Neurofibromatosis type 1 (NF1) is a cancer predisposition disorder that results from inactivation of the tumor-suppressor Neurofibromin, a negative regulator of RAS signaling. NF1 patients present with a wide range of clinical manifestations and the tumor with highest prevalence is cutaneous neurofibroma (cNF). Most patients harboring cNF suffer greatly from the burden of those tumors, which have no effective medical treatment. Ironically, none of the numerous NF1 mouse models developed so far recapitulate cNF. Here, we discovered that Hoxb7 serves as a lineage marker to trace the developmental origin of cNF neoplastic cells. Ablating Nf1 in the Hoxb7 lineage faithfully recapitulates both human cutaneous and plexiform neurofibroma. In addition, we discovered that modulation of the Hippo pathway acts as a “modifier” for neurofibroma tumorigenesis. This mouse model opens the doors for deciphering the evolution of cNF to identify effective therapies, where none exist today.

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Dry eye disease affects over 16 million adults in the U.S. and the majority of cases are due to Meibomian gland dysfunction. Unfortunately, the identity of the stem cells involved in Meibomian gland development and homeostasis are not well-elucidated. Here, we report that loss of Krox20, a zinc-finger transcription factor involved in development of ectoderm-derived tissues, or deletion of KROX20-expressing epithelial cells disrupts Meibomian gland formation and homeostasis, leading to dry eye disease secondary to Meibomian gland dysfunction. Ablation of Krox20-lineage cells in adult mice also resulted in dry eye disease, implicating Krox20 in homeostasis of the mature Meibomian gland. Lineage tracing and expression analyses revealed a restricted KROX20 expression pattern in the ductal areas of the Meibomian gland, although Krox20-lineage cells generate the full, mature Meibomian gland. This suggests that KROX20 marks a stem/progenitor cell population that differentiates to generate the entire Meibomian gland. Our Krox20 mouse models provide a powerful system that delineated the identity of stem cells required for Meibomian gland development and homeostasis, and can be used to investigate the factors underlying these processes. They are also robust models of Meibomian gland dysfunction-related dry eye disease with a potential for use in pre-clinical therapeutic screening.

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From lotus receptacle (seed pod of NeJUmbo rmcifera Gcrerfn.), four alkaloids, nuciferine (I), N-nornuciferine (VIII), oxoushinsunine (IX) and N-norasmepavine (X) were isolated. Identification The genus Nelumbo (Nymphaeaceae) produces a lot of aIkaIoids including aporphine, oxoaporphine, proaporphine, tetrahydroisoquinoline, benzyltetrahydroisoquinoline and biscoclaurine*-J). In the course of continuing search for alkaloids from Formosan NeZumbo nucifeera Gaertn., the ethanol extracts of leaf, petiole and seed-embryo were investigated respectively to isoIate seven alkaloids, nuciferine (I), roemerine (II), 0-nornuciferine @ I ) , isoleinsinine (IV), neferine (V), lotusine (VI) and methylcorypalline CVII), reported in the earlier paperso--". Up to nov, no studies on the chemical principles of lotus receptacle has been reported. In this paper, we wish to describe the isolation and characterization of alkaloids from receptacle in order to clarify the occurrence and difference of chemical constituents in each part of the whole plant. The receptacle or seed pod of Iotus is called "Lien-fang" (BE?) in Chinese. After the seeds have been removed, it looks something like the nozzle Of a garden sprinkler. Its medicinal action is regarded as antihemorrhagic and it is also empIoyed to promote the expulsion of the afterbirth and in watery decoction to counteract the poison o€ deleterious fungi in Chinese drugss). From seed pod, there are four bases (A, B, C and D) obtained from the alcoholic extract. A detailed descriPtion of extraction and isolation procedure was given in the experimental part.