and striatum the R6/1 Huntington's disease (HD) (CAG)~100 transgene, when present in a congenic C57BL/6J (B6) background, incurred expansion-biased repeat mutations, whereas the repeat was stable in a congenic BALB/cByJ (CBy) background. Reciprocal congenic mice revealed the Msh3 gene as the determinant for the differences in repeat instability. Expansion bias was observed in congenic mice homozygous for the B6 Msh3 gene on a CBy background, while the CAG tract was stabilized in congenics homozygous for the CBy Msh3 gene on a B6 background. The CAG stabilization was as dramatic as genetic deficiency of Msh2. The B6 and CBy Msh3 genes had identical promoters but differed in coding regions and showed strikingly different protein levels. B6 MSH3 variant protein is highly expressed and associated with CAG expansions, while the CBy MSH3 variant protein is expressed at barely detectable levels, associating with CAG stability. The DHFR protein, which is divergently transcribed from a promoter shared by the Msh3 gene, did not show varied levels between mouse strains. Thus, naturally occurring MSH3 protein polymorphisms are modifiers of CAG repeat instability, likely through variable MSH3 protein stability. Since evidence supports that somatic CAG instability is a modifier and predictor of disease, our data are consistent with the hypothesis that variable levels of CAG instability associated with polymorphisms of DNA repair genes may have prognostic implications for various repeat-associated diseases