The influence of market orientation on innovation strategies

Purpose – The purpose of this paper is to examine the effects of market orientation on exploratory and exploitative innovation, and the moderating effects of family ownership on these relationships. Design/methodology/approach – This study utilizes multi-group path analysis and confirmatory factor analysis in LISREL on data from 228 firms in the Australian service sector. Findings – This study establishes that both customer and competitor innovation are positively related to exploitative and exploratory innovation. However, customer orientation does not lead to significantly stronger effects on exploitative innovation than on exploratory innovation, and competitor orientation does not lead to significantly stronger effects on exploratory innovation than on exploitative innovation. In addition, the study found that the relationship between customer orientation and exploratory innovation was stronger for family firms, while the relationships between competitor orientation and both exploratory and exploitative innovation were stronger for non-family firms. Research limitations/implications – The cross-sectional design is one weakness of this study. In addition, as firms in the present study came from the service sector the generalizability of the findings to other sectors of the economy need to be determined. Practical implications – These findings of this study highlight the need for managers to build a strong market orientation in order to promote innovation, and consider the effects of ownership structure on innovation strategies. Originality/value – This study is the first to measure the relative influence of customer and competitor orientation on a firm’s use of exploitative and exploratory innovation strategies

A novel stable isotope tracer method to simultaneously quantify skeletal muscle protein synthesis and breakdown

Background/Aims: Methodological challenges have been associated with the dynamic measurement of muscle protein breakdown (MPB), as have the measurement of both muscle protein synthesis (MPS) and MPB within the same experiment. Our aim was to use the transmethylation properties of methionine as proof-of-concept to measure rates of MPB via its methylation of histidine within skeletal muscle myofibrillar proteins, whilst simultaneously utilising methionine incorporation into bound protein to measure MPS.Results: During the synthesis measurement period, incorporation of methyl[D3]-13C-methionine into cellular protein in C2C12 myotubes was observed (representative of MPS), alongside an increase in the appearance of methyl[D3]-methylhistidine into the media following methylation of histidine (representative of MPB). For further validation of this approach, fractional synthetic rates (FSR) of muscle protein were increased following treatment of the cells with the anabolic factors insulin-like growth factor-1 (IGF-1) and insulin, while dexamethasone expectedly reduced MPS. Conversely, rates of MPB were reduced with IGF-1 and insulin treatments, whereas dexamethasone accelerated MPB.Conclusions: This is a novel stable isotope tracer approach that permits the dual assessment of muscle cellular protein synthesis and breakdown rates, through the provision of a single methionine amino acid tracer that could be utilised in a wide range of biological settings

Nutrient modulation in the management of disease-induced muscle wasting: evidence from human studies

Purpose of review: In addition to being essential for movement, skeletal muscles act as both a store and source of key macronutrients. As such, muscle is an important tissue for whole body homeostasis, undergoing muscle wasting in times of starvation, disease, and stress, for example, to provide energy substrates for other tissues. Yet, muscle wasting is also associated with disability, comorbidities, and mortality. As nutrition is so crucial to maintaining muscle homeostasis 'in health', it has been postulated that muscle wasting in cachexia syndromes may be alleviated by nutritional interventions. This review will highlight recent work in this area in relation to muscle kinetics, the acute metabolic (e.g. dietary protein), and longer-term effects of dietary interventions. Recent findings: Whole body and skeletal muscle protein synthesis invariably exhibit deranged kinetics (favouring catabolism) in wasting states; further, many of these conditions harbour blunted anabolic responses to protein nutrition compared with healthy controls. These derangements underlie muscle wasting. Recent trials of essential amino acid and protein-based nutrition have shown some potential for therapeutic benefit. Summary: Nutritional modulation, particularly of dietary amino acids, may have benefits to prevent or attenuate disease-induced muscle wasting. Nonetheless, there remains a lack of recent studies exploring these key concepts to make conclusive recommendations

Recent developments in deuterium oxide tracer approaches to measure rates of substrate turnover: implications for protein, lipid, and nucleic acid research

Purpose of review: Methods that inform on dynamic metabolism that can be applied to clinical populations to understand disease progression and responses to therapeutic interventions are of great importance. This review perspective will highlight recent advances, development, and applications of the multivalent stable isotope tracer deuterium oxide (D2O) to the study of substrate metabolism with particular reference to protein, lipids, and nucleic acids, and how these methods can be readily applied within clinical and pharmaceutical research. Recent findings: Advances in the application of D2O techniques now permit the simultaneous dynamic measurement of a range of substrates (i.e. protein, lipid, and nucleic acids, along with the potential for OMICs methodologies) with minimal invasiveness further creating opportunities for long-term ‘free living’ measures that can be used in clinical settings. These techniques have recently been applied to ageing populations and further in cancer patients revealing altered muscle protein metabolism. Additionally, the efficacy of numerous drugs in improving lipoprotein profiles and controlling cellular proliferation in leukaemia have been revealed. Summary: D2O provides opportunities to create a more holistic picture of in-vivo metabolic phenotypes, providing a unique platform for development in clinical applications, and the emerging field of personalized medicine

Detection of herpes simplex virus type 1 in human ciliary ganglia

PURPOSE. To determine whether herpes simplex virus type 1 (HSV-1) DNA is present in the ciliary ganglion (CG). METHODS. Fifty CG and 47 trigeminal ganglia (TG) were resected from 63 formalin-fixed cadavers between 56 and 98 years of age that had been embalmed within 12 hours of death. The donors had no known active HSV infection at the time of death. DNA was extracted from all ganglia by proteinase-K digestion (TG) or digestion by a mild lysis buffer (CG). DNA was amplified by polymerase chain reaction for sequences from human chromosome 18, D18S1259 (positive control), and from the HSV-1 DNA polymerase gene, U L 30. The amplified DNA was separated by agarose gel electrophoresis, transferred to nylon membranes, and hybridized with the appropriate digoxigenin-labeled probe that was detected by alkaline phosphatase-conjugated monoclonal antibody. RESULTS. The D18S1259 sequence was amplified from 47 TG and 30 CG samples. Of these samples, 32 (68.0%) of the 47 TG samples and 20 (66.6%) of the 30 CG samples were positive for the UL 30 HSV-1 sequence. CONCLUSIONS. Using amplification of HSV-1 DNA as a surrogate marker of latency, the finding that the frequency of HSV-1 in the CG was approximately the same as that of the TG suggests that the CG may be an additional site of HSV-1 latency in humans. Active infection in or reactivation of HSV-1 from non-TG sites may explain why this virus is able to infect sites, such as the retina, that have no direct connections to the trigeminal nerve

The age-related loss of skeletal muscle mass and function: measurement and physiology of muscle fibre atrophy and muscle fibre loss in humans

Age-related loss of skeletal muscle mass and function, sarcopenia, is associated with physical frailty and increased risk of morbidity (chronic diseases), in addition to all-cause mortality. The loss of muscle mass occurs incipiently from middle-age (~1%/year), and in severe instances can lead to a loss of ~50% by the 8-9th decade of life. This review will focus on muscle deterioration with ageing and highlight the two underpinning mechanisms regulating declines in muscle mass and function: muscle fibre atrophy and muscle fibre loss (hypoplasia) – and their measurement. The mechanisms of muscle fibre atrophy in humans relate to imbalances in muscle protein synthesis (MPS) and breakdown (MPB); however, since there is limited evidence for basal alterations in muscle protein turnover, it would appear that “anabolic resistance’ to fundamental environmental cues regulating diurnal muscle homeostasis (namely physical activity and nutrition), underlie age-related catabolic perturbations in muscle proteostasis. While the ‘upstream’ drivers of the desensitization of aged muscle to anabolic stimuli are poorly defined, they most likely relate to impaired efficiency of the conversion of nutritional/exercise stimuli into signalling impacting mRNA translation and proteolysis. Additionally, loss of muscle fibres has been shown in cadaveric studies using anatomical fibre counts, and from iEMG studies demonstrating motor unit loss, albeit with few molecular investigations of this in humans. We suggest that defining countermeasures against sarcopenia requires improved understandings of the co-ordinated regulation of muscle fibre atrophy and fibre loss, which are likely to be inextricably linked

On the optimal relative orientation of radicals in the cryptochrome magnetic compass

This is the author accepted manuscript. The final version is available from AIP Publishing via the DOI in this record.Birds appear to be equipped with an innate magnetic compass. One biophysical model of this sense relies on spin dynamics in photogenerated radical pairs in the protein cryptochrome. This study employs a systematic approach to predict the dependence of the compass sensitivity on the relative orientation of the constituent radicals for spin systems comprising up to 21 hyperfine interactions. Evaluating measures of compass sensitivity (anisotropy) and precision (optimality) derived from the singlet yield, we find the ideal relative orientations for the radical pairs consisting of the flavin anion (F•-) coupled with a tryptophan cation (W•+) or tyrosine radical (Y•). For the geomagnetic field, the two measures are found to be anticorrelated in [F•- W•+]. The angle spanned by the normals to the aromatic planes of the radicals is the decisive parameter determining the compass sensitivity. The third tryptophan of the tryptophan triad/tetrad, which has been implicated with magnetosensitive responses, exhibits a comparably large anisotropy, but unfavorable optimality. Its anisotropy could be boosted by an additional ∼50% by optimizing the relative orientation of the radicals. For a coherent lifetime of 1 μs, the maximal relative anisotropy of [F•- W•+] is 0.27%. [F•- Y•] radical pairs outperform [F•- W•+] for most relative orientations. Furthermore, anisotropy and optimality can be simultaneously maximized. The entanglement decays rapidly, implicating it as a situational by-product rather than a fundamental driver within the avian compass. In magnetic fields of higher intensity, the relative orientation of radicals in [F•- W•+] is less important than for the geomagnetic field.Engineering and Physical Sciences Research Council (EPSRC

A 4-week, lifestyle-integrated, home-based exercise training programme elicits improvements in physical function and lean mass in older men and women: a pilot study

Background: Developing alternative exercise programmes that can alleviate certain barriers to exercise such as psychological, environmental or socio-economical barriers, but provide similar physiological benefits e.g. increases in muscle mass and strength, is of grave importance. This pilot study aimed to assess the efficacy of an unsupervised, 4-week, whole-body home-based exercise training (HBET) programme, incorporated into daily living activities, on skeletal muscle mass, power and strength. Methods: Twelve healthy older volunteers (63±3 years, 7 men: 5 women, BMI: 29±1 kg/m²) carried out the 4-week “lifestyle-integrated” HBET of 8 exercises, 3x12 repetitions each, every day. Before and after HBET, a number of physical function tests were carried out: unilateral leg extension 1-RM (one- repetition maximum), MVC (maximal voluntary contraction) leg extension, lower leg muscle power (via Nottingham Power Rig), handgrip strength and SPPBT (short physical performance battery test). A D3-Creatine method was used for assessment of whole-body skeletal muscle mass, and ultrasound was used to measure the quadriceps cross-sectional area (CSA) and vastus lateralis muscle thickness. Results: Four weeks HBET elicited significant (p<0.05) improvements in leg muscle power (276.7±38.5 vs. 323.4±43.4 W), maximal voluntary contraction (60°: 154.2±18.4 vs. 168.8±15.2 Nm, 90°: 152.1±10.5 vs. 159.1±11.4 Nm) and quadriceps CSA (57.5±5.4 vs. 59.0±5.3 cm2), with a trend for an increase in leg strength (1-RM: 45.7±5.9 vs. 49.6±6.0 kg, P=0.08). This was despite there being no significant differences in whole-body skeletal muscle mass, as assessed via D3-Creatine. Conclusions: This study demonstrates that increases in multiple aspects of muscle function can be achieved in older adults with just 4-weeks of “lifestyle-integrated” HBET, with a cost-effective means. This training mode may prove to be a beneficial alternative for maintaining and/or improving muscle mass and function in older adults

Human skeletal muscle is refractory to the anabolic effects of leucine during the postprandial muscle-full period in older men

Leucine modulates muscle protein synthesis (MPS), with potential to facilitate accrual/maintenance of muscle mass. Animal models suggest that leucine boluses shortly after meals may prolong MPS and delay onset of a “muscle-full” state. However, the effects of nutrient “top-ups” in humans, and particularly older adults where deficits exist, have not been explored. We determined the effects of a leucine top-up after essential amino acid (EAA) feeding on anabolic signaling, MPS, and muscle energy metabolism in older men. During 13C6-phenylalanine infusion, 16 men (∼70 years) consumed 15 g of EAA with (n=8, FED + LEU) or without (n=8, FED) 3 g of leucine top-up 90 min later. Repeated blood and muscle sampling permitted measurement of fasting and postprandial plasma EAA, insulin, anabolic signaling including mTOR complex 1 (mTORC1) substrates, cellular ATP and phosphorylocreatine, and MPS. Oral EAA achieved rapid insulinemia (12.5 iU·ml−1 25 min post-feed), essential aminoacidemia (3000 μM, 45–65 min post-feed), and activation of mTORC1 signaling. Leucine top-up prolonged plasma EAA (2800 μM, 135 min) and leucine availability (1050 μM, 135 min post-feed). Fasting FSRs of 0.046 and 0.056%·h-1 (FED and FED + LEU respectively) increased to 0.085 and 0.085%·h-1 90–180 min post-feed and returned to basal rates after 180 min in both groups. Phosphorylation of mTORC1 substrates returned to fasting levels 240 min post-feed in both groups. Feeding had limited effect on muscle elongation factor 2 (eEF2) phosphorylation. We demonstrate the refractoriness of muscle to nutrient-led anabolic stimulation in the postprandial period; thus, leucine supplements should be taken outside of meals, or with meals containing suboptimal protein in terms of either amount or EAA composition