Copaifera spp. oleoresins and two isolated compounds (ent-kaurenoic and ent-polyalthic acid) inhibit Toxoplasma gondii growth in vitro.

Toxoplasmosis affects about one-third of the world's population. The disease treatment methods pose several side effects and do not efficiently eliminate the parasite, making the search for new therapeutic approaches necessary. We aimed to assess the anti-Toxoplasma gondii activity of four Copaifera oleoresins (ORs) and two isolated diterpene acids, named ent-kaurenoic and ent-polyalthic acid. We used HeLa cells as an experimental model of toxoplasmosis. Uninfected and infected HeLa cells were submitted to the treatments, and the parasite intracellular proliferation, cytokine levels and ROS production were measured. Also, tachyzoites were pre-treated and the parasite invasion was determined. Finally, an in silico analysis was performed to identify potential parasite targets. Our data show that the non-cytotoxic concentrations of ORs and diterpene acids controlled the invasion and proliferation of T. gondii in HeLa cells, thus highlighting the possible direct action on parasites. In addition, some compounds tested controlled parasite proliferation in an irreversible manner. An additional and non-exclusive mechanism of action involves the modulation of host cell components, by affecting the upregulation of the IL-6. Additionally, molecular docking suggested that ent-polyalthic acid has a high affinity for the active site of the TgCDPK1 protein. Copaifera ORs have great antiparasitic activity against T. gondii, and this effect can be partially explained by the presence of the isolated compounds ent-kaurenoic and ent-polyalthic acid.

Decoding the effects of drought stress on popcorn (Zea mays var. everta) flowering combining proteomics and physiological analysis.

Under conditions of soil water limitation and adequate irrigation, we conducted an investigation into the growth dynamics, gas exchange performance, and proteomic profiles of two inbred popcorn lines-L71, characterized as drought-tolerant, and L61, identified as drought-sensitive. Our goal was to uncover the mechanisms associated with tolerance to soil water limitation during the flowering. The plants were cultivated until grain filling in a substrate composed of perlite and peat within 150cm long lysimeter, subjected to two water conditions (WC): i) irrigated (WW) at lysimeter capacity (LC - 100%), and ii) water-stressed (WS). Under WS conditions, the plants gradually reached 45% of LC and were maintained at this level for 10 days. Irrespective of the WC, L71 exhibited the highest values of dry biomass in both shoot and root systems, signifying its status as the most robust genotype. The imposed water limitation led to early senescence, chlorophyll degradation, and increased anthocyanin levels, with a more pronounced impact observed in L61. Traits related to gas exchange manifested differences between the lines only under WS conditions. A total of 1838 proteins were identified, with 169 differentially accumulated proteins (DAPs) in the tolerant line and 386 DAPs in the sensitive line. Notably, differences in energy metabolism, photosynthesis, oxidative stress response, and protein synthesis pathways were identified as the key distinctions between L71 and L61. Consequently, our findings offer valuable insights into the alterations in proteomic profiles associated with the adaptation to soil water limitation in popcorn.

Rhinovirus infection and co-infection in children with severe acute respiratory infection during the COVID-19 pandemic period.

Rhinovirus causes respiratory tract infections in children and is found in co-infections. The objective of this research was to study the clinical profile of rhinovirus infection and co-infection in children with severe acute respiratory infection (SARI) during the COVID-19 pandemic period. We included 606 children ranging in age from 0.1 to 144 months of age from March 2020 to December 2021, hospitalized in the Pediatric Intensive Care Unit (PICU). The samples were collected by secretion from the nasopharynx region. A total of 259 children were tested positive for viral infection, 153 (59.07%) of them had a single rhinovirus infection and, 56 (36.6%) were aged between 60.1 and 144 months. Nine types of co-infections were identified and were found coinfection with three or more viruses (22/104, 21.15%). Observing the seasonality, the number of cases was similar between 2020 (49.53%) and 2021 (51.47%). Patients with a single infection (86.88%) and coinfection (67.30%) were more likely to have coughed. Patients with co-infection required the use of O2 for longer than those with a single rhinovirus infection. Hemogram results obtained from individuals with a single infection had higher levels of urea when compared to patients with co-infection with and other respiratory viruses. Multiple correspondence analyses indicated different clinical symptoms and comorbidities in patients with co-infection compared to those with single infection. The results found that the rhinovirus was much prevalent virus during the pandemic period and was found in co-infection with other virus types, what is important to diagnostic for the correct treatment of patients.

Discovery of new piperaquine hybrid analogs linked by triazolopyrimidine and pyrazolopyrimidine scaffolds with antiplasmodial and transmission blocking activities.

The World Health Organization (WHO) estimated that there were 247 million malaria cases in 2021 worldwide, representing an increase in 2 million cases compared to 2020. The urgent need for the development of new antimalarials is underscored by specific criteria, including the requirement of new modes of action that avoid cross-drug resistance, the ability to provide single-dose cures, and efficacy against both assexual and sexual blood stages. Motivated by the promising results obtained from our research group with [1,2,4]triazolo[1,5-a]pyrimidine and pyrazolo[1,5-a]pyrimidine derivatives, we selected these molecular scaffolds as the foundation for designing two new series of piperaquine analogs as potential antimalarial candidates. The initial series of hybrids was designed by substituting one quinolinic ring of piperaquine with the 1,2,4-triazolo[1,5-a]pyrimidine or pyrazolo[1,5-a]pyrimidine nucleus. To connect the heterocyclic systems, spacers with 3, 4, or 7 methylene carbons were introduced at the 4 position of the quinoline. In the second series, we used piperazine as a spacer to link the 1,2,4-triazolo[1,5-a]pyrimidine or pyrazolo[1,5-a]pyrimidine group to the quinoline core, effectively merging both pharmacophoric groups via a rigid spacer. Our research efforts yielded promising compounds characterized by low cytotoxicity and selectivity indices exceeding 1570. These compounds displayed potent in vitro inhibitory activity in the low nanomolar range against the erythrocytic form of the parasite, encompassing both susceptible and resistant strains. Notably, these compounds did not show cross-resistance with either chloroquine or established P. falciparum inhibitors. Even though they share a pyrazolo- or triazolo-pyrimidine core, enzymatic inhibition assays revealed that these compounds had minimal inhibitory effects on PfDHODH, indicating a distinct mode of action unrelated to targeting this enzyme. We further assessed the compounds' potential to interfere with gametocyte and ookinete infectivity using mature P. falciparum gametocytes cultured in vitro. Four compounds demonstrated significant gametocyte inhibition ranging from 58 % to 86 %, suggesting potential transmission blocking activity. Finally, we evaluated the druggability of these new compounds using in silico methods, and the results indicated that these analogs had favorable physicochemical and ADME (absorption, distribution, metabolism, and excretion) properties. In summary, our research has successfully identified and characterized new piperaquine analogs based on [1,2,4]triazolo[1,5-a]pyrimidine and pyrazolo[1,5-a]pyrimidine scaffolds and has demonstrated their potential as promising candidates for the development of antimalarial drugs with distinct mechanisms of action, considerable selectivity, and P. falciparum transmission blocking activity.

Novel ERLIN2 variant expands the phenotype of Spastic Paraplegia 18.

BACKGROUND: The Brazilian Northeast region is notable for its high prevalence of consanguineous marriages and isolated populations, which has led to a significant prevalence of rare genetic disorders. This study describes the clinical presentation of four affected individuals from the same family, comprising two siblings and their cousins, with ages ranging from 11 to 20 years. METHODS: In a small and isolated community in Northeastern Brazil, affected individuals initially underwent a clinical assessment. Subsequently, written consent was obtained from their legal guardians, and an extensive clinical evaluation was conducted at a medical genetics center. Family data provided the basis for constructing the pedigree, and biological samples (blood or oral swabs) were collected from both affected and unaffected family members. Following informed consent from one patient, Whole Exome Sequencing (WES) was carried out, encompassing exome sequencing, assembly, genotyping, and annotation. A potentially deleterious variant was then singled out for further segregation analysis through Sanger Sequencing, involving both the proband and select family members. RESULTS AND CONCLUSION: These individuals exhibit severe neurodevelopmental delays, encompassing symptoms such as spastic paraplegia, neuropathy, intellectual impairments, and language challenges. Through next-generation sequencing (NGS) techniques, a previously unreported homozygous variant within the ERLIN2 gene linked to spastic paraplegia 18 (SPG18) was identified across all four patients. Also, all patients displayed childhood cataract, expanding the known clinical spectrum of SPG18.

Antileishmanial effects of γCdcPLI, a phospholipase A2 inhibitor from Crotalus durissus collilineatus snake serum, on Leishmania (Leishmania) amazonensis.

BACKGROUND: Leishmaniasis, a neglected disease caused by the parasite Leishmania, is treated with drugs associated with high toxicity and limited efficacy, in addition to constant reports of the emergence of resistant parasites. In this context, snake serums emerge as good candidates since they are natural sources with the potential to yield novel drugs. OBJECTIVES: We aimed to show the antileishmanial effects of γCdcPLI, a phospholipase A2 inhibitor from Crotalus durissus collilineatus snake serum, against Leishmania (Leishmania) amazonensis. METHODS: Promastigotes forms were exposed to γCdcPLI, and we assessed the parasite viability and cell cycle, as well as invasion and proliferation assays. FINDINGS: Despite the low cytotoxicity effect on macrophages, our data indicate that γCdcPLI has a direct effect on parasites promoting an arrest in the G1 phase and reduction in the G2/M phase at the highest dose tested. Moreover, this PLA2 inhibitor reduced the parasite infectivity when promastigotes were pre-treated. Also, we demonstrated that the γCdcPLI treatment modulated the host cell environment impairing early and late steps of the parasitism. MAIN CONCLUSIONS: γCdcPLI is an interesting tool for the discovery of new essential targets on the parasite, as well as an alternative compound to improve the effectiveness of the leishmaniasis treatment.

Trypanosoma cruzi P21 recombinant protein modulates Toxoplasma gondii infection in different experimental models of the human maternal-fetal interface.

Introduction: Toxoplasma gondii is the etiologic agent of toxoplasmosis, a disease that affects about one-third of the human population. Most infected individuals are asymptomatic, but severe cases can occur such as in congenital transmission, which can be aggravated in individuals infected with other pathogens, such as HIV-positive pregnant women. However, it is unknown whether infection by other pathogens, such as Trypanosoma cruzi, the etiologic agent of Chagas disease, as well as one of its proteins, P21, could aggravate T. gondii infection. Methods: In this sense, we aimed to investigate the impact of T. cruzi and recombinant P21 (rP21) on T. gondii infection in BeWo cells and human placental explants. Results: Our results showed that T. cruzi infection, as well as rP21, increases invasion and decreases intracellular proliferation of T. gondii in BeWo cells. The increase in invasion promoted by rP21 is dependent on its binding to CXCR4 and the actin cytoskeleton polymerization, while the decrease in proliferation is due to an arrest in the S/M phase in the parasite cell cycle, as well as interleukin (IL)-6 upregulation and IL-8 downmodulation. On the other hand, in human placental villi, rP21 can either increase or decrease T. gondii proliferation, whereas T. cruzi infection increases T. gondii proliferation. This increase can be explained by the induction of an anti-inflammatory environment through an increase in IL-4 and a decrease in IL-6, IL-8, macrophage migration inhibitory factor (MIF), and tumor necrosis factor (TNF)-α production. Discussion: In conclusion, in situations of coinfection, the presence of T. cruzi may favor the congenital transmission of T. gondii, highlighting the importance of neonatal screening for both diseases, as well as the importance of studies with P21 as a future therapeutic target for the treatment of Chagas disease, since it can also favor T. gondii infection.

Rottlerin impairs early and late steps of Toxoplasma gondii infection in human trophoblast cells and villous explants.

Congenital toxoplasmosis, caused by the opportunistic protozoan parasite T. gondii, can cause stillbirths, miscarriages and fetal abnormalities, as well as encephalitis and chorioretinitis in newborns. Available treatment options rely on antiparasitic drugs that have been linked to serious side effects, high toxicity and the development of drug-resistant parasites. The search for alternative therapeutics to treat this disease without acute toxicity for the mother and child is essential for the advancement of current therapeutic procedures. The present study aimed to unravel the mode of the anti-T. gondii action of Rottlerin, a natural polyphenol with multiple pharmacological properties described. Herein, we further assessed the antiparasitic activity of Rottlerin against T. gondii infection on the human trophoblastic cells (BeWo cells) and, for the first time, on human villous explants. We found that non-cytotoxic doses of Rottlerin impaired early and late steps of parasite infection with an irreversible manner in BeWo cells. Rottlerin caused parasite cell cycle arrest in G1 phase and compromised the ability of tachyzoites to infect new cells, thus highlighting the possible direct action on parasites. An additional and non-exclusive mechanism of action of Rottlerin involves the modulation of host cell components, by affecting lipid droplet formation, mitochondrial function and upregulation of the IL-6 and MIF levels in BeWo cells. Supporting our findings, Rottlerin also controlled T. gondii proliferation in villous explants with low toxicity and reduced the IL-10 levels, a cytokine associated with parasite susceptibility. Collectively, our results highlighted the potential use of Rottlerin as a promising tool to prevent and/or treat congenital toxoplasmosis.

The dangerous link between coal dust exposure and DNA damage: unraveling the role of some of the chemical agents and oxidative stress.

Exposure to coal mining dust poses a substantial health hazard to individuals due to the complex mixture of components released during the extraction process. This study aimed to assess the oxidative potential of residual coal mining dust on human lymphocyte DNA and telomeres and to perform a chemical characterization of coal dust and urine samples. The study included 150 individuals exposed to coal dust for over ten years, along with 120 control individuals. The results revealed significantly higher levels of DNA damage in the exposed group, as indicated by the standard comet assay, and oxidative damage, as determined by the FPG-modified comet assay. Moreover, the exposed individuals exhibited significantly shorter telomeres compared to the control group, and a significant correlation was found between telomere length and oxidative DNA damage. Using the PIXE method on urine samples, significantly higher concentrations of sodium (Na), phosphorus (P), sulfur (S), chlorine (Cl), potassium (K), iron (Fe), zinc (Zn), and bromine (Br) were observed in the exposed group compared to the control group. Furthermore, men showed shorter telomeres, greater DNA damage, and higher concentrations of nickel (Ni), calcium (Ca), and chromium (Cr) compared to exposed women. Additionally, the study characterized the particles released into the environment through GC-MS analysis, identifying several compounds, including polycyclic aromatic hydrocarbons (PAHs) such as fluoranthene, naphthalene, anthracene, 7H-benzo[c]fluorene, phenanthrene, pyrene, benz[a]anthracene, chrysene, and some alkyl derivatives. These findings underscore the significant health risks associated with exposure to coal mining dust, emphasizing the importance of further research and the implementation of regulatory measures to safeguard the health of individuals in affected populations.

Simultaneous recycling of waste solar panels and treatment of persistent organic compounds via supercritical water technology.

The study addresses the application of the supercritical water technology in the simultaneous recycling of obsolete solar panels and treatment of persistent organic compounds. The obsolete solar panels samples were characterized by TEM-EDS, SEM, TG-DTA, XRD, WDXRF, MP-AES and elemental analysis. Initially, the optimized parameters for the degradation of solid organic polymers present in residual solar panels via oxidation in supercritical water were defined by an experimental design. Under optimized conditions, 550 °C, reaction time of 60 min, volumetric flow rate of 10 mL min-1 and hydrogen peroxide as oxidant agent, real laboratory liquid wastewater was used as feed solution to achieve 99.6% of polymers degradation. After the reaction, the solid product free of organic matter was recovered and characterized. On average, a metal recovery efficiency of 76% was observed. Metals such as aluminum, magnesium, copper, and silver, that make up most of the metallic fraction, were identified. Only H2, N2 and CO2 were observed in the gaseous fraction. Then, initial data on the treatment of the liquid decomposition by-products, generated during ScW processing, were reported. A total organic carbon reduction of 99.9% was achieved after the subsequential treatment via supercritical water oxidation using the same experimental apparatus. Finally, insights on the scale-up, energy integration and implementation costs of a ScW solid processing industrial unit were presented using the Aspen Plus V9 software.

Valorization of e-waste via supercritical water technology: An approach for obsolete mobile phones.

The improper handling of electronic waste has not only severe environmental impacts but also results in the loss of high economic potential. To address this issue, the use of supercritical water (ScW) technology for the eco-friendly processing of waste printed circuit boards (WPCBs) obtained from obsolete mobile phones has been explored in this study. The WPCBs were characterized via MP-AES, WDXRF, TG/DTA, CHNS elemental analysis, SEM and XRD. A L9 Taguchi orthogonal array design was employed to evaluate the impact of four independent variables on the organic degradation rate (ODR) of the system. After optimization, an ODR of 98.4% was achieved at a temperature of 600 °C, a reaction time of 50 min, a flowrate of 7 mL min-1, and the absence of an oxidizing agent. The removal of the organic content from the WPCBs resulted in an increase in the metal concentration, with up to 92.6% of the metal content being efficiently recovered. During the ScW process, the decomposition by-products were continuously removed from the reactor system through the liquid or gaseous outputs. The liquid fraction, which was composed of phenol derivatives, was treated using the same experimental apparatus, achieving a total organic carbon reduction of 99.2% at 600 °C using H2O2 as the oxidizing agent. The gaseous fraction was found to contain hydrogen, methane, CO2, and CO as the major components. Finally, the addition of co-solvents, namely ethanol and glycerol, enhanced the production of combustible gases during the ScW processing of WPCBs.

Polyalthic acid and oleoresin from Copaifera trapezifolia Hayne reduce Toxoplasma gondii growth in human villous explants, even triggering an anti-inflammatory profile.

Due to the lack of efficient antiparasitic therapy and vaccines, as well as emerging resistance strains, congenital toxoplasmosis is still a public health issue worldwide. The present study aimed to assess the effects of an oleoresin obtained from the species Copaifera trapezifolia Hayne (CTO), and an isolated molecule found in the CTO, ent-polyalthic acid (ent-15,16-epoxy-8(17),13(16),14-labdatrien-19-oic acid) (named as PA), against T. gondii infection. We used human villous explants as an experimental model of human maternal-fetal interface. Uninfected and infected villous explants were exposed to the treatments; the parasite intracellular proliferation and the cytokine levels were measured. Also, T. gondii tachyzoites were pre-treated and the parasite proliferation was determined. Our findings showed that CTO and PA reduced efficiently the parasite growth with an irreversible action, but without causing toxicity to the villi. Also, treatments reduced the levels of IL-6, IL-8, MIF and TNF by villi, what configures a valuable treatment option for the maintenance of a pregnancy in an infectious context. In addition to a possible direct effect on parasites, our data suggest an alternative mechanism by which CTO and PA alter the villous explants environment and then impair parasite growth, since the pre-treatment of villi resulted in lower parasitic infection. Here, we highlighted PA as an interesting tool for the design of new anti-T. gondii compounds.

BjussuLAAO-II, an l-amino acid oxidase from Bothrops jararacussu snake venom, impairs Toxoplasma gondii infection in human trophoblast cells and villous explants from the third trimester of pregnancy.

One-third of the world's population is estimated to be affected by toxoplasmosis. Pregnancy-related Toxoplasma gondii infection can cause vertical transmission, infect the fetus, and cause miscarriage, stillbirth, and fetal death. The current study showed that both human trophoblast cells (BeWo lineage) and human explant villous were resistant to T. gondii infection after incubation with BjussuLAAO-II, an l-amino acid oxidase isolated from Bothrops jararacussu. Almost 90% of the parasite's ability to proliferate in BeWo cells was decreased by the toxin at 1.56 µg/mL and showed an irreversible anti-T. gondii effect. Also, BjussuLAAO-II impaired the key events of adhesion and invasion of T. gondii tachyzoites in BeWo cells. BjussuLAAO-II antiparasitic properties were associated with the intracellular production of reactive oxygen species and hydrogen peroxide, since the presence of catalase restored the parasite's growth and invasion. In addition, T. gondii growth in human villous explants was decreased to approximately 51% by the toxin treatment at 12.5 µg/mL. Furthermore, BjussuLAAO-II treatment altered IL-6, IL-8, IL-10 and MIF cytokines levels, assuming a pro-inflammatory profile in the control of T. gondii infection. This study contributes to the potential use of a snake venom l-amino acid oxidase for the development of agents against congenital toxoplasmosis and the discovery of new targets in parasites and host cells.

Leaf hydroalcoholic extract and oleoresin from Copaifera multijuga control Toxoplasma gondii infection in human trophoblast cells and placental explants from third-trimester pregnancy.

The conventional treatment of congenital toxoplasmosis is mainly based on the combination of sulfadiazine and pyrimethamine. However, therapy with these drugs is associated with severe side effects and resistance, requiring the study of new therapeutic strategies. There are currently many studies with natural products, including Copaifera oleoresin, showing actions against some pathogens, as Trypanosoma cruzi and Leishmania. In the present study, we investigated the effects of the leaf hydroalcoholic extract and oleoresin from Copaifera multijuga against Toxoplasma gondii in human villous (BeWo) and extravillous (HTR8/SVneo) trophoblast cells, as well as in human villous explants from third-trimester pregnancy. For this purpose, both cells and villous explants were infected or not with T. gondii, treated with hydroalcoholic extract or oleoresin from C. multijuga and analyzed for toxicity, parasite proliferation, cytokine and ROS production. In parallel, both cells were infected by tachyzoites pretreated with hydroalcoholic extract or oleoresin, and adhesion, invasion and replication of the parasite were observed. Our results showed that the extract and oleoresin did not trigger toxicity in small concentrations and were able to reduce the T. gondii intracellular proliferation in cells previously infected. Also, the hydroalcoholic extract and oleoresin demonstrated an irreversible antiparasitic action in BeWo and HTR8/SVneo cells. Next, adhesion, invasion and replication of T. gondii were dampened when BeWo or HTR8/SVneo cells were infected with pretreated tachyzoites. Finally, infected and treated BeWo cells upregulated IL-6 and downmodulated IL-8, while HTR8/SVneo cells did not change significantly these cytokines when infected and treated. Finally, both the extract and oleoresin reduced the T. gondii proliferation in human explants, and no significant changes were observed in relation to cytokine production. Thus, compounds from C. multijuga presented different antiparasitic activities that were dependent on the experimental model, being the direct action on tachyzoites a common mechanism operating in both cells and villi. Considering all these parameters, the hydroalcoholic extract and oleoresin from C. multijuga can be a target for the establishment of new therapeutic strategy for congenital toxoplasmosis.

Pectin-like polysaccharide extracted from leaves Crataeva tapia promotes antioxidant, immunomodulatory and emulsifiers applied in therapeutic formulations.

The objective of this work was to isolate a polysaccharide similar to pectin from Crataeva tapia leaves, not yet reported in the literature, and to evaluate its antioxidant, cytotoxic and immunomodulatory profile. Pectin was extracted from the leaves in three stages, organic solvent followed by acidified water and ethanol precipitation. With the pectin obtained, the physicochemical characterization of the molecule was carried out using high-performance liquid chromatography, Fourier-transform infrared spectroscopy, nuclear magnetic resonance (13C and 1H) and different thermal and elemental analysis. Furthermore, the antioxidant activities were evaluated in vitro, and using human peripheral blood mononuclear cell culture, cytotoxicity and immunostimulatory actions were investigated. Physical and chemical analyses showed characteristic signs of pectin. Antioxidant activity tests showed that pectin had moderate to low antioxidant activity. Furthermore, pectin did not affect the viability of erythrocytes and PBMC and induced an immunostimulatory state when it promoted the production of cytokines IL-6, IL-10 and TNF-α and increased the activation of CD8 + T lymphocytes. This study showed that pectin from Crataeva tapia is not cytotoxic and promoted a pro-inflammatory profile in peripheral blood mononuclear cell with application as an immunostimulating and emulsifying compound.

Adiponectin levels in captive Owl Monkeys (Aotus sp.).

The mean serum value of adiponectin in captive Aotus sp. is 541.99 ng/mL ± 73.05. There is no influence of sex or age, but there is a moderate positive correlation between body weight and adiponectin levels in males.

Dry tobacco leaves: an in vivo and in silico approach to the consequences of occupational exposure.

Exposure of tobacco workers handling dried tobacco leaves has been linked to an increased risk of toxicity and respiratory illness due to the presence of nicotine and other chemicals. This study aimed to evaluate the DNA damage caused by the exposure of tobacco growers during the dry leaf classification process and the relation to cellular mechanisms. A total of 86 individuals participated in the study, divided into a group exposed to dry tobacco (n = 44) and a control group (n = 42). Genotoxicity was evaluated using the alkaline comet assay and lymphocyte micronucleus (MN) assay (CBMN-Cyt), and measurement of telomere length. The levels of oxidative and nitrosative stress were evaluated through the formation of thiobarbituric acid reactive species, and nitric oxide levels, respectively. The inorganic elements were measured in the samples using particle-induced X-ray emission method. The combination of variables was demonstrated through principal component analysis and the interactions were expanded through systems biology. Comet assay, MN, death cells, thiobarbituric acid reactive species, and nitrosative stress showed a significant increase for all exposed groups in relation to the control. Telomere length showed a significant decrease for exposed women and total exposed group in relation to men and control groups, respectively. Bromine (Br) and rubidium (Rb) in the exposed group presented higher levels than control groups. Correlations between nitrate and apoptosis; Br and MN and necrosis; and Rb and telomeres; besides age and DNA damage and death cells were observed. The systems biology analysis demonstrated that tobacco elements can increase the nuclear translocation of NFKB dimers inducing HDAC2 expression, which, associated with BRCA1 protein, can potentially repress transcription of genes that promote DNA repair. Dry tobacco workers exposed to dry leaves and their different agents showed DNA damage by different mechanisms, including redox imbalance.

Correlating Coffea canephora 3D architecture to plant photosynthesis at a daily scale and vegetative biomass allocation.

Coffea canephora (C. canephora) has two botanical varieties, Robusta and Conilon. Intraspecific variability was hypothesized and projected for the selection of C. canephora plants able to maintain production in the context of global climate changes. For that, architectural, C-assimilation and biomass analyses were performed on 17-month-old Robusta (clones 'A1' and '3 V') and Conilon (clones '14' and '19') varieties grown in non-limiting soil, water and mineral nutrient conditions. Nondestructive coffee plant architecture coding, reconstruction and plant photosynthesis estimations were performed using a functional-structural plant modeling platform OpenAlea. 3D reconstructions and inclusion of parameters calculated and estimated from light response curves, such as dark respiration (Rd), maximum rate of carboxylation of RuBisCO and photosynthetic electron transport allowed the estimation of instantaneous and daily plant photosynthesis. The virtual orchard leaf area index was low, and light was not a limiting factor in early C. canephora development stages. Under such conditions, Robusta assimilated more CO2 at the plant and orchard scale and produced higher total biomass than Conilon. Lower plant daily photosynthesis and total biomass were correlated to higher Rd in Conilon than in Robusta. Among the architectural traits, leaf inclination, size and allometry were most highly correlated with plant assimilation and biomass. Relative allocation in leaf biomass was higher in '19' Conilon than in young Robusta plants, indicating intraspecific biomass partitioning. Similarly, variation in relative distribution of the root biomass and the root volume reflected clonal variation in soil occupation, indicating intraspecific variability in space occupation competitiveness. Coffea canephora denoted high root allocation in both Conilon and Robusta clones. However, relevant differences at subspecific levels were found, indicating the high potential of C. canephora to cope with drought events, which are expected to occur more frequently in the future, because of climate changes. The methodology developed here has the potential to be used for other crops and tree species. Highlights Functional-structural plant model was used to estimate photosynthesis on a plant and daily scales in Coffea canephora (C. canephora). Among the architectural traits, leaf shape and inclination had the most impact on photosynthesis and biomass. Under non-limiting conditions, Robusta had higher plant photosynthesis and biomass than Conilon. A higher leaf biomass allocation in Conilon clone '19' than in Robusta suggested variety-specific partitioning. Variation in the relative distribution of the root biomass indicated C. canephora intraspecific soil occupation variability.

Asymmetric dimethyl arginine in captive owl monkeys (Aotus sp).

Only four of 40 animals had measurable asymmetric dimethyl arginine (ADMA) levels. The young primate had the lowest value (53.4 ng/ml) when compared with the two adults (218.8 ± 9.3 ng/ml) and the elderly one (320.5 ng/ml). The ADMA levels in this study may relate to the echocardiographic abnormalities found, and possible hypertensive individuals.