208 research outputs found

    Insights from Austrian Capital and Entrepreneurship Theory

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    Over the last two decades the resource-based view (“RBV”) has become dominant in the strategic management field. It has often been observed that the RBV is lacking in the dynamic dimension. For example, processes of building competitive advantages by means of combining existing complementary resources in novel ways are not inquired into. We argue that the RBV may profitably draw on insights in entrepreneurship and capital theory, drawn from Austrian economists as well as Frank Knight, in order to strengthen its dynamic dimension. We link the RBV and Austrian ideas in the context of the theory of complex systems pioneered by Herbert Simon. We draw a number of implications for strategic management from this synthesis, notably into resource value and sustainability of competitive advantage

    Neuronal circuitry for pain processing in the dorsal horn

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    Neurons in the spinal dorsal horn process sensory information, which is then transmitted to several brain regions, including those responsible for pain perception. The dorsal horn provides numerous potential targets for the development of novel analgesics and is thought to undergo changes that contribute to the exaggerated pain felt after nerve injury and inflammation. Despite its obvious importance, we still know little about the neuronal circuits that process sensory information, mainly because of the heterogeneity of the various neuronal components that make up these circuits. Recent studies have begun to shed light on the neuronal organization and circuitry of this complex region

    Loss of yata, a Novel Gene Regulating the Subcellular Localization of APPL, Induces Deterioration of Neural Tissues and Lifespan Shortening

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    Background: The subcellular localization of membrane and secreted proteins is finely and dynamically regulated through intracellular vesicular trafficking for permitting various biological processes. Drosophila Amyloid precursor protein like (APPL) and Hikaru genki (HIG) are examples of proteins that show differential subcellular localization among several developmental stages. Methodology/Principal Findings: During the study of the localization mechanisms of APPL and HIG, we isolated a novel mutant of the gene, CG1973, which we named yata. This molecule interacted genetically with Appl and is structurally similar to mouse NTKL/SCYL1, whose mutation was reported to cause neurodegeneration. yata null mutants showed phenotypes that included developmental abnormalities, progressive eye vacuolization, brain volume reduction, and lifespan shortening. Exogenous expression of Appl or hig in neurons partially rescued the mutant phenotypes of yata. Conversely, the phenotypes were exacerbated in double null mutants for yata and Appl. We also examined the subcellular localization of endogenous APPL and exogenously pulse-induced APPL tagged with FLAG by immunostaining the pupal brain and larval motor neurons in yata mutants. Our data revealed that yata mutants showed impaired subcellular localization of APPL. Finally, yata mutant pupal brains occasionally showed aberrant accumulation of Sec23p, a component of the COPII coat of secretory vesicles traveling from the endoplasmic reticulum (ER) to the Golgi

    The characteristic response of domestic cats to plant iridoids allows them to gain chemical defense against mosquitoes

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    ネコのマタタビ反応の謎を解明 --マタタビ反応はネコが蚊を忌避するための行動だった--. 京都大学プレスリリース. 2021-01-21.Domestic cats and other felids rub their faces and heads against catnip (Nepeta cataria) and silver vine (Actinidia polygama) and roll on the ground as a characteristic response. While this response is well known, its biological function and underlying mechanism remain undetermined. Here, we uncover the neurophysiological mechanism and functional outcome of this feline response. We found that the iridoid nepetalactol is the major component of silver vine that elicits this potent response in cats and other felids. Nepetalactol increased plasma β-endorphin levels in cats, while pharmacological inhibition of μ-opioid receptors suppressed the classic rubbing response. Rubbing behavior transfers nepetalactol onto the faces and heads of respondents where it repels the mosquito, Aedes albopictus. Thus, self-anointing behavior helps to protect cats against mosquito bites. The characteristic response of cats to nepetalactol via the μ-opioid system provides an important example of chemical pest defense using plant metabolites in nonhuman mammals

    Additive Protection by Antioxidant and Apoptosis-Inhibiting Effects on Mosquito Cells with Dengue 2 Virus Infection

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    Cytopathic effects (CPEs) in mosquito cells are generally trivial compared to those that occur in mammalian cells, which usually end up undergoing apoptosis during dengue virus (DENV) infection. However, oxidative stress was detected in both types of infected cells. Despite this, the survival of mosquito cells benefits from the upregulation of genes related to antioxidant defense, such as glutathione S transferase (GST). A second defense system, i.e., consisting of antiapoptotic effects, was also shown to play a role in protecting mosquito cells against DENV infection. This system is regulated by an inhibitor of apoptosis (IAP) that is an upstream regulator of caspases-9 and -3. DENV-infected C6/36 cells with double knockdown of GST and the IAP showed a synergistic effect on activation of these two caspases, causing a higher rate of apoptosis (>20%) than those with knockdown of each single gene (∼10%). It seems that the IAP acts as a second line of defense with an additional effect on the survival of mosquito cells with DENV infection. Compared to mammalian cells, residual hydrogen peroxide in DENV-infected C6/36 cells may signal for upregulation of the IAP. This novel finding sheds light on virus/cell interactions and their coevolution that may elucidate how mosquitoes can be a vector of DENV and probably most other arboviruses in nature

    Genetic Characterization of Conserved Charged Residues in the Bacterial Flagellar Type III Export Protein FlhA

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    For assembly of the bacterial flagellum, most of flagellar proteins are transported to the distal end of the flagellum by the flagellar type III protein export apparatus powered by proton motive force (PMF) across the cytoplasmic membrane. FlhA is an integral membrane protein of the export apparatus and is involved in an early stage of the export process along with three soluble proteins, FliH, FliI, and FliJ, but the energy coupling mechanism remains unknown. Here, we carried out site-directed mutagenesis of eight, highly conserved charged residues in putative juxta- and trans-membrane helices of FlhA. Only Asp-208 was an essential acidic residue. Most of the FlhA substitutions were tolerated, but resulted in loss-of-function in the ΔfliH-fliI mutant background, even with the second-site flhB(P28T) mutation that increases the probability of flagellar protein export in the absence of FliH and FliI. The addition of FliH and FliI allowed the D45A, R85A, R94K and R270A mutant proteins to work even in the presence of the flhB(P28T) mutation. Suppressor analysis of a flhA(K203W) mutation showed an interaction between FlhA and FliR. Taken all together, we suggest that Asp-208 is directly involved in PMF-driven protein export and that the cooperative interactions of FlhA with FlhB, FliH, FliI, and FliR drive the translocation of export substrate

    Inhibitory Effects of Prior Low-dose X-irradiation on Ischemia-reperfusion Injury in Mouse Paw

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    We have reported that low-dose, unlike high-dose, irradiation enhanced antioxidation function and reduced oxidative damage. On the other hand, ischemia-reperfusion injury is induced by reactive oxygen species. In this study, we examined the inhibitory effects of prior low-dose X-irradiation on ischemia-reperfusion injury in mouse paw. BALB/c mice were irradiated by sham or 0.5 Gy of X-ray. At 4 hrs after irradiation, the left hind leg was bound 10 times with a rubber ring for 0.5, 1, or 2 hrs and the paw thickness was measured. Results show that the paw swelling thickness by ischemia for 0.5 hr was lower than that for 2 hrs. At 1 hr after reperfusion from ischemia for 1 hr, superoxide dismutase activity in serum was increased in those mice which received 0.5 Gy irradiation and in the case of the ischemia for 0.5 or 1 hr, the paw swelling thicknesses were inhibited by 0.5 Gy irradiation. In addition, interstitial edema in those mice which received 0.5 Gy irradiation was less than that in the mice which underwent by sham irradiation. These findings suggest that the ischemia-reperfusion injury is inhibited by the enhancement of antioxidation function by 0.5 Gy irradiation

    Comparability of off the shelf foot orthoses in the redistribution of forces in midfoot osteoarthritis patients

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    Background Midfoot osteoarthritis (OA) is more prevalent and strongly associated with pain than previously thought. Excessive mechanical loading of the midfoot structures may contribute to midfoot OA and studies suggest that functional foot orthoses (FFO) may relieve pain through improving function. This exploratory study aimed to evaluate the mechanical effect of two off-the-shelf FFOs, compared to a sham orthosis in people with midfoot OA. Methods Thirty-three participants with radiographically confirmed symptomatic midfoot OA were randomly assigned to wear either a commercially available FFO or a sham orthosis. After wearing their assigned orthoses for 12 weeks, plantar pressure measurements were obtained under shoe-only and assigned orthoses conditions. Participants assigned to the sham, were additionally tested wearing a second type of FFO at the end of trial. Descriptive mean change (±95% confidence intervals) in plantar pressure for each orthoses condition, versus a shoe only baseline condition are presented. Findings Compared to the shoe only conditions, both FFOs decreased hindfoot and forefoot maximum force and peak pressure, whilst increasing maximum force and contact area under the midfoot. The sham orthosis yielded plantar pressures similar to the shoe-only condition. Interpretation Findings suggest that both types of off-the-shelf FFO may provide mechanical benefit, whilst the sham orthoses produced similar findings to the shoe only condition, indicating appropriate sham properties. This paper provides insight into the mechanisms of action underpinning the use of FFOs and sham orthoses, which can inform future definitive RCTs examining the effect of orthoses on midfoot OA
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