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Abstract Background Group B Streptococcus (GBS) is a commensal of healthy adults and an important pathogen in newborns, the elderly and immunocompromised individuals. GBS displays several virulence factors that promote colonisation and host infection, including the ST-17 strain-specific adhesin Srr2, previously characterised for its binding to fibrinogen. Another common target for bacterial adhesins and for host colonization is fibronectin, a multi-domain glycoprotein found ubiquitously in body fluids, in the extracellular matrix and on the surface of cells. Results In this study, fibronectin was identified as a novel ligand for the Srr2 adhesin of GBS. A derivative of the ST-17 strain BM110 overexpressing the srr2 gene showed an increased ability to bind fibrinogen and fibronectin, compared to the isogenic wild-type strain. Conversely, the deletion of srr2 impaired bacterial adhesion to both ligands. ELISA assays and surface plasmon resonance studies using the recombinant binding region (BR) form of Srr2 confirmed a direct interaction with fibronectin with an estimated Kd of 92 nM. Srr2-BR variants defective in fibrinogen binding also exhibited no interaction with fibronectin, suggesting that Srr2 binds this ligand through the dock-lock-latch mechanism, previously described for fibrinogen binding. The fibronectin site responsible for recombinant Srr2-BR binding was identified and localised in the central cell-binding domain of the protein. Finally, in the presence of fibronectin, the ability of a Δsrr2 mutant to adhere to human cervico-vaginal epithelial cells was significantly lower than that of the wild-type strain. Conclusion By combining genetic and biochemical approaches, we demonstrate a new role for Srr2, namely interacting with fibronectin. We characterised the molecular mechanism of this interaction and demonstrated that it plays a role in promoting the adhesion of GBS to human cervico-vaginal epithelial cells, further substantiating the role of Srr2 as a factor responsible for the hypervirulence of GBS ST-17 strains. The discovery of the previously undescribed interaction between Srr2 and fibronectin establishes this adhesin as a key factor for GBS colonisation of host tissues.

Lithium (Li, atomic number 3), the lightest metal on Earth, is in growing demand due to its use in batteries to power various electrical devices and electric vehicles. Li is also used to stabilize mood and prevent suicide in patients with affective disorders. Geochemical mapping provides a means of visualizing spatial variations in the chemical composition of the surface of the Earth. The objective of the study was to determine the concentration and distribution of Li in soils to identify areas with potential for prospecting and look for relationships with human health. The research was carried out between 2003 and 2017 in 13 Brazilian states, covering an area of 3,313,750 km², in which 3688 soil samples were collected in a grid of 25x25km (625km²). The samples (2kg) collected at the top of the B horizon (up to 30 cm) were reduced at the laboratory with aqua regia and analyzed by ICP-MS. The data indicate that in the total of the 13 states, the concentration of Li in the soils (mg/kg) ranges between 0.5 and 167, with a median of 2. Higher levels stand out in the states of Paraíba (0.5-167.15), Ceará (0.7-63.7), Pernambuco (0.5-63.7), Minas Gerais (0.5-83.2), Alagoas (2.0-40.4) and Mato Grosso do Sul (0.5-61.2). In the Pernambuco and Minas Gerais states, the highest values overlap with the Borborema Province and District of Araçuaí, respectively, which already produce Li hosted in pegmatites and have the potential for new deposits. Anomalous Li values above 11.75 mg/kg (estimated as national reference) cover a prospective area of around 25,225 km², distributed for 140 municipalities, or approximately 0.76% of the studied area. On a regional scale, there was no causal correlation between state suicide rates and the levels of Li in the soil.

While COVID-19’s urgency has diminished since its emergence in late 2019, it remains a significant public health challenge. Recent research reveals that the molecular intricacies of this virus are far more complex than initially understood, with numerous post-translational modifications leading to diverse proteoforms and viral particle heterogeneity. Mass spectrometry-based proteomics of patient serum/plasma emerges as a promising complementary approach to traditional diagnostic methods, offering insights into SARS-CoV-2 protein dynamics and enhancing understanding of the disease and its long-term consequences. This article highlights key findings from three years of pandemic-era proteomics research. It delves into biomarker discovery, diagnostic advancements, and drug development efforts aimed at monitoring COVID-19 onset and progression and exploring treatment options. Additionally, it examines global protein abundance and post-translational modification profiling to elucidate signaling pathway alterations and protein-protein interactions during infection. Finally, it explores the potential of emerging multi-omics analytic strategies in combatting SARS-CoV-2.

This Special Issue, “Mass Spectrometric Proteomics 2 [...]

The Yanomami Indigenous Land in the Amazon has a long history of illegal artisanal gold mining, leading to concerns about mercury (Hg) contamination. This study has conducted a geochemical analysis to assess Hg contamination from these mining activities. Geological materials, including river water and stream sediments, were collected from 14 predetermined points based on the Geological Survey of Brazil’s methodology. The results revealed that water samples did not show Hg contamination above the limits set by the National Council of the Environment (Conama) Resolution 357. However, two stream sediment samples, particularly PJS009 and PJS010 collected from the Mucajaí River, exceeded the Conama Resolution 454’s limit of 0.17 mg/kg. A Hg content of 0.344 mg/kg was found in the sediment sample PJS009, the one collected further upstream in the Mucajaí River, and 1.386 mg/kg was found in sample PJS010, also in the Mucajaí River in the region shortly before the Fumaça Waterfall, indicating that the sediments of the Mucajaí River may be contaminated with Hg from the Fumaça Waterfall upstream.

Neutrophils play a pathogenic role in COVID-19 by releasing Neutrophils Extracellular Traps (NETs) or human neutrophil elastase (HNE). Given that HNE is inhibited by α1-antitrypsin (AAT), we aimed to assess the content of HNE, α1-antitrypsin (AAT) and HNE–AAT complexes (the AAT/HNE balance) in 33 bronchoalveolar lavage fluid (BALf) samples from COVID-19 patients. These samples were submitted for Gel-Electrophoresis, Western Blot and ELISA, and proteins (bound to AAT or HNE) were identified by Liquid Chromatography-Mass Spectrometry. NETs’ release was analyzed by confocal microscopy. Both HNE and AAT were clearly detectable in BALf at high levels. Contrary to what was previously observed in other settings, the formation of HNE–AAT complex was not detected in COVID-19. Rather, HNE was found to be bound to acute phase proteins, histones and C3. Due to the relevant role of NETs, we assessed the ability of free AAT to bind to histones. While confirming this binding, AAT was not able to inhibit NET formation. In conclusion, despite the finding of a high burden of free and bound HNE, the lack of the HNE–AAT inhibitory complex in COVID-19 BALf demonstrates that AAT is not able to block HNE activity. Furthermore, while binding to histones, AAT does not prevent NET formation nor their noxious activity.

While COVID-19's urgency has diminished since its emergence in late 2019, it remains a significant public health challenge. Recent research reveals that the molecular intricacies of this virus are far more complex than initially understood, with numerous post-translational modifications leading to diverse proteoforms and viral particle heterogeneity. Mass spectrometry-based proteomics of patient serum/plasma emerges as a promising complementary approach to traditional diagnostic methods, offering insights into SARS-CoV-2 protein dynamics and enhancing understanding of the disease and its long-term consequences. This article highlights key findings from three years of pandemic-era proteomics research. It delves into biomarker discovery, diagnostic advancements, and drug development efforts aimed at monitoring COVID-19 onset and progression and exploring treatment options. Additionally, it examines global protein abundance and post-translational modification profiling to elucidate signaling pathway alterations and protein-protein interactions during infection. Finally, it explores the potential of emerging multi-omics analytic strategies in combatting SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Human neutrophil elastase (HNE) is involved in SARS-CoV-2 virulence and plays a pivotal role in lung infection of patients infected by COVID-19. In healthy individuals, HNE activity is balanced by α1-antitrypsin (AAT). This is a 52 kDa glycoprotein, mainly produced and secreted by hepatocytes, that specifically inhibits HNE by blocking its activity through the formation of a stable complex (HNE–AAT) in which the two proteins are covalently bound. The lack of this complex, together with the detection of HNE activity in BALf/plasma samples of COVID-19 patients, leads us to hypothesize that potential functional deficiencies should necessarily be attributed to possible structural modifications of AAT. These could greatly diminish its ability to inhibit neutrophil elastase, thus reducing lung protection. The aim of this work was to explore the oxidation state of AAT in BALf/plasma samples from these patients so as to understand whether the deficient inhibitory activity of AAT was somehow related to possible conformational changes caused by the presence of abnormally oxidized residues.

In Antarctica, ice-free areas can be found along the coast, on mountain peaks, and in the McMurdo Dry Valleys, where microorganisms well-adapted to harsh conditions can survive and reproduce. Metabolic analyses can shed light on the survival mechanisms of Antarctic soil communities from both coastal sites, under different plant coverage stages, and inner sites where slow-growing or dormant microorganisms, low water availability, salt accumulation, and a limited number of primary producers make metabolomic profiling difficult. Here, we report, for the first time, an efficient protocol for the extraction and the metabolic profiling of Antarctic soils based on the combination of NMR spectroscopy and mass spectrometry (MS). This approach was set up on samples harvested along different localities of Victoria Land, in continental Antarctica, devoid of or covered by differently developed biological crusts. NMR allowed for the identification of thirty metabolites (mainly sugars, amino acids, and organic acids) and the quantification of just over twenty of them. UPLC-MS analysis identified more than twenty other metabolites, in particular flavonoids, medium- and long-chain fatty acids, benzoic acid derivatives, anthracenes, and quinones. Our results highlighted the complementarity of the two analytical techniques. Moreover, we demonstrated that their combined use represents the “gold standard” for the qualitative and quantitative analysis of little-explored samples, such as those collected from Antarctic soils.

Energy communities (ECs) have become an attractive scholarly target in the last years since they promote more sustainable, democratic, and decentralized electrical systems. Thus, a new research line around the alignments established by the European Union (EU) has arisen. Nevertheless, Latin American initiatives and academic works still lack a standard distinctness, being widely spread, despite commonalities. This study examines regional projects from a critical perspective to fashion a novel framework around South American ECs' experiences. Literature indicates a variety of cases in the region, primarily off-grid isolated ventures that satisfy basic human needs, employing hydropower, solar, wind, biomass, and biogas technologies. Notably, Brazil indicates more profound advancements in on-grid ECs within urban settlements.

The Burkholderia cepacia complex comprises environmental and clinical Gram-negative bacteria that infect particularly debilitated people, such as those with cystic fibrosis. Their high level of antibiotic resistance makes empirical treatments often ineffective, increasing the risk of worst outcomes and the diffusion of multi-drug resistance. However, the discovery of new antibiotics is not trivial, so an alternative can be the use of vaccination. Here, the reverse vaccinology approach has been used to identify antigen candidates, obtaining a short-list of 24 proteins. The localization and different aspects of virulence were investigated for three of them—BCAL1524, BCAM0949, and BCAS0335. The three antigens were localized in the outer membrane vesicles confirming that they are surface exposed. We showed that BCAL1524, a collagen-like protein, promotes bacteria auto-aggregation and plays an important role in virulence, in the Galleria mellonella model. BCAM0949, an extracellular lipase, mediates piperacillin resistance, biofilm formation in Luria Bertani and artificial sputum medium, rhamnolipid production, and swimming motility; its predicted lipolytic activity was also experimentally confirmed. BCAS0335, a trimeric adhesin, promotes minocycline resistance, biofilm organization in LB, and virulence in G. mellonella. Their important role in virulence necessitates further investigations to shed light on the usefulness of these proteins as antigen candidates.

Spermatocytic tumor (ST) is a very rare disease, accounting for approximately 1% of testicular cancers. Previously classified as spermatocytic seminoma, it is currently classified within the non-germ neoplasia in-situ-derived tumors and has different clinical-pathologic features when compared with other forms of germ cell tumors (GCTs). A web-based search of MEDLINE/PubMed library data was performed in order to identify pertinent articles. In the vast majority of cases, STs are diagnosed at stage I and carry a very good prognosis. The treatment of choice is orchiectomy alone. Nevertheless, there are two rare variants of STs having very aggressive behavior, namely anaplastic ST and ST with sarcomatous transformation, that are resistant to systemic treatments and their prognosis is very poor. We have summarized all the epidemiological, pathological and clinical features available in the literature regarding STs that have to be considered as a specific entity compared to other germ GCTs, including seminoma. With the aim of improving the knowledge of this rare disease, an international registry is required.

The constitutional role and authority of the Public Prosecutor’s Office (MP) as an enforcer of law warranted the MP protagonism in the enforcement of environmental legislation and accountability of environmental agencies in Brazil. The MP instituted regional offices to tackle the environmental issue and established a team of experts to provide technical support. This research analyzes the participation of the São Paulo State Public Prosecutor’s Office (MPSP) and the Federal Public Prosecutor’s Office (MPF) experts in the environmental licensing of the Mexilhão Project. The project was located in the coastal region of the state of São Paulo and initially aimed to reduce by half the volume of natural gas imported by the country. Based on the analysis of documents and interviews, this paper shows that there were different interpretations and framings among the MP experts concerning environmental impacts and risks of the project. This study also discusses MP's influence on the decisions of the federal environmental agency about the Mexilhão Project.

Abstract Background Vascular Ehlers–Danlos syndrome (vEDS) is a heritable connective tissue disorder caused by defects in the type III collagen protein. It is generally considered the most severe form of Ehlers–Danlos syndrome (EDS) due to an increased risk of spontaneous artery or organ rupture. vEDS has an extremely heterogeneous presentation and muscle rupture is considered a minor diagnostic criterium. Methods A patient with a long history of inconclusive examinations and investigations was referred to our unit. The clinical picture was mainly characterized by muscle ruptures, whereas the cardiovascular involvement was limited to mitral regurgitation. We performed a panel analysis of genes associated with inheritable heart diseases using the TruSight Cardio kit (Illumina). A skin biopsy was then performed for functional studies to analyze the different forms of collagen molecules produced in vitro by cutaneous fibroblasts. Results The patient presented the novel variant c.3478A>G (p.Ile1160Val) in COL3A1 (NM_000090.3), whose pathogenicity was supported by biochemical analysis of type III collagen. Conclusion In this report, we describe a case of vEDS with predominant and severe musculoskeletal involvement. Our findings provide insight into genetic variants and clinical expression of vEDS, broadening the clinical scenario of the syndrome.

We propose a new organ-conditioning strategy based on mesenchymal stromal cell (MSCs)/extracellular vesicle (EVs) delivery during hypothermic perfusion. MSCs/EVs marker CD73 is present on renal proximal tubular cells, and it protects against renal ischemia-reperfusion injury by converting adenosine monophosphate into adenosine (ADO). In this study, after checking if CD73-silenced EVs (EVsi) would impact in vitro tubular-cell proliferation, we perfused kidneys of a rat model of donation after circulatory death, with Belzer solution (BS) alone, BS supplemented with MSCs, EVs, or EVsi. The ADO and ATP levels were measured in the effluents and tissues. Global renal ischemic damage score (GRS), and tubular cell proliferation index (IPT) were evaluated in the tissue. EVsi did not induce cell proliferation in vitro. Ex vivo kidneys perfused with BS or BS + EVsi showed the worst GRS and higher effluent ADO levels than the MSC- and EV-perfused kidneys. In the EV-perfused kidneys, the tissue and effluent ATP levels and IPT were the highest, but not if CD73 was silenced. Tissue ATP content was positively correlated with tissue ADO content and negatively correlated with effluent ADO level in all groups. In conclusion, kidney conditioning with EVs protects against ischemic damage by activating the CD73/ADO system.

The identification of markers of inflammatory activity at the early stages of pulmonary diseases which share common characteristics that prevent their clear differentiation is of great significance to avoid misdiagnosis, and to understand the intrinsic molecular mechanism of the disorder. The combination of electrophoretic/chromatographic methods with mass spectrometry is currently a promising approach for the identification of candidate biomarkers of a disease. Since the fluid phase of sputum is a rich source of proteins which could provide an early diagnosis of specific lung disorders, it is frequently used in these studies. This report focuses on the state-of-the-art of the application, over the last ten years (2011–2021), of sputum proteomics in the investigation of severe lung disorders such as COPD; asthma; cystic fibrosis; lung cancer and those caused by COVID-19 infection. Analysis of the complete set of proteins found in sputum of patients affected by these disorders has allowed the identification of proteins whose levels change in response to the organism’s condition. Understanding proteome dynamism may help in associating these proteins with alterations in the physiology or progression of diseases investigated.

While conducting the National Program of Environmental Geochemistry and Medical Geology in the states of Minas Gerais and Bahia, the research team Geological Survey of Brazil – CPRM detected a large area with high levels of fluorine in the geochemical results of the soil, stream sediment and surface water. Fluorine levels were detected by an ion-selective electrode (stream sediment and soil samples) or by ion chromatography (water samples). In this low-density survey, the minimum, maximum and median fluorine grades found at the water samples were 0.005 mg/L, 7.56 mg/L and 0.05 mg/L. For the soil, the samples were 15 mg/L, 1720 mg/L and 152 mg/L, and for the stream sediment, the samples were 35 mg/L, 1076 mg/L and 262 mg/L. The region covers 25 municipalities where studies by researchers from Federal Universities of Minas Gerais and Bahia have detected a high incidence of dental fluorosis, especially where public supply is made via deep wells in the Fissure-Karst Aquifer of the Bambuí Group. Moreover, the study area is highly favorable to the mineral deposit of fluorite and secondary Pb-Zn. Because the area is much larger (99,000 km2) than the other known fluorite provinces of Brazil (Santa Catarina is 2,000 km2 and Vale do Ribeira is 5,000 km2), the designation of Geochemical Megaprovince of Fluorine in the Middle São Francisco River, Brazil, is suggested for this region.

Primary myoepithelial carcinoma of the lung (PMC-L) arising from the bronchial glands in lower respiratory tract is exceedingly rare. Thus far, few cases in adults and only one in a pediatric patient have been recorded. To our knowledge, this is the first report of PMC-L successfully removed in a child, focusing on the importance of multidisciplinary primary surgery for the treatment of this tumor. A 7-year-old girl was admitted for persistent cough and fever; she was unresponsive to oral antibiotics. Chest radiography showed loss of volume of left lung sustained by almost total atelectasis. After routine clinical investigations, she was referred for computed tomography scan and magnetic resonance imaging that documented the presence of a mass occupying the entire left upper lobe, infiltrating the pulmonary hilum (main bronchus, pulmonary artery, superior pulmonary vein, and pericardium). After multidisciplinary evaluation, the histopathologic diagnosis of PMC-L was established using ultrasonography-guided transthoracic core needle biopsy and bronchoscopic biopsies. She was then subjected to left pneumonectomy under extracorporeal circulation and positioning of a thoracic expander filled with 200 mL of saline solution. The postoperative course was uneventful. With TREP (very Rare Tumor in Pediatric Age) consent radiotherapy was performed (61.2 Gy). At the 10-month follow-up, the patient was alive, breathing normally without any oxygen support, without recurrence of PMC-L or metastasis, and without any chest deformity. To our knowledge, this is the first case where a pediatric patient was successfully operated for PMC-L involving the whole lung. Extracorporeal circulation enabled us to perform radical primary surgery. Prosthesis implant not only maintained normal chest expansion but also allowed focused radiotherapy, thus enabling us to prevent damage to vital organs.

Nasu-Hakola Disease (NHD) is a recessively inherited systemic leukodystrophy disorder characterized by a combination of frontotemporal presenile dementia and lytic bone lesions. NHD is known to be genetically related to a structural defect of TREM2 and DAP12, two genes that encode for different subunits of the membrane receptor signaling complex expressed by microglia and osteoclast cells. Because of its rarity, molecular or proteomic studies on this disorder are absent or scarce, only case reports based on neuropsychological and genetic tests being reported. In light of this, the aim of this paper is to provide evidence on the potential of a label-free proteomic platform based on the Multidimensional Protein Identification Technology (MudPIT), combined with in-house software and on-line bioinformatics tools, to characterize the protein expression trends and the most involved pathways in NHD. The application of this approach on the Lymphoblastoid cells from a family composed of individuals affected by NHD, healthy carriers and control subjects allowed for the identification of about 3000 distinct proteins within the three analyzed groups, among which proteins anomalous to each category were identified. Of note, several differentially expressed proteins were associated with neurodegenerative processes. Moreover, the protein networks highlighted some molecular pathways that may be involved in the onset or progression of this rare frontotemporal disorder. Therefore, this fully automated MudPIT platform which allowed, for the first time, the generation of the whole protein profile of Lymphoblastoid cells from Nasu-Hakola subjects, could be a valid approach for the investigation of similar neurodegenerative diseases.

Abstract Technologies used for offshore oil exploration, in increasingly remote and extreme environments, potentiate new environmental threats in contemporary societies. In this context and from a theoretical-analytical perspective associated with Environmental Sociology, based on qualitative research results developed between 2013 and 2016, this article aims to comprehend the treatment of Pre-salt environmental threats in Brazil, a sociotechnical enterprise considered as strategic for national development from the governmental point of view. The researchers argue that the possible environmental consequences, even in face of unquantifiable uncertainties, were addressed, mainly from a perspective of measurable and controllable risks, in two of the main stages of the Pre-salt environmental arena: media and environmental licensing process. This treatment did not encourage a consistent public debate on the issue nor any governmental actions about possible unpredictable and uncontrollable consequences that characterize the technological systems, as represented by the Pre-salt.

Este artigo identifica e discute diferentes arenas que influenciam a conservação da Caatinga no semiárido brasileiro. Para tanto, propõem uma abordagem multimétodo (análise situacional, análise documental e aplicação de entrevistas semiestruturadas). Pôde-se identificar três arenas que influenciam a conservação da Caatinga: arena científica, arena econômico-estatal e arena da sustentabilidade. Nelas, a interação entre diversos atores, em múltiplos níveis de organização social, tem promovido uma ressignificação da importância da Caatinga. Constata-se que a conservação e sustentabilidade da Caatinga têm ganhado mais força nas arenas científicas e de sustentabilidade, tensionando a arena econômico-estatal, modificando a forma de se pensar e agir sobre ela.