Why the semicircular canals are not stimulated by linear accelerations.

Head accelerations are sensed by the vestibular system in the inner ear. Linear accelerations stimulate the otolith organs, while the semicircular canals (SCC) sense angular accelerations. Fluid-structure interaction (FSI) models of the cupula sensor (simulated with finite element method (FEM)) and the endolymph fluid (simulated with computational fluid dynamics (CFD)) in the semicircular canal offer the possibility to investigate why the SCC are not stimulated by linear accelerations. Two hypotheses exist in the literature. The first hypothesis focusses on the density of the cupula sensor in the SCC, while the second is based on the continuous loop of fluid in the semicircular canal. However, neither increasing the cupula density, nor disrupting the continuous fluid circulation substantially increase the cupula deformation under linear head acceleration, thereby rejecting both existing hypotheses. We propose an alternative hypothesis, based on the circular geometry of the semicircular canal. During angular head acceleration, the cupula intersects the body of endolymph and 'pushes' it forward because the cupula seals the semicircular canal like a diaphragm. This results in cupula deflection and neural stimulation. During linear head acceleration, on the other hand, a large part of the canal wall also 'pushes' the endolymph forward, which leads to hardly any cupula deflection.

An insight into the antibiofilm properties of Costa Rican stingless bee honeys.

OBJECTIVE: There is an increasing search for antibiofilm agents that either have specific activity against biofilms or may act in synergy with antimicrobials. Our objective is to examine the the antibiofilm properties of stingless bee honeys. METHOD: Meliponini honeys from Costa Rica were examined along with Medihoney as a reference. All honeys were submitted to a screening composed of minimum inhibitory concentration, inhibition of biofilm formation and biofilm destruction microplate-based assays against a Staphylococcus aureus biofilm forming strain. Dialysis led to the isolation of an antibiofilm fraction in Tetragonisca angustula honeys. The honey antibiofilm fraction was evaluated for protease activity and for any synergistic effect with antibiotics on a Staphylococcus aureus biofilm. The active fraction was then separated through activity guided isolation techniques involving SDS-PAGEs, anion exchange and size exclusion fast protein liquid chromatographies. The fractions obtained and the isolated antibiofilm constituents were tested for amylase and DNase activity. RESULTS: A total of 57 Meliponini honeys from Costa Rica were studied in this research. The honeys studied belonged to the Tetragonisca angustula (n=36) and Melipona beecheii (n=21) species. Costa Rican Tetragonisca angustula honeys can inhibit the planktonic growth, biofilm formation, and are capable of destroying a Staphylococcus aureus biofilm. The antibiofilm effect was observed in the protein fraction of Tetragonisca angustula honeys. The biofilm destruction proteins allowed ampicillin and vancomycin to recover their antimicrobial activity over a Staphylococcus aureus biofilm. The antibiofilm proteins are of bee origin, and their activity was not due to serine, cysteine or metalloproteases. There were 2 proteins causing the antibiofilm action; these were named the Tetragonisca angustula biofilm destruction factors (TABDFs). TABDF-1 is a monomeric protein of approximately 50kDa that is responsible of the amylase activity of Tetragonisca angustula honeys. TABDF-2 is a protein monomer of approximately 75kDa. CONCLUSION: Tetragonisca angustula honeys from Costa Rica are a promising candidate for research and development of novel wound dressings focused on the treatment of acute and chronic Staphylococcus aureus biofilm wound infections.

Cyclic movement frequency is associated with muscle typology in athletes.

There is a continuing research interest in the muscle fiber type composition (MFTC) of athletes. Recently, muscle carnosine quantification by proton magnetic resonance spectroscopy (1 H-MRS) was developed as a new non-invasive method to estimate MFTC. This cross-sectional study aims to better understand estimated MFTC in relation to (a) different disciplines within one sport; (b) cyclic sport exercise characteristics; (c) within-athlete variability; and (d) athlete level. A total of 111 elite athletes (74 runners, 7 triathletes, 11 swimmers, 14 cyclists and 5 kayakers) and 188 controls were recruited to measure muscle carnosine in gastrocnemius and deltoid muscle by 1 H-MRS. Within sport disciplines, athletes were divided into subgroups (sprint-, intermediate-, and endurance-type). The controls were used as reference population to allow expression of the athletes' data as Z-scores. Within different sports, endurance-type athletes systematically showed the lowest Z-score compared to sprint-type athletes, with intermediate-type athletes always situated in between. Across the different sports disciplines, carnosine content showed the strongest significant correlation with cyclic movement frequency (R = 0.86, P = 0.001). Both within and between different cyclic sports, estimated MFTC was divergent between sprint- and endurance-type athletes. Cyclic movement frequency, rather than exercise duration came out as the most determining factor for the optimal estimated MFTC in elite athletes.

Discriminant musculo-skeletal leg characteristics between sprint and endurance elite Caucasian runners.

Excellence in either sprinting or endurance running requires specific musculo-skeletal characteristics of the legs. This study aims to investigate the morphology of the leg of sprinters and endurance runners of Caucasian ethnicity. Eight male sprinters and 11 male endurance runners volunteered to participate in this cross-sectional study. They underwent magnetic resonance imaging and after data collection, digital reconstruction was done to calculate muscle volumes and bone lengths. Sprinters have a higher total upper leg volume compared to endurance runners (7340 vs 6265 cm3 ). Specifically, the rectus femoris, vastus lateralis, and hamstrings showed significantly higher muscle volumes in the sprint group. For the lower leg, only a higher muscle volume was found in the gastrocnemius lateralis for the sprinters. No differences were found in muscle volume distribution, center of mass in the different muscles, or relative bone lengths. There was a significant positive correlation between ratio hamstrings/quadriceps volume and best running performance in the sprint group. Sprinters and endurance runners of Caucasian ethnicity showed the greatest distinctions in muscle volumes, rather than in muscle distributions or skeletal measures. Sprinters show higher volumes in mainly the proximal and lateral leg muscles than endurance runners.

Environment-dependent prey capture in the Atlantic mudskipper (Periophthalmus barbarus).

Few vertebrates capture prey in both the aquatic and the terrestrial environment due to the conflicting biophysical demands of feeding in water versus air. The Atlantic mudskipper (Periophthalmus barbarus) is known to be proficient at feeding in the terrestrial environment and feeds predominately in this environment. Given the considerable forward flow of water observed during the mouth-opening phase to assist with feeding on land, the mudskipper must alter the function of its feeding system to feed successfully in water. Here, we quantify the aquatic prey-capture kinematics of the mudskipper and compare this with the previously described pattern of terrestrial feeding. Prior to feeding in the aquatic environment, the gill slits open, allowing water to be expelled through the gill slits. The opposite happens in terrestrial feeding during which the gill slits remain closed at this point. In water, the expansive movements of the head are larger, amounting to a larger volume increase and are initiated slightly later than in the terrestrial environment. This implies the generation of strong suction flows when feeding in water. Consequently, the kinematic patterns of the hydrodynamic tongue during terrestrial feeding and aquatic suction feeding are similar, except for the amplitude of the volume increase and the active closing of the gill slits early during the terrestrial feeding strike. The mudskipper thus exhibits the capacity to change the kinematics of its feeding apparatus to enable successful prey capture in two disparate environments.

Bovine Staphylococcus aureus Secretes the Leukocidin LukMF' To Kill Migrating Neutrophils through CCR1.

UNLABELLED: Although Staphylococcus aureus is best known for infecting humans, bovine-specific strains are a major cause of mastitis in dairy cattle. The bicomponent leukocidin LukMF', exclusively harbored by S. aureus of ruminant origin, is a virulence factor associated with bovine infections. In this study, the molecular basis of the host specificity of LukMF' is elucidated by identification of chemokine receptor CCR1 as its target. Bovine neutrophils, the major effector cells in the defense against staphylococci, express significant cell surface levels of CCR1, whereas human neutrophils do not. This causes the particular susceptibility of bovine neutrophils to pore formation induced by LukMF'. Bovine S. aureus strains produce high levels of LukMF' in vitro. In culture supernatant of the mastitis field isolate S1444, LukMF' was the most important cytotoxic agent for bovine neutrophils. In a fibrin gel matrix, the effects of the in situ secreted toxins on neutrophils migrating toward S. aureus were visualized. Under these physiological ex vivo conditions, bovine S. aureus S1444 efficiently killed approaching neutrophils at a distance through secretion of LukMF'. Altogether, our findings illustrate the coevolution of pathogen and host, provide new targets for therapeutic and vaccine approaches to treat staphylococcal diseases in the cow, and emphasize the importance of staphylococcal toxins in general. IMPORTANCE: This study explains the mechanism of action of LukMF', a bicomponent toxin found in bovine lineages of S. aureus that is associated with mastitis in cattle. At a molecular level, we describe how LukMF' can specifically kill bovine neutrophils. Here, we demonstrate the contribution of toxins in the determination of host specificity and contribute to the understanding of mechanisms of coevolution of pathogen and host. Our study provides new targets that can be used in therapeutic and vaccine approaches to treat staphylococcal diseases in the cow. We also demonstrate the importance of toxins in specific elimination of immune cells, which has broader implications, especially in human infections.

Mechanoreceptor distribution in stag beetle jaws corresponds to the material stress in fights.

Male stag beetles (Lucanidae) use their extremely elongated jaws to pinch their rivals forcefully in male-male battles. The morphology of these jaws has to be a compromise between robustness (to withstand the bite forces), length and weight. Cyclommatus metallifer stag beetles circumvent this trade-off by reducing their bite force when biting with their slender jaw tips. Here we describe the functional mechanism behind the force modulation behaviour. Scanning Electron Microscopy and micro CT imaging show large numbers of small sensors in the jaw cuticle. We find a strong correlation between the distribution of these sensors and that of the material stress in the same jaw region during biting. The jaw sensors are mechanoreceptors with a small protrusion that barely protrudes above the undulating jaw surface. The sensors stimulate dendrites that extend from the neuronal cell body through the entire thickness of the jaw exoskeleton towards the sensors at the external surface. They form a sensory field that functions in a feedback mechanism to control the bite muscle force. This negative feedback mechanism enabled the stag beetles to evolve massive bite muscles without risking overloading their valuable jaws.

Finite-element modelling reveals force modulation of jaw adductors in stag beetles.

Male stag beetles carry large and heavy mandibles that arose through sexual selection over mating rights. Although the mandibles of Cyclommatus metallifer males are used in pugnacious fights, they are surprisingly slender. Our bite force measurements show a muscle force reduction of 18% for tip biting when compared with bites with the teeth located halfway along the mandibles. This suggests a behavioural adaptation to prevent failure. We confirmed this by constructing finite-element (FE) models that mimic both natural bite situations as well as the hypothetical situation of tip biting without muscle force modulation. These models, based on micro-CT images, investigate the material stresses in the mandibles for different combinations of bite location and muscle force. Young's modulus of the cuticle was experimentally determined to be 5.1 GPa with the double indentation method, and the model was validated by digital image correlation on living beetles. FE analysis proves to be a valuable tool in the investigation of the trade-offs of (animal) weapon morphology and usage. Furthermore, the demonstrated bite force modulation in male stag beetles suggests the presence of mechanosensors inside the armature.

Kinematics and dynamics of burst transitions.

Subjects (N = 14) were instructed to walk at comfortable walking speed and to start sprinting on an external (visual) stimulus. This is a burst transition. To accelerate maximally, different strategies can be used. The choice for a strategy was hypothesized to be (a) dependent of the body's dynamical status, which is in its turn dependent on the signal timing within the gait cycle; and (b) influenced by the performance and efficacy of the different strategies. Three-dimensional kinematics and ground reaction forces were used to discriminate between strategies and to calculate work (W(total)). Distance laser data yielded performance measures and the work related to the forward acceleration (W(objective)). Efficacy was calculated as the ratio of W(objective) to W(total). Subjects mainly used 2 strategies among others depending on the timing of the stimulus: (a) subjects placed their body center of mass (BCOM) in front of their center of pressure (COP) by tilting the trunk forward and flexing the knee, resulting in a sudden forward acceleration but a relatively fair efficacy; (b) subjects placed their COP behind their BCOM by placing the foot of the swing leg backward. This led to a high performance with high efficacy and was therefore the most ecologically relevant.

Is the whole more than the sum of its parts? Evolutionary trade-offs between burst and sustained locomotion in lacertid lizards.

Trade-offs arise when two functional traits impose conflicting demands on the same design trait. Consequently, excellence in one comes at the cost of performance in the other. One of the most widely studied performance trade-offs is the one between sprint speed and endurance. Although biochemical, physiological and (bio)mechanical correlates of either locomotor trait conflict with each other, results at the whole-organism level are mixed. Here, we test whether burst (speed, acceleration) and sustained locomotion (stamina) trade off at both the isolated muscle and whole-organism level among 17 species of lacertid lizards. In addition, we test for a mechanical link between the organismal and muscular (power output, fatigue resistance) performance traits. We find weak evidence for a trade-off between burst and sustained locomotion at the whole-organism level; however, there is a significant trade-off between muscle power output and fatigue resistance in the isolated muscle level. Variation in whole-animal sprint speed can be convincingly explained by variation in muscular power output. The variation in locomotor stamina at the whole-organism level does not relate to the variation in muscle fatigue resistance, suggesting that whole-organism stamina depends not only on muscle contractile performance but probably also on the performance of the circulatory and respiratory systems.

Defining consensus leukemia-associated immunophenotypes for detection of minimal residual disease in acute myeloid leukemia in a multicenter setting.

Flow-cytometric detection of minimal residual disease (MRD) has proven in several single-institute studies to have an independent prognostic impact. We studied whether this relatively complex approach could be performed in a multicenter clinical setting. Five centers developed common protocols to accurately define leukemia-associated (immuno)phenotypes (LAPs) at diagnosis required to establish MRD during/after treatment. List mode data files were exchanged, and LAPs were designed by each center. One center, with extensive MRD experience, served as the reference center and coordinator. In quarterly meetings, consensus LAPs were defined, with the performance of centers compared with these. In a learning (29 patients) and a test phase (35 patients), a mean of 2.2 aberrancies/patient was detected, and only 1/63 patients (1.6%) had no consensus LAP(s). For the four centers without (extensive) MRD experience, clear improvement could be shown: in the learning phase, 39-63% of all consensus LAPs were missed, resulting in a median 30% of patients (range 21-33%) for whom no consensus LAP was reported; in the test phase, 27-40% missed consensus LAPs, resulting in a median 16% (range 7-18%) of 'missed' patients. The quality of LAPs was extensively described. Immunophenotypic MRD assessment in its current setting needs extensive experience and should be limited to experienced centers.

Metabolic disregulation in obese adolescents with sleep-disordered breathing before and after weight loss.

OBJECTIVE: Sleep-disordered breathing (SDB) is prevalent in obesity. Weight loss is one of the most effective treatment options. The aim was to assess the association of SDB and metabolic disruption before and after weight loss. DESIGN AND METHODS: Obese adolescents were included when entering an in-patient weight loss program. Fasting blood analysis was performed at baseline and after 4-6 months. Sleep screening was done at baseline and at follow-up in case of baseline SDB. RESULTS: 224 obese adolescents were included. Median age was 15.5 years (10.1-18.0) and mean BMI z-score was 2.74 ± 0.42. About 30% had SDB at baseline (N = 68). High-density lipoprotein (HDL)-cholesterol was associated with mean nocturnal oxygen saturation () (partial r = 0.21; P = 0.002). Aspartate aminotransferase (ASAT) and alanine aminotransferase were related with oxygen desaturation index (partial r = -0.15; P = 0.03 and partial r = -0.15; P = 0.02), but this became insignificant after correction for sex. After weight loss, 24% had residual SDB. Linear regression showed an association between ASAT and (partial r = -0.34; P = 0.002). There were no significant correlations between improvements in laboratory measurements and sleep parameters. HDL-cholesterol improved in relation with the decrease in BMI z-score. CONCLUSION: SDB at baseline was associated with higher levels of liver enzymes and lower HDL-cholesterol concentration. Improvements in sleep parameters were not associated with improvements in laboratory measurements.

Milwaukee shoulder syndrome.

Milwaukee shoulder syndrome or rapid destructive arthropathy of the shoulder is a rare form of arthropathy that mainly affects elderly women. It is characterized by a rapid destruction of the glenohumeral joint and the rotator cuff and by an important noninflammatory joint effusion containing hydroxyapatite crystals. Radiography plays an important role in the evaluation of patients with articular disease. However, magnetic resonance imaging is the method of choice for assessing the full extent of osseous, chondral, and soft-tissue involvement.

Efficacy of relaxation, backflushing, chemical cleaning and clogging removal for an immersed hollow fibre membrane bioreactor.

A pilot-scale hollow fibre immersed MBR, challenged with real municipal wastewater, was studied and operated under conditions identical to those prevailing at full-scale to assess the relative influence of backflushing, relaxation, chemical enhanced backflushing (CEB) and declogging on permeability decline and recovery. The influence of relaxation and backflushing was initially assessed using the conventional flux step method; results indicated reversible fouling to be similar for each method, whilst the irreversible fouling rate was significantly reduced by backflushing. For a given total backflush volume, fouling mitigation was found to be marginally better through employing higher backflush fluxes than longer backflush durations. The impact of the CEB on permeability recovery assessed at low and high fluxes indicated operation at more conservative fluxes to yield more sustained permeability. Under more aggressive operating conditions--fluxes of up to 35 L m⁻² h⁻¹ at specific aeration demand values of 0.25 Nm³/(m² h)--long-term permeability decline took place which was not significantly ameliorated by chemical cleaning. On declogging the membrane through gentle agitation permeability recovery was significant, but was followed by a rapid permeability decline over the course of a few hours. Results suggested control of clogging to be of greater importance than that of fouling in sustaining permeability.

Evasion of Toll-like receptor 2 activation by staphylococcal superantigen-like protein 3.

Toll-like receptors (TLRs) are crucial for our host defense against microbial infections. TLR2 is especially important to fight bacterial infections, as it specifically recognizes bacterial lipoproteins of both Gram-positive and Gram-negative origin. Present on a variety of immune cells, TLR2 is critical for host protection against several bacterial infections, including those caused by Staphylococcus aureus. This major human pathogen causes increasing health care problems due to its increased resistance to antibiotics. S. aureus secretes a wide variety of proteins that inhibit innate immune responses. Recently, several staphylococcal superantigen-like proteins (SSLs) have been described to mediate immune evasive properties. Here, we describe that SSL3 specifically binds and inhibits TLR2 activation on human and murine neutrophils and monocytes. Through binding of the extracellular TLR2 domain, SSL3 inhibits IL-8 production by HEK cells expressing TLR1/2 and TLR2/6 dimers, stimulated with their specific ligands. The SSL3-TLR2 interaction is partially glycan dependent as binding of SSL3 to TLR2 is affected upon removal of sialic acid residues. Moreover, the SSL3(R308A) mutant lacking glycan-binding properties shows lower TLR2 inhibition. An SSL3 mutant, lacking the N-terminal 126 amino acids, still retains full TLR2 inhibiting activity. Of other SSLs tested, only SSL4, which shares the highest homology with SSL3, blocks TLR2 activation. SSL3 is the first-described bacterial protein that blocks TLR2 activation through direct extracellular interaction with the receptor. This unique function of SSL3 adds to the arsenal of immune evasive molecules that S. aureus can employ to subvert both innate and adaptive immunity.

Why the long face? A comparative study of feeding kinematics of two pipefishes with different snout lengths.

This study showed that the mouth of Doryrhamphus dactyliophorus, a species with a relatively long snout, travels a greater distance compared with Doryrhamphus melanopleura, a species with a considerably shorter snout, allowing it to strike at prey that are farther away from the mouth. The long-snouted species also tended to reach significantly higher linear velocities of the mouth approaching the prey. On the other hand, D. melanopleura needed less time to capture its prey. A striking difference in prey-capture success was observed between species: D. melanopleura and D. dactyliophorus had a prey-capture success of 91 and 31%, respectively. The small prey size and the relatively large distance between eyes and prey are potential reasons why directing the mouth accurately to the prey is difficult in D. dactyliophorus, hence possibly explaining the lower prey-capture success in this long-snouted species.

A cross-sectional study about the relationship between morphology and kinematic parameters in children between 15 and 36 months.

Morphology and kinematic parameters were recorded for 31 children between 15 and 36 months to investigate the relation between morphology and the walking pattern. A full 3D gait analysis using a VICON motion system was performed to gather kinematic data. Next, the differences in kinematic parameters between four morphological classes were assigned with a multiple analysis of variance, with a correction for walking experience. Also stepwise linear regressions were performed, to examine the relation between detailed morphological measurements and kinematic parameters. The regression models showed relationships between kinematic parameters of the ankle, hip, thorax and morphology. All results indicated that the upper body played an important role in the coordination of the walking pattern, especially in the frontal plane.

The relationship between morbidity after axillary surgery and long-term quality of life in breast cancer patients: the role of anxiety.

AIMS: Although arm/shoulder morbidity after sentinel lymph node biopsy (SLNB) and/or axillary lymph node dissection (ALND) has been studied before, information is lacking concerning self-imposed restrictions in activities and long-term consequences of both surgical procedures in relationship to quality of life (QoL) and anxiety. METHODS: Eighty-nine disease-free breast cancer survivors completed a set of questionnaires assessing arm/shoulder symptoms, limitations in daily life, anxiety and QoL. Also, the ipsi- and contra lateral arm circumference and the range of shoulder motion were measured. RESULTS: Fifty-one women had SLNB, 25 had SLNB followed by ALND and 13 had ALND. Although ALND patients experienced more shoulder symptoms, limitations in daily life and imposed more restrictions on themselves than SLNB patients, no significant differences during physical examination were found. A decreased range of motion and a higher score on trait anxiety resulted in a lower QoL. Trait anxiety and perceived limitations in daily life predicted long-term quality of life. CONCLUSIONS: There is a discrepancy between experienced and measured limitations in range of shoulder motion. Anxiety and self-imposed restrictions play an important role in predicting long-term QoL and should get the necessary attention when addressing shoulder symptoms in breast cancer patients.