Cyclic mechanical strain guides capillary-like morphology in vitro

Introduction Stretching of tissue stimulates angiogenesis but increased motion at a fracture site hinders revascularisation. In vitro studies have indicated that mechanical stimuli promote angiogenic responses in endothelial cells, but can either inhibit or enhance responses when applied directly to angiogenesis assays. We anticipated that cyclic tension applied during endothelial network assembly would increase vascular structure formation up to a certain threshold. Methods Fibroblast/HUVEC co-cultures were subjected to cyclic equibiaxial strain (1 Hz; 6 h/day; 7 days) using the FlexerCell FX-4000T system and limiting rings for simultaneous application of multiple strain magnitudes (0–13%). Cells were labelled using anti-PECAM-1, and image analysis provided measures of endothelial network length and numbers of junctions. Results Cyclic stretching had no significant effect on the total length of endothelial networks (P > 0.2) but resulted in a strain-dependent decrease in branching and localised alignments of endothelial structures, which were in turn aligned with the supporting fibroblastic construct. Conclusion The organisation of endothelial networks under cyclic strain is dominated by structural adaptation to the supporting construct. It may be that, in fracture healing, the formation and integrity of the granulation tissue and callus is ultimately critical in revascularisation and its failure under severe strain conditions.

Lesions in the bed nucleus of the stria terminalis disrupt corticosterone and freezing responses elicited by a contextual but not by a specific cue-conditioned fear stimulus

The bed nucleus of the stria terminalis (BNST) is believed to be a critical relay between the central nucleus of the amygdala (CE) and the paraventricular nucleus of the hypothalamus in the control of hypothalamic–pituitary– adrenal (HPA) responses elicited by conditioned fear stimuli. If correct, lesions of CE or BNST should block expression of HPA responses elicited by either a specific conditioned fear cue or a conditioned context. To test this, rats were subjected to cued (tone) or contextual classical fear conditioning. Two days later, electrolytic or sham lesions were placed in CE or BNST. After 5 days, the rats were tested for both behavioral (freezing) and neuroendocrine (corticosterone) responses to tone or contextual cues. CE lesions attenuated conditioned freezing and corticosterone responses to both tone and con- text. In contrast, BNST lesions attenuated these responses to contextual but not tone stimuli. These results suggest CE is indeed an essential output of the amygdala for the expres- sion of conditioned fear responses, including HPA re- sponses, regardless of the nature of the conditioned stimu- lus. However, because lesions of BNST only affected behav- ioral and endocrine responses to contextual stimuli, the results do not support the notion that BNST is critical for HPA responses elicited by conditioned fear stimuli in general. Instead, the BNST may be essential specifically for contex- tual conditioned fear responses, including both behavioral and HPA responses, by virtue of its connections with the hippocampus, a structure essential to contextual condition- ing. The results are also not consistent with the hypothesis that BNST is only involved in unconditioned aspects of fear and anxiety.

Myosin light chain kinase regulates synaptic plasticity and fear learning in the lateral amygdala

Learning and memory depend on signaling mole- cules that affect synaptic efficacy. The cytoskeleton has been implicated in regulating synaptic transmission but its role in learning and memory is poorly understood. Fear learning depends on plasticity in the lateral nucleus of the amygdala. We therefore examined whether the cytoskeletal-regulatory protein, myosin light chain kinase, might contribute to fear learning in the rat lateral amygdala. Microinjection of ML-7, a specific inhibitor of myosin light chain kinase, into the lateral nucleus of the amygdala before fear conditioning, but not immediately afterward, enhanced both short-term memory and long-term memory, suggesting that myosin light chain kinase is involved specifically in memory acquisition rather than in posttraining consolidation of memory. Myosin light chain kinase inhibitor had no effect on memory retrieval. Furthermore, ML-7 had no effect on behavior when the train- ing stimuli were presented in a non-associative manner. An- atomical studies showed that myosin light chain kinase is present in cells throughout lateral nucleus of the amygdala and is localized to dendritic shafts and spines that are postsynaptic to the projections from the auditory thalamus to lateral nucleus of the amygdala, a pathway specifically impli- cated in fear learning. Inhibition of myosin light chain kinase enhanced long-term potentiation, a physiological model of learning, in the auditory thalamic pathway to the lateral nu- cleus of the amygdala. When ML-7 was applied without as- sociative tetanic stimulation it had no effect on synaptic responses in lateral nucleus of the amygdala. Thus, myosin light chain kinase activity in lateral nucleus of the amygdala appears to normally suppress synaptic plasticity in the cir- cuits underlying fear learning, suggesting that myosin light chain kinase may help prevent the acquisition of irrelevant fears. Impairment of this mechanism could contribute to pathological fear learning.

Export readiness index : construction and analysis

The internationalisation process of firms has attracted much research interest since the 1970s. It is noted, however, that a significant research gap exists in studies with a primary focus on the pre-internationalisation behaviour of firms. This paper proposes the incorporation of a pre-internationalisation phase into the traditional Uppsala model of firm internationalisation to address the issue of export readiness. Through extensive literature review, the concepts fundamental to the ability of an Uppsala type firm to begin internationalisation through an export entry mode are identified: exposure to stimuli factors, attitudinal commitment of decision makers towards exporting, the firm’s resource capabilities, as well as the moderating effect of lateral rigidity. The concept of export readiness is operationalised in this study through the construction of an export readiness index (ERI) using exploratory and confirmatory factor analysis. The index is then applied to some representative cases and tested using logistic regression to establish its validity as a diagnostic tool. The proposed ERI presents not only a more practical approach towards analysing firms’ export readiness but has also major public policy implications as a possible tool for government export promotion agencies.

Understanding the pre-internationalization phase decision heuristic of Australian SMEs

Since the 1970s, the Uppsala stages model has been one of the dominant explanations of firm internationalization. The model's focus on internationalization as a firm's gradual and incremental process of increasing international involvement has attracted much debate, with one criticism being that it is unclear in explaining how the internationalization process first originates within a firm. In this paper, the Uppsala model is extended through the incorporation of a pre-internationalization phase to explore the antecedents of firm internationalization. Adopting the Uppsala model's theoretical underpinnings, this paper develops and operationalizes a pre-internationalization phase decision heuristic in the form of an ‘export readiness index'. Four constructs are proposed that drive and inhibit export commencement decision-making during a firm's preinternationalization phase: export stimuli, attitudinal/psychological commitment, resources and lateral rigidity. Through a survey of Australian exporting and non-exporting small-medium sized enterprises (SMEs), the Export Readiness Index (ERI) is developed through factor analysis and tested using logistic regression. Results of the study and their potential implications are discussed.

Food reward sensitivity predicts overconsumption of high-fat snack food

Overconsumption of snack foods has been linked to rising rates of obesity, with our ‘obesogenic’ environment and its abundance of palatable, high-calorie foods and associated cues especially implicated. However, it is clear that some individuals are particularly susceptible to overconsumption and weight gain. It was hypothesised that individuals sensitive to the rewarding properties of palatable foods, and associated stimuli, would show elevated consumption. Snack food intake was measured in 50 adults (mean age 34.5 years, BMI 23.9 kg/m2, 56% female) in a repeated measures design, both with and without a ‘food cue’. Trait (BIS/BAS scales), behavioural (computerised CARROT) and food reward were assessed. Sensitivity to food reward, but not generalised reward, was positively associated with snack food intake. This relationship was not affected by the presence of a food cue. Findings are discussed in the context of implications for weight management.

Smart material interfaces : a vision

In this paper, we introduce a vision called Smart Material Interfaces (SMIs), which takes advantage of the latest generation of engineered materials that has a special property defined “smart”. They are capable of changing their physical properties, such as shape, size and color, and can be controlled by using certain stimuli (light, potential difference, temperature and so on). We describe SMIs in relation to Tangible User Interfaces (TUIs) to convey the usefulness and a better understanding of SMIs.

Prospects for studying how high-intensity compression waves cause damage in human blast injuries

Since World War I, explosions have accounted for over 70% of all injuries in conflict. With the development of improved personnel protection of the torso, improved medical care and faster aeromedical evacuation, casualties are surviving with more severe injuries to the extremities. Understanding the processes involved in the transfer of blast-induced shock waves through biological tissues is essential for supporting efforts aimed at mitigating and treating blast injury. Given the inherent heterogeneities in the human body, we argue that studying these processes demands a highly integrated approach requiring expertise in shock physics, biomechanics and fundamental biological processes. This multidisciplinary systems approach enables one to develop the experimental framework for investigating the material properties of human tissues that are subjected to high compression waves in blast conditions and the fundamental cellular processes altered by this type of stimuli. Ultimately, we hope to use the information gained from these studies in translational research aimed at developing improved protection for those at risk and improved clinical outcomes for those who have been injured from a blast wave.

H2-O2 porous fuel injection in a radical farming scramjet

This paper reports on the experimental testing of oxygen compatible ceramic matrix composite porous injectors in a nominally two-dimensional hydrogen fuelled and oxygen enriched radical farming scramjet in the T4 shock tunnel facility. All experiments were performed at a dynamic pressure of 146 kPa, an equivalent flight Mach number of 9.7, a stagnation pressure and enthalpy of 40MPa and 4.3 MJ/kg respectively and at a fuelling condition that resulted in an average equivalence ratio of 0.472. Oxygen was pre-mixed with the fuel prior to injection to achieve enrichment percentages of approximately 13%, 15% and 17%. These levels ensured that the hydrogen-oxidiser mix injected into the engine always remained too fuel rich to sustain a flame without any additional mixing with the captured air. Addition of pre-mixed oxygen with the fuel was found to significantly alter the performance of the engine; enhancing both combustion and ignition and converting a previously observed limited combustion condition into one with sustained and noticeable combustion induced pressure rise. Increases in the enrichment percentage lead to further increases in combustion levels and acted to reduce ignition lengths within the engine. Suppressed combustion runs, where a nitrogen test gas was used, confirmed that the pressure rise observed in these experiments as attributed to the oxygen enrichment and not associated with the increased mass injected.

The effect of high voltage, high frequency pulsed electric field on slain ovine cortical bone

High power, high frequency pulsed electric fields known as pulsed power (PP) has been applied recently in biology and medicine. However, little attention has been paid to investigate the application of pulse power in musculoskeletal system and its possible effect on functional behavior and biomechanical properties of bone tissue. This paper presents the first research investigating whether or not PP can be applied safely on bone tissue as a stimuli and what will be the possible effect of these signals on the characteristics of cortical bone by comparing the mechanical properties of this type of bone pre and post expose to PP and in comparison with the control samples. A positive buck‑boost converter was applied to generate adjustable high voltage, high frequency pulses (up to 500 V and 10 kHz). The functional behavior of bone in response to pulse power excitation was elucidated by applying compressive loading until failure. The stiffness, failure stress (strength) and the total fracture energy (bone toughness) were determined as a measure of the main bone characteristics. Furthermore, an ultrasonic technique was applied to determine and comprise bone elasticity before and after pulse power stimulation. The elastic property of cortical bone samples appeared to remain unchanged following exposure to pulse power excitation for all three orthogonal directions obtained from ultrasonic technique and similarly from the compression test. Nevertheless, the compressive strength and toughness of bone samples were increased when they were exposed to 66 h of high power pulsed electromagnetic field compared to the control samples. As the toughness and the strength of the cortical bone tissue are directly associated with the quality and integrity of the collagen matrix whereas its stiffness is primarily related to bone mineral content these overall results may address that although, the pulse power stimulation can influence the arrangement or the quality of the collagen network causing the bone strength and toughness augmentation, it apparently did not affect the mineral phase of the cortical bone material. The results also confirmed that the indirect application of high power pulsed electric field at 500 V and 10 kHz through capacitive coupling method was safe and did not destroy the bone tissue construction.

Induction of epithelial-mesenchymal transition (EMT) in breast cancer cells is calcium signal dependent

Signals from the tumor microenvironment trigger cancer cells to adopt an invasive phenotype through epithelial-mesenchymal transition (EMT). Relatively little is known regarding key signal transduction pathways that serve as cytosolic bridges between cell surface receptors and nuclear transcription factors to induce EMT. A better understanding of these early EMT events may identify potential targets for the control of metastasis. One rapid intracellular signaling pathway that has not yet been explored during EMT induction is calcium. Here we show that stimuli used to induce EMT produce a transient increase in cytosolic calcium levels in human breast cancer cells. Attenuation of the calcium signal by intracellular calcium chelation significantly reduced epidermal growth factor (EGF)- and hypoxia-induced EMT. Intracellular calcium chelation also inhibited EGF-induced activation of signal transducer and activator of transcription 3 (STAT3), while preserving other signal transduction pathways such as Akt and extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation. To identify calcium-permeable channels that may regulate EMT induction in breast cancer cells, we performed a targeted siRNA-based screen. We found that transient receptor potential-melastatin-like 7 (TRPM7) channel expression regulated EGF-induced STAT3 phosphorylation and expression of the EMT marker vimentin. Although intracellular calcium chelation almost completely blocked the induction of many EMT markers, including vimentin, Twist and N-cadherin, the effect of TRPM7 silencing was specific for vimentin protein expression and STAT3 phosphorylation. These results indicate that TRPM7 is a partial regulator of EMT in breast cancer cells, and that other calcium-permeable ion channels are also involved in calcium-dependent EMT induction. In summary, this work establishes an important role for the intracellular calcium signal in the induction of EMT in human breast cancer cells. Manipulation of calcium-signaling pathways controlling EMT induction in cancer cells may therefore be an important therapeutic strategy for preventing metastases.

Transcriptional regulation of flavonoid biosynthesis in nectarine (Prunus persica) by a set of R2R3 MYB transcription factors

Background Flavonoids such as anthocyanins, flavonols and proanthocyanidins, play a central role in fruit colour, flavour and health attributes. In peach and nectarine (Prunus persica) these compounds vary during fruit growth and ripening. Flavonoids are produced by a well studied pathway which is transcriptionally regulated by members of the MYB and bHLH transcription factor families. We have isolated nectarine flavonoid regulating genes and examined their expression patterns, which suggests a critical role in the regulation of flavonoid biosynthesis. Results In nectarine, expression of the genes encoding enzymes of the flavonoid pathway correlated with the concentration of proanthocyanidins, which strongly increases at mid-development. In contrast, the only gene which showed a similar pattern to anthocyanin concentration was UDP-glucose-flavonoid-3-O-glucosyltransferase (UFGT), which was high at the beginning and end of fruit growth, remaining low during the other developmental stages. Expression of flavonol synthase (FLS1) correlated with flavonol levels, both temporally and in a tissue specific manner. The pattern of UFGT gene expression may be explained by the involvement of different transcription factors, which up-regulate flavonoid biosynthesis (MYB10, MYB123, and bHLH3), or repress (MYB111 and MYB16) the transcription of the biosynthetic genes. The expression of a potential proanthocyanidin-regulating transcription factor, MYBPA1, corresponded with proanthocyanidin levels. Functional assays of these transcription factors were used to test the specificity for flavonoid regulation. Conclusions MYB10 positively regulates the promoters of UFGT and dihydroflavonol 4-reductase (DFR) but not leucoanthocyanidin reductase (LAR). In contrast, MYBPA1 trans-activates the promoters of DFR and LAR, but not UFGT. This suggests exclusive roles of anthocyanin regulation by MYB10 and proanthocyanidin regulation by MYBPA1. Further, these transcription factors appeared to be responsive to both developmental and environmental stimuli.

Red colouration in apple fruit is due to the activity of the MYB transcription factor, MdMYB10

Anthocyanin concentration is an important determinant of the colour of many fruits. In apple (Malus x domestica), centuries of breeding have produced numerous varieties in which levels of anthocyanin pigment vary widely and change in response to environmental and developmental stimuli. The apple fruit cortex is usually colourless, although germplasm does exist where the cortex is highly pigmented due to the accumulation of either anthocyanins or carotenoids. From studies in a diverse array of plant species, it is apparent that anthocyanin biosynthesis is controlled at the level of transcription. Here we report the transcript levels of the anthocyanin biosynthetic genes in a red-fleshed apple compared with a white-fleshed cultivar. We also describe an apple MYB transcription factor, MdMYB10, that is similar in sequence to known anthocyanin regulators in other species. We further show that this transcription factor can induce anthocyanin accumulation in both heterologous and homologous systems, generating pigmented patches in transient assays in tobacco leaves and highly pigmented apple plants following stable transformation with constitutively expressed MdMYB10. Efficient induction of anthocyanin biosynthesis in transient assays by MdMYB10 was dependent on the co-expression of two distinct bHLH proteins from apple, MdbHLH3 and MdbHLH33. The strong correlation between the expression of MdMYB10 and apple anthocyanin levels during fruit development suggests that this transcription factor is responsible for controlling anthocyanin biosynthesis in apple fruit; in the red-fleshed cultivar and in the skin of other varieties, there is an induction of MdMYB10 expression concurrent with colour formation during development. Characterization of MdMYB10 has implications for the development of new varieties through classical breeding or a biotechnological approach.

Quantitative sensory measures distinguish office workers with varying levels of neck pain and disability

This study was undertaken to investigate any relationship between sensory features and neck pain in female office workers using quantitative sensory measures to better understand neck pain in this group. Office workers who used a visual display monitor for more than four hours per day with varying levels of neck pain and disability were eligible for inclusion. There were 85 participants categorized according to their scores on the neck disability index (NDI): 33 with no pain (NDI < 8); 38 with mild levels of pain and disability (NDI 9–29); 14 with moderate levels of pain (NDI ⩾ 30). A fourth group of women without neck pain (n = 22) who did not work formed the control group. Measures included: thermal pain thresholds over the posterior cervical spine; pressure pain thresholds over the posterior neck, trapezius, levator scapulae and tibialis anterior muscles, and the median nerve trunk; sensitivity to vibrotactile stimulus over areas of the hand innervated by the median, ulnar and radial nerves; sympathetic vasoconstrictor response. All tests were conducted bilaterally. ANCOVA models were used to determine group differences between the means for each sensory measure. Office workers with greater self-reported neck pain demonstrated hyperalgesia to thermal stimuli over the neck, hyperalgesia to pressure stimulation over several sites tested; hypoaesthesia to vibration stimulation but no changes in the sympathetic vasoconstrictor response. There is evidence of multiple peripheral nerve dysfunction with widespread sensitivity most likely due to altered central nociceptive processing initiated and sustained by nociceptive input from the periphery.

Do left and right asymmetries of hemispheric preference interact with attention to predict local and global performance in applied tasks?

Many cognitive neuroscience studies show that the ability to attend to and identify global or local information is lateralised between the two hemispheres in the human brain; the left hemisphere is biased towards the local level, whereas the right hemisphere is biased towards the global level. Results of two studies show attention-focused people with a right ear preference (biased towards the left hemisphere) are better at local tasks, whereas people with a left ear preference (biased towards the right hemisphere) are better at more global tasks. In a third study we determined if right hemisphere-biased followers who attend to global stimuli are likely to have a stronger relationship between attention and globally based supervisor ratings of performance. Results provide evidence in support of this hypothesis. Our research supports our model and suggests that the interaction between attention and lateral preference is an important and novel predictor of work-related outcomes.