Tax principles, product differentiation and the nature of competition

We analyze the choice between the origin and destination principles of taxation when there is product differentiation and Bertrand competition. If taxes are redistributed to consumers and demand is linear the origin principle dominates the destination principle whatever the degree of product differentiation and extent of economic integration. With nonlinear demand the origin principle dominates if there is sufficient economic integration. When the social value assigned to tax revenue is higher than the private value, the destination principle dominates for intermediate values of product differentiation and economic integration. The same results are also shown to hold with Cournot competition.

Applying Jackson’s methodological ideal-types: problems of differentiation and classification

In The Conduct of Inquiry in International Relations, Patrick Jackson situates methodologies in International Relations in relation to their underlying philosophical assumptions. One of his aims is to map International Relations debates in a way that ‘capture[s] current controversies’ (p. 40). This ambition is overstated: whilst Jackson’s typology is useful as a clarificatory tool, (re)classifying existing scholarship in International Relations is more problematic. One problem with Jackson’s approach is that he tends to run together the philosophical assumptions which decisively differentiate his methodologies (by stipulating a distinctive warrant for knowledge claims) and the explanatory strategies that are employed to generate such knowledge claims, suggesting that the latter are entailed by the former. In fact, the explanatory strategies which Jackson associates with each methodology reflect conventional practice in International Relations just as much as they reflect philosophical assumptions. This makes it more difficult to identify each methodology at work than Jackson implies. I illustrate this point through a critical analysis of Jackson’s controversial reclassification of Waltz as an analyticist, showing that whilst Jackson’s typology helps to expose inconsistencies in Waltz’s approach, it does not fully support the proposed reclassification. The conventional aspect of methodologies in International Relations also raises questions about the limits of Jackson’s ‘engaged pluralism’.

Isotopic examination of links between diet, social differentiation and DISH at the post-medieval Carmelite Friary of Aalst, Belgium

Stable isotope ratios (δ13C and δ15N) were measured in human burials from the post-medieval (16th–18th c. AD) Carmelite friary burial grounds at Aalst, a town in Flanders, Belgium. Dietary patterns of 39 adult individuals were analyzed, from a mixed monastic and lay population buried in three different locations, reflecting groups with differing social status. The data show significant variation in the consumption of perhaps meat, but certainly also marine protein between females and males. This result represents a remarkable continuity with medieval dietary patterns, suggesting that the social and economic changes of the early modern period had a limited effect on everyday life. When both sexes were examined together, individuals buried in the cloister garth consumed significantly less marine protein compared to people buried in the church, likely reflecting social stratification. No statistical differences were observed between isotopic values from the church and the cloister alley, suggesting a similarly diverse diet of the monastic part of the buried population and that of the richer lay population. Finally, the hypothesis that diffuse idiopathic skeletal hyperostosis (DISH) is linked to a diet rich in animal protein was tested. No systematic or statistically significant differences between pathological and non-pathological bones from the same individuals affected with DISH were observed, and no statistical differences were found between individuals with DISH and individuals without DISH

An endogenous regulator of inflammation, resolvin E1, modulates osteoclast differentiation and bone resorption

Background and purpose: The inflammation-resolving lipid mediator resolvin E1 (RvE1) effectively stops inflammation-induced bone loss in vivo in experimental periodontitis. It was of interest to determine whether RvE1 has direct actions on osteoclast (OC) development and bone resorption. Experimental approach: Primary OC cultures derived from mouse bone marrow were treated with RvE1 and analysed for OC differentiation, cell survival and bone substrate resorption. Receptor binding was measured using radiolabelled RvE1. Nuclear factor (NF)-kappa B activation and Akt phosphorylation were determined with western blotting. Lipid mediator production was assessed with liquid chromatography tandem mass spectrometry. Key results: OC growth and resorption pit formation were markedly decreased in the presence of RvE1. OC differentiation was inhibited by RvE1 as demonstrated by decreased number of multinuclear OC, a delay in the time course of OC development and attenuation of receptor activator of NF-kappa B ligand-induced nuclear translocation of the p50 subunit of NF-kappa B. OC survival and apoptosis were not altered by RvE1. Messenger RNA for both receptors of RvE1, ChemR23 and BLT(1) is expressed in OC cultures. Leukotriene B(4) (LTB(4)) competed with [(3)H] RvE1 binding on OC cell membrane preparations, and the LTB(4) antagonist U75302 prevented RvE1 inhibition of OC growth, indicating that BLT(1) mediates RvE1 actions on OC. Primary OC synthesized the RvE1 precursor 18R-hydroxy-eicosapentaenoic acid and LTB(4). Co-incubation of OC with peripheral blood neutrophils resulted in transcellular RvE1 biosynthesis. Conclusions and implications: These results indicate that RvE1 inhibits OC growth and bone resorption by interfering with OC differentiation. The bone-sparing actions of RvE1 are in addition to inflammation resolution, a direct action in bone remodelling.

Impaired dendritic cell differentiation and maturation in the absence of C3

Human monocytes can be differentiated into immature dendritic cells (DCs) in the presence of serum and cytokines. One of the main functions of immature DCs is to capture and process antigens. Following maturation, they differentiate into antigen presenting cells. The role of complement in the differentiation process from monocytes towards immature DCs remains elusive. Here we demonstrate that complement 3 (C3) has a regulatory impact on the expression of specific DC surface molecules and DC-derived cytokine production during DC differentiation. We isolated human adherent peripheral blood mononuclear cells, which were cultured in the presence of GM-CSF plus IL-4 in medium supplemented with normal human serum or C3 deficient serum. The lack of C3 during DC differentiation negatively impacted the expression of C-type lectin receptor DC-SIGN, the antigen presenting molecules HLA-DR and CD1a, and the costimulatory molecules CD80 and CD86. Further, the spontaneous production of IL-6 and IL-12 was reduced in the absence of C3. Moreover, the maturation of immature DCs in response to LPS challenge was impaired in the absence of C3 as evidenced by reduced MHC-II, co-stimulatory molecule expression as well as modulated IL-12 and TNF-alpha production. Collectively, our results provide evidence for a novel role of C3 as a critical cofactor in human DC differentiation and maturation. (C) 2007 Elsevier Ltd. All rights reserved.

Deficiency of thrombospondin-1 reduces Th17 differentiation and attenuates experimental autoimmune encephalomyelitis

Transforming growth factor beta (TGF-beta) plays a role both in the induction of Treg and in the differentiation of the IL-17-secreting T cells (Th17) which drive inflammation in experimental autoimmune encephalomyelitis (EAE). We investigated the role that thrombospondin-1 (TSP-1) dependent activation of TGF-beta played in the generation of an encephalitic Th17 response in EAE. Upon immunization with myelin oligodendrocyte glycoprotein peptide (MOG(35-55)), TSP-1 deficient (TSP-1(null)) mice and MOG(35-55) TCR transgenic mice that lack of TSP-1 (2D2.TSP-1(null)) exhibited an attenuated form of EAE, and secreted lower levels of IL-17. Adoptive transfer of in vitro-activated 2D2.TSP-1(null) T cells induced a milder form of EAE, independent of TSP-1 expression in the recipient mice. Furthermore, in vitro studies demonstrated that anti-CD3/anti-CD28 pre-activated CD4+ T cells transiently upregulated latent TGF-beta in a TSP-1 dependent way, and such activation of latent TGF-beta was required for the differentiation of Th17 cells. These results demonstrate that TSP-1 participates in the differentiation of Th17 cells through its ability to activate latent TGF-beta, and enhances the inflammatory response in EAE. (C) 2009 Elsevier Ltd. All rights reserved.

The Thyroid Hormone Receptor (TR) beta-Selective Agonist GC-1 Inhibits Proliferation But Induces Differentiation and TR beta mRNA Expression in Mouse and Rat Osteoblast-Like Cells

Previous studies showed anabolic effects of GC-1, a triiodothyronine (T3) analogue that is selective for both binding and activation functions of thyroid hormone receptor (TR) beta 1 over TR alpha 1, on bone tissue in vivo. The aim of this study was to investigate the responsiveness of rat (ROS17/2.8) and mouse (MC3T3-E1) osteoblast-like cells to GC-1. As expected, T3 inhibited cellular proliferation and stimulated mRNA expression of osteocalcin or alkaline phosphatase in both cell lineages. Whereas equimolar doses of T3 and GC-1 equally affected these parameters in ROS17/2.8 cells, the effects of GC-1 were more modest compared to those of T3 in MC3T3-E1 cells. Interestingly, we showed that there is higher expression of TR alpha 1 than TR beta 1 mRNA in rat (similar to 20-90%) and mouse (similar to 90-98%) cell lineages and that this difference is even higher in mouse cells, which highlights the importance of TR alpha 1 to bone physiology and may partially explain the modest effects of GC-1 in comparison with T3 in MC3T3-E1 cells. Nevertheless, we showed that TR beta 1 mRNA expression increases (similar to 2.8- to 4.3-fold) as osteoblastic cells undergo maturation, suggesting a key role of TR beta 1 in mediating T3 effects in the bone forming cells, especially in mature osteoblasts. It is noteworthy that T3 and GC-1 induced TR beta 1 mRNA expression to a similar extent in both cell lineages (similar to 2- to 4-fold), indicating that both ligands may modulate the responsiveness of osteoblasts to T3. Taken together, these data show that TR beta selective T3 analogues have the potential to directly induce the differentiation and activity of osteoblasts.

High levels of genetic differentiation and selfing in the Brazilian cerrado fruit tree Dipteryx alata Vog. (Fabaceae)

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Cranial differentiation and evolution in Thrichomys apereoides (Rodentia: Echimyidae)

Thrichomys apereoides is an echimyid rodent which ranges in distribution from north-eastern and central Brazil into Paraguay, and currently five subspecies are recognized. Recent morphometric analyses of population samples formally assignable to T. a. laurentius and T. a. inermis, which occur in north-eastern Brazil, have shown that a major group of populations including both subspecies differ in cranial shape from a single population allocated to T. a. laurentius. In this study we employed mathematical models of evolutionary quantitative genetics to assess the role that random drift and selection may have played in the evolution of cranial shape differences in T. apereoides. The hypothesis of evolution due to drift was rejected and the selective forces necessary to account for shape differences were estimated. Minimum selective mortalities of the order of 10(-3) per generation were sufficient to explain the observed morphologic differentiation.

Population differentiation and speciation in the genus Characidium (Characiformes: Crenuchidae): effects of reproductive and chromosomal barriers

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Male Gonadal Differentiation and the Paedomorphic Evolution of the Testis in Teleostei

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Differentiation and species status of the Neotropical yellow-eared bats Vampyressa pusilla and V. thyone (Phyllostomidae) with a molecular phylogeny and review of the genus

A systematic re-evaluation of Vampyressa pusilla warrants the elevation of V. p. thyone from subspecies to species rank based on its distinction from the allopatric V. p. pusilla. Morphological, mensural, chromosomal, and mitochondrial differences define each of these two taxa as divergent lineages. Vampyressa pusilla is endemic to the Atlantic Forest of southeastern South America and V. thyone is found allopatrically in northwestern South America, Central America, and southern Mexico. A molecular phylogenetic analysis of the mtDNA ND3-4 gene region using restriction endonuclease cut sites resulted in a monophyletic, although weakly supported Vampyressa ingroup with Chiroderma, and a clade of Mesophylla and Ectophylla as successive basal outgroup lineages. The phylogeny within Vampyressa, with the exception of V. melissa which is most similar to V. thyone based on karyotypes and morphology, had a topology of ((pusilla + thyone) + ((brocki + nymphaea) + bidens))).

Contemporary and historic factors influence differently genetic differentiation and diversity in a tropical palm

Population genetics theory predicts loss in genetic variability because of drift and inbreeding in isolated plant populations; however, it has been argued that long-distance pollination and seed dispersal may be able to maintain gene flow, even in highly fragmented landscapes. We tested how historical effective population size, historical migration and contemporary landscape structure, such as forest cover, patch isolation and matrix resistance, affect genetic variability and differentiation of seedlings in a tropical palm (Euterpe edulis) in a human-modified rainforest. We sampled 16 sites within five landscapes in the Brazilian Atlantic forest and assessed genetic variability and differentiation using eight microsatellite loci. Using a model selection approach, none of the covariates explained the variation observed in inbreeding coefficients among populations. The variation in genetic diversity among sites was best explained by historical effective population size. Allelic richness was best explained by historical effective population size and matrix resistance, whereas genetic differentiation was explained by matrix resistance. Coalescence analysis revealed high historical migration between sites within landscapes and constant historical population sizes, showing that the genetic differentiation is most likely due to recent changes caused by habitat loss and fragmentation. Overall, recent landscape changes have a greater influence on among-population genetic variation than historical gene flow process. As immediate restoration actions in landscapes with low forest amount, the development of more permeable matrices to allow the movement of pollinators and seed dispersers may be an effective strategy to maintain microevolutionary processes.

MIF induces osteoclast differentiation and contributes to progression of periodontal disease in mice

Periodontal disease (PD) is a chronic inflammatory and alveolar bone destructive disease triggered by microorganisms from the oral biofilm. Oral inoculation of mice with the periodontopathogen Aggregatibacter actinomycetemcomitans (Aa) induces marked alveolar bone loss and local production of inflammatory mediators, including Macrophage Migration Inhibitory Factor (MW). The role of MW for alveolar bone resorption during PD is not known. In the present study, experimental PD was induced in BALB/c wild-type mice (WT) and MW knockout mice (MIF-/-) through oral inoculation of Aa. Despite enhanced number of bacteria, MIF-/- mice had reduced infiltration of TRAP-positive cells and reduced alveolar bone loss. This was associated with decreased neutrophil accumulation and increased levels of IL-10 in periodontal tissues. TNF-alpha production was similar in both groups. In vitro, LPS from Aa enhanced osteoclastic activity in a MIF-dependent manner. In conclusion, MIF has role in controlling bacterial growth in the context of PD but contributes more significantly to the progression of bone loss during PD by directly affecting differentiation and activity of osteoclasts. (C) 2011 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Serum amyloid A is a growth factor for 3T3-L1 adipocytes, inhibits differentiation and promotes insulin resistance

BACKGROUND/OBJECTIVES: Serum amyloid A (SAA) is an acute-phase protein that has been recently correlated with obesity and insulin resistance. Therefore, we first examined whether human recombinant SAA (rSAA) could affect the proliferation, differentiation and metabolism of 3T3-L1 preadipocytes. DESIGN: Preadipocytes were treated with rSAA and analyzed for changes in viability and [H-3-methyl]-thymidine incorporation as well as cell cycle perturbations using flow cytometry analysis. The mRNA expression profiles of adipogenic factors during the differentiation protocol were also analyzed using real-time PCR. After differentiation, 2-deoxy-[1,2-H-3]-glucose uptake and glycerol release were evaluated. RESULTS: rSAA treatment caused a 2.6-fold increase in cell proliferation, which was consistent with the results from flow cytometry showing that rSAA treatment augmented the percentage of cells in the S phase (60.9 +/- 0.54%) compared with the control cells (39.8 +/- 2.2%, ***P<0.001). The rSAA-induced cell proliferation was mediated by the ERK1/2 signaling pathway, which was assessed by pretreatment with the inhibitor PD98059. However, the exposure of 3T3-L1 cells to rSAA during the differentiation process resulted in attenuated adipogenesis and decreased expression of adipogenesis-related factors. During the first 72 h of differentiation, rSAA inhibited the differentiation process by altering the mRNA expression kinetics of adipogenic transcription factors and proteins, such as PPAR gamma 2 (peroxisome proliferator-activated receptor gamma 2), C/EBP beta (CCAAT/enhancer-binding protein beta) and GLUT4. rSAA prevented the intracellular accumulation of lipids and, in fully differentiated cells, increased lipolysis and prevented 2-deoxy-[1,2-H-3]-glucose uptake, which favors insulin resistance. Additionally, rSAA stimulated the secretion of proinflammatory cytokines interleukin 6 and tumor necrosis factor alpha, and upregulated SAA3 mRNA expression during adipogenesis. CONCLUSIONS: We showed that rSAA enhanced proliferation and inhibited differentiation in 3T3-L1 preadipocytes and altered insulin sensitivity in differentiated cells. These results highlight the complex role of SAA in the adipogenic process and support a direct link between obesity and its co-morbidities such as type II diabetes.