Detection of fruit and the selection of primate visual pigments for color vision

Primates have X chromosome genes for cone photopigments with sensitivity maxima from 535 to 562 nm. Old World monkeys and apes (catarrhines) and the New World ( platyrrhine) genus Alouatta have separate genes for 535-nm ( medium wavelength; M) and 562-nm ( long wavelength; L) pigments. These pigments, together with a 425-nm ( short wavelength) pigment, permit trichromatic color vision. Other platyrrhines and prosimians have a single X chromosome gene but often with alleles for two or three M/L photopigments. Consequently, heterozygote females are trichromats, but males and homozygote females are dichromats. The criteria that affect the evolution of M/L alleles and maintain genetic polymorphism remain a puzzle, but selection for finding food may be important. We compare different types of color vision for detecting more than 100 plant species consumed by tamarins ( Saguinus spp.) in Peru. There is evidence that both frequency-dependent selection on homozygotes and heterozygote advantage favor M/L polymorphism and that trichromatic color vision is most advantageous in dim light. Also, whereas the 562-nm allele is present in all species, the occurrence of 535- to 556-nm alleles varies between species. This variation probably arises because trichromatic color vision favors widely separated pigments and equal frequencies of 535/543- and 562-nm alleles, whereas in dichromats, long-wavelength pigment alleles are fitter.

Long-term evaluation of AAV-mediated sFlt-1 gene therapy for ocular neovascularization in mice and monkeys

Vascular endothelial growth factor (VEGF) is one of the major mediators of retinal ischemia-associated neovascularization. We have shown here that adeno-associated virus (AAV)-mediated expression of sFIt-1, a soluble form of the Flt-1 VEGF receptor, was maintained for up to 8 and 17 months postinjection in mice and in monkeys, respectively. The expression of sFIt-1 was associated with the long-term (8 months) regression of neovascular vessels in 85% of trVEGF029 eyes. In addition, it resulted in the maintenance of retinal morphology, as the majority of the treated trVEGF029 eyes (75%) retained high numbers of photoreceptors, and in retinal function as measured by electroretinography. AAV-mediated expression of sFIt-1 prevented the development of laser photocoagulation-incluced choroidal neovascularization in all treated monkey eyes. There were no clinically or histologically detectable signs of toxicity present in either animal model following AAV.sFlt injection. These results suggest that AAV-mediated secretion gene therapy could be considered for treatment of retinal and choroidal neovascularizations.

Disulfide bond mutagenesis and the structure and function of the head-to-tail macrocyclic trypsin inhibitor SFTI-1

SFTI-1 is a novel 14 amino acid peptide comprised of a circular backbone constrained by three proline residues, a hydrogen-bond network, and a single disulfide bond. It is the smallest and most potent known Bowman-Birk trypsin inhibitor and the only one with a cyclic peptidic backbone. The solution structure of [ABA(3,11)]SFTI-1, a disulfide-deficient analogue of SFTI-1, has been determined by H-1 NMR spectroscopy. The lowest energy structures of native SFTI-1 and [ABA(3,11)]SFTI-1 are similar and superimpose with a root-mean-square deviation over the backbone and heavy atoms of 0.26 +/- 0.09 and 1.10 +/- 0.22 Angstrom, respectively. The disulfide bridge in SFTI-1 was found to be a minor determinant for the overall structure, but its removal resulted in a slightly weakened hydrogen-bonding network. To further investigate the role of the disulfide bridge, NMR chemical shifts for the backbone H-alpha protons of two disulfide-deficient linear analogues of SFTI-1, [ABA(3,11)]SFTI-1[6,5] and [ABA(3,11)]SFTI-1[1,14] were measured. These correspond to analogues of the cleavage product of SFTI-1 and a putative biosynthetic precursor, respectively. In contrast with the cyclic peptide, it was found that the disulfide bridge is essential for maintaining the structure of these open-chain analogues. Overall, the hydrogen-bond network appears to be a crucial determinant of the structure of SFTI-1 analogues.

Effects of tourism development on the local poor people - Case study in Taibai Region China

In China, protected areas are one of the main destinations attracting tourists and homeland for many poor people living in and around them. Based on a case study, the paper focuses on correlation between tourism and poverty alleviation by tracing the cash flows to the local poor. It also reviews the social and environmental effects of tourism on local area. The case study is conducted in a group of protected areas in Qinling Mountain Region in Shaanxi, a western province in China. Qinling Mountain is one of the most important distribution zones for Giant Panda and some other endangered wildlife such as Golden Takin and Golden Monkey. The tourism development in the region is happening. Research indicates that there is 29.33%, of tourist expenditure is going to local households, directly or indirectly. Tourist spends US$7.11 (13.67%) in food and beverage, and US$6.39 (12.23%) in accommodation service, which are the greatest contributors to local households in terms of tourism benefits. Local households can get US$8.15 from food/beverage and accommodation sectors, taking 56.64% of total income from tourism. Generally, tourism development benefits all stakeholders. However, poor people get less benefit. The paper analyses the barriers for the poor to be involved in tourism development, and discusses the government roles, major issues in implementation of Sustainable Tourism-Eliminating Poverty (ST-EP) model. [ABSTRACT FROM AUTHOR]

Short-Term Perturbations and Tourism Effects: The case of SARS in China

In China, protected areas are one of the main destinations attracting tourists and homeland for many poor people living in and around them. Based on a case study, the paper focuses on correlation between tourism and poverty alleviation by tracing the cash flows to the local poor. It also reviews the social and environmental effects of tourism on local area. The case study is conducted in a group of protected areas in Qinling Mountain Region in Shaanxi, a western province in China. Qinling Mountain is one of the most important distribution zones for Giant Panda and some other endangered wildlife such as Golden Takin and Golden Monkey. The tourism development in the region is happening. Research indicates that there is 29.33%, of tourist expenditure is going to local households, directly or indirectly. Tourist spends US$7.11 (13.67%) in food and beverage, and US$6.39 (12.23%) in accommodation service, which are the greatest contributors to local households in terms of tourism benefits. Local households can get US$8.15 from food/beverage and accommodation sectors, taking 56.64% of total income from tourism. Generally, tourism development benefits all stakeholders. However, poor people get less benefit. The paper analyses the barriers for the poor to be involved in tourism development, and discusses the government roles, major issues in implementation of Sustainable Tourism-Eliminating Poverty (ST-EP) model.

First development of a polyurethane keratoprosthesis and its Australian connection: An unbeknown episode in the history of artificial cornea

This paper is aimed at establishing a particular chronological priority issue in the convoluted history of artificial cornea. According to existing records, the first keratoprosthesis made from polyurethane was developed by Caldwell and Jacob-Labarre in the late 1980s. This paper demonstrates that in fact the first polyurethane keratoprosthesis was proposed and designed in 1985 by Lawrence Hirst, an Australian ophthalmologist then working in St Louis, USA. The first prototype was manufactured in January 1986 by Thermedics Inc according to Dr Hirst's instructions from Tecoflex, a transparent polyurethane developed by the same company. This keratoprosthesis, which also had a porous skirt, was inserted intralamellarly in a monkey cornea and followed up clinically for about 3 months. There were no significant postoperative complications, and the histology of the explant indicated proper biointegration of the prosthetic skirt within the host stromal tissue. Because of a delay in the manufacture of further prototypes and to Dr Hirst's decision to return to Australia, the project was eventually abandoned. As no report was published on this development, the present paper is entirely based on original documents held in Dr Hirst's archives.

The missing link:Analogous human and primate cortical gamma oscillations

Recent animal studies highlighting the relationship between functional imaging signals and the underlying neuronal activity have revealed the potential capabilities of non-invasive methods. However, the valuable exchange of information between animal and human studies remains restricted by the limited evidence of direct physiological links between species. In this study we used magnetoencephalography (MEG) to investigate the occurrence of 30-70 Hz (gamma) oscillations in human visual cortex, induced by the presentation of visual stimuli of varying contrast. These oscillations, well described in the animal literature, were observed in retinotopically concordant locations of visual cortex and show striking similarity to those found in primate visual cortex using surgically implanted electrodes. The amplitude of the gamma oscillations increases linearly with stimulus contrast in strong correlation with the gamma oscillations found in the local field potential (LFP) of the macaque. We demonstrate that non-invasive magnetic field measurements of gamma oscillations in human visual cortex concur with invasive measures of activation in primate visual cortex, suggesting both a direct representation of underlying neuronal activity and a concurrence between human and primate cortical activity. © 2005 Elsevier Inc. All rights reserved.

Sustained release of the CCR5 inhibitors CMPD167 and maraviroc from vaginal rings in rhesus macaques

Antiretroviral entry inhibitors are now being considered as vaginally administered microbicide candidates for the prevention of the sexual transmission of human immunodeficiency virus. Previous studies testing the entry inhibitors maraviroc and CMPD167 in aqueous gel formulations showed efficacy in the macaque challenge model, although protection was highly dependent on the time period between initial gel application and subsequent challenge. In this paper, we describe the sustained release of maraviroc and CMPD167 from matrix-type silicone elastomer vaginal rings both in vitro and in vivo. Both inhibitors were released continuously during 28 days from rings in vitro at rates of 100 to 2,500 µg/day. In 28-day pharmacokinetic studies in rhesus macaques, the compounds were measured in the vaginal fluid and vaginal tissue; steady-state fluid concentrations were ~10(6)-fold greater than the 50% inhibitory concentrations (IC(50)s) for simian human immunodeficiency virus 162P3 inhibition in macaque lymphocytes in vitro. Plasma concentrations for both compounds were very low. The pretreatment of macaques with Depo-Provera (DP), which is commonly used in macaque challenge studies, was shown to significantly modify the biodistribution of the inhibitors but not the overall amount released. Vaginal fluid and tissue concentrations were significantly decreased while plasma levels increased with DP pretreatment. These observations have implications for designing macaque challenge experiments and also for ring performance during the human female menstrual cycle.

Attentional shifting and the role of the dorsal pathway in visual word recognition

A substantial amount of evidence has been collected to propose an exclusive role for the dorsal visual pathway in the control of guided visual search mechanisms, specifically in the preattentive direction of spatial selection [Vidyasagar, T. R. (1999). A neuronal model of attentional spotlight: Parietal guiding the temporal. Brain Research and Reviews, 30, 66-76; Vidyasagar, T. R. (2001). From attentional gating in macaque primary visual cortex to dyslexia in humans. Progress in Brain Research, 134, 297-312]. Moreover, it has been suggested recently that the dorsal visual pathway is specifically involved in the spatial selection and sequencing required for orthographic processing in visual word recognition. In this experiment we manipulate the demands for spatial processing in a word recognition, lexical decision task by presenting target words in a normal spatial configuration, or where the constituent letters of each word are spatially shifted relative to each other. Accurate word recognition in the Shifted-words condition should demand higher spatial encoding requirements, thereby making greater demands on the dorsal visual stream. Magnetoencephalographic (MEG) neuroimaging revealed a high frequency (35-40 Hz) right posterior parietal activation consistent with dorsal stream involvement occurring between 100 and 300 ms post-stimulus onset, and then again at 200-400 ms. Moreover, this signal was stronger in the shifted word condition, compared to the normal word condition. This result provides neurophysiological evidence that the dorsal visual stream may play an important role in visual word recognition and reading. These results further provide a plausible link between early stage theories of reading, and the magnocellular-deficit theory of dyslexia, which characterises many types of reading difficulty. © 2006 Elsevier Ltd. All rights reserved.

The activity of pH membrane disruptive pseudopeptides and their subcellular fate in mammalian cells cultured in-vitro

This thesis describes investigations upon pseudopeptides which were conducted to improve our understanding of the fate of synthetic macromolecules in cells and to develop approaches to influence that fate. The low uptake of molecules across the external cellular membrane is the principal barrier against effective delivery of therapeutic products to within the cell structure. In nature, disruption of this membrane by amphiphilic peptides plays a central role in the pathogenesis by bacterial and toxin infections. These amphiphilic peptides contain both hydrophobic and weakly charged hydrophilic amino acid residues and upon activation they become integrated into the lipid bilayers of the extracellular or endosomal membranes. The architectures of the pseudopeptides described here were designed to display similar pH dependent membrane rupturing activity to that of peptides derived from the influenza virus hemagglutinin HA-2. This HA protein promotes fusion of the influenza virus envelope with the cell endosome membrane due to a change in conformation in response to the acidic pH of the endosome lumen (pH 5.0-6.0). The pseudopeptides were obtained by the copolymerisation of L-lysine and L-lysine ethyl-ester with various dicarboxylic acid moieties. In this way a linear polyamide comprising of alternating pendant carboxylic acids and pendant hydrophobic moieties was made. At physiological pH (pH 7.4), electrostatic repulsion of pendant anionic carboxyl groups along the polymer backbone is sufficient to overcome the intramolecular association of the hydrophobic groups resulting in an extended conformation. At low pH (typically pH 4.8) loss of charge results in increased intramolecular hydrophobic association and the polymer chain collapses to a compact conformation, leading to precipitation of the polymer. Consequently, a conformation dependent functional property could be made to respond to small changes in the environmental pH. Pseudopepides were investigated for their cytoxicity towards a well known cell line, namely C26 (colorectal adenocarcinoma) and were shown through the use of a cell viability assay, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide) to be well tolerated by C26 cells over a range of concentrations (2-500,μg/ml) at physiological pH (pH 7.4). A modified version of a shorter 30-minute coupled enzymatic assay, the LDH (lactate dehydrogenase) assay was used to evaluate the ability of the pseudopeptides to disrupt the membrane of two different cell lines (COS-1; African green monkey, kidney and A2780; human ovarian carcinoma) at low pH (pH 5.5). The cell membrane disruption property of the pseudopeptides was successfully demonstrated for COS-I and A2780 cell lines at this pH (pH 5.5). A variety of cell lines were chosen owing to limited availability and to compare the cytotoxic action of these pH responsive psudopeptides towards normal and tumorogenic cell lines. To investigate the intracellular delivery of one of the pseudopeptides, poly (L-lysine iso-phthalamide) and its subcellular location, a Cy3 bisamine fluorophore was conjugated into its backbone, at ratios of dye:lysine of 1:20, 1:30, 1:40, 1:60 and 1:80. Native polyacrylacrylamide gel electrophoresis (PAGE) and high voltage paper electrophoresis (HVPE) studies of the polydyes were conducted and provided evidence that that the Cy3 bisamine fluorophore was conjugated into the backbone of the polymer, poly (L-lysine iso-phthalamide). The subcellular fate of the fluorescentlylabelled "polydye" (hereafter PD20) was monitored by laser scanning confocal microscopy (LSCM) in CHO (Chinese hamster ovary) cells cultured in-vitro at various pH values (pH 7.4 and 5.0). LSCM images depicting time-dependent internalisation of PD20 indicated that PD20 traversed the extracellular membrane of CHO cells cultured in-vitro within ten minutes and migrated towards the endosomal regions where the pH is in the region of 5.0 to 6.0. Nuclear localisation of PD20 was demonstrated in a subpopulation of CHO cells. A further study was completed in CHO and HepG2 (hepatocellular carcinoma) cells cultured in-vitro using a lower molecular weight polymer to demonstrate that the molecular weight of "polydye" could be tailored to attain nuclear trafficking in cells. Prospective use of this technology encompasses a method of delivering a payload into a living cell based upon the hypercoiling nature of the pseudopeptides studied in this thesis and has led to a patent application (GB0228525.2; 20(2).

Do long-tailed macaques (Macaca fascicularis) know what others can and cannot hear?

Theory of mind has been defined as the ability to attribute mental sates such as perceptions, knowledge, and belief to others. Studies examining theory of mind in primates have been the center of intense controversy. Much of the research on this subject has focused on designing methodologies to test a primate’s ability to discern the perceptions of others. Namely, many studies have examined an individual’s knowledge of what others can and cannot see. However, other sensory modalities have not undergone as much extensive research. This study aimed to replicate the methodology of a previous experiment with the addition of two novel experimental conditions. Individual long-tailed macaques (Macaca fascicularis) were allowed to approach one of two identical, lidded, clear boxes which had jingle bells attached to them. One of the boxes had the metal bits removed from inside of the jingle bells attached to it, thus creating one “silent” box and leaving the remaining one “noisy”. The experimenter either looked directly at the subject, down at the ground between their knees, or in the novel conditions, turned their back to the subject, or wore a welder’s mask while facing the subject after demonstrating each box’s auditory properties. It was predicted that subjects would choose to approach the silent container in the latter three conditions. The results indicated that subjects selected boxes at random in all conditions. Additionally, in order to explore the possibility of perspective-taking representing a derived trait in the genus Macaca, a phylogeny of the genus was created and annotated to display the presence of perspective-taking as a phenotypic trait in extant species. Three likely evolutionary scenarios leading to the current distribution of perspective-taking are postulated and analyzed for parsimony through the number of assumed gains and losses. The most parsimonious tree suggests that perspective taking could be a conserved trait among the order, giving credence to the argument that some other variable was responsible the negative results in this experiment. It is suggested that the results of the present study represent an artifact of the social environment of the subject population. Moreover, arguments are made for the development of more naturalistic studies for examining mental state attribution in primates.

Étude des relations entre le développement professionnel des enseignants du postsecondaire et leur bien-être psychologique au travail

Réalisé en milieu collégial (cégep)

Advances in Dynamic Modeling and Computation for Count Data

A class of multi-process models is developed for collections of time indexed count data. Autocorrelation in counts is achieved with dynamic models for the natural parameter of the binomial distribution. In addition to modeling binomial time series, the framework includes dynamic models for multinomial and Poisson time series. Markov chain Monte Carlo (MCMC) and Po ́lya-Gamma data augmentation (Polson et al., 2013) are critical for fitting multi-process models of counts. To facilitate computation when the counts are high, a Gaussian approximation to the P ́olya- Gamma random variable is developed.

Three applied analyses are presented to explore the utility and versatility of the framework. The first analysis develops a model for complex dynamic behavior of themes in collections of text documents. Documents are modeled as a “bag of words”, and the multinomial distribution is used to characterize uncertainty in the vocabulary terms appearing in each document. State-space models for the natural parameters of the multinomial distribution induce autocorrelation in themes and their proportional representation in the corpus over time.

The second analysis develops a dynamic mixed membership model for Poisson counts. The model is applied to a collection of time series which record neuron level firing patterns in rhesus monkeys. The monkey is exposed to two sounds simultaneously, and Gaussian processes are used to smoothly model the time-varying rate at which the neuron’s firing pattern fluctuates between features associated with each sound in isolation.

The third analysis presents a switching dynamic generalized linear model for the time-varying home run totals of professional baseball players. The model endows each player with an age specific latent natural ability class and a performance enhancing drug (PED) use indicator. As players age, they randomly transition through a sequence of ability classes in a manner consistent with traditional aging patterns. When the performance of the player significantly deviates from the expected aging pattern, he is identified as a player whose performance is consistent with PED use.

All three models provide a mechanism for sharing information across related series locally in time. The models are fit with variations on the P ́olya-Gamma Gibbs sampler, MCMC convergence diagnostics are developed, and reproducible inference is emphasized throughout the dissertation.

Decision-Making in the Primate Brain

Making decisions is fundamental to everything we do, yet it can be impaired in various disorders and conditions. While research into the neural basis of decision-making has flourished in recent years, many questions remain about how decisions are instantiated in the brain. Here we explored how primates make abstract decisions and decisions in social contexts, as well as one way to non-invasively modulate the brain circuits underlying decision-making. We used rhesus macaques as our model organism. First we probed numerical decision-making, a form of abstract decision-making. We demonstrated that monkeys are able to compare discrete ratios, choosing an array with a greater ratio of positive to negative stimuli, even when this array does not have a greater absolute number of positive stimuli. Monkeys’ performance in this task adhered to Weber’s law, indicating that monkeys—like humans—treat proportions as analog magnitudes. Next we showed that monkeys’ ordinal decisions are influenced by spatial associations; when trained to select the fourth stimulus from the bottom in a vertical array, they subsequently selected the fourth stimulus from the left—and not from the right—in a horizontal array. In other words, they begin enumerating from one side of space and not the other, mirroring the human tendency to associate numbers with space. These and other studies confirmed that monkeys’ numerical decision-making follows similar patterns to that of humans, making them a good model for investigations of the neurobiological basis of numerical decision-making.

We sought to develop a system for exploring the neuronal basis of the cognitive and behavioral effects observed following transcranial magnetic stimulation, a relatively new, non-invasive method of brain stimulation that may be used to treat clinical disorders. We completed a set of pilot studies applying offline low-frequency repetitive transcranial magnetic stimulation to the macaque posterior parietal cortex, which has been implicated in numerical processing, while subjects performed a numerical comparison and control color comparison task, and while electrophysiological activity was recorded from the stimulated region of cortex. We found tentative evidence in one paradigm that stimulation did selectively impair performance in the number task, causally implicating the posterior parietal cortex in numerical decisions. In another paradigm, however, we manipulated the subject’s reaching behavior but not her number or color comparison performance. We also found that stimulation produced variable changes in neuronal firing and local field potentials. Together these findings lay the groundwork for detailed investigations into how different parameters of transcranial magnetic stimulation can interact with cortical architecture to produce various cognitive and behavioral changes.

Finally, we explored how monkeys decide how to behave in competitive social interactions. In a zero-sum computer game in which two monkeys played as a shooter or a goalie during a hockey-like “penalty shot” scenario, we found that shooters developed complex movement trajectories so as to conceal their intentions from the goalies. Additionally, we found that neurons in the dorsolateral and dorsomedial prefrontal cortex played a role in generating this “deceptive” behavior. We conclude that these regions of prefrontal cortex form part of a circuit that guides decisions to make an individual less predictable to an opponent.

Wear and its effects on dental topography measures in howling monkeys (Alouatta palliata).

OBJECTIVES: Three dental topography measurements: Dirichlet Normal Energy (DNE), Relief Index (RFI), and Orientation Patch Count Rotated (OPCR) are examined for their interaction with measures of wear, within and between upper and lower molars in Alouatta palliata. Potential inferences of the "dental sculpting" phenomenon are explored. MATERIALS AND METHODS: Fifteen occluding pairs of howling monkey first molars (15 upper, 15 lower) opportunistically collected from La Pacifica, Costa Rica, were selected to sample wear stages ranging from unworn to heavily worn as measured by the Dentine Exposure Ratio (DER). DNE, RFI, and OPCR were measured from three-dimensional surface reconstructions (PLY files) derived from high-resolution CT scans. Relationships among the variables were tested with regression analyses. RESULTS: Upper molars have more cutting edges, exhibiting significantly higher DNE, but have significantly lower RFI values. However, the relationships among the measures are concordant across both sets of molars. DER and EDJL are curvilinearly related. DER is positively correlated with DNE, negatively correlated with RFI, and uncorrelated with OPCR. EDJL is not correlated with DNE, or RFI, but is positively correlated with OPCR among lower molars only. DISCUSSION: The relationships among these metrics suggest that howling monkey teeth adaptively engage macrowear. DNE increases with wear in this sample presumably improving food breakdown. RFI is initially high but declines with wear, suggesting that the initially high RFI safeguards against dental senescence. OPCR values in howling monkey teeth do not show a clear relationship with wear changes.