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A GH3-like gene, CcGH3, isolated from Capsicum chinense L. fruit is regulated by auxin and ethylene.

Auxin, which has been implicated in multiple biochemical and physiological processes, elicits three classes of genes (Aux/IAAs, SAURs and GH3s) that have been characterized by their early or primary responses to the hormone. A new GH3-like gene was identified from a suppressive subtraction hybridization (SSH) library of pungent pepper (Capsicum chinense L.) cDNAs. This gene, CcGH3, possessed several auxin- and ethylene-inducible elements in the putative promoter region. Upon further investigation, CcGH3 was shown to be auxin-inducible in shoots, flower buds, sepals, petals and most notably ripening and mature pericarp and placenta. Paradoxically, this gene was expressed in fruit when auxin levels were decreasing, consistent with ethylene-inducibility. Further experiments demonstrated that CcGH3 was induced by endogenous ethylene, and that transcript accumulation was inhibited by 1-methylcyclopropene, an inhibitor of ethylene perception. When over-expressed in tomato, CcGH3 hastened ripening of ethylene-treated fruit. These results implicate CcGH3 as a factor in auxin and ethylene regulation of fruit ripening and suggest that it may be a point of intersection in the signaling by these two hormones.

Arabidopsis↗

Adipocyte differentiation from the inside out.

Improved knowledge of all aspects of adipose biology will be required to counter the burgeoning epidemic of obesity. Interest in adipogenesis has increased markedly over the past few years with emphasis on the intersection between extracellular signals and the transcriptional cascade that regulates adipocyte differentiation. Many different events contribute to the commitment of a mesenchymal stem cell to the adipocyte lineage including the coordination of a complex network of transcription factors, cofactors and signalling intermediates from numerous pathways.

Adipocytes↗

Primary cutaneous carcinosarcoma arising in a patient with nevoid basal cell carcinoma syndrome.

BACKGROUND: Nevoid basal cell carcinoma syndrome (NBCC) is an autosomal dominant disorder characterized by developmental abnormalities and neoplasms including basal cell carcinoma (BCC) and sarcomas (i.e. leiomyosarcoma, rhabdomyosarcoma, and fibrosarcoma). Primary cutaneous carcinosarcoma (PCC), a rare tumor composed of malignant epithelial and mesenchymal components, has never been previously described in association with this syndrome. CASE REPORT: A 61-year-old Hispanic man with a history of NBCC presented with a 4 cm nodule on the right proximal medial thigh. PATHOLOGIC FINDINGS: Areas of typical BCC merged with intersecting fascicles of large atypical spindle cells that stained for vimentin and were negative for actin, desmin, CD-34, and S-100 protein. Scattered bizarre solitary cytokeratin-positive epithelioid cells were embedded within the fibrocytic proliferation. CONCLUSIONS: Several carcinosarcomas have been reported to contain BCC as the malignant epithelial component, but to our knowledge, this is the first report of PCC associated with NBCC. Mutation in patched tumor suppressor gene on chromosome 9q occurs in BCCs of NBCC, and aberrancies on chromosome 9q are also reported in some carcinosarcomas. It is possible that the known genetic defect on chromosome 9 in this patient contributed to the development of carcinosarcoma. Bhattacharjee P, Leffell D, McNiff JM. Primary cutaneous carcinosarcoma arising in a patient with nevoid basal cell carcinoma syndrome.

Basal Cell Nevus Syndrome↗

[Populations and heredity: at an intersection].

A population can be defined using different criteria, for example criteria of a geographical or medical nature. Researchers, or even patients and journalists, have complementary or contradictory views of this notion. Heredity is not only a biological fact; it is also a social fact. A systematic study of the genealogical corpus of a group of patients makes it possible to evaluate the soundness of the phenotypic criterion used to define a subpopulation that shares a common pathological heredity.

Genetics↗

ETHYLENE RESPONSE FACTOR1 integrates signals from ethylene and jasmonate pathways in plant defense.

Cross-talk between ethylene and jasmonate signaling pathways determines the activation of a set of defense responses against pathogens and herbivores. However, the molecular mechanisms that underlie this cross-talk are poorly understood. Here, we show that ethylene and jasmonate pathways converge in the transcriptional activation of ETHYLENE RESPONSE FACTOR1 (ERF1), which encodes a transcription factor that regulates the expression of pathogen response genes that prevent disease progression. The expression of ERF1 can be activated rapidly by ethylene or jasmonate and can be activated synergistically by both hormones. In addition, both signaling pathways are required simultaneously to activate ERF1, because mutations that block any of them prevent ERF1 induction by any of these hormones either alone or in combination. Furthermore, 35S:ERF1 expression can rescue the defense response defects of coi1 (coronative insensitive1) and ein2 (ethylene insensitive2); therefore, it is a likely downstream component of both ethylene and jasmonate signaling pathways. Transcriptome analysis in Col;35S:ERF1 transgenic plants and ethylene/jasmonate-treated wild-type plants further supports the notion that ERF1 regulates in vivo the expression of a large number of genes responsive to both ethylene and jasmonate. These results suggest that ERF1 acts downstream of the intersection between ethylene and jasmonate pathways and suggest that this transcription factor is a key element in the integration of both signals for the regulation of defense response genes.

Arabidopsis↗

Genetics and physiology of proline utilization in Saccharomyces cerevisiae: enzyme induction by proline.

Proline is converted to glutamate in the yeast Saccharomyces cerevisiae by the sequential action of two enzymes, proline oxidase and delta 1-pyrroline-5-carboxylate (P5C) dehydrogenase. The levels of these enzymes appear to be controlled by the amount of proline in the cell. The capacity to transport proline is greatest when the cell is grown on poor nitrogen sources, such as proline or urea. Mutants have been isolated which can no longer utilize proline as the sole source of nitrogen. Mutants in put1 are deficient in proline oxidase, and those in put2 lack P5C dehydrogenase. The put1 and put2 mutations are recessive, segregate 2:2 in tetrads, and appear to be unlinked to one another. Proline induces both proline oxidase and P5C dehydrogenase. The arginine-degradative pathway intersects the proline-degradative pathway at P5C. The P5C formed from the breakdown of arginine or ornithine can induce both proline-degradative enzymes by virtue of its conversion to proline.

Enzyme Induction↗

Temporal profiles of nuclear receptor gene expression reveal coordinate transcriptional responses during Drosophila development.

The recent completion of the Drosophila genome sequence revealed 21 members of the nuclear receptor superfamily. Many of these genes are transcriptionally regulated by the steroid hormone ecdysone and play a role during the onset of metamorphosis, including the EcR/USP ecdysone receptor heterodimer. As a first step toward a genomic analysis of this gene family, we have characterized the temporal patterns of expression for all detectable nuclear receptor transcripts throughout major ecdysone-regulated developmental transitions in the life cycle: embryogenesis, a larval molt, puparium formation, and the prepupal-pupal transition. We find an unexpected close temporal relationship between DHR3, E75B, and betaFTZ-F1 expression after each major ecdysone pulse examined, reflecting the known cross-regulatory interactions of these genes in prepupae and suggesting that they act together at other stages in the life cycle. In addition, E75A, E78B, and DHR4 are expressed in a reproducible manner with DHR3, E75B, and betaFTZ-F1, suggesting that they intersect with this regulatory cascade. Finally, we find that known ecdysone-inducible primary-response transcripts are coordinately induced at times when the ecdysteroid titer is low, implying the existence of novel, as yet uncharacterized, temporal signals in Drosophila.

Animals↗

Assisted reproduction: who qualifies?

Assisted reproductive technologies (ARTs) have been the focus of considerable debate in which a range of social issues has been addressed, yet the question of who is eligible for ART, who can get access, who is excluded and by what means, has received little attention in comparison with other issues. In Australia social policies presently exist in some (but not all) states which address this question, however several recently publicised cases have highlighted the need for an examination of inclusion/exclusion practices from a social justice perspective. This paper seeks to explore the issue of access and eligibility for ART with a particular interest in exposing the contradictions, inconsistencies and assumptions inherent in arguments put forward for particular inclusions and exclusions. It is my contention that social policy relating to criteria for eligibility and access to ART invests the medical profession with a gatekeeping role which holds the power to define and create different classes of women. Moreover, discourses of 'medical indication' and the 'best interests of children' intersect to inscribe a form of discursive eugenic practice which in turn sustains sexism and discrimination against childless women. Finally, this paper seeks to alert the nursing profession to requirements emerging from social policy which influence practice, interfere in client-nurse relationships, and may ultimately result in unethical conduct.

Adult↗

Leiomyoma with atypical cells (atypical leiomyoma) in the larynx.

AIMS: To report and confirm the identity of laryngeal leiomyoma with many atypical cells, which has not been described previously. CASE DETAILS: A 53-year-old man was found to have a polypoid tumour in the larynx. The tumour was excised and the patient has shown no evidence of recurrence over a 5-year period. The tumour tissue comprised intersecting fascicles of spindle-shaped tumour cells with blunt-ended nuclei. Many of the tumour cells showed marked atypia. Mitotic activity in the tumour cells was low, and no atypical mitoses were found. Immunohistochemically, the tumour cells were positive for smooth muscle actin and desmin. p53 overexpression was identified in many tumour cells; the p53 labelling index of the tumour cells was 45%. DNA from tumour cells showed loss of heterozygosity on chromosomes 3p, 5q, 8p, 9p, 10q, 17p and 18q. We diagnosed this case as leiomyoma with atypical cells (atypical leiomyoma) based on the clinical course and pathological and genetic findings. CONCLUSION: This is the first report of atypical leiomyoma in the larynx. The clinical course and pathological findings indicate that although laryngeal atypical leiomyoma contains numerous atypical cells, it is a benign neoplasm.

Actins↗

Telomere induced senescence: end game signaling.

The telomere-based model of cell aging has proven to among been among the most enduring hypotheses in cell biology. This model, suggesting that the gradual loss of telomere sequences during the proliferation of cultured human somatic cells imposes a barrier on cellular replicative potential, has been strongly supported by recent genetic and biochemical studies. In addition, evidence implicating telomere dynamics in organismal ageing and cancer progression in vivo suggest that such a process is likely to have considerable physiological relevance in homeostasis and disease. What is the sensing mechanism for shortened telomeres and what is the molecular basis for the ensuing checkpoint response? Moreover, what is the outcome when such failsafe mechanisms are lost? Here we will review the signaling pathways that are induced by alterations in telomere length and integrity and illustrate how these processes provoke downstream effects on cell proliferation and survival. In addition, we discuss how the telomere-induced pathways intersect with the DNA damage response and document how the failure in either process results in unrestrained chromosomal instability.

Aging↗

Kowalevsky, comparative evolutionary embryology, and the intellectual lineage of evo-devo.

Alexander Kowalevsky was one of the most significant 19th century biologists working at the intersection of evolution and embryology. The reinstatement of the Alexander Kowalevsky Medal by the St. Petersburg Society of Naturalists for outstanding contributions to understanding evolutionary relationships in the animal kingdom, evolutionary developmental biology, and comparative zoology is timely now that Evo-devo has emerged as a major research discipline in contemporary biology. Consideration of the intellectual lineage of comparative evolutionary embryology explicitly forces a reconsideration of some current conceptions of the modern emergence of Evo-devo, which has tended to exist in the shadow of experimental embryology throughout the 20th century, especially with respect to the recent success of developmental biology and developmental genetics. In particular we advocate a sharper distinction between the heritage of problems and the heritage of tools for contemporary Evo-devo. We provide brief overviews of the work of N. J. Berrill and D. T. Anderson to illustrate comparative evolutionary embryology in the 20th century, which provides an appropriate contextualization for a conceptual review of our research on the sea urchin genus Heliocidaris over the past two decades. We conclude that keeping research questions rather than experimental capabilities at the forefront of Evo-devo may be an antidote to any repeat of the stagnation experienced by the first group of evolutionary developmental biologists over one hundred years ago and acknowledges Kowalevsky's legacy in evolutionary embryology.

Animals↗

[Fibromatosis of the breast: a clinical, radiological and pathological study of 6 cases].

We describe the clinical, radiological and pathological features of a series of six cases of primary fibromatosis of the breast. Most patients (5 of 6) were women of 22-58 years of age; one case occurred in a 47-year-old man. The fibromatosis of the breast in all cases presented as a monolateral solid nodule, clinically suspicious for malignancy and in three cases was also associated with cutaneous and/or nipple retraction. None of the patients was affected by any genetic disorder characterized by fibromatoses involving multiple sites, including breast. Both echographic and mammographic examinations revealed solid masses with irregular margins but without calcifications, mimicking scirrhous carcinoma. All cases were surgically treated by lumpectomy (4 of 6) or quadrantectomy (2 of 6), and after a follow-up period ranging from 5 months to 13 years all patients are well and disease-free. Histological examination revealed finger-like infiltrating margins entrapping adjacent breast parenchyma and adipose tissue in all cases. The hallmark of the lesion was the presence of bland-looking spindle cells, with a low mitotic index, organized in long sweeping and intersecting fascicles. Three different morphological phases (i.e. proliferative, involutional and residual), identical to those observed in Dupuytren's superficial fibromatosis, variably coexisted in each case. At immunohistochemistry the cells which comprised the lesion exhibited a diffuse expression of vimentin and a heterogeneous immunoreactivity to a-smooth muscle actin, thus confirming their fibro-myofibroblastic nature. No expression of estrogen, progesterone or androgen receptors or of pS2 correlated-estrogen protein was observed. We discuss both the pathogenesis of the mammary fibromatosis, pointing to the fibroblastic cells of the mammary stroma as the putative precursors, and the differential diagnosis versus the bland-looking, monomorphic spindle cell tumor-like or tumorous lesions of the breast.

Adult↗

Automated measurement of Drosophila wings.

BACKGROUND: Many studies in evolutionary biology and genetics are limited by the rate at which phenotypic information can be acquired. The wings of Drosophila species are a favorable target for automated analysis because of the many interesting questions in evolution and development that can be addressed with them, and because of their simple structure. RESULTS: We have developed an automated image analysis system (WINGMACHINE) that measures the positions of all the veins and the edges of the wing blade of Drosophilid flies. A video image is obtained with the aid of a simple suction device that immobilizes the wing of a live fly. Low-level processing is used to find the major intersections of the veins. High-level processing then optimizes the fit of an a priori B-spline model of wing shape. WINGMACHINE allows the measurement of 1 wing per minute, including handling, imaging, analysis, and data editing. The repeatabilities of 12 vein intersections averaged 86% in a sample of flies of the same species and sex. Comparison of 2400 wings of 25 Drosophilid species shows that wing shape is quite conservative within the group, but that almost all taxa are diagnosably different from one another. Wing shape retains some phylogenetic structure, although some species have shapes very different from closely related species. The WINGMACHINE system facilitates artificial selection experiments on complex aspects of wing shape. We selected on an index which is a function of 14 separate measurements of each wing. After 14 generations, we achieved a 15 S.D. difference between up and down-selected treatments. CONCLUSION: WINGMACHINE enables rapid, highly repeatable measurements of wings in the family Drosophilidae. Our approach to image analysis may be applicable to a variety of biological objects that can be represented as a framework of connected lines.

Animals↗

Purification and kinetic analysis of eIF2B from Saccharomyces cerevisiae.

Eukaryotic translation initiation factor 2B (eIF2B) is the heteropentameric guanine nucleotide exchange factor for translation initiation factor 2 (eIF2). Recent studies in the yeast Saccharomyces cerevisiae have served to characterize genetically the exchange factor. However, enzyme kinetic studies of the yeast enzyme have been hindered by the lack of sufficient quantities of protein suitable for biochemical analysis. We have purified yeast eIF2B and characterized its catalytic properties in vitro. Values for K(m) and V(max) were determined to be 12.2 nm and 250.7 fmol/min, respectively, at 0 degrees C. The calculated turnover number (K(cat)) of 43.2 pmol of GDP released per min/pmol of eIF2B at 30 degrees C is approximately 1 order of magnitude lower than values previously reported for the mammalian factor. Reciprocal plots at varying fixed concentrations of the second substrate were linear and intersected to the left of the y axis. This is consistent with a sequential catalytic mechanism and argues against a ping-pong mechanism similar to that proposed for EF-Tu/EF-Ts. In support of this model, our yeast eIF2B preparations bind guanine nucleotides, with an apparent dissociation constant for GTP in the low micromolar range.

Blotting, Western↗

Translocation (X;18) in a biphasic synovial sarcoma with morphologic features of neural differentiation.

The authors report a recurred neoplasm showing distinctive histologic, immunophenotypic, and ultrastructural features characteristic of biphasic synovial sarcoma with neural differentiation. The features include areas with a growth pattern of densely packed spindle cells in irregularly intersecting, broad fascicles, diffuse vimentin and HBA 71 immunoreactivity, expression of S-100 protein, and other neural markers. Moreover, areas with glandular structures and cellular expression of cytokeratin and epithelial membrane antigen were noted. Additionally, areas of neural-like growth pattern were positive for neuron-specific enolase, HNK-1, and protein gene product 9.5. Furthermore, cytogenetic analysis, two-color interphase fluorescence in situ hybridization, and reverse transcription polymerase chain reaction demonstrated the reciprocal translocation between chromosomes X and 18 associated with the different subtypes of tumor cells. The establishment and characterization of the tumor cell line are detailed. This cell line retains the distinct morphologic and genetic characteristics of the original biphasic synovial sarcoma with neural differentiation.

Adult↗

Cellular pathways leading to melanoma differentiation: therapeutic implications.

The induction of differentiation, as evidenced by benign growth characteristics, dendritic morphology, pigmentation capability, and a mature antigenic phenotype, is an attractive theoretical basis for therapy in human melanoma. Melanoma differentiation can be experimentally induced by modulating intracellular pathways involving protein kinase C, tyrosine kinases, and protein kinase A, or by modulating nuclear transcription with retinoids, DNA-damaging agents, and chemotherapeutic drugs. Other experimental differentiating agents include the amino acid tyrosine, histamine receptor antagonists, polyamine antagonists, dimethylsulphoxide, caffeic acid ester, and butyrate. The mechanisms involved in the actions of many of these agents are beginning to be understood and the pathways are often intersecting; cross-talk in the form of negative and positive feedback loops is extensive. Uncoupling of pathways is also seen, with some agents leading to simultaneous increases in both differentiated and transformed characteristics. While clinical benefits of this approach have so far been sparse, greater understanding of the cellular pathways of differentiation may open new therapeutic options in melanoma.

Cell Transformation, Neoplastic↗

A cellular function for the RNA-interference enzyme Dicer in the maturation of the let-7 small temporal RNA.

The 21-nucleotide small temporal RNA (stRNA) let-7 regulates developmental timing in Caenorhabditis elegans and probably in other bilateral animals. We present in vivo and in vitro evidence that in Drosophila melanogaster a developmentally regulated precursor RNA is cleaved by an RNA interference-like mechanism to produce mature let-7 stRNA. Targeted destruction in cultured human cells of the messenger RNA encoding the enzyme Dicer, which acts in the RNA interference pathway, leads to accumulation of the let-7 precursor. Thus, the RNA interference and stRNA pathways intersect. Both pathways require the RNA-processing enzyme Dicer to produce the active small-RNA component that represses gene expression.

Animals↗

Xist and the order of silencing.

X inactivation is the mechanism by which mammals adjust the genetic imbalance that arises from the different numbers of gene-rich X-chromosomes between the sexes. The dosage difference between XX females and XY males is functionally equalized by silencing one of the two X chromosomes in females. This dosage-compensation mechanism seems to have arisen concurrently with early mammalian evolution and is based on the long functional Xist RNA, which is unique to placental mammals. It is likely that previously existing mechanisms for other cellular functions have been recruited and adapted for the evolution of X inactivation. Here, we critically review our understanding of dosage compensation in placental mammals and place these findings in the context of other cellular processes that intersect with mammalian dosage compensation.

Animals↗