The B subunit of Escherichia coli heat-labile toxin alters the development and antigen-presenting capacity of dendritic cells

Escherichia coli’s heat-labile enterotoxin (Etx) and its non-toxic B subunit (EtxB) have been characterized as adjuvants capable of enhancing T cell responses to co-administered antigen. Here, we investigate the direct effect of intravenously administered EtxB on the size of the dendritic and mye-loid cell populations in spleen. EtxB treatment appears to enhance the development and turnover of dendritic and myeloid cells from precursors within the spleen. EtxB treatment also gives a dendritic cell (DC) population with higher viability and lower activation status based on the reduced expression of MHC-II, CD80 and CD86. In this respect, the in vivo effect of EtxB differs from that of the highly inflammatory mediator lipopolysaccharide. In in vi-tro bone marrow cultures, EtxB treatment was also found to enhance the development of DC from precursors dependent on Flt3L. In terms of the in vivo effect of EtxB on CD4 and CD8 T cell responses in mice, the interaction of EtxB directly with DC was demonstrated following conditional deple-tion of CD11c+ DC. In summary, all results are consistent with EtxB displaying adjuvant ability by enhancing the turnover of DC in spleen, leading to newly mature myeloid and DC in spleen, thereby increasing DC capacity to perform as antigen-presenting cells on encounter with T cells

Copper-induced conformational change in a marsupial prion protein repeat peptide probed using FTIR spectroscopy

AbstractWe report the first Fourier transform infrared analysis of prion protein (PrP) repeats and the first study of PrP repeats of marsupial origin. Large changes in the secondary structure and an increase in hydrogen bonding within the peptide groups were evident from a red shift of the amide I band by >7 cm−1 and an approximately five-fold reduction in amide hydrogen–deuterium exchange for peptide interacting with Cu2+ ions. Changes in the tertiary structure upon copper binding were also evident from the appearance of a new band at 1564 cm−1, which arises from the ring vibration of histidine. The copper-induced conformational change is pH dependent, and occurs at pH >7

General description of quasi-adiabatic dynamical phenomena near exceptional points

The appearance of so-called exceptional points in the complex spectra of non-Hermitian systems is often associated with phenomena that contradict our physical intuition. One example of particular interest is the state-exchange process predicted for an adiabatic encircling of an exceptional point. In this work we analyse this and related processes for the generic system of two coupled oscillator modes with loss or gain. We identify a characteristic system evolution consisting of periods of quasi-stationarity interrupted by abrupt non-adiabatic transitions, and we present a qualitative and quantitative description of this switching behaviour by connecting the problem to the phenomenon of stability loss delay. This approach makes accurate predictions for the breakdown of the adiabatic theorem as well as the occurrence of chiral behavior observed previously in this context, and provides a general framework to model and understand quasi-adiabatic dynamical effects in non-Hermitian systems.Comment: Main text: 9 pages; 5 figures. Appendix: 4 pages; 1 figur

Cognitive performance and leukocyte telomere length in two narrow age-range cohorts: a population study

BACKGROUND Cognitive function and telomere length both decline with age. A correlation between these two measures would suggest that they may be influenced by the same underlying age-related biological process. Several studies suggest telomere length may be positively correlated with cognitive performance but the evidence is equivocal. In this report, the relationships between telomere length and cognitive performance at Wave 2 and cognitive change from Wave 1 to Wave 2 are assessed in two narrow age-range population cohorts. METHODS We tested the hypothesis that leukocyte telomere length correlates positively with cognitive performance and cognitive decline in two community cohorts of middle-aged (n = 351, 44-49 years) and older (n = 295, 64-70 years) adults, who participated in two waves of a longitudinal study undertaken in the Canberra-Queanbeyan region of Australia. Telomere length was estimated at Wave 2. Cognitive performance was measured using the Symbol Digit Modalities Test, the immediate recall test of the California Verbal Learning Test, reaction time (simple & choice) and the Trails Test Part B. RESULTS Cross-sectionally at Wave 2, telomere length correlated with Symbol Digit Modalities Test scores (men) and simple reaction time (women) for the older cohort only, although the latter finding was in the opposite direction to that hypothesised. Telomere length measured at Wave 2 was not associated with cognitive change from Wave 1 to Wave 2 for either cohort, except for two associations of small magnitude (immediate recall in the older cohort, choice reaction time in older women), which were also in the contrary direction to that predicted. CONCLUSIONS These results do not give strong support to the hypothesis that leukocyte telomere length is associated with either levels of cognitive performance or age-related cognitive change.This work was supported by an Australian National Health and Medical Research Council Program Grant 179805 and an R.M. Gibson Grant from the Australian Association of Gerontology. A.F. Jorm, K.J. Anstey and H. Christensen are funded by NHMRC Fellowships

Causal asymmetry from the perspective of a causal agent

Agency accounts of causation are often criticised as being unacceptably subjective or anthropocentric. According to such criticisms, if there were no human agents then there would be no causal relations, or, at the very least, if humans had been different then so too would causal relations. Here we describe a model of a causal agent that is not human with a view to exploring this latter claim. This model obeys the known laws of physics, and we claim that it endows the causal agent with a "causal viewpoint: a distinctive mix of knowledge, ignorance and practical ability that a creature must apparently exemplify, if it is to be capable of employing causal concepts" (Price, 2007, p.255). We argue that this model of a causal agent provides a clear illustration of the epistemic constraints that define such a 'causal perspective', and we employ the model to demonstrate how shared constraints lead to a shared perspective. Furthermore, we use this model to scrutinise the alignment of three familiar asymmetries with the causal asymmetry: the thermodynamic arrow, the arrow of time, and the arrow of deliberation and action

How clocks define physical time

It is the prevailing paradigm in contemporary physics to model the dynamical evolution of physical systems in terms of a real parameter conventionally denoted as 't' ('little tee'). We typically call such dynamical models laws of nature' and t we call 'physical time'. It is common in the philosophy of time to regard t as time itself, and to take the global structure of general relativity as the ultimate guide to physical time, and so consequently the true nature of time. In this paper we defend the idea that physical time, t, is rather better defined as an operational modelling parameter: we measure relations between changing physical quantities using bespoke physical systems---i.e. clocks---that coordinate local coincidences. We argue that the sorts of physical systems that make good clocks---what we call precision clocks---are those that exhibit self-sustained oscillations known as limit cycles, which are ubiquitous in open, driven, stable, dissipative systems. We develop the physical and philosophical ramifications of this conception of physical time, particularly the notion that physical time does not track something 'out there' in the world. As a result, we speculate that physical time is perhaps not as different from manifest time as many philosophers of time (and apparently general relativity) seem to suggest

Stepping down from mere appearance: Modelling the 'actuality' of time

In her paper, 'The Open Universe: Totality, Self-reference and Time', Ismael argues that the agent experience of dynamic time, in which the world comes into being, is more than 'mere appearance'. The key to her argument is that the actual world includes agents (minds) and their corresponding agential (mental) activity, which Ismael describes as 'the crucial step down from 'mere appearance' to actuality'. We present here a model of an agent as a complex physical system with a view to providing a tenable illustration of Ismael's schema for understanding the 'actuality' of time. The radical implication for physical time as a result is that there is, in Ismael's words, 'no pure... conception of the way [the] world is independently of ourselves and our representational activity', but rather only 'embodied and engaged' knowledge of the world

A kinematic analysis of the spine during rugby scrummaging on natural and synthetic turfs

Artificial surfaces are now an established alternative to grass (natural) surfaces in rugby union. Little is known, however, about their potential to reduce injury. This study characterises the spinal kinematics of rugby union hookers during scrummaging on third-generation synthetic (3G) and natural pitches. The spine was sectioned into five segments, with inertial sensors providing three-dimensional kinematic data sampled at 40 Hz/sensor. Twenty-two adult, male community club and university-level hookers were recruited. An equal number were analysed whilst scrummaging on natural or synthetic turf. Players scrummaging on synthetic turf demonstrated less angular velocity in the lower thoracic spine for right and left lateral bending and right rotation. The general reduction in the range of motion and velocities, extrapolated over a prolonged playing career, may mean that the synthetic turf could result in fewer degenerative injuries. It should be noted, however, that this conclusion considers only the scrummaging scenario