Fenneropenaeus indicus is protected from white spot disease by oral administration of inactivated white spot syndrome virus

Fenneropenaeus indicus could be protected from white spot disease (WSD) caused by white spot syndrome virus (WSSV) using a formalin-inactivated viral preparation (IVP) derived from WSSV-infected shrimp tissue. The lowest test quantity of lyophilized IVP coated onto feed at 0.025 g–1 (dry weight) and administered at a rate of 0.035 g feed g–1 body weight d–1 for 7 consecutive days was sufficient to provide protection from WSD for a short period (10 d after cessation of IVP administration). Shrimp that survived challenges on the 5th and 10th days after cessation of IVP administration survived repeated challenges although they were sometimes positive for the presence of WSSV by a polymerase chain reaction (PCR) assay specific for WSSV. These results suggest that F. indicus can be protected from WSD by simple oral administration of IVP

Adrenergic and muscarinic receptor subtypes functional regulation during diabetogenesis: Effect of curcumin and vitamin D3 pre-treatment

In the present study, the initial phase was directed to confirm the effects of curcumin and vitamin D3 in preventing or delaying diabetes onset by studying the blood glucose and insulin levels in the pre-treated and diabetic groups. Behavioural studies were conducted to evaluate the cognitive and motor function in experimental rats. The major focus of the study was to understand the cellular and neuronal mechanisms that ensure the prophylactic capability of curcumin and vitamin D3. To elucidate the mechanisms involved in conferring the antidiabetogenesis effect, we examined the DNA and protein profiles using radioactive incorporation studies for DNA synthesis, DNA methylation and protein synthesis. Furthermore the gene expression studies of Akt-1, Pax, Pdx-1, Neuro D1, insulin like growth factor-1 and NF-κB were done to monitor pancreatic beta cell proliferation and differentiation. The antioxidant and antiapoptotic actions of curcumin and vitamin D3 were examined by studying the expression of antioxidant enzymes - SOD and GPx, and apoptotic mediators like Bax, caspase 3, caspase 8 and TNF-α. In order to understand the signalling pathways involved in curcumin and vitamin D3 action, the second messengers, cAMP, cGMP and IP3 were studied along with the expression of vitamin D receptor in the pancreas. The neuronal regulation of pancreatic beta cell maintenance, proliferation and insulin release was studied by assessing the adrenergic and muscarinic receptor functional regulation in the pancreas, brain stem, hippocampus and hypothalamus. The receptor number and binding affinity of total muscarinic, muscarinic M1, muscarinic M3, total adrenergic, α adrenergic and β adrenergic receptor subtypes were studied in pancreas, brain stem and hippocampus of experimental rats. The mRNA expression of muscarinic and adrenergic receptor subtypes were determined using Real Time PCR. Immunohistochemistry studies using confocal microscope were carried out to confirm receptor density and gene expression results. Cell signalling alterations in the pancreas and brain regions associated with diabetogenesis and antidiabetogenesis were assessed by examining the gene expression profiles of vitamin D receptor, CREB, phospholipase C, insulin receptor and GLUT. This study will establish the anti-diabetogenesis activity of curcumin and vitamin D3 pre-treatment and will attempt to understand the cellular, molecular and neuronal control mechanism in the onset of diabetes.Administration of MLD-STZ to curcumin and vitamin D3 pre-treated rats induced only an incidental prediabetic condition. Curcumin and vitamin D3 pretreated groups injected with MLD-STZ exhibited improved circulating insulin levels and behavioural responses when compared to MLD-STZ induced diabetic group. Activation of beta cell compensatory response induces an increase in pancreatic insulin output and beta cell mass expansion in the pre-treated group. Cell signalling proteins that regulate pancreatic beta cell survival, insulin release, proliferation and differentiation showed a significant increase in curcumin and vitamin D3 pre-treated rats. Marked decline in α2 adrenergic receptor function in pancreas helps to relent sympathetic inhibition of insulin release. Neuronal stimulation of hyperglycemia induced beta cell compensatory response is mediated by escalated signalling through β adrenergic, muscarinic M1 and M3 receptors. Pre-treatment mediated functional regulation of adrenergic and cholinergic receptors, key cell signalling proteins and second messengers improves pancreatic glucose sensing, insulin gene expression, insulin secretion, cell survival and beta cell mass expansion in pancreas. Curcumin and vitamin D3 pre-treatment induced modulation of adrenergic and cholinergic signalling in brain stem, hippocampus and hypothalamus promotes insulin secretion, beta cell compensatory response, insulin sensitivity and energy balance to resist diabetogenesis. Pre-treatment improved second messenger levels and the gene expression of intracellular signalling molecules in brain stem, hippocampus and hypothalamus, to retain a functional neuronal response to hyperglycemia. Curcumin and vitamin D3 protect pancreas and brain regions from oxidative stress by their indigenous antioxidant properties and by their ability to stimulate cellular free radical defence system. The present study demonstrates the role of adrenergic and muscarinic receptor subtypes functional regulation in curcumin and vitamin D3 mediated anti-diabetogenesis. This will have immense clinical significance in developing effective strategies to delay or prevent the onset of diabetes.

Functional genomics of the Drosophila melanogaster X chromosome and the role of DWnt5 during development

The collection of X chromosome insertions (PX) lethal lines, which was isolated from a screen for essential genes on the X chromosome, was characterized by means of cloning the insertion sites, mapping the sites within genomic DNA and determination of the associated reporter gene expresssion patterns. The established STS flanking the P element insertion sites were submitted to EMBL nucleotide databases and their in situ data together with the enhancer trap expression patterns have been deposited in the FlyView database. The characterized lines are now available to be used by the scientific community for a detailed analysis of the newly established lethal gene functions. One of the isolated genes on the X chromosome was the Drosophila gene Wnt5 (DWnt5). From two independent screens, one lethal and three homozygous viable alleles were recovered, allowing the identification of two distinct functions for DWnt5 in the fly. Observations on the developing nervous system of mutant embryos suggest that DWnt5 activity affects axon projection pattern. Elevated levels of DWNT5 activity in the midline cells of the central nervous system causes improper establishment and maintenance of the axonal pathways. Our analysis of the expression and mutant phenotype indicates that DWnt5 function in a process needed for proper organization of the nervous system. A second and novel function of DWnt5 is the control of the body size by regulation of the cell number rather than affecting the size of cells. Moreover, experimentally increased DWnt5 levels in a post-mitotic region of the eye imaginal disc causes abnormal cell cycle progression, resulting in additional ommatidia in the adult eye when compared to wild type. The increased cell number and the effects on the cell cycle after exposure to high DWNT5 levels is the result of a failure to downregulate cyclin B and therefore the unsuccessful establishment of a G1 arrest.

Fidelización, estrategia de perdurabilidad basada en calidad para el FNA

El presente documento hace referencia a la calidad como herramienta para la fidelización y la perdurabilidad en el Fondo Nacional del Ahorro. Para comprender la utilidad de la relación anteriormente descrita se realizará una presentación del FNA, su historia y el propósito que tiene como Institución, además de un breve recorrido por la historia del sector de la vivienda en el país. Por otra parte, se retomarán los conceptos más relevantes relacionados con la calidad, la fidelidad y la perdurabilidad y otros conceptos como la competitividad, la responsabilidad y la estrategia. Por último, se retoma la evaluación de calidad realizada al FNA por parte del ICONTEC en 2010, y a partir de ésta, y considerando además, que en la actualidad el FNA no cuenta con una estrategia de fidelización de clientes, se propone al final del documento el concepto y estrategias de fidelización para la Entidad.

Análisis comparativo de la situación actual de los puertos secos en tres contextos diferentes: Colombia, México, España

El presente trabajo tiene como finalidad analizar y comparar Puertos Secos en tres países diferentes: Colombia, México y España; y con ello determinar las claves o herramientas para el éxito de estos. Para esto, la investigación se llevó a cabo a nivel documental y teórico, abarcando desde documentos de investigación académicos y de entidades supranacionales, hasta documentos de carácter legislativo de diferente orden, para los tres países de estudio, incluyendo estudios privados y herramientas estadísticas propias de los Puertos Secos o sus empresas concesionarias. Gracias a todo esto, se pudo desarrollar el documento con la siguiente estructura: Historia, Referencias, Legislación y Descripción. En la primera etapa, resalta el enfoque de desarrollo portuario y de promoción del tren como medio de transporte y herramienta comercial; en la segunda etapa, se corrobora la dificultad que estos proyectos enfrentan en Colombia por parte del sector público centralista y carente de visión y una precaria participación del sector privado; en la tercera etapa se ratifica esto al ser la principal diferencia el enfoque logístico en la legislación, partiendo de la constitución misma, y su presencia o ausencia en los marcos legales de cada país; y se termina con el resultado de estos elementos previos condensado en elementos tangibles en México y España, y tan solo ilusiones y fracasos para Colombia. Por todo lo anterior, se llega a la conclusión que un Marco Jurídico bien estructurado, una fuerte Inversión del Sector Público y Privado, y una Voluntad Política de largo impulso son las claves para el éxito de estos proyectos, y todo lo que viene ligado a ellos.

"Identification and Diversity of Killer Cell Ig-Like Receptors in Aotus vociferans, a New World Monkey "

Previous BAC clone analysis of the Platyrrhini owl monkey KIRs have shown an unusual genetic structure in some loci. Therefore, cDNAs encoding KIR molecules from eleven Aotus vociferans monkeys were characterized here; tenputative KIR loci were found, some of which encoded atypical proteins such as KIR4DL and transcripts predicted to encode a D0+D1 configuration (AOTVOKIR2DL1*01v1) which appear to be unique in the Aotus genus. Furthermore, alternative splicing was found as a likely mechanism for producing activator receptors in A. vociferans species. KIR proteins from New World monkeys may be split into three new lineages according to domain by domain phylogenetic analysis. Although the A. vociferans KIR family displayed a high divergence among paralogous genes, individual loci were limited in their genetic polymorphism. Selection analysis showed that both constrained and rapid evolution may operate within the AvKIR family. The frequent alternative splicing (as a likely mechanism generating activator receptors), the presence of KIR4DL and KIR2DL1 (D0+D1) molecules and other data reported here suggest that the KIR family in Aotus has had a rapid evolution, independent from its Catarrhini counterparts.from its Catarrhini counterparts.

Convergencia de vías de señalización en un modelo de apoptosis

La sepsis es un evento inflamatorio generalizado del organismo inducido por un daño causado generalmente por un agente infeccioso. El patógeno más frecuentemente asociado con esta entidad es el Staphylococcus aureus, responsable de la inducción de apoptosis en células endoteliales debida a la producción de ceramida. Se ha descrito el efecto protector de la proteína C activada (PCA) en sepsis y su relación con la disminución de la apoptosis de las células endoteliales. En este trabajo se analizó la activación de las quinasas AKT, ASK1, SAPK/JNK y p38 en un modelo de apoptosis endotelial usando las técnicas de Western Blotting y ELISA. Las células endoteliales (EA.hy926), se trataron con C2-ceramida (130μM) en presencia de inhibidores químicos de cada una de estas quinasas y PCA. La supervivencia de las células en presencia de inhibidores químicos y PCA fue evaluada por medio de ensayos de activación de las caspasas 3, 7 y 9, que verificaban la muerte celular por apoptosis. Los resultados evidencian que la ceramida reduce la activación de AKT y aumenta la activación de las quinasas ASK, SAPK/JNK y p38, en tanto que PCA ejerce el efecto contrario. Adicionalmente se encontró que la tiorredoxina incrementa la activación/fosforilación de AKT, mientras que la quinasa p38 induce la defosforilación de AKT.

Consumo de sustancias y noxas prenatales en madres de pacientes con síndrome de Möbius y Möbius Like

Introducción: El síndrome de Möbius y Möbius Like es una entidad poco frecuente caracterizada principalmente por parálisis congénita del VI y VII par craneal. Su etiología es poco conocida aunque se ha asociado a inductores del aborto. El objetivo de este estudio es describir factores anómalos, tóxicos o nocivos que hayan estado presentes en el embarazo de las madres de estos pacientes. Metodología: se realizó una encuesta auto-diligenciable a 15 madres de pacientes con el diagnóstico, indagando sobre condiciones anómalas y/o exposicionales del embarazo, el padre y el ambiente. Resultados: Las madres se encontraban entre los 16 y 34 años al momento de quedar embarazadas, en su mayoría eran solteras, estudiantes y sin planes de embarazo. Once en total usaron algún medicamento y/o sustancias durante la gestación; seis de ellas Misoprostol (40%). Las otras sustancias utilizadas incluyeron: alternativas, cigarrillo, alcohol, ibuprofeno, anticonceptivos, otros. Como anomalías del periodo prenatal se reportaron sangrado activo y/o amenaza de aborto, infección, exposición a químicos ambientales y enfermedad materna activa. Las condiciones paternas descritas fueron alcoholismo y/o drogadicción, enfermedad y edad ≥ 40 años en bajo porcentaje. Conclusión: El síndrome de Möbius y Möbius Like es una patología poco frecuente de la cual aún se debe seguir investigando sobre su etiología, para plantear posibles medidas de prevención.

Vida y Muerte Empresarial. Caso de estudio Jeans and Jackets.

Dentro de este estudio de caso se busca identificar las posibles causas por las cuales una empresa de alto prestigio y reconocimiento por los consumidores colombianos, como lo era Jeans and Jackets, luego de treinta (30) años de funcionamiento se vio en la necesidad de acogerse a la Ley de Reestructuración Económica (Ley 550 de 1999) con el fin de reestructurar sus pasivos en un momento de crisis global que fue impredecible para muchas compañías. Desde el principio, el “Core Business” de Jeans and Jackets era la venta de prendas sofisticadas y de alta calidad a los jóvenes, especialmente en la capital de la República, con el fin de convertirse en la marca líder de este segmento de la industria. Este estudio de caso pretende identificar cuáles fueron las decisiones estratégicas implementadas por parte de la alta gerencia de la compañía en el contexto mencionado anteriormente que llevaron a la empresa a una crisis de liquidez. La metodología utilizada para el desarrollo de este estudio de caso se basa en variables cualitativas que permitan realizar un análisis profundo y la indagación sobre el fenómeno de morbilidad empresarial; De la misma manera se utilizan variables cuantitativas para observar la situación de la empresa financieramente y el desempeño económico de la misma.

Select-divide-and-conquer method for large-scale configuration interaction

A select-divide-and-conquer variational method to approximate configuration interaction (CI) is presented. Given an orthonormal set made up of occupied orbitals (Hartree-Fock or similar) and suitable correlation orbitals (natural or localized orbitals), a large N-electron target space S is split into subspaces S0,S1,S2,...,SR. S0, of dimension d0, contains all configurations K with attributes (energy contributions, etc.) above thresholds T0={T0egy, T0etc.}; the CI coefficients in S0 remain always free to vary. S1 accommodates KS with attributes above T1≤T0. An eigenproblem of dimension d0+d1 for S0+S 1 is solved first, after which the last d1 rows and columns are contracted into a single row and column, thus freezing the last d1 CI coefficients hereinafter. The process is repeated with successive Sj(j≥2) chosen so that corresponding CI matrices fit random access memory (RAM). Davidson's eigensolver is used R times. The final energy eigenvalue (lowest or excited one) is always above the corresponding exact eigenvalue in S. Threshold values {Tj;j=0, 1, 2,...,R} regulate accuracy; for large-dimensional S, high accuracy requires S 0+S1 to be solved outside RAM. From there on, however, usually a few Davidson iterations in RAM are needed for each step, so that Hamiltonian matrix-element evaluation becomes rate determining. One μhartree accuracy is achieved for an eigenproblem of order 24 × 106, involving 1.2 × 1012 nonzero matrix elements, and 8.4×109 Slater determinants

A human ribonuclease induces apoptosis associated with p21WAF1/CIP1 induction and JNK inactivation

Ribonucleases are promising agents for use in anticancer therapy. Among the different ribonucleases described to be cytotoxic, a paradigmatic example is onconase which manifests cytotoxic and cytostatic effects, presents synergism with several kinds of anticancer drugs and is currently in phase II/III of its clinical trial as an anticancer drug against different types of cancer. The mechanism of cytotoxicity of PE5, a variant of human pancreatic ribonuclease carrying a nuclear localization signal, has been investigated and compared to that of onconase. Methods: Cytotoxicity was measured by the MTT method and by the tripan blue exclusion assay. Apoptosis was assessed by flow cytometry, caspase enzymatic detection and confocal microscopy. Cell cycle phase analysis was performed by flow cytometry. The expression of different proteins was analyzed by western blot.n Results: We show that the cytotoxicity of PE5 is produced through apoptosis, that it does not require the proapoptotic activity of p53 and is not prevented by the multiple drug resistance phenotype. We also show that PE5 and onconase induce cell death at the same extent although the latter is also able to arrest the cell growth. We have compared the cytotoxic effects of both ribonucleases in the NCI/ADR-RES cell line by measuring their effects on the cell cycle, on the activation of different caspases and on the expression of different apoptosis- and cell cycle-related proteins. PE5 increases the number of cells in S and G2/M cell cycle phases, which is accompanied by the increased expression of cyclin E and p21WAF1/CIP1 together with the underphosphorylation of p46 forms of JNK. Citotoxicity of onconase in this cell line does not alter the cell cycle phase distribution and it is accompanied by a decreased expression of XIAP. Conclusions: We conclude that PE5 kills the cells through apoptosis associated with the p21WAF1/CIP1 induction and the inactivation of JNK. This mechanism is significantly different from that found for onconase

Estudo in vivo sobre a influência do fototipo na resposta da pele humana ao contacto com lauril sulfato de sódio

O Lauril Sulfato de Sódio (LSS) é um tensioactivo aniónico utilizado em muitas formas farmacêuticas, que apresenta, no entanto, algum potencial de irritação. Também por esse motivo o LSS é utilizado como agente provocador em diversos micrométodos de exploração in vivo da fisiopatologia da pele. Factores como a idade, sexo, hidratação da pele, região anatómica, afectam a resposta da pele ao contacto com LSS, O objectivo deste estudo foi estudar a influência do fototipo na recuperação da integridade da pele humana ao contacto com LSS. Após selecção dos voluntários (n=12) com base nos seus fototipos (Grupo I : Fototipo III-IV e Grupo II: Fototipo V-VI) foi aplicado um penso contendo uma solução de LSS a 2% no antebraço, durante 24h(D0. Após remoção do penso, os voluntários foram sujeitos (D1,D2,D7) a exame dermatológico e à medição das variáveis biométricas: perda de água trans-epidermica, hidratação (por 2 métodos complementares) grau de eritema e fluxo sanguíneo local. Os resultados mostram que existem diferenças entre os dois grupos para a PTEA, LDF e grau de eritema, sugerindo uma maior susceptibilidade para os fototipos mais claros e uma maior rapidez de recuperação para os fototipos mais elevados.

A atitude dos alunos face à inclusão dos seus pares com deficiência

RESUMO: A escola actual encontra-se perante o desafio de responder com afectividade às necessidades educativas especiais de uma população cada vez mais heterogénea, onde se adopte um modelo de atendimento adequado a cada um. Neste contexto, consideramos os alunos, os professores e os encarregados de educação elementos chave de todo o processo, sobre os quais recaem responsabilidades acrescidas na concretização da filosofia inclusiva. O presente estudo tem como objectivo averiguar a atitude dos alunos face à inclusão dos seus pares com deficiência, determinando o modo como estes percepcionam as atitudes dos professores e dos pais face à inclusão de alunos com NEE de carácter permanente, vantagens e desvantagens da inclusão de alunos com NEE de carácter permanente e a cooperação entre alunos com e sem deficiência, tendo em conta a tipologia da deficiência (motora e mental). No caso do nosso estudo, contámos com a participação de 520 alunos (N= 270 género feminino e N=250 do género masculino), uma amostra distribuída pelo 2ºciclo, 3º ciclo e secundário dos distritos de Setúbal e Lisboa. A recolha de dados concretizou-se pela aplicação do AID – EF, questionário da autoria de Ramos Leitão, 2011.Esta metodologia de recolha e tratamento de informação permitiu-nos concluir que, na opinião dos alunos ditos normais a atitude dos professores face à inclusão de alunos com NEE de carácter permanente (dimensão d1), não varia em função da tipologia da deficiência (deficiência motora e mental). Da mesma forma, não foram encontradas diferenças significativas entre os dois grupos (deficiência motora e mental), na opinião dos alunos ditos normais, no que respeita às vantagens da inclusão dos alunos com NEE de carácter permanente (dimensão d2). Na opinião dos alunos ditos normais os resultados demonstraram que a cooperação entre alunos com e sem deficiência (dimensão d3), varia em função da tipologia da deficiência (deficiência motora e mental), apontando esses resultados para uma maior cooperação entre os alunos ditos normais e os seus pares com deficiência mental. Não foram igualmente encontradas diferenças significativas no que respeita às desvantagens da inclusão dos alunos com NEE de carácter permanente (dimensão 4), quando temos em consideração a tipologia da deficiência (deficiência motora e mental). Da mesma forma, na opinião dos alunos normais ditos normais a atitude dos pais face à inclusão de alunos com NEE de carácter permanente (dimensão d5) não variam em função da tipologia da deficiência (deficiência motora e mental).ABSTRACT: Currently the school is faced with the challenge of responding affectionately to the special educational needs of an increasingly heterogeneous population, where a standard model is adopted for each individual. In this context, we consider the students, teachers and guardians, key elements in the whole process, over which fall increased responsibilities in the implementation of the inclusive philosophy. The present study aims to determine the attitude of students towards the inclusion of peers with disabilities, determining how they perceive the attitudes of teachers and parents towards the inclusion of pupils with permanent special education needs, advantages and disadvantages of including students with permanent special education needs and the cooperation between students with and without disabilities, taking into account the type of disability (mental and motor). In the case of our study, we had the participation of 520 students (N = 270 N = female and 250 male), a sample distributed to the 2nd cycle, 3rd cycle and Secondary schools in the districts of Setúbal and Lisbon. The data collected was enabled by the application of the IDA - EF, questionnaire by Ramos Leitão, 2011. This methodology of collecting and processing information allowed us to conclude that, in the opinion of the so-called normal students the teachers´ attitude towards the inclusion of pupils with permanent special education needs (dimension d1) does not vary according to the type of disability (motor and mental). Likewise, no significant differences were found between the two groups (mental and motor), in the opinion of the so-called normal students, with regard to the benefits of the inclusion of pupils with permanent special education needs (dimension d2). In the opinion of the so-called normal students, the results demonstrated that the cooperation between students with and without disabilities (dimension d3), vary depending on the type of disability (mental and motor), these results pointing to a greater cooperation between the so-called normal students and their peers with mental disabilities. There were also no significant differences with respect to the disadvantages of inclusion of pupils with permanent special education needs (dimension d4), when we take into account the type of disability (mental and motor). Similarly, in the opinion of the so-called normal students, the parents´ attitude towards the inclusion of pupils with permanent special education needs (dimension d5) does not vary according to the type of disability (mental and motor).

Mechanisms and dynamics of protein clustering on a solid surface

A methodology for discovering the mechanisms and dynamics of protein clustering on solid surfaces is presented. In situ atomic force microscopy images are quantitatively compared to Monte Carlo simulations using cluster statistics to differentiate various models. We study lysozyme adsorption on mica as a model system and find that all surface-supported clusters are mobile, not just the monomers, with diffusion constant inversely related to cluster size. The surface monomer diffusion constant is measured to be D1∼9×10-16  cm2 s-1, such a low value being difficult to measure using other techniques.

Over expression of Plk1 does not induce cell division in rat cardiac myocytes in vitro

BACKGROUND: Mammalian cardiac myocytes withdraw from the cell cycle during post-natal development, resulting in a non-proliferating, fully differentiated adult phenotype that is unable to repair damage to the myocardium, such as occurs following a myocardial infarction. We and others previously have shown that forced expression of certain cell cycle molecules in adult cardiac myocytes can promote cell cycle progression and division in these cells. The mitotic serine/threonine kinase, Polo-like kinase-1 (Plk1), is known to phosphorylate and activate a number of mitotic targets, including Cdc2/Cyclin B1, and to promote cell division. PRINCIPAL FINDINGS: The mammalian Plk family are all differentially regulated during the development of rat cardiac myocytes, with Plk1 showing the most dramatic decrease in both mRNA, protein and activity in the adult. We determined the potential of Plk1 to induce cell cycle progression and division in cultured rat cardiac myocytes. A persistent and progressive loss of Plk1 expression was observed during myocyte development that correlated with the withdrawal of adult rat cardiac myocytes from the cell cycle. Interestingly, when Plk1 was over-expressed in cardiac myocytes by adenovirus infection, it was not able to promote cell cycle progression, as determined by cell number and percent binucleation. CONCLUSIONS: We conclude that, in contrast to Cdc2/Cyclin B1 over-expression, the forced expression of Plk1 in adult cardiac myocytes is not sufficient to induce cell division and myocardial repair.