12 research outputs found

    Regulation of mammary gland branching morphogenesis by the extracellular matrix and its remodeling enzymes.

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    A considerable body of research indicates that mammary gland branching morphogenesis is dependent, in part, on the extracellular matrix (ECM), ECM-receptors, such as integrins and other ECM receptors, and ECM-degrading enzymes, including matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs). There is some evidence that these ECM cues affect one or more of the following processes: cell survival, polarity, proliferation, differentiation, adhesion, and migration. Both three-dimensional culture models and genetic manipulations of the mouse mammary gland have been used to study the signaling pathways that affect these processes. However, the precise mechanisms of ECM-directed mammary morphogenesis are not well understood. Mammary morphogenesis involves epithelial 'invasion' of adipose tissue, a process akin to invasion by breast cancer cells, although the former is a highly regulated developmental process. How these morphogenic pathways are integrated in the normal gland and how they become dysregulated and subverted in the progression of breast cancer also remain largely unanswered questions

    Failure of SOX9 Regulation in 46XY Disorders of Sex Development with SRY, SOX9 and SF1 Mutations

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    In human embryogenesis, loss of SRY (sex determining region on Y), SOX9 (SRY-related HMG box 9) or SF1 (steroidogenic factor 1) function causes disorders of sex development (DSD). A defining event of vertebrate sex determination is male-specific upregulation and maintenance of SOX9 expression in gonadal pre-Sertoli cells, which is preceded by transient SRY expression in mammals. In mice, Sox9 regulation is under the transcriptional control of SRY, SF1 and SOX9 via a conserved testis-specific enhancer of Sox9 (TES). Regulation of SOX9 in human sex determination is however poorly understood.We show that a human embryonal carcinoma cell line (NT2/D1) can model events in presumptive Sertoli cells that initiate human sex determination. SRY associates with transcriptionally active chromatin in NT2/D1 cells and over-expression increases endogenous SOX9 expression. SRY and SF1 co-operate to activate the human SOX9 homologous TES (hTES), a process dependent on phosphorylated SF1. SOX9 also activates hTES, augmented by SF1, suggesting a mechanism for maintenance of SOX9 expression by auto-regulation. Analysis of mutant SRY, SF1 and SOX9 proteins encoded by thirteen separate 46,XY DSD gonadal dysgenesis individuals reveals a reduced ability to activate hTES.We demonstrate how three human sex-determining factors are likely to function during gonadal development around SOX9 as a hub gene, with different genetic causes of 46,XY DSD due a common failure to upregulate SOX9 transcription

    Democratization of mathematics through Cremona's correspondence with foreign colleagues (1860-1901)

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    Between the 19th and 20th centuries many common traits were shared by national mathematical communities far apart geographically (from the Czech lands to Japan), culturally (from north to south Europe) or as to the dynamism of original research (from Germany to the United States). Societies and journals in the national language were launched, thanks to the widening of the social platform of mathematics and the emergence of a national leadership; the deployment of the state school systems increased mathematical information; and mathematics played a role and received encouragement from the processes of social and economical modernization and development of state institutions. Intellectual competition among nations, much in the spirit of the 19th century, seem to prevail on the early Modern European universalism. A panorama of almost planetary diffusion of Western mathematics resulted from this evolution, and eventually a reinforcement of international circulation of knowledge, which survived two world wars. The collection of letters written to Luigi Cremona conserved at the Sapienza University of Rome throws light on several aspects of this evolution. Letters offer a point of view on the "backstage", in contrast with official proclamations; they show the interplay between national leaders and the circles in the capitals and mathematicians working in isolation; they show a variety of connected activities – research, institutional commitments, and cultural fostering, including translations and textbooks. International dialog grew out of this nebula of initiatives driven by national passion, by philosophical and political convictions; in contrast with the present European trend to entrust the circulations of ideas – and the production of knowledge – to initiatives governed from the top, and standardized (design, funding and assessment), far beyond what would be needed. The edition (in the Académie Internationale d'Histoire des Sciences series "De diversis artibus") has been carried out by a European team directed by Giorgio Israel

    Recent advances of marine ornamental fish larviculture: broodstock reproduction, live prey and feeding regimes, and comparison between demersal and pelagic spawners

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    Marine ornamental fish are a key component of the multimillion‐dollar marine aquarium trade industry, a controversial industry due to current heavy reliance on wild‐collected specimens. Aquaculture of marine ornamental fish is considered as a sustainable alternative, but it is still in the early stage of development. This review focuses on the current state of marine ornamental fish aquaculture, by covering topics on reef fish reproductive biology in captivity, traditional and novel live feeds, feeding regimes and visual environment in larviculture. Where possible, major differences between demersal and pelagic spawners are compared and discussed. Overall, for many ornamental fish species, natural spawning can be achieved in a captive environment without the use of hormone induction; however, sex identification and successful pairing for reef fish species could be a challenge. With the use of both traditional (rotifers and Artemia) and novel live feeds (e.g. marine copepods and ciliates), a range of breakthroughs in larval rearing of both demersal and pelagic spawning ornamental fish species have been achieved in recent years, although larval survival varies. To further improve the larval rearing success of marine ornamental fish, this review suggests that future research should focus on optimizing the use of live feed in terms of both quality and quantity, and establishment of well‐defined species‐specific larval feeding regime, as well as providing appropriate rearing condition through improved manipulation of light conditions and the 'greenwater' techniques in larval rearing
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