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Huntington's disease (HD) is an inherited neurodegenerative disorder caused by polyglutamine expansion mutations in the huntingtin protein. Despite its ubiquitous distribution, expression of mutant huntingtin (mHtt) is particularly detrimental to medium spiny neurons within the striatum. Mitochondrial dysfunction has been associated with HD pathogenesis. Here we review the current evidence for mHtt-induced abnormalities in mitochondrial dynamics and quality control, with a particular focus on brain and neuronal data pertaining to striatal vulnerability. We address mHtt effects on mitochondrial biogenesis, protein import, complex assembly, fission and fusion, mitochondrial transport, and on the degradation of damaged mitochondria via autophagy (mitophagy). For an integrated perspective on potentially converging pathogenic mechanisms, we also address impaired autophagosomal transport and abnormal mHtt proteostasis in HD.

Four indicator genes were monitored by quantitative PCR in hospital effluent (HE) and in the raw and treated wastewater of the municipal wastewater treatment plant receiving the hospital discharge. The indicator genes were the class 1 integrase gene intl1, to assess the capacity of bacteria to be involved in horizontal gene transfer processes; bla(TEM), one of the most widespread antibiotic resistance genes in the environment, associated with Enterobacteriaceae; vanA, an antibiotic resistance gene uncommon in the environment and frequent in clinical isolates; and marA, part of a locus related to the stress response in Enterobacteriaceae. Variation in the abundance of these genes was analysed as a function of the type of water, and possible correlations with cultivable bacteria, antimicrobial residue concentrations, and bacterial community composition and structure were analysed. HE was confirmed as an important source of bla(TEM) and vanA genes, and wastewater treatment showed a limited capacity to remove these resistance genes. The genes bla(TEM) and vanA presented the strongest correlations with culturable bacteria, antimicrobial residues and some bacterial populations, representing interesting candidates as indicator genes to monitor resistance in environmental samples. The intl1 gene was the most abundant in all samples, demonstrating that wastewater bacterial populations hold a high potential for gene acquisition.

The concentrations of six urinary monohydroxyl metabolites (OH-PAHs) of polycyclic aromatic hydrocarbons, namely 1-hydroxynaphthalene, 1-hydroxyacenaphthene, 2-hydroxyfluorene, 1-hydroxyphenanthrene, 1-hydroxypyrene (1OHPy), and 3-hydroxybenzo[a]pyrene, were assessed in the post-shift urine of wildland firefighters involved in fire combat activities at six Portuguese fire corporations, and compared with those of non-exposed subjects. Overall, median levels of urinary individual and total OH-PAHs (ΣOH-PAHs) suggest an increased exposure to polycyclic aromatic hydrocarbons during firefighting activities with ΣOH-PAH levels in exposed firefighters 1.7-35 times higher than in non-exposed ones. Urinary 1-hydroxynaphthalene and/or 1-hydroxyacenapthene were the predominant compounds, representing 63-98% of ΣOH-PAHs, followed by 2-hydroxyfluorene (1-17%), 1-hydroxyphenanthrene (1-13%), and 1OHPy (0.3-10%). A similar profile was observed when gender discrimination was considered. Participation in fire combat activities promoted an increase of the distribution percentage of 1-hydroxynaphthalene and 1-hydroxyacenaphthene, while contributions of 1-hydroxyphenanthrene and 1OHPy decreased. The detected urinary 1OHPy concentrations (1.73×10(-2) to 0.152μmol/mol creatinine in exposed subjects versus 1.21×10(-2) to 5.44×10(-2)μmol/mol creatinine in non-exposed individuals) were lower than the benchmark level (0.5μmol/mol creatinine) proposed by the American Conference of Governmental Industrial Hygienists. This compound, considered the biomarker of exposure to PAHs, was the less abundant one from the six analyzed biomarkers. Thus the inclusion of other metabolites, in addition to 1OHPy, in future studies is suggested to better estimate firefighters' occupational exposure to PAHs. Moreover, strong to moderate Spearman correlations were observed between individual compounds and ΣOH-PAHs corroborating the prevalence of an emission source. This study was financed by European (FEDER funds through COMPETE) and National (Fundação para a Ciência e Tecnologia project UID/QUI/50006/2013) funds and in the scope of the P2020 Partnership Agreement Project POCI-01-0145-FEDER-006939 (Laboratory for Process Engineering, Environment, Biotechnology and Energy—LEPABE) funded by FEDER funds through COMPETE2020—Programa Operacional Competitividade e Internacionalização (POCI). Authors are also grateful to for the financial support through the fellowships (SFRH/BD/80113/2011 and SFRH/BPD/65722/2009).

This work characterizes levels of eighteen polycyclic aromatic hydrocarbons (PAHs) in the breathing air zone of firefighters during their regular work shift at eight Portuguese fire stations, and the firefighters' total internal dose by six urinary monohydroxyl metabolites (OH-PAHs). Total PAHs (ΣPAHs) concentrations varied widely (46.4-428ng/m(3)), mainly due to site specificity (urban/rural) and characteristics (age and layout) of buildings. Airborne PAHs with 2-3 rings were the most abundant (63.9-95.7% ΣPAHs). Similarly, urinary 1-hydroxynaphthalene and 1-hydroxyacenaphthene were the predominant metabolites (66-96% ΣOH-PAHs). Naphthalene contributed the most to carcinogenic ΣPAHs (39.4-78.1%) in majority of firehouses; benzo[a]pyrene, the marker of carcinogenic PAHs, accounted with 1.5-10%. Statistically positive significant correlations (r≥0.733, p≤0.025) were observed between ΣPAHs and urinary ΣOH-PAHs for firefighters of four fire stations suggesting that, at these sites, indoor air was their major exposure source of PAHs. Firefighter's personal exposure to PAHs at Portuguese fire stations were well below the existent occupational exposure limits. Also, the quantified concentrations of post-shift urinary 1-hydroxypyrene in all firefighters were clearly lower than the benchmark level (0.5μmol/mol) recommended by the American Conference of Governmental Industrial Hygienists. This work was supported by European Union (FEDER funds through COMPETE) and National Funds (FCT)through projects UID/QUI/50006/2013 and UID/EQU/00511/2013-LEPABE, by the FCT/MEC with national funds and co-funded by FEDER in the scope of the P2020 Partnership Agreement. Additional financial support was provided by FCT through fellowships SFRH/BD/80113/2011 and SFRH/BPD/65722/2009.

Human biomonitoring is an important tool in environmental medicine that is used to assess the level of internal exposure to environmental pollutants. Firefighters are one of the most exposed and least studied occupations. During fire suppression, firefighters are heavily exposed to a wide range of chemicals. Polycyclic aromatic hydrocarbons (PAH) are ubiquitous environmental pollutants that are considered as the largest known group of carcinogens due to their cytotoxic and mutagenic properties. Smoke and ashes released during a fire are important sources of PAH. Firefighters can be also exposed to PAH through smoking, via polluted ambient air, water, soil, and through consumption of food. Metabolites of PAH (OH-PAHs), such as 1-hydroxynaphthalene (1OHNapt), 1-hydroxyacenaphthene(1OHAce), 1-hydroxypyrene (1OHPy) and 3-hydroxybenzo[a]pyrene (3OHB[a]P) have been used as biological markers for measurements of human internal exposure to PAH. The present work aims to quantify the urinary metabolites of PAH, namely 1OHNapt, 1OHAce, 1OHPy and 3OHB[a]P in study population of firefighters. Firemen exposed to fires that occurred during 2014 season were asked to fill a post-fire questionnaire and to collect urinary samples. A control study population group was selected to collect samples of urines during the pre-fires season (winter). Among all participating firemen only healthy no-smoking subjects were considered. OH-PAHs were analysed by high-performance liquid chromatography with fluorescence detection. Overall, 1OHNapt and 1OHAce were the most abundant OH-PAHs in firemen urine samples, accounting for approximately 90% of the total OH-PAHs. The urinary OH-PAHs in exposed firefighters were higher than those of control group. Data collected with the individual questionnaire were further used to analyse the concentrations of OH-PAH between (and within) control and exposed groups of firemen. Additionally, 1OHPy concentrations in the exposed firefighters will be compared with the available proposed guidelines.

Cystic fibrosis (CF) is a genetic disorder associated with multispecies infections where interactions between classical and newly identified bacteria might be crucial to understanding the persistent colonisation in CF lungs. This study investigated the interactions between two emerging species, Inquilinus limosus and Dolosigranulum pigrum, and the conventional CF pathogen Pseudomonas aeruginosa by evaluating the ability to develop biofilms of mixed populations and then studying their susceptibility patterns to eight different antimicrobials. Monospecies biofilms formed by I. limosus and D. pigrum produced significantly less biomass than P. aeruginosa and displayed greater sensitivity to antimicrobials. However, when in dual-species biofilms with P. aeruginosa, the emerging species I. limosus and D. pigrum were crucial in increasing tolerance of the overall consortia to most antibiotics, even without a change in the number of biofilm-encased cells. These results may suggest that revising these and other species interactions in CF might enable the development of more suitable and effective therapies in the future., Financial support was provided by the Portuguese Foundation for Science and Technology [grant SFRH/BD/47613/2008 (to SPL) and project PTDC/SAU-ESA/64609/2006].

We have previously identified the expression of an estradiol (E2)-related molecule by Schistosoma haematobium total antigen (Sh). We now show that this molecule has an antagonistic effect of estradiol in vitro. Our results are consistent with the existence of an estrogenic molecule that antagonizes the activity of estradiol. We found evidence for this molecule as we identified and characterized by mass spectrometry new estrogenic molecules previously unknown, present in schistosome worm extracts and sera of Schistosoma-infected individuals. We also show that Sh is able to interact in vitro with estrogen receptor (ER), explaining how host endocrine system can favor the establishment of schistosomes. These findings highlight the exploitation of the host endocrine system by schistosomes and represent an additional regulatory component of schistosome development that defines a novel paradigm enabling host-parasite interactions. The identification of these molecules opens new ways for the development of alternative drugs to treat schistosomiasis.