The renin-angiotensin system (RAS) is a key player in the control of the cardiovascular system and hydroelectrolyte balance, with an influence on organs and functions throughout the body. The ...classical view of this system saw it as a sequence of many enzymatic steps that culminate in the production of a single biologically active metabolite, the octapeptide angiotensin (ANG) II, by the angiotensin converting enzyme (ACE). The past two decades have revealed new functions for some of the intermediate products, beyond their roles as substrates along the classical route. They may be processed in alternative ways by enzymes such as the ACE homolog ACE2. One effect is to establish a second axis through ACE2/ANG-(1-7)/MAS, whose end point is the metabolite ANG-(1-7). ACE2 and other enzymes can form ANG-(1-7) directly or indirectly from either the decapeptide ANG I or from ANG II. In many cases, this second axis appears to counteract or modulate the effects of the classical axis. ANG-(1-7) itself acts on the receptor MAS to influence a range of mechanisms in the heart, kidney, brain, and other tissues. This review highlights the current knowledge about the roles of ANG-(1-7) in physiology and disease, with particular emphasis on the brain.
Sesquiterpene lactones (SL), characterized by their high prevalence in the
family, are one of the major groups of secondary metabolites found in plants. Researchers from distinct research fields, ...including pharmacology, medicine, and agriculture, are interested in their biological potential. With new SL discovered in the last years, new biological activities have been tested, different action mechanisms (synergistic and/or antagonistic effects), as well as molecular structure-activity relationships described. The review identifies the main sesquiterpene lactones with interconnections between immune responses and anti-inflammatory actions, within different cellular models as well in in vivo studies. Bioaccessibility and bioavailability, as well as molecular structure-activity relationships are addressed. Additionally, plant metabolic engineering, and the impact of sesquiterpene lactone extraction methodologies are presented, with the perspective of biological activity enhancement. Sesquiterpene lactones derivatives are also addressed. This review summarizes the current knowledge regarding the therapeutic potential of sesquiterpene lactones within immune and inflammatory activities, highlighting trends and opportunities for their pharmaceutical/clinical use.
Disposable facemasks represent a new form of environmental contamination worldwide. This study aimed at addressing the abundance of facemasks in an overlooked natural environment with high ecological ...and economic value – the wetlands (Ria de Aveiro, Portugal, as study case), evaluating their potential biodegradation using naturally occurring fungi and assessing the potential ecotoxicity of released microfibres on local bivalves.
All masks collected within 6500 m2 area of Aveiro wetland were 100 % disposable ones (PP-based, confirmed by Fourier transform infrared spectroscopy - FTIR) with an initial abundance of 0.0023 items/m2 in Sept. 2021, which was reduced by ∼40 % in Apr. 2022 and ∼87 % in Sept. 2022, as a reflection of the government policies. Analysis of the carbonyl index (0.03 to 1.79) underlined their state of degradation, primarily due to sun exposure during low tides. In laboratory conditions, 1 mm2 microplastics obtained from new disposable facemasks were prone to biodegradation by Penicillium brevicompactum and Zalerion maritimum inferred from microplastics mass loss (∼22 to −26 % and ∼40 to 50 %, respectively) and FTIR spectra (particularly in the hydroxyl and carbonyl groups). In addition, microfibres released from facemasks induced sublethal effects on the clam, Venerupis corrugata, mostly in their UV-aged form when compared to pristine ones, characterised by a decrease in cellular energy allocation (CEA) and an increase in aerobic energy metabolism (ETS). Concomitantly, clams exposed to 1250 items/L of UV-aged microplastics (similar to field-reported concentrations) expressed greater clearance capacity, indicating a need to compensate for the potential energy unbalance.
This study provides the first baseline monitoring of facemasks in wetlands while bringing new evidence on their biodegradation and ecotoxicity, considering environmentally relevant conditions and keystone organisms in such environments. Such studies require scientific attention for rapid regulatory action against this emerging and persistent pollutant, also targeting remediation and mitigation strategies considering these items under pandemic scenarios.
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•Facemasks became a new normal when facing infections, even in the post-pandemic.•Facemasks littering in natural environments, eg. wetlands, may threaten the biota.•Facemasks' density in Aveiro is one of the highest reported in natural environment.•Facemasks' microplastics are prone to biodegradation by fungi.•Facemasks' microfibers UV-aged induced sublethal effects on clams.
The Norway rat (Rattus norvegicus) is the principal reservoir for leptospirosis in many urban settings. Few studies have identified markers for rat infestation in slum environments while none have ...evaluated the association between household rat infestation and Leptospira infection in humans or the use of infestation markers as a predictive model to stratify risk for leptospirosis.
We enrolled a cohort of 2,003 urban slum residents from Salvador, Brazil in 2004, and followed the cohort during four annual serosurveys to identify serologic evidence for Leptospira infection. In 2007, we performed rodent infestation and environmental surveys of 80 case households, in which resided at least one individual with Leptospira infection, and 109 control households. In the case-control study, signs of rodent infestation were identified in 78% and 42% of the households, respectively. Regression modeling identified the presence of R. norvegicus feces (OR, 4.95; 95% CI, 2.13-11.47), rodent burrows (2.80; 1.06-7.36), access to water (2.79; 1.28-6.09), and un-plastered walls (2.71; 1.21-6.04) as independent risk factors associated with Leptospira infection in a household. We developed a predictive model for infection, based on assigning scores to each of the rodent infestation risk factors. Receiver operating characteristic curve analysis found that the prediction score produced a good/excellent fit based on an area under the curve of 0.78 (0.71-0.84).
Our study found that a high proportion of slum households were infested with R. norvegicus and that rat infestation was significantly associated with the risk of Leptospira infection, indicating that high level transmission occurs among slum households. We developed an easily applicable prediction score based on rat infestation markers, which identified households with highest infection risk. The use of the prediction score in community-based screening may therefore be an effective risk stratification strategy for targeting control measures in slum settings of high leptospirosis transmission.
Tau pathology is defined by the intracellular accumulation of abnormally phosphorylated Tau (MAPT) and is prevalent in several neurodegenerative disorders. The identification of modulators of Tau ...abnormal phosphorylation and aggregation is key to understanding disease progression and developing targeted therapeutic approaches. In this study, we identified String (Stg)/Cdc25 phosphatase as a suppressor of abnormal Tau phosphorylation and associated toxicity. Using a Drosophila model of tauopathy, we showed that Tau dephosphorylation by Stg/Cdc25 correlates with reduced Tau oligomerization, brain vacuolization and locomotor deficits in flies. Moreover, using a disease mimetic model, we provided evidence that Stg/Cdc25 reduces Tau phosphorylation levels independently of Tau aggregation status and delays neurodegeneration progression in the fly. These findings uncover a role for Stg/Cdc25 phosphatases as regulators of Tau biology that extends beyond their well-characterized function as cell-cycle regulators during cell proliferation, and indicate Stg/Cdc25-based approaches as promising entry points to target abnormal Tau phosphorylation.
Leptospirosis is an important public health problem affecting vulnerable urban slum populations in developing country settings. However, the complex interaction of meteorological factors driving the ...temporal trends of leptospirosis remain incompletely understood.
From March 1996-March 2010, we investigated the association between the weekly incidence of leptospirosis and meteorological anomalies in the city of Salvador, Brazil by using a dynamic generalized linear model that accounted for time lags, overall trend, and seasonal variation. Our model showed an increase of leptospirosis cases associated with higher than expected rainfall, lower than expected temperature and higher than expected humidity. There was a lag of one-to-two weeks between weekly values for significant meteorological variables and leptospirosis incidence. Independent of the season, a weekly cumulative rainfall anomaly of 20 mm increased the risk of leptospirosis by 12% compared to a week following the expected seasonal pattern. Finally, over the 14-year study period, the annual incidence of leptospirosis decreased significantly by a factor of 2.7 (8.3 versus 3.0 per 100,000 people), independently of variations in climate.
Strategies to control leptospirosis should focus on avoiding contact with contaminated sources of Leptospira as well as on increasing awareness in the population and health professionals within the short time window after low-level or extreme high-level rainfall events. Increased leptospirosis incidence was restricted to one-to-two weeks after those events suggesting that infectious Leptospira survival may be limited to short time intervals.
Abstract We have examined the mutagenic effects of the fungicide Elatus® on tadpoles of Rana catesbeiana and Leptodactylus latrans. Sixty-four tadpoles of each species have been exposed to three ...concentrations of Elatus® (10, 20, and 50 µg/L-1) during 96 hours. We’ve carried out the micronucleus test (MN) and erythrocyte nuclear abnormalities (ENAs) in 32 tadpoles of each species, the others 32 tadpoles of each species remained in a solution free of Elatus® during 96 hours, in order to assess the ability to recover from the damage caused by the fungicide. There was significant difference in MNs frequency between the treatment exposed to 50µg/L-1 and the control groups for R. catesbeiana, while for L. latrans, we’ve found difference between the treatment of 20 µg/L-1, followed by a period without exposure to the contaminant and the control group when all ENAs were analyzed. When we compared the two species, R. catesbeiana presented a higher frequency of MNs than L. latrans in the treatment exposed to 50 µg/L-1of the fungicide. Our findings highlight the need to monitor amphibians in places where this product is widely used.
Peptidoglycan is the main component of the bacterial wall and protects cells from the mechanical stress that results from high intracellular turgor. Peptidoglycan biosynthesis is very similar in all ...bacteria; bacterial shapes are therefore mainly determined by the spatial and temporal regulation of peptidoglycan synthesis rather than by the chemical composition of peptidoglycan. The form of rod-shaped bacteria, such as Bacillus subtilis or Escherichia coli, is generated by the action of two peptidoglycan synthesis machineries that act at the septum and at the lateral wall in processes coordinated by the cytoskeletal proteins FtsZ and MreB, respectively. The tubulin homologue FtsZ is the first protein recruited to the division site, where it assembles in filaments-forming the Z ring-that undergo treadmilling and recruit later divisome proteins. The rate of treadmilling in B. subtilis controls the rates of both peptidoglycan synthesis and cell division. The actin homologue MreB forms discrete patches that move circumferentially around the cell in tracks perpendicular to the long axis of the cell, and organize the insertion of new cell wall during elongation. Cocci such as Staphylococcus aureus possess only one type of peptidoglycan synthesis machinery, which is diverted from the cell periphery to the septum in preparation for division. The molecular cue that coordinates this transition has remained elusive. Here we investigate the localization of S. aureus peptidoglycan biosynthesis proteins and show that the recruitment of the putative lipid II flippase MurJ to the septum, by the DivIB-DivIC-FtsL complex, drives peptidoglycan incorporation to the midcell. MurJ recruitment corresponds to a turning point in cytokinesis, which is slow and dependent on FtsZ treadmilling before MurJ arrival but becomes faster and independent of FtsZ treadmilling after peptidoglycan synthesis activity is directed to the septum, where it provides additional force for cell envelope constriction.
Every year, millions of people suffer some form of illness associated with the consumption of contaminated food. Escherichia coli (E. coli), found in the intestines of humans and other animals, is ...commonly associated with various diseases, due to the existence of pathogenic strains. Strict monitoring of food products for human consumption is essential to ensure public health, but traditional cell culture-based methods are associated with long waiting times and high costs. New approaches must be developed to achieve cheap, fast, and on-site monitoring. Thus, in this work, we developed optical fiber sensors based on surface plasmon resonance. Gold and cysteamine-coated fibers were functionalized with anti-E. coli antibody and tested using E. coli suspensions with concentrations ranging from 1 cell/mL to 10
cells/mL. An average logarithmic sensitivity of 0.21 ± 0.01 nm/log(cells/mL) was obtained for three independent assays. An additional assay revealed that including molybdenum disulfide resulted in an increase of approximately 50% in sensitivity. Specificity and selectivity were also evaluated, and the sensors were used to analyze contaminated water samples, which verified their promising applicability in the aquaculture field.
Background
Melanoma is the most lethal skin cancer, and its incidence has increased worldwide. About 10% of cases are classified as hereditary melanoma (HM). CDKN2A and CDK4 are the major high‐risk ...genes. Families are also more prone to develop pancreatic cancer, and different forms of oncological surveillance are recommended.
Objectives
Describe the prevalence of CDKN2A/CDK4 germline mutations in melanoma‐prone patients and their phenotypic and histopathological features.
Methods
A total of 69 patients meeting the clinical criteria for HM were included in this cross‐sectional descriptive study. Amplification by PCR and genomic sequencing were used. The variants were classified according to American College of Medical Genetics (ACMG) criteria.
Results
The mean age at first diagnosis of melanoma was 44.8 years (SD ± 17.83). Most patients had phototype II (44.9%), more than 50 melanocytic nevi (76.8%), atypical nevus syndrome (72.5%), history of sunburn (76.8%), and multiple primary melanomas without a family history of this tumor (74.3%). Two hundred melanomas were observed. Most tumors had a Breslow index ≤1.0 mm (84.5%), location in the trunk (60.5%), and superficial spreading histological subtype (22.5%). Four variants were found in CDKN2A exons in seven patients (c.305C>A, c.26T>A, c.361G>A e c.442G>A), two variants in the 5′UTR region in five patients (c.‐25C>T and c.‐33G>C), and two variants in the 3′UTR region in 21 patients (c.*29C>G and c.*69C>T). One likely pathogenic variant (c.305C>A) was identified in one patient (1.4%). No variant was found in CDK4.
Conclusion
The prevalence of CDKN2A mutations was 1.4% in Brazilian patients meeting clinical criteria for HM.
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