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1.
Chaos ; 28(8): 081105, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30180624

RESUMO

We investigate the basin of attraction properties and its boundaries for chimera states in a circulant network of Hénon maps. It is known that coexisting basins of attraction lead to a hysteretic behaviour in the diagrams of the density of states as a function of a varying parameter. Chimera states, for which coherent and incoherent domains occur simultaneously, emerge as a consequence of the coexistence of basin of attractions for each state. Consequently, the distribution of chimera states can remain invariant by a parameter change, and it can also suffer subtle changes when one of the basins ceases to exist. A similar phenomenon is observed when perturbations are applied in the initial conditions. By means of the uncertainty exponent, we characterise the basin boundaries between the coherent and chimera states, and between the incoherent and chimera states. This way, we show that the density of chimera states can be not only moderately sensitive but also highly sensitive to initial conditions. This chimera's dilemma is a consequence of the fractal and riddled nature of the basin boundaries.

2.
Genet Mol Res ; 15(2)2016 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-27323043

RESUMO

Robust adaptation is a critical ability of gene regulatory network (GRN) to survive in a fluctuating environment, which represents the system responding to an input stimulus rapidly and then returning to its pre-stimulus steady state timely. In this paper, the GRN is modeled using the Michaelis-Menten rate equations, which are highly nonlinear differential equations containing 12 undetermined parameters. The robust adaption is quantitatively described by two conflicting indices. To identify the parameter sets in order to confer the GRNs with robust adaptation is a multi-variable, multi-objective, and multi-peak optimization problem, which is difficult to acquire satisfactory solutions especially high-quality solutions. A new best-neighbor particle swarm optimization algorithm is proposed to implement this task. The proposed algorithm employs a Latin hypercube sampling method to generate the initial population. The particle crossover operation and elitist preservation strategy are also used in the proposed algorithm. The simulation results revealed that the proposed algorithm could identify multiple solutions in one time running. Moreover, it demonstrated a superior performance as compared to the previous methods in the sense of detecting more high-quality solutions within an acceptable time. The proposed methodology, owing to its universality and simplicity, is useful for providing the guidance to design GRN with superior robust adaptation.


Assuntos
Redes Reguladoras de Genes , Modelos Genéticos , Algoritmos , Simulação por Computador , Interpretação Estatística de Dados , Cinética
3.
Biosystems ; 116: 43-8, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24333154

RESUMO

In this work we investigate a mathematical model describing tumour growth under a treatment by chemotherapy that incorporates time-delay related to the conversion from resting to hunting cells. We study the model using values for the parameters according to experimental results and vary some parameters relevant to the treatment of cancer. We find that our model exhibits a dynamical behaviour associated with the suppression of cancer cells, when either continuous or pulsed chemotherapy is applied according to clinical protocols, for a large range of relevant parameters. When the chemotherapy is successful, the predation coefficient of the chemotherapic agent acting on cancer cells varies with the infusion rate of chemotherapy according to an inverse relation. Finally, our model was able to reproduce the experimental results obtained by Michor and collaborators [Nature 435 (2005) 1267] about the exponential decline of cancer cells when patients are treated with the drug glivec.


Assuntos
Antineoplásicos/administração & dosagem , Modelos Biológicos , Neoplasias/patologia , Neoplasias/tratamento farmacológico
4.
Blood ; 88(9): 3363-70, 1996 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-8896401

RESUMO

Severe suppression of the hematopoietic system is a major factor in limiting chemotherapy dose escalation. To determine whether a combination of human recombinant granulocyte colony-stimulating factor (G-CSF) and thrombopoietin (TPO) would alter recovery of platelets, red blood cells (RBCs), or neutrophils after myeloablative therapy, myelosuppressed mice were treated with sc injections of TPO (90 micrograms/kg), G-CSF (250 micrograms/kg). TPO plus G-CSF or vehicle and complete blood counts were measured. Marrow and spleen cells were obtained at various times and assayed for erythroid, myeloid, and megakaryocytic progenitors. The prolonged neutropenia in vehicle controls (14 days) was significantly shortened in mice treated with G-CSF or TPO for 14 days. The combination of TPO plus G-CSF further reduced the duration of neutropenia. TPO and TPO plus G-CSF treatments also significantly shortened thrombocytopenia compared to vehicle. Recovery of RBCs was also enhanced in mice treated with either G-CSF or TPO, or the combination. Furthermore, treatment with G-CSF and/or TPO hastened myeloid, erythroid, and megakaryocyte progenitor recovery compared to vehicle controls. These results show that the combination of TPO plus G-CSF acts synergistically to accelerate neutrophil recovery in myelosuppressed mice and does not compromise the platelet or RBC response to TPO therapy.


Assuntos
Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Neutrófilos/patologia , Trombopoetina/administração & dosagem , Animais , Contagem de Células/efeitos dos fármacos , Sinergismo Farmacológico , Feminino , Células-Tronco Hematopoéticas/efeitos dos fármacos , Células-Tronco Hematopoéticas/patologia , Células-Tronco Hematopoéticas/efeitos da radiação , Humanos , Injeções Subcutâneas , Camundongos , Camundongos Endogâmicos BALB C , Neutrófilos/efeitos dos fármacos , Neutrófilos/efeitos da radiação , Proteínas Recombinantes/administração & dosagem , Irradiação Corporal Total
5.
Exp Hematol ; 24(10): 1238-46, 1996 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-8765500

RESUMO

The recent cloning of thrombopoietin (TPO) has allowed us to study its in vivo effects in normal and myelosuppressed mice. Normal Balb/c mice were treated with recombinant human TPO (hTPO) at doses ranging from 1 to 20 kU for 7 days, and complete blood counts (CBCs) and the number of megakaryocytes in the bone marrow were determined. Platelet counts were increased starting on day 5 after mice were treated with hTPO. Platelet counts reached a peak between days 8 and 11 and returned to baseline between days 16 and 20. hTPO treatment increased the number of megakaryocytes in the bone marrow starting on day 3. In normal mice, hTPO treatment did not affect red or white blood cell (RBC or WBC) counts. To test the effects of hTPO in myelosuppressed mice, Balb/c mice were irradiated with 350 cGy total-body irradiation and dosed with 1.2 mg carboplatin, resulting in severe and prolonged thrombocytopenia, anemia, and neutropenia. Treatment with 5-20 kU hTPO for 7 days accelerated the recovery of platelet, RBC, and neutrophil counts in myelosuppressed mice and also significantly improved their nadirs. In addition, bone marrow megakaryocyte numbers recovered 11 days earlier and reticulocyte counts recovered 10 days earlier in hTPO-treated myelosuppressed mice than in controls. These results indicate that TPO can improve hematopoietic recovery in myelosuppressed mice, affecting multiple cell lineages.


Assuntos
Plaquetas/citologia , Medula Óssea/patologia , Eritrócitos/citologia , Hematopoese/efeitos dos fármacos , Neutrófilos/citologia , Trombopoetina/farmacologia , Anemia , Animais , Plaquetas/efeitos dos fármacos , Medula Óssea/efeitos dos fármacos , Medula Óssea/efeitos da radiação , Carboplatina/toxicidade , Eritrócitos/efeitos dos fármacos , Feminino , Hematopoese/fisiologia , Hematopoese/efeitos da radiação , Humanos , Megacariócitos/citologia , Megacariócitos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Neutropenia , Neutrófilos/efeitos dos fármacos , Proteínas Recombinantes/farmacologia , Reticulócitos/citologia , Reticulócitos/efeitos dos fármacos , Trombocitopenia , Irradiação Corporal Total
6.
J Clin Invest ; 96(3): 1683-7, 1995 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-7657840

RESUMO

Thrombopoietin (TPO), the ligand for the receptor protooncogene c-mpl, has been cloned and shown to be the critical regulator of platelet production. Several features of c-Mpl expression, including its presence on erythroid cell lines, and the panmyeloid transformation characteristic of myeloproliferative leukemia (MPL) viral disease led us to investigate whether this receptor-ligand system may play a role in erythropoiesis. We report that although TPO alone did not support the growth of either early or late erythroid progenitors, it acted in synergy with erythropoietin to expand these populations. Moreover, while the effects on erythropoiesis in normal animals were modest, TPO greatly expanded the number of erythroid progenitors and blood reticulocytes and was associated with accelerated red cell recovery in myelosuppressed mice. Together, these data strongly suggest that erythroid progenitors respond to TOP and that this newly cloned cytokine, critical for platelet production, can augment erythropoiesis in states of marrow failure.


Assuntos
Carboplatina/toxicidade , Eritropoese/efeitos dos fármacos , Células-Tronco Hematopoéticas/efeitos dos fármacos , Proteínas de Neoplasias , Trombopoetina/farmacologia , Animais , Medula Óssea/efeitos dos fármacos , Medula Óssea/efeitos da radiação , Células da Medula Óssea , Células Cultivadas , Ensaio de Unidades Formadoras de Colônias , Eritrócitos/efeitos dos fármacos , Eritrócitos/fisiologia , Feminino , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/fisiologia , Camundongos , Camundongos Endogâmicos BALB C , Proteínas Proto-Oncogênicas/metabolismo , Proto-Oncogenes , Receptores de Citocinas/metabolismo , Receptores Imunológicos/metabolismo , Receptores de Trombopoetina , Proteínas Recombinantes/farmacologia , Baço/citologia , Baço/efeitos dos fármacos , Baço/efeitos da radiação , Trombopoetina/metabolismo , Fatores de Tempo , Irradiação Corporal Total
7.
Anat Rec ; 236(3): 449-58, 1993 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-8363050

RESUMO

Recent studies of the urethral glands in the male mouse and rat have suggested that they are testosterone-dependent glands that may be potential sites for secretory immunity in the male genital tract. In the present study we describe the ultrastructural features of these glands in normal mice and provide quantitative data on the sizes of the acinar cells and their organelles in sham-, oil-, and testosterone-treated castrated mice. Acinar cells in urethral glands from normal mice contain numerous secretory granules, prominent Golgi complexes, elongated mitochondria, and an abundance of rough endoplasmic reticulum (RER) with large and dilated cisternae, all of which are features characteristic of secretory cells. In some acinar cells the cisternae of the RER were filled with closely packed, unbranched, straight, tubular structures that were oriented parallel to one another, that radiated from aggregates of dense material, or that were randomly arranged. In other acinar cells the cisternae of the RER showed a network of branching and anastomosing vesicular-like structures whose limiting membranes were occasionally seen in continuity with the membranes of the RER. Secretory acini showed large, unbranched tubules in the acinar lumen. When cut at right angles the large tubules exhibited a distinct fuzzy outer coat with fine projections radiating outwards. The ultrastructure of the acinar cells and the presence of tubules in the lumen suggests that they are engaged in secretion of a tubular protein. Morphometric analysis of acinar cells in the urethral glands showed that the mean volumes of nuclei, cytoplasm, secretory granules, vacuoles, and mitochondria were significantly reduced in castrated mice in comparison to either normal or testosterone-treated castrated mice. This confirms earlier observations that the urethral glands are targets of testosterone.


Assuntos
Glândulas Bulbouretrais/ultraestrutura , Orquiectomia , Testosterona/farmacologia , Animais , Glândulas Bulbouretrais/efeitos dos fármacos , Glândulas Bulbouretrais/imunologia , Tamanho Celular , Grânulos Citoplasmáticos/ultraestrutura , Retículo Endoplasmático/ultraestrutura , Masculino , Camundongos , Camundongos Endogâmicos ICR/anatomia & histologia , Microscopia Eletrônica , Proteínas/metabolismo
8.
Biol Reprod ; 47(6): 1031-9, 1992 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-1493167

RESUMO

The occurrence and possible functions of mucosal immunity in the male urogenital tract have not been extensively investigated. In this study we used immunolabeling to localize secretory component (SC) and immunoglobulin (Ig) A in the urogenital tract of the male mouse. SC was located in the ventral prostate, while SC and IgA plasma cells were both detected in the urethral glands in the pelvic and bulbous portions of the urethra. SC and IgA were not observed elsewhere in the urogenital tract. We also examined the ventral prostate and urethral glands of sham-castrated, oil-treated castrated, and testosterone-treated castrated mice. There was a striking reduction in the size of the ventral prostate and urethral glands in oil-treated castrates compared to the other two groups, based on gross and histological morphology. Morphometric analysis showed that the cell and nuclear sizes of the urethral gland acinar cells were reduced after castration and restored to normal size by testosterone treatment. Androgen receptors (AR) were localized in the nuclei of urethral gland cells by immunocytochemistry using anti-AR antibodies. Labeling of SC and IgA plasma cells was similar in the urethral glands and ventral prostates of sham- and testosterone-treated castrates, but was reduced or absent at these sites in oil-treated castrates. These studies show that the ventral prostate and urethral glands may be sites for secretory immunity in the male murine urogenital tract, and that the urethral glands are targets for testosterone.


Assuntos
Imunoglobulina A/biossíntese , Camundongos Endogâmicos C3H/fisiologia , Plasmócitos/metabolismo , Componente Secretório/biossíntese , Uretra/citologia , Animais , Castração , Masculino , Camundongos , Microscopia de Fluorescência , Receptores Androgênicos/biossíntese , Testosterona/metabolismo , Sistema Urogenital/metabolismo
9.
Endocrinology ; 131(1): 498-508, 1992 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-1612031

RESUMO

Short and long term responses of the rat Leydig cell were studied posthypophysectomy, at times when germ cell degeneration was first prominent (6 days) and after long term regression of the testis (28 days). In the short term, virtually all structural parameters relating to the volume and surface area of the Leydig cell and its subcellular organelles were significantly lowered compared with those in control animals. Exceptions were the volumes of the nucleolus, heterochromatin, and lysosomes and the surface areas of the nucleus. Structural decreases were generally on the order of 2- to 5-fold in the 6-day period. A statistical analysis of the percent decreases in the short term was performed to determine whether any particular structural features were more sensitive to hypophysectomy than any others. In most instances, no particular organelles were decreased compared to others. However, lipid, although not commonly seen in rat Leydig cells, showed significantly greater percent decreases compared with several other organelles, indicating that the small amount of lipid present is rapidly lost (used) in the short term. After long term hypophysectomy, all structural parameters of the Leydig cell were significantly lowered compared with those in pituitary-intact animals. Only a few parameters (mitochondrial volume, cell surface area, and the surface areas of inner and outer mitochondrial membranes and smooth endoplasmic reticulum) showed more significant decreases in the long term compared with the short term hypophysectomized animals. Most organelle volumes and surface areas correlated positively and significantly with serum and tissue testosterone levels; the exceptions were the volumes of the nucleolus, heterochromatin, lipid, and lysosomes. Compared with the pituitary-intact animal, the content of LH receptors expressed per testis and per Leydig cell was significantly lower in both hypophysectomized groups; however, the number of receptors per given area of individual Leydig cell plasma membrane remained unchanged. Overall, data show that the Leydig cell manifests marked structural changes during early spermatogenic dysfunction.


Assuntos
Hipofisectomia , Células Intersticiais do Testículo/ultraestrutura , Receptores do LH/metabolismo , Testosterona/metabolismo , Animais , Nucléolo Celular/ultraestrutura , Heterocromatina/ultraestrutura , Células Intersticiais do Testículo/fisiologia , Metabolismo dos Lipídeos , Lisossomos/ultraestrutura , Masculino , Microscopia Eletrônica , Organelas/ultraestrutura , Ratos , Ratos Endogâmicos , Testosterona/sangue
10.
Tissue Cell ; 24(4): 565-73, 1992.
Artigo em Inglês | MEDLINE | ID: mdl-1440579

RESUMO

Desmosome-gap (D-G) junctions were quantified in relation to germ cell meiosis in the male, specifically to test the hypothesis that the loss of these junctions is related to successful passage of cells through diplotene phase of Meiosis I and the two cytokineses that follow. Such a hypothesis has been proposed as the cause for the resumption of meiosis that occurs prior to ovulation in the female. D-G junctions were quantified in pachytene spermatocytes (stage XII), diplotene spermatocytes (stage XII), secondary spermatocytes (stage XIV) and step 1 spermatids (stage I). These were referred to as the cells of interest as compared with spermatocytes (zygotene spermatocytes, zygotene spermatocytes, pachytene spermatocytes, pachytene spermatocytes) in the same stages, respectively, that served as controls termed control cells. Since gap junctions are not easily recognized in the average sectioned profile of a desmosome-gap junction, only the desmosomal component was quantified. The data were expressed as both numbers and length of junctions per tubule, per cell profile and per unit lineal membrane length to overcome errors inherent in the methodologies utilized. There was no indication that numbers of junctions changed specifically in the cells of interest after passage through diplotene suggesting that these junctions do not have a comparable role in meiotic continuance in the male as proposed for the female. Interestingly, the control cells always showed greater numbers and length of junctions than the cells of interest suggesting that junction may relate more to the period of initiation of meiosis than to its continuance.


Assuntos
Junções Intercelulares/ultraestrutura , Células de Sertoli/ultraestrutura , Espermatócitos/ultraestrutura , Animais , Desmossomos/ultraestrutura , Masculino , Meiose , Ratos , Ratos Sprague-Dawley
11.
Am J Anat ; 192(2): 121-8, 1991 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-1759679

RESUMO

Segments and subsegments are the smallest unit of synchrony thus far described within longitudinal sections of seminiferous tubules. It is known that cells in a clone joined by intercellular bridges are at the same phase of development and are also thought to be units of synchrony. This study was designed to determine if it is possible that the synchrony seen in cells joined by intercellular bridges is the same as that cataloged along the long axis of the seminiferous tubule. In the present study, the maximum number of rat spermatids joined by intercellular bridges (a clone) was obtained. It was hypothesized that if the clone size were larger than the smallest known units of synchrony (segments or subsegments) in the long axis of the seminiferous tubule, then intercellular bridges would most likely govern the synchronous development of segments or subsegments (or finer subdivisions thereof). If the clone size is smaller than the number of cells present in a segment or subsegment, then other factors must govern synchrony in the longitudinal aspect of the tubule. In the determination of spermatid clone size, rat testes were injected with cytochalasin D which opens intercellular bridges of a spermatid clone to produce large symplasts. The number of nuclei in the symplasts was determined from serially sectioned tissue, by drawing nuclei with a camera-lucida, and by counting nuclei. After extensive examination of tubules, the number of spermatids found in the suspected five largest clones observed was determined to be 650, 607, 338, 240, and 177.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Células Germinativas/fisiologia , Espermatogênese/fisiologia , Animais , Células Clonais , Citocalasina D/farmacologia , Masculino , Ratos , Ratos Endogâmicos , Contagem de Espermatozoides , Espermátides/citologia
12.
Am J Anat ; 188(1): 21-30, 1990 May.
Artigo em Inglês | MEDLINE | ID: mdl-2111966

RESUMO

Morphometric studies were performed on 12 mammalian species (degu, dog, guinea pig, hamster, human, monkey, mouse, opossum, rabbit, rat, stallion, and woodchuck) to determine volume density percentage (Vv%), volume (V), and numerical density (Nv) of seminiferous tubule components, especially those related to the Sertoli cell, and to make species comparisons. For most species, measurements were taken both from stages where elongate spermatids were deeply embedded within the Sertoli cell and from stages near sperm release where elongate spermatids were in shallow crypts within the Sertoli cell. Montages, prepared from electron micrographs, were used to determine Vv% of Sertoli cell components in seminiferous tubules. Excluding the tubular lumen, the Sertoli cell occupied from a high of 43.1% (woodchuck) to a low of 14.0% (mouse) of the tubular epithelium. There was a strong negative correlation (r = -0.83; P less than 0.005) of volume occupancy of Sertoli cells with sperm production. Nuclear volume, as determined by serial reconstruction using serial thick sections, ranged from a high of 848.4 microns 3 (opossum) to a low of 273.8 microns 3 (degu). There was no correlation (r = 0.02) of nuclear volume with volume occupancy (Vv%) in the tubule. Sertoli cell volume was determined by point-counting morphometry at the electron-microscope level as the product of the nuclear size and points determined over the entire cell divided by points over the nucleus. Sertoli cell V ranged from 2,035.3 microns 3 (degu) to 7,011.6 microns 3 (opossum) and was highly correlated (r = 0.85; P less than 0.001) with nuclear size. However, there was no significant correlation between the Sertoli cell size (V) and volume occupancy (Vv%; r = 0.13) or sperm production (r = -0.21). Stereological estimates of the numerical density (Nv) of Sertoli cells ranged from a high of 101.9 x 10(6) (monkey) to a low of 24.9 x 10(6) (rabbit) cells per cm3 of testicular tissue. There was no correlation of numerical density of Sertoli cells with sperm production (r = 0.002). A negative correlation was, however, observed between the numerical density of the Sertoli cells and the Sertoli cell size (r = -0.79; P less than 0.002). Data from the present study are compared with those previously published. This is the first study to compare Sertoli cell morphological measurements using unbiased sampling techniques. Morphometric data are provided which will serve as a basis for other morphometric studies.


Assuntos
Mamíferos/anatomia & histologia , Túbulos Seminíferos/citologia , Células de Sertoli/citologia , Testículo/citologia , Animais , Contagem de Células , Núcleo Celular/ultraestrutura , Cães , Cobaias , Haplorrinos , Cavalos , Humanos , Masculino , Marmota , Camundongos , Gambás , Coelhos , Ratos , Ratos Endogâmicos , Roedores , Túbulos Seminíferos/anatomia & histologia , Especificidade da Espécie , Espermatozoides/citologia
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