Acute bouts of aerobic and resistance exercise similarly alter inhibitory control and response time while inversely modifying plasma BDNF concentrations in middle-aged and older adults with type 2 diabetes.

Impairments in several domains of cognitive functions are observed in people with Type 2 Diabetes Mellitus (T2DM), often accompanied by low Brain-derived neurotrophic factor (BDNF) concentrations. Although aerobic and resistance exercise enhances cognitive functions and raises BDNF concentrations in several populations, it remained uncertain in T2DM subjects. This study compared the effects of a single bout of aerobic (AER, 40 min of treadmill walk at 90-95% of the maximum walk speed) or resistance (RES, 3 × 10 repetitions in eight exercises at 70% of 10-RM) exercise on specific cognitive domain performance and plasma BDNF concentrations of physically active T2DM subjects. Eleven T2DM subjects (9 women/2 men; 63 ± 7 years) performed two counterbalanced trials on non-consecutive days. Stroop Color and Word (SCW) task [assessing the attention (congruent condition) and inhibitory control (incongruent condition)], Visual response time (assessing the response time), and blood collection (for plasma BDNF concentrations) were performed pre and post-exercise sessions. With distinct magnitude, both AER and RES improved the incongruent-SCW (d = - 0.26 vs. - 0.43 in AER and RES, respectively; p < 0.05), RT(best) (d = - 0.31 vs. - 0.52, p < 0.05), and RT(1-5) (d = - 0.64 vs. - 0.21, p < 0.05). The congruent-SCW and RT(6-10) were not statistically different. Plasma BDNF concentrations were elevated 11% in AER (d = 0.30) but decreased by 15% in RES (d = - 0.43). A single session of aerobic or resistance exercise similarly improved the inhibitory control and response time of physically active T2DM subjects. Nevertheless, aerobic and resistance exercise sessions induced an opposite clinical effect in plasma BDNF concentrations.

Construction of an In Silico Structural Profiling Tool Facilitating Mechanistically Grounded Classification of Aquatic Toxicants.

The performance of chemical safety assessment within the domain of environmental toxicology is often impeded by a shortfall of appropriate experimental data describing potential hazards across the many compounds in regular industrial use. In silico schemes for assigning aquatic-relevant modes or mechanisms of toxic action to substances, based solely on consideration of chemical structure, have seen widespread employment─including those of Verhaar, Russom, and later Bauer (MechoA). Recently, development of a further system was reported by Sapounidou, which, in common with MechoA, seeks to ground its classifications in understanding and appreciation of molecular initiating events. Until now, this Sapounidou scheme has not seen implementation as a tool for practical screening use. Accordingly, the primary purpose of this study was to create such a resource─in the form of a computational workflow. This exercise was facilitated through the formulation of 183 structural alerts/rules describing molecular features associated with narcosis, chemical reactivity, and specific mechanisms of action. Output was subsequently compared relative to that of the three aforementioned alternative systems to identify strengths and shortcomings as regards coverage of chemical space.

Diversity and pathogenesis of Staphylococcus aureus from bovine mastitis: current understanding and future perspectives.

Staphylococcus aureus is a leading cause of bovine mastitis worldwide. Despite some improved understanding of disease pathogenesis, progress towards new methods for the control of intramammary infections (IMI) has been limited, particularly in the field of vaccination. Although herd management programs have helped to reduce the number of clinical cases, S. aureus mastitis remains a major disease burden. This review summarizes the past 16 years of research on bovine S. aureus population genetics, and molecular pathogenesis that have been conducted worldwide. We describe the diversity of S. aureus associated with bovine mastitis and the geographical distribution of S. aureus clones in different continents. We also describe studies investigating the evolution of bovine S. aureus and the importance of host-adaptation in its emergence as a mastitis pathogen. The available information on the prevalence of virulence determinants and their functional relevance during the pathogenesis of bovine mastitis are also discussed. Although traits such as biofilm formation and innate immune evasion are critical for the persistence of bacteria, the current understanding of the key host-pathogen interactions that determine the outcome of S. aureus IMI is very limited. We suggest that greater investment in research into the genetic and molecular basis of bovine S. aureus pathogenesis is essential for the identification of novel therapeutic and vaccine targets.

A scheme to evaluate structural alerts to predict toxicity - Assessing confidence by characterising uncertainties.

Structure-activity relationships (SARs) in toxicology have enabled the formation of structural rules which, when coded as structural alerts, are essential tools in in silico toxicology. Whilst other in silico methods have approaches for their evaluation, there is no formal process to assess the confidence that may be associated with a structural alert. This investigation proposes twelve criteria to assess the uncertainty associated with structural alerts, allowing for an assessment of confidence. The criteria are based around the stated purpose, description of the chemistry, toxicology and mechanism, performance and coverage, as well as corroborating and supporting evidence of the alert. Alerts can be given a confidence assessment and score, enabling the identification of areas where more information may be beneficial. The scheme to evaluate structural alerts was placed in the context of various use cases for industrial and regulatory applications. The analysis of alerts, and consideration of the evaluation scheme, identifies the different characteristics an alert may have, such as being highly specific or generic. These characteristics may determine when an alert can be used for specific uses such as identification of analogues for read-across or hazard identification.

Influence of Mental Fatigue on Physical Performance, and Physiological and Perceptual Responses of Judokas Submitted to the Special Judo Fitness Test.

ABSTRACT: Campos, BT, Penna, EM, Rodrigues, JGS, Mendes, TT, Maia-Lima, A, Nakamura, FY, Vieira, ÉLM, Wanner, SP, and Prado, LS. Influence of mental fatigue on physical performance, and physiological and perceptual responses of judokas submitted to the Special Judo Fitness Test. J Strength Cond Res 36(2): 461-468, 2022-Mentally fatigued athletes present impaired aerobic performance, strength endurance, and manual dexterity, despite no changes in anaerobic performance and maximal muscle strength and power. Noteworthy, the effect of mental fatigue on physical performance during high-intensity intermittent tests that require specific motor skills of fighting sports has not been investigated. Therefore, this study aimed to verify whether mental fatigue influences performance and physiological and perceptual responses of judokas subjected to a high-intensity intermittent test designed specifically and validated for judo. Each judoka performed 2 experimental trials-a control trial one and the other one after the induction of mental fatigue. These trials were scheduled in a random and balanced order. In both trials, lactate, glucose, and cortisol concentrations, the heart rate variability, and perceptual variables were collected after the initial treatment and after the Special Judo Fitness Test (SJFT). The initial treatment consisted of a 30-minute cognitive demanding task (Stroop Color test) or watching a movie (control) and was followed by the SJFT. The Stroop Color test increased the perceptions of mental fatigue and effort, without affecting motivation for subsequent testing. Unexpectedly, mentally fatigued athletes did not show reduced performance during the SJFT. Regarding the physiological variables, no significant differences were identified between the 2 experimental conditions. We conclude that physical performance measured during a specific test for judokas is not impaired by a previous 30-minute cognitive task that causes mental fatigue. In addition, this cognitive task did not influence the physiological changes induced by the specific physical test.

Development of an Enhanced Mechanistically Driven Mode of Action Classification Scheme for Adverse Effects on Environmental Species.

This study developed a novel classification scheme to assign chemicals to a verifiable mechanism of (eco-)toxicological action to allow for grouping, read-across, and in silico model generation. The new classification scheme unifies and extends existing schemes and has, at its heart, direct reference to molecular initiating events (MIEs) promoting adverse outcomes. The scheme is based on three broad domains of toxic action representing nonspecific toxicity (e.g., narcosis), reactive mechanisms (e.g., electrophilicity and free radical action), and specific mechanisms (e.g., associated with enzyme inhibition). The scheme is organized at three further levels of detail beyond broad domains to separate out the mechanistic group, specific mechanism, and the MIEs responsible. The novelty of this approach comes from the reference to taxonomic diversity within the classification, transparency, quality of supporting evidence relating to MIEs, and that it can be updated readily.

Metal Bioaccumulation by the Neotropical Clam Anomalocardia flexuosa to Estimate the Quality of Estuarine Sediments.

This investigation evaluated the bioaccumulation potential of the tropical estuarine bivalve Anomalocardia flexuosa for trace metals. To this aim, chemical and sedimentological analyses and bioaccumulation tests were performed. The sediments were mainly composed by fine-sands and mud, with variable levels of organic matter and CaCO3. Muddy sediments from a depositional site (P2) presented the highest concentrations of metals, despite SEM/AVS not indicating bioavailability. Bioaccumulation factors showed high ratios for Cd, Ni, and Zn, while associations between the contents of mud, organic matter, CaCO3 and metals in sediments and tissues of A. flexuosa were indicated by a principal component analysis. The SEM/AVS was not effective to predict the bioavailability through dissolved metals. The results showed that contaminants were bioavailable, while the performed bioaccumulation test proved to be a reliable technique for assessing sediment contamination in estuarine regions. Moreover, A. flexuosa was considered an adequate test organism for bioaccumulation studies.

Interactions between in vivo neuronal-glial markers, side of hippocampal sclerosis, and pharmacoresponse in temporal lobe epilepsy.

OBJECTIVE: To evaluate the interactions of metabolic neuronal-glial changes with the presence and hemispheric-side of hippocampal sclerosis (HS) and its potential role in predicting pharmacoresistance in temporal lobe epilepsy (TLE). METHODS: We included structural magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (1 H-MRS) metabolic data for 91 patients with unilateral TLE and 50 healthy controls. We measured the values of total N-acetyl aspartate/total creatine (tNAA/tCr), glutamate/tCr (Glu/tCr), and myo-inositol/tCr (mIns/tCr). To assess the influence of the pharmacoresponse and hemispheric-side of HS on metabolic data, the relationship between clinical and MRI data, and the predictive value of NAA/Cr, we used analysis of variance/covariance and built a logistic regression model. We used bootstrap simulations to evaluate reproducibility. RESULTS: Bilateral tNAA/tCr reduction was associated with pharmacoresistance and with left HS, a decrease of Glu/tCr ipsilateral to the seizure focus was associated with pharmacoresistance, and ipsilateral mIns/tCr increase was related to pharmacoresistance and the presence of left HS. The logistic regression model containing clinical and 1 H-MRS data discriminated pharmacoresistance (area under the curve [AUC] = 0.78). However, the reduction of tNAA/tCr was the main predictor, with the odds 2.48 greater for pharmacoresistance. SIGNIFICANCE: Our study revealed a spectrum of neuronal-glial changes in TLE, which was associated with pharmacoresistance, being more severe in left-sided HS and less severe in MRI-negative TLE. These noninvasive, in vivo biomarkers provide valuable additional information about the interhemispheric differences in metabolic dysfunction, seizure burden, and HS, and may help to predict pharmacoresistance.

Heavy Metals in Tissues of Blue Crabs Callinectes danae from a Subtropical Protected Estuary Influenced by Mining Residues.

This short note aims to report in detail a preliminary assessment of the concentrations of Cd, Hg and Pb in tissues of blue crabs Callinectes danae collected from the Cananéia-Iguape-Peruíbe estuarine complex (CIP), in the South of São Paulo State coast, Brazil. In October 2014, blue crabs were collected from CIP. Tissues were removed by dissection and metal determination was performed by GF-AAS and CV-AAS. According to statistical analysis, Pb and Cd concentrations in gills were significantly higher than those found in muscles and hepatopancreas, respectively. There were no significant differences in Hg concentrations between samples. Cd, Hg and Pb concentrations in gills and hepatopancreas were lower than those reported in a previous study performed at CIP. However, Cd concentration in hepatopancreas was higher than the Brazilian limit for consumption and new efforts to monitor Cd concentrations in C. danae tissues must be performed.

Effects of Single and Combined Low Concentrations of Neuroactive Drugs on Daphnia magna Reproduction and Transcriptomic Responses.

Assessing the risk of neuroactive pharmaceuticals in the environment requires an understanding of their joint effects at low concentrations across species. Here, we assessed reproductive and transcriptional effects of single and ternary equi-effective mixture exposure to propranolol, diazepam, and carbamazepine on the crustacean Daphnia magna at environmentally relevant concentrations. The three compounds enhanced reproduction in adults and induced specific transcriptome changes in preadolescent individuals. Comparison of the results from single exposures to a ternary equi-effective mixture of the three compounds showed additive action. Transcriptomic analyses identified 3248 genes affected by at least one of the treatments, which were grouped into four clusters. Two clusters (1897 gene transcripts in total) behaved similarly, appearing either over- or under-represented relative to control, in all single and mixture treatments. The third and fourth clusters grouped genes differently transcribed upon exposure to diazepam and propranolol, respectively. Functional transcriptomics analysis indicated that the four clusters shared major deregulated signaling pathways implicated on energy, growth, reproduction, and neurologically related processes, which may be responsible for the observed reproductive effects. Thus, our study showed additive effects at the transcriptional and physiological level and provides a novel approach to the analysis of environmentally relevant mixtures of neuroactive compounds.

Levels of metals and toxicity in sediments from a Ramsar site influenced by former mining activities.

This study aimed to evaluate the sediment quality in a Ramsar site located in the Southeast Brazil, by using several lines of evidence (LOEs). Chemical and sedimentological analyses, ecotoxicological tests, and whole-sediment Toxicity Identification Evaluation (TIE) were performed. The sediments were predominantly composed of fine sands and muds. Higher concentrations of metals in the sediments collected close to Iguape were observed; however according to the SEM/AVS analyses, most sediments should not be toxic and the potentially toxic samples could occur along the whole channel. In fact, sediments of most stations were toxic in at least one survey. The PCA revealed associations between mud, metals and toxicity. Acutely toxic sediments presented Pb concentrations above the threshold effect levels, while chronic toxicity seemed to be influenced also by SEM. The most contaminated and toxic areas are not necessarily those located close to the primary sources, but are actually those with finer sediments. Toxicity Identification and Evaluation (TIE) showed that metals and ammonia were responsible for the toxicity. The results suggest that metals from former mining areas located at the upper Ribeira de Iguape River are transported to the Cananéia Iguape Peruíbe Protected Area and accumulate in the sediments at potentially toxic levels. The location of muddy and more contaminated sediments appears to move along the estuary, accompanying the displacement of the maximum turbidity zone, which, in turn, depends on seasonal freshwater inputs. The results also showed that using several lines of evidences to asses contamination in a protected area provides reliable information to subsidise further actions to control the sources of contaminants.

Differential gene transcription across the life cycle in Daphnia magna using a new all genome custom-made microarray.

BACKGROUND: Unravelling the link between genes and environment across the life cycle is a challenging goal that requires model organisms with well-characterized life-cycles, ecological interactions in nature, tractability in the laboratory, and available genomic tools. Very few well-studied invertebrate model species meet these requirements, being the waterflea Daphnia magna one of them. Here we report a full genome transcription profiling of D. magna during its life-cycle. The study was performed using a new microarray platform designed from the complete set of gene models representing the whole transcribed genome of D. magna. RESULTS: Up to 93% of the existing 41,317 D. magna gene models showed differential transcription patterns across the developmental stages of D. magna, 59% of which were functionally annotated. Embryos showed the highest number of unique transcribed genes, mainly related to DNA, RNA, and ribosome biogenesis, likely related to cellular proliferation and morphogenesis of the several body organs. Adult females showed an enrichment of transcripts for genes involved in reproductive processes. These female-specific transcripts were essentially absent in males, whose transcriptome was enriched in specific genes of male sexual differentiation genes, like doublesex. CONCLUSION: Our results define major characteristics of transcriptional programs involved in the life-cycle, differentiate males and females, and show that large scale gene-transcription data collected in whole animals can be used to identify genes involved in specific biological and biochemical processes.

Chemometrics comparison of gas chromatography with mass spectrometry and comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry Daphnia magna metabolic profiles exposed to salinity.

The performances of gas chromatography with mass spectrometry and of comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry are examined through the comparison of Daphnia magna metabolic profiles. Gas chromatography with mass spectrometry and comprehensive two-dimensional gas chromatography with mass spectrometry were used to compare the concentration changes of metabolites under saline conditions. In this regard, a chemometric strategy based on wavelet compression and multivariate curve resolution-alternating least squares is used to compare the performances of gas chromatography with mass spectrometry and comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry for the untargeted metabolic profiling of Daphnia magna in control and salinity-exposed samples. Examination of the results confirmed the outperformance of comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry over gas chromatography with mass spectrometry for the detection of metabolites in D. magna samples. The peak areas of multivariate curve resolution-alternating least squares resolved elution profiles in every sample analyzed by comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry were arranged in a new data matrix that was then modeled by partial least squares discriminant analysis. The control and salt-exposed daphnids samples were discriminated and the most relevant metabolites were estimated using variable importance in projection and selectivity ratio values. Salinity de-regulated 18 metabolites from metabolic pathways involved in protein translation, transmembrane cell transport, carbon metabolism, secondary metabolism, glycolysis, and osmoregulation.

Implications on the Pb bioaccumulation and metallothionein levels due to dietary and waterborne exposures: The Callinectes danae case.

This study aimed to assess the bioaccumulation of Pb and induction of metallothionein-like proteins (MT) in Callinectes danae through single and combined dietary and waterborne exposures. Male C. danae individuals were collected in the south area of the Cananéia-Iguape-Peruíbe Protected Area (APA-CIP), in São Paulo State, Brazil. After an acclimatization period, exposure assays were performed during 7 and 14 days, at two Pb concentrations (0.5 e 2.0 µg/g) in 4 treatments: 1) control; 2) contaminated water only; 3) contaminated food only; 4) contaminated water and food. The results indicate that C. danae is highly tolerant to Pb exposure at the evaluated concentrations. In gills, Pb bioaccumulation is more dependent of water efflux and time of exposure (higher Pb values). However, pathways act simultaneously in the induction of MT expression in this tissue. The decreases in Pb accumulation in the combined treatments and MT increases after 14 days in gills suggests that these proteins play a detoxification function in the presence of Pb. In hepatopancreas, depending on the predominance of a certain pathway or combined pathways, accumulation occured at different times. For muscle tissue, bioaccumulation was observed due to contaminated water exposure, but not dietary exposure, probably because Pb concentrations were low.

Mental Fatigue Impairs Physical Performance in Young Swimmers.

PURPOSE: This study aimed to investigate the impact of mental fatigue on heart rate variability, subjective measures of fatigue, and swimming performance in young athletes. METHODS: Sixteen swimmers [15.45 (0.51) y old, 7.35 (2.20) y of swimming experience] performed a 1500-m time trial on 2 occasions separated by an interval of at least 72 hours. The 1500-m swimming was preceded by a 30-minute treatment that consisted of performing the Stroop Color and Word test to induce mental fatigue (experimental trial) or watching an emotionally neutral video (control trial). RESULTS: Participants reported higher ratings of mental fatigue and mental effort following the Stroop test when compared with the control trial, but no differences in motivation were observed. The induction of mental fatigue impaired swimming performance, as evidenced by a slower time (1.2%) to complete the 1500-m trial. No intertrial differences were identified for rating of perceived exertion during the swimming test or in heart rate variability after the Stroop and swimming tests. CONCLUSION: The results indicate that induction of mental fatigue impairs 1500-m swimming performance without changing heart rate variability.

Depressing Antidepressant: Fluoxetine Affects Serotonin Neurons Causing Adverse Reproductive Responses in Daphnia magna.

Selective serotonin reuptake inhibitors (SSRIs) are widely used antidepressants. As endocrine disruptive contaminants in the environment, SSRIs affect reproduction in aquatic organisms. In the water flea Daphnia magna, SSRIs increase offspring production in a food ration-dependent manner. At limiting food conditions, females exposed to SSRIs produce more but smaller offspring, which is a maladaptive life-history strategy. We asked whether increased serotonin levels in newly identified serotonin-neurons in the Daphnia brain mediate these effects. We provide strong evidence that exogenous SSRI fluoxetine selectively increases serotonin-immunoreactivity in identified brain neurons under limiting food conditions thereby leading to maladaptive offspring production. Fluoxetine increases serotonin-immunoreactivity at low food conditions to similar maximal levels as observed under high food conditions and concomitantly enhances offspring production. Sublethal amounts of the neurotoxin 5,7-dihydroxytryptamine known to specifically ablate serotonin-neurons markedly decrease serotonin-immunoreactivity and offspring production, strongly supporting the effect to be serotonin-specific by reversing the reproductive phenotype attained under fluoxetine. Thus, SSRIs impair serotonin-regulation of reproductive investment in a planktonic key organism causing inappropriately increased reproduction with potentially severe ecological impact.

Mechanisms of Action of Compounds That Enhance Storage Lipid Accumulation in Daphnia magna.

Accumulation of storage lipids in the crustacean Daphnia magna can be altered by a number of exogenous and endogenous compounds, like 20-hydroxyecdysone (natural ligand of the ecdysone receptor, EcR), methyl farnesoate, pyrirproxyfen (agonists of the methyl farnesoate receptor, MfR), and tributyltin (agonist of the retinoid X acid receptor, RXR). This effect, analogous to the obesogenic disruption in mammals, alters Daphnia's growth and reproductive investment. Here we propose that storage lipid accumulation in droplets is regulated in Daphnia by the interaction between the nuclear receptor heterodimer EcR:RXR and MfR. The model was tested by determining changes in storage lipid accumulation and on gene transcription in animals exposed to different effectors of RXR, EcR, and MfR signaling pathways, either individually or in combination. RXR, EcR, and MfR agonists increased storage lipid accumulation, whereas fenarimol and testosterone (reported inhibitors of ecdysteroid synthesis and an EcR antagonist, respectively) decreased it. Joint effects of mixtures with fenarimol, testosterone, and ecdysone were antagonistic, mixtures of juvenoids showed additive effects following a concentration addition model, and combinations of tributyltin with juvenoids resulted in greater than additive effects. Co-exposures of ecdysone with juvenoids resulted in deregulation of ecdysone- and farnesoid-regulated genes, accordingly with the observed changes in lipid accumulation These results indicate the requirement of ecdysone binding to the EcR:RXR:MfR complex to regulate lipid storage and that an excess of ecdysone disrupts the whole process, probably by triggering negative feedback mechanisms.

Distribution of tolypeutes illiger, 1811 (xenarthra: cingulata) with comments on its biogeography and conservation.

This study reviews the data available on the distribution of three-banded armadillos of the genus Tolypeutes, identifying potential geographic barriers and evaluating possible biogeographic processes that may account for the present-day distribution of the species and its conservation status. The database was derived from published records, interviews, and voucher specimens, over a timescale ranging from the fossil record to specimens collected in 2013. A total of 236 localities were recorded, with 68 attributed to Tolypeutes matacus and 168 to Tolypeutes tricinctus. The vegetation within the range of the genus is predominantly a xerophytic mosaic of grassland, savannas, open woodland, and xeric thorn forest. The marine transgressions of the Miocene and the uplifting of the Brazilian Shield may have contributed to the vicariant separation of the ancestral populations of T. matacus, to the west and south, and T. tricinctus, to the north and east. The three-banded armadillo is possibly one of the most threatened of Brazilian mammals, considering the low number of recent records and the fact that it is hunted intensively throughout its range.

Treatment with triterpenic fraction purified from Baccharis uncinella leaves inhibits Leishmania (Leishmania) amazonensis spreading and improves Th1 immune response in infected mice.

The current medications used to treat leishmaniasis have many side effects for patients; in addition, some cases of the disease are refractory to treatment. Therefore, the search for new leishmanicidal compounds is indispensable. Recently, it was demonstrated that oleanolic- and ursolic-containing fraction from Baccharis uncinella leaves eliminated the promastigote and amastigote forms of Leishmania (Leishmania) amazonensis and L. (Viannia) braziliensis without causing toxic effects for J774 macrophages. Thus, the aim of the present work was to characterize the therapeutic effect of the triterpenic fraction in L. (L.) amazonensis-infected BALB/c mice. Oleanolic- and ursolic acid-containing fraction was extracted from B. uncinella leaves using organic solvents and chromatographic procedures. L. (L.) amazonensis-infected BALB/c mice were treated intraperitoneally with triterpenic fraction during five consecutive days with 1.0 and 5.0 mg/kg of triterpenic fraction, or with 10.0 mg/kg of amphotericin B drug. Groups of mice treated with the triterpenic fraction, presented with decreased lesion size and low parasitism of the skin-both of which were associated with high amounts of interleukin-12 and interferon gamma. The curative effect of this fraction was similar to amphotericin B-treated mice; however, the final dose, required to eliminate amastigotes, was lesser than amphotericin B. Moreover, triterpenic fraction did not cause microscopic alterations in liver, spleen, heart, lung, and kidney of experimental groups. This work suggests that this fraction possesses compounds that are characterized by leishmanicidal and immunomodulatory activities. From this perspective, the triterpenic fraction can be explored as a new therapeutic agent for use against American Tegumentar Leishmaniasis.

Combination of computational new approach methodologies for enhancing evidence of biological pathway conservation across species.

The ability to predict which chemicals are of concern for environmental safety is dependent, in part, on the ability to extrapolate chemical effects across many species. This work investigated the complementary use of two computational new approach methodologies to support cross-species predictions of chemical susceptibility: the US Environmental Protection Agency Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS) tool and Unilever's recently developed Genes to Pathways - Species Conservation Analysis (G2P-SCAN) tool. These stand-alone tools rely on existing biological knowledge to help understand chemical susceptibility and biological pathway conservation across species. The utility and challenges of these combined computational approaches were demonstrated using case examples focused on chemical interactions with peroxisome proliferator activated receptor alpha (PPARα), estrogen receptor 1 (ESR1), and gamma-aminobutyric acid type A receptor subunit alpha (GABRA1). Overall, the biological pathway information enhanced the weight of evidence to support cross-species susceptibility predictions. Through comparisons of relevant molecular and functional data gleaned from adverse outcome pathways (AOPs) to mapped biological pathways, it was possible to gain a toxicological context for various chemical-protein interactions. The information gained through this computational approach could ultimately inform chemical safety assessments by enhancing cross-species predictions of chemical susceptibility. It could also help fulfill a core objective of the AOP framework by potentially expanding the biologically plausible taxonomic domain of applicability of relevant AOPs.