Climate determines transmission hotspots of Polycystic Echinococcosis, a life-threatening zoonotic disease, across Pan-Amazonia.

Polycystic Echinococcosis (PE), a neglected life-threatening zoonotic disease caused by the cestode Echinococcus vogeli, is endemic in the Amazon. Despite being treatable, PE reaches a case fatality rate of around 29% due to late or missed diagnosis. PE is sustained in Pan-Amazonia by a complex sylvatic cycle. The hunting of its infected intermediate hosts (especially the lowland paca Cuniculus paca) enables the disease to further transmit to humans, when their viscera are improperly handled. In this study, we compiled a unique dataset of host occurrences (~86000 records) and disease infections (~400 cases) covering the entire Pan-Amazonia and employed different modeling and statistical tools to unveil the spatial distribution of PE's key animal hosts. Subsequently, we derived a set of ecological, environmental, climatic, and hunting covariates that potentially act as transmission risk factors and used them as predictors of two independent Maximum Entropy models, one for animal infections and one for human infections. Our findings indicate that temperature stability promotes the sylvatic circulation of the disease. Additionally, we show how El Niño-Southern Oscillation (ENSO) extreme events disrupt hunting patterns throughout Pan-Amazonia, ultimately affecting the probability of spillover. In a scenario where climate extremes are projected to intensify, climate change at regional level appears to be indirectly driving the spillover of E. vogeli. These results hold substantial implications for a wide range of zoonoses acquired at the wildlife-human interface for which transmission is related to the manipulation and consumption of wild meat, underscoring the pressing need for enhanced awareness and intervention strategies.

The central role of pyruvate metabolism on the epigenetic maturation and transcriptional profile of bovine oocytes.

In brief: Pyruvate metabolism is one of the main metabolic pathways during oocyte maturation. This study demonstrates that pyruvate metabolism also regulates the epigenetic and molecular maturation in bovine oocytes. Abstract: Pyruvate, the final product of glycolysis, undergoes conversion into acetyl-CoA within the mitochondria of oocytes, serving as a primary fuel source for the tricarboxylic acid (TCA) cycle. The citrate generated in the TCA cycle can be transported to the cytoplasm and converted back into acetyl-CoA. This acetyl-CoA can either fuel lipid synthesis or act as a substrate for histone acetylation. This study aimed to investigate how pyruvate metabolism influences lysine 9 histone 3 acetylation (H3K9ac) dynamics and RNA transcription in bovine oocytes during in vitro maturation (IVM). Bovine cumulus-oocyte complexes were cultured in vitro for 24 h, considering three experimental groups: Control (IVM medium only), DCA (IVM supplemented with sodium dichloroacetate, a stimulant of pyruvate oxidation into acetyl-CoA), or IA (IVM supplemented with sodium iodoacetate, a glycolysis inhibitor). The results revealed significant alterations in oocyte metabolism in both treatments, promoting the utilization of lipids as an energy source. These changes during IVM affected the dynamics of H3K9ac, subsequently influencing the oocyte's transcriptional activity. In the DCA and IA groups, a total of 148 and 356 differentially expressed genes were identified, respectively, compared to the control group. These findings suggest that modifications in pyruvate metabolism trigger the activation of metabolic pathways, particularly lipid metabolism, changing acetyl-CoA availability and H3K9ac levels, ultimately impacting the mRNA content of in vitro matured bovine oocytes.

Exposing illegal hunting and wildlife depletion in the world's largest tropical country through social media data.

Globally, illegal sport hunting can threaten prey populations when unregulated. Due to its covert nature, illegal sport hunting poses challenges for data collection, hindering efforts to understand the full extent of its impacts. We gathered social media data to analyze patterns of illegal sport hunting and wildlife depletion across Brazil. We collected data for 2 years (2018-2020) across 5 Facebook groups containing posts depicting pictures of illegal sport hunting events of native fauna. We described and mapped these hunting events by detailing the number of hunters involved, the number of species, the mean body mass of individuals, and the number and biomass of individuals hunted per unit area, stratified by Brazilian biome. We also examined the effects of defaunation on hunting yield and composition via regression models, rank-abundance curves, and spatial interpolation. We detected 2046 illegal sport hunting posts portraying the hunting of 4658 animals (∼29 t of undressed meat) across all 27 states and 6 natural biomes of Brazil. Of 157 native species targeted by hunters, 19 are currently threatened with extinction. We estimated that 1414 hunters extracted 3251 kg/million km2. Some areas exhibited more pronounced wildlife depletion, in particular the Atlantic Forest and Caatinga biomes. In these areas, there was a shift from large mammals and reptiles to small birds as the main targeted taxa, and biomass extracted per hunting event and mean body mass across all taxonomic groups were lower than in other areas. Our results highlight that illegal sport hunting adds to the pressures of subsistence hunting and the wild meat trade on Brazil's wildlife populations. Enhanced surveillance efforts are needed to reduce illegal sport hunting levels and to develop well-managed sustainable sport hunting programs. These can support wildlife conservation and offer incentives for local communities to oversee designated sport hunting areas.

Exposición de la caza ilegal y la reducción de fauna en el país tropical más grande del mundo por medio de datos de las redes sociales Resumen En todo el mundo, la caza recreativa ilegal puede amenazar a las poblaciones de presas cuando no está regulada. Debido a su naturaleza encubierta, la caza recreativa ilegal plantea dificultades para la recopilación de datos, lo que dificulta la comprensión de su impacto. Recopilamos datos de redes sociales para analizar los patrones de caza recreativa ilegal y agotamiento de la vida silvestre en todo Brasil. Recopilamos datos durante 2 años (2018­2020) a través de cinco grupos de Facebook que contenían publicaciones que mostraban imágenes de eventos de caza recreativa ilegal de fauna nativa. Describimos y mapeamos estos eventos de caza detallando el número de cazadores involucrados, el número de especies, la masa corporal media de los individuos y el número y la biomasa de los individuos cazados por unidad de área, estratificados por bioma brasileño. También examinamos los efectos de la deforestación en el rendimiento y la composición de la caza mediante modelos de regresión, curvas de abundancia e interpolación espacial. Detectamos 2,046 puestos de caza recreativa ilegal que mostraban la caza de 4,658 animales (∼29 t de carne sin desollar) en los 27 estados y 6 biomas naturales de Brasil. De las 157 especies autóctonas objetivo de los cazadores, 18 están actualmente en peligro de extinción. Se calcula que 1,414 cazadores extrajeron 3,251 kg/millón de km2. Algunas zonas mostraron una defaunación más pronunciada, en particular los biomas de la Mata Atlántica y la Caatinga. En estas áreas, se produjo un cambio de grandes mamíferos y reptiles a pequeñas aves como principales taxones objetivo, y la biomasa extraída por evento de caza y la masa corporal media en todos los grupos taxonómicos fueron menores que en otras áreas. Nuestros resultados ponen de manifiesto que la caza recreativa ilegal se suma a las presiones de la caza de subsistencia y el comercio de carne salvaje sobre las poblaciones de fauna de Brasil. Es necesario intensificar los esfuerzos de vigilancia para reducir los niveles de caza recreativa ilegal y desarrollar programas de caza recreativa sostenibles y bien gestionados. Estos programas pueden contribuir a la conservación de la fauna y ofrecer incentivos a las comunidades locales para que supervisen las zonas designadas para la caza recreativa.

"Antibacterial effect and possible mechanism of action of 1,3,4-oxadiazole in Staphylococcus aureus".

Staphylococcus aureus is one of the main etiological agents causing foodborne diseases, and the development of new antibacterial agents is urgent. This study evaluated the antibacterial activity and the possible mechanism of action of the 1,3,4-oxadiazole LMM6 against S. aureus. The minimum inhibitory concentration (MIC) of LMM6 ranged from 1.95 to 7.81 µg ml-1. The time-kill assay showed that 48-h treatment at 1× to 8× MIC reduced S. aureus by 4 log colony forming unit (CFU), indicating a bacteriostatic effect. Regarding the possible mechanism of action of LMM6, there was accumulation of reactive oxygen species (ROS) and an increase in the absorption of crystal violet (∼50%) by the cells treated with LMM6 at 1× and 2× MIC for 6-12 h. In addition, there was increased propidium iodide uptake (∼84%) after exposure to LMM6 for 12 h at 2× MIC. After 48 h of treatment, 100% of bacteria had been injured. Scanning electron microscopy observations demonstrated that LMM6-treated cells were smaller compared with the untreated group. LMM6 exhibited bacteriostatic activity and its mechanism of action involves increase of intracellular ROS and disturbance of the cell membrane, which can be considered a key target for controlling the growth of S. aureus.

Subtilisin of Leishmania amazonensis as Potential Druggable Target: Subcellular Localization, In Vitro Leishmanicidal Activity and Molecular Docking of PF-429242, a Subtilisin Inhibitor.

Subtilisin proteases, found in all organisms, are enzymes important in the post-translational steps of protein processing. In Leishmania major and L. donovani, this enzyme has been described as essential to their survival; however, few compounds that target subtilisin have been investigated for their potential as an antileishmanial drug. In this study, we first show, by electron microscopy and flow cytometry, that subtilisin has broad localization throughout the cytoplasm and membrane of the parasite in the promastigote form with foci in the flagellar pocket. Through in silico analysis, the similarity between subtilisin of different Leishmania species and that of humans were determined, and based on molecular docking, we evaluated the interaction capacity of a serine protease inhibitor against both life cycle forms of Leishmania. The selected inhibitor, known as PF-429242, has already been used against the dengue virus, arenaviruses, and the hepatitis C virus. Moreover, it proved to have antilipogenic activity in a mouse model and caused hypolipidemia in human cells in vitro. Here, PF-429242 significantly inhibited the growth of L. amazonensis promastigotes of four different strains (IC50 values = 3.07 ± 0.20; 0.83 ± 0.12; 2.02 ± 0.27 and 5.83 ± 1.2 µM against LTB0016, PH8, Josefa and LV78 strains) whilst having low toxicity in the host macrophages (CC50 = 170.30 µM). We detected by flow cytometry that there is a greater expression of subtilisin in the amastigote form; however, PF-429242 had a low effect against this intracellular form with an IC50 of >100 µM for intracellular amastigotes, as well as against axenic amastigotes (94.12 ± 2.8 µM for the LV78 strain). In conclusion, even though PF-429242 does not affect the intracellular forms, this drug will serve as a tool to explore pharmacological and potentially leishmanicidal targets.

Effects of caffeine supplementation on muscle endurance, maximum strength, and perceived exertion in adults submitted to strength training: a systematic review and meta-analyses.

This study aimed to determine the effects of caffeine supplementation on muscle endurance, maximum strength, and ratings of perceived exertion (RPE) in individuals undergoing strength training with external resistance exercises. A search of three databases (PubMed, LiLACS, and CENTRAL) and gray literature was carried out to find randomized controlled trials, with a double-blind design, which investigated the effects of caffeine supplementation in healthy adults. Meta-analyses of weighted mean differences (WMD) and standardized mean differences (SMD) between caffeine and placebo groups from individual studies were performed using a random-effects model. Nineteen studies were included in the quantitative synthesis. Only the bench press and the leg press exercises were assessed in a sufficient number of studies to be included in meta-analyses. In the bench press exercise, caffeine supplementation improved strength resistance (WMD 0.87 (95% confidence interval (CI): 0.33, 1.41) repetitions, P = 0.001; 15 studies), and maximum strength (WMD 2.01 (95% CI: 0.20, 3.80) kg, P = 0.02; 7 studies), but showed no effect in RPE (SMD -0.45 (95% CI: -1.40, 0.48), P = 0.34, 7 studies) In the leg press exercise, no significant improvement were observed in muscle endurance (WMD: 1.24 (95% CI: -0.21, 2.70) repetitions, P = 0.09, 8 studies), maximum strength (WMD 8.49 (95% CI: -11.91, 28.90) kg, P = 0.415, 3 studies), and in RPE (SMD -0.17 (95% CI: -1.62, 1.27), P = 0.812, 3 studies). Caffeine supplementation showed a significant ergogenic effect on muscle endurance and maximum strength in the bench press exercise. More investigations are needed to clarify the contradictions in its effects regarding lower-body exercises.

Sialolipomas of minor salivary glands: A multi-institutional study and literature review.

BACKGROUND: Sialolipoma is a rare histological variant of lipoma commonly misdiagnosed and composed of a proliferation of mature adipocytes with secondary entrapment of normal salivary gland tissue. The purpose of the present study is to report the clinicopathologic and immunohistochemical features of 10 new cases of sialolipomas in conjunction with a review of the literature. METHODS: A retrospective descriptive cross-sectional study was performed. A total of 54,190 biopsy records of oral and maxillofacial lesions from four oral and maxillofacial pathology services in Brazil were analysed. All cases of lipomas were reviewed, and clinical, demographic and histopathological data were collected of all cases compatible with sialolipomas. In addition, immunohistochemistry stains (AE1/AE3, CK7, 34ßE12, S-100, HHF35, α-SMA and Ki-67) and a literature review based on a search of three electronic databases (PubMed, Web of Science and Scopus) were performed. RESULTS: Among all lipomas reviewed, there were 10 cases of sialolipomas. The series comprised of 7 females (70.0%) and 3 males (30.0%), with a mean age of 46.1 ± 21.5 years (range: 11-71 years) and a 2.3:1 female-to-male ratio. The lower lip (n = 3, 30.0%) and tongue (n = 2, 20.0%) were the most common locations, presenting clinically as a nodule of slow growth and normal colour. Conservative surgical excision was the treatment in all cases. No recurrence was observed. CONCLUSION: Sialolipomas are a rare histological variant of lipoma, affecting the salivary glands, mainly in the parotid gland and palate of female adults. Pathologists must recognise sialolipomas to avoid misdiagnoses with other lipomatous tumours that can affect salivary glands.

Quantifying anthropogenic threats affecting Marine Protected Areas in developing countries.

Conservation's capacity to deal with anthropogenic environmental threats within Marine Protected Areas (MPAs) varies enormously, especially in developing countries that are often immersed in weak enforcement, ineffective management and shortages of resources. A deeper understanding of the causes of these threats is fundamental for identifying effective management solutions. Here, we investigate the presumptive drivers of environmental threats across 40 Brazilian MPAs. We categorized and quantified environmental threats from two independent sources: i) the results of systematic social surveys carried out as part of WWF's RAPPAM assessment, as primary data source, and; ii) data gathered from news media articles related to the MPAs (secondary data source). We identified 461 reports of threats that we classified into three general categories: overexploitation, urbanization and land use threats. The presence of overexploitation threats was strongly associated with extreme poverty of local communities close to the MPAs. Threats also seem to be more frequent in category V MPAs, which in Brazil are Environmental Protection Areas (EPA), with multiple use objectives. Threats were concentrated on the North and Southeast coasts of Brazil. We found that data from news media can be used for qualitative assessment of threats, but has limited potential for quantification. Our findings highlight the need for policy makers and MPA managers to adopt a broader perspective that considers the role of social inequalities in promoting and exacerbating environmental threats. While recognizing that conservation has limited capacity to address the widespread social inequalities found in many tropical developing countries, if the socioeconomic context of local communities is significantly compromising conservation efforts it may be necessary to target and prioritize social interventions as a prerequisite for effective MPA management and governance.

An extensive intraoral blue nevus in an elder patient.

OBJECTIVE: To report a rare case of intraoral extensive blue nevus in an elder patient. BACKGROUND: Oral blue nevi is a well-recognised skin melanocytic neoplasm that rarely occurs in the oral cavity and may mimic melanoma in the early stages. METHODS: An incisional biopsy was performed, and the diagnosis was blue nevus. CONCLUSION: Both the clinician and pathologist must be aware of such a presentation to diagnose and treat appropriately.

Are Protected Areas undervalued? An asset-based analysis of Brazilian Protected Area Management Plans.

When effectively managed, Protected Areas (PAs) are capable of generating multiple forms of value, both tangible and intangible, for individuals and institutions. However, the value-generating potential of many PAs may be going unrecognized and underutilized due to a limited view of management objectives as codified within the parks' Management Plan. Here, we test the hypothesis that PAs are undervalued by evaluating the degree to which Management Plans from four different Brazilian designations (National Parks, Ecological Stations, Environmental Protected Areas and National Forests) recognize different categories of nature-related assets (entities, attributes and relationships that can be protected, managed and/or invested in to generate forms of value). Based on a recently proposed PA Asset Framework, we identify what assets are mentioned by Management Plans and what assets are under-represented. Our results indicate that Human and Cultural assets are the least represented of the major asset classes (Biophysical, Human, Infrastructural, Institutional and Cultural) and that many asset sub-categories that should reasonably be expected to be present in Management Plans are frequently not mentioned. Assets that are not being considered in Management Plans are, by extension, less likely to be managed and/or invested in. Given the strong similarities between PA Management Plans in different countries, these results probably reflect a general trend. A simple way to ensure that PAs maximize the value generating potential (within the context of their designation) would be to survey their assets and generate a 'PA Asset Management and Investment Plan' to supplement and support existing planning documentation.

How do physicochemical properties contribute to inhibitory activity of promising peptides against Zika Virus NS3 protease?

CONTEXT AND RESULTS: Flavivirus diseases' cycles, especially Dengue and Yellow Fever, can be observed all over Brazilian territory, representing a great health concern. Additionally, there are no drugs available in therapy. In this scenario, in silico methodologies were applied to obtain physicochemical properties, as well as to better understand the ligand-biological target interaction mode of 20 previously reported NS2B/NS3 protease inhibitors of Dengue virus. Since catalytic site of flavivirus hold similarities, such as the same catalytic triad (His51, Asp75 e Ser135), the ability of this series of molecules to fit in Zika NS3 domains can be achieved. We performed an exploratory data analysis, using statistical methodologies, such as PCA (Principal Component Analysis) and HCA (Hierarchical Component Analysis), to assist the comprehension of how physicochemical properties impact the interaction observed by the docking studies, as well as to build a correlation between the respective ranked characteristics. Based on these previous studies, peptides were selected for the dynamics simulations, which were useful to better understand the ligand-protein interactions. Information relating to, for instance, energy, ΔG, average number of hydrogen bonds and distance from Ser135 (one of the main amino acids in the catalytic pocket) were discussed. In this sense, peptides 15 (considering ΔG value and Hbond number), 7 (ΔG and energy) and 1, 6, 7 and 15 (the proximity to Ser135 throughout the dynamics simulation) were highlighted as promising. Those interesting results could contribute to future studies regarding Zika virus drug design, since this infection represents a great concern in neglected populations. METHODS: The models were constructed in the ChemDraw software. The ligand parametrization was performed in the CHEM3D 17.0, UCSF Chimera. Docking simulations were carried out in the GOLD software, after the redocking validation. We used ASP as the function score. Additionally, for dynamics simulations we applied GROMACS software, exploring, mainly, free binding energy calculations. Exploratory analysis was carried out in Minitab 17.3.1 statistical software. Prior to the exploratory analysis, data of quantum chemical properties of the peptides were collected in Microsoft Excel spreadsheet and organized to obtain Hierarchical Cluster Analysis (HCA) and Principal Component Analysis (PCA).

Optimization of the Erythrosine-mediated photodynamic therapy against Escherichia coli using response surface methodology.

BACKGROUND: The efficacy of photodynamic therapy (PDT) depends on the combination of light and a photosensitizer for inactivation of microorganisms. However, finding the ideal conditions for the factors involved in this technique is time and cost-consuming. The rotational composite central design (RCCD) is a tool that can be allied with PDT to achieve precise results within a shorter working time. METHODS: This study used the response surface methodology to optimize the parameters of PDT mediated by Erythrosine (ERY) and green light-emitting diodes (LED) in different Escherichia coli strains by applying RCCD. RESULTS: The RCCD predicted optimum values of ERY and light exposure on PDT. According to the experimental results, the light exposure time showed the most significant influence on the inactivation of the evaluated bacteria. The optimized operating conditions were validated in laboratory tests, and no viable cells were recovered with ERY at 116 µmol L-1 and 30 min of light (33.34 J cm2) for E. coli ATCC 25922, 108 µmol L-1 and 40 min (44.38 J cm2) for E. coli ATCC 35218, and 108 µmol L-1 and 29.3 min (32.5 J cm2) for E. coli O157:H7 EDL 933. CONCLUSION: The adjusted polynomial models provided accurate information on the combined effects of ERY and lighting time with green LED on PDT. The application of the RCCD, in addition to reducing the number of experiments, also allows for increased quantity and quality of the results. Therefore, surface response methodology combined with PDT is a promising approach to inactivate E. coli.

Multi-targets of antimicrobial photodynamic therapy mediated by erythrosine against Staphylococcus aureus identified by proteomic approach.

Staphylococcus aureus is a global challenge to the clinical field and food industry. Therefore, the development of antimicrobial photodynamic therapy (aPDT) has become one of the valuable methods to control this pathogen. The antibacterial activity of photoinactivation by erythrosine (Ery) against S. aureus has been reported, but its modes of action are unclear. This study aimed to employ a proteomic approach to analyze modes of action of Ery-aPDT against S. aureus. We determined the antibacterial effect by Ery-aPDT assays, quantified reactive oxygen species (ROS) and injury to the cell membrane, and determined protein expression using a proteomic approach combined with bioinformatic tools. Ery-aPDT was effective in reducing S. aureus to undetectable levels. In addition, the increment of ROS accompanied the increase in the reduction of cell viability, and damage to cellular membranes was shown by sublethal injury. In proteomic analysis, we found 17 differentially expressed proteins. These proteins revealed changes mainly associated with defense to oxidative stress, energy metabolism, translation, and protein biosynthesis. Thus, these results suggest that the effectiveness of Ery-aPDT is due to multi-targets in the bacterial cell that cause the death of S. aureus.

Physical exercise is essential for increasing ventricular contractility in hypertensive rats treated with losartan.

The treatment of hypertensive patients with losartan is very common. Despite the reduction in blood pressure, its effects on cardiac contractility and sympathetic autonomic drive are still controversial. In turn, aerobic physical training (APT) also presents an important therapeutic option, providing significant improvements in cardiovascular autonomic control, however little is known about its effects on cardiac contractility, especially when associated with losartan. Therefore, we investigated in spontaneously hypertensive rats (SHR) the effects of losartan and APT on cardiac hemodynamics and functionality, with emphasis on autonomic tonic balance and cardiac contractility. Sixty-four SHR (18 weeks old) were divided into four groups (N = 16): vehicle; vehicle submitted to APT through swimming for 12 weeks; treated with losartan (5 mg·kg-1·d-1) for 12 weeks; and treated with losartan associated with APT. The groups were submitted to cardiac morphological and functional analysis by echocardiography; double blockade of cardiac autonomic receptors with atropine and propranolol; and coronary bed reactivity and left ventricular contractility analyses by the Langendorff technique. APT improved functional parameters and autonomic balance by reducing sympathetic drive and/or increasing vagal drive. In contrast, it promoted a concentric remodeling of the left ventricle (LV). Treatment with losartan reduced sympathetic autonomic drive and cardiac morphological parameters, but there were no significant gains in cardiac functionality and contractility. When combined, the concentric remodeling of the LV to APT was abolished and gains in cardiac functionality and contractility were observed. Our findings suggest that the effects of losartan and APT are complementary and should be applied together in the treatment of hypertension. In spontaneously hypertensive rats, the combination of aerobic physical training with losartan treatment was crucial to greater blood pressure reductions and an increase in left ventricular contractility. Furthermore, losartan treatment prevented the concentric left ventricular remodeling caused by aerobic physical training.

Contributions of human cultures to biodiversity and ecosystem conservation.

The expansion of globalized industrial societies is causing global warming, ecosystem degradation, and species and language extinctions worldwide. Mainstream conservation efforts still focus on nature protection strategies to revert this crisis, often overlooking the essential roles of Indigenous Peoples and Local Communities (IP&LC) in protecting biodiversity and ecosystems globally. Here we assess the scientific literature to identify relationships between biodiversity (including ecosystem diversity) and cultural diversity, and investigate how these connections may affect conservation outcomes in tropical lowland South America. Our assessment reveals a network of interactions and feedbacks between biodiversity and diverse IP&LC, suggesting interconnectedness and interdependencies from which multiple benefits to nature and societies emerge. We illustrate our findings with five case studies of successful conservation models, described as consolidated or promising 'social-ecological hope spots', that show how engagement with IP&LC of various cultures may be the best hope for biodiversity and ecosystem conservation, particularly when aligned with science and technology. In light of these five inspiring cases, we argue that conservation science and policies need to recognize that protecting and promoting both biological and cultural diversities can provide additional co-benefits and solutions to maintain ecosystems resilient in the face of global changes.

2,3-Diarylindoles as COX-2 Inhibitors: Exploring the Structure-activity Relationship through Molecular Docking Simulations.

BACKGROUND: Arylindole derivatives are promising scaffolds in the design of new drugs. These scaffolds exhibit a wide biological activity, including inhibition of COX-2, antitumor activity, receptor GABA agonism, and estrogen receptor modulation. OBJECTIVES: Taking this into account, this paper presents a study to understand the inhibitory action of certain 2-arylindole derivatives, specifically a series of 2,3-diarylindoles with IC50 values from 0.006 nM to 100 nM, on the COX-2 enzyme and supports its structural-activity relationship (SAR) through molecular docking simulations. METHODS: Applying molecular modelling, especially molecular docking, we assessed the SAR of a series of 2,3-arylindoles derivatives in the COX-2 enzyme. RESULTS: The results indicated that Gly 526 and Phe 381 residues are relevant for improving inhibitory activity on para-substituted 3-phenyl- compounds. Arg 120 was also demonstrated to be an important residue for COX-2 inhibition since it enables a π-cation interaction with the best compound in series A5 (experimental IC50 = 0.006 nM determined in advance). Furthermore, COX-2 presents flexibility in some regions of the active site to adequately accommodate 5-substituted compounds containing an indole ring. CONCLUSION: Therefore, such structural features can be used as support for further Structural-Based Drug Design (SBDD) and/or Ligand-Based Drug Design (LBDD) studies on new selective COX-2 inhibitors.

Adaptative response to changes in pyruvate metabolism on the epigenetic landscapes and transcriptomics of bovine embryos.

The epigenetic reprogramming that occurs during the earliest stages of embryonic development has been described as crucial for the initial events of cell specification and differentiation. Recently, the metabolic status of the embryo has gained attention as one of the main factors coordinating epigenetic events. In this work, we investigate the link between pyruvate metabolism and epigenetic regulation by culturing bovine embryos from day 5 in the presence of dichloroacetate (DCA), a pyruvate analog that increases the pyruvate to acetyl-CoA conversion, and iodoacetate (IA), which inhibits the glyceraldehyde-3-phosphate dehydrogenase (GAPDH), leading to glycolysis inhibition. After 8 h of incubation, both DCA and IA-derived embryos presented higher mitochondrial membrane potential. Nevertheless, in both cases, lower levels of acetyl-CoA, ATP-citrate lyase and mitochondrial membrane potential were found in blastocysts, suggesting an adaptative metabolic response, especially in the DCA group. The metabolic alteration found in blastocysts led to changes in the global pattern of H3K9 and H3K27 acetylation and H3K27 trimethylation. Transcriptome analysis revealed that such alterations resulted in molecular differences mainly associated to metabolic processes, establishment of epigenetic marks, control of gene expression and cell cycle. The latter was further confirmed by the alteration of total cell number and cell differentiation in both groups when compared to the control. These results corroborate previous evidence of the relationship between the energy metabolism and the epigenetic reprogramming in preimplantation bovine embryos, reinforcing that the culture system is decisive for precise epigenetic reprogramming, with consequences for the molecular control and differentiation of cells.

Ranging ecology and resource selection of white-lipped peccaries (Tayassu pecari) in the world's largest tropical agricultural frontier.

Agricultural commodity production is one the main drivers of deforestation in Legal Brazilian Amazonia resulting in a deforested and/or fragmented landscape formed by forest remnants of different sizes and shape embedded within the agricultural matrix. As an ecosystem engineer and a crucial seed predator, white-lipped peccaries (Tayassu pecari) play a pivotal role in forest structure, biodiversity, and nutrient cycling. However, they are highly sensitive to habitat fragmentation and hunting pressure. White-lipped peccaries are, therefore, a wide-ranging "landscape species," the spatial and ecological requirements of which can be used to guide conservation planning in human-modified landscapes. Using data from GPS-tracked individuals in large-scale mechanized agriculture landscapes in the state of Mato Grosso, Brazil's largest soybean and maize producer, we investiated the home range size and resource selection during both the crop and non-crop season. We observed a seasonal variation in home range size and an increased selection for croplands during the crop season. White-lipped peccaries favored native vegetation patches and also exhibited avoidance of locations distant from perennial water bodies and distant cropland locations far from forest remmants. This study can contribute to inform effective conservation strategies and land management practices aimed at preserving suitable habitats and promoting wildlife coexistence with working agricultural landscapes.

Proteomic Investigation over the Antimicrobial Photodynamic Therapy Mediated by Rose Bengal Against Staphylococcus aureus.

In order, understanding the antimicrobial action of photodynamic therapy and how this technique can contribute to its application in the control of pathogens. The objective of the study was to employ a proteomic approach to investigate the protein profile of Staphylococcus aureus after antimicrobial photodynamic therapy mediated by rose bengal (RB-aPDT). S. aureus was treated with RB (10 nmoL L-1 ) and illuminated with green LED (0.17 J cm-2 ) for cell viability evaluation. Afterward, proteomic analysis was employed for protein identification and bioinformatic tools to classify the differentially expressed proteins. The reduction in S. aureus after photoinactivation was ~2.5 log CFU mL-1 . A total of 12 proteins (four up-regulated and eight down-regulated) correspond exclusively to alteration by RB-aPDT. Functionally, these proteins are distributed in protein binding, structural constituent of ribosome, proton transmembrane transporter activity and ATPase activity. The effects of photodamage include alterations of levels of several proteins resulting in an activated stress response, altered membrane potential and effects on energy metabolism. These 12 proteins required the presence of both light and RB suggesting a unique response to photodynamic effects. The information about this technique contributes valuable insights into bacterial mechanisms and the mode of action of photodynamic therapy.