Showing papers by "University of Geneva published in 2000"
TL;DR: The campaign produced a sustained improvement in compliance with hand hygiene, coinciding with a reduction of nosocomial infections and MRSA transmission, and the promotion of bedside, antiseptic handrubs largely contributed to the increase in compliance.
2,404 citations
TL;DR: Theoretical and experimental work concerned with dynamic fluctuations has developed into a very active and fascinating subfield of mesoscopic physics as discussed by the authors, which can be used to obtain information on a system which is not available through conductance measurements.
2,086 citations
TL;DR: It is shown that temporal feeding restriction under light-dark or dark-dark conditions can change the phase of circadian gene expression in peripheral cell types by up to 12 h while leaving thephase of cyclic gene expressionIn the SCN unaffected.
Abstract: In mammals, circadian oscillators exist not only in the suprachiasmatic nucleus, which harbors the central pacemaker, but also in most peripheral tissues. It is believed that the SCN clock entrains the phase of peripheral clocks via chemical cues, such as rhythmically secreted hormones. Here we show that temporal feeding restriction under light–dark or dark–dark conditions can change the phase of circadian gene expression in peripheral cell types by up to 12 h while leaving the phase of cyclic gene expression in the SCN unaffected. Hence, changes in metabolism can lead to an uncoupling of peripheral oscillators from the central pacemaker. Sudden large changes in feeding time, similar to abrupt changes in the photoperiod, reset the phase of rhythmic gene expression gradually and are thus likely to act through a clock-dependent mechanism. Food-induced phase resetting proceeds faster in liver than in kidney, heart, or pancreas, but after 1 wk of daytime feeding, the phases of circadian gene expression are similar in all examined peripheral tissues.
2,083 citations
TL;DR: Suggestions are presented for reporting complex mutations in a unified manner for efficient and accurate reporting, testing, and curation of the growing number of disease mutations and useful polymorphisms being discovered in the human genome.
Abstract: Consistent gene mutation nomenclature is essential for efficient and accurate reporting, testing, and curation of the growing number of disease mutations and useful polymorphisms being discovered in the human genome. While a codified mutation nomenclature system for simple DNA lesions has now been adopted broadly by the medical genetics community, it is inherently difficult to represent complex mutations in a unified manner. In this article, suggestions are presented for reporting just such complex mutations.
1,744 citations
TL;DR: It is shown that the glucocorticoid hormone analog dexamethasone induces circadian gene expression in cultured rat-1 fibroblasts and transiently changes the phase of circadian gene Expression in liver, kidney, and heart, however, dexamETHasone does not affect cyclic geneexpression in neurons of the suprachiasmatic nucleus.
Abstract: In mammals, circadian oscillators reside not only in the suprachiasmatic nucleus of the brain, which harbors the central pacemaker, but also in most peripheral tissues. Here, we show that the glucocorticoid hormone analog dexamethasone induces circadian gene expression in cultured rat-1 fibroblasts and transiently changes the phase of circadian gene expression in liver, kidney, and heart. However, dexamethasone does not affect cyclic gene expression in neurons of the suprachiasmatic nucleus. This enabled us to establish an apparent phase-shift response curve specifically for peripheral clocks in intact animals. In contrast to the central clock, circadian oscillators in peripheral tissues appear to remain responsive to phase resetting throughout the day.
1,650 citations
TL;DR: In this article, the authors reported the sequence and gene catalogue of the long arm of chromosome 21 and sequenced 33,546,361 base pairs (bp) of DNA with very high accuracy, the largest contig being 25,491,867 bp.
Abstract: Chromosome 21 is the smallest human autosome. An extra copy of chromosome 21 causes Down syndrome, the most frequent genetic cause of significant mental retardation, which affects up to 1 in 700 live births. Several anonymous loci for monogenic disorders and predispositions for common complex disorders have also been mapped to this chromosome, and loss of heterozygosity has been observed in regions associated with solid tumours. Here we report the sequence and gene catalogue of the long arm of chromosome 21. We have sequenced 33,546,361 base pairs (bp) of DNA with very high accuracy, the largest contig being 25,491,867 bp. Only three small clone gaps and seven sequencing gaps remain, comprising about 100 kilobases. Thus, we achieved 99.7% coverage of 21q. We also sequenced 281,116 bp from the short arm. The structural features identified include duplications that are probably involved in chromosomal abnormalities and repeat structures in the telomeric and pericentromeric regions. Analysis of the chromosome revealed 127 known genes, 98 predicted genes and 59 pseudogenes.
1,404 citations
TL;DR: Data indicate that GDNF delivery using a lentiviral vector system can prevent nigrostriatal degeneration and induce regeneration in primate models of PD and might be a viable therapeutic strategy for PD patients.
Abstract: Lentiviral delivery of glial cell line-derived neurotrophic factor (lenti-GDNF) was tested for its trophic effects upon degenerating nigrostriatal neurons in nonhuman primate models of Parkinson's disease (PD). We injected lenti-GDNF into the striatum and substantia nigra of nonlesioned aged rhesus monkeys or young adult rhesus monkeys treated 1 week prior with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Extensive GDNF expression with anterograde and retrograde transport was seen in all animals. In aged monkeys, lenti-GDNF augmented dopaminergic function. In MPTP-treated monkeys, lenti-GDNF reversed functional deficits and completely prevented nigrostriatal degeneration. Additionally, lenti-GDNF injections to intact rhesus monkeys revealed long-term gene expression (8 months). In MPTP-treated monkeys, lenti-GDNF treatment reversed motor deficits in a hand-reach task. These data indicate that GDNF delivery using a lentiviral vector system can prevent nigrostriatal degeneration and induce regeneration in primate models of PD and might be a viable therapeutic strategy for PD patients.
1,254 citations
TL;DR: Cardiac dysfunction in obesity is caused by lipoapoptosis and is prevented by reducing cardiac lipids and Troglitazone therapy lowered myocardial TG and ceramide and completely prevented DNA laddering and loss of cardiac function.
Abstract: To determine the mechanism of the cardiac dilatation and reduced contractility of obese Zucker Diabetic Fatty rats, myocardial triacylglycerol (TG) was assayed chemically and morphologically. TG was high because of underexpression of fatty acid oxidative enzymes and their transcription factor, peroxisome proliferator-activated receptor-α. Levels of ceramide, a mediator of apoptosis, were 2–3 times those of controls and inducible nitric oxide synthase levels were 4 times greater than normal. Myocardial DNA laddering, an index of apoptosis, reached 20 times the normal level. Troglitazone therapy lowered myocardial TG and ceramide and completely prevented DNA laddering and loss of cardiac function. In this paper, we conclude that cardiac dysfunction in obesity is caused by lipoapoptosis and is prevented by reducing cardiac lipids.
1,247 citations
TL;DR: It is suggested that restricted host ranges are limited to specific niches and represent specialization of widespread and more ancestral promiscuous symbioses.
Abstract: Eukaryotes often form symbioses with microorganisms. Among these, associations between plants and nitrogen-fixing bacteria are responsible for the nitrogen input into various ecological niches. Plants of many different families have evolved the capacity to develop root or stem nodules with diverse genera of soil bacteria. Of these, symbioses between legumes and rhizobia (Azorhizobium, Bradyrhizobium, Mesorhizobium, and Rhizobium) are the most important from an agricultural perspective. Nitrogen-fixing nodules arise when symbiotic rhizobia penetrate their hosts in a strictly controlled and coordinated manner. Molecular codes are exchanged between the symbionts in the rhizosphere to select compatible rhizobia from pathogens. Entry into the plant is restricted to bacteria that have the “keys” to a succession of legume “doors”. Some symbionts intimately associate with many different partners (and are thus promiscuous), while others are more selective and have a narrow host range. For historical reasons, narrow host range has been more intensively investigated than promiscuity. In our view, this has given a false impression of specificity in legume-Rhizobium associations. Rather, we suggest that restricted host ranges are limited to specific niches and represent specialization of widespread and more ancestral promiscuous symbioses. Here we analyze the molecular mechanisms governing symbiotic promiscuity in rhizobia and show that it is controlled by a number of molecular keys.
932 citations
TL;DR: In this article, practical and numerical information for undertaking and evaluating absolute structure and configuration determinations is provided for macromolecular structures, the dangers of polar-dispersion errors, Euclidean normalizers of space groups, detection and reporting of molecular symmetry, enantiopurity and optical activity in solution.
Abstract: Detailed practical and numerical information is provided for undertaking and evaluating absolute-structure and absolute-configuration determinations. The interpretation of numerical values of x, the Flack [Acta Cryst. (1983), A39, 876–881] parameter, and its standard uncertainty u are explained in terms of the inversion-distinguishing power. Moreover, the conditions to obtain reliable values of x(u) are detailed. Further explanatory material is provided on the use of right-handed axes, valid intensity data, the application to macromolecular structures, the dangers of polar-dispersion errors, Euclidean normalizers of space groups, the detection and reporting of molecular symmetry, enantiopurity and optical activity in solution. New CIF data names are introduced.
921 citations
TL;DR: Evidence is presented for rhamnolipids being the actual surfactant involved in swarming motility, which explains the involvement of the cell-to-cell signaling circuitry of P. aeruginosa in this type of surface motility.
Abstract: We describe swarming in Pseudomonas aeruginosa as a third mode of surface translocation in addition to the previously described swimming and twitching motilities. Swarming in P. aeruginosa is induced on semisolid surfaces (0.5 to 0.7% agar) under conditions of nitrogen limitation and in response to certain amino acids. Glutamate, aspartate, histidine, or proline, when provided as the sole source of nitrogen, induced swarming, while arginine, asparagine, and glutamine, among other amino acids, did not sustain swarming. Cells from the edge of the swarm were about twice as long as cells from the swarm center. In both instances, bacteria possessing two polar flagella were observed by light and electron microscopy. While a fliC mutant of P. aeruginosa displayed slightly diminished swarming, a pilR and a pilA mutant, both deficient in type IV pili, were unable to swarm. Furthermore, cells with mutations in the las cell-to-cell signaling system showed diminished swarming behavior, while rhl mutants were completely unable to swarm. Evidence is presented for rhamnolipids being the actual surfactant involved in swarming motility, which explains the involvement of the cell-to-cell signaling circuitry of P. aeruginosa in this type of surface motility.
TL;DR: The islet alpha- and beta-cell lineages appear to arise independently during ontogeny, probably from a common precursor.
Abstract: To analyze cell lineage in the pancreatic islets, we have irreversibly tagged all the progeny of cells through the activity of Cre recombinase. Adult glucagon alpha and insulin beta cells are shown to derive from cells that have never transcribed insulin or glucagon, respectively. Also, the beta-cell progenitors, but not alpha-cell progenitors, transcribe the pancreatic polypeptide (PP) gene. Finally, the homeodomain gene PDX1, which is expressed by adult beta-cells, is also expressed by alpha-cell progenitors. Thus the islet alpha- and beta-cell lineages appear to arise independently during ontogeny, probably from a common precursor.
TL;DR: The biochemical composition of the postsynaptic membrane and the structure of dendritic spines may be rapidly modulated by synaptic activity and a model of sequentially occurring expression mechanisms is proposed.
Abstract: The biochemical composition of the postsynaptic membrane and the structure of dendritic spines may be rapidly modulated by synaptic activity. Here we review these findings, discuss their implications for long-term potentiation (LTP) and long-term depression (LTD) and propose a model of sequentially occurring expression mechanisms.
TL;DR: A new algorithm based on polar maps is detailed for the accurate and efficient recovery of the template in an image which has undergone a general affine transformation and results are presented which demonstrate the robustness of the method against some common image processing operations.
Abstract: Digital watermarks have been proposed as a method for discouraging illicit copying and distribution of copyrighted material. This paper describes a method for the secure and robust copyright protection of digital images. We present an approach for embedding a digital watermark into an image using the Fourier transform. To this watermark is added a template in the Fourier transform domain to render the method robust against general linear transformations. We detail a new algorithm based on polar maps for the accurate and efficient recovery of the template in an image which has undergone a general affine transformation. We also present results which demonstrate the robustness of the method against some common image processing operations such as compression, rotation, scaling, and aspect ratio changes.
TL;DR: Diseases arising from anomalies in the 3′ untranslated region, that affect the expression of one or more genes are described.
Abstract: The role of the 3' untranslated region in posttranscriptional regulation of mRNA expression is being elucidated. Here we describe diseases arising from anomalies in this region, that affect the expression of one or more genes.
TL;DR: In this article, the authors present a framework that includes parameters to be considered for hand-hygiene promotion in hospitals based on epidemiologically driven evidence and review of the current knowledge.
Abstract: Hand hygiene prevents cross-infection in hospitals, but compliance with recommended instructions often is poor among healthcare workers. Although some previous interventions to improve compliance have been successful, none has achieved lasting improvement. This article reviews reported barriers to appropriate hand hygiene and factors associated with poor compliance. Easy access to hand hygiene in a timely fashion and the availability of skin-care lotion both appear to be necessary prerequisites for appropriate hand-hygiene behavior. In particular, in high-demand situations, hand rub with an alcohol-based solution appears to be the only alternative that allows a decent compliance. The hand-hygiene compliance level does not rely on individual factors alone, and the same can be said for its promotion. Because of the complexity of the process of change, it is not surprising that solo interventions often fail, and multimodal, multidisciplinary strategies are necessary. A framework that includes parameters to be considered for hand-hygiene promotion is proposed, based on epidemiologically driven evidence and review of the current knowledge. Strategies for promotion in hospitals should include reasons for noncompliance with recommendations at individual, group, and institutional levels. Potential tools for change should address each of these elements and consider their interactivity.
TL;DR: This scheme combines the advantages of using photon pairs instead of faint laser pulses and the possibility to preserve energy-time entanglement over long distances and no fast random change of bases is required in this setup.
Abstract: We present a setup for quantum cryptography based on photon pairs in energy-time Bell states and show its feasibility in a laboratory experiment. Our scheme combines the advantages of using photon pairs instead of faint laser pulses and the possibility to preserve energy-time entanglement over long distances. Moreover, using four-dimensional energy-time states, no fast random change of bases is required in our setup: Nature itself decides whether to measure in the energy or in the time base, thus rendering eavesdropper attacks based on “photon number splitting” less efficient. PACS numbers: 03.67.Dd, 03.67.Hk Quantum communication is probably one of the most rapidly growing and most exciting fields of physics within the last years [1]. Its most mature application is quantum cryptography [also called quantum key distribution (QKD)], ensuring the distribution of a secret key between two parties. This key can be used afterwards to encrypt and decrypt secret messages using the one time pad [2]. In opposition to the mostly used “public key” systems [2], the security of quantum cryptography is not based on mathematical complexity, but on an inherent property of single quanta. Roughly speaking, since it is not possible to measure an unknown quantum system without modifying it, an eavesdropper manifests herself by introducing errors in the transmitted data. During the past years, several prototypes based on faint laser pulses have been developed, demonstrating that quantum cryptography not only works inside the laboratory, but in the “real world” as well [1,3,4]. Besides, it has been shown that two-photon entanglement can be preserved over large distances [5], especially when being entangled in energy and time [6]. As pointed out by Ekert in 1991 [7], the nonlocal correlations engendered by such states can also be used to establish sequences of correlated bits at distant places. Besides improvements in the domain of QKD, recent experimental progress in generating, manipulating, and measuring the so-called Bell states [8], has lead to fascinating applications like quantum teleportation [9], dense coding [10], and entanglement swapping [11]. In a recent paper, we proposed and tested a novel source for quantum communication generating a new kind of Bell states based on energy-time entanglement [12]. In this paper, we present a first application, exploiting this new source for quantum cryptography. Our scheme follows Ekert’s initial idea concerning the use of photon-pair correlations. However, in opposition, it implements Bell states and can thus be seen in the broader context of quantum communication. Moreover, the fact that energy-time entanglement can be preserved over long distances renders our source particulary interesting for long-distance applications. To understand the principle of our idea, we look at Fig. 1. A short light pulse emitted at time t0 enters an interferometer having a path length difference which is large compared to the duration of the pulse. The pulse is thus split into two pulses of smaller amplitudes, following each other with a fixed phase relation. The light is then focused into a nonlinear crystal where some of the pump photons are down-converted into photon pairs. Working with pump energies low enough to ensure that generation of two photon pairs can be neglected, a created photon pair is described by jc 1 p 2 jsPjsP 1 e if jlPjlP . (1)
TL;DR: This work considers quantum cryptographic schemes where the carriers of information are 3-state particles and one protocol uses four mutually unbiased bases and appears to provide better security than obtainable with 2-state carriers.
Abstract: We consider quantum cryptographic schemes where the carriers of information are 3-state particles. One protocol uses four mutually unbiased bases and appears to provide better security than obtainable with 2-state carriers. Another possible method allows quantum states to belong to more than one basis. Security is not better, but many curious features arise.
TL;DR: It is proposed that Plk1 is an important target of the DNA damage checkpoint, enabling cell-cycle arrests at multiple points in G2 and mitosis, and blocking mitotic exit.
Abstract: Polo-like kinases (PLKs) have an important role in several stages of mitosis. They contribute to the activation of cyclin B/Cdc2 and are involved in centrosome maturation and bipolar spindle formation at the onset of mitosis. PLKs also control mitotic exit by regulating the anaphase-promoting complex (APC) and have been implicated in the temporal and spatial coordination of cytokinesis. Experiments in budding yeast have shown that the PLK Cdc5 may be controlled by the DNA damage checkpoint. Here we report the effects of DNA damage on Polo-like kinase-1 (Plk1) in a variety of human cell lines. We show that Plk1 is inhibited by DNA damage in G2 and in mitosis. In line with this, we show that DNA damage blocks mitotic exit. DNA damage does not inhibit the kinase activity of Plk1 mutants in which the conserved threonine residue in the T-loop has been changed to aspartic acid, suggesting that DNA damage interferes with the activation of Plk1. Significantly, expression of these mutants can override the G2 arrest induced by DNA damage. On the basis of these data we propose that Plk1 is an important target of the DNA damage checkpoint, enabling cell-cycle arrests at multiple points in G2 and mitosis.
TL;DR: It is shown that cAMP, protein kinase C, glucocorticoid hormones and Ca2+ can all trigger a transient surge of Per1 transcription and elicit rhythmic gene expression in Rat-1 cells, suggesting that the SCN pacemaker may exploit multiple chemical cues to synchronize peripheral oscillators in vivo.
TL;DR: The identification of a Y‐box transcription factor, ZONAB, that binds to the SH3 domain of ZO‐1, a submembrane protein of tight junctions indicates that tightjunctions directly participate in the control of gene expression and suggest that they function in the regulation of epithelial cell differentiation.
Abstract: Epithelial tight junctions regulate paracellular diffusion and restrict the intermixing of apical and basolateral plasma membrane components. We now identify a Y-box transcription factor, ZONAB (ZO-1-associated nucleic acid-binding protein), that binds to the SH3 domain of ZO-1, a submembrane protein of tight junctions. ZONAB localizes to the nucleus and at tight junctions, and binds to sequences of specific promoters containing an inverted CCAAT box. In reporter assays, ZONAB and ZO-1 functionally interact in the regulation of the ErbB-2 promoter in a cell density-dependent manner. In stably transfected overexpressing cells, ZO-1 and ZONAB control expression of endogenous ErbB-2 and function in the regulation of paracellular permeability. These data indicate that tight junctions directly participate in the control of gene expression and suggest that they function in the regulation of epithelial cell differentiation.
TL;DR: It is proposed that the green tea extract is effective in stimulating thermogenesis by relieving inhibition at different control points along the NA–cAMP axis, and a synergistic interaction between catechin-polyphenols and caffeine to augment and prolong sympathetic stimulation of thermogenesis could be of value in assisting the management of obesity.
Abstract: The thermogenic effect of tea is generally attributed to its caffeine content. We report here that a green tea extract stimulates brown adipose tissue thermogenesis to an extent which is much greater than can be attributed to its caffeine content per se, and that its thermogenic properties could reside primarily in an interaction between its high content in catechin-polyphenols and caffeine with sympathetically released noradrenaline (NA). Since catechin-polyphenols are known to be capable of inhibiting catechol-O-methyl-transferase (the enzyme that degrades NA), and caffeine to inhibit trancellular phosphodiesterases (enzymes that break down NA-induced cAMP), it is proposed that the green tea extract, via its catechin-polyphenols and caffeine, is effective in stimulating thermogenesis by relieving inhibition at different control points along the NA-cAMP axis. Such a synergistic interaction between catechin-polyphenols and caffeine to augment and prolong sympathetic stimulation of thermogenesis could be of value in assisting the management of obesity. International Journal of Obesity (2000) 24, 252-258
TL;DR: This review describes the underlying technology and illustrates several areas of biomedical research, ranging from pathogenesis of neurological disorders to drug and vaccine design, in which potential clinical applications are being explored.
TL;DR: An increased error rate is found compared to two-dimensional systems, hence an advantage for the legitimate users to detect an eavesdropper, and an experimental realization using an interferometric setup is proposed.
Abstract: Like all of quantum information theory, quantum cryptography is traditionally based on two-level quantum systems. In this paper, a protocol for quantum key distribution based on higher-dimensional systems is presented. An experimental realization using an interferometric setup is also proposed. Analyzing this protocol from the practical side, one finds an increased key creation rate while keeping the initial laser pulse rate constant. Analyzing it for the case of intercept/resend eavesdropping strategy, an increased error rate is found compared to two-dimensional systems, hence an advantage for the legitimate users to detect an eavesdropper.
TL;DR: A multiple-approach prevention strategy, targeted at the insertion and maintenance of vascular access, can decrease rates of vascular-access infections and can have a substantial impact on the overall incidence of ICU-acquired infections.
TL;DR: Evidence is presented that circadian Dbp transcription requires the basic helix-loop-helix-PAS protein CLOCK, an essential component of the negative-feedback circuitry generating circadian oscillations in mammals and fruit flies.
Abstract: DBP, the founding member of the PAR leucine zipper transcription factor family, is expressed according to a robust daily rhythm in the suprachiasmatic nucleus and several peripheral tissues. Previous studies with mice deleted for the Dbp gene have established that DBP participates in the regulation of several clock outputs, including locomotor activity, sleep distribution, and liver gene expression. Here we present evidence that circadian Dbp transcription requires the basic helix–loop–helix–PAS protein CLOCK, an essential component of the negative-feedback circuitry generating circadian oscillations in mammals and fruit flies. Genetic and biochemical experiments suggest that CLOCK regulates Dbp expression by binding to E-box motifs within putative enhancer regions located in the first and second introns. Similar E-box motifs have been found previously in the promoter sequence of the murine clock gene mPeriod1. Hence, the same molecular mechanisms generating circadian oscillations in the expression of clock genes may directly control the rhythmic transcription of clock output regulators such as Dbp.
TL;DR: It is proposed that VEGF is actively responsible for hypertrophic cartilage neovascularization through a paracrine release by chondrocytes, with invading endothelial cells as a target.
Abstract: Vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) induces endothelial cell migration and proliferation in culture and is strongly angiogenic in vivo. VEGF synthesis has been shown to occur in both normal and transformed cells. The receptors for the factor have been shown to be localized mainly in endothelial cells, however, the presence of VEGF synthesis and the VEGF receptor in cells other than endothelial cells has been demonstrated. Neoangiogenesis in cartilage growth plate plays a fundamental role in endochondral ossification. We have shown that, in an avian in vitro system for chondrocyte differentiation, VEGF was produced and localized in cell clusters totally resembling in vivo cartilage. The factor was synthesized by hypertrophic chondrocytes and was released into their conditioned medium, which is highly chemotactic for endothelial cells. Antibodies against VEGF inhibited endothelial cell migration induced by chondrocyte conditioned media. Similarly, endothelial cell migration was inhibited also by antibodies directed against the VEGF receptor 2/Flk1 (VEGFR2). In avian and mammalian embryo long bones, immediately before vascular invasion, VEGF was distinctly localized in growth plate hypertrophic chondrocytes. In contrast, VEGF was not observed in quiescent and proliferating chondrocytes earlier in development. VEGF receptor 2 colocalized with the factor both in hypertrophic cartilage in vivo and hypertrophic cartilage engineered in vitro, suggesting an autocrine loop in chondrocytes at the time of their maturation to hypertrophic cells and of cartilage erosion. Regardless of cell exposure to exogenous VEGF, VEGFR-2 phosphorylation was recognized in cultured hypertrophic chondrocytes, supporting the idea of an autocrine functional activation of signal transduction in this non-endothelial cell type as a consequence of the endogenous VEGF production. In summary we propose that VEGF is actively responsible for hypertrophic cartilage neovascularization through a paracrine release by chondrocytes, with invading endothelial cells as a target. Furthermore, VEGF receptor localization and signal transduction in chondrocytes strongly support the hypothesis of a VEGF autocrine activity also in morphogenesis and differentiation of a mesoderm derived cell.
TL;DR: In this paper, the authors evaluate carbon taxes with regard to their competitiveness, distributional and environmental impacts and show that carbon taxes may be an interesting policy option and that their main negative impacts may be compensated through the design of the tax and the use of the generated fiscal revenues.
TL;DR: A system for direct pharmacologic control of protein secretion was developed to allow rapid and pulsatile delivery of therapeutic proteins and may make gene therapy a viable method for delivery of polypeptides that require rapid and regulated delivery.
Abstract: A system for direct pharmacologic control of protein secretion was developed to allow rapid and pulsatile delivery of therapeutic proteins. A protein was engineered so that it accumulated as aggregates in the endoplasmic reticulum. Secretion was then stimulated by a synthetic small-molecule drug that induces protein disaggregation. Rapid and transient secretion of growth hormone and insulin was achieved in vitro and in vivo. A regulated pulse of insulin secretion resulted in a transient correction of serum glucose concentrations in a mouse model of hyperglycemia. This approach may make gene therapy a viable method for delivery of polypeptides that require rapid and regulated delivery.