ROCK Inhibitor Enhances Adhesion and Wound Healing of Human Corneal Endothelial Cells.

Maintenance of corneal transparency is crucial for vision and depends mainly on the endothelium, a non-proliferative monolayer of cells covering the inner part of the cornea. When endothelial cell density falls below a critical threshold, the barrier and "pump" functions of the endothelium are compromised which results in corneal oedema and loss of visual acuity. The conventional treatment for such severe disorder is corneal graft. Unfortunately, there is a worldwide shortage of donor corneas, necessitating amelioration of tissue survival and storage after harvesting. Recently it was reported that the ROCK inhibitor Y-27632 promotes adhesion, inhibits apoptosis, increases the number of proliferating monkey corneal endothelial cells in vitro and enhance corneal endothelial wound healing both in vitro and in vivo in animal models. Using organ culture human cornea (N = 34), the effect of ROCK inhibitor was evaluated in vitro and ex vivo. Toxicity, corneal endothelial cell density, cell proliferation, apoptosis, cell morphometry, adhesion and wound healing process were evaluated by live/dead assay standard cell counting method, EdU labelling, Ki67, Caspase3, Zo-1 and Actin immunostaining. We demonstrated for the first time in human corneal endothelial cells ex vivo and in vitro, that ROCK inhibitor did not induce any toxicity effect and did not alter cell viability. ROCK inhibitor treatment did not induce human corneal endothelial cells proliferation. However, ROCK inhibitor significantly enhanced adhesion and wound healing. The present study shows that the selective ROCK inhibitor Y-27632 has no effect on human corneal endothelial cells proliferative capacities, but alters cellular behaviours. It induces changes in cell shape, increases cell adhesion and enhances wound healing ex vivo and in vitro. Its absence of toxicity, as demonstrated herein, is relevant for its use in human therapy.

The Na+-dependent chloride-bicarbonate exchanger SLC4A8 mediates an electroneutral Na+ reabsorption process in the renal cortical collecting ducts of mice.

Regulation of sodium balance is a critical factor in the maintenance of euvolemia, and dysregulation of renal sodium excretion results in disorders of altered intravascular volume, such as hypertension. The amiloride-sensitive epithelial sodium channel (ENaC) is thought to be the only mechanism for sodium transport in the cortical collecting duct (CCD) of the kidney. However, it has been found that much of the sodium absorption in the CCD is actually amiloride insensitive and sensitive to thiazide diuretics, which also block the Na-Cl cotransporter (NCC) located in the distal convoluted tubule. In this study, we have demonstrated the presence of electroneutral, amiloride-resistant, thiazide-sensitive, transepithelial NaCl absorption in mouse CCDs, which persists even with genetic disruption of ENaC. Furthermore, hydrochlorothiazide (HCTZ) increased excretion of Na+ and Cl- in mice devoid of the thiazide target NCC, suggesting that an additional mechanism might account for this effect. Studies on isolated CCDs suggested that the parallel action of the Na+-driven Cl-/HCO3- exchanger (NDCBE/SLC4A8) and the Na+-independent Cl-/HCO3- exchanger (pendrin/SLC26A4) accounted for the electroneutral thiazide-sensitive sodium transport. Furthermore, genetic ablation of SLC4A8 abolished thiazide-sensitive NaCl transport in the CCD. These studies establish what we believe to be a novel role for NDCBE in mediating substantial Na+ reabsorption in the CCD and suggest a role for this transporter in the regulation of fluid homeostasis in mice.

Production of renewable polymers from crop plants

Plants produce a range of biopolymers for purposes such as maintenance of structural integrity, carbon storage, and defense against pathogens and desiccation. Several of these natural polymers are used by humans as food and materials, and increasingly as an energy carrier. In this review, we focus on plant biopolymers that are used as materials in bulk applications, such as plastics and elastomers, in the context of depleting resources and climate change, and consider technical and scientific bottlenecks in the production of novel or improved materials in transgenic or alternative crop plants. The biopolymers discussed are natural rubber and several polymers that are not naturally produced in plants, such as polyhydroxyalkanoates, fibrous proteins and poly-amino acids. In addition, monomers or precursors for the chemical synthesis of biopolymers, such as 4-hydroxybenzoate, itaconic acid, fructose and sorbitol, are discussed briefly

PANACEA (Platform for Automatic, Normalised Annotation and Cost-Effective Acquisition of Language Resources for Human Language Technologies)

The objective of PANACEA is to build a factory of LRs that automates the stages involved in the acquisition, production, updating and maintenance of LRs required by MT systems and by other applications based on language technologies, and simplifies eventual issues regarding intellectual property rights. This automation will cut down the cost, time and human effort significantly. These reductions of costs and time are the only way to guarantee the continuous supply of LRs that MT and other language technologies will be demanding in the multilingual Europe.

Well-being and the frailty process in later life: an evaluation of the effectiveness of downward social comparison

This article, which is based on a longitudinal study conducted with a cohort ofoctogenarians, examines downward social comparison and its effectiveness as an adjustment mechanism during the frailty process. First of all, a paradoxical stability of subjective well-being is to be observed: it remains stable over five years notwithstanding the general decline in health. Next, an analysis based on individual health trajectories reveals that downward social comparison is associated with the maintenance of a stable level of well-being, whereas, when it is not associated with well-being, the latter tends to vary.

Antagonistic roles of Notch and p63 in controlling mammary epithelial cell fates.

The breast epithelium has two major compartments, luminal and basal cells, that are established and maintained by poorly understood mechanisms. The p53 homolog, p63, is required for the formation of mammary buds, but its function in the breast after birth is unknown. We show that in primary human breast epithelial cells, maintenance of basal cell characteristics depends on continued expression of the p63 isoform, DeltaNp63, which is expressed in the basal compartment. Forced expression of DeltaNp63 in purified luminal cells confers a basal phenotype. Notch signaling downmodulates DeltaNp63 expression and mimics DeltaNp63 depletion, whereas forced expression of DeltaNp63 partially counteracts the effects of Notch. Consistent with Notch activation specifying luminal cell fate in the mammary gland, Notch signaling activity is specifically detected in mice at sites of pubertal ductal morphogenesis where luminal cell fate is determined. Basal cells in which Notch signaling is active show decreased p63 expression. Both constitutive expression of DeltaNp63 and ablation of Notch signaling are incompatible with luminal cell fate. Thus, the balance between basal and luminal cell compartments of the breast is regulated by antagonistic functions of DeltaNp63 and Notch.Cell Death and Differentiation advance online publication, 9 April 2010; doi:10.1038/cdd.2010.37.

Movement, impacts and management of plant distributions in response to climate change: insights from invasions

A major challenge in this era of rapid climate change is to predict changes in species distributions and their impacts on ecosystems, and, if necessary, to recommend management strategies for maintenance of biodiversity or ecosystem services. Biological invasions, studied in most biomes of the world, can provide useful analogs for some of the ecological consequences of species distribution shifts in response to climate change. Invasions illustrate the adaptive and interactive responses that can occur when species are confronted with new environmental conditions. Invasion ecology complements climate change research and provides insights into the following questions: i) how will species distributions respond to climate change? ii) how will species movement affect recipient ecosystems? and iii) should we, and if so how can we, manage species and ecosystems in the face of climate change? Invasion ecology demonstrates that a trait-based approach can help to predict spread speeds and impacts on ecosystems, and has the potential to predict climate change impacts on species ranges and recipient ecosystems. However, there is a need to analyse traits in the context of life-history and demography, the stage in the colonisation process (e.g., spread, establishment or impact), the distribution of suitable habitats in the landscape, and the novel abiotic and biotic conditions under which those traits are expressed. As is the case with climate change, invasion ecology is embedded within complex societal goals. Both disciplines converge on similar questions of "when to intervene?" and "what to do?" which call for a better understanding of the ecological processes and social values associated with changing ecosystems.

Effect of mating history on gender preference in the hermaphroditic snail physa acuta

Several internally fertilizing hermaphroditic animals can only perform one sexual role at a time. In such species, two individuals that engage in a copulation may have different interests in acting as male or female. A gender choice must be made which, if both individuals have the same preference, may give rise to a severe sexual conflict. Here we tested the hypothesis that gender choice could be influenced by mating history, using the freshwater snail, Physa acuta. We recorded the copulatory behaviour of 240 pairs composed of a focal individual and a partner, each either short- or long-isolated. We found that the time to the first copulation was unaffected by isolation status, suggesting that first contacts in this species are random processes. In contrast, the duration of copulations and the frequency of rejection behaviours suggested that individual gender preference switches from male biased to female biased as isolation increases. In addition, snails rejected copulations more frequently when presented to a partner with the same isolation status. Reciprocity, measured as the rate of gender swapping between the first and second copulations, was high irrespective of gender status. We suggest possible evolutionary causes for this gender preference switch and discuss its potential importance in natural population as well as its consequences for the maintenance of hermaphroditism

Enhanced visuospatial memory following intracerebroventricular administration of nerve growth factor

The present work assessed the effects of intracerebroventricular injections of rh recombined human nerve growth factor (rh NGF) (5 micrograms/2.5 microl) at postnatal days 12 and 13 upon the development of spatial learning capacities. The treated rats were trained at the age of 22 days to escape onto an invisible platform at a fixed position in space in a Morris navigation task. For half of the subjects, the training position was also cued, a procedure aimed at facilitating escape and at reducing attention to the distant spatial cues. Later, at the age of 6 months, all the rats were trained in a radial-arm maze task. Treatment effects were found in both immature and adult rats. The injection of NGF improved the performance in the Morris navigation task in both training conditions. There was a significant reduction in the escape latency and an increased bias toward the training platform quadrant during probe trials. The most consistent effect was the precocious development of an adult-like spatial memory. In the radial-arm maze, the NGF-treated rats made significantly fewer reentries than vehicle rats and this effect was particularly marked in the treated female rats. Taken together, these experiments reveal that the development and the maintenance of an accurate spatial representation are tightly related to the development of brain structures facilitated by the action of NGF. Moreover, these experiments demonstrate that an acute pharmacological treatment that leads to a transient modification in the choline acetyltransferase activity can induce a behavioral change long after the treatment.

Parameters for successful monthly extended dosing of darbepoetin-alpha in patients undergoing hemodialysis.

AIM: To document the feasibility and report the results of dosing darbepoetin-alpha at extended intervals up to once monthly (QM) in a large dialysis patient population. MATERIAL: 175 adult patients treated, at 23 Swiss hemodialysis centres, with stable doses of any erythropoiesis-stimulating agent who were switched by their physicians to darbepoetin-alpha treatment at prolonged dosing intervals (every 2 weeks [Q2W] or QM). METHOD: Multicentre, prospective, observational study. Patients' hemoglobin (Hb) levels and other data were recorded 1 month before conversion (baseline) to an extended darbepoetin-alpha dosing interval, at the time of conversion, and once monthly thereafter up to the evaluation point (maximum of 12 months or until loss to follow-up). RESULTS: Data for 161 evaluable patients from 23 sites were included in the final analysis. At 1 month prior to conversion, 73% of these patients were receiving darbepoetin-alpha weekly (QW) and 27% of the patients biweekly (Q2W). After a mean follow-up of 9.5 months, 34% received a monthly (QM) dosing regimen, 52% of the patients were receiving darbepoetin-alpha Q2W, and 14% QW. The mean (SD) Hb concentration at baseline was 12.3 +/- 1.2 g/dl, compared to 11.9 +/- 1.2 g/dl at the evaluation point. The corresponding mean weekly darbepoetin-alpha dose was 44.3 +/- 33.4 microg at baseline and 37.7 +/- 30.8 microg at the evaluation point. CONCLUSIONS: Conversion to extended darbepoetin-alpha dosing intervals of up to QM, with maintenance of initial Hb concentrations, was successful for the majority of stable dialysis patients.

O Impacto Fiscal Decorrente do processo de Rememoração de Activos Fixos Tangíveis

O objectivo deste estudo consiste em evidenciar a politica contabilística de revalorização de activos fixos tangíveis e o seu impacto numa entidade, principalmente a nível da tributação dos rendimentos. A abordagem é direccionada para o meio empresarial cabo-verdiano onde se pretende dar a conhecer o enquadramento legal e fiscal existente, assim como ilustrar com um caso prático. O trabalho foi preparado com base em consulta de bibliografia especializada, de normativos estabelecidos no país e ainda a recolha de dados práticos sobre o tema e entrevistas com profissionais na área. Partimos do geral para o particular, isto é, começamos por trabalhar o conteúdo dos activos fixos tangíveis no geral, para posteriormente entrarmos no objecto de estudo: a revalorização dos activos fixos tangíveis, e assim dar a conhecer os impactos que este tema traz para uma entidade. O trabalho inicia com um enquadramento teórico de conceitos relacionados com os fenómenos que levam com que um bem perca valor ao longo dos anos, assim como outras matérias directamente ligadas às revalorizações (exemplo da manutenção de capital físico e financeiro). É feita uma abordagem normativa e conceitual geral sobre os activos fixos tangíveis: o reconhecimento, a mensuração inicial e subsequente, a divulgação e o Desreconhecimento. É uma abordagem comparativa com o sistema contabilístico anterior (Plano Nacional de Contabilidade). No tratamento da mensuração subsequente dos activos fixos tangíveis introduzimos o estudo da Revalorização do Activos Fixos Tangíveis, referindo as normas contabilísticas e as leis fiscais relacionadas e os impactos que traz para a empresa. aim of this research consist in show evidences about the accounting policy of value of revalorization of Tangible Assets and its impact in an entity, mainly in terms of taxation incoming. The approach is directed to the Cape-Verdean enterprise environment where is intended to give to know the legal and tax framing, as well illustrate with a practical case. This task was prepared based on specialized bibliographic researches, of normative established in the country and also the collecting of practical data about the theme and interviews with professionals in the area. We start from general to particular, that is, we started working on the contents of Tangible Assets in general, to later on get into the study object: the revalorization of Tangible Assets and thus give to know the impacts that this brings to an entity. The task tarts with the theoretical framing of concepts related with the phenomenon that lead one good lose its value along the years, as well other material goods directly connected to revalorization (example of maintenance of physical and financial capital). It is made a normative and general conceptual approach about the Tangible Assets: the recognizing, the measurable initiate and subsequently, the divulgation and the unknown. It is a comparative approach with the previous accounting system (National Accounting Plan). In the treatment of the measurable of Tangible Assets we introduced the study of Revalorization of Tangible Assets, referring the accounting rules and the related fiscal laws and the impacts that bring to the company.

Blood pressure response to central and/or peripheral inhibition of phenylethanolamine N-methyltransferase in normotensive and hypertensive rats

We studied the effects on blood pressure and heart rate of two different phenylethanolamine N-methyltransferase (PNMT) inhibitors in normotensive, in two-kidney renal hypertensive, and in deoxycorticosterone-salt (DOC-salt) hypertensive rats. One compound (SK&F 64139) blocks the conversion of norepinephrine to epinephrine in both the central and the peripheral nervous system, whereas the other (SK&F 29661) does not cross the blood-brain barrier and therefore is active mostly in the adrenal glands. In the rats given SK&F 29661, practically no acute blood pressure changes were in the adrenal glands. In the rats given SK&F 64139 induced only a minor blood pressure and heart rate response in normotensive and two-kidney renal hypertensive rats. However, in DOC-salt hypertensive rats, it reduced arterial pressure to approximately normal levels and concomitantly slowed pulse rate. There was a close correlation between the magnitude of the blood pressure response observed in all SK&F 64139-treated animals and the control plasma norepinephrine (4 = -0.795, P less than 0.001) and epinephrine (r = -0.789, P less than 0.001) levels. These results suggest an important role for central epinephrine in regulating the peripheral sympathoadrenomedullary and the baroreceptor reflex activity, particularly when the maintenance of the high blood pressure is not renin-dependent.

Hidrossedimentologia e disponibilidade hídrica da bacia hidrográfica da Barragem de Poilão

TEIXEIRA, José João Lopes. Departamento de Engenharia Agrícola, Centro de Ciências Agrárias da Universidade Federal do Ceará, Agosto de 2011. Hidrossedimentologia e disponibilidade hídrica da bacia hidrográfica da Barragem de Poilão, Cabo Verde. Orientador: José Carlos de Araújo. Examinadores: George Leite Mamede, Pedro Henrique Augusto Medeiros. O Arquipélago de Cabo Verde, situado na costa ocidental africana, sofre influência do deserto de Saara tornando o clima caraterizado por pluviometria muito baixa e distribuída irregularmente no espaço e no tempo. As chuvas são muito concentradas, gerando grandes escoamentos para o mar. O aumento da disponibilidade hídrica requer além da construção e manutenção de infraestrutura de captação e conservação de águas pluviais, uma gestão eficiente destes recursos. Atualmente, constitui um dos eixos estratégicos da política do estado de Cabo Verde, a captação, armazenamento e mobilização de águas superficiais através de construção de barragens. Estudos do comportamento hidrológico e sedimentológico do reservatório e da sua bacia de contribuição constituem premissas básicas para um ótimo dimensionamento, gestão e monitoramento da referida infraestrutura. É neste sentido que o presente estudo objetivou sistematizar informações hidrológicas e sedimentológicas da bacia hidrográfica da Barragem de Poilão (BP) e apresentar proposta operacional de longo prazo. A área de estudo ocupa 28 km² a montante da Bacia Hidrográfica da Ribeira Seca (BHRS) na Ilha de Santiago. A altitude da bacia varia de 99 m, situada na cota da barragem, até 1394 m. Para o estudo, foram utilizados e sistematizados, série pluviométrica de 1973 a 2010, registos de vazão instantânea do período 1984 a 2000 e registos agroclimáticos da área de estudo (1981 a 2004). Para o preenchimento das falhas tanto dos escoamentos como da descarga sólida em suspensão, foi utilizado o método de curva chave. Para estimativa de produção de sedimentos na bacia, aplicou-se a Equação Universal de Perda de Solo (USLE) e a razão de aporte de sedimentos (SDR). O índice de retenção de sedimentos no reservatório foi estimado pelo método de Brune e a distribuição de sedimento pelo método empírico de redução de área descrito por Borland e Miller e, revisado por Lara. Para gerar e simular curvas de vazão versus garantia foi utilizado código computacional VYELAS, desenvolvido por Araújo e baseado na abordagem de Campos. Também foi avaliada a redução da vazão de retirada do período 2006 a 2026, provocado pelo assoreamento do reservatório. Concluiu-se que em média a precipitação anual é de 323 mm, concentrando-se 73% nos meses de agosto e setembro; a bacia de contribuição apresenta como valor um número de curva (CN) de 76, com abstração inicial (Ia) de 26 mm, coeficiente de escoamento de 19% e uma vazão anual afluente de 1,7 hm³(cv= 0,73); a disponibilidade hídrica para uma garantia de 85% é avaliada em 0,548 hm³/ano e não 0,671 hm³/ano como indica o projeto original. Com uma descarga sólida estimada em 22.185 m³/ano conclui-se que até o ano de 2026, a capacidade do reservatório reduz a uma taxa de 1,8 % ao ano, devido ao assoreamento, provocando uma redução de 41% da disponibilidade hídrica inicial. Nessa altura, as perdas por evaporação e sangria serão da ordem de 81% da vazão afluente de entrada no reservatório. Na base desses resultados se apresentou proposta de operação da BP.

Soil and water conservation strategies and impact on sustainable livelihood in Cape Verde – Case study of Ribeira Seca watershed

Cape Verde, located off the coast of Senegal in western Africa, is a volcanic archipelago where a combination of human, climatic, geomorphologic and pedologic factors has led to extensive degradation of the soils. Like other Sahelian countries, Cape Verde has suffered the effects of desertification through the years, threatening the livelihood of the islands population and its fragile environment. In fact, the steep slopes in the ore agricultural islands, together with semi-arid and arid environments, characterized by an irregular and poorly distributed rainy season, with high intensity rainfall events, make dryland production a challenge. To survive in these fragile conditions, the stabilization of the farming systems and the maintenance of sustainable yields have become absolute priorities, making the islands an erosion control laboratory. Soil and water conservation strategies have been a centerpiece of the government0s agricultural policies for the last half century. Aiming to maintain the soil in place and the water inside the soil, the successive governments of Cape Verde have implemented a number of soil and water conservation techniques, the most common ones being terraces, half moons, live barriers, contour rock walls, contour furrows and microcatchments, check dams and reforestation with drought resistant species. The soil and water conservation techniques implemented have contributed to the improvement of the economical and environmental conditions of the treated landscape, making crop production possible, consequently, improving the livelihood of the people living on the islands. In this paper, we survey the existing soil and water conservation techniques, analyze their impact on the livelihood condition of the population through a thorough literature review and field monitoring using a semi-quantitative methodology and evaluate their effectiveness and impact on crop yield in the Ribeira Seca watershed. A brief discussion is given on the cost and effectiveness of the techniques to reduce soil erosion and to promote rainfall infiltration. Finally, we discuss the critical governance factors that lead to the successful implementation of such strategy in a country with scarce natural resources.

Lane Closure Policy Development, Enforcement, and Exceptions: A Survey of Seven State Transportation Agencies, February 2007

Traffic volume increases and an aging infrastructure create the need for reconstruction, rehabilitation, and maintenance of existing facilities. As more motorists feel that delays should be minimal during highway renewal projects, lane closures that reduce capacity through the work zone should not create unreasonable delays. In order to facilitate the determination of when a lane closure is permitted during the day, some state transportation agencies (STAs) have developed lane closure policies, or strategies, that they use as guidance in determining daily permitted lane closure times. Permitted lane closure times define what times of the day, week, or season a lane closure is allowed on a facility and at a specific location or segment. This research addresses the lane closure policies of several STAs that were reputed to have good lane closures policies or strategies and that were selected by the project advisory committee for further research.