The Origins of New Industries: The Case of the Mobile Internet

This paper describes a model of new industry formation that is based on evolutionary theories of technical change. It represents the origins of new network industries as the interaction between multiple technological trajectories that are specific to a particular technology or broadly defined technological regime. The speed with which these multiple trajectories cause industry formation depends on their effective application to the most economical applications; this process occurs through the interaction between design hierarchies and market concepts. Growth in these initial applications causes sub-trajectories or sub-regimes, where competition in the new industry initially takes place, to emerge from the main trajectories. The model is applied to the mobile Internet, an industry that has just started to grow particularly in Japan and Korea.Origins, Industry, Technology, Trajectory, Design, Hierarchy, Market, Competition, Cooperation, Disruptive, Mobile, Internet

Muscular dystrophy meets protein biochemistry, the mother of invention

Muscular dystrophies result from a defect in the linkage between the muscle fiber cytoskeleton and the basement membrane (BM). Congenital muscular dystrophy type MDC1A is caused by mutations in laminin α2 that either reduce its expression or impair its ability to polymerize within the muscle fiber BM. Defects in this BM lead to muscle fiber damage from the force of contraction. In this issue of the JCI, McKee and colleagues use a laminin polymerization–competent, designer chimeric BM protein in vivo to restore function of a polymerization-defective laminin, leading to normalized muscle structure and strength in a mouse model of MDC1A. Delivery of such a protein to patients could ameliorate many aspects of their disease

Cationic amphiphilic drugs cause a marked expansion of apparent lysosomal volume: Implications for an intracellular distribution-based drug interaction

How a drug distributes within highly compartmentalized mammalian cells can affect both the activity and pharmacokinetic behavior. Many commercially available drugs are considered to be lysosomotropic, meaning they are extensively sequestered in lysosomes by an ion trapping-type mechanism. Lysosomotropic drugs typically have a very large apparent volume of distribution and a prolonged half-life in vivo, despite minimal association with adipose tissue. In this report we tested the prediction that the accumulation of one drug (perpetrator) in lysosomes could influence the accumulation of a secondarily administered one (victim), resulting in an intracellular distribution-based drug interaction. To test this hypothesis cells were exposed to nine different hydrophobic amine-containing drugs, which included imipramine, chlorpromazine and amiodarone, at a 10 µM concentration for 24 to 48 hours. After exposure to the perpetrators the cellular accumulation of LysoTracker Red (LTR), a model lysosomotropic probe, was evaluated both quantitatively and microscopically. We found that all of the tested perpetrators caused a significant increase in the cellular accumulation of LTR. Exposure of cells to imipramine caused an increase in the cellular accumulation of other lysosomotropic probes and drugs including LyosTracker Green, daunorubicin, propranolol and methylamine; however, imipramine did not alter the cellular accumulation of non-lysosomotropic amine-containing molecules including MitoTracker Red and sulforhodamine 101. In studies using ionophores to abolish intracellular pH gradients we were able to resolve ion trapping-based cellular accumulation from residual pH-gradient independent accumulation. Results from these evaluations in conjunction with lysosomal pH measurements enabled us to estimate the relative aqueous volume of lysosomes of cells before and after imipramine treatment. Our results suggest that imipramine exposure caused a 4-fold expansion in the lysosomal volume, which provides the basis for the observed drug interaction. The imipramine-induced lysosomal volume expansion was shown to be both time- and temperature-dependent and reversed by exposing cells to hydroxypropyl-β-cyclodextrin, which reduced lysosomal cholesterol burden. This suggests that the expansion of lysosomal volume occurs secondary to perpetrator-induced elevations in lysosomal cholesterol content. In support of this claim, the cellular accumulation of LTR was shown to be higher in cells isolated from patients with Niemann-Pick Type C disease, which are known to hyper-accumulate cholesterol in lysosomes

Evaluating Mechanisms of RNA Editing in Plants

RNA editing is one of several post-transcriptional RNA processes. This process generates RNA and protein diversity in eukaryotes and results in specific amino acid substitutions, deletions, and changes in gene expression levels. It occurs in both plastids and mitochondria and typically involves the changing of specific C to U (cytosine to uracil). Welwitschia belongs to the gymnosperms (a group of seed-producing plants that includes conifers, cycads, Ginkgo, and Gnetales). It has already been substantiated that Welwitschia mirabilis has a major loss of cis-spliced introns and unusual trans-splicing introns. Research in the Mower lab has already proven that ancestral gymnosperm has high editing sites, from examining Ginkgo and Cycas. Knowing these high editing sites in other Gymnosperms, a prediction was made in Welwitschia mirabilis for a major loss of editing. In this study, we wished to evaluate the accuracy of this prediction. Data confirmed that RNA editing is very low in Welwitschia, and surprisingly, even lower than the predicted number. Within the 16 examined functional protein-coding genes in Welwitschia mitogenome, RNA editing sites were detected from only 5 of them

Evaluating Mechanisms of RNA Editing in Plants

RNA editing is one of several post-transcriptional RNA processes. This process generates RNA and protein diversity in eukaryotes and results in specific amino acid substitutions, deletions, and changes in gene expression levels. It occurs in both plastids and mitochondria and typically involves the changing of specific C to U (cytosine to uracil). Welwitschia belongs to the gymnosperms (a group of seed-producing plants that includes conifers, cycads, Ginkgo, and Gnetales). It has already been substantiated that Welwitschia mirabilis has a major loss of cis-spliced introns and unusual trans-splicing introns. Research in the Mower lab has already proven that ancestral gymnosperm has high editing sites, from examining Ginkgo and Cycas. Knowing these high editing sites in other Gymnosperms, a prediction was made in Welwitschia mirabilis for a major loss of editing. In this study, we wished to evaluate the accuracy of this prediction. Data confirmed that RNA editing is very low in Welwitschia, and surprisingly, even lower than the predicted number. Within the 16 examined functional protein-coding genes in Welwitschia mitogenome, RNA editing sites were detected from only 5 of them

Effect of group size and chlortetracycline on Salmonella in swine

The objective of this study was to evaluate the effect of stocking density and subtherapeutic chlortetracycline (CTC) on Salmonella prevalence in swine

Anaxipha hyalicetra sp. n. (Gryllidae, Trigonidiinae), a new sword-tailed cricket species from Arizona

A new Anaxipha species is described from a locality in southeastern Arizona adjacent to the border with Mexico. The species is unique among the North American fauna by virtue of the broad tegmina, distinctive male genitalia, and calling song phrased in an irregular chirp with a variable pulse train rate. The possibility that the behavioral repertoire of this species includes aggressive song as well as calling song is discussed

Contributions of carotid bodies, retrotrapezoid nucleus neurons and preBötzinger complex astrocytes to the CO2-sensitive drive for breathing

Current models of respiratory CO2 chemosensitivity are centred around the function of a specific population of neurons residing in the medullary retrotrapezoid nucleus (RTN). However, there is significant evidence suggesting that chemosensitive neurons exist in other brainstem areas, including the rhythm-generating region of the medulla oblongata – the preBötzinger complex (preBötC). There is also evidence that astrocytes, non-neuronal brain cells, contribute to central CO2 chemosensitivity. In this study, we reevaluated the relative contributions of the RTN neurons, the preBötC astrocytes, and the carotid body chemoreceptors in mediating the respiratory responses to CO2 in experimental animals (adult laboratory rats). To block astroglial signalling via exocytotic release of transmitters, preBötC astrocytes were targeted to express the tetanus toxin light chain (TeLC). Bilateral expression of TeLC in preBötC astrocytes was associated with ∼20% and ∼30% reduction of the respiratory response to CO2 in conscious and anaesthetized animals, respectively. Carotid body denervation reduced the CO2 respiratory response by ∼25%. Bilateral inhibition of RTN neurons transduced to express Gi-coupled designer receptors exclusively activated by designer drug (DREADDGi) by application of clozapine-N-oxide reduced the CO2 response by ∼20% and ∼40% in conscious and anaesthetized rats, respectively. Combined blockade of astroglial signalling in the preBötC, inhibition of RTN neurons and carotid body denervation reduced the CO2-induced respiratory response by ∼70%. These data further support the hypothesis that the CO2-sensitive drive to breathe requires inputs from the peripheral chemoreceptors and several central chemoreceptor sites. At the preBötC level, astrocytes modulate the activity of the respiratory network in response to CO2, either by relaying chemosensory information (i.e. they act as CO2 sensors) or by enhancing the preBötC network excitability to chemosensory inputs