Functional Implications of Variation in Tooth Spacing and Crown Size in Pinnipedimorpha (Mammalia: Carnivora)

Pinnipeds (seals, sea lions, and walruses) show variation in tooth morphology that relates to ecology. However, crown size and spacing are two aspects of morphology that have not been quantified in prior studies. We measured these characters for nearly all extant pinnipeds and three fossil taxa and then determined the principal sources of variation in tooth size and spacing using principal components (PCAs) and hierarchical cluster analysis (HCA). PCA and HCA showed that species sorted into three groups: taxa with small crowns and large diastemata, taxa with large crowns and small diastemata, and taxa that fell between these two extremes. We then performed discriminant function analysis (DFA) to determine if tooth morphology correlated with foraging strategy or diet. DFA results indicated weak correlation with diet, and stronger correlation with prey capture strategies. Tooth size and spacing were most strongly correlated with the importance of teeth in prey acquisition, with tooth size decreasing and tooth spacing increasing as teeth become less necessary in capturing food items. Taxa which relied on teeth for filtering prey from the water column or processing larger or tougher food items generally had larger crowns and smaller tooth spacing then taxa which swallowed prey whole. We found the fossil taxa Desmatophoca and Enaliarctos were most similar in tooth morphology to extant otariids, suggesting that both taxa were generalist feeders. This study established the relationship between tooth size and feeding behavior, and provides a new tool to explore the paleoecology of fossil pinnipeds and other aquatic tetrapods. Anat Rec, 298:878–902, 2015. © 2014 Wiley Periodicals, Inc.     

Modelling the human pharyngeal airway: validation of numerical simulations using in vitro experiments

In the presented study, a numerical model which predicts the flow-induced collapse within the pharyngeal airway is validated using in vitro measurements. Theoretical simplifications were considered to limit the computation time. Systematic comparisons between simulations and measurements were performed on an in vitro replica, which reflects asymmetries of the geometry and of the tissue properties at the base of the tongue and in pathological conditions (strong initial obstruction). First, partial obstruction is observed and predicted. Moreover, the prediction accuracy of the numerical model is of 4.2% concerning the deformation (mean quadratic error on the constriction area). It shows the ability of the assumptions and method to predict accurately and quickly a fluid–structure interaction.

The evolution of bite force in horned lizards: the influence of dietary specialization

Dietary specialization is an important driver of the morphology and performance of the feeding system in many organisms, yet the evolution of phenotypic specialization has only rarely been examined within a species complex. Horned lizards are considered primarily myrmecophagous (ant eating), but variation in diet among the 17 species of horned lizards (Phrynosoma) makes them an ideal group to examine the relationship between dietary specialization and the resultant morphological and functional changes of the feeding system. In this study, we perform a detailed analysis of the jaw adductor musculature and use a biomechanical model validated with in vivo bite force data to examine the evolution of bite force in Phrynosoma. Our model simulations demonstrate that bite force varies predictably with respect to the gape angle and bite position along the tooth row, with maximal bite forces being attained at lower gape angles and at the posterior tooth positions. Maximal bite forces vary considerably among horned lizards, with highly myrmecophagous species exhibiting very low bite forces. In contrast, members of the short‐horned lizard clade are able to bite considerably harder than even closely related dietary generalists. This group appears to be built for performing crushing bites and may represent a divergent morphology adapted for eating hard prey items. The evolutionary loss of processing morphology (teeth, jaw and muscle reduction) and bite force in ant specialists may be a response to the lack of prey processing rather than a functional adaptation per se.     

Effects of exercise‐induced intracellular acidosis on the phosphocreatine recovery kinetics: a 31P MRS study in three muscle groups in humans

Little is known about the metabolic differences that exist among different muscle groups within the same subjects. Therefore, we used ³¹P‐magnetic resonance spectroscopy (³¹P‐MRS) to investigate muscle oxidative capacity and the potential effects of pH on PCr recovery kinetics between muscles of different phenotypes (quadriceps (Q), finger (FF) and plantar flexors (PF)) in the same cohort of 16 untrained adults. The estimated muscle oxidative capacity was lower in Q (29 ± 12 mM min^‐1, CV_{inter‐subject} = 42%) as compared with PF (46 ± 20 mM min^‐1, CV_{inter‐subject} = 44%) and tended to be higher in FF (43 ± 35 mM min^‐1, CV_{inter‐subject} = 80%). The coefficient of variation (CV) of oxidative capacity between muscles within the group was 59 ± 24%. PCr recovery time constant was correlated with end‐exercise pH in Q (p < 0.01), FF (p < 0.05) and PF (p <0.05) as well as proton efflux rate in FF (p < 0.01), PF (p < 0.01) and Q (p = 0.12). We also observed a steeper slope of the relationship between end‐exercise acidosis and PCr recovery kinetics in FF compared with either PF or Q muscles. Overall, this study supports the concept of skeletal muscle heterogeneity by revealing a comparable inter‐ and intra‐individual variability in oxidative capacity across three skeletal muscles in untrained individuals. These findings also indicate that the sensitivity of mitochondrial respiration to the inhibition associated with cytosolic acidosis is greater in the finger flexor muscles compared with locomotor muscles, which might be related to differences in permeability in the mitochondrial membrane and, to some extent, to proton efflux rates. Copyright © 2013 John Wiley & Sons, Ltd.     

Noninvasive assessment of in vivo glycogen kinetics in humans: effect of increased physical activity on glycogen breakdown and synthesis

In vivo glycogen kinetics was estimated with the simultaneous use of indirect calorimetry and tracer technology in healthy humans during 24-h periods with low or moderate physical activity (1 or 3 exercise sessions each day). Two ¹³C-carbohydrates meals were administered at 9.30 a.m. and 1.30 p.m., and one ¹²C-carbohydrates meal at 6.30 p.m. Net carbohydrate oxidation (net CHO ox) was measured over a 24 h period by indirect calorimetry and oxidation of ¹³C-labelled carbohydrates (13C CHO ox) was estimated from ¹³CO₂ production. Glycogen breakdown, assessed for the period 8.15 a.m.-6.30 p.m. as the difference between net CHO ox and ¹³C CHO ox, was increased 1.6 times with three exercise sessions [123.3 (SEM 8.0) g] versus one session [77.9 (SEM 7.7) g, P<0.0001]. Carbohydrate balances over 24 h were close to zero under both conditions, indicating that glycogen breakdown was matched by an equivalent glycogen synthesis. It was concluded that simultaneous use of indirect calorimetry and tracer technology may make possible the estimation of glycogen kinetics in humans. Moderate physical activity enhanced both glycogen breakdown and synthesis. This stimulation of glycogen metabolism may therefore play a role in the enhanced insulin sensitivity induced by physical exercise.     

Step vs. progressive exercise: the kinetics of phosphocreatine hydrolysis in human muscle

It is well known that the VPO ₂ readjustment rate of the whole body is faster when carrying out a given constant work load starting from a baseline of moderate exercise than from rest. However, it has not been established whether the above change is the result of faster kinetics of the oxidative machinery or, alternatively, the consequence of a reduced involvement of confounding factors such as anaerobic glycolysis or tissue O₂ stores. The problem, earlier approached by chemical methods, was studied in man by ³¹P-NMRS assessment of the kinetics of phosphocreatine (PC) hydrolysis at the muscle level which is known to reflect the readjustment rate of the oxidative reactions. Twelve normal subjects carried out in a 90 cm bore modified Picker (1.5 T) magnet, a series of contractions by the plantar flexors reaching pre-set submaximal loads either in single steps (constant load, CL) or progressively (incremental exercise, I). If preceding exercise (I), compared to rest, influenced the rate of oxidations, the PC concentration at the target loads would be different for the two exercise modes, reflecting different energy deficits. This was not the case. Thus the present results show that the rate of readjustment of oxidations at the muscle level is not affected by priming exercise confirming previous findings and showing that theoretical models of VPO ₂ control are experimentally applicable to man.     

Contraction of the rat portal vein in hypertonic and isotonic medium: mechanical properties and effects of Mg2+

The contracture elicited in the rat portal vein by hyperosmotic solutions (HC) has been investigated with respect to its Mg²⁺-dependence and its mechanical properties. Comparison was made with K⁺-induced contractures (KC) of similar force. In contrast to its relative resistance to Ca²⁺-depletion, HC is entirely abolished after depletion of both Ca²⁺ and Mg²⁺ ions. After readdition of Mg²⁺ alone, HC can be partially restored again. Isotonic quick release expts were performed on muscles in HC, KC and after passive stretch (PS) to a similar total tension and the length responses following the releases were analyzed. The immediate elastic response showed that stiffness was markedly higher in HC than in KC. whereas in PS it was much lower. After the elastic response a quickly decaying exponential component could be distinguished from the later more steady length change. The time constant of this transient response was 40–50 ms (KC) or 25–30 ms (HC). On release to a minimal afterload the amplitude of the transient response was about 1 % (KC) or 0.5 % (HC) of the initial muscle length, decreasing with increasing afterload. A corresponding transient lengthening response was seen after a step to a force greater than the isometric tension. Transient length responses in PS were much smaller than in KC or HC following force steps producing similar elastic recoils. The late shortening in HC and KC, interpreted as the isotonic response of the contractile system, could be fitted to Hill's eq. V_max in KC ([Ca²⁺]=0.5 mM) was 0. 25times;0.02 and in HC 0.05×0.01 (SE, n=6) lengths/s. The results of this investigation support the conclusion that HC originates in the contractile system of the muscle. The quantitative differences in mechanical properties are discussed against possible alterations in HC of cross-bridge behaviour and/or filament structure.     

Modification of myo-electric power spectrum in fatigue from 15% maximal voluntary contraction of human elbow flexor muscles,to limit of endurance: reflection of conduction velocity variation and/or centrally mediated mechanisms?

Summary Isometric flexion of the right elbow at 15% of the maximal voluntary contraction (MVC) was maintained to the limit of endurance (elbow angle 135°). The surface electromyogram (EMG) of the brachioradialis (BR) and biceps brachii (BB) muscles was recorded for calculation of conduction velocity (CV) by the cross-correlation method, and determination of median frequency (fm) and root mean square (rms) amplitude. Perceived exertion was rated for both muscles, and heart rate and blood pressure were measured. The EMG of ten brief 15% MVC contractions distributed over a 30-min recovery period was also recorded. Eleven males in their twenties volunteered for the investigation. The average endurance time was 906 (SD 419) s. Mean CV for the unfatigued muscles was 4.2 (SD 0.41) m·s^–1 (BR), and 4.3 (SD 0.29) m·s^–1 (BB). The contraction caused a significant decrease in CV of BR (12%,P<0.001) whereas CV variation of BB remained insignificant. Concurrently the meanf _m of both muscles dropped to approximately 66% of their initial values and their average rms amplitudes grew by approximately 380% (BR and BB:P<0.001, both parameters). The 1st min of recovery lowered the rms amplitudes by approximately 60% (BR and BB:P<0.01), while thef _m increased to approximately 88% of the initial recording (BR,P<0.01; BB,P<0.05). The accompanying small increases in CV were beyond the level of significance. Over the next 29 min a significant parallel restitution inf _m and CV took place; changes inf _m evidenced a simple one to one reflection of relative CV variation. A similar uncomplicated linear causality between relative changes in CV andf _m was hypothesized for the endurance contraction. Consequently, the 12% CV decrease of the BR accounted for only one-third of the fatigue inducedf _m reduction of 33%, while two-thirds were assumed to be attributable to centrally mediated regulatory interventions in motor unit (MU) performance. Independent of contributions from the virtually unchanged CV, thef _m of the BB muscle decreased by 35%; from one subject exhibiting a remarkably manifest burst-type pattern of MU activity it is argued that synchronization/grouping of MU firing predominantly determined the power redistribution in the BB spectrum.     

The variable coupling between force and myosin light chain phosphorylation in Triton-skinned chicken gizzard fibre bundles: role of myosin light chain phosphatase

The mechanism responsible for the regulation of smooth muscle tone at low levels of myosin light chain (MLC) phosphorylation is still poorly understood. According to one model, so-called latchbridges, which contribute to force maintenance at low levels of MLC phosphorylation, are generated by dephosphorylation of attached and phosphorylated crossbridges. The model predicts that the force generated for a given level of MLC phosphorylation depends on the activity of the MLC phosphatase. We tested this hypothesis by reducing the activity of the phosphatase by at least 80% in two ways: inhibition with okadaic acid and extraction. Under both conditions, higher levels of MLC phosphorylation were required to support a given level of force, suggesting a decreased flux of attached phosphorylated to attached dephosphorylated crossbridges, as predicted by this model. Although, under both conditions, the relationship between force and MLC phosphorylation was shifted to the right, the curves did not superimpose as would have been expected if the phosphatase activity were the only determinant of the coupling between force and phosphorylation. In the extracted fibres, two more proteins, calponin and SM22, were significantly reduced in addition. Therefore, these proteins might be involved in modulating the relationship between force and MLC phosphorylation.     

Induction of heme oxygenase in guinea‐pig stomach: roles in contraction and in single muscle cell ionic currents

The role of heme oxygenase reaction products in modulation of stomach fundus excitability was studied. The presence of constitutive heme oxygenase 2 was verified in myenteric ganglia by immunohistochemistry. The role of inducible heme oxygenase isoenzyme was investigated after invivo treatment of animals with CoCl₂ (80 mg kg^?1 b.w) injected subcutaneously 24 h before they were killed. This treatment resulted in increased production of bilirubin and positive staining for the inducible isoform in stomach smooth muscle and vast induction in the liver. In both control and treated animals haemin, applied to the bath as a substrate of heme oxygenase caused significant decrease of prostaglandin F_2α‐induced tone, and ameliorated the relaxatory response of the fundic strips to electrical field stimulation. Both effects were antagonized by Sn‐protoporphyrin IX, competitive heme oxygenase inhibitor, and were found to be neuronally dependent. In single freshly isolated smooth muscle cells from control animals haemin caused a concentration‐dependent increase of the whole cell K⁺ currents, which was not affected by Sn‐protoporphyrin IX, cyclic guanosine monophosphate (cGMP)‐dependent protein kinase or guanylyl cyclase antagonists, but was reversed by various antioxidants and abolished by an NO scavenger. In cells from treated animals the K⁺ current increasing effect of haemin did not depend on the presence of antioxidants, but was abolished by protein kinase G and guanylyl cyclase inhibitors, depletors of intracellular Ca²⁺ pools or Sn‐protoporphyrin IX. Biliverdin did not affect contraction or ionic currents. Thus, this is the first study demonstrating that heme oxygenase is an inducible enzyme in guinea‐pigs, which exerts a modulatory role on gastric smooth muscle excitability via carbon monoxide production.     

Stretch-activated ion channels in smooth muscle: a mechanism for the initiation of stretch-induced contraction

As in many smooth muscle tissue preparations, single smooth muscle cells freshly dissociated from the stomach of the toadBufo marinus contract when stretched. Stretch-activated channels have been identified in these cells using patch-clamp techniques. In both cell-attached and excised inside-out patches, the probability of the channel being open (P _o) increases when the membrane is stretched by applying negative pressure to the extracellular surface through the patch pipette. The increase inP _o is mainly due to a decrease in closed time durations, but an increase in open time duration is also seen. The open-channel current-voltage relationship shows inward rectification and is not appreciably altered when K⁺ is substituted for Na⁺ as the charge-carrying cation in Ca²⁺-free (2 mM EGTA) pipette solutions bathing the extracellular surface of the patch. The inclusion of physiological concentrations of Ca²⁺ (1.8 mM) in pipette solutions (containing high concentrations of Na⁺ and low K⁺) significantly decreases the slope conductance as well as the unitary amplitude. The channel also conducts Ca²⁺, since inward currents were observed using pipette solutions in which Ca²⁺ ions were the only inorganic cations. When simulating normal physiological conditions, we find that substantial ionic current is conducted into the cell when the channel is open. These characteristics coupled with the high density of the stretch-activated channels point to a key role for them in the initiation of stretch-induced contraction.     

Myofascial force transmission in dynamic muscle conditions: effects of dynamic shortening of a single head of multi-tendoned rat extensor digitorum longus muscle

This study investigated the effects of myofascial force transmission during dynamic shortening of head III of rat extensor digitorum longus muscle (EDL III). The anterior crural compartment was left intact. Force was measured simultaneously at the distal EDL III tendon, the proximal EDL tendon and the distal tendons of tibialis anterior and extensor hallucis longus muscles (TA+EHL). Two types of distal shortening of EDL III were studied: (1) sinusoidal shortening (2 mm) and (2) isokinetic shortening (8 mm). Sinusoidal shortening of EDL III caused a decrease in force exerted at the distal tendon of EDL III: from 0.58 (0.08) N to 0.26 (0.04) N. In contrast, hardly any changes in proximal EDL force and distal TA+EHL force were found. Maximal concentric force exerted at the distal tendon of EDL III was higher than maximal isometric force expected on the basis of the physiological cross-sectional area of EDL III muscle fibers (Maas et al. 2003). Therefore, a substantial fraction of this force must originate from sources other than muscle fibers of EDL III. Isokinetic shortening of EDL III caused high changes in EDL III force from 0.97 (0.15) N to zero. In contrast, changes in proximal EDL force were much smaller: from 2.44 (0.25) N to 1.99 (0.19) N. No effects on TA+EHL force could be shown. These results are explained in terms of force transmission between the muscle belly of EDL III and adjacent tissues. Thus, also in dynamic muscle conditions, muscle fiber force is transmitted via myofascial pathways.     

Role of nitric oxide in skeletal muscle: synthesis,distribution and functional importance

Over the last two decades, nitric oxide (NO) has been established as a novel mediator of biological processes, ranging from vascular control to long-term memory, from tissue inflammation to penile erection. This paper reviews recent research which shows that NO and its derivatives also are synthesized within skeletal muscle and that NO derivatives influence various aspects of muscle function. Individual muscle fibres express one or both of the constitutive NO synthase (NOS) isoforms. Type I (neuronal) NOS is localized to the sarcolemma of fast fibres; type III (endothelial) NOS is associated with mitochondria. Isolated skeletal muscle produces NO at low rates under resting conditions and at higher rates during repetitive contraction. NO appears to mediate cell–cell interactions in muscle, including vasodilation and inhibition of leucocyte adhesion. NO also acts directly on muscle fibres to alter cell function. Muscle metabolism appears to be NO-sensitive at several sites, including glucose uptake, glycolysis, mitochondrial oxygen consumption and creatine kinase activity. NO also modulates muscle contraction, inhibiting force output by altering excitation–contraction coupling. The mechanisms of NO action are likely to include direct effects on redox-sensitive regulatory proteins, interaction with endogenous reactive oxygen species, and activation of second messengers such as cyclic guanosine monophosphate (cGMP). In conclusion, research published over the past few years makes it clear that skeletal muscle produces NO and that endogenous NO modulates muscle function. Much remains to be learned, however, about the physiological importance of NO actions and about their underlying mechanisms.     

Dynamic three‐dimensional imaging of phosphocreatine recovery kinetics in the human lower leg muscles at 3T and 7T: a preliminary study

The rate of phosphocreatine (PCr) resynthesis after physical exercise has been extensively studied with phosphorus (³¹P)‐MRS. Previous studies have used small surface coils that were limited to measuring one superficial muscle per experiment. This study focuses on the development and implementation of a spectrally selective three‐dimensional turbo spin echo (3D‐TSE) sequence at 3T and 7T with temporal resolution of 24 s, using two geometrically identical volume coils. We acquired imaging data of PCr recovery from four healthy volunteers and one diabetic patient, who performed plantar flexions using resistance bands. We segmented the anatomical regions of six different muscles from the lower leg, namely the gastrocnemius [lateral (GL) and medial (GM)], the tibialis [anterior (TA) and posterior (TP)], the soleus (S) and the peroneus (P) and measured the local PCr resynthesis rate constants. During the same examination, we also acquired unlocalized ³¹P‐MRS data at a temporal resolution of 6 s. At 3T, the PCr resynthesis rate constants were measured at 25.4 ± 3.7 s [n = 4, mean ± standard deviation (SD)] using the MRS method and 25.6 ± 4.4 s using the MRI method. At 7T, the measured rates were 26.4 ± 3.2 s and 26.2 ± 4.7 s for MRS and MRI. Using our imaging method, we measured the local PCr resynthesis rate constants in six individual muscles of the lower leg (min/max 20.2/31.7 s). The recovery rate constants measured for the diabetic patient were 55.5 s (MRS) and 52.7 s (MRI). The successful implementation of our 3D‐method suggests that imaging is possible at both fields with a relatively high spatial resolution (voxel size: 4.2 mL at 3T and 1.6 mL at 7T) using volume coils and that local PCr resynthesis rates can be obtained in a single measurement. The advantage of the imaging method is that it can highlight differences in PCr resynthesis rates between different muscles in a single measurement in order to study spatial gradients of metabolic properties of diseased states for which very little is currently known. Copyright © 2012 John Wiley & Sons, Ltd.     

Regulation of airway smooth muscle cell immunomodulatory function: role in asthma

General agreement exists that in asthma, airway smooth muscle contracts, narrowing the airway lumen and thereby causing airflow obstruction and dyspnoea. New evidence is emerging that airway smooth muscle may also fulfil an immunomodulatory role by providing a rich source of pro-inflammatory cytokines and chemokines, polypeptide growth factors, extracellular matrix (ECM) proteins, cell adhesion receptors and co-stimulatory molecules. Together, the available data support a role for airway smooth muscle in actively perpetuating airway mucosal inflammatory processes including mast cell and leukocyte (T cell, neutrophil, eosinophil) activation and recruitment. Production of anti-inflammatory mediators by airway smooth muscle such as prostaglandin E(2) suggests that it is also capable of exerting a 'braking' effect on local inflammation. Recognition of this newly described property of airway smooth muscle makes it important to consider therapeutic targets for suppressing the synthesis and secretion of immunomodulatory mediators from this cell. However, it remains imperative to establish to what extent the secretory potential of airway smooth muscle is quantitatively important in vivo and in asthmatic subjects.