A three-dimensional, six-segment chain analysis of forceful overarm throwing.

A three-dimensional, six-segment model was applied to the pitching motion of three professional pitchers to analyze the kinematics and kinetics of the hips, upper trunk, humerus and forearm plus hand of both the upper limbs. Subjects were filmed at 250 frames per second. An inverse dynamics approach and angular momentum principle with respect to the proximal endpoint of a rigid segment were employed in the analysis. Results showed considerable similarities between subjects in the kinetic control of trunk rotation about the spine's longitudinal axis, but variability in the control of trunk lean both to the side and forward. The kinetics of the throwing shoulder and elbow joint were comparable between subjects, but the contribution of the non-throwing upper limb was minimal and variable. The upper trunk rotators played a key role in accelerating the ball to an early, low velocity near stride foot contact. After a brief pause they resumed acting strongly in a positive direction, though not enough to prevent trunk angular velocity slowing, as the musculature of the arm applied a load at the throwing shoulder. The interaction moment from the proximal segments assisted the forearm extensor in slowing flexion and producing rapid elbow extension near ball release. The temporal onset of muscular torques was not in a strictly successive proximal-to-distal sequence.     

A three-dimensional analysis of overarm throwing in experienced handball players

The aim of this study was to investigate the contribution of upper extremity, trunk, and lower extremity movements in overarm throwing in team handball. In total, 11 joint movements during the throw were analyzed. The analysis consists of maximal angles, angles at ball release, and maximal angular velocities of the joint movements and their timing during the throw. Only the elbow angle (extension movement range) and the level of internal rotation velocity of the shoulder at ball release showed a significant relationship with the throwing performance. Also, a significant correlation was found for the timing of the maximal pelvis angle with ball velocity, indicating that better throwers started to rotate their pelvis forward earlier during the throw. No other significant correlations were found, indicating that the role of the trunk and lower limb are of minor importance for team handball players.     

Function of otolith organ in goldfish revealed from analysis of eye movement induced by acceleration.

An otolith organ on ground behave as a detector of both gravity and linear acceleration, and play an important role in controlling posture and eye movement for tilt of the head or translational motion. On the other hand, a gravitational acceleration ingredient to an otolith organ disappears in microgravity environment. However, linear acceleration can be received by otolith organ and produce a sensation that is different from that on Earth. It is suggested that in microgravity signal from the otolith organ may cause abnormality of posture control and eye movement. Therefore, the central nervous system may re-interprets all output from the otolith organ to indicate linear motion. A study of eye movement has been done a lot as one of a reflection related to an otolith organ system. In this study, we examined function of otolith organ in goldfish revealed from analysis of eye movement induced by linear acceleration or the tilt of body. We analyzed both torsional and vertical eye movements from video images frame by frame. For tilting stimulation, torsional eye movements induced by head down was larger than that induced by head up for larger tilt angle than 30 degrees. In the case of linear acceleration below 0.4 G, however, no clear differences were observed in both torsional and vertical eye movement. These results suggest that body tilt and linear acceleration may not be with equivalent stimulation to cause eye movement on the ground.     

Kinetic analysis of megakaryopoiesis induced by recombinant human interleukin 11 in myelosuppressed mice

Recombinant human interleukin 11 (rhIL-11) has previously been shown to ameliorate thrombocytopenia in several animal models. To elucidate the mechanisms involved in rhIL-11-induced hematopoiesis, a kinetic analysis of megakaryopoiesis was performed in mitomycin C (MMC)-induced myelosuppressive mice. Mice intravenously injected with MMC (2 mg/kg) for two consecutive days from day -1 developed severe thrombocytopenia with a nadir of platelet counts at 24x10(4)/microl on day 12 and neutropenia. Treatment with rhIL-11 (500 microg/kg/day) from day 1 to 21 significantly ameliorated the degree and duration of thrombocytopenia and enhanced the platelet recovery, and also enhanced the recovery from neutropenia. In MMC-treated mice, the decreases in bone marrow megakaryocyte progenitors and megakaryocyte counts preceded the decrease in platelet counts by MMC treatment. RhIL-11 induced an increase in the number of megakaryocyte progenitors from day 4 to 14, followed by an increase in the megakaryocytes by day 20. There was a ploidy shift in megakaryocytes towards lower ploidy cells by day 9 in myelosuppressed mice. RhIL-11 caused a shift towards a higher ploidy with 32 and 64N on day 4, and 32N on day 14. These results suggest that rhIL-11 ameliorates the thrombocytopenia via the stimulation of both the maturation and commitment followed by the proliferation of megakaryocytic cells.     

Eye movements induced by linear acceleration in humans.

The otolith-function study is remarkably behind the semicanal-function study. In the present paper, we introduced briefly our on-going studies on eye movements including nystagmic elicitation during lateral (Gy) linear acceleration with step and sinusoidal modes using a sled-type accelerator. The eye movements were recorded by EOGs (DC) from subjects who looked at an imaginary target of their straight ahead in darkness during G-loading up to 0.5 G. Corresponding to the +Gy and -Gy segments, nystagmus and/or deviation in eye position were frequently induced in some subjects, but none or slightly in the other. The nystagmus changed the beating direction dependently on the Gy direction, while the eye-deviation could be either direction of compensatory or anticompensatory. In half of subjects, nystagmus elicitation was absent or low at 0.3 G, while it tended to increase above 0.3 G. The nystagmic elicitation was similar to each other between the both modes of acceleration, and directional preponderance (DP) was observed in some subjects. There was no correlation between the DP and the nystagmic slow-phase velocity. Functional meanings of these findings were discussed.     

Inflation waves induced by axial acceleration of the aorta

The phenomenon of high-amplitude inflation waves resulting from a sharp axial acceleration of the aorta, as may occur in road accidents, is investigated theoretically. The aorta is modeled as an axisymmetric tapered membranic shell (tube) made of an incompressible, nonlinear viscoelastic material with cylindrical orthotropy. It is filled with an inviscid, incompressible fluid whose flow is considered as quasi-one dimensional along the tube axis. The equations of motion of the tube and of the fluid are solved numerically, by using a two-step explicit scheme, for several axial acceleration profiles. The solutions shows that an inflation wave is generated and it propagates in opposite direction to that of the acceleration. The wall stresses, deformations and their time derivatives as well as fluid velocity and pressure are determined along the tube at different time intervals. Peak axial and circumferential stresses are high, with the latter far exceeding the former. These stresses may cause rupture of the aorta.     

Inhibition and acceleration of erythrocyte aggregation induced by small macromolecules

The aggregation (especially the 'rouleau' formation) of human erythrocytes induced by polysaccharide and polyglutamic acid was quantitatively examined by using a low-shear rheoscope combined with a television image analyzer and a computer. (1) The morphological characteristics of rouleaux induced by these macromolecules are presented. (2) Polysaccharides with high molecular weights of 70 400 and 494 000 and poly(glutamic acids) with weights of 50 000 and 66 000 formed the rouleaux (then the three-dimensional aggregates). But polysaccharides with the low molecular weights of 10 300 and 42 500 and poly(glutamic acids) with weights of 8000 and 20 000 did not. The dependences of the velocity of rouleau formation on the macromolecule concentration and on the shear rate are shown. (3) The erythrocyte aggregation induced by high-molecular-weight polysaccharides was inhibited by low-molecular-weight polysaccharides and glucose, but was not affected by low-molecular-weight poly(glutamic acids). (4) The aggregation induced by high-molecular-weight poly(glutamic acids) was inhibited by poly(glutamic acid) with a molecular weight of 8000, but was accelerated by that of 20 000. The poly(glutamic acid)-induced aggregation was not affected by low-molecular-weight polysaccharides. (5) The stereochemical structure-dependent interaction (or the mode of bridging) of macromolecules with erythrocytes was stressed for the mechanism of erythrocyte aggregation.     

Kinetic analysis of psi-DNA structure formation induced by histone H1 and its C-terminal domain

In this paper we have studied the kinetics of psi-DNA structure formation induced by H1 and H1 peptides containing the C-terminal domain, namely the CTB peptide, obtained by thrombin digestion, and the CNBS peptide, derived from N-bromosuccinimide treatment of H1. The time course for the formation of the psi structure has been followed by measuring the changes in ellipticity at 270 nm as a function of time under different experimental conditions. In all cases studied here, we have observed the existence of two elementary processes: one fast, the other slow. Kinetic experiments performed with high molecular weight DNA showed that the greater the salt concentration, the higher was the apparent rate of psi structure formation. In complexes formed with sonicated DNA and H1, CNBS and CTB, we observed that the greater the content of the C-terminal domain, the higher was the apparent rate at which the final psi structure was reached. Thus, the presence of increasing amounts of either salt or C-terminal domain facilitates the formation of the psi structure. The molecular basis for these phenomena is discussed. The influence of the order of addition of the different components of the complex on the kinetics of psi structure induction is also studied.     

Kinetic heterogeneity of an experimental tumour revealed by BrdUrd incorporation and mathematical modelling

In the present paper we propose a method of analysis of the cell kinetic characteristics of in vivo experimental tumours, that uses DNA-BrdUrd flow cytometry data at various times after the bromodeoxyuridine (BrdUrd) injection and mathematical modelling. The model of the cell population takes into account the cell-cell heterogeneity of the progression rate across cell cycle phases within the tumour, and assumes a strict correlation between the durations of S and G2M phases. The model also allows for a nonconstant DNA synthesis rate across S phase. In addition, the measurement process is modelled, considering the possibility of nonimpulsive labelling and providing a representation of the time course of the bivariate DNA-BrdUrd fluorescence distribution. Sequential DNA-BrdUrd distributions were obtained in vivo from a human ovarian carcinoma transplanted in mice and, for comparison, in vitro from a cell line of the same origin. From these data, that included the fractional density and the mean BrdUrd-fluorescence of BrdUrd-positive cells as a function of the DNA-fluorescence, kinetic parameters such as the potential doubling time (T _pot) and the mean and variance of the transit times in S and G2M phases, were estimated. This study revealed the presence of a substantial heterogeneity in S and G2M phases within the in vivo cell population and of a lower heterogeneity in the in vitro population. Moreover, our analysis suggests a nonnegligible effect of the BrdUrd pharmacokinetics in the in vivo cell labelling.     

Bh3 induced conformational changes in Bcl‐Xl revealed by crystal structure and comparative analysis

Apoptosis or programmed cell death is a regulatory process in cells in response to stimuli perturbing physiological conditions. The Bcl‐2 family of proteins plays an important role in regulating homeostasis during apoptosis. In the process, the molecular interactions among the three members of this family, the pro‐apoptotic, anti‐apoptotic and BH3‐only proteins at the mitochondrial outer membrane define the fate of a cell. Here, we report the crystal structures of the human anti‐apoptotic protein Bcl‐X_L in complex with BH3‐only BID^BH3 and BIM^BH3 peptides determined at 2.0 Å and 1.5 Å resolution, respectively. The BH3 peptides bind to the canonical hydrophobic pocket in Bcl‐X_L and adopt an alpha helical conformation in the bound form. Despite a similar structural fold, a comparison with other BH3 complexes revealed structural differences due to their sequence variations. In the Bcl‐X_L‐BID^BH3 complex we observed a large pocket, in comparison with other BH3 complexes, lined by residues from helices α1, α2, α3, and α5 located adjacent to the canonical hydrophobic pocket. These results suggest that there are differences in the mode of interactions by the BH3 peptides that may translate into functional differences in apoptotic regulation. Proteins 2015; 83:1262–1272. © 2015 Wiley Periodicals, Inc.     

Deformation of the human brain induced by mild angular head acceleration

Deformation of the human brain was measured in tagged magnetic resonance images (MRI) obtained dynamically during angular acceleration of the head. This study was undertaken to provide quantitative experimental data to illuminate the mechanics of traumatic brain injury (TBI). Mild angular acceleration was imparted to the skull of a human volunteer inside an MR scanner, using a custom MR-compatible device to constrain motion. A grid of MR "tag" lines was applied to the MR images via spatial modulation of magnetization (SPAMM) in a fast gradient echo imaging sequence. Images of the moving brain were obtained dynamically by synchronizing the imaging process with the motion of the head. Deformation of the brain was characterized quantitatively via Lagrangian strain. Consistent patterns of radial-circumferential shear strain occur in the brain, similar to those observed in models of a viscoelastic gel cylinder subjected to angular acceleration. Strain fields in the brain, however, are clearly mediated by the effects of heterogeneity, divisions between regions of the brain (such as the central fissure and central sulcus) and the brain's tethering and suspension system, including the dura mater, falx cerebri, and tentorium membranes.     

Parasite persistence in treated chagasic patients revealed by xenodiagnosis and polymerase chain reaction

Polymerase chain reaction (PCR) was compared with xenodiagnosis performed 20 years after trypanocidal chemotherapy to investigate parasite clearance. Eighty-five seropositive individuals for Chagas disease presenting a positive xenodiagnosis were treated with specific drugs; 37 in the acute phase and 48 in the chronic phase. Fifteen chronic asymptomatic patients received a placebo. Treatment in the acute phase led to PCR negative results in 73% of the cases, while xenodiagnosis was negative in 86%. In the chronic phase, PCR was negative in 65% of the patients and 83% led to xenodiagnosis negative results. Regarding the untreated group (placebo), 73% gave negative results by xenodiagnosis, of which 36% were positive by PCR. Individuals that were considered seronegative (n=10), presented unequivocally negative results in the PCR demonstrating the elimination of parasite DNA. Seventeen individuals had their antibodies titers decreased to such a level that the final results were considered as doubtful and 16 of them presented negative PCR. The molecular method represents a clear advantage over conventional techniques to demonstrate persistent infections in Chagas disease patients that underwent chemotherapy.     

The targets of 2,2',5,5'-tetrachlorobiphenyl in the respiratory chain of rat liver mitochondria revealed by modular kinetic analysis

The response of the respiratory subsystem of oxidative phosphorylation to the environmental pollutant, 2,2',5,5'-tetrachlorobiphenyl (2,2',5,5'-TCB) was investigated by modular kinetic approach. The effects of 20 M 2,2',5,5'-TCB on the activity of the respiratory chain modules in rat liver mitochondria oxidizing succinate (+ rotenone) in state 3 were assessed. The toxin inhibited the rate of respiration by 23%. Analysis around cytochrome c revealed that 2,2',5,5'-TCB inhibited both cytochrome c-oxidizing and - reducing modules. The toxin inhibited also CoQ-oxidizing module, however it did not affect the kinetics of CoQ-reducing module. Taken together, these data indicated that 2,2',5,5'-TCB inhibited cytochrome bc₁ but had no effect on succinate dehydrogenase.     

Kinetic pathway for folding of the Tetrahymena ribozyme revealed by three UV-inducible crosslinks.

The kinetics of RNA folding were examined in the L-21 ribozyme, an RNA enzyme derived from the self-splicing Tetrahymena intron. Three UV-inducible crosslinks were mapped, characterized, and used as indicators for the folded state of the ribozyme. Together these data suggest that final structures are adopted first by the P4-P6 independently folding domain and only later in a region that positions the P1 helix (including the 5' splice site), a region whose folding is linked to that of a portion of the catalytic core. At intermediate times, a non-native structure forms in the region of the triple helical scaffold, which connects the major folding domains. At 30 degrees C, the unfolded ribozyme passes through these stages with a half-life of 2 min from the time magnesium cations are provided. At higher temperatures, the half-life is shortened but the order of events is unchanged. Thermal melting of the fully folded ribozyme also revealed a multi-stage process in which the steps of folding are reversed: the kinetically slowest structure is the least stable and melts first. These structures of the ribozyme also bind Mg2+ cooperatively and their relative affinity for binding seems to be a major determinant in the order of events during folding. Na+ can also substitute for Mg2+ to give rise to the same crosslinkable structures, but only at much higher concentrations. Specific binding sites for Mg2+ may make this cation particularly efficient at electrostatic stabilization during folding of these ribozyme structures.     

Kinetic study of von Willebrand factor self-aggregation induced by ristocetin

Von Willebrand factor (VWF) is a multimeric glycoprotein present in circulating blood and in secretory granules of endothelial cells and platelets. VWF is sensitive to hydrodynamic shear stress that promotes conformational changes, rendering it able to interact with subendothelial proteins and platelets, thus promoting primary haemostasis. Likewise, the binding of the glycopeptide antibiotic ristocetin to VWF triggers hemostatically relevant conformational transitions. These changes reveal both the interaction site for platelet receptor GpIbα and the Tyr1605-Met1606 peptide bond, which is cleaved by the regulatory metalloprotease ADAMTS-13. In this study we investigated by a combined approach of light scattering spectroscopy and turbidimetry the ability of VWF to self-associate in solution in the presence of ristocetin and in the absence of any protein adsorbing surface. Micro- and macro-aggregates induced by ristocetin, have been characterized under static conditions in the early stage of formation and on a longer time scale (up to 10 h). These findings show that VWF multimers form supramolecular structures favoring platelet trapping not only under high shear stress or interaction with external surfaces, but also in solution under static conditions when the conformational state of the protein is changed only by chemical potential of allosteric effectors.