LOCATION DETERMINANTS OF FDI: A LITERATURE REVIEW

The development of economic activity and the rise in foreign direct investment (FDI) in recent decades has prompted a great deal of research into the phenomenon of multinational companies. A vast amount of empirical literature on FDI catalogues a long list of determinants that try to explain direct investment by multinational companies in a particular location, but it is noticeable that the results are not always consensual. This article provides a review of the theoretical approaches to and empirical studies on FDI in an attempt to single out the most robust factors for explaining the geographic distribution of FDI flows worldwide. It also suggests paths for future research in this area.FDI, determinants of FDI, literature review

Impaired glucose transporter-1 degradation and increased glucose transport and oxidative stress in response to high glucose in chondrocytes from osteoarthritic versus normal human cartilage

Introduction Disorders that affect glucose metabolism, namely diabetes mellitus (DM), may favor the development and/or progression of osteoarthritis (OA). Thus far, little is known regarding the ability of chondrocytes to adjust to variations in the extracellular glucose concentration, resulting from hypoglycemia and hyperglycemia episodes, and so, to avoid deleterious effects resulting from deprivation or intracellular accumulation of glucose. The aim of this study was to compare the ability of normal and OA chondrocytes to regulate their glucose transport capacity in conditions of insufficient or excessive extracellular glucose and to identify the mechanisms involved and eventual deleterious consequences, namely the production of reactive oxygen species (ROS).1Center for Neurosciences and Cell Biology, and Faculty of Pharmacy, University of Coimbra, 3004-517 Coimbra, Portugal 2Orthopaedics Department, University Hospital of Coimbra, Avenida Bissaya Barreto, Bloco de Celas, 3000-075 Coimbra, Portugal 3Division of Veterinary Medicine, School of Veterinary Science and Medicine, Sutton Bonington Campus, University of Nottingham, Sutton Bonington LE12 5RD, U

Expression and function of K(ATP) channels in normal and osteoarthritic human chondrocytes: possible role in glucose sensing

ATP-sensitive potassium [K(ATP)] channels sense intracellular ATP/ADP levels, being essential components of a glucose-sensing apparatus in various cells that couples glucose metabolism, intracellular ATP/ADP levels and membrane potential. These channels are present in human chondrocytes, but their subunit composition and functions are unknown. This study aimed at elucidating the subunit composition of K(ATP) channels expressed in human chondrocytes and determining whether they play a role in regulating the abundance of major glucose transporters, GLUT-1 and GLUT-3, and glucose transport capacity. The results obtained show that human chondrocytes express the pore forming subunits, Kir6.1 and Kir6.2, at the mRNA and protein levels and the regulatory sulfonylurea receptor (SUR) subunits, SUR2A and SUR2B, but not SUR1. The expression of these subunits was no affected by culture under hyperglycemia-like conditions. Functional impairment of the channel activity, using a SUR blocker (glibenclamide 10 or 20 nM), reduced the protein levels of GLUT-1 and GLUT-3 by approximately 30% in normal chondrocytes, while in cells from cartilage with increasing osteoarthritic (OA) grade no changes were observed. Glucose transport capacity, however, was not affected in normal or OA chondrocytes. These results show that K(ATP) channel activity regulates the abundance of GLUT-1 and GLUT-3, although other mechanisms are involved in regulating the overall glucose transport capacity of human chondrocytes. Therefore, K(ATP) channels are potential components of a broad glucose sensing apparatus that modulates glucose transporters and allows human chondrocytes to adjust to varying extracellular glucose concentrations. This function of K(ATP) channels seems to be impaired in OA chondrocytes

New fluorescent heterocyclic materials: Synthesis, solvatochromic and fluorescence properties

Thienyl- and bithienyl-1,3-benzothiazoles 1 and 2 were synthesised by reacting various formyl thienyl and bithienyl derivatives with o-aminobenzenethiol in moderate to excellent yields. Evaluation of the solvatochromic and fluorescence properties of these compounds was carried out. Due to their strong fluorescence and also the strong push-pull character, benzothiazole derivatives 1 and 2 can be used as potential NLO materials or as fluorescent markers.Fundação para a Ciência e Tecnologia (FCT

Elevated glucose changes the expression of ionotropic glutamate receptor subunits and impairs calcium homeostasis in retinal neural cells

PURPOSE. Altered glutamatergic neurotransmission and calcium homeostasis may contribute to retinal neural cell dysfunction and apoptosis in diabetic retinopathy (DR). The purpose of this study was to determine the effect of high glucose on the protein content of -amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and kainate glutamate receptor subunits, particularly the GluR2 subunit, because it controls Ca2 permeability of AMPA receptor-associated channels. The effect of high glucose on the concentration of cytosolic free calcium ([Ca2 ]i) was also investigated. METHODS. The protein content of GluR1, GluR2, GluR6/7, and KA2 subunits was assessed by Western blot. Cobalt staining was used to identify cells containing calcium/cobalt-permeable AMPA receptors. The [Ca2 ]i changes evoked by KCl or kainate were recorded by live-cell confocal microscopy in R28 cells and in primary cultures of rat retina, loaded with fluo-4. RESULTS. In primary cultures, high glucose significantly decreased the protein content of GluR1 and GluR6/7 subunits and increased the protein content of GluR2 and KA2 subunits. High glucose decreased the number of cobalt-positive cells, suggesting a decrease in calcium permeability through AMPA receptor-associated channels. In high-glucose–treated cells, changes in [Ca2 ]i were greater than in control cells, and the recovery to basal levels was delayed. However, in the absence of Na , to prevent the activation of voltage-sensitive calcium channels, the [Ca2 ]i changes evoked by kainate in the presence of cyclothiazide, which inhibits AMPA receptor desensitization, were significantly lower in high-glucose–treated cells than in control cultures, further indicating that AMPA receptors were less permeable to calcium. Mannitol, used as an osmotic control, did not cause significant changes compared with the control. CONCLUSIONS. The results suggest that elevated glucose may alter glutamate neurotransmission and calcium homeostasis in the retina, which may have implications for the mechanisms of vision loss in DR.Foundation for Science and Technology, Portugal and FEDER (Grant POCTI/CBO/38545/01), The Juvenile Diabetes Research Foundation, The American Diabetes Association and the Pennsylvania Lions Sight Conservation and Eye Eye Research Foundation

Compartmentalized PDE4A5 signaling impairs hippocampal synaptic plasticity and long-term memory

Alterations in cAMP signaling are thought to contribute to neurocognitive and neuropsychiatric disorders. Members of the cAMP-specific phosphodiesterase 4 (PDE4) family, which contains >25 different isoforms, play a key role in determining spatial cAMP degradation so as to orchestrate compartmentalized cAMP signaling in cells. Each isoform binds to a different set of protein complexes through its unique N-terminal domain, thereby leading to targeted degradation of cAMP in specific intracellular compartments. However, the functional role of specific compartmentalized PDE4 isoforms has not been examined in vivo. Here, we show that increasing protein levels of the PDE4A5 isoform in mouse hippocampal excitatory neurons impairs a long-lasting form of hippocampal synaptic plasticity and attenuates hippocampus-dependent long-term memories without affecting anxiety. In contrast, viral expression of a truncated version of PDE4A5, which lacks the unique N-terminal targeting domain, does not affect long-term memory. Further, overexpression of the PDE4A1 isoform, which targets a different subset of signalosomes, leaves memory undisturbed. Fluorescence resonance energy transfer sensor-based cAMP measurements reveal that the full-length PDE4A5, in contrast to the truncated form, hampers forskolin-mediated increases in neuronal cAMP levels. Our study indicates that the unique N-terminal localization domain of PDE4A5 is essential for the targeting of specific cAMP-dependent signaling underlying synaptic plasticity and memory. The development of compounds to disrupt the compartmentalization of individual PDE4 isoforms by targeting their unique N-terminal domains may provide a fruitful approach to prevent cognitive deficits in neuropsychiatric and neurocognitive disorders that are associated with alterations in cAMP signaling

The nuclear receptor LXRα controls the functional specialization of splenic macrophages.

Macrophages are professional phagocytic cells that orchestrate innate immune responses and have considerable phenotypic diversity at different anatomical locations. However, the mechanisms that control the heterogeneity of tissue macrophages are not well characterized. Here we found that the nuclear receptor LXRα was essential for the differentiation of macrophages in the marginal zone (MZ) of the spleen. LXR-deficient mice were defective in the generation of MZ and metallophilic macrophages, which resulted in abnormal responses to blood-borne antigens. Myeloid-specific expression of LXRα or adoptive transfer of wild-type monocytes restored the MZ microenvironment in LXRα-deficient mice. Our results demonstrate that signaling via LXRα in myeloid cells is crucial for the generation of splenic MZ macrophages and identify an unprecedented role for a nuclear receptor in the generation of specialized macrophage subsets

Characterization of Laptop Fires in Spacecraft

An accidental fire involving the Lithium-Ion (Li-ion) battery in a laptop computer is one of the most likely fire scenarios on-board a spacecraft. These fires can occur from a defect in the battery that worsens with time, over-charging the battery and leading to failure or accidental damage caused by thermal runaway. While this is a relatively likely fire scenario, very little is known about the how a laptop computer fire would impact a sealed spacecraft. The heat release would likely cause a pressure rise, possibly exceeding the pressure limit of the vehicle and causing a relief valve to open. The combustion products from the fire could pose a short-term and long-term health hazard to the crew and the fire itself could cause injury to the crew and damage to the spacecraft. Despite the hazard posed by a laptop fire, there is little quantitative data on the fire size, heat release and toxic product formation. This paper presents the results of initial attempts to quantify the fire resulting from a failed laptop fire tested at the NASA White Sands Test Facility (WSTF). The data from the testing is useful to attempt to determine the fire size and characteristics such as maximum heat release rate, total heat release, maximum temperatures and fire duration are determined. Using existing models and correlations for fires, the measured fire characteristics are extrapolated to laptop fires on a vehicle the approximate size of the Orion spacecraft

Physical exercise neuroprotects ovariectomized 3xTg-AD mice through BDNF mechanisms

Postmenopausal women may be more vulnerable to cognitive loss and Alzheimer's disease (AD) than premenopausal women because of their deficiency in estrogens, in addition to their usually older age. Aerobic physical exercise has been proposed as a therapeutic approach for maintaining health and well-being in postmenopausal women, and for improving brain health and plasticity in populations at high risk for AD. To study the neuroprotective mechanisms of physical exercise in a postmenopausal animal model, we submitted previously ovariectomized, six-month old non-transgenic and 3xTg-AD mice to three months of voluntary exercise in a running wheel. At nine months of age, we observed lower grip strength and some exacerbation of the behavioral and psychological symptoms of dementia (BPSD)-like involving active exploratory activities. A similar major cognitive impairment was observed of ovariectomized 3xTg-AD mice in comparison with sham-operated 3xTg-AD mice. A reduction of bodily fitness and lack of retention of memory were observed in the ovariectomized non-transgenic mice. Physical exercise protected against all deleterious behaviors and normalized learning and memory. It also protected against body frailty, as expected. Analyses of hippocampal key markers of antioxidant and neuroplasticity signaling pathways, showed that ovariectomy impairs the activation of CREB through physical exercise. Furthermore, molecular and behavioral correlates suggested a central role of BDNF in the neuroprotection mediated by physical exercise therapy against apathy and memory loss induced by ovariectomy and the AD-genotype. © 2014 Elsevier Ltd.This study was supported by grants: SAF2009-13093-C02-02, SAF2010-19498, SAF2012-39852-C02-02 and CSD2010-00045 from the Spanish MINECO; 2009/SGR/214 from the Generalitat and 062931 from the Fundació La Marató de TV3, of Catalonia; and 35NEURO GentxGent. Yoelvis García-Mesa acknowledges support received from the Fundació La Marató de TV3Peer Reviewe

Evaluation of the antigen-antibody complex vaccine of Gumboro disease administered in ovo in broiler chickens challenged with F52/70 strain

El objetivo del presente estudio fue evaluar la protección y seguridad del complejo vacunal antígeno-anticuerpo administrado in ovo frente a un desafío experimental con la cepa F52/70 de la Enfermedad de Gumboro en pollos de carne. Se utilizaron 450 pollos de la línea Cobb Vantress, de un día de edad, distribuidos en tres grupos: Grupo A, vacunado, vía agua de bebida, a los 9 días con la cepa intermedia suave tipo Lukert y revacunado a los 19 días con la cepa intermedia intermedia 2512; grupo B, vacunado vía in ovo a los 18 días de incubación con el complejo vacunal antígeno-anticuerpo; y grupo C, control no vacunado. A los 35 días de edad, 20 aves de cada grupo fueron desafiadas, vía ocular, con la cepa F52/70 de la enfermedad de Gumboro. La seguridad del complejo vacunal se evaluó semanalmente hasta los 47 días de edad mediante la determinación del índice bursal, lesiones macroscópicas, lesiones histopatológicas de bursa y respuesta serológica. Las lesiones post desafío se caracterizaron por edema y hemorragias petequiales en la bursa. El grupo B presentó la mejor protección con 75% comparado con el grupo A (68%) y el grupo control (30%). Las lesiones post desafío se caracterizaron por edema y hemorragias petequiales en la bursa. En las aves no desafiadas no se observó diferencias significativas entre los grupos A y B para el índice bursal y lesiones histopatológicas hasta los 28 días de edad; sin embargo, a partir de los 35 días el grupo A fue significativamente diferente de los grupos B y C (p<0.05). Al final del estudio el grupo A obtuvo títulos de 1948 y 2047 más de anticuerpos que el grupo B y el control, respectivamente.The objective of the study was to evaluate the protection and safety for in ovo vaccination against Infection Bursal Disease. Cobb Vantress broilers of one day of age (n=450) were distributed in three groups: Group A, vaccinated at 9 and 19 days with two commercial live vaccines containing Lukert and 2512 strains, respectively; group B, vaccinated in ovo with the antigen-antibody complex at 18 days of incubation; and group C, unvaccinated. At 35 days of age, 20 birds from each group were challenged, ocular via, with the F52/70 strain of Gumboro disease. The security of the complex vaccine was evaluated weekly until 47 days of age by determining the bursal index, gross lesions, histopathological lesions of the bursa, and serological response. Group B showed the best protection with 75% as compared with groups A (68%) and C (30%). Injuries after challenge were characterized by swelling, bleeding, and petechiae in the bursa. In non-challenged birds were none significant differences between groups A and B for the index and bursal histopathology lesions until 28 days of age; however, group A differed from groups B and C at 35 days of age (p<0.05). At the end of the study, group A had 1948 and 2047 antibodies titers higher than groups B and control respectively