Catch-up growth strategies differ between body structures: interactions between age and structure-specific growth in wild nestling Alpine swifts

1. Little is known on the occurrence and magnitude of faster than normal (catch-up) growth in response to periods of undernutrition in the wild, and the extent to which different body structures compensate and over what timescales is poorly understood. 2. We investigated catch-up growth in nestling Alpine Swifts, Apus melba, by comparing nestling growth trajectories in response to a naturally occurring 1-week period of inclement weather and undernutrition with growth of nestlings reared in a good year. 3. In response to undernutrition, nestlings exhibited a hierarchy of tissues preservation and compensation, with body mass being restored quickly after the end of the period of undernutrition, acceleration of skeletal growth occurring later in development, and compensation in wing length occurring mostly due to a prolongation of growth and delayed fledging. 4. The effect of undernutrition and subsequent catch-up growth was age-dependent, with older nestlings being more resilient to undernutrition, and in turn having less need to compensate later in the development. 5. This shows that young in a free-living bird population can compensate in body mass and body size for a naturally occurring period of undernutrition, and that the timing and extent of compensation varies with age and between body structures.

Resistance to extreme strategies, rather than prosocial preferences, can explain human cooperation in public goods games.

The results of numerous economic games suggest that humans behave more cooperatively than would be expected if they were maximizing selfish interests. It has been argued that this is because individuals gain satisfaction from the success of others, and that such prosocial preferences require a novel evolutionary explanation. However, in previous games, imperfect behavior would automatically lead to an increase in cooperation, making it impossible to decouple any form of mistake or error from prosocial cooperative decisions. Here we empirically test between these alternatives by decoupling imperfect behavior from prosocial preferences in modified versions of the public goods game, in which individuals would maximize their selfish gain by completely (100%) cooperating. We found that, although this led to higher levels of cooperation, it did not lead to full cooperation, and individuals still perceived their group mates as competitors. This is inconsistent with either selfish or prosocial preferences, suggesting that the most parsimonious explanation is imperfect behavior triggered by psychological drives that can prevent both complete defection and complete cooperation. More generally, our results illustrate the caution that must be exercised when interpreting the evolutionary implications of economic experiments, especially the absolute level of cooperation in a particular treatment.

The Value of the County Engineer: Strategies to Expand the Shrinking Employment Pool, HR-338, 1993

The first phase of this research involved an effort to identify the issues relevant to gaining a better understanding of the County Engineering profession. A related objective was to develop strategies to attract responsible, motivated and committed professionals to pursue County Engineering positions. In an era where a large percentage of County Engineers are reaching retirement age, the shrinking employment pool may eventually jeopardize the quality of secondary road systems not only in Iowa, but nationwide. As we move toward the 21st century, in an era of declining resources, it is likely that professional staff members in charge of secondary roads will find themselves working with less flexible budgets for the construction and maintenance of roads and bridges. It was important to understand the challenges presented to them, and the degree to which those challenges will demand greater expertise in prioritizing resource allocations for the rehabilitation and maintenance of the 10 million miles of county roads nationwide. Only after understanding what a county engineer is and what this person does will it become feasible for the profession to begin "selling itself", i.e., attracting a new generation of County Engineers. Reaching this objective involved examining the responsibilities, goals, and, sometimes, the frustrations experienced by those persons in charge of secondary road systems in the nine states that agreed to participate in the study. The second phase of this research involved addressing ways to counter the problems associated with the exodus of County Engineers who are reaching retirement age. Many of the questions asked of participants asked them to compare the advantages and disadvantages of public sector work with the private sector. Based on interviews with nearly 50 County Engineers and feedback from 268 who returned surveys for the research, issues relevant to the profession were analyzed and recommendations were made to the profession as it prepares to attract a new generation. It was concluded that both State and Regional Associations for County Engineers, and the National Association of County Engineers are most well-situated to present opportunities for continued professional development. This factor is appealing for those who are interested in competitive advantages as professionals. While salaries in the public sector may not be able to effectively compete with those offered by the private sector, it was concluded that this is only one factor of concern to those who are in the business of "public service". It was concluded, however, that Boards of Supervisors and their equivalents in other states will need to more clearly understand the value of the contributions made by County Engineers. Then the selling points the profession can hope to capitalize on can focus on the strength of state organizations and a strong national organization that act as clearinghouses of information and advocates for the profession, as well as anchors that provide opportunities for staying current on issues and technologies.

Strategies for preventing late-onset cytomegalovirus disease in organ transplant recipients.

Objective: The incidence of late-onset cytomegalovirus disease (i.e. disease appearing after discontinuation of antiviral prophylaxis) in solid-organ transplant recipients remains excessively high. This review will focus on describing the several strategies that could potentially reduce the incidence of late-onset cytomegalovirus disease. Methods: We reviewed the literature and presented our own clinical experience in the field. Results: The incidence of late-onset cytomegalovirus disease in recent trials can be as high as 36% in high-risk patients (donor positive/recipient negative for cytomegalovirus). The extension of antiviral prophylaxis to six months has recently proven in a prospective randomized controlled trial to be effective for reducing late-onset cytomegalovirus disease. The monitoring of cytomegalovirus viral load by PCR after the discontinuation of prophylaxis seems to be of moderate usefulness in low/intermediate-risk patients. The use of low-dose valganciclovir could reduce drug toxicity and costs while maintaining similar efficacy, but further studies are needed. A potentially interesting approach to predict the individual risk for development of cytomegalovirus disease appears to be the assessment of specific cell-mediated immune response. If cell-mediated immunity assays become widely available in transplant centers in the future, these assays may possibly be used to tailor the cytomegalovirus preventive strategy on an individual basis. Finally, recent prospective trials have evaluated novel cytomegalovirus vaccines that merit further evaluation in the transplant setting, although currently there is no cytomegalovirus vaccine that has been approved for routine clinical use. Conclusions: Several studies have recently evaluated novel strategies to reduce the incidence of late-onset cytomegalovirus disease. It is therefore expected that this improvement in preventive strategies will allow to further reduce the negative effects of cytomegalovirus disease after transplantation.

PGC-1α induces mitochondrial and myokine transcriptional programs and lipid droplet and glycogen accumulation in cultured human skeletal muscle cells

The transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1α) is a chief activator of mitochondrial and metabolic programs and protects against atrophy in skeletal muscle (skm). Here we tested whether PGC-1α overexpression could restructure the transcriptome and metabolism of primary cultured human skm cells, which display a phenotype that resembles the atrophic phenotype. An oligonucleotide microarray analysis was used to reveal the effects of PGC-1α on the whole transcriptome. Fifty-three different genes showed altered expression in response to PGC-1α: 42 upregulated and 11 downregulated. The main gene ontologies (GO) associated with the upregulated genes were mitochondrial components and processes and this was linked with an increase in COX activity, an indicator of mitochondrial content. Furthermore, PGC-1α enhanced mitochondrial oxidation of palmitate and lactate to CO2, but not glucose oxidation. The other most significantly associated GOs for the upregulated genes were chemotaxis and cytokine activity, and several cytokines, including IL-8/CXCL8, CXCL6, CCL5 and CCL8, were within the most highly induced genes. Indeed, PGC-1α highly increased IL-8 cell protein content. The most upregulated gene was PVALB, which is related to calcium signaling. Potential metabolic regulators of fatty acid and glucose storage were among mainly regulated genes. The mRNA and protein level of FITM1/FIT1, which enhances the formation of lipid droplets, was raised by PGC-1α, while in oleate-incubated cells PGC-1α increased the number of smaller lipid droplets and modestly triglyceride levels, compared to controls. CALM1, the calcium-modulated δ subunit of phosphorylase kinase, was downregulated by PGC-1α, while glycogen phosphorylase was inactivated and glycogen storage was increased by PGC-1α. In conclusion, of the metabolic transcriptome deficiencies of cultured skm cells, PGC-1α rescued the expression of genes encoding mitochondrial proteins and FITM1. Several myokine genes, including IL-8 and CCL5, which are known to be constitutively expressed in human skm cells, were induced by PGC-1α.

Constraining ACT-R models of decision strategies: An experimental paradigm

It has been repeatedly debated which strategies people rely on in inference. These debates have been difficult to resolve, partially because hypotheses about the decision processes assumed by these strategies have typically been formulated qualitatively, making it hard to test precise quantitative predictions about response times and other behavioral data. One way to increase the precision of strategies is to implement them in cognitive architectures such as ACT-R. Often, however, a given strategy can be implemented in several ways, with each implementation yielding different behavioral predictions. We present and report a study with an experimental paradigm that can help to identify the correct implementations of classic compensatory and non-compensatory strategies such as the take-the-best and tallying heuristics, and the weighted-linear model.

Thyroid hormones stimulate expression and modification of cytoskeletal protein during rat sciatic nerve regeneration.

Peripheral neurons can regenerate after axotomy; in this process, the role of cytoskeletal proteins is important because they contribute to formation and reorganization, growth, transport, stability and plasticity of axons. In the present study, we examined the effects of thyroid hormones (T3) on the expression of major cytoskeletal proteins during sciatic nerve regeneration. At various times after sciatic nerve transection and T3 local administration, segments of operated nerves from T3-treated rats and control rats were examined by Western blotting for the presence of neurofilament, tubulin and vimentin. Our results revealed that, during the first week after surgery, T3 treatment did not significantly alter the level of NF subunits and tubulin in the different segments of operated nerves compared to control nerves. Two or 4 weeks after operation, the concentration of NF-H and NF-M isoforms was clearly increased by T3 treatment. Moreover, under T3-treatment, NF proteins appeared more rapidly in the distal segment of operated nerves. Likewise, the levels of betaIII, and of acetylated and tyrosinated tubulin isotypes, were also up-regulated by T3-treatment during regeneration. However, only the tyrosinated tubulin form appeared earlier in the distal nerve segments. At this stage of regeneration, T3 had no effect on the level of vimentin expression. In conclusion, thyroid hormone improves and accelerates peripheral nerve regeneration and exerts a positive effect on cytoskeletal protein expression and transport involved in axonal regeneration. These results help us to understand partially the mechanism by which thyroid hormones enhance peripheral nerve regeneration. The stimulating effect of T3 on peripheral nerve regeneration may have considerable therapeutic potential.

Modification of Ca-Montmorillonite by Low-Temperature Heat Treatment, HR-106, 1964

Objectives of this investigation were to measure the effects of moderate heat treatments (below the dehydroxylation temperature) on physical and chemical properties of a calcium-montmorillonite clay. Previous workers have noted the reduction in cation exchange capacity and swelling property after heating in the range 200 to 400°C, and have suggested several possible explanations, such as hysteresis effect, increased inter-layer attractions due to removal of inter-layer water, or changes in the disposition of inter-layer or layer surface ions. The liquid limits of Ca-montmorillonite were steadily decreased with increased temperature of treatment, levelling at about 450°C. The plastic limit decreased slightly up to 350°C, above which samples could no longer be rolled into threads. The gradual change is in contrast with sudden major changes noted for weight loss (maximum rates of change at l00°C and 500°C), glycol retention surface area (520°C), and d001 diffraction peak intensity (17.7 A spacing) and breadth after glycolation (530°C). Other properties showing more gradual reductions with heat treatment were amount of exchangeable calcium (without water soaking), cation exchange capacity by NH4AC method, and d001 intensity (21 A spacing) after storing at 100% r.h. one month and re-wetting with water. Previous water soaking allowed much greater release of fixed Ca++ up to 450°C. Similar results were obtained with cation exchange capacities when samples were treated with N CaCl2 solution. The 21.0 A peak intensity curve showed close similarity to the liquid limit and plastic index curves in the low temperature range, and an explanation is suggested.

The Local Rural Road System: Alternative Investment Strategies, HR-242, 1989

A benefit-cost analysis was used to examine the effects of alternative investment strategies on the local rural road system. The study first estimated the change in costs to the traveling public of various investment strategies, then compared the change for each investment strategy to the cost of implementing that strategy on the county rural road system. The basic purpose of this study was to develop guidelines for local supervisors and engineers in evaluating investment or disinvestment proposals, and to provide information to state legislatures in developing local rural road and bridge policies. Three case study areas of 100 sq mi each were selected in Iowa. A questionnaire was used to collect data from farm and non-farm residents in the study areas. Data were obtained on the number of 1982 trips by origin, destination, and type of vehicle.

Differential insertion of GPI-anchored GFPs into lipid rafts of live cells.

Partitioning of proteins in cholesterol and sphingolipid enriched plasma membrane microdomains, called lipid rafts, is critical for many signal transduction and protein sorting events. Although raft partitioning of many signaling molecules remains to be determined, glycosylphosphatidyl-inositol (GPI)-anchored proteins possess high affinity for lipid rafts and are currently exploited as markers to investigate fundamental mechanisms in protein sorting and signal transduction events. In this study, we demonstrate that two recombinant GPI-anchored green fluorescent proteins (GFP-GPIs) that differ in their GPI signal sequence confer distinct localization in plasma membrane microdomains. GFP fused to the GPI signal of the decay accelerating factor GFP-GPI(DAF) partitioned exclusively in lipid rafts, whereas GFP fused to the GPI signal of TRAIL-R3, GFP-GPI(TRAIL-R3), associated only minimally with microdomains. In addition, we investigated the unique ability of purified GFP-GPIs to insert into membrane microdomains of primary lymphocytes. This cell surface painting allows rapid, stable, and functional association of the GPI-anchored proteins with the target cell plasma membrane. The distinct membrane localization of the two GFP-GPIs was observed irrespective of whether the GPI-anchored molecules were painted or transfected. Furthermore, we show that painted GFP-GPI(DAF) was totally dependent on the GPI anchor and that the membrane insertion was increased by the addition of raft-associated lipids such as cholesterol, sphingomyelin, and dipalmitoyl-phosphatidylethanolamine. Thus, this study provides evidence that different GPI signal sequences lead to distinct membrane microdomain localization and that painted GFP-GPI(DAF) serves as an excellent fluorescent marker for lipid rafts in live cells.

Comparison of fat suppression strategies in 3D spiral coronary magnetic resonance angiography.

PURPOSE: In the present study, the impact of the two different fat suppression techniques was investigated for free breathing 3D spiral coronary magnetic resonance angiography (MRA). As the coronary arteries are embedded in epicardial fat and are adjacent to myocardial tissue, magnetization preparation such as T(2)-preparation and fat suppression is essential for coronary discrimination. MATERIALS AND METHODS: Fat-signal suppression in three-dimensional (3D) thin- slab coronary MRA based on a spiral k-space data acquisition can either be achieved by signal pre-saturation using a spectrally selective inversion recovery pre-pulse or by spectral-spatial excitation. In the present study, the performance of the two different approaches was studied in healthy subjects. RESULTS: No significant objective or subjective difference was found between the two fat suppression approaches. CONCLUSION: Spectral pre-saturation seems preferred for coronary MRA applications due to the ease of implementation and the shorter cardiac acquisition window.

Role of the epithelial sodium channel (ENaC) in the epidermal barrier function of the skin

Abstract In humans, the skin is the largest organ of the body, covering up to 2m2 and weighing up to 4kg in an average adult. Its function is to preserve the body from external insults and also to retain water inside. This barrier function termed epidermal permeability barrier (EPB) is localized in the functional part of the skin: the epidermis. For this, evolution has built a complex structure of cells and lipids sealing the surface, the stratum corneum. The formation of this structure is finely tuned since it is not only formed once at birth, but renewed all life long. This active process gives a high plasticity and reactivity to skin, but also leads to various pathologies. ENaC is a sodium channel extensively studied in organs like kidney and lung due to its importance in regulating sodium homeostasis and fluid volume. It is composed of three subunits α, ß and r which are forming sodium selective channel through the cell membrane. Its presence in the skin has been demonstrated, but little is known about its physiological role. Previous work has shown that αENaC knockout mice displayed an abnormal epidermis, suggesting a role in differentiation processes that might be implicated in the EPB. The principal aim of this thesis has been to study the consequences for EPB function in mice deficient for αENaC by molecular and physiological means and to investigate the underlying molecular mechanisms. Here, the barrier function of αENaC knockout pups is impaired. Apparently not immediately after birth (permeability test) but 24h later, when evident water loss differences appeared compared to wildtypes. Neither the structural proteins of the epithelium nor the tights junctions showed any obvious alterations. In contrary, stratum corneum lipid disorders are most likely responsible for the barrier defect, accompanied by an impairment of skin surface acidification. To analyze in details this EPB defect, several hypotheses have been proposed: reduced sensibility to calcium which is the key activator far epidermal formation, or modification of ENaC-mediated ion fluxes/currents inside the epidermis. The cellular localization of ENaC and the action in the skin of CAPl, a positive regulator of ENaC, have been also studied in details. In summary, this study clearly demonstrates that ENaC is a key player in the EPB maintenance, because αENaC knockout pups are not able to adapt to the new environment (ex utero) as efficiently as the wildtypes, most likely due to impaired of sodium handling inside the epidermis. Résumé Chez l'homme, la peau est le plus grand organe, couvrant presque 2m2 et pesant près de 4kg chez l'adulte. Sa fonction principale est de protéger l'organisme des agressions extérieures mais également de conserver l'eau à l'intérieur du corps. Cette fonction nommée barrière épithéliale est localisée dans la partie fonctionnelle de la peau : l'épiderme. A cette fin, l'évolution s'est dotée d'une structure complexe composée de cellules et de lipides recouvrant la surface, la couche cornée. Sa formation est finement régulée, car elle n'est pas seulement produite à la naissance mais constamment renouvelée tout au long de la vie, ce qui lui confère une grande plasticité mais ce qui est également la cause de nombreuses pathologies. ENaC est un canal sodique très étudié dans le rein et le poumon pour son importance dans la régulation de l'homéostasie sodique et la régulation du volume du milieu intérieur. Il est composé de 3 sous unités, α, ß et y qui forment un pore sélectif pour le sodium dans les membranes. Ce canal est présent dans la peau mais sa fonction n'y est pas connue. Des travaux précédents ont pu montrer que les souris dont le gène codant pour αENaC a été invalidé présentent un épiderme pathologique, suggérant un rôle dans la différentiation et pourrait même être impliqué dans la barrière épithéliale. Le but de cette thèse fut l'étude de la barrière dans ces souris knockouts avec des méthodes moléculaires et physiologiques et la caractérisation des mécanismes moléculaire impliqués. Dans ce travail, il a été montré que les souris mutantes présentaient un défaut de la barrière. Ce défaut n'est pas visible immédiatement à la naissance (test de perméabilité), mais 24h plus tard, lorsque les tests de perte d'eau transépithéliale montrent une différence évidente avec les animaux contrôles. Ni les protéines de structures ni les jonctions serrées de l'épiderme ne présentaient d'imperfections majeures. A l'inverse, les lipides de la couche cornée présentaient un problème de maturation (expliquant le phénotype de la barrière), certainement consécutif au défaut d'acidification à la surface de la peau que nous avons observé. D'autres mécanismes ont été explorées afin d'investiguer cette anomalie de la barrière, comme la réduction de sensibilité au calcium qui est le principal activateur de la formation de l'épiderme, ou la modification des flux d'ions entre les couches de l'épiderme. La localisation cellulaire d'ENaC, et l'action de son activateur CAPl ont également été étudiés en détails. En résumé, cette étude démontre clairement qu'ENaC est un acteur important dans la formation de la barrière épithéliale, car la peau des knockouts ne s'adapte pas aussi bien que celle des sauvages au nouvel environnement ex utero à cause de la fonction d'ENaC dans les mouvements de sodium au sein même de l'épiderme. Résumé tout public Chez l'homme, la peau est le plus grand organe, couvrant presque 2m2 et pesant près de 4kg chez l'adulte. Sa fonction principale est de protéger l'organisme des agressions extérieures mais également de conserver l'eau à l'intérieur du corps. Cette fonction nommée barrière épithéliale est localisée dans la partie fonctionnelle de la peau : l'épiderme. A cette fin, l'évolution s'est dotée d'une structure complexe composée de cellules et de lipides recouvrant la surface, la couche cornée. Sa formation est finement régulée, car elle n'est pas seulement produite à la naissance mais constamment renouvelée tout au long de la vie, ce qui lui confère une grande plasticité mais ce qui est également la cause de nombreuses maladies. ENaC est une protéine formant un canal qui permet le passage sélectif de l'ion sodium à travers la paroi des cellules. Il est très étudié dans le rein pour son importance dans la récupération du sel lors de la concentration de l'urine. Ce canal est présent dans la peau mais sa fonction n'y est pas connue. Des travaux précédents ont pu montrer que les souris où le gène codant pour αENaC a été invalidé présentent un épiderme pathologique, suggérant un rôle dans la peau et plus particulièrement la fonction de barrière de l'épiderme. Le but de cette thèse fut l'étude de la fonction de barrière dans ces souris mutantes, au niveau tissulaire et cellulaire. Dans ce travail, il a été montré que les souris mutantes présentaient une peau plus perméable que celle des animaux contrôles, grâce à une machine mesurant la perte d'eau à travers la peau. Ce défaut n'est visible que 24h après la naissance, mais nous avons pu montrer que les animaux mutants perdaient quasiment 2 fois plus d'eau que les contrôles. Au niveau moléculaire, nous avons pu montrer que ce défaut provenait d'un problème de maturation des lipides qui composent la barrière de la peau. Cette maturation est incomplète vraisemblablement à cause d'un défaut de mouvement des ions dans les couches les plus superficielles de l'épiderme, et cela à cause de l'absence du canal ENaC. En résumé, cette étude démontre clairement qu'ENaC est un acteur important dans la formation de la barrière épithéliale, car la peau des mutants ne s'adapte pas aussi bien que celle des sauvages au nouvel environnement ex utero à cause de la fonction d'ENaC dans les mouvements de sodium au sein même de l'épiderme.

Stratégies diagnostiques des diarrhées chroniques de l'adulte [Chronic diarrhea in adults: diagnostic strategies]

The presence of chronic diarrhea requires a prompt diagnostic strategy in order to avoid risks of malnutrition and electrolytic disturbances. Two different clinical situations, i.e. collagen colitis and secretory diarrhea, exemplify the diagnostic evaluation of a single symptom. This non exhaustive review should lead to a diagnostic strategy of chronic diarrhea.