Across the river : urban borderland development in the Republic of Haiti + the Dominican Republic : the case of Dajabo'n + Ouanaminthe

Border cities have to cope with divergent interests more than other cities, because in the same place protection of national sovereignty clashes with local practices and international cross-border movements. The question of how economic, political, and societal transformations linked to the globalisation process shape the urban space of border towns should thus be answered through a multifaceted analysis. This article introduces the analytical framework of border intermediation, dealing with the internal characteristics of the city, its function in national and transnational networks, its relation to the direct rural environment and the ways in which the border conditions these dimensions. The two towns studied, Ouanaminthe and Dajabón, are located on the Haitian- Dominican border, which is strongly marked by its complex history since the times of French and Spanish colonization. This case study is based on qualitative methods — such as mapping use of urban space and interviewing local stakeholders and residents. Cartography and other primary and secondary sources complement these observations. Following the economic opening of the border, the remarkable demographic and spatial growth of both towns has dramatically changed ground property values. Urban development remained principally in the hands of landowners. Cross-border exchanges and the establishment of a “maquiladora” industry have had a different impact on the relations between both towns. At the local level, recognition of common problems has built some basic cross-border solidarity, supported by civil society and local governments. But this apprehension is not shared by the central governments and transnational economic actors, and it is undermined by strong prejudices of people on both sides. Both towns develop, following their own inherent characteristics, and despite the fact that they play common roles in cross-border networks, no bi-national urban space exists. The links between both towns are mainly functional and not strong enough for creating the sentiment of belonging together

Villes à la frontière et transformation de l'espace:le cas de Haïti et la République Dominicaine

Few borders exist which separate two countries as dramatically disparate as the Dominican Republic and Haiti. Both share the territory of the Hispaniola island, but a profound process of differentiation rooted in the colonial division of the island between France and Spain and ideologically maintained by both modern nations, has lead to what Théodat (1998, 2003) calls the "twofold insularity" – each country behaves as if it were located on a separate island. In spite of all prejudices and ethnical, historical, linguistic, social, economic or religious differences, people living in the border regions established cross-border relations which, even if largely based on economic interests, are much more frequent and important to both nations than officially admitted (De Jesus Cerdano and Dilla, 2005; Sillé & Segura & Cabral, 2002). The local dynamic created by this exchange becomes palpable when one observes the busy binational market in the border towns of Ouanaminthe (Haiti) and Dajabón (Dominican Republic). Twice a week, people from nearly the whole northern part of both countries travel to these towns located on either side of the Masacre River, in order to buy and sell goods or to offer services in the market of Dajabón. The other days, tons of cargo transit to Haiti, to the extent that the once small borderland settlements have become an important junction in the economic subsystem of the northern part of the island. Moreover, the construction of a free zone in Ouanaminthe in 2002 –to produce textiles for the US-market– has connected the borderland towns to the international economy. This recent development is set within a context of progressive opening of borders (Martinez, 1994). It is the result of international policies that have been decided in the capitals, without consulting the concerned regions. In Ouanaminthe and Dajabón, local institutions are weak and receive no or little financial and administrative support from central administration. They do not have the means to cope with growing pressure on land and infrastructure, as the emergence of legal and illegal livelihood opportunities in the borderland has generated a threefold increase of the overall population in the past twenty years (Dajabón grew from 8'500 inhabitants in 1980 to 16'000 in 2002 and Ouanaminthe from 7'000 in 1981 to 39'000 in 2003). How did these recent economic, political and societal transformations shape the urban space of the two borderland towns? I addressed this issue by analyzing the motivation of stakeholders involved in the process of spatial transformation, and the impact of their actions. In my work I refer to the conceptual framework of urban intermediation (Bolay and Rabinovich, 2004), i.e. the spatial issues that each town has to address according to its internal characteristics, its function in national and international networks and its relation to the direct rural environment. In order to use this framework for the borderland issues, the conceptual part of this study proposes to develop the concept of "borderland intermediation". To the existing urban intermediation concept, it adds the influence of the characteristics of the border (based on policy and political aspects, economic issues, local identities, social networks, national defense issues and geographical insertion). By doing so, it relates the bi-national system of borderland towns to the intermediation concept. Data has been collected over three and a half years during several periods of fieldwork: observation and mapping of occupation and use of urban space, cartography, qualitative interviews with local stakeholders and residents, completed by other primary and secondary sources. This study shows that the recent transformations have accentuated the existing unbalanced relationship between the two towns. The powerlessness of the municipality of Ouanaminthe to meet population growth and to impose regulations or taxes related to the growing trade has enhanced its dependency to the Dominican town. For a growing number of Haitians, it is of existential importance to cross over to Dajabón in order to seek income, healthcare and education and this, in spite of latent racism and mistreatments. Founded on a strong sentiment of exploitation, Haitians often criticize the capitalist or even colonialist relationship imposed by their neighbors: not only the fact that the bi-national market takes place in Dajabón, but also that Dominican enterprises develop subsidiaries in Ouanaminthe, taking advantage of cheap labor and the absence of local production. On the contrary, the majority of Dajabón residents interviewed do not need to cross the river for their living. Most of them have never been to Ouanaminthe, but consider it insalubrious, out of control and dangerous. Both towns lack application of regulations in urban planning matters. Thus, spatial growth has entirely been ruled by landowner structure and land occupation practices. Around Dajabón, the adjacent land belongs mainly to two landowners, whose strategy –to enhance soil value through development of equipped middleclass neighborhoods– has restricted the urban sprawl. In Ouanaminthe land belongs to a multitude of small peasants. The selling and illegal occupation of rather small plots leads to sprawling urban growth, guided by rural pathways and leaving entire parts of neighborhoods inaccessible to motor vehicles. Population growth has also been absorbed by high densification of existing neighborhoods. No formal collaborations exist between the two municipalities. Informal ones do, through the implication of the two mayors, but overall, cross-border collaboration is left to NGOs and professional associations who militate for human rights, environmental issues and fair treatment inside the bi-national market. International development agencies present in the borderland initiate projects with bi-national concern, but these are disconnected from the local level and strongly influenced by the fact that these agencies relate directly to the central governments. We also observe a process of internal segregation in both towns, as commercial establishments progressively occupy parts of the town centers and the emergent middle class gathers in specific neighborhoods. Ouanaminthe and Dajabón are functionally interlinked and their transformation is undeniably governed by the progressive permeability of the border. Nevertheless, this border separates two completely different urban landscapes that are deeply marked by the internal characteristics of each town. Furthermore, the unequal and complex relationship of both populations creates the paradox that their spatial proximity accentuates the segregation in both towns, as it allows the citizens of both countries to stay in their environment and to commute –if necessary– even daily. This work shows that the application of the intermediation concept is relevant for the study of complex relationships that govern borderland space. The analysis based on this concept has enabled to study, on a local level, processes that are taking place on a global level. In so doing, it has allowed us to provide some answers to the central question: "How do local populations, national and international firms and governments react when a territorial economy, based on agriculture, is progressively linked to international networks?

Extensive Regulation of Diurnal Transcription and Metabolism by Glucocorticoids.

Altered daily patterns of hormone action are suspected to contribute to metabolic disease. It is poorly understood how the adrenal glucocorticoid hormones contribute to the coordination of daily global patterns of transcription and metabolism. Here, we examined diurnal metabolite and transcriptome patterns in a zebrafish glucocorticoid deficiency model by RNA-Seq, NMR spectroscopy and liquid chromatography-based methods. We observed dysregulation of metabolic pathways including glutaminolysis, the citrate and urea cycles and glyoxylate detoxification. Constant, non-rhythmic glucocorticoid treatment rescued many of these changes, with some notable exceptions among the amino acid related pathways. Surprisingly, the non-rhythmic glucocorticoid treatment rescued almost half of the entire dysregulated diurnal transcriptome patterns. A combination of E-box and glucocorticoid response elements is enriched in the rescued genes. This simple enhancer element combination is sufficient to drive rhythmic circadian reporter gene expression under non-rhythmic glucocorticoid exposure, revealing a permissive function for the hormones in glucocorticoid-dependent circadian transcription. Our work highlights metabolic pathways potentially contributing to morbidity in patients with glucocorticoid deficiency, even under glucocorticoid replacement therapy. Moreover, we provide mechanistic insight into the interaction between the circadian clock and glucocorticoids in the transcriptional regulation of metabolism

Involvement of NDPK-B in Glucose Metabolism-Mediated Endothelial Damage via Activation of the Hexosamine Biosynthesis Pathway and Suppression of O-GlcNAcase Activity

Our previous studies identified that retinal endothelial damage caused by hyperglycemia or nucleoside diphosphate kinase-B (NDPK-B) deficiency is linked to elevation of angiopoietin-2 (Ang-2) and the activation of the hexosamine biosynthesis pathway (HBP). Herein, we investigated how NDPK-B is involved in the HBP in endothelial cells (ECs). The activities of NDPK-B and O-GlcNAcase (OGA) were measured by in vitro assays. Nucleotide metabolism and O-GlcNAcylated proteins were assessed by UPLC-PDA (Ultra-performance liquid chromatography with Photodiode array detection) and immunoblot, respectively. Re-expression of NDPK-B was achieved with recombinant adenoviruses. Our results show that NDPK-B depletion in ECs elevated UDP-GlcNAc levels and reduced NDPK activity, similar to high glucose (HG) treatment. Moreover, the expression and phosphorylation of glutamine:fructose-6-phosphate amidotransferase (GFAT) were induced, whereas OGA activity was suppressed. Furthermore, overall protein O-GlcNAcylation, along with O-GlcNAcylated Ang-2, was increased in NDPK-B depleted ECs. Pharmacological elevation of protein O-GlcNAcylation using Thiamet G (TMG) or OGA siRNA increased Ang-2 levels. However, the nucleoside triphosphate to diphosphate (NTP/NDP) transphosphorylase and histidine kinase activity of NDPK-B were dispensable for protein O-GlcNAcylation. NDPK-B deficiency hence results in the activation of HBP and the suppression of OGA activity, leading to increased protein O-GlcNAcylation and further upregulation of Ang-2. The data indicate a critical role of NDPK-B in endothelial damage via the modulation of the HBP

Glucosamine protects against neuronal but not vascular damage in experimental diabetic retinopathy

Objective: Glucosamine, an intermetabolite of the hexosamine biosynthesis pathway (HBP), is a widely used nutritional supplement in osteoarthritis patients, a subset of whom also suffer from diabetes. HBP is activated in diabetic retinopathy (DR). The aim of this study is to investigate the yet unclear effects of glucosamine on DR. Methods: In this study, we tested the effect of glucosamine on vascular and neuronal pathology in a mouse model of streptozotocin-induced DR in vivo and on cultured endothelial and Müller cells to elucidate the underlying mechanisms of action in vitro. Results: Glucosamine did not alter the blood glucose or HbA1c levels in the animals, but induced body weight gain in the non-diabetic animals. Interestingly, the impaired neuronal function in diabetic animals could be prevented by glucosamine treatment. Correspondingly, the activation of Müller cells was prevented in the retina as well as in cell culture. Conversely, glucosamine administration in the normal retina damaged the retinal vasculature by increasing pericyte loss and acellular capillary formation, likely by interfering with endothelial survival signals as seen in vitro in cultured endothelial cells. Nevertheless, under diabetic conditions, no further increase in the detrimental effects were observed. Conclusions: In conclusion, the effects of glucosamine supplementation in the retina appear to be a double-edged sword: neuronal protection in the diabetic retina and vascular damage in the normal retina. Thus, glucosamine supplementation in osteoarthritis patients with or without diabetes should be taken with care

Acetobacter indonesiensis Pneumonia after Lung Transplant

International audienc

Hypoxia Routes Tryptophan Homeostasis Towards Increased Tryptamine Production

The liver is the central hub for processing and maintaining homeostatic levels of dietary nutrients especially essential amino acids such as tryptophan (Trp). Trp is required not only to sustain protein synthesis but also as a precursor for the production of NAD, neurotransmitters and immunosuppressive metabolites. In light of these roles of Trp and its metabolic products, maintaining homeostatic levels of Trp is essential for health and well-being. The liver regulates global Trp supply by the immunosuppressive enzyme tryptophan-2,3-dioxygenase (TDO2), which degrades Trp down the kynurenine pathway (KP). In the current study, we show that isolated primary hepatocytes when exposed to hypoxic environments, extensively rewire their Trp metabolism by reducing constitutive Tdo2 expression and differentially regulating other Trp pathway enzymes and transporters. Mathematical modelling of Trp metabolism in liver cells under hypoxia predicted decreased flux through the KP while metabolic flux through the tryptamine branch significantly increased. In line, the model also revealed an increased accumulation of tryptamines under hypoxia, at the expense of kynurenines. Metabolic measurements in hypoxic hepatocytes confirmed the predicted reduction in KP metabolites as well as accumulation of tryptamine. Tdo2 expression in cultured primary hepatocytes was reduced upon hypoxia inducible factor (HIF) stabilisation by dimethyloxalylglycine (DMOG), demonstrating that HIFs are involved in the hypoxic downregulation of hepatic Tdo2. DMOG abrogated hepatic luciferase signals in Tdo2 reporter mice, indicating that HIF stability also recapitulates hypoxic rewiring of Trp metabolism in vivo. Also in WT mice HIF stabilization drove homeostatic Trp metabolism away from the KP towards enhanced tryptamine production, leading to enhanced levels of tryptamine in liver, serum and brain. As tryptamines are the most potent hallucinogens known, the observed upregulation of tryptamine in response to hypoxic exposure of hepatocytes may be involved in the generation of hallucinations occurring at high altitude. KP metabolites are known to activate the aryl hydrocarbon receptor (AHR). The AHR-activating properties of tryptamines may explain why immunosuppressive AHR activity is maintained under hypoxia despite downregulation of the KP. In summary our results identify hypoxia as an important factor controlling Trp metabolism in the liver with possible implications for immunosuppressive AHR activation and mental disturbances