Abstract Risk assessment of chemicals needs reliable scientific information and one source of information is the characterization of the metabolic fate and toxicokinetics of a chemical. Metabolism is often the most important factor contributing to toxicokinetics. Cytochrome P450 (CYP) enzymes are a superfamily of microsomal proteins playing a pivotal role in xenobiotic metabolism. In the present study, pesticides were used as representative xenobiotics since exposure to pesticides is a global challenge to risk assessment. Human and animal in vitro hepatic models were applied with the advantage of novel analytical techniques (LC/TOF-MS and LC/MS-MS) to elucidate the in vitro metabolism and interaction of selected pesticides. The results of these studies demonstrate that CYP enzymes catalyze the bioactivation of profenofos, diuron and carbosulfan into their more toxic metabolites desthiopropylprofenofos, N-demethyldiuron and carbofuran, respectively. The suspected carcinogenic metabolite of metalaxyl, 2,6-dimethylaniline, was not detected. CYP3A4 and CYP2C19 activities may be important in determining the toxicity arising from exposure to profenofos and carbosulfan. Individuals with high CYP1A2 and CYP2C19 activities might be more susceptible to diuron toxicity. Qualitative results of in vitro metabolism were generally in agreement with the results obtained from the published in vivo data, at least for the active chemical moiety and major metabolites. Considerable differences in the quantities of the metabolites produced within the species, as well as in the ratios of the metabolites among the species, were observed. These findings illustrate that in vitro screening of qualitative and quantitative differences are needed to provide a firm basis for interspecies and in vitro-in vivo extrapolations. Based on our findings, in vitro-in vivo extrapolation based on the elucidation of the in vitro metabolic pattern of pesticides in human and animal hepatic models could be a good model for understanding and extending the results of pesticides metabolism studies to human health risk assessment.

Master of Science / Department of Geology / Matthew Kirk / A growing body of evidence demonstrates that methanogenesis and Fe(III) reduction can occur simultaneously. However, environmental controls on interactions between each are poorly understood. In this study we considered pH as a control on interactions between Fe(III) reduction and methanogenesis in anoxic sediment bioreactors. The reactors consisted of 100mL of synthetic aqueous media, and 1 g of marsh sediment amended with goethite (1mmol). One set of reactors received acidic media (pH 6), and the other alkaline media (pH 7.5). Each set received media containing acetate (0.25 mM) to serve as an electron donor. Control reactors, deficient in acetate, were also included. We maintained a fluid residence time of 35 days by sampling and feeding the reactors every seven days. For pH 6.0 and pH 7.5 reactors, the measured pH of effluent samples averaged 6.33 and 7.37, respectively. The extent of Fe(III) reduction and methanogenesis varied considerably between each set of reactors. More Fe(III) was reduced in the pH 6 reactors (646.39 μmoles on avg.) than the pH 7.5 reactors (31.32 μmoles on avg.). Conversely, more methane formed in pH 7.5 reactors (127.5 μmoles on avg.) than the pH 6 reactors (78.9 μmoles on avg.). Alkalinity concentrations during the middle and end of the experiment averaged 9.6 meq/L and 5.2 meq/L in pH 6 and pH7.5 reactors, respectively Although much less Fe(III) reduction occurred in pH 7.5 reactors, the relative abundance of Fe(III) reducers in them decreased little from levels observed in the pH 6 reactors. Sequences classified within Geobacter, a genus of bacteria known primarily as dissimilatory metal reducers, accounted for 22% and 13.45% of the sequences in the pH 6 and pH 7.5 reactors and only 0.8% of the sequences in the marsh sediment inoculum. In contrast, sequences classified within orders of methanogens were low in abundance, making up only 0.47% and 1.04% of the sequences in the pH 6 and pH 7.5 reactors, respectively. Mass balance calculations demonstrate that the amount of electron donor consumed by each group varied considerably between the sets of reactors. Expressed as a quantity of acetate, the reactions consumed about 160μM of electron donor each in pH 6 reactors. In contrast, methanogenesis consumed over 30 times more electron donor than Fe(III) reduction in the pH 7.5 reactors. Thus, the results of our experiment indicate that the decrease in electron donor consumption by Fe(III) reduction at basic pH was nearly matched by the increase in electron donor consumption by methanogens. Results of geochemical modeling calculations indicate that more energy was available for Fe(III) reduction in the pH 6.0 reactors than the pH 7.5 reactors, matching variation in Fe(III) reduction rates, and that the density of sorbed ferrous iron was higher in pH 6 reactors than pH 7.5 reactors. Thus, the calculation results are consistent with bioenergetics, but not variation in ferrous iron sorption, as a potential mechanism driving variation in the balance between each reaction with pH.

An outgroup can be defined as that which is perceived as different or dissimilar from oneself. The Interspecies Model of Prejudice (TIMP) predicts that negativity to human outgroups align with animal negativity. Human-centered and anti-egalitarian beliefs have shown to correlate with outgroup rejection. Experiencing a close relationship to nature has, on the other hand, been linked to outgroup acceptance. The aim of this study was to investigate the valuation of animal charismatic appeal overall, and as a function of outgroup acceptance - rejection. An online survey collected data on animal image ratings, attitude instruments, psychosocial and demographic factors from 231 high school senior students in the greater Stockholm area. Images of human-similar (anthropomorphic highcharismaticmammals) versus human-dissimilar (feral low-charismatic insects) animals were used to, respectively, predict the attitudes anthropocentrism, ethnocentrism and nature relatedness. Overall, mammals were rated significantly more positively than insects. The findings also suggest support for TIMP. It may be inferred that animal charismatic appeal is linked to individual differences in outgroup cognitions. Anthropocentrism and ethnocentrism associated negatively with general animal liking, and were predicted by insect negativity once significant covariates adjusted the models. Nature relatedness correlated positively with animal liking and was predicted by insect positivity. Our valuation of animal charisma may, thus, be linked to our appraisal of their more or less human-like qualities. Our valuations are proposed as underlied by identification mechanismsthat may guide our varying tendencies to divide the world into ‘us and them’. The findings could be informative of psychological factors involved in intergroup behaviors and environmental concerns.

In recent twenty years dogs have become model subjects of comparing studies. These experiments show us that specific cognitive skills have developed during their domestication as an adaptation to anthropomorphic environment. For example dogs can follow human gaze and understand gestures. An important topic of today researches are linguistic skills of dogs. Knowledge from this area would help to discover more from evolution processes which formed human language. Last studies have proven dogs can distinguish a new object by a fast mapping. But when distinguishing two new objects, dogs had problems. That is why I decided to verify if dogs are able to remember two new words and match them with correct objects during one session. For this experiment I worked on a new methodical procedure and used three border collies dogs. The results showed that after some training dogs were able to correctly distinguish two new words in case the experimentalist stood in front of them and they used multisenzorial perception. In case they had only one communication source (visual or acoustic), they made more mistakes. The results show that functional reactions of dogs to human vocalization are getting better if they can use visual and acoustic source in one time during an interspecies communication. Key words: dog,...

Dogs and humans have through domestication and co-evolution established a close relationship and can communicate and understand each other. The objective of the present study was to deepen the understanding of the communication between dogs and humans, with focus on the vocalized communication. The study was based on video and audio recordings of dog-human communications from a total of 36 dogs in their home environment. The mean gap size in the communication ranged from 0.651.16 seconds and the overlap in communication had a percentage range of 14-50 %. These results are within the frame of other species communication with turn-taking. With these considerations, it clearly indicates that turn-taking occurs in interspecies communication between dogs and humans. The present study suggests that dogs intentionally communicate through vocalisation with their owners to gain the attention of the owner. In addition, age and sex of the dog influence their communication with their owners.

We evaluated the genetic diversity of Penstemon's Centromeric Histone 3 (CENH3), which localizes to chromosome centromeres in eukaryotes. From RNA extractions of 56 species, we successfully amplified two CENH3s (termed CENH3a and CENH3b), which share approximately 69% sequence homology across the length of the gene and about 85% across the histone fold domain (HFD). CENH3a is generally 72 bp longer than CENH3b and contains seven exons while CENH3b is made of five. Unlike studies of CENH3 in other plants, Penstemon's CENH3 N-tail was found to be highly conserved, indicative that the genus has undergone a short evolutionary history. Surprisingly, of the 99 CENH3 sequences obtained during this study, 32 appeared to be mis-spliced and contained premature stop codons. Of those aberrant transcripts, 84.4% originated from CENH3b genomic DNA. Most mis-spliced transcripts resulted from the retention of all or part of an intron. In some cases, all or portions of an exon were missing, including one that was missing the L1 motif. Second, we systematically cataloged interspecific breeding data in Penstemon, on which we then conducted a network analysis. The resulting network provides breeders with a better visualization of successful parental combinations and also identifies gaps in interspecific breeding. This method allowed for the identification of species with a high degree of interspecific compatibility, which we compared to the CENH3 sequencing data. Finally, we studied the performance of soil streaming in high tunnel production of tomatoes (Solanum lycopersicum L.). Our experiments revealed that soil steaming and mulch reduced weed coverage of Palmer amaranth (Amaranthus palmeri S. Watson), large crabgrass (Digitaria sanguinalis L.), and yellow nutsedge (Cyperus esculentus L.). Steam and mulch increased the tomato plant size, fruit size, fruit number, and fruit yield. Additionally, soil steaming reduced tomato southern blight, caused by Sclerotium rolfsii, by 5.8-fold. These findings provide promising results for high tunnel tomato producers, particularly those involved in organic production where pesticide and fumigation use is limited.

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This research developed validated QSPKR and PK-AS models for predicting human systemic PK properties of three, preselected, pharmacological classes of drugs, namely opioids, β-adrenergic receptor ligands (β-ARL) and β-lactam antibiotics (β-LAs) using pertinent human and animal systemic PK properties (fu,, CLtot, Vdss, fe) and their biologically relevant unbound counterparts from the published literature, followed by an assessment of the effect of different molecular descriptors on these PK properties and on the PK-AS slopes for CLtot and Vdss from two species (rat and dog). Lipophilicity (log (D)7.4) and molecular weight (MW) were found to be the most statistically significant and biologically plausible, molecular properties affecting the biologically relevant, systemic PK properties: For compounds with log (D)7.4 > -2.0 and MW < 350 D (e.g., most opioids and β-ARL), increased log (D)7.4 resulted in decreased fu and increased Vdssu, CLtotu and CLnonrenu, indicating the prevalence of hydrophobic interactions with biological membrane/proteins. As result, the final QSPKR models using log (D)7.4 provided acceptable predictions for fu, Vdssu, CLtotu and CLnonrenu. CLnonrenu and CLtotu. For both the datasets, inclusion of drugs undergoing extrahepatic clearance worsened the QSPKR predictions. For compounds with log (D)7.4 < -2.0 and MW > 350 D (e.g., β-LA), increased MW (leading to more hydrogen bond donors/acceptors) resulted in a decrease in fu, likely indicating hydrogen bonding interactions with plasma proteins. In general, it was more difficult to predict PK parameters for β-LAs, as their Vdssu approached plasma volume and CLrenu and CLnonrenu were low - as a result of their high hydrophilicity and large MW, requiring specific drug transporters for distribution and excretion. The PK-AS analysis showed that animal body size accounted for most of the observed variability (r2> 0.80) in systemic PK variables, with single species methods, particularly those using dog, gave the best predictions. The fu correction of PK variables improved goodness of fit and predictability of human PK. There were no apparent effects of molecular properties on the predictions. CLren, CLrenu, CLnonren, and CLnonrenu were the most difficult variables to predict, possibly due to the associated interspecies differences in the metabolism, renal and hepatobiliary drug transporters.

Les spumavirus (SV) sont des rétrovirus exogènes de la sous-famille des Spumavirinae appartenant à la famille des Retroviridae. L’infection naturelle chez les primates non humains (PNH) est décrite dans la nature et en captivité, avec 75 à 100% de singes adultes infectés. Chez les PNH, la transmission des SV se fait à travers des morsures très graves. Par ailleurs, ces virus ont été isolés chez des travailleurs de zoo, exposés aux animaux infectés dans le cadre de leur travail. Récemment, des études ont aussi montré l’infection dans le milieu naturel chez des chasseurs au Cameroun. Cependant, aucune pathologie n’a jamais pu être associée à l’infection par ces virus. Au Gabon, les infections par des SV n’ont été que très peu étudiées. Les objectifs de cette thèse sont donc :1) D’évaluer au Gabon, la prévalence des SV dans la colonie de Mandrills en captivité au centre de primatologie (CDP) du CIRMF, ainsi que dans la nature chez un grand nombre d’espèces de primates non humains ;2) De caractériser sur le plan moléculaire les souches SV circulant au Gabon ;3) D’identifier chez des personnes mordues par un PNH des cas de transmission interespèces.Dans la première partie de ce travail, nous avons montré que 83% (70/84) des mandrills du CDP (38 males et 46 femelles) et 60% (9/15) des mandrills sauvages étaient infectés par le SV. L’infection augmentait avec l’âge et la différence entre les males et les femelles n’était pas significative (84% et 82%, respectivement). Un fragment de 425pb de l’integrase a été amplifié dans 60/69 et 53 nouvelles séquences ont été isolées. L’analyse phylogénétique a mis en évidence la circulation de 11 souches différentes dans la colonie, toutes étroitement liées sauf une. La confirmation de ces résultats à l’aide de séquences de virus chez des mandrills sauvages démontre l’existence de deux groupes de mandrills (nord et sud) localisés de part et d’autre du fleuve Ogooué. En plus, nous avons étudié 497 échantillons de plasma et tissus prélevés chez 13 espèces simiennes dans la nature. L’analyse sérologique a montré l’infection par SV chez 10.8% (31/286). Le fragment de l’integrase a été caractérisé dans 38/497 échantillons, avec la description de nouvelles infections naturelles chez les C. solatus, C. nictitans et C. cephus. Dans la deuxième partie, nous avons décrit l’infection chez 20% (4/20) des travailleurs du CDP. La caractérisation moléculaire a été faite chez deux d’entre eux: l’un a été mordu il y a 10 ans par un mandrill clairement identifié, et l’autre par un macaque 25 ans auparavant. En milieu naturel, nous avons testé 78 personnes mordues par un PNH. Au total, 19 personnes mordues (24%) étaient séropositives pour le SV. Sur ces 19 individus, 15 séquences virales ont été obtenues dont 12 de gorilles, 2 de chimpanzés et une de cercopithèque. Ces résultats montrent que les PNH du Gabon sont infectés par les SV et que la transmission inter espèces des SV intervient chez des personnes mordues par ces animaux. / Foamy viruses are members of the Spumavirus genus of the Retroviridae family. These complex exogenous retroviruses are highly prevalent in several animal species, including nonhuman primates (NHP). The seroprevalence of antibodies to Simian foamy virus (SFVs) in captive adult NHP populations can reach 75-100%. SFV infection has been reported in people occupationally exposed to nonhuman primates in zoos. Recently, naturally acquired SFV infections were described in a group of hunters living in Cameroon, central Africa.In Gabon, foamy viruses are less studied. In our study, we evaluated the natural history of SFV in a free-ranging colony of mandrills (CIRMF primate center) and in mandrills living in natura in Gabon (central Africa). We also determined the SFV prevalence in a series of 497 NHP living in different parts of Gabon. Lastly, we investigated the possible transmission of SFVs to humans.First, SFV infection was determined by specific serological (Western blot) and molecular (nested PCR of the integrase region in the polymerase gene) assays. Seropositivity for SFV was found in 70/84 (83%) captive and 9/15 (60%) wild-caught mandrills. The 425-bp SFV integrase fragment was detected in peripheral blood DNA from 53 captive and 8 wild-caught mandrills.Sequence and phylogenetic studies demonstrated the presence of two distinct strains of mandrill SFV, one clade including SFVs from mandrills living in the northern part of Gabon and the second consisting of SFV from animals living in the south. Among the NHP, 10.8% (31/286) of the plasma/sera were SFV seropositive. Integrase gene was characterized in 38 samples with novel SFVs in several species of Cercopithecus.Second, the presence of SFV was also evaluated in 20 people who worked closely with mandrills and other NHP. Integrase region of 425 bp was found in 2/20 (10%) humans. One man who had been bitten 10 years earlier by a mandrill and another bitten 22 years earlier by a macaque were found to be SFV-infected, both at the Primate Centre. Comparative sequence analysis of the virus from the first man and from the mandrill showed nearly identical sequences, indicating genetic stability of SFV over time. The second man had a sequence close to SFVmac sequences. Of the 78 people, mostly hunters, who had been bitten or scratched by NHPs, 19 were SFV seropositive, with 15 cases confirmed by PCR. All but one were infected with ape SFV. We thus found novel SFV strains in NHPs in Gabon and high interspecies transmission of SFVs from gorilla bites.