An Ising-Like model for protein mechanical unfolding

The mechanical unfolding of proteins is investigated by extending the Wako-Saito-Munoz-Eaton model, a simplified protein model with binary degrees of freedom, which has proved successful in describing the kinetics of protein folding. Such a model is generalized by including the effect of an external force, and its thermodynamics turns out to be exactly solvable. We consider two molecules, the 27th immunoglobulin domain of titin and protein PIN1. In the case of titin we determine equilibrium force-extension curves and study nonequilibrium phenomena in the frameworks of dynamic loading and force clamp protocols, verifying theoretical laws and finding the position of the kinetic barrier which hinders the unfolding of the molecule. The PIN1 molecule is used to check the possibility of computing the free energy landscape as a function of the molecule length by means of an extended form of the Jarzynski equality.Comment: 4 pages + appendi

Immunogenicity and effectiveness of virosomal adjuvanted vaccines against influenza: a brief review of their utility in the elderly population

The World Health Organisation (WHO) estimates that seasonal influenza affects approximately 5-15% of the population on an annual basis and these outbreaks are responsible for significant morbidity and mortality resulting in increased hospital admissions. Annual vaccination remains the main public health strategy for containing influenza. Inactivated influenza vaccines offer a great deal of protection against influenza but these vaccines are not optimal for older adults due to their waning immunity and other factors affecting immunogenicity. Virosomes, stimulate the immune system in a similar way as a natural infection and studies have shown that the virosomal adjuvanted influenza vaccine is immunogenic and safe in different population groups including: the elderly, children and immunocompromised subjects. Currently available data suggest improved immunogenicity of the virosomal adjuvanted vaccine in the elderly and in subjects without protective antibody as compared to conventional vaccines

Traditional vs non-motorized curve treadmill: differences in energetic requirements

Previous studies suggest that exercise performed on curve surface treadmill (CT) can increase energy expenditure more than exercise performed on a traditional motorized treadmill (MT). However, to date, there are no data about energy cost that confirm this hypothesis. Thus, the purpose of the study is to analyze the physiological requirements of walking and running on a CT as compared to a traditional MT. 26 subjects (11M + 15W) (24.1±3.4yy; 64.7±11.2kg; 171.1±8.6cm) performed preferred walking speed test and running ramp test to exhaustion on both treadmill in two separated sessions. The gross energy cost of walking (Cw) is greater (p<.05) in CT than in MT (3.79±0.35 j/m/kg, 2.43±0.38 j/m/kg, respectively). The gross energy cost of running (Cr) is greater (p<.05) in CT than in MT (5.05±1.67 j/m/kg, 4.09±0.70 j/m/kg, respectively). Moreover, MT allows to reach higher speeds than CT (MT:15.5±1.7 km/h, CT:13.9±1.4 km/h, p<.05) with lower peak blood lactate concentrations (MT: 8.98±2.43 mmol/L, CT: 10.75±2.76 mmol/L, p<.05). Our data confirm that i) the Cw, matched for speed, is greater in CT than MT; ii) the Cr, analyzed during incremental ramp test, is greater in CT than MT; iii) during the ramp test, for the same metabolic load, the mechanical load is lower in the CT compared to MT. The increased physical effort is due to the greater frictional characteristics and force generation requirements inherent with the use of a CT

Benefits of 8 weeks of High Intensity Training in healthy women: the Trion project

Aim High-intensity training (HIT) has recently been shown to be a suitable alternative time-saving strategy to improve athletic performance, cardiovascular fitness and muscle metabolism1. Nevertheless, women have rarely participated in studies investigating the efficacy of HIT2. Therefore, the aim of this study was to evaluate in moderately active women the effectiveness of an HIT intervention performed on a new device called Trion. Methods Before and after 8 weeks of HIT (3 time/week, 7reps x 30sec all-out interspersed with 2 min of active rest), in 35 healthy women volunteers (22.5±3.7 yy; BMI: 21.2±2.6), we measured maximal oxygen uptake (V’O2max), ventilatory threshold (VT), anaerobic performance, muscle structure, body composition, hematochemical (CHOLtot) and blood pressure profile at rest. The HIT workout was performed running on non-motorized curve treadmill and cycling on an competition bike mounted on an electromagnetic roller. Results Absolute and relative V’O2max significantly increased by 10% (p<.05); maximal power and power@VT increased by 7.2% and 6.3 % (p<.05), respectively; peak anaerobic performance significantly increased by 10% (p<.05). Large significant differences (p<.05) were identified for vastus lateralis thickness and pennation angle, +4.9% and +10.1%, respectively. Fat mass and CHOLtot decreased by 3.9% and 5.7% (p<.05), respectively. Conclusions Our results confirm the feasibility and effectiveness of HIT to improve exercise performance and health related parameters: HIT performed on Trion device was absolutely safe and well tolerated by the subjects. As confirmed in previous studies, our findings shows that exercise intensity, rather than duration, is the key factor in determining functional benefits. References 1Weston M, Effects of Low-Volume High-Intensity-Interval-Training (HIT) on Fitness in Adults: A Meta-Analysis of Controlled and Non-Controlled Trials Sports Med. 2014; 44(7): 1005–1017. 2Batacan, RB Jr. Effects of high-intensity-interval-training on cardiometabolic health: a systematic review and meta-analysis of intervention studies. Br J Sports Med. 2017 Mar;51(6):494-503

Anatomically asymmetrical runners move more asymmetrically at the same metabolic cost.

We hypothesized that, as occurring in cars, body structural asymmetries could generate asymmetry in the kinematics/dynamics of locomotion, ending up in a higher metabolic cost of transport, i.e. more 'fuel' needed to travel a given distance. Previous studies found the asymmetries in horses' body negatively correlated with galloping performance. In this investigation, we analyzed anatomical differences between the left and right lower limbs as a whole by performing 3D cross-correlation of Magnetic Resonance Images of 19 male runners, clustered as Untrained Runners, Occasional Runners and Skilled Runners. Running kinematics of their body centre of mass were obtained from the body segments coordinates measured by a 3D motion capture system at incremental running velocities on a treadmill. A recent mathematical procedure quantified the asymmetry of the body centre of mass trajectory between the left and right steps. During the same sessions, runners' metabolic consumption was measured and the cost of transport was calculated. No correlations were found between anatomical/kinematic variables and the metabolic cost of transport, regardless of the training experience. However, anatomical symmetry significant correlated to the kinematic symmetry, and the most trained subjects showed the highest level of kinematic symmetry during running. Results suggest that despite the significant effects of anatomical asymmetry on kinematics, either those changes are too small to affect economy or some plastic compensation in the locomotor system mitigates the hypothesized change in energy expenditure of running

Anatomically asymmetrical runners move more asymmetrically at the same metabolic cost

We hypothesized that, as occurring in cars, body structural asymmetries could generate asymmetry in the kinematics/dynamics of locomotion, ending up in a higher metabolic cost of transport, i.e. more 'fuel' needed to travel a given distance. Previous studies found the asymmetries in horses' body negatively correlated with galloping performance. In this investigation, we analyzed anatomical differences between the left and right lower limbs as a whole by performing 3D cross-correlation of Magnetic Resonance Images of 19 male runners, clustered as Untrained Runners, Occasional Runners and Skilled Runners. Running kinematics of their body centre of mass were obtained from the body segments coordinates measured by a 3D motion capture system at incremental running velocities on a treadmill. A recent mathematical procedure quantified the asymmetry of the body centre of mass trajectory between the left and right steps. During the same sessions, runners' metabolic consumption was measured and the cost of transport was calculated. No correlations were found between anatomical/kinematic variables and the metabolic cost of transport, regardless of the training experience. However, anatomical symmetry significant correlated to the kinematic symmetry, and the most trained subjects showed the highest level of kinematic symmetry during running. Results suggest that despite the significant effects of anatomical asymmetry on kinematics, either those changes are too small to affect economy or some plastic compensation in the locomotor system mitigates the hypothesized change in energy expenditure of running

Axonal Odorant Receptors Mediate Axon Targeting

In mammals, odorant receptors not only detect odors but also define the target in the olfactory bulb, where sensory neurons project to give rise to the sensory map. The odorant receptor is expressed at the cilia, where it binds odorants, and at the axon terminal. The mechanism of activation and function of the odorant receptor at the axon terminal is, however, still unknown. Here, we identify phosphatidylethanolamine- binding protein 1 as a putative ligand that activates the odorant receptor at the axon terminal and affects the turning behavior of sensory axons.Genetic ablation of phosphatidylethanolamine-binding protein 1 in mice results in a strongly disturbed olfactory sensory map. Our data suggest that the odorant receptor at the axon terminal of olfactory neurons acts as an axon guidance cue that responds to molecules originating in the olfactory bulb. The dual function of the odorant receptor links specificity of odor perception and axon targeting

Hepatitis B immunity in teenagers vaccinated as infants: an Italian 17-year follow-up study

AbstractWe assessed the persistence of hepatitis B surface antigen antibody (anti-HBs) and immune memory in a cohort of 571 teenagers vaccinated against hepatitis B as infants, 17 years earlier. Vaccinees were followed-up in 2003 and in 2010 (i.e. 10 years and 17 years after primary vaccination, respectively). When tested in 2003, 199 vaccinees (group A) had anti-HBs <10 mIU/mL and were boosted, 372 (group B) were not boosted because they had anti-HBs ≥10 mIU/mL (n = 344) or refused booster (n = 28) despite anti-HBs <10 mIU/mL. In 2010, 72.9% (416/571) of participants had anti-HBs ≥10 mIU/mL (67.3% in group A vs. 75.8% in group B; p 0.03). The geometric mean concentrations (GMCs) were similar in both groups. Between 2003 and 2010, anti-HBs concentrations in previously boosted individuals markedly declined with GMC dropping from 486 to 27.7 mIU/mL (p <0.001). Fifteen vaccinees showed a marked increase of antibody, possibly due to natural booster. In 2010, 96 individuals (37 of group A and 59 of group B) with anti-HBs <10 mIU/mL were boosted; all vaccinees of the former group and all but two of the latter had an anamnestic response. Post-booster GMC was higher in group B (895.6 vs. 492.2 mIU/mL; p 0.039). This finding shows that the immune memory for HBsAg persists beyond the time at which anti-HBs disappears, conferring long-term protection

Resolving fluorescent species by their brightness and diffusion using correlated photon-counting histograms

Fluorescence fluctuation spectroscopy (FFS) refers to techniques that analyze fluctuations in the fluorescence emitted by fluorophores diffusing in a small volume and can be used to distinguish between populations of molecules that exhibit differences in brightness or diffusion. For example, fluorescence correlation spectroscopy (FCS) resolves species through their diffusion by analyzing correlations in the fluorescence over time; photon counting histograms (PCH) and related methods based on moment analysis resolve species through their brightness by analyzing fluctuations in the photon counts. Here we introduce correlated photon counting histograms (cPCH), which uses both types of information to simultaneously resolve fluorescent species by their brightness and diffusion. We define the cPCH distribution by the probability to detect both a particular number of photons at the current time and another number at a later time. FCS and moment analysis are special cases of the moments of the cPCH distribution, and PCH is obtained by summing over the photon counts in either channel. cPCH is inherently a dual channel technique, and the expressions we develop apply to the dual colour case. Using simulations, we demonstrate that two species differing in both their diffusion and brightness can be better resolved with cPCH than with either FCS or PCH. Further, we show that cPCH can be extended both to longer dwell times to improve the signal-to-noise and to the analysis of images. By better exploiting the information available in fluorescence fluctuation spectroscopy, cPCH will be an enabling methodology for quantitative biology