Matrix-assisted laser desorption ionization-time of flight mass spectrometry for direct bacterial identification from positive blood culture pellets.

An ammonium chloride erythrocyte-lysing procedure was used to prepare a bacterial pellet from positive blood cultures for direct matrix-assisted laser desorption-ionization time of flight (MALDI-TOF) mass spectrometry analysis. Identification was obtained for 78.7% of the pellets tested. Moreover, 99% of the MALDI-TOF identifications were congruent at the species level when considering valid scores. This fast and accurate method is promising.

Distinct neurophysiological mechanisms mediate mixing costs and switch costs.

Using event-related potentials (ERPs), we investigated the neural response associated with preparing to switch from one task to another. We used a cued task-switching paradigm in which the interval between the cue and the imperative stimulus was varied. The difference between response time (RT) to trials on which the task switched and trials on which the task repeated (switch cost) decreased as the interval between cue and target (CTI) was increased, demonstrating that subjects used the CTI to prepare for the forthcoming task. However, the RT on repeated-task trials in blocks during which the task could switch (mixed-task blocks) were never as short as RTs during single-task blocks (mixing cost). This replicates previous research. The ERPs in response to the cue were compared across three conditions: single-task trials, switch trials, and repeat trials. ERP topographic differences were found between single-task trials and mixed-task (switch and repeat) trials at approximately 160 and approximately 310 msec after the cue, indicative of changes in the underlying neural generator configuration as a basis for the mixing cost. In contrast, there were no topographic differences evident between switch and repeat trials during the CTI. Rather, the response of statistically indistinguishable generator configurations was stronger at approximately 310 msec on switch than on repeat trials. By separating differences in ERP topography from differences in response strength, these results suggest that a reappraisal of previous research is appropriate.

Employment Protection, Flexibility and Firms’ Strategic Location Decisions under Uncertainty

We construct a model in which oligopolistic firms decide between locating in a country where employment protection implies costly output adjustments and in one without employment protection. Using a two-period three-stage game with uncertainty, we demonstrate that location is influenced by both flexibility and strategic concerns. The strategic effects under Cournot work towards domestic anchorage in the country with employment protection while those under Bertrand do not. Strategic agglomeration can occur in the inflexible country under Cournot and even under Bertrand, provided uncertainty and foreign direct investment costs are low.

Trade Costs, International Competition and Selection: The Effects of Unionisation on Market Size

Within a two-country model of international trade in which heterogeneous firms face firm-specific unions, we study the effects of different forms of trade liberalisation on market structure and competitive selection in the presence of inter-country asymmetries in size and labour market institutions. For given levels of trade openness, an increase in a country’s relative unions’ strength reduces the average productivity of its domestic producers but increases that of its exporters. Whilst an unfavourable union power differential, by increasing wages, weakens a country’s firms’ competitive position, the higher wages reinforce standard market access mechanisms to give rise to aggregate income effects. When the initial levels of trade openness are sufficiently low, this ‘expansionary’ aggregate effect can attract industry in the country with stronger unions and also result in an increase in the extensive margin of exports. For sufficiently large inter-country differences in the bargaining power of unions, trade liberalization can then result in a pro-variety effect, with an increase in the total availability of varieties to consumers in both countries, regardless of there being inter-country differences in size.

Evidence against a direct role of klotho in insulin resistance.

The klotho gene may be involved in the aging process. Klotho is a coactivator of FGF23, a regulator of phosphate and vitamin D metabolism. It has also been reported to be downregulated in insulin resistance syndromes and paradoxically to directly inhibit IGF-1 and insulin signaling. Our aim was to study klotho's regulation and effects on insulin and IGF-1 signaling to unravel this paradox. We studied klotho tissue distribution and expression by quantitative real-time polymerase chain reaction and Western blotting in obese Zucker rats and high-fat fed Wistar rats, two models of insulin resistance. Klotho was expressed in kidneys but at much lower levels (<1.5%) in liver, muscle, brain, and adipose tissue. There were no significant differences between insulin resistant and control animals. We next produced human recombinant soluble klotho protein (KLEC) and studied its effects on insulin and IGF-1 signaling in cultured cells. In HEK293 cells, FGF23 signaling (judged by FRS2-alpha and ERK1/2 phosphorylation) was activated by conditioned media from KLEC-producing cells (CM-KLEC); however, IGF-1 signaling was unaffected. CM-KLEC did not inhibit IGF-1 and insulin signaling in L6 and Hep G2 cells, as judged by Akt and ERK1/2 phosphorylation. We conclude that decreased klotho expression is not a general feature of rodent models of insulin resistance. Further, the soluble klotho protein does not inhibit IGF-1 and/or insulin signaling in HEK293, L6, and HepG2 cells, arguing against a direct role of klotho in insulin signaling. However, the hypothesis that klotho indirectly regulates insulin sensitivity via FGF23 activation remains to be investigated.

FDI, Trade Costs and Regional Asymmetries

We set up a trade model where three countries compete for an exogenous number of firms. Our innovation lies in the geography of the model. Of the three countries, one is the hub through which all trade takes place. First, we establish the natural geography of the region, which is given by the equilibrium distribution of industrial activity in the absence of taxes or subsidies. We then examine the implications for corporate taxes when the countries compete with each other to attract firms. We find that, even when all countries are the same size, the centrality of the hub gives it an advantage in tax setting, such that its equilibrium tax can be larger than that of the spokes and yet it still attracts a disproportionate share of industry. Thus geographic advantage in tax competition has a second dimension, centrality in addition to size.

Indirect costs of parasitism are shaped by variation in the type of immune challenge and food availability

Parasites can inflict indirect fitness costs to their hosts by eliciting costly immune responses. These costs depend on the type and amount of immunostimulants presented to the host immune system but also on the amount of resources available to fuel host immune responses. Here, we investigated how the relative costs of two different types of immune challenge are modulated by variation in food availability. We injected nestling tawny owls (Strix aluco) with either 10 mu g of phytohaemagglutinin (PHA) or 20 mu g of lipopolysaccharide (LPS), and subsequently raised them under two different food regimes (food-restricted vs. ad libitum). After controlling for food consumption, we found that LPS-injected nestlings lost more body mass than PHA-injected ones only when food-restricted. We also found that body mass gain of owlets fed ad libitum decreased with the intensity of the skin swelling response against LPS, but not PHA. These experimental and correlative results suggest that nestling tawny owls suffered greater immune costs when treated with LPS than PHA, and that variation in the costs of two different types of immune challenge can be exacerbated under conditions of low food availability. Our study highlights the importance of taking into consideration the interplay between host immunity and nutrition in the study of indirect costs of parasitism.

Transaction Costs and Institutions: Investments in Exchange

This paper proposes a simple model for understanding transaction costs for their composition, size and policy implications. We distinguish between investments in institutions that facilitate exchange and the cost of conducting exchange itself. Institutional quality and market size are determined by the decisions of risk averse agents and conditions are discussed under which the efficient allocation may be decentralized. We highlight a number of differences with models where transaction costs are exogenous, including the implications for taxation and measurement issues.

Tracking cost savings from competitive tendering in the short and long run

A major initiative of the Thatcher and Major Conservative administrations was that public sector ancillary and professional services provided by incumbent direct service organisations [DSOs] be put out to tender. Analyses of this initiative, in the UK and elsewhere, found costs were often reduced in the short run. However, few if any studies went beyond the first round of tendering. We analyze data collected over successive rounds of tendering for cleaning and catering services of Scottish hospitals in order to assess the long term consequences of this initiative. The experience of the two services was very different. Cost savings for cleaning services tended to increase with each additional round of tendering and became increasingly stable. In accordance with previous results in the literature, DSOs produced smaller cost reductions than private contractors: probably an inevitable consequence of the tendering process at the time. Cost savings from DSOs tended to disappear during the first round of tendering, but they appear to have been more permanent in successive rounds. Cost savings for catering, on the other hand, tended to be much smaller, and these were not sustained.

A cost-benefit analisys of chagas disease control

Chagas disease transmission can be effetively interrupted by insecticidal control of its triatomine bug vectors. We present here a simple model comparing the costs and benefits of such a programme, designed to eliminate domestic populations of Triatoma infestans throughout its known area of distribution over the seven southernmost countries of Latin America. The model has been simplified to require only four financial estimates relating to the unit cost of housing spraying and benefits due to avoidance of premature death in the acute phase of the disease, avoidance of supportive treatment and care in the chronic phase of the disease, and avoidance of corrective digestive and cardiac surgery. Exceptfor these direct medical costs, al other potential benefits have been ignored. Nevertheless, the model shows that the direct financial benefits of such a programme would far outweigh the costs, and the project would support a remarkably high internal rate of return under the least optimistic estimates.

The costs of parasitism and anti-parasitic defense in the common vole

Résumé : Les relations entre un parasite et son hôte sont avant tout marquées par le coût pour l'hôte que représente la ponction de ressources au profit du parasite et ses conséquences sur les traits d'histoires de vie de l'hôte. Pour contenir la réduction de leur valeur reproductive, les hôtes ont acquis au cours de l'évolution des mécanismes soit de lutte contre les parasites, soit de réallocations des ressources. Curieusement les effets des ectoparasites sur la biologie de mammifères ont été peu étudiés. Dans une première expérience à long terme, nous avons examiné sous un angle intégratif si les puces Nosopsyllus fasciatus affectent certains paramètres physiologiques des campagnols des champs Microtus arvalis. Nous avons également testé si les puces peuvent réduire la longévité et si oui, si ce pourrait être dû à une accélération de la sénescence. Ensuite nous avons testé si la simple activation répétée du système immunitaire comme lors d'une infestation chronique pouvait aussi réduire la longévité. Dans une dernière expérience, nous avons d'abord testé si l'infestation par des puces de jeunes campagnols au stade néonatal (21 jours) pouvait modifier leur développement et leur phénotype adulte. Puis nous avons testé si la modification du phénotype adulte est une réponse prédite et potentiellement adaptative pour minimiser les effets des puces à l'âge adulte. Nos résultats montrent que l'infestation par des puces réduit la croissance subadulte, induit une forte anémie et une immunodépression, et augmente le métabolisme de repos. De plus les puces réduisent la longévité et la taille des testicules, réduisant fortement le succès reproducteur potentiel des individus parasités. La taille finale, c'est-à-dire le développement pré-adulte, détermine en grande part la longévité. La réduction de longévité ne devrait pas être due à l'investissement au profit du système immunitaire car l'activation chronique seule du système immunitaire ne réduit pas la longévité. L'infestation néonatale retarde légèrement le développement mais surtout modifie l'hématocrite et réduit les performances locomotrices des campagnols plus de 3 mois après l'infestation. Les effets immédiats du parasitisme sur la physiologie semblent bien supérieurs comparés aux effets à long terme. Nous n'avons pas d'éléments permettant d'affirmer que le parasitisme néonatal prépare les campagnols à faire face aux puces à l'âge adulte. Au contraire, le parasitisme néonatal interagit sur le parasitisme adulte pour augmenter le métabolisme de repos. Cette thèse offre une vision intégrative des mécanismes par lesquels les puces peuvent affecter la valeur reproductive de leurs hôtes. De façon générale, ces résultats 35 montrent l'importance des puces comme force de sélection chez les campagnols. Il est indispensable de prendre en compte les ectoparasites dans l'étude de l'écologie et des dynamiques de populations chez les mammifères. Summary : The relationship between a parasite and its host is fundamentally marked by the costs for host of the withdrawals of resources by parasite and the subsequent reduction in host life-history traits. Hosts have evolved a number of strategies to reduce these costs, either by fighting against the parasite directly or by reallocating resources to reduce costs on lifetime reproductive value. The effects of ectoparasites on burrowing mammals have been scarcely studied. In a first long-term experiment, we examined how fleas Nosopsyllus fasciatus affect physiological levels of the common vole, Microtus arvalis. We also examined whether fleas reduce longevity and if so, if it is due to an early senescence pattern. Then we tested if experimental activation of the immune system by repeated injections of an antigen could result in a shorter longevity. In the last experiment, we tested if short-lasting neonatal parasitism can have long-term effects on phenotype, and if these effects could induce a predictive response to reduce damages when parasitized at the adult stage. We found that parasitism by flea reduced subadult growth, induced anaemia and immunodepression, and increased energy consumption even when resting. Moreover fleas reduce longevity and testes size associated to splenomegaly, suggesting an overall reduction in fitness but we did not find any pattern of accelerated senescence explaining the early death of parasitized voles compared to non-parasitzed. The cost of mounting an immune response throughout life does not impair longevity, suggesting that it is the cost of parasitism that limits the longevity and not the immune investment. Neonatal infestation by fleas has long-term effects on physiology and reduces motor activity more than 3 months after infestation. The modification of physiology due to long-term effects seems weak compared to the immediate effects of adult infestation. We found no evidence that neonatal parasitism prepares voles to mount a predictive adaptive response in order to reduce effects of fleas on fitness components. On the contrary, neonatal parasitism seems to worsen the effect of adult parasitism. This thesis offers an integrative view of mechanisms by which fleas affect their host at the individual level. Overall, our results demonstrate the importance of fleas as a selective force in voles. These results highlight the importance of ectoparasitism in ecology of micromarnrnals and suggest a role in the dynamic of host populations.

Predator-prey chemical warfare determines the expression of biocontrol genes by rhizosphere-associated Pseudomonas fluorescens.

Soil bacteria are heavily consumed by protozoan predators, and many bacteria have evolved defense strategies such as the production of toxic exometabolites. However, the production of toxins is energetically costly and therefore is likely to be adjusted according to the predation risk to balance the costs and benefits of predator defense. We investigated the response of the biocontrol bacterium Pseudomonas fluorescens CHA0 to a common predator, the free-living amoeba Acanthamoeba castellanii. We monitored the effect of the exposure to predator cues or direct contact with the predators on the expression of the phlA, prnA, hcnA, and pltA genes, which are involved in the synthesis of the toxins, 2,4-diacetylphloroglucinol (DAPG), pyrrolnitrin, hydrogen cyanide, and pyoluteorin, respectively. Predator chemical cues led to 2.2-, 2.0-, and 1.2-fold increases in prnA, phlA, and hcnA expression, respectively, and to a 25% increase in bacterial toxicity. The upregulation of the tested genes was related to the antiprotozoan toxicity of the corresponding toxins. Pyrrolnitrin and DAPG had the highest toxicity, suggesting that bacteria secrete a predator-specific toxin cocktail. The response of the bacteria was elicited by supernatants of amoeba cultures, indicating that water-soluble chemical compounds were responsible for induction of the bacterial defense response. In contrast, direct contact of bacteria with living amoebae reduced the expression of the four bacterial toxin genes by up to 50%, suggesting that protozoa can repress bacterial toxicity. The results indicate that predator-prey interactions are a determinant of toxin production by rhizosphere P. fluorescens and may have an impact on its biocontrol potential.

Vitamin D has a direct immunomodulatory effect on CD8+ T cells of patients with early multiple sclerosis and healthy control subjects.

Little is known on a putative effect of vitamin D on CD8+ T cells. Yet, these cells are involved in the immmunopathogenesis of MS. We assessed the cytokine profile of EBV-specific CD8+ T cells of 10 early MS patients and 10 healthy control subjects with or without 1,25(OH)(2)D(3) and found that, with 1,25(OH)(2)D(3), these cells secreted less IFN-γ and TNF-α and more IL-5 and TGF-β. CD4+ T cell depletion or even culture with CD8+ T cells only did not abolish the immunomodulatory effect of 1,25(OH)(2)D(3) on CD8+ T cells, suggesting that 1,25(OH)(2)D(3) can act directly on CD8+ T cells.