Neuroimaging evidence implicating cerebellum in support of sensory/cognitive processes associated with thirst.

Recent studies implicate the cerebellum, long considered strictly a motor control structure, in cognitive, sensory, and affective phenomenon. The cerebellum, a phylogenetically ancient structure, has reciprocal ancient connections to the hypothalamus, a structure important in vegetative functions. The present study investigated whether the cerebellum was involved in vegetative functions and the primal emotions engendered by them. Using positron emission tomography, we examined the effects on the cerebellum of the rise of plasma sodium concentration and the emergence of thirst in 10 healthy adults. The correlation of regional cerebral blood flow with subjects' ratings of thirst showed major activation in the vermal central lobule. During the development of thirst, the anterior and posterior quadrangular lobule, lingula, and the vermis were activated. At maximum thirst and then during irrigation of the mouth with water to alleviate dryness, the cerebellum was less activated. However, 3 min after drinking to satiation, the anterior quadrangular lobule and posterior cerebellum were highly activated. The increased cerebellar activity was not related to motor behavior as this did not occur. Instead, responses in ancient cerebellar regions (vermis, fastigal nucleus, archicerebellum) may be more directly related to vegetative and affective aspects of thirst experiences, whereas activity in neocerebellar (posterior) regions may be related to sensory and cognitive aspects. Moreover, the cerebellum is apparently not involved in the computation of thirst per se but rather is activated during changes in thirst/satiation state when the brain is "vigilant" and is monitoring its sensory systems. Some neocerebellar activity may also reflect an intentionality for gratification by drinking inherent in the consciousness of thirst

Decision Making about Risk of Infection by Young Adults with CF

Young people with cystic fibrosis (CF) are asked to avoid a number of environments associated with increased infection risk, but in practice they need to balance this with competing priorities such as building and sustaining relationships with friends and family. This study explored the process by which young people make these decisions. Mixed methods were used: a vignette study presenting choices around engaging in activities involving a degree of infection risk and a thematic analysis of participant's accounts of their decision making. The eight participants chose to engage in high risk behaviours in 59% of the choices. All participants chose to engage in at least one risky behavior, though this was less likely when the risk was significant. Thematic analysis revealed large areas of misunderstanding and lack of knowledge, leading to some potentially worrying misconceptions about the nature of infections and risk. Young people with CF are not currently making informed decisions around activities that involve increased risk of infection, and there is an urgent need for CF teams to address this in information provision

Ionospheric response to the corotating interaction region-driven geomagnetic storm of October 2002

Unlike the geomagnetic storms produced by coronal mass ejections (CMEs), the storms generated by corotating interaction regions (CIRs) are not manifested by dramatic enhancements of the ring current. The CIR-driven storms are however capable of producing other phenomena typical for the magnetic storms such as relativistic particle acceleration, enhanced magnetospheric convection and ionospheric heating. This paper examines ionospheric plasma anomalies produced by a CIR-driven storm in the middle- and high-latitude ionosphere with a specific focus on the polar cap region. The moderate magnetic storm which took place on 14–17 October 2002 has been used as an example of the CIR-driven event. Four-dimensional tomographic reconstructions of the ionospheric plasma density using measurements of the total electron content along ray paths of GPS signals allow us to reveal the large-scale structure of storm-induced ionospheric anomalies. The tomographic reconstructions are compared with the data obtained by digital ionosonde located at Eureka station near the geomagnetic north pole. The morphology and dynamics of the observed ionospheric anomalies is compared qualitatively to the ionospheric anomalies produced by major CME-driven storms. It is demonstrated that the CIR-driven storm of October 2002 was able to produce ionospheric anomalies comparable to those produced by CME-driven storms of much greater Dst magnitude. This study represents an important step in linking the tomographic GPS reconstructions with the data from ground-based network of digital ionosondes

Some considerations concerning the challenge of incorporating social variables into epidemiological models of infectious disease transmission

Incorporation of ‘social’ variables into epidemiological models remains a challenge. Too much detail and models cease to be useful; too little and the very notion of infection —a highly social process in human populations—may be considered with little reference to the social. The French sociologist Emile Durkheim proposed that the scientific study of society required identification and study of ‘social currents.’ Such ‘currents’ are what we might today describe as ‘emergent properties,’ specifiable variables appertaining to individuals and groups, which represent the perspectives of social actors as they experience the environment in which they live their lives. Here we review the ways in which one particular emergent property, hope, relevant to a range of epidemiological situations, might be used in epidemiological modelling of infectious diseases in human populations. We also indicate how such an approach might be extended to include a range of other potential emergent properties to repre

Weighted-density approximation for general nonuniform fluid mixtures

In order to construct a general density-functional theory for nonuniform fluid mixtures, we propose an extension to multicomponent systems of the weighted-density approximation (WDA) of Curtin and Ashcroft [Phys. Rev. A 32, 2909 (1985)]. This extension corrects a deficiency in a similar extension proposed earlier by Denton and Ashcroft [Phys. Rev. A 42, 7312 (1990)], in that that functional cannot be applied to the multi-component nonuniform fluid systems with spatially varying composition, such as solid-fluid interfaces. As a test of the accuracy of our new functional, we apply it to the calculation of the freezing phase diagram of a binary hard-sphere fluid, and compare the results to simulation and the Denton-Ashcroft extension.Comment: 4 pages, 4 figures, to appear in Phys. Rev. E as Brief Repor

Vaccine-induced skewing of T cell responses protects against Chikungunya virus disease

Chikungunya virus (CHIKV) infections can cause severe and debilitating joint and muscular pain that can be long lasting. Current CHIKV vaccines under development rely on the generation of neutralizing antibodies for protection; however, the role of T cells in controlling CHIKV infection and disease is still unclear. Using an overlapping peptide library, we identified the CHIKV-specific T cell receptor epitopes recognized in C57BL/6 infected mice at 7 and 14 days post-infection. A fusion protein containing peptides 451, 416, a small region of nsP4, peptide 47, and an HA tag (CHKVf5) was expressed using adenovirus and cytomegalovirus-vectored vaccines. Mice vaccinated with CHKVf5 elicited robust T cell responses to higher levels than normally observed following CHIKV infection, but the vaccine vectors did not elicit neutralizing antibodies. CHKVf5-vaccinated mice had significantly reduced infectious viral load when challenged by intramuscular CHIKV injection. Depletion of both CD

Reduced exercise capacity in patients with systemic sclerosis is associated with lower peak tissue oxygen extraction: a cardiovascular magnetic resonance-augmented cardiopulmonary exercise study

Background: Exercise intolerance in systemic sclerosis (SSc) is typically attributed to cardiopulmonary limitations. However, problems with skeletal muscle oxygen extraction have not been fully investigated. This study used cardiovascular magnetic resonance (CMR)-augmented cardiopulmonary exercise testing (CMR-CPET) to simultaneously measure oxygen consumption and cardiac output. This allowed calculation of arteriovenous oxygen content gradient, a recognized marker of oxygen extraction. We performed CMR-CPET in 4 groups: systemic sclerosis (SSc); systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH); non-connective tissue disease pulmonary hypertension (NC-PAH); and healthy controls. Methods: We performed CMR-CPET in 60 subjects (15 in each group) using a supine ergometer following a ramped exercise protocol until exhaustion. Values for oxygen consumption, cardiac output and oxygen content gradient, as well as ventricular volumes, were obtained at rest and peak-exercise for all subjects. In addition, T1 and T2 maps were acquired at rest, and the most recent clinical measures (hemoglobin, lung function, 6-min walk, cardiac and catheterization) were collected. Results: All patient groups had reduced peak oxygen consumption compared to healthy controls (p<0.022). The SSc and SSc-PAH groups had reduced peak oxygen content gradient compared to healthy controls (p<0.03). Conversely, the SSc-PAH and NC-PH patients had reduced peak cardiac output compared to healthy controls and SSc patients (p<0.006). Higher hemoglobin was associated with higher peak oxygen content gradient (p=0.025) and higher myocardial T1 was associated with lower peak stroke volume (p=0.011). Conclusions: Reduced peak oxygen consumption in SSc patients is predominantly driven by reduced oxygen content gradient and in SSc-PAH patients this was amplifed by reduced peak cardiac output

Effects of tyrosine kinase inhibitors on protein kinase-independent systems

AbstractTyrosine kinase inhibitors have been widely used to probe the role of tyrosine phosphorylation in cellular signalling. These inhibitors exhibit an apparent specificity for tyrosine kinases over the serine/threonine kinases but little is known about their effects on other enzymes or biological systems. We demonstrate that genistein, erbstatin and α-cyanoeinnamamides (tyrphostins) have inhibitory effects on fatty acid synthesis, lactate transport, mitochondrial oxidative phosphorylation and aldehyde dehydrogenase. We propose, therefore, that results obtained using tyrosine kinase inhibitors should be interpreted with caution, particularly if used at concentrations sufficient to inhibit these non-protein kinase-dependent events