Toxoplasma on the Brain: Understanding Host-Pathogen Interactions in Chronic CNS Infection

Toxoplasma gondii is a prevalent obligate intracellular parasite which chronically infects more than a third of the world's population. Key to parasite prevalence is its ability to form chronic and nonimmunogenic bradyzoite cysts, which typically form in the brain and muscle cells of infected mammals, including humans. While acute clinical infection typically involves neurological and/or ocular damage, chronic infection has been more recently linked to behavioral changes. Establishment and maintenance of chronic infection involves a balance between the host immunity and parasite evasion of the immune response. Here, we outline the known cellular interplay between Toxoplasma gondii and cells of the central nervous system and review the reported effects of Toxoplasma gondii on behavior and neurological disease. Finally, we review new technologies which will allow us to more fully understand host-pathogen interactions

Social function in schizophrenia and schizoaffective disorder: Associations with personality, symptoms and neurocognition

BACKGROUND: Research has indicated that stable individual differences in personality exist among persons with schizophrenia spectrum disorders predating illness onset that are linked to symptoms and self appraised quality of life. Less is known about how closely individual differences in personality are uniquely related to levels of social relationships, a domain of dysfunction in schizophrenia more often linked in the literature with symptoms and neurocognitive deficits. This study tested the hypothesis that trait levels of personality as defined using the five-factor model of personality would be linked to social function in schizophrenia. METHODS: A self-report measure of the five factor model of personality was gathered along with ratings of social function, symptoms and assessments of neurocognition for 65 participants with schizophrenia or schizoaffective disorder. RESULTS: Univariate correlations and stepwise multiple regression indicated that frequency of social interaction was predicted by higher levels of the trait of Agreeableness, fewer negative symptoms, better verbal memory and at the trend level, lesser Neuroticism (R(2 )= .42, p < .0001). In contrast, capacity for intimacy was predicted by fewer negative symptoms, higher levels of Agreeableness, Openness, and Conscientiousness and at the trend level, fewer positive symptoms (R(2 )= .67, p < .0001). CONCLUSIONS: Taken together, the findings of this study suggest that person-centered variables such as personality, may account for some of the broad differences seen in outcome in schizophrenia spectrum disorders, including social outcomes. One interpretation of the results of this study is that differences in personality combine with symptoms and neurocognitive deficits to affect how persons with schizophrenia are able to form and sustain social connections with others

On-Chip Cavity Optomechanical Coupling

On-chip cavity optomechanics, in which strong co-localization of light and mechanical motion is engineered, relies on efficient coupling of light both into and out of the on-chip optical resonator. Here we detail our particular style of tapered and dimpled optical fibers, pioneered by the Painter group at Caltech, which are a versatile and reliable solution to efficient on-chip coupling. First, a brief overview of tapered, single mode fibers is presented, in which the single mode cutoff diameter is highlighted. The apparatus used to create a dimpled tapered fiber is then described, followed by a comprehensive account of the procedure by which a dimpled tapered fiber is produced and mounted in our system. The custom-built optical access vacuum chambers in which our on-chip optomechanical measurements are performed are then discussed. Finally, the process by which our optomechanical devices are fabricated and the method by which we explore their optical and mechanical properties is explained. It is our expectation that this manuscript will enable the novice to develop advanced optomechanical experiments.Comment: 31 pages, 9 figure

A Killing tensor for higher dimensional Kerr-AdS black holes with NUT charge

In this paper, we study the recently discovered family of higher dimensional Kerr-AdS black holes with an extra NUT-like parameter. We show that the inverse metric is additively separable after multiplication by a simple function. This allows us to separate the Hamilton-Jacobi equation, showing that geodesic motion is integrable on this background. The separation of the Hamilton-Jacobi equation is intimately linked to the existence of an irreducible Killing tensor, which provides an extra constant of motion. We also demonstrate that the Klein-Gordon equation for this background is separable.Comment: LaTeX, 14 pages. v2: Typo corrected and equation added. v3: Reference added, introduction expanded, published versio

Investigation of bradyzoite differentiation initiation in Toxoplasma gondii

Like other eukaryotic organisms, Toxoplasma gondii promoters feature both constitutive and life-stage regulated cis-elements. Using a transcriptomic microarray approach, a cluster of transcripts upregulated early during bradyzoite differentiation was identified. Computational analysis of the promoter regions of these “up-early” transcripts identified a shared upstream consensus motif, a putative transcription factor binding site. Using a dual luciferase assay adapted for recombinational cloning and reporter gene quantification by qPCR, we demonstrate developmental stage-specific expression of the luciferase reporter gene inserted downstream of the transcription factor binding site. The shared consensus motif was found to be an autonomous cis-element by conversion of a constitutive promoter into a bradyzoite growth condition-inducible promoter. A gel-shift experiment showed the cis-element’s binding to bradyzoite nuclear proteins. Mass spectrometry of the shifted gel band identified a protein possessing an apicomplexan AP2 transcription factor domain. Much detail concerning the mechanism of differentiation is yet to be discovered and this work highlights the mediation of life cycle progression by bradyzoite differential gene expression. Taken together, these data demonstrate the control an early bradyzoite promoter element exercises on stage differentiation

A high-fat diet containing whole walnuts (Juglans regia) reduces tumour size and growth along with plasma insulin-like growth factor 1 in the transgenic adenocarcinoma of the mouse prostate model.

Prostate cancer (PCa) has been linked to fat intake, but the effects of both different dietary fat levels and types remain inconsistent and incompletely characterised. The effects on PCa in the transgenic adenocarcinoma of the mouse prostate (TRAMP) cancer model of an elevated fat (20 % of energy as fat) diet containing 155 g of whole walnuts were compared to those of an elevated fat (20 % of energy as soyabean oil) diet with matched macronutrients, tocopherols as well as a low-fat (8 % of energy as soyabean oil) diet. Mice, starting at 8 weeks of age, consumed one of the three different diets ad libitum; and prostates, livers and blood were obtained after 9, 18 or 24 weeks of feeding. No differences were observed in whole animal growth rates in either high-fat (HF) diet group, but prostate tumour weight and growth rate were reduced in the walnut diet group. Walnut diet group prostate weight, plasma insulin-like growth factor 1, resistin and LDL were lower at 18 weeks, while no statistically significant prostate weight differences by diet were seen at 9 or 24 weeks. Multiple metabolites in the livers differed by diet at 9 and 18 weeks. The walnut diet's beneficial effects probably represent the effects of whole walnuts' multiple constituents and not via a specific fatty acid or tocopherols. Moreover, as the two HF diets had dissimilar effects on prostate tumour growth rate and size, and yet had the same total fat and tocopherol composition and content, this suggests that these are not strongly linked to PCa growth

Detection of Intestinal Pathogens in River, Shore, and Drinking Water in Lima, Peru

Water quality management is an ongoing struggle for many locations worldwide. Current testing of water supplies can be time-consuming, expensive, and lack sensitivity. This study describes an alternative, easy-to-use, and inexpensive method to water sampling and testing at remote locations. This method was employed to detect a number of intestinal pathogens in various locations of Lima, Peru. A total of 34 PCR primer pairs were tested for specificity and high-yield amplification for 12 different pathogens using known DNA templates. Select primers for each pathogen were then tested for minimum detection limits of DNA. Water samples were collected from 22 locations. PCR was used to detect the presence of a pathogen, virulence factors, or differentiate between pathogenic species. In 22 water samples, cholera toxin gene was detected in 4.5% of samples, C. perfringens DNA was detected in 50% of samples, E. histolytica DNA was detected in 54.5% of samples, Giardia intestinalis DNA was detected in 4.5% of samples, Leptospira spp. DNA was detected in 29% of samples, and T. gondii DNA was detected in 31.8% of samples. DNA from three pathogens, C. perfringens, E. histolytica, and T. gondii, were found in residential samples, which accounted for 10 out of 22 samples

Detection of Intestinal Pathogens in River, Shore, and Drinking Water in Lima, Peru

Water quality management is an ongoing struggle for many locations worldwide. Current testing of water supplies can be time-consuming, expensive, and lack sensitivity. This study describes an alternative, easy-to-use, and inexpensive method to water sampling and testing at remote locations. This method was employed to detect a number of intestinal pathogens in various locations of Lima, Peru. A total of 34 PCR primer pairs were tested for specificity and high-yield amplification for 12 different pathogens using known DNA templates. Select primers for each pathogen were then tested for minimum detection limits of DNA. Water samples were collected from 22 locations. PCR was used to detect the presence of a pathogen, virulence factors, or differentiate between pathogenic species. In 22 water samples, cholera toxin gene was detected in 4.5% of samples, C. perfringens DNA was detected in 50% of samples, E. histolytica DNA was detected in 54.5% of samples, Giardia intestinalis DNA was detected in 4.5% of samples, Leptospira spp. DNA was detected in 29% of samples, and T. gondii DNA was detected in 31.8% of samples. DNA from three pathogens, C. perfringens, E. histolytica, and T. gondii, were found in residential samples, which accounted for 10 out of 22 samples

Vibronic resonances facilitate excited state coherence in light harvesting proteins at room temperature

Until recently it was believed that photosynthesis, a fundamental process for life on earth, could be fully understood with semi-classical models. However, puzzling quantum phenomena have been observed in several photosynthetic pigment-protein complexes, prompting questions regarding the nature and role of these effects. Recent attention has focused on discrete vibrational modes that are resonant or quasi-resonant with excitonic energy splittings and strongly coupled to these excitonic states. Here we unambiguously identify excited state coherent superpositions in photosynthetic light-harvesting complexes using a new experimental approach. Decoherence on the timescale of the excited state lifetime allows low energy (56 cm-1) oscillations on the signal intensity to be observed. In conjunction with an appropriate model, these oscillations provide clear and direct experimental evidence that the persistent coherences observed require strong vibronic mixing among excited states