Water Contaminants Associated With Unconventional Oil and Gas Extraction Cause Immunotoxicity to Amphibian Tadpoles

Chemicals associated with unconventional oil and gas (UOG) operations have been shown to contaminate surface and ground water with a variety of endocrine disrupting compounds (EDCs) inducing multiple developmental alteration in mice. However, little is known about the impacts of UOG-associated contaminants on amphibian health and resistance to an emerging ranavirus infectious disease caused by viruses in the genus Ranavirus, especially at the vulnerable tadpole stage. Here we used tadpoles of the amphibian Xenopus laevis and the ranavirus Frog virus 3 (FV3) as a model relevant to aquatic environment conservation research for investigating the immunotoxic effects of exposure to a mixture of 23 UOG-associated chemicals with EDC activity. Xenopus tadpoles were exposed to an equimass mixture of 23 UOG-associated chemicals (range from 0.1 to 10 µg/l) for 3 weeks prior to infection with FV3. Our data show that exposure to the UOG chemical mixture is toxic for tadpoles at ecological doses of 5 to 10 µg/l. Lower doses significantly altered homeostatic expression of myeloid lineage genes and compromised tadpole responses to FV3 through expression of TNF-α, IL-1β, and Type I IFN genes, correlating with an increase in viral load. Exposure to a subset of 6 UOG chemicals was still sufficient to perturb the antiviral gene expression response. These findings suggest that UOG-associated water pollutants at low but environmentally relevant doses have the potential to induce acute alterations of immune function and antiviral immunity

Altered Velocity Processing in Schizophrenia during Pursuit Eye Tracking

Smooth pursuit eye movements (SPEM) are needed to keep the retinal image of slowly moving objects within the fovea. Depending on the task, about 50%–80% of patients with schizophrenia have difficulties in maintaining SPEM. We designed a study that comprised different target velocities as well as testing for internal (extraretinal) guidance of SPEM in the absence of a visual target. We applied event-related fMRI by presenting four velocities (5, 10, 15, 20°/s) both with and without intervals of target blanking. 17 patients and 16 healthy participants were included. Eye movements were registered during scanning sessions. Statistical analysis included mixed ANOVAs and regression analyses of the target velocity on the Blood Oxygen Level Dependency (BOLD) signal. The main effect group and the interaction of velocity×group revealed reduced activation in V5 and putamen but increased activation of cerebellar regions in patients. Regression analysis showed that activation in supplementary eye field, putamen, and cerebellum was not correlated to target velocity in patients in contrast to controls. Furthermore, activation in V5 and in intraparietal sulcus (putative LIP) bilaterally was less strongly correlated to target velocity in patients than controls. Altered correlation of target velocity and neural activation in the cortical network supporting SPEM (V5, SEF, LIP, putamen) implies impaired transformation of the visual motion signal into an adequate motor command in patients. Cerebellar regions seem to be involved in compensatory mechanisms although cerebellar activity in patients was not related to target velocity

Whose Science and whose Religion? Reflections on the Relations between Scientific and Religious Worldviews

Arguments about the relationship between science and religion often proceed by identifying a set of essential characteristics of scientific and religious worldviews and arguing on the basis of these characteristics for claims about a relationship of conflict or compatibility between them. Such a strategy is doomed to failure because science, to some extent, and religion, to a much larger extent, are cultural phenomena that are too diverse in their expressions to be characterized in terms of a unified worldview. In this paper I follow a different strategy. Having offered a loose characterization of the nature of science, I pose five questions about specific areas where religious and scientific worldviews may conflict - questions about the nature of faith, the belief in a God or Gods, the authority of sacred texts, the relationship between scientific and religious conceptions of the mind/soul, and the relationship between scientific and religious understandings of moral behavior. My review of these questions will show that they cannot be answered unequivocally because there is no agreement amongst religious believers as to the meaning of important religious concepts. Thus, whether scientific and religious worldviews conflict depends essentially upon whose science and whose religion one is considering. In closing, I consider the implications of this conundrum for science education

Intrinsic gain modulation and adaptive neural coding

In many cases, the computation of a neural system can be reduced to a receptive field, or a set of linear filters, and a thresholding function, or gain curve, which determines the firing probability; this is known as a linear/nonlinear model. In some forms of sensory adaptation, these linear filters and gain curve adjust very rapidly to changes in the variance of a randomly varying driving input. An apparently similar but previously unrelated issue is the observation of gain control by background noise in cortical neurons: the slope of the firing rate vs current (f-I) curve changes with the variance of background random input. Here, we show a direct correspondence between these two observations by relating variance-dependent changes in the gain of f-I curves to characteristics of the changing empirical linear/nonlinear model obtained by sampling. In the case that the underlying system is fixed, we derive relationships relating the change of the gain with respect to both mean and variance with the receptive fields derived from reverse correlation on a white noise stimulus. Using two conductance-based model neurons that display distinct gain modulation properties through a simple change in parameters, we show that coding properties of both these models quantitatively satisfy the predicted relationships. Our results describe how both variance-dependent gain modulation and adaptive neural computation result from intrinsic nonlinearity.Comment: 24 pages, 4 figures, 1 supporting informatio

Dietary meat and fat intake and prevalence of rhinoconjunctivitis in pregnant Japanese women: baseline data from the Kyushu Okinawa Maternal and Child Health Study

<p>Abstract</p> <p>Background</p> <p>Dietary fat exerts numerous complex effects on proinflammatory and immunologic pathways. Several epidemiological studies have examined the relationships between intake of fatty acids and/or foods high in fat and allergic rhinitis, but have provided conflicting findings. The current cross-sectional study investigated such relationships in Japan.</p> <p>Methods</p> <p>Study subjects were 1745 pregnant women. The definition of rhinoconjunctivitis was based on criteria from the International Study of Asthma and Allergies in Childhood. Information on dietary factors was collected using a validated self-administered diet history questionnaire. Adjustment was made for age; gestation; region of residence; number of older siblings; number of children; smoking; secondhand smoke exposure at home and at work; family history of asthma, atopic eczema, and allergic rhinitis; household income; education; and body mass index.</p> <p>Results</p> <p>The prevalence of rhinoconjunctivitis in the past 12 months was 25.9%. Higher meat intake was significantly associated with an increased prevalence of rhinoconjunctivitis: the adjusted odds ratio between extreme quartiles was 1.71 (95% confidence interval: 1.25-2.35, <it>P </it>for trend = 0.002). No measurable association was found between fish intake and rhinoconjunctivitis. Intake of total fat, saturated fatty acids, monounsaturated fatty acids, n-3 polyunsaturated fatty acids, α-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, n-6 polyunsaturated fatty acids, linoleic acid, arachidonic acid, and cholesterol and the ratio of n-3 to n-6 polyunsaturated fatty acid intake were not evidently related to the prevalence of rhinoconjunctivitis.</p> <p>Conclusions</p> <p>The current results suggest that meat intake may be positively associated with the prevalence of rhinoconjunctivitis in young adult Japanese women.</p

Manipulation of an Innate Escape Response in Drosophila: Photoexcitation of acj6 Neurons Induces the Escape Response

Background: The genetic analysis of behavior in Drosophila melanogaster has linked genes controlling neuronal connectivity and physiology to specific neuronal circuits underlying a variety of innate behaviors. We investigated the circuitry underlying the adult startle response, using photoexcitation of neurons that produce the abnormal chemosensory jump 6 (acj6) transcription factor. This transcription factor has previously been shown to play a role in neuronal pathfinding and neurotransmitter modality, but the role of acj6 neurons in the adult startle response was largely unknown. Principal Findings: We show that the activity of these neurons is necessary for a wild-type startle response and that excitation is sufficient to generate a synthetic escape response. Further, we show that this synthetic response is still sensitive to the dose of acj6 suggesting that that acj6 mutation alters neuronal activity as well as connectivity and neurotransmitter production. Results/Significance: These results extend the understanding of the role of acj6 and of the adult startle response in general. They also demonstrate the usefulness of activity-dependent characterization of neuronal circuits underlying innat

Origins of the Qualitative Aspects of Consciousness: Evolutionary Answers to Chalmers' Hard Problem

According to David Chalmers, the hard problem of consciousness consists of explaining how and why qualitative experience arises from physical states. Moreover, Chalmers argues that materialist and reductive explanations of mentality are incapable of addressing the hard problem. In this chapter, I suggest that Chalmers’ hard problem can be usefully distinguished into a ‘how question’ and ‘why question,’ and I argue that evolutionary biology has the resources to address the question of why qualitative experience arises from brain states. From this perspective, I discuss the different kinds of evolutionary explanations (e.g., adaptationist, exaptationist, spandrel) that can explain the origins of the qualitative aspects of various conscious states. This argument is intended to clarify which parts of Chalmers’ hard problem are amenable to scientific analysis

NT2 Derived Neuronal and Astrocytic Network Signalling

A major focus of stem cell research is the generation of neurons that may then be implanted to treat neurodegenerative diseases. However, a picture is emerging where astrocytes are partners to neurons in sustaining and modulating brain function. We therefore investigated the functional properties of NT2 derived astrocytes and neurons using electrophysiological and calcium imaging approaches. NT2 neurons (NT2Ns) expressed sodium dependent action potentials, as well as responses to depolarisation and the neurotransmitter glutamate. NT2Ns exhibited spontaneous and coordinated calcium elevations in clusters and in extended processes, indicating local and long distance signalling. Tetrodotoxin sensitive network activity could also be evoked by electrical stimulation. Similarly, NT2 astrocytes (NT2As) exhibited morphology and functional properties consistent with this glial cell type. NT2As responded to neuronal activity and to exogenously applied neurotransmitters with calcium elevations, and in contrast to neurons, also exhibited spontaneous rhythmic calcium oscillations. NT2As also generated propagating calcium waves that were gap junction and purinergic signalling dependent. Our results show that NT2 derived astrocytes exhibit appropriate functionality and that NT2N networks interact with NT2A networks in co-culture. These findings underline the utility of such cultures to investigate human brain cell type signalling under controlled conditions. Furthermore, since stem cell derived neuron function and survival is of great importance therapeutically, our findings suggest that the presence of complementary astrocytes may be valuable in supporting stem cell derived neuronal networks. Indeed, this also supports the intriguing possibility of selective therapeutic replacement of astrocytes in diseases where these cells are either lost or lose functionality

Predictors of dropout in the German disease management program for type 2 diabetes

Background: To improve and assess the effectiveness of disease management programs (DMPs), it is critical to understand how many people drop out of disease management programs and why. Methods: We used routine data provided by a statutory health insurance fund from the regions North Rhine, North Wurttemberg and Hesse. As part of the German DMP for type 2 diabetes, the insurance fund received regular documentation of all members participating in the program. We followed 10,989 patients who enrolled in the DMP between July 2004 and December 2005 until the end of 2007 to study how many patients dropped out of the program. Dropout was defined based on the discontinuation of program documentation on a particular patient, excluding situations in which the patient died or left the insurance fund. Predictors of dropout, assessed at the time of program enrolment, were explored using logistic regression analysis. Results: 5.5% of the patients dropped out of the disease management program within the observation period. Predictors of dropout at the time of enrolment were: region; retirement status; the number of secondary diseases; presence of a disabling secondary disease; doctors recommendations to stop smoking or to seek nutritional counselling; and the completion and outcome of the routine foot and eye exams. Different trends of dropout were observed among retired and employed patients: retired patients of old age, who possibly drop out of the program due to other health care priorities and employed people of younger age who have not yet developed many secondary diseases, but were recommended to change their lifestyle. Conclusions: Overall, dropout rates for the German disease management programs for type 2 diabetes were low compared to other studies. Factors assessed at the time of program enrolment were predictive of later dropout and should be further studied to provide information for future program improvements