RESUMEN
Cell Therapy Clinical Trial and Preclinical Research databases have been established by the Cell Therapy Catapult to document current and future cell therapy clinical trials in the UK. We identified 41 ongoing trials in April 2014, an increase of seven trials from April 2013. In addition, we identified 45 late-stage preclinical research projects. The majority of the clinical trials are early phase, primarily led by academic groups. The leading therapeutic areas are cancer, cardiology and neurology. The trends in the UK are also seen globally. As the field matures, more later phase and commercial studies will emerge and the challenges will likely evolve into how to manufacture sufficient cell quantities, manage complex logistics for multi-center trials and control cost.
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Trasplante de Células/métodos , Tratamiento Basado en Trasplante de Células y Tejidos/tendencias , Ensayos Clínicos como Asunto , Financiación Gubernamental , Geografía , Humanos , Inmunoterapia , Estudios Multicéntricos como Asunto , Neoplasias/inmunología , Neoplasias/terapia , Proyectos de Investigación , Reino UnidoRESUMEN
Diseases transmitted between animals and people have made up more than 50% of emerging infectious diseases in humans over the last 60 years and have continued to arise in recent months. Yet, public health and animal disease surveillance programs continue to operate independently. Here, we assessed whether recent emerging zoonotic pathogens (n = 143) are known to cause morbidity or mortality in their animal host and if so, whether they were first detected with an animal morbidity/mortality event. We show that although sick or dead animals are often associated with these pathogens (52%), only 9% were first detected from an animal morbidity or mortality event prior to or concurrent with signs of illness in humans. We propose that an animal morbidity and mortality reporting program will improve detection and should be an essential component of early warning systems for zoonotic diseases. With the use of widespread low-cost technology, such a program could engage both the public and professionals and be easily tested and further incorporated as part of surveillance efforts by public health officials.
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Enfermedades Transmisibles Emergentes/epidemiología , Vigilancia de la Población/métodos , Zoonosis/epidemiología , Enfermedades de los Animales/microbiología , Enfermedades de los Animales/mortalidad , Enfermedades de los Animales/virología , Animales , Animales Domésticos/microbiología , Animales Domésticos/virología , Animales Salvajes/microbiología , Animales Salvajes/virología , Enfermedades Transmisibles Emergentes/diagnóstico , Enfermedades Transmisibles Emergentes/mortalidad , Humanos , Zoonosis/diagnóstico , Zoonosis/mortalidadRESUMEN
Billions of animals migrate each year. To successfully reach their destination, migrants must have evolved an appropriate genetic program and suitable developmental, morphological, physiological, biomechanical, behavioral, and life-history traits. Moreover, they must interact successfully with biotic and abiotic factors in their environment. Migration therefore provides an excellent model system in which to address several of the "grand challenges" in organismal biology. Previous research on migration, however, has often focused on a single aspect of the phenomenon, largely due to methodological, geographical, or financial constraints. Integrative migration biology asks 'big questions' such as how, when, where, and why animals migrate, which can be answered by examining the process from multiple ecological and evolutionary perspectives, incorporating multifaceted knowledge from various other scientific disciplines, and using new technologies and modeling approaches, all within the context of an annual cycle. Adopting an integrative research strategy will provide a better understanding of the interactions between biological levels of organization, of what role migrants play in disease transmission, and of how to conserve migrants and the habitats upon which they depend.
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Migración Animal/fisiología , Evolución Biológica , Ecología , Animales , Ecosistema , Ambiente , Genoma/fisiología , FenotipoRESUMEN
BACKGROUND: How migration evolved represents one of the most poignant questions in evolutionary biology. While studies on the evolution of migration in birds are well represented in the literature, migration in bats has received relatively little attention. Yet, more than 30 species of bats are known to migrate annually from breeding to non-breeding locations. Our study is the first to test hypotheses on the evolutionary history of migration in bats using a phylogenetic framework. METHODS AND PRINCIPAL FINDINGS: In addition to providing a review of bat migration in relation to existing hypotheses on the evolution of migration in birds, we use a previously published supertree to formulate and test hypotheses on the evolutionary history of migration in bats. Our results suggest that migration in bats has evolved independently in several lineages potentially as the need arises to track resources (food, roosting site) but not through a series of steps from short- to long-distance migrants, as has been suggested for birds. Moreover, our analyses do not indicate that migration is an ancestral state but has relatively recently evolved in bats. Our results also show that migration is significantly less likely to evolve in cave roosting bats than in tree roosting species. CONCLUSIONS AND SIGNIFICANCE: This is the first study to provide evidence that migration has evolved independently in bat lineages that are not closely related. If migration evolved as a need to track seasonal resources or seek adequate roosting sites, climate change may have a pivotal impact on bat migratory habits. Our study provides a strong framework for future research on the evolution of migration in chiropterans.
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Migración Animal , Evolución Biológica , Animales , Quirópteros , Cambio Climático , Ecosistema , Ambiente , Evolución Molecular , Vuelo Animal , Filogenia , Dinámica Poblacional , Análisis de Regresión , Especificidad de la EspecieRESUMEN
Dependent young are often easy targets for predators, so for many parent vertebrates, responding to offspring-directed threats is a fundamental part of reproduction. We tested the parental adrenocortical response of the endangered black-capped vireo (Vireo atricapilla) and the common white-eyed vireo (V. griseus) to acute and chronic threats to their offspring. Like many open-nesting birds, our study species experience high offspring mortality. Parents responded behaviorally to a predator decoy or human 1-2m from their nests, but, in contrast to similar studies of cavity-nesting birds, neither these acute threats nor chronic offspring-directed threats altered plasma corticosterone concentrations of parents. Although parents in this study showed no corticosterone response to offspring-directed threats, they always increased corticosterone concentrations in response to capture. To explain these results, we propose that parents perceive their risk of nest-associated death differently depending on nest type, with cavity-nesting adults perceiving greater risk to themselves than open-nesters that can readily detect and escape from offspring-directed threats. Our results agree with previous studies suggesting that the hypothalamic-pituitary-adrenal axis, a major physiological mechanism for coping with threats to survival, probably plays no role in coping with threats to offspring when risks to parents and offspring are not correlated. We extend that paradigm by demonstrating that nest style may influence how adults perceive the correlation between offspring-directed and self-directed threats.
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Corticoesteroides/sangre , Sistema Hipotálamo-Hipofisario/fisiología , Comportamiento de Nidificación/fisiología , Passeriformes/fisiología , Sistema Hipófiso-Suprarrenal/fisiología , Conducta Predatoria , Estrés Psicológico/sangre , Animales , Corticosterona/sangre , Passeriformes/sangreRESUMEN
Prostate cancer cells with stem cell characteristics were identified in human prostate cancer cell lines by their ability to form from single cells self-renewing prostaspheres in non-adherent cultures. Prostaspheres exhibited heterogeneous expression of proliferation, differentiation and stem cell-associated makers CD44, ABCG2 and CD133. Treatment with WNT inhibitors reduced both prostasphere size and self-renewal. In contrast, addition of Wnt3a caused increased prostasphere size and self-renewal, which was associated with a significant increase in nuclear beta-catenin, keratin 18, CD133 and CD44 expression. As a high proportion of LNCaP and C4-2B cancer cells express androgen receptor we determined the effect of the androgen receptor antagonist bicalutamide. Androgen receptor inhibition reduced prostasphere size and expression of PSA, but did not inhibit prostasphere formation. These effects are consistent with the androgen-independent self-renewal of cells with stem cell characteristics and the androgen-dependent proliferation of transit amplifying cells. As the canonical WNT signaling effector beta-catenin can also associate with the androgen receptor, we propose a model for tumour propagation involving a balance between WNT and androgen receptor activity. That would affect the self-renewal of a cancer cell with stem cell characteristics and drive transit amplifying cell proliferation and differentiation. In conclusion, we provide evidence that WNT activity regulates the self-renewal of prostate cancer cells with stem cell characteristics independently of androgen receptor activity. Inhibition of WNT signaling therefore has the potential to reduce the self-renewal of prostate cancer cells with stem cell characteristics and improve the therapeutic outcome.
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Neoplasias de la Próstata/metabolismo , Células Madre/fisiología , Proteínas Wnt/metabolismo , Antagonistas de Receptores Androgénicos , Diferenciación Celular , Proliferación Celular , Tamaño de la Célula , Humanos , Masculino , Neoplasias de la Próstata/patología , Receptores Androgénicos/metabolismo , Transducción de Señal , Células Tumorales Cultivadas , Proteína Wnt3 , Proteína Wnt3A , beta Catenina/metabolismoRESUMEN
Migratory birds can be efficient dispersers of pathogens, yet we know little about the effect of migration and season on the microbial community in avian plumage. This is the first study to describe and compare the microbial plumage community of adult and juvenile migratory birds during the annual cycle and compare the plumage community of migrants to that of resident birds at both neotropical and nearctic locations. We used length heterogeneity PCR (16S rRNA) to describe the microbial assemblage sampled from the plumage of 66 birds in two age classes and from 16 soil samples. Resident birds differed significantly in plumage microbial community composition from migrants (R > or = 0.238, P < 0.01). Nearctic resident birds had higher plumage microbial diversity than nearctic migrants (R = 0.402, P < 0.01). Plumage microbial composition differed significantly between fall premigratory and either breeding (R > or = 0.161, P < 0.05) or nonbreeding stages (R = 0.267, P < 0.01). Six bacterial operational taxonomic units contributed most to the dissimilarities found in this assay. Soil microbial community composition was significantly different from all samples of plumage microbial communities (R > or = 0.700, P < 0.01). The plumage microbial community varies in relation to migration strategy and stage of the annual cycle. We suggest that plumage microbial acquisition begins in the first year at natal breeding locations and reaches equilibrium at the neotropical wintering sites. These data lead us to conclude that migration and season play an important role in the dynamics of the microbial community in avian plumage and may reflect patterns of pathogen dispersal by birds.
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Migración Animal , Bacterias/genética , Aves/microbiología , Plumas/microbiología , Estaciones del Año , Animales , Bacterias/clasificación , ADN Bacteriano/genética , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Suelo/análisis , Microbiología del SueloRESUMEN
Anthropogenic or natural disturbances can have a significant impact on wild animals. Therefore, understanding when, how and what type of human and natural events disturb animals is a central problem in wildlife conservation. However, it can be difficult to identify which particular environmental stressor affects an individual most. We use heart rate telemetry to quantify the energy expenditure associated with different types of human-mediated and natural disturbances in a breeding passerine, the white-eyed vireo (Vireo griseus). We fitted 0.5g heart rate transmitters to 14 male vireos and continuously recorded heart rate and activity for two days and three nights on a military installation. We calibrated heart rate to energy expenditure for five additional males using an open-flow, push-through respirometry system showing that heart rate predicted 74 per cent of energy expenditure. We conducted standardized disturbance trials in the field to experimentally simulate a natural stressor (predator presence) and two anthropogenic stressors. Although birds initially showed behavioural and heart rate reactions to some disturbances, we could not detect an overall increase in energy expenditure during 1- or 4-hours disturbances. Similarly, overall activity rates were unaltered between control and experimental periods, and birds continued to perform parental duties despite the experimental disturbances. We suggest that vireos quickly determined that disturbances were non-threatening and thus showed no (costly) physiological response. We hypothesize that the lack of a significant response to disturbance in vireos is adaptive and may be representative of animals with fast life histories (e.g. short lifespan, high reproductive output) so as to maximize energy allocation to reproduction. Conversely, we predict that energetic cost of human-mediated disturbances will be significant in slow-living animals.
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Metabolismo Energético , Pájaros Cantores/fisiología , Animales , Actividades Humanas , Masculino , Conducta PaternaRESUMEN
OBJECTIVES: Androgen-deprivation therapy effectively shrinks hormone-naïve prostate cancer, both in the prostate and at sites of distant metastasis. However prolonged androgen deprivation generally results in relapse and androgen-independent tumour growth, which is inevitably fatal. The molecular events that enable prostate cancer cells to proliferate in reduced androgen conditions are poorly understood. Here we investigate the role of Hedgehog signalling in androgen-independent prostate cancer (AIPC). METHODS: Activity of the Hedgehog signalling pathway was analysed in cultured prostate cancer cells, and circulating prostate tumour cells were isolated from blood samples of patients with AIPC. RESULTS: AIPC cells were derived through prolonged culture in reduced androgen conditions, modelling hormone therapy in patients, and expressed increased levels of Hedgehog signalling proteins. Exposure of cultured AIPC cells to cyclopamine, which inhibits Hedgehog signalling, resulted in inhibition of cancer cell growth. The expression of the Hedgehog receptor PTCH and the highly prostate cancer-specific gene DD3(PCA3) was significantly higher in circulating prostate cancer cells isolated from patients with AIPC compared with samples prepared from normal individuals. There was an association between PTCH and DD3(PCA3) expression and the length of androgen-ablation therapy. CONCLUSIONS: Our data are consistent with reports implicating overactivity of Hedgehog signalling in prostate cancer and suggest that Hedgehog signalling contributes to the androgen-independent growth of prostate cancer cells. As systemic anti-Hedgehog medicines are developed, the Hedgehog pathway will become a potential new therapeutic target in advanced prostate cancer.
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Proteínas Hedgehog/fisiología , Neoplasias de la Próstata/etiología , Transducción de Señal , Anciano , Anciano de 80 o más Años , Andrógenos/fisiología , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Billions of songbirds migrate several thousand kilometers from breeding to wintering grounds and are challenged with crossing ecological barriers and facing displacement by winds along the route. A satisfactory explanation of long-distance animal navigation is still lacking, partly because of limitations on field-based study. The navigational tasks faced by adults and juveniles differ fundamentally, because only adults migrate toward wintering grounds known from the previous year. Here, we show by radio tracking from small aircraft that only adult, and not juvenile, long-distance migrating white-crowned sparrows rapidly recognize and correct for a continent-wide displacement of 3,700 km from the west coast of North America to previously unvisited areas on the east coast. These results show that the learned navigational map used by adult long-distance migratory songbirds extends at least on a continental scale. The juveniles with less experience rely on their innate program to find their distant wintering areas and continue to migrate in the innate direction without correcting for displacement.
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Migración Animal , Pájaros Cantores , Animales , Estados UnidosRESUMEN
We used molecular methods to determine the microbial community of soil and avian plumage across biogeographic, ecological, and taxonomic scales. A total of 17 soil and 116 feather samples were collected from five avian species across multiple habitat types within one Neotropical and one temperate locality. Hypotheses regarding patterns of microbial composition relative to acquisition and dispersal of plumage bacteria in the ecosystem were tested by comparing microbial communities within and between soil and plumage. Samples from the plumage of American Redstarts (Setophaga ruticilla) were collected across both habitat types and geographic scales for intraspecific comparisons. The microbial diversity in avian plumage was moderately diverse and was dominated by Pseudomonas species. Despite a highly significant individual bird effect on microbial composition of the plumage, we detected significant biogeographic and type of habitat effects. Pseudomonas species were more abundant on the temperate site when all avian species were included in the analysis, and Bacillus subtilis and Xanthomonas groups were more abundant on the Neotropical site for redstarts alone. However, 16S rDNA sequence libraries were not significantly different between Jamaican and Maryland redstarts. Biogeographic and habitat effects were significant and more pronounced for soil samples indicating lower dispersal of soil microbiota. We detected a significant difference between soil and plumage microbial communities suggesting that soil plays a small role in plumage bacterial acquisition. Our results suggest bacterial communities on the plumage of birds are dynamic and may change at different stages in a bird's annual cycle.
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Bacterias/clasificación , Aves/microbiología , Plumas/microbiología , Microbiología del Suelo , Animales , Bacterias/genética , Biodiversidad , Biblioteca de Genes , Geografía , ARN Ribosómico 16S/química , Análisis de Secuencia de ADN , Especificidad de la EspecieRESUMEN
Raman microspectroscopy was used to determine biochemical markers during the differentiation of embryonic murine stem cells (mES) in vitro. Such markers are useful to determine the differentiation status of ES cells cultured on biomaterials. Raman spectra of mES cells as undifferentiated, spontaneously differentiated (4 days), and differentiated cells via formation of embryoid bodies (16, 20 days) were analyzed. Unsupervised hierarchical cluster analysis and principal component analysis were used to determine biochemical differences between mES cells in various states of differentiation. The undifferentiated cells were characterized by high scores of the first principal component (PC1, 49% variance). Similarity between the PC1 loading and the Raman spectrum of RNA indicated a high concentration of RNA in mES cells compared to differentiated cells. The ratio between the peak areas of RNA and proteins was used as a measure of mRNA translation. Using the same peak area ratio, it was possible to differentiate even between mES as undifferentiated and in early stages of differentiation (4 days). These findings were correlated with biological studies reporting high levels of nontranslated mRNA during early embryonic development. Therefore, the RNA translation obtained from the Raman spectra can be used as marker of differentiation state of mES cells.
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Embrión de Mamíferos/citología , Embrión no Mamífero , Biosíntesis de Proteínas/genética , Espectrometría Raman/métodos , Células Madre/citología , Animales , Diferenciación Celular , Células Madre/química , Células Madre/ultraestructuraRESUMEN
In tissue engineering, degradable or non-degradable polymer matrices can act as cell-carrier-scaffolds. Cell adhesion and growth on these scaffolds can be promoted by immobilizing extracellular matrix proteins. Therefore, in this study, polymer poly(ethylene terephthalate) (PET) films were surface modified by graft polymerization of acrylic acid, to subsequently allow collagen (types I and III) immobilization and human smooth muscle cell expansion. The surfaces of PET were activated by plasma, followed by acrylic acid graft polymerization, resulting in covalently bound brushes, containing an average of either 0.22+/-0.1 or 5.93+/-0.87 microg/cm2 of poly(acrylic acid) (PAA). Subsequent electrostatic adsorption of collagen gave a surface concentration of 4.96 and 17.2 microg/cm2, respectively, as determined using radiolabelled 125I collagen. Both PET films grafted with 0.22 microg/cm2 of PAA with or without adsorbed collagen were apt for smooth muscle cell adhesion and proliferation. However, films grafted with 5.93 microg/cm2 were not. PAA-grafted PET films, onto which serum proteins of the culture medium adsorbed spontaneously, proved to be better matrices than films on which collagen has been immobilized. It, therefore, can be speculated that other serum proteins are more important than collagen for the human smooth muscle cell adhesion and growth on surface-modified polymer matrices.
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Materiales Biocompatibles , Músculo Liso/citología , Tereftalatos Polietilenos , Vejiga Urinaria/química , Resinas Acrílicas , Adhesión Celular , División Celular , Células Cultivadas , Células Inmovilizadas , Colágeno , Humanos , Ensayo de Materiales , Microscopía Electrónica de Rastreo , Propiedades de Superficie , Ingeniería de TejidosRESUMEN
OBJECTIVES: Tissue engineering methods can be applied to regenerate diseased, or congenitally missing, urinary tract tissues. Urinary tract tissue cell cultures must be established in vitro and adequate matrices, acting as cell carriers, must be developed. Although degradable and nondegradable polymer matrices offer adequate mechanical stability, they are not optimal for cell adherence and growth. To overcome this problem, extracellular matrix proteins, permitting cell adhesion and regulation of cell proliferation and differentiation, can be adsorbed to the surface-modified polymer. METHODS: In this study, nondegradable polymer films, poly(ethylene terephthalate), were used as an experimental model. Films were modified by graft polymerization of acrylic acid to subsequently allow collagen type I and III immobilization. The following adhesion, proliferation of human urothelial cells, and induction of their stratification were analyzed. RESULTS: Collagen adsorption on 0.2 microg/cm2 poly(acrylic acid)-grafted polymer films rendered the matrix apt for human urothelial cell adhesion and proliferation. Furthermore, stratification of urothelial cells was demonstrated on these surface-modified matrices. CONCLUSIONS: These results have shown that surface-modified polymer matrices can be used to act as cell carriers for cultured human urothelial cells. Such a cell-matrix construct could be applied in reparative surgery of the urinary tract.
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Tereftalatos Polietilenos , Ingeniería de Tejidos/métodos , Urotelio/citología , Animales , Adhesión Celular/fisiología , Diferenciación Celular/fisiología , División Celular/fisiología , Células Cultivadas , Colágeno , Medio de Cultivo Libre de Suero , Proteínas de la Matriz Extracelular , Humanos , Músculo Liso/citología , Conejos , Sistema Urinario/cirugíaRESUMEN
Graft polymerization of acrylic acid onto plasma treated poly(ethylene terephthalate) (PET) films was carried out to develop surfaces for protein immobilization and smooth muscle cell seeding. Films with various graft densities were characterized by contact angle measurements, attenuated total reflectance infrared spectroscopy, X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM). The contact angle was observed to decrease from 72.9 degrees for the virgin PET films to between 26 degrees and 33 degrees depending on the graft density. Storage of grafted films led to an increase in the contact angle, suggesting molecular rearrangement at the surface. However, films with the lowest graft levels showed maximum enhancement in the contact angle up on storage. XPS confirmed the presence of the polyacrylic acid grafts at the film surface and AFM showed a marked increase in the wavelength of the surface roughness as the graft density increased. The amount of collagen immobilized at the surface of the grafted films also increased as the graft density increased. The collagen immobilized films provided an excellent substrate for the growth of human smooth muscle cells.