XRF identification of sharp-force trauma in fresh and dry human bone under varied experimental heat conditions.

Heat-induced fractures can be hard to distinguish from sharp force traumas. This challenge can negatively impact medico-legal analysis. The present study aimed to experimentally assess if X-ray fluorescence (XRF) can be used to detect chemical traces transferred from the blade of a sharp instrument onto both fresh and dry human bones. This was performed by inducing sharp force traumas with five different instruments on 20 fresh and 20 dry human clavicles. All bone samples were probed before and after experimental burning (at 500 °C, 700 °C, 900 °C and 1100 °C). Our results show that XRF is potentially useful for detecting iron traces in fresh human bone, both unburned and burned. However, we were not able to clearly detect iron traces from the blades in bones that have been previously inhumed, since exogenous iron acquired during diagenesis masks the iron traces originating from the blade.

Calcium modulation of bacterial wilt disease on potato.

Ralstonia solanacearum species complex (RSSC) is a phytopathogenic bacterial group that causes bacterial wilt in several crops, being potato (Solanum tuberosum) one of the most important hosts. The relationship between the potato plant ionome (mineral and trace elements composition) and the resistance levels to this pathogen has not been addressed until now. Mineral content of xylem sap, roots, stems and leaves of potato genotypes with different levels of resistance to bacterial wilt was assessed in this work, revealing a positive correlation between divalent calcium (Ca) cation concentrations and genotype resistance. The aim of this study was to investigate the effect of Ca on bacterial wilt resistance, and on the growth and virulence of RSSC. Ca supplementation significantly decreased the growth rate of Ralstonia pseudosolanacearum GMI1000 in minimal medium and affected several virulence traits such as biofilm formation and twitching motility. We also incorporate for the first time the use of microfluidic chambers to follow the pathogen growth and biofilm formation in conditions mimicking the plant vascular system. By using this approach, a reduction in biofilm formation was observed when both, rich and minimal media, were supplemented with Ca. Assessment of the effect of Ca amendments on bacterial wilt progress in potato genotypes revealed a significant delay in disease progress, or a complete absence of wilting symptoms in the case of partially resistant genotypes. This work contributes to the understanding of Ca effect on virulence of this important pathogen and provides new strategies for an integrated control of bacterial wilt on potato. IMPORTANCE: Ralstonia solanacearum species complex (RSSC) includes a diverse group of bacterial strains that cause bacterial wilt. This disease is difficult to control due to pathogen aggressiveness, persistence, wide range of hosts, and wide geographic distribution in tropical, subtropical, and temperate regions. RSSC causes considerable losses depending on the pathogen strain, host, soil type, environmental conditions, and cultural practices. In potato, losses of $19 billion per year have been estimated for this pathogen worldwide. In this study, we report for the first time the mineral composition found in xylem sap and plant tissues of potato germplasm with different levels of resistance to bacterial wilt. This study underscores the crucial role of calcium (Ca) concentration in the xylem sap and stem in relation to the resistance of different genotypes. Our in vitro experiments provide evidence of Ca's inhibitory effect on the growth, biofilm formation, and twitching movement of the model RSSC strain R. pseudosolanacearum GMI1000. This study introduces a novel element, the Ca concentration, which should be included into the integrated disease control management strategies for bacterial wilt in potatoes.

Bioaccumulation and biological effects of hydrogenated cement particles in the marine bivalve, Mytilusgalloprovincialis.

The decommissioning and normal functioning of nuclear facilities can result in the production and release of airborne particles in the environment. Aquatic biota are expected to be exposed to these particles considering that nuclear facilities are often located near water bodies. Aerosols, such as cement dust, can interact with radionuclides as well as with heavy metals, and therefore elicit not only radiological impacts but also chemical toxicity. In the present study, we aimed to determine the effects of hydrogenated cement particles (HCPs) as a first step before evaluating any radiotoxicity of tritiated cement particles in the marine mussels, Mytilus galloprovincialis. Responses at different levels of biological organisation were assessed, including clearance rate (CR), tissue specific accumulation, DNA damage and transcriptional expression of key stress related genes. Acute (5 h) and medium-term, chronic (11 d) exposures to 1000 µg L-1 HCPs showed that bioaccumulation, assessed using Cu as a proxy and determined by inductively coupled plasma mass spectrometry, was time and tissue dependent. The highest levels of Cu were found in the digestive gland (DG) after 11 d. HCP exposure caused changes in the expression of oxidative and other stress-related genes, including mt20 in DG and gst and sod in the gill after 5 h exposure, while an overexpression of hsp70 in the gill was observed after 11 d. Genotoxic effects in haemocytes were observed after 11 d of HCP exposure. Multivariate analysis indicated that oxidative stress is the most probable factor contributing to overall physiological dysfunction. Our results provide a baseline to perform further studies employing tritiated cement particles. Specifically, future work should focus on the DG since only this tissue showed significant bioaccumulation when compared to the negative control.

WITHANICANDRIN ISOLATED FROM Datura Ferox PROMOTES ANTINOCICEPTION BY MODULATING THE ASICS AND TRPS CHANNELS AND ANTI-INFLAMMATION IN ADULT ZEBRAFISH.

This is the first study to analyze the anti-inflammatory and antinociceptive effect of withanicandrin, isolated from Datura Ferox leaves, and the possible mechanism of action involved in adult zebrafish (ZFa). To this end, the animals were treated intraperitoneally (i.p.) with withanicandrin (4; 20 and 40 mg/kg; 20 µL) and subjected to locomotor activity and acute toxicity. Nociception tests were also carried out with chemical agents, in addition to tests to evaluate inflammatory processes induced by κ-Carrageenan 1.5% and a Molecular Docking study. As a result, withanicandrin reduced nociceptive behavior by capsaicin at a dose of 40 mg/kg and by acid saline at doses of 4 and 40 mg/kg, through neuromodulation of TRPV1 channels and ASICs, identified through blocking the antinociceptive effect of withanicandrin by the antagonists capsazepine and naloxone. Furthermore, withanicandrin caused an anti-inflammatory effect through the reduction of abdominal edema, absence of leukocyte infiltrate in the liver tissue and reduction of ROS in thel liver tissue and presented better affinity energy compared to control morphine (TRPV1) and ibuprofen (COX-1 and COX-2).

The BALA project: A pioneering monitoring of Azorean forest invertebrates over two decades (1999-2022).

Globally, there is a concerning decline in many insect populations, and this trend likely extends to all arthropods, potentially impacting unique island biota. Native non-endemic and endemic species on islands are under threat due to habitat destruction, with the introduction of exotic, and potentially invasive, species, further contributing to this decline. While long-term studies of plants and vertebrate fauna are available, long-term arthropod datasets are limited, hindering comparisons with better-studied taxa. The Biodiversity of Arthropods of the Laurisilva of the Azores (BALA) project has allowed gathering comprehensive data since 1997 in the Azorean Islands (Portugal), using standardised sampling methods across islands. The dataset includes arthropod counts from epigean (pitfall traps) and canopy-dwelling (beating samples) communities, enriched with species information, biogeographic origins, and IUCN categories. Metadata associated with the sample protocol and events, like sample identifier, archive number, sampled tree species, and trap type are also recorded. The database is available in multiple formats, including Darwin Core, which facilitates the ecological analysis of pressing environmental concerns, such as arthropod population declines and biological invasions.

Is there any association between fluoride exposure and thyroid function modulation? A systematic review.

Numerous pre-clinical and observational studies have explored the potential effects of fluoride (F) at varying concentrations on diverse systems and organs. While some have assessed the endocrinological conditions of children and adults, a consensus regarding the interaction between F and the thyroid remains elusive. This systematic review aimed to gather primary evidence on the association between F and changes in the thyroid at optimal and high levels in water supply as stipulated by the World Health Organization. A search strategy, incorporating terms pertinent to the studies, was employed across PubMed, Scopus, Web of Science, Lilacs, and Google Scholar. Following the review of studies, data were extracted and analyzed using the Grading of Recommendations, Assessment, Development, and Evaluations to assess the quality of the evidence. Our results yielded 3,568 studies, of which seven met the inclusion criteria for this review. Five of the seven studies identified an association between high F exposure and thyroid function. In the analysis of methodological quality, every study was found to have major or minor methodological issues and significant risk of bias. The overall confidence in the evidence was deemed low for all outcomes in the seven studies. The evidence compiled in this review suggests a potential association between chronic high levels of F exposure and thyroid damage. Nonetheless, further studies with robust design and high methodological quality are required to provide evidence for policy makers and health care practitioners.

Unstable Angina Risk Stratification Using High-Sensitivity Cardiac Troponin and Coronary Angiography.

Patients formerly diagnosed with unstable angina (UA) are being reclassified as non-ST-elevation myocardial infarction with the widespread adoption of high-sensitivity troponin (hsTn) assays, leading to significant changes in the incidence and prognosis of UA. This study aimed to evaluate the value of hsTn and the presence of significant obstructive coronary artery disease (CAD) in the risk stratification of patients with UA. We conducted a retrospective, single-center study of 742 patients hospitalized for UA between 2016 and 2021. The primary end point of this study was all-cause mortality. The secondary outcome (major adverse cardiac events [MACEs]) was defined as a composite of nonfatal myocardial infarction (MI), hospitalization for heart failure (hHF), and repeated coronary angiography because of recurring UA (rUA) after the index event. The outcomes were assessed within 1 month, 1 year, and up to 5 years of follow-up. The average follow-up duration was 45 ± 24 months, and 37.2% (n = 276) of patients completed a 5-year follow-up. No in-hospital death was observed, and 6.9% of patients died during follow-up, which was more commonly a late event (>12 months). The composite secondary end point (MI+hHF+rUA) was observed in 16.7% of the patients. There were 3.2% nonfatal MI, 2.3% hHF, and 11.6% rUA during follow-up. We developed a risk model (UA mortality risk) using variables with the highest discriminatory power: age, hsTn, and ST-segment deviation. Our model performed well against the Global Registry of Acute Coronary Events and Thrombolysis in Myocardial Infarction risk scores in predicting death during follow-up. Obstructive CAD on coronary angiography was the only independent predictor of MACEs during follow-up. In conclusion, a contemporary cohort of patients with UA presented with favorable prognosis, particularly, within the first year after the index event. Nonsignificant increases in hsTn levels add to the risk stratification of patients with UA, and the presence of obstructive CAD was the only independent predictor of MACEs, highlighting the potential importance of assessing coronary anatomy.

Brain surface morphology and ecological and macroevolutionary inferences of avian New World suboscines (Aves, Passeriformes, Tyrannides).

The New World suboscines (Passeriformes and Tyrannides) are one of the biggest endemic vertebrate radiations in South America, including the families Furnariidae and Tyrannidae. Avian brain morphology is a reliable proxy to study their evolution. The aim of this work is to elucidate whether the brains of these families reflect the ecological differences (e.g., feeding behavior) and to clarify macroevolutionary aspects of their neuroanatomy. Our hypotheses are as follows: Brain size is similar between both families and with other Passeriformes; brain morphology in Tyrannides is the result of the pressure of ecological factors; and brain disparity is low since they share ecological traits. Skulls of Furnariidae and Tyrannidae were micro-computed tomography-scanned, and three-dimensional models of the endocast were generated. Regression analyses were performed between brain volume and body mass. Linear and surface measurements were used to build phylomorphospaces and to calculate the amount of phylogenetic signal. Tyrannidae showed a larger brain disparity than Furnariidae, although it is not shaped by phylogeny in the Tyrannides. Furnariidae present enlarged Wulsts (eminentiae sagittales) but smaller optic lobes, while in Tyrannidae, it is the opposite. This could indicate that in Tyrannides there is a trade-off between the size of these two visual-related brain structures.

Nitrogen-containing andrographolide derivatives with multidrug resistance reversal effects in cancer cells.

Multidrug resistance (MDR) remains a challenging issue in cancer treatment. Aiming at finding anticancer agents to overcome MDR, the triacetyl derivative (2) of the labdane diterpenoid lactone andrographolide (1) underwent the Michael-type addition reaction followed by elimination, yielding twenty-three new derivatives, bearing nitrogen-containing substituents (3-25). Their structures were assigned, mainly, by 1D and 2D NMR experiments. The MDR reversal potential of compounds 1-25 was assessed, by functional and chemosensitivity assays, using resistant human ABCB1-gene transfected L5178Y mouse lymphoma cells as a model. Several derivatives exhibited remarkable P-glycoprotein (P-gp) inhibitory ability. Compounds 13 and 20, bearing thiosemicarbazide moieties, were the most active exhibiting a strong MDR reversal effect at 2 µM. Some compounds showed selectivity towards the resistant cells, with compound 5 exhibiting a collateral sensitivity effect associated with significant antiproliferative activity (IC50 = 5.47 ± 0.22 µM). Moreover, all selected compounds displayed synergistic interaction with doxorubicin, with compound 3 being the most active. In the ATPase assay, selected compounds exhibited characteristics of P-gp inhibitors.

Portfólio: percepção de estudantes de graduação da área da saúde / Portafolio: percepción de los estudiantes de pregrado en eláreade la salud / Portfolio: perception of undergraduate students in the healthcare field

Introdução:A formação em saúde norteia a prática profissional, incidindo diretamente na atenção e assistência à saúde ofertada à população. Nesse sentido, o uso de métodos ativos de aprendizagem e avaliação, como por exemplo, o portfólio, podem contribuir para a construção de conhecimentos crítico-reflexivos. Objetivo:Evidenciara percepção de estudantes dos cursos da área da saúde, que cursam a disciplina de Saúde e Cidadania na Universidade Federal do Rio Grande do Norte sobre o uso do portfólio enquanto instrumento de avaliação do ensino aprendizagem. Metodologia:Os dados foram obtidos por meio da formação de grupo focaleanalisados pela análise do conteúdo. Definiram-se, então, as categorias temáticas:percepção sobre o portfólio; a elaboração do portfólio e a sua contribuição para a formação; dificuldades para formulação doportfólio;o portfólio como instrumento de avaliação. Resultados:Os estudantes compreendem o portfólio como instrumento de diálogo entre docentes e discentes, através dos relatos das vivências em grupo nos equipamentos sociais e reflexões individuais na construção de conceitos e aprofundamento teórico. Ainda referem inseguranças e dúvidas acerca da estruturação e confecção do instrumento, no entanto, percebem o portfólio como potente e inovador no auxílio aconstrução do conhecimento uma vez que permite oacompanhamento do processo de ensino-aprendizagem, possibilitando maior interação entre educador-educando, com produção de uma aprendizagem significativa.Conclusões:o portfólio estimula a reflexão e a crítica acerca das vivências nos cenários de práticas onde se desenvolve o componente curricular Saúde e Cidadaniacorroborando, sobremaneira, para a construção do conhecimento dos estudantes (AU).

Introduction:A degreein healthcare guides the professional practice, directly affecting the healthcare attention and assistance offered to the population. In this sense, the use of active learning and assessment methods, such as portfolios, can contribute to the construction of critical-reflective knowledge. Objective:To highlight the perception of students from health courses, who study the Health and Citizenship discipline at the Federal University of Rio Grande do Norte, regarding the use of the portfolio as an instrument for evaluating teaching and learning.Methodology:Data were obtained through the formation of a focus group and analyzed using content analysis. Thematic categories were then defined: perception of the portfolio; the preparation of the portfolio and its contribution to training; difficulties in formulating the portfolio; the portfolio as an assessment tool. Results:Students understand the portfolio as an instrument of dialogue between teachers and students, through reports of group experiences in social facilities and individual reflections in the construction of concepts and theoretical deepening. They still report insecurities and doubts about the structuring and creation of the instrument, however, they perceive the portfolio as powerful and innovativein helping to build knowledge as it allows the monitoring of the teaching-learning process, enabling greater interaction between educator and student, with the production of significant learning. Conclusions:The portfolio encourages reflection and criticism about the experiences in the practical scenarios where the curricular component -SACI is developed, greatly supporting the construction of students' knowledge (AU).

Introducción:La formación en salud orienta la práctica profesional, incidiendo directamente en la atención y asistencia sanitaria que se ofrece a la población. En este sentido, el uso de métodos activos de aprendizaje y evaluación, como los portafolios, puedecontribuir a la construcción de conocimiento crítico-reflexivo. Objetivo:Resaltar la percepción de estudiantes de carreras de salud, que cursan la disciplina Salud y Ciudadanía de la Universidad Federal de Rio Grande do Norte, sobre el uso del portafolios como instrumento de evaluación de la enseñanza y del aprendizaje. Metodología:Los datos se obtuvieron mediante la formación de un grupo focal y se analizaron mediante análisis de contenido. Luego se definieron categorías temáticas: percepción del portafolio; la elaboración del portafolio y su contribución a la formación; dificultades para formular el portafolio; el portafolio como herramienta de evaluación.Resultados:Los estudiantes entienden el portafolio como un instrumento de diálogo entre docentes y estudiantes, a través de relatos de experiencias grupales en establecimientos sociales y reflexiones individuales en la construcción de conceptos y profundización teórica. Aún reportan inseguridades y dudas sobre la estructuración y creación del instrumento, sin embargo, perciben el portafolio como poderoso e innovador para ayudar a la construcción de conocimiento ya que permite el seguimiento del proceso de enseñanza-aprendizaje, posibilitando una mayor interacción entre educador y estudiante, con la producción de aprendizajes significativos.Conclusiones: El portafolio incentiva la reflexión y crítica sobre las experiencias en los escenarios prácticos donde se desarrolla el componente curricular -SACI, apoyando en gran medida la construcción del conocimiento de los estudiantes (AU).

Systematic Review of Music Therapy and Musical Interventions for Patients with Moderate and Severe Mental Disorders.

Objective: This systematic review aims to assess the impact of music therapy and musical interventions on neuropsychiatric outcomes among patients with moderate and severe mental disorders, in comparison with conventional treatment in isolation. Methods: The review follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A comprehensive search was conducted on November 16, 2021, using the following databases and search interfaces: Cumulative Index to Nursing and Allied Health Literature, Embase, SCOPUS, Web of Science; PubMed, PsycINFO, Literatura Latino-Americana e do Caribe em Ciências da Saúde, and Scientific Electronic Library Online. Two authors independently assessed the studies for inclusion criteria, extracted the data, and evaluated the quality of the included studies using critical appraisal tools. Results: In total, 17 studies were included, 9 of which were randomized controlled trials. The experimental studies involved 5,082 adult and elderly patients. The most prevalent symptoms assessed in the studies were anxiety, depression, and positive and negative symptoms of psychotic disorders. Music interventions were predominantly conducted by music therapists and nurses, providing passive interventions with the selection of musical repertoire by therapists and patients. The frequency with which musical interventions occurred varied greatly in terms of session duration, number of times per week, and number of times during the day. The identified study designs included clinical and quasi-experimental studies. In terms of methodological quality, clinical studies showed weaknesses regarding deviations from intended interventions. Conclusion: The effectiveness of music therapy and musical interventions for neuropsychiatric symptoms in patients with moderate and severe mental disorders was evident in quasi-experimental and clinical studies with satisfactory methodological quality. Musical interventions, in various forms of application, represent an interdisciplinary therapeutic tool that complements and enhances conventional treatment. Unlike conventional treatments, the immersive and integrative nature of music interventions allows access to both intrapersonal and interpersonal dimensions during periods of psychic suffering. These findings highlight the importance of researchers addressing methodological limitations, such as deviations from intended interventions, and advocate for the expansion the use of music in community treatment settings.

Changes in biomarkers levels from gingival crevicular fluid in pre- and postmenopausal women undergoing orthodontic treatment : A systematic review.

PURPOSE: This study aimed to verify whether there is a difference in biomarker levels in the gingival crevicular fluid between premenopausal and postmenopausal women undergoing orthodontic treatment. METHODS: As eligibility criteria, prospective or retrospective observational studies evaluating women undergoing orthodontic treatment (P), comparing postmenopausal (E) and premenopausal (C) women, and analyzing differences in gingival crevicular fluid biomarkers (O) were included. An electronic search was conducted in seven databases (PubMed, Scopus, Web of Science, LILACS, The Cochrane Library, Embase, and EBSCO: Dentistry & Oral Science) and one grey literature source (Google Scholar). All databases were searched from September 2022 to March 2023. After duplicate exclusion and data extraction, the Newcastle-Ottawa scale was applied to assess the quality and risk of bias, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool was used to verify the certainty of evidence. RESULTS: Three case-control studies that analyzed receptor activator of nuclear factor kappa­B ligand (RANKL), osteopontin (OPN), and interleukin (IL)-17A levels were included. One study reported a significant difference for RANKL and another for OPN levels. A third study reported that there was a higher expression of IL17­A in the postmenopausal group. However, the small number of articles limits our systematic review. The heterogeneity and imprecision in the study results cast doubt on the findings' internal validity. CONCLUSION: The studies reported alterations in biomarker levels but differed in their conclusions. Therefore, further studies must include other types of bone and inflammatory biomarkers in female patients who are pre- or postmenopausal and undergoing orthodontic treatment. REGISTRATION: The review was registered at the Open Science Framework ( https://doi.org/10.17605/OSF.IO/Q9YZ8 ).

FTIR Spectroscopy and Blood-Derived Extracellular Vesicles Duo in Alzheimer's Disease.

Background: Alzheimer's disease (AD) diagnosis is difficult, and new accurate tools based on peripheral biofluids are urgently needed. Extracellular vesicles (EVs) emerged as a valuable source of biomarker profiles for AD, since their cargo is disease-specific and these can be easily isolated from easily accessible biofluids, as blood. Fourier Transform Infrared (FTIR) spectroscopy can be employed to analyze EVs and obtain the spectroscopic profiles from different regions of the spectra, simultaneously characterizing carbohydrates, nucleic acids, proteins, and lipids. Objective: The aim of this study was to identify blood-derived EVs (bdEVs) spectroscopic signatures with AD discriminatory potential. Methods: Herein, FTIR spectra of bdEVs from two biofluids (serum and plasma) and distinct sets of Controls and AD cases were acquired, and EVs' spectra analyzed. Results: Analysis of bdEVs second derivative peaks area revealed differences between Controls and AD cases in distinct spectra regions, assigned to carbohydrates and nucleic acids, amides, and lipids. Conclusions: EVs' spectroscopic profiles presented AD discriminatory value, supporting the use of bdEVs combined with FTIR as a screening or complementary tool for AD diagnosis.

Rosuvastatin effect on atherosclerotic plaque metabolism: A subclinical atherosclerosis imaging study with 18F-NaF PET-CT.

BACKGROUND AND AIMS: Atherosclerotic plaque fluorine-18 sodium fluoride (18F-NaF) uptake on positron emission tomography with computed tomography (PET-CT) identifies active microcalcification and has been shown to correlate with clinical instability in patients with cardiovascular (CV) disease. Statin therapy promotes coronary macrocalcification over time. Our aim was to investigate rosuvastatin effect on atheroma 18F-NaF uptake. METHODS: Subjects with high CV risk but without CV events underwent 18F-NaF-PET-CT in a single-centre. Those with subclinical atherosclerosis and significant 18F-NaF plaque uptake were included in a single-arm clinical trial, treated with rosuvastatin 20 mg/daily for six months, and re-evaluated by 18F-NaF-PET-CT. Primary endpoint was reduction in maximum atheroma 18F-NaF uptake in the coronary, aortic or carotid arteries, assessed by the tissue-to-background ratio (TBR). The secondary endpoint was corrected uptake per lesion (CUL) variation. RESULTS: Forty individuals were enrolled and 38 included in the pharmacological trial; mean age was 64 years, two-thirds were male and most were diabetic. The 10-year expected CV risk was 9.5% (6.0-15.3) for SCORE2 and 31.7 ± 18.7% for ASCVD systems. After six months of rosuvastatin treatment (n = 34), low-density lipoprotein cholesterol lowered from 133.6 ± 33.8 to 58.8 ± 20.7 mg dL-1 (60% relative reduction, p < 0.01). There was a significant 19% reduction in maximum plaque 18F-NaF uptake after treatment, from 1.96 (1.78-2.22) to 1.53 (1.40-2.10), p < 0.001 (primary endpoint analysis). The secondary endpoint CUL was reduced by 23% (p = 0.003). CONCLUSION: In a single-centre non-randomized clinical trial of high CV risk individuals with subclinical atherosclerosis, the maximum atherosclerotic plaque 18F-NaF uptake was significantly reduced after six months of high-intensity statin.

Noncanonical and reversible cysteine ubiquitination prevents the overubiquitination of PEX5 at the peroxisomal membrane.

PEX5, the peroxisomal protein shuttling receptor, binds newly synthesized proteins in the cytosol and transports them to the organelle. During its stay at the peroxisomal protein translocon, PEX5 is monoubiquitinated at its cysteine 11 residue, a mandatory modification for its subsequent ATP-dependent extraction back into the cytosol. The reason why a cysteine and not a lysine residue is the ubiquitin acceptor is unknown. Using an established rat liver-based cell-free in vitro system, we found that, in contrast to wild-type PEX5, a PEX5 protein possessing a lysine at position 11 is polyubiquitinated at the peroxisomal membrane, a modification that negatively interferes with the extraction process. Wild-type PEX5 cannot retain a polyubiquitin chain because ubiquitination at cysteine 11 is a reversible reaction, with the E2-mediated deubiquitination step presenting faster kinetics than PEX5 polyubiquitination. We propose that the reversible nonconventional ubiquitination of PEX5 ensures that neither the peroxisomal protein translocon becomes obstructed with polyubiquitinated PEX5 nor is PEX5 targeted for proteasomal degradation.

Neuromodulation of Acid-Sensitive Ion Channels (ASICs) and Anti-Inflammatory Potential by Lichenxanthone in Adult Zebrafish (Danio rerio): Experimental and Docking Studies.

The xanthone lichenxanthone did not show toxic effects (LC50>1.0 mg/mL). lichenxanthone prevented nociceptive behavior induced by acidic saline, and its analgesic effect was blocked by amiloride, highlighting the involvement of neuromodulation of acid-sensitive ion channels (ASICs). In the analysis of anti-inflammatory activity, concentrations of 0.1 and 0.5 mg/mL of lichenxanthone reduced the edema induced by k-carrageenan 3.5 %, observed from the fourth hour of analysis. This effect was similar to that observed with ibuprofen (positive control). No leukocyte infiltrates were observed in lichenxanthone, suggesting that the compound acts in the acute inflammatory response. The results of the molecular docking study revealed that lichenxanthone exhibited better affinity energy when compared to the ibuprofen control against the two targets evaluated.

First register of microplastic contamination in oysters (Crassostrea gasar) farmed in Amazonian estuaries.

The present study investigated the contamination of oysters farmed in Amazonian estuaries by microplastics (MPs). A total of 120 adult oysters (Crassostrea gasar) were collected from four sites along the Mangrove Coast of Pará/Brazil: S1, S2, S3 and S4, with 30 oyster for each. Overall, 58.33 % of the oyster samples contained microplastics, with mean concentrations of 0.23 MPs/g and 1.9 MPs/ind. The concentration of microplastics varied among the four sites, where S1 and S3 had the highest values while S4 had the lowest. PA fibers were the majority of particles (91 %), followed by PS fragments (9 %). The hepatopancreas and the gonad concentrated more microplastics than the rest of the body. As an important species for aquaculture in Amazon, we recommend additional regulation to reduce human exposure to microplastics, such as the installation of depuration facilities and constant monitoring of the contamination of oysters from farms in the region.

Phosphoproteome Microarray Analysis of Extracellular Particles as a Tool to Explore Novel Biomarker Candidates for Alzheimer's Disease.

Phosphorylation plays a key role in Alzheimer's disease (AD) pathogenesis, impacting distinct processes such as amyloid-beta (Aß) peptide production and tau phosphorylation. Impaired phosphorylation events contribute to senile plaques and neurofibrillary tangles' formation, two major histopathological hallmarks of AD. Blood-derived extracellular particles (bdEP) can represent a disease-related source of phosphobiomarker candidates, and hence, in this pilot study, bdEP of Control and AD cases were analyzed by a targeted phosphoproteomics approach using a high-density microarray that featured at least 1145 pan-specific and 913 phosphosite-specific antibodies. This approach, innovatively applied to bdEP, allowed the identification of 150 proteins whose expression levels and/or phosphorylation patterns were significantly altered across AD cases. Gene Ontology enrichment and Reactome pathway analysis unraveled potentially relevant molecular targets and disease-associated pathways, and protein-protein interaction networks were constructed to highlight key targets. The discriminatory value of both the total proteome and the phosphoproteome was evaluated by univariate and multivariate approaches. This pilot experiment supports that bdEP are enriched in phosphotargets relevant in an AD context, holding value as peripheral biomarker candidates for disease diagnosis.