Oxidative protein folding in the mitochondrial intermembrane space

Disulfide bond formation is a crucial step for oxidative folding and necessary for the acquisition of a protein's native conformation. Introduction of disulfide bonds is catalyzed in specialized subcellular compartments and requires the coordinated action of specific enzymes. The intermembrane space of mitochondria has recently been found to harbor a dedicated machinery that promotes the oxidative folding of substrate proteins by shuttling disulfide bonds. The newly identified oxidative pathway consists of the redox-regulated receptor Mia40 and the sulfhydryl oxidase Erv1. Proteins destined to the intermembrane space are trapped by a disulfide relay mechanism that involves an electron cascade from the incoming substrate to Mia40, then on to Erv1, and finally to molecular oxygen via cytochrome c. This thiol–disulfide exchange mechanism is essential for the import and for maintaining the structural stability of the incoming precursors. In this review we describe the mechanistic parameters that define the interaction and oxidation of the substrate proteins in light of the recent publications in the mitochondrial oxidative folding field

More On The Connection Between Planar Field Theory And String Theory

We continue work on the connection between world sheet representation of the planar phi^3 theory and string formation. The present article, like the earlier work, is based on the existence of a solitonic solution on the world sheet, and on the zero mode fluctuations around this solution. The main advance made in this paper is the removal of the cutoff and the transition to the continuum limit on the world sheet. The result is an action for the modes whose energies remain finite in this limit (light modes). The expansion of this action about a dense background of graphs on the world sheet leads to the formation of a string.Comment: 27 pages, 3 figure

Field Theory On The World Sheet: Improvements And Generalizations

This article is the continuation of a project of investigating planar phi^3 model in various dimensions. The idea is to reformulate them on the world sheet, and then to apply the classical (meanfield) approximation, with two goals: To show that the ground state of the model is a solitonic configuration on the world sheet, and the quantum fluctuations around the soliton lead to the formation of a transverse string. After a review of some of the earlier work, we introduce and discuss several generalizations and new results. In 1+2 dimensions, a rigorous upper bound on the solitonic energy is established. A phi^4 interaction is added to stabilize the original phi^3 model. In 1+3 and 1+5 dimensions, an improved treatment of the ultraviolet divergences is given. And significantly, we show that our approximation scheme can be imbedded into a systematic strong coupling expansion. Finally, the spectrum of quantum fluctuations around the soliton confirms earlier results: In 1+2 and 1+3 dimensions, a transverse string is formed on the world sheet.Comment: 29 pages, 5 figures, several typos and eqs.(74) and (75) are corrected, a comment added to section

Case study of a female ocean racer: prerace preparation and nutritional intake during the Vendee Globe 2008.

The Vendée Globe is a solo round-the-world sailing race without stopovers or assistance, a physically demanding challenge for which appropriate nutrition should maintain energy balance and ensure optimum performance. This is an account of prerace nutritional preparation with a professional and experienced female racer and assessment of daily nutritional intake (NI) during the race using a multimethod approach. A daily energy intake (EI) of 15.1 MJ/day was recommended for the race and negotiated down by the racer to 12.7 MJ/day, with carbohydrate and fluid intake goals of 480 g/day and 3,020 ml/day, respectively. Throughout the 99-day voyage, daily NI was recorded using electronic food diaries and inventories piloted during training races. NI was assessed and a postrace interview and questionnaire were used to evaluate the intervention. Fat mass (FM) and fat-free mass (FFM) were assessed pre- (37 days) and postrace (11 days) using dual-energy X-ray absorptiometry, and body mass was measured before the racer stepped on the yacht and immediately postrace. Mean EI was 9.2 MJ/day (2.4-14.3 MJ/day), representing a negative energy balance of 3.5 MJ/day under the negotiated EI goal, evidenced by a 7.9-kg loss of body mass (FM -7.5 kg, FFM -0.4 kg) during the voyage, with consequent underconsumption of carbohydrate by ~130 g/day. According to the postrace yacht food inventory, self-reported EI was underreported by 7%. This intervention demonstrates the practicality of the NI approach and assessment, but the racer's nutrition strategy can be further improved to facilitate meeting more optimal NI goals for performance and health. It also shows that evaluation of NI is possible in this environment over prolonged periods, which can provide important information for optimizing nutritional strategies for ocean racing

3D Depthwise Convolution: Reducing Model Parameters in 3D Vision Tasks

Standard 3D convolution operations require much larger amounts of memory and computation cost than 2D convolution operations. The fact has hindered the development of deep neural nets in many 3D vision tasks. In this paper, we investigate the possibility of applying depthwise separable convolutions in 3D scenario and introduce the use of 3D depthwise convolution. A 3D depthwise convolution splits a single standard 3D convolution into two separate steps, which would drastically reduce the number of parameters in 3D convolutions with more than one order of magnitude. We experiment with 3D depthwise convolution on popular CNN architectures and also compare it with a similar structure called pseudo-3D convolution. The results demonstrate that, with 3D depthwise convolutions, 3D vision tasks like classification and reconstruction can be carried out with more light-weighted neural networks while still delivering comparable performances.Comment: Work in progres

The Creation and Validation of a Large-Scale Computer Model of the Golf Swing

The aim of this study was to create and validate a full-body musculoskeletal model of a golfer performing a swing with their driver club. An elite female participant performed ten shots with her driver while wearing retro-reflective markers. An optical 3-D 6-camera system captured the kinematics of the markers at 400 Hz on the participant for each trial. A launch monitor device recorded the ball and club head conditions at impact. The kinematic data from one representative trial was selected to drive inverse and forward dynamics simulations of the created model. The validation results showed a very high level of agreement between experimental and simulated trajectories for selected markers (mean r = 0.966

The Effect of the Application of Different Levels of Movement Variability on Movement Outcome

The aim of this study was to assess the effect of the application of a previously validated golfer computer model on different levels of movement variability relative to a shot outcome measure: club head velocity. Movement variability was applied to the computer model on six measures sequentially throughout the body of the computer model. Four different levels of variability, 25%, 50%, 75% and 100% variability, were applied to x, y and z positional data of the aforementioned measures. Simulations were then performed with ADAMS/LifeMOD software for each level of movement variability applied to the measures in question. Club head velocity was measured during the simulation. The results suggest that movement variability application at these landmarks does not have an effect on outcome. These results potentially have implications for the coaching of the participant

Numerical Simulations of Dynamos Generated in Spherical Couette Flows

We numerically investigate the efficiency of a spherical Couette flow at generating a self-sustained magnetic field. No dynamo action occurs for axisymmetric flow while we always found a dynamo when non-axisymmetric hydrodynamical instabilities are excited. Without rotation of the outer sphere, typical critical magnetic Reynolds numbers $Rm_c$ are of the order of a few thousands. They increase as the mechanical forcing imposed by the inner core on the flow increases (Reynolds number $Re$). Namely, no dynamo is found if the magnetic Prandtl number $Pm=Rm/Re$ is less than a critical value $Pm_c\sim 1$. Oscillating quadrupolar dynamos are present in the vicinity of the dynamo onset. Saturated magnetic fields obtained in supercritical regimes (either $Re>2 Re_c$ or $Pm>2Pm_c$) correspond to the equipartition between magnetic and kinetic energies. A global rotation of the system (Ekman numbers $E=10^{-3}, 10^{-4}$) yields to a slight decrease (factor 2) of the critical magnetic Prandtl number, but we find a peculiar regime where dynamo action may be obtained for relatively low magnetic Reynolds numbers ($Rm_c\sim 300$). In this dynamical regime (Rossby number $Ro\sim -1$, spheres in opposite direction) at a moderate Ekman number ($E=10^{-3}$), a enhanced shear layer around the inner core might explain the decrease of the dynamo threshold. For lower $E$ ($E=10^{-4}$) this internal shear layer becomes unstable, leading to small scales fluctuations, and the favorable dynamo regime is lost. We also model the effect of ferromagnetic boundary conditions. Their presence have only a small impact on the dynamo onset but clearly enhance the saturated magnetic field in the ferromagnetic parts. Implications for experimental studies are discussed

Duration of shedding of respiratory syncytial virus in a community study of Kenyan children

Background: Our understanding of the transmission dynamics of respiratory syncytial virus (RSV) infection will be better informed with improved data on the patterns of shedding in cases not limited only to hospital admissions. Methods: In a household study, children testing RSV positive by direct immunofluorescent antibody test (DFA) were enrolled. Nasal washings were scheduled right away, then every three days until day 14, every 7 days until day 28 and every 2 weeks until a maximum of 16 weeks, or until the first DFA negative RSV specimen. The relationship between host factors, illness severity and viral shedding was investigated using Cox regression methods. Results: From 151 families a total of 193 children were enrolled with a median age of 21 months (range 1-164 months), 10% infants and 46% male. The rate of recovery from infection was 0.22/person/day (95% CI 0.19-0.25) equivalent to a mean duration of shedding of 4.5 days (95%CI 4.0-5.3), with a median duration of shedding of 4 days (IQR 2-6, range 1-14). Children with a history of RSV infection had a 40% increased rate of recovery i.e. shorter duration of viral shedding (hazard ratio 1.4, 95% CI 1.01-1.86). The rate of cessation of shedding did not differ significantly between males and females, by severity of infection or by age. Conclusion: We provide evidence of a relationship between the duration of shedding and history of infection, which may have a bearing on the relative role of primary versus re-infections in RSV transmission in the community

Extracellular ATP inhibits twitching motility-mediated biofilm expansion by Pseudomonas aeruginosa

© 2015 Nolan et al.; licensee BioMed Central. Background: Pseudomonas aeruginosa is an opportunistic pathogen that exploits damaged epithelia to cause infection. Type IV pili (tfp) are polarly located filamentous structures which are the major adhesins for attachment of P. aeruginosa to epithelial cells. The extension and retraction of tfp powers a mode of surface translocation termed twitching motility that is involved in biofilm development and also mediates the active expansion of biofilms across surfaces. Extracellular adenosine triphosphate (eATP) is a key "danger" signalling molecule that is released by damaged epithelial cells to alert the immune system to the potential presence of pathogens. As P. aeruginosa has a propensity for infecting damaged epithelial tissues we have explored the influence of eATP on tfp biogenesis and twitching motility-mediated biofilm expansion by P. aeruginosa. Results: In this study we have found that eATP inhibits P. aeruginosa twitching motility-mediated expansion of interstitial biofilms at levels that are not inhibitory to growth. We have determined that eATP does not inhibit expression of the tfp major subunit, PilA, but reduces the levels of surface assembled tfp. We have also determined that the active twitching zone of expanding P. aeruginosa interstitial biofilms contain large quantities of eATP which may serve as a signalling molecule to co-ordinate cell movements in the expanding biofilm. The inhibition of twitching motility-mediated interstitial biofilm expansion requires eATP hydrolysis and does not appear to be mediated by the Chp chemosensory system. Conclusions: Endogenous eATP produced by P. aeruginosa serves as a signalling molecule to co-ordinate complex multicellular behaviours of this pathogen. Given the propensity for P. aeruginosa to infect damaged epithelial tissues, our observations suggest that eATP released by damaged cells may provide a cue to reduce twitching motility of P. aeruginosa in order to establish infection at the site of damage. Furthermore, eATP produced by P. aeruginosa biofilms and by damaged epithelial cells may play a role in P. aeruginosa pathogenesis by inducing inflammatory damage and fibrosis. Our findings have significant implications in the development and pathogenesis of P. aeruginosa biofilm infections