Análisis económico de la relocalización de empresas

En las últimas décadas se ha incrementado de forma notoria las inversiones que las empresas realizan en países extranjeros, que en muchos casos han venido acompañadas de deslocalizaciones de empresas. En este trabajo se analiza, desde un punto de vista económico, el porqué de las deslocalizaciones de empresas en los países desarrollados, así como su efecto sobre el mercado donde producen. Utilizamos para ello el ejemplo de la empresa Reckitt, que trasladó una fábrica de Güeñes a Polonia en 2007. Haciendo una simplificación de la realidad, suponemos un modelo con un producto homogéneo en el mercado único europeo, cuya producción se reparten entre Reckitt y otras tres fábricas. Las empresas tienen costes de transporte, de producción y de capacidad productiva, que difieren en función de donde están situadas. Comparando los resultados de dos casos diferenciados, se demuestra que tanto los beneficios de Reckitt como su cuota de mercado aumentan en caso de deslocalizarse. Para el resto de empresas con las que compite, en cambio, el efecto sobre sus cuotas de mercados y sus beneficios es el contrario. Finalmente, realizando un análisis del bienestar, se demuestra que la UE se beneficia de la deslocalización de Reckitt.

Análisis económico de la relocalización de empresas

En las últimas décadas se ha incrementado de forma notoria las inversiones que las empresas realizan en países extranjeros, que en muchos casos han venido acompañadas de deslocalizaciones de empresas. En este trabajo se analiza, desde un punto de vista económico, el porqué de las deslocalizaciones de empresas en los países desarrollados, así como su efecto sobre el mercado donde producen. Utilizamos para ello el ejemplo de la empresa Reckitt, que trasladó una fábrica de Güeñes a Polonia en 2007. Haciendo una simplificación de la realidad, suponemos un modelo con un producto homogéneo en el mercado único europeo, cuya producción se reparten entre Reckitt y otras tres fábricas. Las empresas tienen costes de transporte, de producción y de capacidad productiva, que difieren en función de donde están situadas. Comparando los resultados de dos casos diferenciados, se demuestra que tanto los beneficios de Reckitt como su cuota de mercado aumentan en caso de deslocalizarse. Para el resto de empresas con las que compite, en cambio, el efecto sobre sus cuotas de mercados y sus beneficios es el contrario. Finalmente, realizando un análisis del bienestar, se demuestra que la UE se beneficia de la deslocalización de Reckitt.

A contribution to the algal flora of the Kola Peninsula [Translation from: Trudy Institut Botaniki Trudy Institut Botaniki Kharkivskii. Univ Vol. 4, pp. 53-76, 1941]

During recent years in connection with the industrialisation of the Kola Peninsula, the study of this district in the botanical respect, in particular the study of the microflora of various bodies of water, began to advance markedly. This article describes the algal flora of the Kola Peninsula. Morphological descriptions are given for three Tetraspora: Tetraspora simplex, Tetraspora tenera, Tetraspora imperfecta. Chlorophysema aduata is also described, and short descriptions of further algae found in the Kola Peninsula are given.

Avaliação do metabolismo ósseo em modelos de plasticidade ontogenética

O aumento da prevalência da obesidade e osteoporose, bem como a identificação de mecanismos comuns que ligam a osteogênese e a adipogênese, sugerem que a obesidade e osteoporose podem ser distúrbios relacionados, e além disso, ambos podem ter suas origens no início da vida. Em 3 modelos diferentes de plasticidade ontogenética foi observado obesidade na vida adulta. Sendo assim, o objetivo deste trabalho foi investigar o impacto desses 3 modelos, o desmame precoce mecânico (DPM) e o farmacológico (DPF), e a supernutrição neonatal (SN) no tecido ósseo da prole durante o desenvolvimento. Para tanto, 2 experimentos foram realizados. No experimento 1, ratas lactantes foram divididas em 3 grupos: controle - os filhotes tiveram livre acesso ao leite durante toda a lactação; DPM - as mães foram envolvidas com uma atadura nos últimos 3 dias de lactação; DPF - as mães foram tratadas com bromocriptina (0,5 mg/duas vezes/dia) 3 dias antes do desmame padrão. No experimento 2, o tamanho da ninhada foi reduzido para 3 filhotes machos no 3o dia de lactação até o desmame (SN); o grupo controle permaneceu com 10 filhotes durante toda a lactação. Realizou-se absorciometria de raios-x de dupla energia, tomografia computadorizada, microtomografia computadorizada, teste biomecânico e análises séricas. Os dados foram considerados significativos quando P<0,05. No experimento 1, ao desmame, os filhotes DPM e DPF apresentaram menor massa corporal, massa gorda, densidade mineral óssea total (DMO), conteúdo mineral ósseo total (CMO), área óssea e osteocalcina sérica, e maior telopeptídeo carboxi-terminal do colágeno tipo I (CTX-I). O cálcio ionizado sérico foi menor apenas na prole DPM, a 25-hidroxivitamina D (25(OH)D) foi maior e o PTH menor apenas na prole DPF. Aos 180 dias, as proles DPM e DPF apresentaram maior massa corporal, maior massa de gordura visceral, hiperleptinemia, maior 25(OH)D e menor CTX-I. Ambos os grupos apresentaram aumento da DMO total, do CMO, da DMO da coluna vertebral e da área óssea aos 150 e 180 dias de idade. Nas avaliações ósseas individuais, as proles DPM e DPF também apresentaram aumento da DMO do fêmur e da vértebra lombar, da radiodensidade da cabeça femoral e do corpo vertebral; melhora da microarquitetura trabecular óssea e da resistência óssea. No experimento 2, observamos aumento da massa corporal, da massa gorda e da massa magra, do CMO e da área óssea no grupo SN desde o desmame até a idade adulta. Aos 180 dias, a prole SN também apresentou aumento da DMO total, da DMO do fêmur e da vértebra lombar, da radiodensidade da cabeça femoral e do corpo vertebral; melhora da microarquitetura trabecular óssea e da resistência óssea, maior osteocalcina e menor CTX-I. Demonstramos que, apesar de fatores de imprinting opostos, ambos os modelos causam melhora da massa, do metabolismo, da qualidade e da resistência óssea. Porém, parece que este efeito protetor sobre o tecido ósseo não é um resultado direto da programação deste tecido, mas sim consequência das alterações fisiopatológicas da obesidade programada pelos três modelos.

Evidence for Positive Selection on the Osteogenin (BMP3) Gene in Human Populations

Background: Human skeletal system has evolved rapidly since the dispersal of modern humans from Africa, potentially driven by selection and adaptation. Osteogenin (BMP3) plays an important role in skeletal development and bone osteogenesis as an antagonist of the osteogenic bone morphogenetic proteins, and negatively regulates bone mineral density. Methodology/Principal Findings: Here, we resequenced the BMP3 gene from individuals in four geographically separated modern human populations. Features supportive of positive selection in the BMP3 gene were found including the presence of an excess of nonsynonymous mutations in modern humans, and a significantly lower genetic diversity that deviates from neutrality. The prevalent haplotypes of the first exon region in Europeans demonstrated features of long-range haplotype homogeneity. In contrast with findings in European, the derived allele SNP Arg192Gln shows higher extended haplotype homozygosity in East Asian. The worldwide allele frequency distribution of SNP shows not only a high-derived allele frequency in Asians, but also in Americans, which is suggestive of functional adaptation. Conclusions/Significance: In conclusion, we provide evidence for recent positive selection operating upon a crucial gene in skeletal development, which may provide new insight into the evolution of the skeletal system and bone development.

The nanocomposite scaffold of poly(lactide-co-glycolide) and hydroxyapatite surface-grafted with L-lactic acid oligomer for bone repair

Nanohydroxyapatite (op-HA) surface-modified with L-lactic acid oligomer (LAc oligomer) was prepared by LAc oligomer grafted onto the hydroxyapatite (HA) surface. The nanocomposite of op-HA/PLGA with different op-HA contents of 5, 10, 20 and 40 wt.% in the composite was fabricated into three-dimensional scaffolds by the melt-molding and particulate leaching methods. PLGA and the nanocomposite of HA/PLGA with 10 wt.% of ungrafted hydroxyapatite were used as the controls. The scaffolds were highly porous with evenly distributed and interconnected pore structures, and the porosity was around 90%. Besides the macropores of 100-300 mu m created by the leaching of NaCl particles, the micropores (1-50 mu m) in the pore walls increased with increasing content of op-HA in the composites of op-HA/PLGA. The op-HA particles could disperse more uniformly than those of pure HA in PLGA matrix. The 20 wt.% op-HA/PLGA sample exhibited the maximum mechanical strength, including bending strength (4.14 MPa) and compressive strength (2.31 MPa). The cell viability and the areas of the attached osteoblasts on the films of 10 wt.% op-HA/PLGA and 20 wt.% op-HA/PLGA were evidently higher than those on the other composites.

Efectos de cambios impositivos en un modelo de equilibrio general aplicado: un análisis de la reforma de 1995

En este trabajo se analizan los efectos de una disminución de los tipos de las cotizaciones sociales, compensada con un incremento en los tipos del impuesto sobre el valor añadido, como la que tuvo lugar en España en 1995. Para ello se utiliza un modelo de equilibrio general aplicado a la economía española, que se presenta en dos versiones: una donde los sectores productivos se modelizan en competencia perfecta, y otra donde los mismos sectores se modelizan como oligopolistas a la Cournot, lo cual nos permite analizar la influencia del supuesto de competencia imperfecta sobre los resultados. Se ha realizado asimismo una simulación adicional aplicando un supuesto de equal yield por el que el déficit público y el nivel de bienestar del sector público se mantienen constantes tras la aplicación de la nueva política, con objeto de aislar los efectos secundarios que se podrían derivar de un cambio en el comportamiento del sector público.

Genetic engineering of mesenchymal stem cells and its application in human disease therapy.

The use of stem cells for tissue regeneration and repair is advancing both at the bench and bedside. Stem cells isolated from bone marrow are currently being tested for their therapeutic potential in a variety of clinical conditions including cardiovascular injury, kidney failure, cancer, and neurological and bone disorders. Despite the advantages, stem cell therapy is still limited by low survival, engraftment, and homing to damage area as well as inefficiencies in differentiating into fully functional tissues. Genetic engineering of mesenchymal stem cells is being explored as a means to circumvent some of these problems. This review presents the current understanding of the use of genetically engineered mesenchymal stem cells in human disease therapy with emphasis on genetic modifications aimed to improve survival, homing, angiogenesis, and heart function after myocardial infarction. Advancements in other disease areas are also discussed.

Chondrogenesis and mineralization during in vitro culture of human mesenchymal stem cells on three-dimensional woven scaffolds.

Human mesenchymal stem cells (hMSCs) and three-dimensional (3D) woven poly(ɛ-caprolactone) (PCL) scaffolds are promising tools for skeletal tissue engineering. We hypothesized that in vitro culture duration and medium additives can individually and interactively influence the structure, composition, mechanical, and molecular properties of engineered tissues based on hMSCs and 3D poly(ɛ-caprolactone). Bone marrow hMSCs were suspended in collagen gel, seeded on scaffolds, and cultured for 1, 21, or 45 days under chondrogenic and/or osteogenic conditions. Structure, composition, biomechanics, and gene expression were analyzed. In chondrogenic medium, cartilaginous tissue formed by day 21, and hypertrophic mineralization was observed in the newly formed extracellular matrix at the interface with underlying scaffold by day 45. Glycosaminoglycan, hydroxyproline, and calcium contents, and alkaline phosphatase activity depended on culture duration and medium additives, with significant interactive effects (all p < 0.0001). The 45-day constructs exhibited mechanical properties on the order of magnitude of native articular cartilage (aggregate, Young's, and shear moduli of 0.15, 0.12, and 0.033 MPa, respectively). Gene expression was characteristic of chondrogenesis and endochondral bone formation, with sequential regulation of Sox-9, collagen type II, aggrecan, core binding factor alpha 1 (Cbfα1)/Runx2, bone sialoprotein, bone morphogenetic protein-2, and osteocalcin. In contrast, osteogenic medium produced limited osteogenesis. Long-term culture of hMSC on 3D scaffolds resulted in chondrogenesis and regional mineralization at the interface between soft, newly formed engineered cartilage, and stiffer underlying scaffold. These findings merit consideration when developing grafts for osteochondral defect repair.

The use of mineral trioxide aggregate in endodontics - status report

Mineral trioxide aggregate (MTA) is a clinical product comprising a mixture of Portland cement and bismuth oxide which is currently used as a root−filling material in dentistry. It has good biological compatibility, is capable of promoting both osteogenesis and cementogensis, and is finding increasing use in endodontic therapy. It is dimensionally stable, and provides an acceptable and durable seal for endodontically treated teeth. This article reviews the chemistry and applications of MTA, and highlights the fact that very little is currently known about the hydration chemistry, phase evolution and stability of this cement in physiological environments. However, biological effects of MTA have been well documented and are considered in detail. The article concludes that this material is a useful addition to the range of materials available for clinical application in endodontics.

Bioreactor Expansion of Human Adult Bone Marrow-Derived Mesenchymal Stem Cells

Supplementation of mesenchymal stem cells (MSCs) during hematopoietic stem cell transplantation (HSCT) alleviates complications such as graft-versus-host disease, leading to a speedy recovery of hematopoiesis. To meet such clinical demand, a fast MSCs expansion method is required. In the present study, we examined the feasibility of expanding MSCs from the isolated bone marrow mononuclear cells using a rotary bioreactor system. The cells were cultured in a rotary bioreactor with Myelocult� medium containing a combination of supplementary factors, including stem cell factor (SCF), interleukin 3 and 6 (IL-3, IL-6). After 8 days of culture, total cell numbers, Stro-1+CD44+CD34- MSCs and CD34+CD44+Stro-1- HSCs were increased 9, 29, and 8 folds respectively. Colony forming efficiency-fibroblast per day (CFE-F/day) of the bioreactor-treated cells was 1.44-fold higher than that of the cells without bioreactor treatment. The bioreactor-expanded MSCs showed expression of primitive MSCs markers endoglin (SH2) and vimentin, whereas markers associated with lineage differentiation including osteocalcin (osteogenesis), Type II collagen (chondrogenesis) and C/EBPα (adipogenesis) were not detected. Upon induction, the bioreactor-expanded MSCs were able to differentiate into osteoblasts, chondrocytes and adipocytes. Taken together, we conclude that the rotary bioreactor with the modified Myelocult� medium reported in this study may be used to rapidly expand MSCs.

Osteoclastogenesis induced by sRANKL and M-CSF from the non-adherent cell population of human bone marrow is inhibited by rhBMP-2 alone or together with rhVEGF

During bone development and repair, angiogenesis, osteogenesis and bone remodelling are closely associated processes that share some common mediators. In the present study non-adherent human bone marrow mononuclear cells under the induction of sRANKL and M-CSF, differentiated into osteoclasts with TRAP positive staining, VNR expression, and Ca-P resorptive activity. The effects of various combinations of rhBMP-2 (0, 3, 30, 300 ng/ml) and rhVEGF (0, 25 ng/ml) on osteoclastogenesis potentials were examined in this experimental system. The percentages of TRAP-positive multiple nucleated cells represent osteoclast differentiation potential and the percentages of resorptive areas in the Ca-P coated plates resemble osteoclast resorption capability. The presence of rhBMP-2 at 30 and 300 ng/ml showed inhibitory effects on osteoclast differentiation and their resorptive capability in the human osteoclast culture system. rhVEGF (25 ng/ml) enhanced the resorptive function of osteoclast whenever it was used alone or combined with 3 ng/ml rhBMP-2. However, rhVEGF induced resorptive function was inhibited by 30 ng/ml and 300 ng/ml rhBMP-2 at a dose-dependent manner. Statistical analysis demonstrated that an interactive effect exists between rhBMP-2 and rhVEGF on human osteoclastogenesis. These findings suggested that an interactive regulation may exist between BMPs and VEGF signaling pathways during osteoclastogenesis, exact mechanisms are yet to be elucidated.

The molecular signature of the stroma response in prostate cancer-induced osteoblastic bone metastasis highlights expansion of hematopoietic and prostate epithelial stem cell niches

The reciprocal interaction between cancer cells and the tissue-specific stroma is critical for primary and metastatic tumor growth progression. Prostate cancer cells colonize preferentially bone (osteotropism), where they alter the physiological balance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption, and elicit prevalently an osteoblastic response (osteoinduction). The molecular cues provided by osteoblasts for the survival and growth of bone metastatic prostate cancer cells are largely unknown. We exploited the sufficient divergence between human and mouse RNA sequences together with redefinition of highly species-specific gene arrays by computer-aided and experimental exclusion of cross-hybridizing oligonucleotide probes. This strategy allowed the dissection of the stroma (mouse) from the cancer cell (human) transcriptome in bone metastasis xenograft models of human osteoinductive prostate cancer cells (VCaP and C4-2B). As a result, we generated the osteoblastic bone metastasis-associated stroma transcriptome (OB-BMST). Subtraction of genes shared by inflammation, wound healing and desmoplastic responses, and by the tissue type-independent stroma responses to a variety of non-osteotropic and osteotropic primary cancers generated a curated gene signature ("Core" OB-BMST) putatively representing the bone marrow/bone-specific stroma response to prostate cancer-induced, osteoblastic bone metastasis. The expression pattern of three representative Core OB-BMST genes (PTN, EPHA3 and FSCN1) seems to confirm the bone specificity of this response. A robust induction of genes involved in osteogenesis and angiogenesis dominates both the OB-BMST and Core OB-BMST. This translates in an amplification of hematopoietic and, remarkably, prostate epithelial stem cell niche components that may function as a self-reinforcing bone metastatic niche providing a growth support specific for osteoinductive prostate cancer cells. The induction of this combinatorial stem cell niche is a novel mechanism that may also explain cancer cell osteotropism and local interference with hematopoiesis (myelophthisis). Accordingly, these stem cell niche components may represent innovative therapeutic targets and/or serum biomarkers in osteoblastic bone metastasis.

Identification and molecular characterization of bone-related micrornas: functional implications

Tese de doutoramento, Ciências Biomédicas, Departamento de Ciências Biomédicas e Medicina, Universidade do Algarve, 2014

Translation of biomechanical concepts in bone tissue engineering: from animal study to revision knee arthroplasty.

Bone defects in revision knee arthroplasty are often located in load-bearing regions. The goal of this study was to determine whether a physiologic load could be used as an in situ osteogenic signal to the scaffolds filling the bone defects. In order to answer this question, we proposed a novel translation procedure having four steps: (1) determining the mechanical stimulus using finite element method, (2) designing an animal study to measure bone formation spatially and temporally using micro-CT imaging in the scaffold subjected to the estimated mechanical stimulus, (3) identifying bone formation parameters for the loaded and non-loaded cases appearing in a recently developed mathematical model for bone formation in the scaffold and (4) estimating the stiffness and the bone formation in the bone-scaffold construct. With this procedure, we estimated that after 3 years mechanical stimulation increases the bone volume fraction and the stiffness of scaffold by 1.5- and 2.7-fold, respectively, compared to a non-loaded situation.