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Purpose: MitraClip is the sole percutaneous device approved for functional mitral regurgitation (MR; FMR) but MR recurs in over one third of patients. As device-induced mechanical effects are a potential cause for MR recurrence, we tested the hypothesis that MitraClip increases leaflet stress and procedure-related strain in sub-valvular left ventricular (LV) myocardium in FMR associated with coronary disease (FMR-CAD). Methods: Simulations were performed using finite element models of the LV + mitral valve based on MRI of 5 sheep with FMR-CAD. Models were modified to have a 20% increase in LV volume (↑LV_VOLUME) and MitraClip was simulated with contracting beam elements (virtual sutures) placed between nodes in the center edge of the anterior (AL) and posterior (PL) mitral leaflets. Effects of MitraClip on leaflet stress in the peri-MitraClip region of AL and PL, septo-lateral annular diameter (SLAD), and procedure-related radial strain (Err) in the sub-valvular myocardium were calculated. Results: MitraClip increased peri-MitraClip leaflet stress at end-diastole (ED) by 22.3±7.1 kPa (p<0.0001) in AL and 14.8±1.2 kPa (p<0.0001) in PL. MitraClip decreased SLAD by 6.1±2.2 mm (p<0.0001) and increased Err in the sub-valvular lateral LV myocardium at ED by 0.09±0.04 (p<0.0001)). Furthermore, MitraClip in ↑LV_VOLUME was associated with persistent effects at ED but also at end-systole where peri-MitraClip leaflet stress was increased in AL by 31.9±14.4 kPa (p = 0.0268) and in PL by 22.5±23.7 kPa (p = 0.0101). Conclusions: MitraClip for FMR-CAD increases mitral leaflet stress and radial strain in LV sub-valvular myocardium. Mechanical effects of MitraClip are augmented by LV enlargement. [ABSTRACT FROM AUTHOR]

Fricative consonants are known to be pronounced by controlling turbulent flow inside a vocal tract. In this study, a simplified vocal tract model was proposed to investigate the characteristics of flow and sound during production of the fricative [s] in a word context. By controlling the inlet flow rate and tongue speed, the acoustic characteristics of [s] were reproduced by the model. The measurements with a microphone and a hot-wire anemometer showed that the flow velocity at the teeth gap and far-field sound pressure started oscillating before the tongue reached the /s/ position, and continued during tongue descent. This behaviour was not affected by the changes of the tongue speed. These results indicate that there is a time shift between source generation and tongue movement. This time shift can be a physical constraint in the articulation of words which include /s/. With the proposed model, we could investigate the effects of tongue speed on the flow and sound generation in a parametric way. The proposed methodology is applicable for other phonemes to further explore the aeroacoustics of phonation. [ABSTRACT FROM AUTHOR]

Background: Fetal monitoring based on electrocardiographic (ECG) morphology is obtained from a single unipolar fetal scalp electrode. Ideally, it should be obtained from multiple leads, as ECG waveform depends on alignment between electrode and electrical heart axis. This alignment is unknown in fetuses. Besides, fetuses are surrounded by conductive media, which may influence ECG waveform. We explored the influence of electrode position and head orientation on ECG waveforms of unipolar and bipolar scalp ECGs recorded in air and in conductive medium. Methods: We recorded ECGs in one adult subject at five different scalp positions in five different head orientations both in dry and immersed conditions. The ratio between T-amplitude and QRS-amplitude (T/QRS ratio) of unipolar and bipolar scalp ECGs was determined and compared between all conditions. Results: In the dry condition, we observed in the unipolar leads little to no difference between different electrode positions (maximal T/QRS difference 0.00–0.01) and minor differences between head orientations (0.02–0.03), whereas bipolar leads showed no recognizable ECG signal at all. During the immersed condition, we found variation in the unipolar leads, both between electrode positions (maximal T/QRS difference 0.02–0.05) and between head orientations (0.03–0.06). Bipolar leads showed different ECG signals in contrasting head orientations. Conclusions: Both unipolar and bipolar scalp lead-derived ECG waveforms are influenced by electrode position and head orientation when the subject is submerged in a conductive medium. Fetal monitoring based on single scalp lead ECG waveform might be suboptimal, as it lacks correction for fetal head orientation and electrode position. [ABSTRACT FROM AUTHOR]

Objectives: An extended-wavelength diffuse reflectance spectroscopy (EWDRS) technique was evaluated for its ability to differentiate between and classify different skin and tissue types in an in vivo pig model. Materials and methods: EWDRS recordings (450–1550 nm) were made on skin with different degrees of pigmentation as well as on the pig snout and tongue. The recordings were used to train a support vector machine to identify and classify the different skin and tissue types. Results: The resulting EWDRS curves for each skin and tissue type had a unique profile. The support vector machine was able to classify each skin and tissue type with an overall accuracy of 98.2%. The sensitivity and specificity were between 96.4 and 100.0% for all skin and tissue types. Conclusion: EWDRS can be used in vivo to differentiate between different skin and tissue types with good accuracy. Further development of the technique may potentially lead to a novel diagnostic tool for e.g. non-invasive tumor margin delineation. [ABSTRACT FROM AUTHOR]

Superoxide dismutases (SODs), as a family of metalloenzymes related to the removal of reactive oxygen species (ROS), have not previously been investigated at genome-wide level in tea plant. In this study, 10 CsSOD genes were identified in tea plant genome, including 7 Cu/Zn-SODs (CSDs), 2 Fe-SODs (FSDs) and one Mn-SOD (MSD), and phylogenetically classified in three subgroups, respectively. Physico-chemical characteristic, conserved motifs and potential protein interaction analyses about CsSOD proteins were carried out. Exon-intron structures and codon usage bias about CsSOD genes were also examined. Exon-intron structures analysis revealed that different CsSOD genes contained various number of introns. On the basis of the prediction of regulatory miRNAs of CsSODs, a modification 5' RNA ligase-mediated (RLM)-RACE was performed and validated that csn-miR398a-3p-1 directly cleaves CsCSD4. By prediction of cis-acting elements, the expression patterns of 10 CsSOD genes and their regulatory miRNAs were detected under cold, drought, exogenous methyl jasmonate (MeJA) and gibberellin (GA3) treatments. The results showed that most of CsSODs except for CsFSD2 were induced under cold stress and CsCSDs may play primary roles under drought stress; exogenous GA3 and MeJA could also stimulated/inhibited distinct CsSODs at different stages. In addition, we found that csn-miR398a-3p-1 negatively regulated the expression of CsCSD4 may be a crucial regulatory mechanism under cold stress. This study provides a certain basis for the studies about stress resistance in tea plants, even provide insight into comprehending the classification, evolution, diverse functions and influencing factors of expression patterns for CsSOD genes. [ABSTRACT FROM AUTHOR]

Honey bees, Apis mellifera, are a globally significant pollinator species and are currently in decline, with losses attributed to an array of interacting environmental stressors. Extremely low frequency electromagnetic fields (ELF EMFs) are a lesser-known abiotic environmental factor that are emitted from a variety of anthropogenic sources, including power lines, and have recently been shown to have a significant impact on the cognitive abilities and behaviour of honey bees. Here we have investigated the effects of field-realistic levels of ELF EMFs on aversive learning and aggression levels, which are critical factors for bees to maintain colony strength. Bees were exposed for 17 h to 100 μT or 1000 μT ELF EMFs, or a sham control. A sting extension response (SER) assay was conducted to determine the effects of ELF EMFs on aversive learning, while an intruder assay was conducted to determine the effects of ELF EMFs on aggression levels. Exposure to both 100 μT and 1000 μT ELF EMF reduced aversive learning performance by over 20%. Exposure to 100 μT ELF EMFs also increased aggression scores by 60%, in response to intruder bees from foreign hives. These results indicate that short-term exposure to ELF EMFs, at levels that could be encountered in bee hives placed under power lines, reduced aversive learning and increased aggression levels. These behavioural changes could have wider ecological implications in terms of the ability of bees to interact with, and respond appropriately to, threats and negative environmental stimuli. [ABSTRACT FROM AUTHOR]

The origins of agriculture in Southwest Asia over 10,000 years ago and its subsequent spread into Europe during the Neolithic have been the focus of much archaeological research over the past several decades. Increasingly more sophisticated analytical techniques have allowed for better understanding of the complex interactions that occurred amongst humans, animals, and their environments during this transition. The Aegean Islands are critically situated where Anatolia and the mainland Greece meet, making the region pivotal for understanding the movement of the Neolithic into Europe. Located on the largest Turkish Aegean island of Gökçeada, the site of Uğurlu Höyük dates to the early Neolithic and has been the subject of ongoing excavations and research integrating a rigorous dating program with comprehensive zooarchaeological research. This paper focuses on the combination of bone collagen and tooth enamel stable isotope data with existing archaeological data to develop a fine-resolution picture of the spread of the Neolithic, particularly the importation and management of domestic fauna on Gökçeada, with broader relevance for understanding Aegean-Anatolian interactions. The stable isotope values from the fauna at Uğurlu have been used for both diachronic intrasite analyses and intersite comparisons between contemporaneous mainland sites. Integrating stable isotope and zooarchaeological datasets makes Uğurlu one of the first island sites to provide a comprehensive understanding of the geographic origin of Neolithic livestock populations and the timing of their spread from Anatolia into Europe during the process of Neolithization. [ABSTRACT FROM AUTHOR]

For early breast cancer detection, mammography is nowadays the commonly used standard imaging approach, offering a valuable clinical tool for visualization of suspicious findings like microcalcifications and tumors within the breast. However, due to the superposition of anatomical structures, the sensitivity of mammography screening is limited. Within the last couple of years, the implementation of contrast-enhanced spectral mammography (CESM) based on K-edge subtraction (KES) imaging helped to improve the identification and classification of uncertain findings. In this study, we introduce another approach for CESM based on a two-material decomposition, with which we expect fundamental improvements compared to the clinical procedure. We demonstrate the potential of our proposed method using the quasi-monochromatic radiation of a compact synchrotron source—the Munich Compact Light Source (MuCLS)—and a modified mammographic accreditation phantom. For direct comparison with the clinical CESM approach, we also performed a standard dual-energy KES at the MuCLS, which outperformed the clinical CESM images in terms of contrast-to-noise ratio (CNR) and spatial resolution. However, the dual-energy-based two-material decomposition approach achieved even higher CNR values. Our experimental results with quasi-monochromatic radiation show a significant improvement of the image quality at lower mean glandular dose (MGD) than the clinical CESM. At the same time, our study indicates the great potential for the material-decomposition instead of clinically used KES to improve the quantitative outcome of CESM. [ABSTRACT FROM AUTHOR]

Plantar fasciitis is a frequently occurring overuse injury of the foot. Shoes with a stiff rocker profile are a commonly prescribed treatment modality used to alleviate complaints associated with plantar fasciitis. In rocker shoes the apex position was moved proximally as compared to normal shoes, limiting the progression of the ground reaction forces (GRF) and peak plantarflexion moments during gait. A stiff sole minimizes dorsiflexion of the toes. The aim of this study was to investigate whether the biomechanical effects of rocker shoes lead to minimization of plantar aponeurosis (PA) strain during gait in patients with plantar fasciitis and in healthy young adults. 8 patients with plantar fasciitis (1 male, 7 females; mean age 55.0 ± 8.4 years) and 8 healthy young adults (8 females; mean age 24.1 ± 1.6 years) participated in the study. Each participant walked for 1 minute on an instrumented treadmill while wearing consecutively in random order shoes with a normal apex position (61.2 ± 2.8% apex) with flexible insole (FN), normal apex position with stiff insole (SN), proximal apex position (56.1 ± 2.6% apex) with flexible insole (FR) and proximal apex position with stiff insole (SR). Marker position data of the foot and lower leg and GRF were recorded. An OpenSim foot model was used to compute the change in PA length based on changes in foot segment positions during gait. The changes in PA length due to increases in Achilles tendon forces were computed based on previous data of a cadaver study. PA strain computed from both methods was not statistically different between shoe conditions. Peak Achilles tendon force, peak first metatarsophalangeal (MTP1) joint angle and peak plantarflexion moment were significantly lower when walking with the rocker shoe with a proximal apex position and a stiff insole for all subjects (p<.05). Changes in Achilles tendon forces during gait accounted for 65 ± 2% of the total PA strain. Rocker shoes with a stiff insole reduce peak dorsiflexion angles of the toes and plantar flexion moments, but not PA strain because the effects of a proximal apex position and stiff insole do not occur at the same time, but independently affect PA strain at 80–90% and 90–100% of the stance phase. Rocker shoes with an apex position of ~56% are insufficient to significantly reduce peak PA strain values in patients with plantar fasciitis and healthy young adults. [ABSTRACT FROM AUTHOR]

Swim-up is a sperm purification method that is being used daily in andrology labs around the world as a simple step for in vitro sperm selection. This method accumulates the most motile sperm in the upper fraction and leaves sperm with low or no motility in the lower fraction. However, the underlying reasons are not fully understood. In this article, we compare metabolic rate, motility and sperm tail length of bovine sperm cells of the upper and lower fraction. The metabolic assay platform reveals oxygen consumption rates and extracellular acidification rates simultaneously and thereby delivers the metabolic rates in real time. Our study confirms that the upper fraction of bull sperm has not only improved motility compared to the cells in the lower fraction but also shows higher metabolic rates and longer flagella. This pattern was consistent across media of two different levels of viscosity. We conclude that the motility-based separation of the swim-up technique is also reflected in underlying metabolic differences. Metabolic assays could serve as additional or alternative, label-free method to evaluate sperm quality. [ABSTRACT FROM AUTHOR]

The neural representation and perceptual salience of tonal signals presented in different noise maskers were investigated. The properties of the maskers and signals were varied such that they produced different amounts of either monaural masking release, binaural masking release, or a combination of both. The signals were then presented at different levels above their corresponding masked thresholds and auditory evoked potentials (AEPs) were measured. It was found that, independent of the masking condition, the amplitude of the P2 component of the AEP was similar for the same stimulus levels above masked threshold, suggesting that both monaural and binaural effects of masking release were represented at the level of the auditory pathway where P2 is generated. The perceptual salience of the signal was evaluated at equal levels above masked threshold using a rating task. In contrast to the electrophysiological findings, the subjective ratings of the perceptual signal salience were less consistent with the signal level above masked threshold and varied strongly across listeners and masking conditions. Overall, the results from the present study suggest that the P2 amplitude of the AEP represents an objective indicator of the audibility of a target signal in the presence of complex acoustic maskers. [ABSTRACT FROM AUTHOR]

Breaks filled with different break activities often interrupt cognitive performance in everyday life. Previous studies have reported that both enhancing and deteriorating effects on challenging ongoing tasks such as working memory updating, depend on the type of break activity. However, neural mechanisms of these break-related alterations in working memory performance have not been studied, to date. Therefore, we conducted a brain imaging study to identify the neurobiological correlates of effects on the n-back working memory task related to different break activities. Before performing the n-back task in the magnetic resonance imaging (MRI) scanner, young adults were exposed to break activities in the MRI scanner involving (i) eyes-open resting, (ii) listening to music, and (iii) playing the video game "Angry Birds". Heart rate was measured by a pulse oximeter during the experiment. We found that increased heart rate during gaming as well as decreased relaxation levels after a video gaming break was related to poorer n-back task performance, as compared to listening to music. On the neural level, video gaming reduced supplementary motor area activation during working memory performance. These results may indicate that video gaming during a break may affect working memory performance by interfering with arousal state and frontal cognitive control functions. [ABSTRACT FROM AUTHOR]

Recent experimental work has revealed unusual features of the effect of certain drugs on cardiac inwardly rectifying potassium currents, including the constitutively active and acetylcholine-induced components of acetylcholine-sensitive current (IKAch). These unusual features have included alternating susceptibility of the current components to activation and inhibition induced by ethanol or nicotine applied at various concentrations, and significant correlation between the drug effect and the current magnitude measured under drug-free conditions. To explain these complex drug effects, we have developed a new type of quantitative model to offer a possible interpretation of the effect of ethanol and nicotine on the IKAch channels. The model is based on a description of IKAch as a sum of particular currents related to the populations of channels formed by identical assemblies of different α-subunits. Assuming two different channel populations in agreement with the two reported functional IKAch-channels (GIRK1/4 and GIRK4), the model was able to simulate all the above-mentioned characteristic features of drug-channel interactions and also the dispersion of the current measured in different cells. The formulation of our model equations allows the model to be incorporated easily into the existing integrative models of electrical activity of cardiac cells involving quantitative description of IKAch. We suppose that the model could also help make sense of certain observations related to the channels that do not show inward rectification. This new ionic channel model, based on a concept we call population type, may allow for the interpretation of complex interactions of drugs with ionic channels of various types, which cannot be done using the ionic channel models available so far. [ABSTRACT FROM AUTHOR]

Activated platelets release adenosine trisphosphate (ATP) and bioluminescence analysis of ATP release is usually used to monitor activation of platelets induced by various stimulants. However, bioluminescence analysis of ATP possesses poor linearity, the signal is quickly attenuated, and the accuracy of ATP release from platelets is hard to determine accurately enough to be used in a high throughput screening of platelet inhibitors. The present study was designed to optimize bioluminescence analysis of ATP released by platelets and expand its application in high throughput screening of platelet inhibitors. The results showed that accuracy of ATP analysis was significantly improved by adding coenzyme A (CoA) and signal attenuation of ATP analysis was greatly postponed by adding bovine serum albumin (BSA) both in Hank's balanced salt solution (HBSS) and Tyrode's buffer. Furthermore, ATP release of activated platelets and inhibitory effects of Ly294002 and Staurosporine on platelet activation were accurately determined by our optimized bioluminescence analysis of ATP. Thus, we have successfully constructed an optimized bioluminescence analysis of ATP which can be used in high throughput screening of platelet inhibitors. [ABSTRACT FROM AUTHOR]

Malignant gliomas remain incurable with a poor prognosis despite of aggressive treatment. We have been studying the development of brain tumors in a glioma rat model, where rats develop brain tumors after prenatal exposure to ethylnitrosourea (ENU), and there is a sizable interval between when the first pathological changes are noted and tumors become detectable with MRI. Our aim to define a molecular timeline through proteomic profiling of the cerebrospinal fluid (CSF) such that brain tumor commitment can be revealed earlier than at the presymptomatic stage. A comparative proteomic approach was applied to profile CSF collected serially either before, at and after the time MRI becomes positive. Elastic net (EN) based models were developed to infer the timeline of normal or tumor development respectively, mirroring a chronology of precisely timed, "clocked", adaptations. These CSF changes were later quantified by longitudinal entropy analyses of the EN predictive metric. False discovery rates (FDR) were computed to control the expected proportion of the EN models that are due to multiple hypothesis testing. Our ENU rat brain tumor dating EN model indicated that protein content in CSF is programmed even before tumor MRI detection. The findings of the precisely timed CSF tumor microenvironment changes at presymptomatic stages, deviation from the normal development timeline, may provide the groundwork for the understanding of adaptation of the brain environment in tumorigenesis to devise effective brain tumor management strategies. [ABSTRACT FROM AUTHOR]

Although there is good evidence to indicate a major role of intrinsic impairment of the contractile apparatus in muscle weakness seen in several pathophysiological conditions, the factors responsible for control of myofibrillar function are not fully understood. To investigate the role of mechanical load in myofibrillar function, we compared the skinned fiber force between denervated (DEN) and dexamethasone-treated (DEX) rat skeletal muscles with or without neuromuscular electrical stimulation (ES) training. DEN and DEX were induced by cutting the sciatic nerve and daily injection of dexamethasone (5 mg/kg/day) for 7 days, respectively. For ES training, plantarflexor muscles were electrically stimulated to produce four sets of five isometric contractions each day. In situ maximum torque was markedly depressed in the DEN muscles compared to the DEX muscles (-74% vs. -10%), whereas there was not much difference in the degree of atrophy in gastrocnemius muscles between DEN and DEX groups (-24% vs. -17%). Similar results were obtained in the skinned fiber preparation, with a greater reduction in maximum Ca2+-activated force in the DEN than in the DEX group (-53% vs. -16%). Moreover, there was a parallel decline in myosin heavy chain (MyHC) and actin content per muscle volume in DEN muscles, but not in DEX muscles, which was associated with upregulation of NADPH oxidase (NOX) 2, neuronal nitric oxide synthase (nNOS), and endothelial NOS expression, translocation of nNOS from the membrane to the cytosol, and augmentation of mRNA levels of muscle RING finger protein 1 (MuRF-1) and atrogin-1. Importantly, mechanical load evoked by ES protects against DEN- and DEX-induced myofibrillar dysfunction and these molecular alterations. Our findings provide novel insights regarding the difference in intrinsic contractile properties between DEN and DEX and suggest an important role of mechanical load in preserving myofibrillar function in skeletal muscle. [ABSTRACT FROM AUTHOR]

Migratory cells use distinct motility modes to navigate different microenvironments, but it is unclear whether these modes rely on the same core set of polarity components. To investigate this, we disrupted actin-related protein 2/3 (Arp2/3) and the WASP-family verprolin homologous protein (WAVE) complex, which assemble branched actin networks that are essential for neutrophil polarity and motility in standard adherent conditions. Surprisingly, confinement rescues polarity and movement of neutrophils lacking these components, revealing a processive bleb-based protrusion program that is mechanistically distinct from the branched actin-based protrusion program but shares some of the same core components and underlying molecular logic. We further find that the restriction of protrusion growth to one site does not always respond to membrane tension directly, as previously thought, but may rely on closely linked properties such as local membrane curvature. Our work reveals a hidden circuit for neutrophil polarity and indicates that cells have distinct molecular mechanisms for polarization that dominate in different microenvironments. [ABSTRACT FROM AUTHOR]

There is an urgent need for new anti-tubercular agents which can lead to a shortened treatment time by targeting persistent or non-replicating bacilli. In order to assess compound activity against non-replicating Mycobacterium tuberculosis, we developed a method to detect the bactericidal activity of novel compounds within 7 days. Our method uses incubation at low pH in order to induce a non-replicating state. We used a strain of M. tuberculosis expressing luciferase; we first confirmed the linear relationship between luminescence and viable bacteria (determined by colony forming units) under our assay conditions. We optimized the assay parameters in 96-well plates in order to achieve a reproducible assay. Our final assay used M. tuberculosis in phosphate-citrate buffer, pH 4.5 exposed to compounds for 7 days; viable bacteria were determined by luminescence. We recorded the minimum bactericidal concentration at pH 4.5 (MBC4.5) representing >2 logs of kill. We confirmed the utility of the assay with control compounds. The ionophores monensin, niclosamide, and carbonyl cyanide 3-chlorophenylhydrazone and the anti-tubercular drugs pretomanid and rifampicin were active, while several other drugs such as isoniazid, ethambutol, and linezolid were not. [ABSTRACT FROM AUTHOR]

To understand the effect of attention on neuronal dynamics, we propose a multi-module network, with each module consisting of fully interconnected groups of excitatory and inhibitory neurons. This network shows transitive dynamics among quasi-attractors as its typical dynamics. When the release of acetylcholine onto the network is simulated by attention, the transitive dynamics change into stable dynamics in which the system converges to an attractor. We found that this network can reproduce three experimentally observed properties of attention-dependent response modulation, namely an increase in the firing rate, a decrease in the Fano factor of the firing rate, and a decrease in the correlation coefficients between the firing rates of pairs of neurons. Moreover, we also showed theoretically that the release of acetylcholine increases the sensitivity to bottom-up inputs by changing the response function. [ABSTRACT FROM AUTHOR]

Extrusion of xenobiotics is essential for allowing animals to remove toxic substances present in their diet or generated as a biproduct of their metabolism. By transporting a wide range of potentially noxious substrates, active transporters of the ABC transporter family play an important role in xenobiotic extrusion. One such class of transporters are the multidrug resistance P-glycoprotein transporters. Here, we investigated P-glycoprotein transport in the Malpighian tubules of the desert locust (Schistocerca gregaria), a species whose diet includes plants that contain toxic secondary metabolites. To this end, we studied transporter physiology using a modified Ramsay assay in which ex vivo Malpighian tubules are incubated in different solutions containing the P-glycoprotein substrate dye rhodamine B in combination with different concentrations of the P-glycoprotein inhibitor verapamil. To determine the quantity of the P-glycoprotein substrate extruded we developed a simple and cheap method as an alternative to liquid chromatography–mass spectrometry, radiolabelled alkaloids or confocal microscopy. Our evidence shows that: (i) the Malpighian tubules contain a P-glycoprotein; (ii) tubule surface area is positively correlated with the tubule fluid secretion rate; and (iii) as the fluid secretion rate increases so too does the net extrusion of rhodamine B. We were able to quantify precisely the relationships between the fluid secretion, surface area, and net extrusion. We interpret these results in the context of the life history and foraging ecology of desert locusts. We argue that P-glycoproteins contribute to the removal of xenobiotic substances from the haemolymph, thereby enabling gregarious desert locusts to maintain toxicity through the ingestion of toxic plants without suffering the deleterious effects themselves. [ABSTRACT FROM AUTHOR]

Background: Australia has one of the highest skin cancer rates in the world. 'SunSmart' is a multi-component, internationally recognised community-wide skin cancer prevention program implemented in Melbourne, Australia, since summer 1988-1989. Following recent reductions in melanoma rates among younger Australian cohorts, the extent of behaviour change and the potential contribution of prevention programs to this decline in melanoma rates are of interest. Sun protection is a multifaceted behaviour. Measures previously applied to monitor change over time in preventive behaviour for this population focused on individual behaviours. The omission of multiple behaviours that reduce exposure to ultraviolet radiation (UV) may have led to underestimates of behaviour change, meriting further analysis of long-term trends to contribute to this debate.Methods and Findings: A population-based survey was conducted in Melbourne in the summer before SunSmart commenced (1987-1988) and across summers in 3 subsequent decades (1988-2017). During summer months, residents (14-69 years) were recruited to cross-sectional weekly telephone interviews assessing their tanning attitudes, sun protection behaviour, and sunburn incidence on the weekend prior to interview. Quotas were used to ensure the sample was proportional to the population by age and sex, while younger respondents were oversampled in some years. The majority of the respondents reported their skin was susceptible to sunburn. Changes in sun protection behaviour were analysed for N = 13,285 respondents in multivariable models, cumulating surveys within decades (1987-1988: N = 1,655; 1990s: N = 5,258; 2000s: N = 3,385; 2010s: N = 2,987) and adjusting for relevant ambient weather conditions and UV levels on weekend dates. We analysed specific and composite behaviours including a novel analysis of the use of maximal sun protection, which considered those people who stayed indoors during peak UV hours together with those people well-protected when outdoors. From a low base, use of sun protection increased rapidly in the decade after SunSmart commenced. The odds of use of at least 1 sun protection behaviours on summer weekends was 3 times higher in the 1990s than pre-SunSmart (adjusted odds ratio [AOR] 3.04, 95% CI 2.52-3.68, p < 0.001). There was a smaller increase in use of maximal sun protection including shade (AOR = 1.68, 95% CI 1.44-1.97, p < 0.001). These improvements were sustained into the 2000s and continued to increase in the 2010s. Inferences about program effects are limited by the self-reported data, the absence of a control population, the cross-sectional study design, and the fact that the survey was not conducted in all years. Other potential confounders may include increasing educational attainment among respondents over time and exposure to other campaigns such as tobacco and obesity prevention.Conclusions: With an estimated 20-year lag between sun exposure and melanoma incidence, our findings are consistent with SunSmart having contributed to the reduction in melanoma among younger cohorts. [ABSTRACT FROM AUTHOR]

Deficits in the ankle plantarflexor muscles, such as weakness and contracture, occur commonly in conditions such as cerebral palsy, stroke, muscular dystrophy, Charcot-Marie-Tooth disease, and sarcopenia. While these deficits likely contribute to observed gait pathologies, determining cause-effect relationships is difficult due to the often co-occurring biomechanical and neural deficits. To elucidate the effects of weakness and contracture, we systematically introduced isolated deficits into a musculoskeletal model and generated simulations of walking to predict gait adaptations due to these deficits. We trained a planar model containing 9 degrees of freedom and 18 musculotendon actuators to walk using a custom optimization framework through which we imposed simple objectives, such as minimizing cost of transport while avoiding falling and injury, and maintaining head stability. We first generated gaits at prescribed speeds between 0.50 m/s and 2.00 m/s that reproduced experimentally observed kinematic, kinetic, and metabolic trends for walking. We then generated a gait at self-selected walking speed; quantitative comparisons between our simulation and experimental data for joint angles, joint moments, and ground reaction forces showed root-mean-squared errors of less than 1.6 standard deviations and normalized cross-correlations above 0.8 except for knee joint moment trajectories. Finally, we applied mild, moderate, and severe levels of muscle weakness or contracture to either the soleus (SOL) or gastrocnemius (GAS) or both of these major plantarflexors (PF) and retrained the model to walk at a self-selected speed. The model was robust to all deficits, finding a stable gait in all cases. Severe PF weakness caused the model to adopt a slower, "heel-walking" gait. Severe contracture of only SOL or both PF yielded similar results: the model adopted a "toe-walking" gait with excessive hip and knee flexion during stance. These results highlight how plantarflexor weakness and contracture may contribute to observed gait patterns. [ABSTRACT FROM AUTHOR]

Dendritic cells (DCs) are the most effective professional antigen-presenting cell. They ferry antigen from the extremities to T cells and are essential for the initiation of an adaptive immune response. Despite interest in how DCs respond to chemical stimuli, there have been few attempts to model DC migration. In this paper, we simulate the motility of DCs by modeling the generation of forces by filopodia and a force balance on the cell. The direction of fliopodial extension is coupled to differential occupancy of cognate chemokine receptors across the cell. Our model simulates chemokinesis and chemotaxis in a variety of chemical and mechanical environments. Simulated DCs undergoing chemokinesis were measured to have a speed of 5.1 ± 0.07 μm·min-1 and a persistence time of 3.2 ± 0.46 min, consistent with experiment. Cells undergoing chemotaxis exhibited a stronger chemotactic response when exposed to lower average chemokine concentrations, also consistent with experiment. We predicted that when placed in two opposing gradients, cells will cluster in a line, which we call the “line of equistimulation;” this clustering has also been observed. We calculated the effect of varying gradient steepness on the line of equistimulation, with steeper gradients resulting in tighter clustering. Moreover, gradients are found to be most potent when cells are in a gradient of chemokine whose mean concentration is close to the binding of the Kd to the receptor, and least potent when the mean concentration is 0.1Kd. Comparing our simulations to experiment, we can give a quantitative measure of the strength of certain chemokines relative to others. Assigning the signal of CCL19 binding CCR7 a baseline strength of 1, we found CCL21 binding CCR7 had a strength of 0.28, and CXCL12 binding CXCR4 had a strength of 0.30. These differences emerge despite both chemokines having virtually the same Kd, suggesting a mechanism of signal amplification in DCs requiring further study. [ABSTRACT FROM AUTHOR]

Mechanical loading is essential for the maintenance of musculoskeletal homeostasis. Cartilage has been demonstrated to be highly mechanoresponsive, but the mechanisms by which chondrocytes respond to mechanical stimuli are not clearly understood. The goal of the study was to determine how LRP4, LRP5, and LRP6 within canonical Wnt-signaling are regulated in simulated microgravity and cyclic hydrostatic pressure, and to investigate the potential role of LRP 4/5/6 in cartilage degeneration. Rat chondrosacroma cell (RCS) pellets were stimulated using either cyclic hydrostatic pressure (1Hz, 7.5 MPa, 4hr/day) or simulated microgravity in a rotating wall vessel (RWV) bioreactor (11RPM, 24hr/day). LRP4/5/6 mRNA expression was assessed by RT-qPCR and LRP5 protein expression was determined by fluorescent immunostaining. To further evaluate our in vitro findings in vivo, mice were subjected to hindlimb suspension for 14 days and the femoral heads stained for LRP5 expression. We found that, in vitro, LRP4/5/6 mRNA expression is modulated in a time-dependent manner by mechanical stimulation. Additionally, LRP5 protein expression is upregulated in response to both simulated microgravity and cyclic hydrostatic pressure. LRP5 is also upregulated in vivo in the articular cartilage of hindlimb suspended mice. This is the first study to examine how LRP4/5/6, critical receptors within musculoskeletal biology, respond to mechanical stimulation. Further elucidation of this mechanism could provide significant clinical benefit for the identification of pharmaceutical targets for the maintenance of cartilage health. [ABSTRACT FROM AUTHOR]

Purpose: The effects of gravity on bevacizumab or the recommended head position after intraocular bevacizumab injection have not been reported. To evaluate the effect of gravity on bevacizumab in vitro, we added bevacizumab to the upper part of a test tube filled with balanced salt solution (BSS) and examined its distribution over time. Materials and methods: Sixty-four test tubes were divided equally into two groups; group 1 (32, collected from upper part of the tube) and group 2 (32, collected from lower part of the tube). Each test tube was filled with 5 mL BSS before bevacizumab (1.25 mg/0.05 mL) was added, and then stored at 36°C. Bevacizumab concentration in 8 test tubes from each group was measured at 12, 24, 48, and 168 h using an enzyme-linked immunosorbent analysis (ELISA) kit. Mann–Whitney and Jonckheere–Terpstra tests were used for statistical analysis. Results: Bevacizumab concentration was significantly higher in Group 2 than in Group 1 at 12, 24, 48, and 168 h (12, 24, 48, and 168 h; P < 0.01 each; Mann–Whitney test). The mean change in bevacizumab concentration over time tended to increase in Group 1 (P < 0.01; Jonckheere–Terpstra test), but tended to decrease in Group 2 (P < 0.01; Jonckheere–Terpstra test). Conclusions: The significant differences in concentration between the upper and lower parts even after a considerable amount of storage time showed that bevacizumab did not dissolve immediately and diffused evenly throughout the solution. It appeared that more bevacizumab settled in the lower part of the tube than in the upper part because of gravitational force. However, the concentration difference between the upper and lower parts decreased as bevacizumab gradually diffused over time, indicating that the difference in concentration due to gravity was more significant at the beginning of bevacizumab injection. [ABSTRACT FROM AUTHOR]

Stress has become a widely experienced state all around the world, and previous literature has found that stress impacts individuals’ cognition, emotion, coping behaviors and psychological well-being in general. Relatively little is known about how stress influences individuals’ perception of stimuli changes, a ubiquitous phenomenon known as scope sensitivity. In the current work, we explore whether individuals with higher levels of chronic stress are sensitive to stimuli changes, such as price and quantity differences. Two empirical studies consistently show that chronically stressed individuals exhibit scope insensitivity, as they rated the expensiveness of two hotel rooms with different prices as being less different and indicated a smaller difference in their willingness-to-buy five CDs versus ten CDs. Possible explanations and theoretical and practical implications in the broader field are discussed. [ABSTRACT FROM AUTHOR]

When we perform a movement we generally have a clear distinction between which parts of the world constitute our body and which parts do not. However, how the sense of ownership over our body supports movement is not yet fully understood. We aimed to see whether a sense of ownership over the hand supports the performance of rapid hand movements. In three experiments (n = 48, n = 30, n = 24), we presented participants with congruent and incongruent visuotactile and visuoproprioceptive information regarding their own hand. In keeping with previous experiments, multisensory disintegration resulted in a reduction in the subjective sensation of ownership over the hand, as reflected in questionnaire responses. Following sensory stimulation, participants were required to rapidly abduct their index finger whilst the movement was tracked. We examined the hypothesis that, should a sense of ownership over the limb be necessary for generating rapid movements with that limb, reaction time would increase when hand ownership was reduced, whilst the acceleration and velocity of the movement would decrease. We observed that reductions in own hand ownership did not interfere with rapid index finger abduction, suggesting that the motor system may not be reliant on a subjective sense of ownership over the body in order to generate movement. [ABSTRACT FROM AUTHOR]

The nicotinic acetylcholine receptor (nAChR) is an excitatory pentameric ligand-gated ion channel (pLGIC), homologous to the inhibitory γ-aminobutyric acid (GABA) type A receptor targeted by pharmaceuticals and endogenous sedatives. Activation of the GABAA receptor by the neurosteroid allopregnanolone can be inhibited competitively by thyroid hormone (L-3,3’,5-triiodothyronine, or T3), but modulation of nAChR by T3 or neurosteroids has not been investigated. Here we show that allopregnanolone inhibits the nAChR from Torpedo californica at micromolar concentrations, as do T3 and the anionic neurosteroid pregnenolone sulfate (PS). We test for the role of protein and ligand charge in mediated receptor inhibition by varying pH in a narrow range around physiological pH. We find that both T3 and PS become less potent with increasing pH, with remarkably similar trends in IC50 when T3 is neutral at pH < 7.3. After deprotonation of T3 (but no additional deprotonation of PS) at pH 7.3, T3 loses potency more slowly with increasing pH than PS. We interpret this result as indicating the negative charge is not required for inhibition but does increase activity. Finally, we show that both T3 and PS affect nAChR channel desensitization, which may implicate a binding site homologous to one that was recently indicated for accelerated desensitization of the GABAA receptor by PS. [ABSTRACT FROM AUTHOR]

Previous studies reported a significant association between postural control and lower-limb strength of several muscle groups, however, they were focused especially on knee muscles and ankle plantar and dorsal flexors. The aim of the present study is to examine the correlation between the muscle strength of ankle invertors, evertors, plantar flexors, and dorsal flexors and the control of bipedal stance in young and older adults. Thirty one young (aged 22.8 ± 2.6 years) and thirty one older adults (aged 70.5 ± 7.2 years) voluntarily participated in this study. Ankle muscle strength was evaluated by an isokinetic dynamometer. Normalized peak torque and work were averaged for four repetitions and for both lower limbs. The control of bipedal stance was evaluated by the sample entropy derived from an accelerometer placed on the lumbar spine while the subject stood on a foam pad with eyes open. Results showed significant age-related differences in ankle muscle strength and sample entropy in medial-lateral direction. More interestingly, the correlation between ankle muscle strength and the sample entropy was significantly different between young and older adults. Indeed, no significant correlation was observed in the younger adults. Conversely, in the older adults, the work of the ankle evertors positively correlated with sample entropy in the medial-lateral direction during bipedal stance (r = 0.36), whereas the peak torque and work of the dorsal flexors were significantly correlated with sample entropy in the anterior-posterior direction during bipedal stance (r = 0.44 for both variables). In the young adults, results suggest that, standing on foam with eyes open is a relatively easy postural task that does not require the full ankle muscle strength capacity. Taken together, the present findings suggest that older adults have a different association between ankle muscle strength and the sample entropy during bipedal stance. [ABSTRACT FROM AUTHOR]

The transport and distribution of charged molecules in polyelectrolyte solutions are of both fundamental and practical importance. A practical example, which is the specific subject addressed in the present paper, is the transport and distribution of charged species into cartilage. The charged species could be a contrast agent or a drug molecule involved in diagnosis or treatment of the widespread degenerative disease osteoarthritis, which leads to degradation of articular cartilage. Associated scientific issues include the rate of transport and the equilibrium concentrations of the charged species in the cartilage and the synovial fluid. To address these questions, we present results from magnetic resonance micro-imaging experiments on a model system of articular cartilage. The experiments yield temporally and spatially resolved data on the transport of a negatively charged contrast agent (charge = -2), used in medical examinations of cartilage, into a polyelectrolyte solution, which is designed to capture the electrostatic interactions in cartilage. Also presented is a theoretical analysis of the transport where the relevant differential equations are solved using finite element techniques as well as treated with approximate analytical expressions. In the analysis, non-ideal effects are included in the treatment of the mobile species in the system. This is made possible by using results from previous Monte Carlo simulations. The results demonstrate the importance of taking non-idealities into account when data from measurements of transport of charged solutes in a system with fixed charges from biological polyelectrolytes are analyzed. [ABSTRACT FROM AUTHOR]

Predictive coding is a key mechanism to understand the computational processes underlying brain functioning: in a hierarchical network, higher levels predict the activity of lower levels, and the unexplained residuals (i.e., prediction errors) are passed back to higher layers. Because of its recursive nature, we wondered whether predictive coding could be related to brain oscillatory dynamics. First, we show that a simple 2-level predictive coding model of visual cortex, with physiological communication delays between levels, naturally gives rise to alpha-band rhythms, similar to experimental observations. Then, we demonstrate that a multilevel version of the same model can explain the occurrence of oscillatory traveling waves across levels, both forward (during visual stimulation) and backward (during rest). Remarkably, the predictions of our model are matched by the analysis of 2 independent electroencephalography (EEG) datasets, in which we observed oscillatory traveling waves in both directions. [ABSTRACT FROM AUTHOR]

Predictive processing (e.g., predictive coding) is a predominant paradigm in cognitive neuroscience. This Primer considers the various levels of commitment neuroscientists have to the neuronal process theories that accompany the principles of predictive processing. Specifically, it reviews and contextualises a recent PLOS Biology study of alpha oscillations and travelling waves. We will see that alpha oscillations emerge naturally under the computational architectures implied by predictive coding-and may tell us something profound about recurrent message passing in brain hierarchies. Specifically, the bidirectional nature of forward and backward waves speaks to opportunities to understand attention and how it nuances bottom-up and top-down influences. [ABSTRACT FROM AUTHOR]

Plant trichomes originate from epidermal cell, forming protective structure from abiotic and biotic stresses. Different from the unicellular trichome in Arabidopsis, tomato trichomes are multicellular structure and can be classified into seven different types based on cell number, shape and the presence of glandular cells. Despite the importance of tomato trichomes in insect resistance, our understanding of the tomato trichome morphogenesis remains elusive. In this study, we quantitatively analyzed morphological traits of trichomes in tomato and further performed live imaging of cytoskeletons in stably transformed lines with actin and microtubule markers. At different developmental stages, two types of cytoskeletons exhibited distinct patterns in different trichome cells, ranging from transverse, spiral to longitudinal. This gradual transition of actin filament angle from basal to top cells could correlate with the spatial expansion mode in different cells. Further genetic screen for aberrant trichome morphology led to the discovery of a number of independent mutations in SCAR/WAVE and ARP2/3 complex, which resulted in actin bundling and distorted trichomes. Disruption of microtubules caused isotropic expansion while abolished actin filaments entirely inhibited axial extension of trichomes, indicating that microtubules and actin filaments may control distinct aspects of trichome cell expansion. Our results shed light on the roles of cytoskeletons in the formation of multicellular structure of tomato trichomes. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) were obtained from human bone marrow and amplified in cultures supplemented with human platelet lysate in order to generate myofibroblasts. When MSCs were seeded in solid collagen scaffolds, they differentiated into myofibroblasts that were observed to strongly bind to the substrate, forming a 3D cell scaffold network that developed tension and shortening after KCl stimulation. Moreover, MSC-laden scaffolds recapitulated the Frank-Starling mechanism so that active tension increased in response to increases in the initial length of the contractile system. This constituted a bioengineering tissue that exhibited the contractile properties observed in both striated and smooth muscles. By using the A. F. Huxley formalism, we determined the myosin crossbridge (CB) kinetics of attachment (f1) and detachment (g1 and g2), maximum myosin ATPase activity, molar myosin concentration, unitary CB force and maximum CB efficiency. CB kinetics were dramatically slow, characterizing the non-muscle myosin type IIA (NMMIIA) present in myofibroblasts. When MSCs were seeded in solid collagen scaffolds functionalized with Arg-Gly-Asp (RGD), contractility increased and CB kinetics were modified, whereas the unitary NMMIIA-CB force and maximum CB efficiency did not change. In conclusion, we provided a non-muscle bioengineering tissue whose molecular mechanical characteristics of NMMIIA were very close to those of a non-muscle contractile tissue such as the human placenta. [ABSTRACT FROM AUTHOR]

Purpose: Development of a supervised machine-learning model capable of predicting clinically relevant molecular subtypes of pancreatic ductal adenocarcinoma (PDAC) from diffusion-weighted-imaging-derived radiomic features. Methods: The retrospective observational study assessed 55 surgical PDAC patients. Molecular subtypes were defined by immunohistochemical staining of KRT81. Tumors were manually segmented and 1606 radiomic features were extracted with PyRadiomics. A gradient-boosted-tree algorithm was trained on 70% of the patients (N = 28) and tested on 30% (N = 17) to predict KRT81+ vs. KRT81- tumor subtypes. A gradient-boosted survival regression model was fit to the disease-free and overall survival data. Chemotherapy response and survival were assessed stratified by subtype and radiomic signature. Radiomic feature importance was ranked. Results: The mean±STDEV sensitivity, specificity and ROC-AUC were 0.90±0.07, 0.92±0.11, and 0.93±0.07, respectively. The mean±STDEV concordance indices between the disease-free and overall survival predicted by the model based on the radiomic parameters and actual patient survival were 0.76±0.05 and 0.71±0.06, respectively. Patients with a KRT81+ subtype experienced significantly diminished median overall survival compared to KRT81- patients (7.0 vs. 22.6 months, HR 4.03, log-rank-test P = <0.001) and a significantly improved response to gemcitabine-based chemotherapy over FOLFIRINOX (10.14 vs. 3.8 months median overall survival, HR 2.33, P = 0.037) compared to KRT81- patients, who responded significantly better to FOLFIRINOX over gemcitabine-based treatment (30.8 vs. 13.4 months median overall survival, HR 2.41, P = 0.027). Entropy was ranked as the most important radiomic feature. Conclusions: The machine-learning based analysis of radiomic features enables the prediction of subtypes of PDAC, which are highly relevant for disease-free and overall patient survival and response to chemotherapy. [ABSTRACT FROM AUTHOR]

The objective was to evaluate vaginal temperature as a thermoregulatory response of Nellore heifers under different microclimatic conditions. The study was conducted during one year in an experimental area located at 54°37′W, 20°27′S, and 530 m of altitude in Brazil. Twenty-four Nellore females were reared in integrated crop-livestock-forestry systems with different shading patterns. The randomized complete block experimental design was utilized with a sub subdivided plots scheme, with plot corresponding to the production systems, the subplot to the season of the year, and the sub subplot, the hours of the day. To characterize the microclimate, data regarding air and black globe temperatures, and air relative humidity were collected and from them, temperature-humidity index was calculated. Vaginal temperature was obtained by using a bottom-type temperature logger (i-button) attached to an adapted intravaginal device. The black-globe temperature explained the variation on vaginal temperature. Increases on vaginal temperature were only observed, on average, two hours after the increase of black-globe temperature. The microclimatic conditions found in the systems, resulting from the various tree densities, modify the vaginal temperature in different degrees, demonstrating that the shading effect is not always accompanied by improvements in thermal comfort. The system with intermediate density showed a better microclimatic condition and, consequently, a lower increase in vaginal temperature. The interaction between air temperature, humidity and solar radiation resulted in adverse environmental conditions, however, Nellore heifers showed good adaptation to the environment. In conclusion, vaginal temperature is a good indicator to evaluate the thermoregulatory response in Nellore heifers. [ABSTRACT FROM AUTHOR]

Inertial measurement unit (IMU)-based gait analysis can be used to quantitatively analyze the bilateral coordination and gait asymmetry (GA). The purpose of this study was to investigate changes in bilateral coordination and GA due to gait speed using an IMU based gait analysis and identify spatiotemporal factors affecting bilateral coordination and GA. Eighty healthy adults (40 men and 40 women) participated in the study. The mean age was 26.2 years, and the mean body mass index was 22.8 kg/m2. Three different walking speeds (80%, 100%, and 120% of preferred walking speed) on a treadmill were applied for 1 min of continuous level walking using a shoe-type IMU-based gait analysis system. The phase coordination index (PCI) and GA were calculated on three different walking speeds. Several variables (gait speed, height, body mass index, cadence, and step length) were analyzed as possible factors affecting the PCI and GA. Bilateral coordination and GA improved during fast walking (p = 0.005 and p = 0.019, respectively) and deteriorated during slow walking (p<0.001 and p = 0.008, respectively), compared with the participants’ preferred walking speeds. The correlation analysis revealed that PCI was negatively correlated with step length at each walking condition and lower gait speed was negatively correlated with PCI and GA during slow walking. Both bilateral coordination and GA had a negative linear relationship with gait speed, showing an improvement in the fast walking condition and deterioration in the slow walking condition. Step length was the factor associated with the change in the bilateral coordination. [ABSTRACT FROM AUTHOR]

Research on pro-social rat behaviour is growing within the fields of comparative psychology and social neuroscience. However, much work remains on mapping important variables influencing this behaviour, and there is even disagreement on whether this behaviour is empathetically motivated and correctly labelled pro-social, or whether the behaviour is motivated by social contact. The present study used the helping behaviour paradigm where a rat can release a familiar cagemate from a restrainer. Prior to testing with a trapped cagemate, restrainer door opening was trained and baseline opening latencies when the restrainer was empty or baited with food were established. The findings show that the first-time release occurred sooner than in previous research and that rats used a previously demonstrated response to release the trapped cagemate. Further, rats opened the restrainer door more often and with shorter latencies when the restrainer contained a cagemate than when the restrainer was empty, but less often and with longer latencies than when the restrainer contained food. The test of whether illumination levels affect door-opening included in the study showed no effects. [ABSTRACT FROM AUTHOR]

Electrical impedance myography (EIM) is a technique for the assessment of muscle health and composition and has been shown to be sensitive to a variety of muscle pathologies including neurogenic atrophy and connective tissue deposition. However, it has been minimally studied in pure inflammation. In this study, we sought to assess EIM sensitivity to experimental inflammation induced by the localized intramuscular injection of λ-carrageenan. A total of 91 mice underwent 1–1000 kHz EIM measurements of gastrocnemius using a needle array, followed by injection of either 0.3% λ-carrageenan in phosphate-buffered saline (PBS) or PBS alone. Animals were then remeasured with EIM at 4, 24, 48, or 72 hours and euthanized and quantitative assessment of muscle histology was performed. Parallel alterations in both 5 and 50 kHz EIM values were identified at 4 and 24 hours, including reductions in phase, reactance, and resistance. In PBS-treated animals these values normalized by 48 hours, whereas substantial reductions in phase and reactance in 5 kHz EIM values persisted at 48 and 72 hours (i.e., values of phase 72 hours post-injection were 6.51 ± 0.40 degrees for λ-carrageenan versus 8.44 ± 0.35 degrees for PBS p<0.001, n = 11 per group). The degree of basophilic area observed in muscle sections by histology correlated to the degree of phase change at these two time points (Rspearman = -0.51, p = 0.0029). Changes in low frequency EIM parameters are sensitive to the presence of inflammatory infiltrates, and have the potential of serving as a simple means of quantifying the presence and extent of muscle inflammation without the need for biopsy. [ABSTRACT FROM AUTHOR]

Background: Toxigenic Vibrio cholerae resides in aquatic reservoirs of cholera-endemic areas mostly in a dormant form known as conditionally viable environmental cells (CVEC) in which the bacteria remain embedded in an exopolysaccharide matrix, and fail to grow in routine bacteriological culture. The CVEC can be resuscitated by supplementing culture media with either of two autoinducers CAI-1 and AI-2, which are signal molecules controlling quorum sensing, a regulatory network of bacterial gene expression dependent on cell density. This study investigated possible existence of variant strains that overproduce AIs, sufficient to resuscitate CVEC in environmental waters. Methods: Environmental V. cholerae isolates and Tn insertion mutants of a V. cholerae strain C6706 were screened for production of AIs using bioluminescent reporter strains. Relevant mutations in environmental strains which overproduced AI-2 were characterized by nucleotide sequencing and genetic complementation studies. Effect of AIs produced in culture supernatants of relevant strains on reactivation of CVEC in water was determined by resuscitation assays. Results: Two of 54 environmental V. cholerae isolates were found to overproduce AI-2. Screening of a Tn-insertion library of V. cholerae strain C6706, identified a mutant which overproduced AI-2, and carried Tn insertion in the cqsS gene. Nucleotide sequencing also revealed mutations inactivating the cqsS gene in environmental isolates which overproduced AI-2, and this property was reversed when complemented with a wild type cqsS gene. Culture of river water samples supplemented with spent medium of these mutants resuscitated dormant V. cholerae cells in water. Significance: V. cholerae strains with inactivated cqsS gene may offer a convenient source of AI-2 in enhanced assays for monitoring bacteriological quality of water. The results also suggest a potential role of naturally occurring cqsS mutants in the environmental biology of V. cholerae. Furthermore, similar phenomenon may have relevance in the ecology of other waterborne bacterial pathogens beyond V. cholerae. [ABSTRACT FROM AUTHOR]

Many animals are able to sense the earth’s magnetic field, including varieties of arthropods and members of all major vertebrate groups. While the existence of this magnetic sense is widely accepted, the mechanism of action remains unknown. Building from recent work on synthetic magnetoreceptors, we propose a new model for natural magnetosensation based on the rotating magnetocaloric effect (RME), which predicts that heat generated by magnetic nanoparticles may allow animals to detect features of the earth’s magnetic field. Using this model, we identify the conditions for the RME to produce physiological signals in response to the earth’s magnetic field and suggest experiments to distinguish between candidate mechanisms of magnetoreception. [ABSTRACT FROM AUTHOR]

Background and objectives: The construction of whole-body magnetic resonance (MR) imaging atlases allows to perform statistical analysis with applications in anomaly detection, longitudinal, and correlation studies. Atlas-based methods require a common coordinate system to which all the subjects are mapped through image registration. Optimisation of the reference space is an important aspect that affects the subsequent analysis of the registered data, and having a reference space that is neutral with respect to local tissue volume is valuable in correlation studies. The purpose of this work is to generate a reference space for whole-body imaging that has zero voxel-wise average volume change when mapped to a cohort. Methods: This work proposes an approach to register multiple whole-body images to a common template using volume changes to generate a synthetic reference space, starting with an initial reference and refining it by warping it with a deformation that brings the voxel-wise average volume change associated to the mappings of all the images in the cohort to zero. Results: Experiments on fat/water separated whole-body MR images show how the method effectively generates a reference space neutral with respect to volume changes, without reducing the quality of the registration nor introducing artefacts in the anatomy, while providing better alignment when compared to an implicit reference groupwise approach. Conclusions: The proposed method allows to quickly generate a reference space neutral with respect to local volume changes, that retains the registration quality of a sharp template, and that can be used for statistical analysis of voxel-wise correlations in large datasets of whole-body image data. [ABSTRACT FROM AUTHOR]

Humans and other animals effortlessly identify natural sounds and categorize them into behaviorally relevant categories. Yet, the acoustic features and neural transformations that enable sound recognition and the formation of perceptual categories are largely unknown. Here, using multichannel neural recordings in the auditory midbrain of unanesthetized female rabbits, we first demonstrate that neural ensemble activity in the auditory midbrain displays highly structured correlations that vary with distinct natural sound stimuli. These stimulus-driven correlations can be used to accurately identify individual sounds using single-response trials, even when the sounds do not differ in their spectral content. Combining neural recordings and an auditory model, we then show how correlations between frequency-organized auditory channels can contribute to discrimination of not just individual sounds but sound categories. For both the model and neural data, spectral and temporal correlations achieved similar categorization performance and appear to contribute equally. Moreover, both the neural and model classifiers achieve their best task performance when they accumulate evidence over a time frame of approximately 1–2 seconds, mirroring human perceptual trends. These results together suggest that time-frequency correlations in sounds may be reflected in the correlations between auditory midbrain ensembles and that these correlations may play an important role in the identification and categorization of natural sounds. [ABSTRACT FROM AUTHOR]

Nucleases are enzymes that can degrade genomic DNA and RNA that decrease the accuracy of quantitative measures of those nucleic acids. Here, we study conventional heating, standard microwave irradiation, and Lyse-It, a microwave-based lysing technology, for the potential to fragment and inactivate DNA and RNA endonucleases. Lyse-It employs the use of highly focused microwave irradiation to the sample ultimately fragmenting and inactivating RNase A, RNase B, and DNase I. Nuclease size and fragmentation were determined visually and quantitatively by SDS polyacrylamide gel electrophoresis and the mini-gel Agilent 2100 Bioanalyzer system, with a weighted size calculated to depict the wide range of nuclease fragmentation. Enzyme activity assays were conducted, and the rates were calculated to determine the effect of various lysing conditions on each of the nucleases. The results shown in this paper clearly demonstrate that Lyse-It is a rapid and highly efficient way to degrade and inactivate nucleases so that nucleic acids can be retained for down-stream detection. [ABSTRACT FROM AUTHOR]

Microbial fuel cells (MFCs) can evolve in a viable technology if environmentally sound materials are developed and became available at low cost for these devices. This is especially important not only for the designing of large wastewater treatment systems, but also for the fabrication of low-cost, single-use devices. In this work we synthesized membranes by a simple procedure involving easily-biodegradable and economic materials such as poly (vinyl alcohol) (PVA), chitosan (CS) and the composite PVA:CS. Membranes were chemical and physically characterized and compared to Nafion®. Performance was studied using the membrane as separator in a typical H-Type MFCs showing that PVA:CS membrane outperform Nafion® 4 times (power production) while being 75 times more economic. We found that performance in MFC depends over interactions among several membrane characteristics such as oxygen permeability and ion conductivity. Moreover, we design a paper-based micro-scale MFC, which was used as a toxicity assay using 16 μL samples containing formaldehyde as a model toxicant. The PVA:CS membrane presented here can offer low environmental impact and become a very interesting option for point of need single-use analytical devices, especially in low-income countries where burning is used as disposal method, and toxic fluoride fumes (from Nafion®) can be released to the environment. [ABSTRACT FROM AUTHOR]

Background: Alcohol is a major risk factor for liver cirrhosis. Recently, it was proposed that colder climate might causally lead to increased consumption of alcohol. Methods: We performed an ecologic study, using monthly updated data on mean temperature, sunlight hours and alcohol consumption from ten regions in Sweden, using publicly available data. A generalised additive model, adjusted for region, was applied to examine the association between mean temperature and mean sunlight hours with mean alcohol consumption. Results: We found a non-linear inverse association between mean monthly temperature and mean alcohol consumption, suggesting that warmer temperature was associated with increased alcohol consumption and colder temperature with a decreased consumption. We found no association between mean sunlight hours and alcohol consumption. Consumption was highest during public holidays. Conclusions: We found no association between a colder climate and increased alcohol consumption. Socio-economic factors are likely to explain the suggested association. [ABSTRACT FROM AUTHOR]

Collapse of the lateral cerebral ventricles after ventriculo-peritoneal drainage is a fatal complication in dogs with internal hydrocephalus. It occurs due to excessive outflow of cerebrospinal fluid into the peritoneal cavity (overshunting). In most shunt systems, one-way valves with different pressure settings regulate flow into the distal catheter to avoid overshunting. The rationale for the choice of an appropriate opening pressure is a setting at the upper limit of normal intracranial pressure in dogs. However, physiological intraventricular pressure in normal dogs vary between 5 and 12 mm Hg. Furthermore, we hypothesise that intraventricular pressure in hydrocephalic dogs might differ from pressure in normal dogs and we also consider that normotensive hydrocephalus exists in dogs, as in humans. In order to evaluate intraventricular pressure in hydrocephalic dogs, twenty-three client owned dogs with newly diagnosed communicating internal hydrocephalus were examined before implantation of a ventriculo-peritoneal shunt using a single use piezo-resistive strain-gauge sensor (MicroSensor ICP probe). Ventricular volume and brain volume were measured before surgery, based on magnetic resonance images. Total ventricular volume was calculated and expressed in relation to the total volume of the brain, including the cerebrum, cerebellum, and brainstem (ventricle-brain index). Multiple logistic regression analysis was performed to assess the influence of the covariates “age”, “gender”, “duration of clinical signs”, “body weight”, and “ventricle-brain index” on intraventricular pressure. The mean cerebrospinal fluid pressure in the hydrocephalic dogs was 8.8 mm Hg (standard deviation 4.22), ranging from 3–18 mm Hg. The covariates “age”, (P = 0.782), “gender” (P = 0.162), “body weight”, (P = 0.065), or ventricle-brain index (P = 0.27)” were not correlated with intraventricular pressure. The duration of clinical signs before surgery, however, was correlated with intraventricular pressure (P< 0.0001). Dogs with internal hydrocephalus do not necessarily have increased intraventricular pressure. Normotensive communicating hydrocephalus exists in dogs. [ABSTRACT FROM AUTHOR]

Purpose: To analyze the change of CT texture features of esophageal squamous cell carcinoma (ESC) during RT delivery and to correlate these changes with the RT responses and survival. Methods: A total of 61 ESC patients received radical RT were screened. Weekly CTs (4–6 sets for each patient) were acquired during RT. The tumors, normal esophageal mucosa tissue (NEC) of 5 cm and the spinal cord in the relevant area were delineated. CT texture features were extracted with a home-made tool. The changes of these features were analyzed by t-test. The correlations of the changes of features with RT responses and with patient survival were investigated by Pearson analysis. Results: The average changes were increased by 0.00072 ±0.00197 for coarseness, by 0.14 ±0.40 for entropy, and by 2.34 ±3.56 for strength. In addition, the average changes were reduced by 8.88 ±15.71cc for volume and by 0.07 ±0.11 for busyness. The changes of the coarseness, strength, STD and entropy in ESC were different for the good and poor response groups. The survival rate of the patients was significantly correlated with the change of coarseness and strength (P = 0.0027 and P = 0.0001). Conclusions: During RT, changes of CT texture features of ESC, e.g., coarseness, strength, STD, entropy and volume are correlated with radiation response and survival rate. With more clinical data and robust research, CT features, e.g., coarseness and strength, can be selected as outstanding imaging biomarkers for prediction of RT prognosis of ESC. [ABSTRACT FROM AUTHOR]

Introduction: Percutaneous pedicle screw (PPS) can provide internal fixation of the thoracolumbar spine through a minimally invasive surgical procedure. PPS fixation has been widely used to treat various spinal diseases. Rigid fixation of PPS is essential for managing osteoporotic spine in order to prevent the risks of screw loosening and implant failure. We recently developed a novel augmentation method using hydroxyapatite (HA) granules for PPS fixation. The aim of this study was to evaluate the strength and stiffness of PPS fixation augmented with HA granules using an osteoporotic bone model. Methods: Screws were inserted into uniform synthetic bone (sawbones) with and without augmentation. The uniaxial pullout strength and insertion torque of the screws were evaluated. In addition, each screw underwent cyclic toggling under incrementally increasing physiological loads until 2 mm of screwhead displacement occurred. The maximal pullout strength (N), maximal insertion torque (N·cm), number of toggle cycles and maximal load (N) required to achieve 2-mm screwhead displacement were compared between the screws with and without augmentation. Results: The maximal pullout strength was significantly stronger for screws with augmentation than for those without augmentation (302 ± 19 N vs. 254 ± 17 N, p < 0.05). In addition, the maximal insertion torque was significantly increased in screws with augmentation compared to those without augmentation (48 ± 4 N·cm vs. 26 ± 5 N·cm, p < 0.05). Furthermore, the number of toggle cycles and the maximal load required to reach 2 mm of displacement were significantly greater in screws with augmentation than in those without augmentation (106 ± 9 vs. 52 ± 10 cycles; 152 ± 4 N vs. 124 ± 5 N, p < 0.05). Conclusions: Augmentation using HA granules significantly enhanced the rigidity of PPS fixation in the osteoporotic bone model. The present study suggested that novel augmentation with HA granules may be a useful technique for PPS fixation in patients with osteoporotic spine. [ABSTRACT FROM AUTHOR]

Purpose: Diffusion magnetic resonance imaging and tractography has an important role in the visualization of brain white matter and assessment of tissue microstructure. There is a lack of correspondence between diffusion metrics of live tissue, ex vivo tissue, and histological findings. The objective of this study is to elucidate this connection by determining the specific diffusion alterations between live and ex vivo brain tissue. This may have an important role in the incorporation of diffusion imaging in ex vivo studies as a complement to histological sectioning as well as investigations of novel neurosurgical techniques. Methods: This study presents a method of high angular resolution diffusion imaging and tractography of intact and non-fixed ex vivo piglet brains. Most studies involving ex vivo brain specimens have been formalin-fixed or excised from their original biological environment, processes both of which are known to affect diffusion parameters. Thus, non-fixed ex vivo tissue is used. A region-of-interest based analysis of diffusion tensor metrics are compared to in vivo subjects in a selection of major white matter bundles in order to assess the translatability of ex vivo diffusion measurements. Results: Tractography was successfully achieved in both in vivo and ex vivo groups. No significant differences were found in tract connectivity, average streamline length, or apparent fiber density. Significantly decreased diffusivity (mean, axial, and radial; p<0.0005) in the non-fixed ex vivo group and unaltered fractional anisotropy (p>0.059) between groups were observed. Conclusion: This study validates the extrapolation of non-fixed fractional anisotropy measurements to live tissue and the potential use of ex vivo tissue for methodological development. [ABSTRACT FROM AUTHOR]