How to build a molecular shock absorber

Newly determined structures of the alpha-helical repeats that make up the key 'rod' domains of spectrin and alpha-actinin - which serve as spacers between their actin-binding domains - have provided important insights into how these proteins function as molecular shock absorbers in cells.     

The slug foot as a site of uptake of copper molluscicide

Copper has been demonstrated in the feet of slugs exposed to the molluscicide copper sulfate. Using the scanning electron microscope coupled with X-ray microanalysis, copper was localized to the epithelium of the foot. Under the transmission electron microscope the subcellular distribution of copper was obtained by precipitating the molluscicide with potassium ferrocyanide. The reaction product was both electron opaque and insoluble in the preparative media. The precipitate was localized in the zonula adhaerens and septate junctions between adjacent epithelial cells. Reaction product was also present in some of the pinocytotic vesicles of the epithelial cells. The identity of the reaction product was confirmed using X-ray microanalysis.     

The series elastic shock absorber: tendon elasticity modulates energy dissipation by muscle during burst deceleration

During downhill running, manoeuvring, negotiation of obstacles and landings from a jump, mechanical energy is dissipated via active lengthening of limb muscles. Tendon compliance provides a ‘shock-absorber’ mechanism that rapidly absorbs mechanical energy and releases it more slowly as the recoil of the tendon does work to stretch muscle fascicles. By lowering the rate of muscular energy dissipation, tendon compliance likely reduces the risk of muscle injury that can result from rapid and forceful muscle lengthening. Here, we examine how muscle–tendon mechanics are modulated in response to changes in demand for energy dissipation. We measured lateral gastrocnemius (LG) muscle activity, force and fascicle length, as well as leg joint kinematics and ground-reaction force, as turkeys performed drop-landings from three heights (0.5–1.5 m centre-of-mass elevation). Negative work by the LG muscle–tendon unit during landing increased with drop height, mainly owing to greater muscle recruitment and force as drop height increased. Although muscle strain did not increase with landing height, ankle flexion increased owing to increased tendon strain at higher muscle forces. Measurements of the length–tension relationship of the muscle indicated that the muscle reached peak force at shorter and likely safer operating lengths as drop height increased. Our results indicate that tendon compliance is important to the modulation of energy dissipation by active muscle with changes in demand and may provide a mechanism for rapid adjustment of function during deceleration tasks of unpredictable intensity.     

Potentiation of foot shock analgesia by thyrotropin releasing hormone

Thyrotropin releasing hormone (TRH) interacts with both opioid and non-opioid systems in mediating hypothermic, hypoactive, cataleptic, respiratory and analgesic effects. While TRH neither antagonizes opioid analgesia nor alters pain thresholds itself, it blocks neurotensin analgesia. Different forms of pain-inhibition in rats can be activated by selectively altering the parameters of shock: while analgesia induced by 20 inescapable tail-shocks is not reversed by naltrexone, exposure to 60 or 80 shocks does elicit naltrexone-reversible analgesia. The first experiment examined whether intracerebroventricular administration of TRH (0, 10, or 50 micrograms) would alter the elevations in tail-flick latencies in rats induced by 20 or 80 foot shocks and found that TRH significantly lengthened the duration and magnitude of analgesia induced by 20 and 80 foot shocks in a dose-dependent manner. The second experiment extended these findings to the writhing test, a visceral pain test. While the number and duration of writhes of vehicle-treated rats exposed to 80 foot shocks failed to differ from baseline values. TRH (50 micrograms)-treated rats exposed to 80 foot shocks displayed significant decreases in the number and duration of writhes. The third experiment indicated that the differential effects of naltrexone upon analgesia induced by 20 or 80 tail shocks were not apparent when foot shocks were employed, precluding a definitive statement that TRH may be involved in the modulation of both opioid and non-opioid forms of analgesia.     

Biomechanical efficiency of wrist guards as a shock isolator

Despite the use of wrist guards during skate- and snowboard activities, fractures still occur at the wrist or at further proximal locations of the forearm. The main objectives of this study were to conduct a human subject testing under simulated falling conditions for measurement of the impact force on the hand, to model wrist guards as a shock isolator, to construct a linear mass-spring-damper model for quantification of the impact force attenuation (Q-ratio) and energy absorption (S-ratio), and to determine whether wrist guards play a role of an efficient shock isolator. While the falling direction (forward and backward) significantly influenced the impact responses, use of wrist guards provided minimal improvements in the Q- and S-ratios. It was suggested based on the results under the submaximal loading conditions that protective functions of the common wrist guard design could be enhanced with substantial increase in the damping ratio so as to maximize the energy absorption. This would bring forth minor deterioration in the impact force attenuation but significant increase in the energy absorption by 19%, which would help better protection against fall-related injuries of the upper extremity.     

Fear conditioning induces guinea pig auditory cortex activation by foot shock alone

The present study used an optical imaging paradigm to investigate plastic changes in the auditory cortex induced by fear conditioning, in which a sound (conditioned stimulus, CS) was paired with an electric foot-shock (unconditioned stimulus, US). We report that, after conditioning, auditory information could be retrieved on the basis of an electric foot-shock alone. Before conditioning, the auditory cortex showed no response to a foot-shock presented in the absence of sound. In contrast, after conditioning, the mere presentation of a foot-shock without any sound succeeded in eliciting activity in the auditory cortex. Additionally, the magnitude of the optical response in the auditory cortex correlated with variation in the electrocardiogram (correlation coefficient: −0.68). The area activated in the auditory cortex, in response to the electric foot-shock, statistically significantly had a larger cross-correlation value for tone response to the CS sound (12 kHz) compared to the non-CS sounds in normal conditioning group. These results suggest that integration of different sensory modalities in the auditory cortex was established by fear conditioning.     

Skin as a potential source of infectious foot and mouth disease aerosols

This review examines whether exfoliated, virus-infected animal skin cells could be an important source of infectious foot and mouth disease virus (FMDV) aerosols. Infectious material rafting on skin cell aerosols is an established means of transmitting other diseases. The evidence for a similar mechanism for FMDV is: (i) FMDV is trophic for animal skin and FMDV epidermis titres are high, even in macroscopically normal skin; (ii) estimates for FMDV skin cell aerosol emissions appear consistent with measured aerosol emission rates and are orders of magnitude larger than the minimum infectious dose; (iii) the timing of infectious FMDV aerosol emissions is consistent with the timing of high FMDV skin concentrations; (iv) measured FMDV aerosol sizes are consistent with skin cell aerosols; and (v) FMDV stability in natural aerosols is consistent with that expected for skin cell aerosols. While these findings support the hypothesis, this review is insufficient, in and of itself, to prove the hypothesis and specific follow-on experiments are proposed. If this hypothesis is validated, (i) new FMDV detection, management and decontamination approaches could be developed and (ii) the relevance of skin cells to the spread of viral disease may need to be reassessed as skin cells may protect viruses against otherwise adverse environmental conditions.     

The head and foot of Pelmatohydra oligactis,pall., as unipotent systems

Summary The head and foot ofPelmatohydra oligactis function in regeneration as unipotent systems. The exact extent of the unipotent tissue immediately posterior to the tentacles and anterior to the foot is not determined in these experiments. The intermediate tissue is pluripotent.The potentiality for head formation is stronger at the oral end and decreases towards the aboral end as the potentiality for foot formation increases.In these grafting experiments the stock has no influence over the graft which retains its individuality.Preliminary account im Akademischen Anzeiger, Wien, No. 24. 22. November 1923: Mitteilungen aus der Biologischen Versuchsanstalt der Akademie der Wissenschaften in Wien, Zoologische Abteilung, Vorstand:H. Przibram. Nr. 113. Kopf und Fuß des Süßwasserpolypen,Pelmatohydra oligactis Pall., als unipotente Systeme vonD. R. R. Burt.     

The caspase-1 digestome identifies the glycolysis pathway as a target during infection and septic shock

Caspase-1 is an essential effector of inflammation, pyroptosis, and septic shock. Few caspase-1 substrates have been identified to date, and these substrates do not account for its wide range of actions. To understand the function of caspase-1, we initiated the systematic identification of its cellular substrates. Using the diagonal gel proteomic approach, we identified 41 proteins that are directly cleaved by caspase-1. Among these were chaperones, cytoskeletal and translation machinery proteins, and proteins involved in immunity. A series of unexpected proteins along the glycolysis pathway were also identified, including aldolase, triose-phosphate isomerase, glyceraldehyde-3-phosphate dehydrogenase, alpha-enolase, and pyruvate kinase. With the exception of the latter, the identified glycolysis enzymes were specifically cleaved in vitro by recombinant caspase-1, but not caspase-3. The enzymatic activity of wild-type glyceraldehyde-3-phosphate dehydrogenase, but not a non-cleavable mutant, was dampened by caspase-1 processing. In vivo, stimuli that fully activated caspase-1, including Salmonella typhimurium infection and septic shock, caused a pronounced processing of these proteins in the macrophage and diaphragm muscle, respectively. Notably, these stimuli inhibited glycolysis in wild-type cells compared with caspase-1-deficient cells. The systematic characterization of caspase-1 substrates identifies the glycolysis pathway as a caspase-1 target and provides new insights into its function during pyroptosis and septic shock.     

Thermal shock and dilution shock as the causes of freezing injury

We suggest that during slow freezing, cellular membranes are altered by the hypertonic solutions produced. This alteration in itself does not cause membrane leakage of normally impermeant solutes but it renders the cells susceptible to solute leakage on the application of a stress, which is provided during freezing by the reduction in temperature (thermal shock) and during thawing by dilution (dilution shock).During slow freezing the effects of cooling rate changes are due to the different times available for the hypertonic solutions to affect the membrane. At a given cooling rate cryoprotective agents reduce the effect on the cells at each temperature during freezing perhaps by reducing the ionic strength. The thermal shock stress during cooling and the dilution shock during thawing thus damages the cells less. With rapid freezing, there is insufficient time for these effects to take place during cooling, which allows the cells to reach low temperatures without thermal shock damage. However, the presence of extracellular ice and the formation of intracellular ice provide hypertonic conditions that render the cells liable to dilution shock on thawing. The slower the rate of thawing of rapidly cooled cells the greater will be the damage from this dilution shock.