Heat-induced hyperventilation causes hypocapnia (reduced arterial CO2 pressure), which increases cerebral vascular tone and reduces cerebral blood flow (CBF). Hyperthermia also causes hypohydration, which can further elevate ventilation. However, no studies have examined the dose-response relation of hyperthermia and CBF, irrespective of hydration status. This study tested two hypotheses: 1. that a core temperature threshold exists above which hyperventilation occurs, resulting in hypocapnia and compromised CBF and cerebral oxygenation; and 2. hypohydration exacerbates hyperthermic-induced hyperventilation and related hypocapnia, further decreasing CBF.

Ten males, lying supine in a water-perfused suit, underwent normothermic and progressive hyperthermia trials, while euhydrated (EUH) and while hypohydrated by 1.5 - 2.0% body mass (HYPO; attained previous evening). Cerebral artery blood velocity (MCAv; transcranial Doppler ultrasound), cerebral oxygenation (Near-infrared spectroscopy), heart rate (HR; electrocardiography), mean arterial blood pressure (MAP; finometer) and partial pressure of end-tidal carbon dioxide (PETCO2) were measured continuously at baseline and at 0.5°C increments in core (oesophageal) temperature to +2°C.

In HYPO, baseline MCAv and HR were elevated (P < 0.05 vs EUH). Compared with baseline (P < 0.05; pooled by hydration; repeated measures ANOVA), heating reduced PETCO2 [-5 ± 1 mmHg at 1°C; -16 ± 4 mmHg at 2°C] and MCAv [-15 ± 3% (1°C); -32 ± 5% (2°C)], with hydration status having no effect on these variables (P > 0.05). MAP was reduced at +1°C, especially in EUH (-19 ± 10 mmHg EUH, -10 ± 8 mmHg HYPO, P < 0.05). Reductions in MCAv with rising core temperature were related to level of hypocapnia (r = 0.95 EUH, 0.97 HYPO, P < 0.05). Cerebral oxygenation was unchanged with heating (P > 0.05).

These results indicate that a core temperature threshold exists, above which hyperthermic-induced hypocapnia and hydration-dependent hypotension occurs. Despite reduced MCAv, cerebral oxygenation is maintained, presumably via greater O2-extraction.

Forward head posture has been identified as a risk factor for neck pain with some evidence to show that simple ergonomic correction may reduce its incidence. The effect of using a lumbar roll on cervical spine posture has not been previously investigated experimentally, but rather assumed to have positive influence on the basis of clinical views. The purpose of this study was to investigate the possible influence of positional adjustments to the standard office chair and use of lumbar support with a McKenzie lumbar roll on the resting head and neck posture in the sagittal plane, as defined by the craniovertebral (CV) angle.

Thirty healthy male participants aged between 18-30 years were photographed whilst registered in the natural head resting position in four different sitting positions, with and without a McKenzie lumbar roll. The CV angles were measured using the NIH ImageJ software taken from digitized photographs of the eight postural registrations for each participant. Comparisons between all positions were analysed using a linear mixed model and adjusted for multiple comparisons. It was found that the most significant effect on the head and neck position with the lumbar roll in situ was in the backrest 110˚ position (difference = 2.32°, P < 0.001). A more forward head and neck posture was correlated with higher body mass index (P < 0.005).

Despite the clinical impression that use of a lumbar roll in sitting promotes a more retracted head position, this may not necessarily be the case, at least in young healthy males. Rather, the backrest position of the chair may be the more important factor influencing sagittal alignment of head and neck posture. These results highlight to the physiotherapist the need for consideration of the inherent chair adjustments before utilising ancillary lumbar support when providing postural advice.

Bicarbonate (HCO3-) secretion occurs throughout the human body. The cellular mechanism by which this secretion occurs is still contentious. One proposed model of secretion involves HCO3- entering the cell across the basolateral membrane via a NaHCO3 co-transporter and being secreted across the apical membrane via the cystic fibrosis transmembrane conductance regulator (CFTR), a recognised chloride channel. In this study CFTR from possum intestine which only secretes HCO3- has been utilised to investigate the possibility that CFTR can function as a HCO3- channel.

Fischer rat thyroid (FRT) cells previously transfected with possum CFTR (pCFTR) were cultured and used in whole-cell patch clamping. Cells were clamped between -100 and +100 mV in 20 mV steps and the current was recorded. Initially it was investigated whether pCFTR had the same functional properties as CFTR from other species. pCFTR was found to be similar to other species. A chloride current was stimulated following an increase in intracellular cAMP (Icl-80mV before = 27 ± 8, mean ± SEM; Icl-80mV after = 1558 ± 474; n = 5). This current was time- and voltage-independent, and inhibited by CFTR inhibitor-172 (1 µM) (Icl-80mV before = 587 ± 194; Icl-80mV after = 29 ± 4; n = 4). Subsequently it was shown that pCFTR is permeable to HCO3- (PCl:PHCO3 = ~0.25). However, HCO3- also caused a time-dependent inhibition (Icl-80mV before = 403 ± 148, IHCO3-80mV after = 152 ± 96; n = 4), an effect that was irreversible.

These results show that pCFTR has a significant but low HCO3- permeability. This low permeability of pCFTR, combined with the fact that it is inhibited by HCO3-, suggests that it may not have the properties to function as a HCO3- channel in secretory epithelia. However, for this to be confirmed experiments on native tissue need to be conducted.

Agmatine, the metabolite of L-arginine, is a novel neurotransmitter. It binds to α-adrenergic and imidazoline receptors, blocks N-methyl-D-aspartate receptors and regulates production of nitric oxide and the polyamine putrescine. Several previous studies have investigated the effects of agmatine administered systemically on learning and memory and the overall findings are controversial. The present study investigates the effects of intracerebroventricular microinfusion of agmatine on spatial learning and memory using the radial arm maze task.

Adult male Sprague-Dawley rats anaesthetised with halothane were implanted with a cannula into the lateral ventricle. Behavioural testing was begun 10 days post-surgery. Agmatine (10 μg in 5μl, n = 9) or saline (5μl, n = 9) was infused into the lateral ventricle over 2 min. The rats were tested 7 min after completion of the treatment. In the standard version of the task, the agmatine-treated group made significantly less errors over 5 days of training compared to the saline control group (agmatine: 8.8 ± 1.0, saline: 15.7 ± 2.8, mean ± SEM, P < 0.05, unpaired t-test) with no significant difference between the two groups in the number of adjacent arm entries. By contrast, in the reference memory version of the task there was no significant difference between the agmatine and saline groups in the number of trials to reach the criterion or the number of errors made across the first 5 days of training.

The present study, for the first time, demonstrates the facilitating effect of agmatine on the spatial working memory, but not the reference memory, version of the radial arm maze task. These results suggest that agmatine may have an important role in modulating learning and memory in a task-dependent manner.

The 70 kDa heat-shock proteins (Hsp70s) are ubiquitous molecular chaperones that function primarily to assist protein folding by binding to non-native protein states. They also have additional diverse roles such as uncoating of clathrin-coated pits in synaptic vesicle fusion. These functions depend on the ability to bind and release hydrophobic peptides in an ATP-dependent manner. DnaK is the Escherichia coli Hsp70 homologue, and like all Hsp70 proteins DnaK consists of an ATPase domain and a peptide-binding domain. Two-way allosteric communication between domains is essential to Hsp70 function, and involves a global ATP-induced conformational change. The aim of this research was to derive a structural model for the conformational change and domain arrangement of DnaK in both ATP-bound and nucleotide-free states, using fluorescence resonance energy transfer (FRET) and small-angle X-ray scattering (SAXS).

SAXS analysis showed that DnaK undergoes a dramatic compaction on ATP binding, from a radius of gyration of 37 Å to 28 Å, and also demonstrated that the two domains of DnaK do not interact in the nucleotide-free form. FRET analysis showed that in ATP-bound DnaK the distances from residue 102 of the ATPase domain to residues 413, 449 and 517 of the peptide-binding domain were 29 ± 4 Å, 25 ± 5 Å and 21 ± 3 Å respectively, while in nucleotide-free DnaK residue 449 was 30 ± 4 Å from residue 102, and other residues were too distant to measure. Using results from both methods, a model was developed for the arrangement of the ATPase and peptide-binding domains in ATP-bound DnaK. These results, supported by information from previous studies, suggest a mechanism of interdomain communication where the two domains do not interact in the absence of ATP, and come together when ATP binds to mutually affect each other’s activity via a specific interface.

Virus-like particles (VLPs) are highly immunogenic inert shells formed when viral capsid proteins self-assemble into particulate structures. They can be used as carriers for vaccine antigens. The present study investigates the ability of rabbit haemorrhagic disease virus (RHDV) VLPs to activate human monocyte-derived dendritic cells (MoDC), which are necessary to initiate an immune response. Since RHDV does not infect humans, there is no destructive pre-existing immunity to these VLPs.

RHDV VLPs were prepared using a recombinant baculovirus expression system and their integrity was demonstrated by transmission electron microscopy. When human MoDC were pulsed with varying concentrations of native RHDV VLPs for 24 h, they did not up-regulate cell surface activation markers including major histocompatibilty complex (MHC) class II, CD80 and CD83. However, addition of an adjuvant polyriboinosinic:polyribocyidylic acid (Poly(I:C)) to the VLPs induced MoDC to up-regulate the characteristic MoDC activation marker, CD83 (52 ± 6%, mean ± SEM, n = 8, P < 0.005; paired t-test compared with the negative untreated control cells 14 ± 5%, n = 8). MoDC from a range of genetically different donors activated by this combination were shown to produce significantly more interleukin (IL)-12, a cell-mediated immunity driving cytokine, intracellularly (69 ± 8%, n = 5, P < 0.01) compared to the MoDC treated with either Poly(I:C) (34 ± 9%, n = 5) or RHDV VLPs (27 ± 6%, n = 5) alone. Significant levels of IL-12 were also found in the supernatants of these activated MoDC (229 ± 45 ng/ml, n = 5) compared to negative controls (0 ng/ml).

Since IL-12 induction is essential for a vaccine to protect against intracellular infections and tumours, this work suggests that RHDV VLPs co-delivered with a ‘danger signal’ by way of Poly(I:C) adjuvant may provide effective vehicles to enhance human immunity to such antigens.