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Origin and regenerative potential of vertebrate mechanoreceptor-associated stem cells
No full textWidera D, Hauser S, Kaltschmidt C, Kaltschmidt B. Origin and regenerative potential of vertebrate mechanoreceptor-associated stem cells. Anatomy Research International. 2012;2012:1-9.Meissner corpuscles and Merkel cell neurite complexes are highly specialized mechanoreceptors present in the hairy and glabrous skin, as well as in different types of mucosa. Several reports suggest that after injury, such as after nerve crush, freeze injury, or dissection of the nerve, they are able to regenerate, particularly including reinnervation and repopulation of the mechanoreceptors by Schwann cells. However, little is known about mammalian cells responsible for these regenerative processes. Here we review cellular origin of this plasticity in the light of newly described adult neural crest-derived stem cell populations. We also discuss further potential multipotent stem cell populations with the ability to regenerate disrupted innervation and to functionally recover the mechanoreceptors. These capabilities are discussed as in context to cellularly reprogrammed Schwann cells and tissue resident adult mesenchymal stem cells
Brief an Garlieb H. Merkel
No full textMs. 930a, Nr. 18, Bl. 45r-46v
Justus C. Loder. Brief an GarliebH. Merkel, Jena, den 19. Jul[i] 1799
Autora rokraksts / Autograph, vācuval. / Deutsch [2] lpp. / S.
Attēlu numuri / Bildnummern: 930a-018-1, 930a-018-2
Der kurze Brief, der wahrscheinlich von Justus C. Loder stammt, hat vor allem zum Ziel, scheinbar erneut, Merkel einzuladen und die Verbundenheit mit ihm zum Ausdruck zu bringen.Loder, der zu diesem Zeitpunkt Professor für Medizin in Jena war, stammte aus Riga, woraus sich ein besonderes Verhältnis zu Livland und zum Adressaten entstammt haben könnte. Es ist naheliegend, dass Merkel während seines kurzen, aber nicht zu Ende geführten Medizinstudiums, das er in Leipzig begann und in Jena fortführt hat, in Kontakt mit Loder gekommen war. Dieser beglückwünscht Merkel ferner zu seinem Werk „Die Vorzeit Lieflands“ (1798), dessen Lektüre er so genau betrieben habe, dass der Autor ihn daraus examinieren könne.
Interessant ist die Tatsache, dass der Brief an Merkel in Weimar adressiert ist, obwohl unklar ist, ob sich dieser zu dem Zeitpunkt überhaupt dort aufhielt und wie der Brief ansonsten an Merkel gelangt ist.
Atslēgvārdi / Stichwörter
Rückkehr, Bürgerkrone [Kranz aus Eichenlaub für Verdienste um das Gemeinwohl]
Minētās personas / Erwähnten Personen:
Loder, Justus Christian v. (1753-1832); Merkel, Garlieb Helwig(1769-1850); Loder, Charlotte Louise Augusta (1773-?)
Minētās vietas / Erwähnten Orte
Jena, Weimar, Livlan
Integration and democracy in the European Community: the contours of a dilemma
No full textWolfgang Merkel. 30 cm. He presented this paper at a seminar held at the Center for Advanced Study in the Social Sciences of the Juan March Institute in Madrid, on December 4, 1992. - T.p. Bibliography: p. 38-41
Molecular expression associated with vibrissa follicle development and differentiation
No full textThe hair follicle is a complex mini-organ formed as a result of epithelial mesenchymal interactions, provided by three different stem cell sources: epithelial, neural crest and mesenchymal. Hair follicle morphogenesis is directed by a distinct set of molecular signals which are unique to each stage of development. These interactions continue into the adult cycle, represented by periods of rapid growth (anagen), apoptosis driven regression (catagen), a period of relative quiescence (telogen) and shedding of the club hair (exogen). Many of the molecules involved have been elucidated such as Wnts, Bmps, Fgfs, TGF-ßs and Shh amongst others. However, the nature of their regulation and effect on gene expression is still unclear. Id proteins are emerging as powerful players in the transcriptional control of many fundamental biological processes, such as the cell cycle, proliferation and differentiation, apoptosis and lineage commitment. As a result, the expression patterns of Id2 and Ids were investigated by immunocytochemistry in developing and adult vibrissae. Wistar rats aged E14toP4 were used to cover all stages of vibrissae development (stages 0-6+) and 3-6 month old rats for the adult stages. This thesis reports that high Id2 expression was seen in specialised neuroendocrine cells (Merkel cells) of the hair follicle and basal epidermis, confirmed by co-expression of the Merkel cell marker, cytokeratin-20. This post-mitotic Id2 expression continued through postnatal ages and into the adult follicle. Staining with Id3 was characterised by cytoplasmic, basally polarised expression in the epithelia of stage 1-4 follicles. After this stage, expression switched to being nuclear with high levels in many different cell types including the dermal papilla, dermal sheath and outer root sheath, ш and Id3 expression was also investigated in retinole acid induced differentiation of E13.5 and E14 mystacial pads, studying the glandular morphogenesis of vibrissae and the effect on Id protein expression. Ш and Id3 immunoreactivity was cytoplasmic and polarised but no evidence of nuclear staining was seen.Id2 and ИЗ expression in developing vibrissae is reported here for the first time, describing the profiles of these proteins during hair follicle development and differentiation. These findings highlight an important cytoplasmic role for Id proteins in development and may have implications for reciprocal epithelial- mesenchymal interactions, pattern formation and stem cells in the hair follicle
Distinct retinoic gene signatures discriminate Merkel cell polyomavirus-positive from -negative Merkel cell carcinoma cells
No full textLimited molecular knowledge of Merkel cell polyomavirus (MCPyV)-positive and -negative Merkel cell carcinoma (MCC) subsets (MCCP/MCCN) has prevented so far the identification of the MCC origin cell type and, therefore, the development of effective therapies. The retinoic gene signature was investigated in various MCCP, MCCN, and control fibroblast/epithelial cell lines to elucidate the heterogeneous nature of MCC. Hierarchical clustering and principal component analysis indicated that MCCP and MCCN cells were clusterizable from each other and control cells, according to their retinoic gene signature. MCCP versus MCCN differentially expressed genes (n = 43) were identified. Protein-protein interaction network indicated SOX2, ISL1, PAX6, FGF8, ASCL1, OLIG2, SHH, and GLI1 as upregulated hub genes and JAG1 and MYC as downregulated hub genes in MCCP compared to MCCN. Numerous MCCP-associated hub genes were DNA-binding/-transcription factors involved in neurological and Merkel cell development and stemness. Enrichment analyses indicated that MCCP versus MCCN differentially expressed genes predominantly encode for to DNA-binding/-transcription factors involved in development, stemness, invasiveness, and cancer. Our findings suggest the neuroendocrine origin of MCCP, by which neuronal precursor cells could undergo an MCPyV-driven transformation. These overarching results might open the way to novel retinoid-based MCC therapies
Merkel Cell Polyomavirus and Merkel Cell Carcinoma
No full textMerkel cell carcinoma (MCC) is a rare, highly aggressive neuroendocrine skin cancer. More than 80% of MCC have Merkel cell polyomavirus (MCPyV) clonally integrated into the human genome (VP-MCC) while the remaining 20% are virus negative (VN-MCC) but linked with chronic exposure to UV sunlight. MCC is particularly associated with immune suppression with 8-48 folds increase in incidence in immunosuppressive conditions. Another hallmark of VPMCC is expression of a truncated variant of one of MCPyV’s oncoproteins, i.e. large T-antigen. This thesis aims to study the role of the oncoproteins of MCPyV on inflammatory mediator regulation contributing to MCC development and on non-MCC tumor initiation and/or development. This knowledge will provide a better understanding of MCPyV-induced MCC, a prerequisite for developing novel therapeutic approaches. We have found that MCPyV fulllength large T-antigen inhibited while truncated large T antigen stimulated both early and late promoters activities of MCPyV. We have also observed that MCPyV oncoproteins upregulated CCL17/TARC and IL-33 expression in MCC. CCL17/TARC is a chemokine that helps in recruitment of regulatory T cells while IL-33 is IL-1 family member cytokine that creates immunosuppressive and pro-tumorigenic microenvironment, respectively. Human MCC tissues showed a strong staining of CCL17/TARC, CCR4, IL-33, ST2/IL1RL1 and IL1RAcP in both VP- and VN-MCC. Recent findings reported MCPyV co-infection with high-risk human papilloma virus (HR-HPV) -positive cervical cancers. We demonstrated that MCPyV oncoproteins also increase expression of HPV16/18 E6 and E7 expression that are linked with cervical cancer. Taken together, our studies have highlighted critical role of inflammatory mediators associated with MCC development. So, targeting inflammatory signaling pathways could be a better option for treating MCC
Epigenetic Dysregulations in Merkel Cell Polyomavirus-Driven Merkel Cell Carcinoma
No full textMerkel cell polyomavirus (MCPyV) is a small DNA virus with oncogenic potential. MCPyV is the causative agent of Merkel Cell Carcinoma (MCC), a rare but aggressive tumor of the skin. The role of epigenetic mechanisms, such as histone posttranslational modifications (HPTMs), DNA methylation, and microRNA (miRNA) regulation on MCPyV-driven MCC has recently been highlighted. In this review, we aim to describe and discuss the latest insights into HPTMs, DNA methylation, and miRNA regulation, as well as their regulative factors in the context of MCPyV-driven MCC, to provide an overview of current findings on how MCPyV is involved in the dysregulation of these epigenetic processes. The current state of the art is also described as far as potentially using epigenetic dysregulations and related factors as diagnostic and prognostic tools is concerned, in addition to targets for MCPyV-driven MCC therapy. Growing evidence suggests that the dysregulation of HPTMs, DNA methylation, and miRNA pathways plays a role in MCPyV-driven MCC etiopathogenesis, which, therefore, may potentially be clinically significant for this deadly tumor. A deeper understanding of these mechanisms and related factors may improve diagnosis, prognosis, and therapy for MCPyV-driven MCC
Abstract 1375: Paranuclear retention of c-KIT by Merkel cell polyomavirus large T-antigen suppresses autophagy through interaction with Beclin 1 essential for Merkel cell carcinoma cell survival
No full textAbstract Merkel cell carcinoma (MCC) is a very aggressive skin cancer most commonly caused by Merkel cell polyomavirus (MCPyV). While the strong expression of the human proto-oncogene c-KIT in MCC is well established, the functional relevance of this expression is unknown. Here, we demonstrate that paranuclear presence of c-KIT suppresses autophagy which is essential for maintenance of MCC cells. Specifically, after its phosphorylation, c-KIT traffics by clathrin-dependent endocytosis to late endosomes where it is sequestered in the paranuclear compartment by the MCPyV-encoded large transforming antigen (LT) via its Vam6p binding site, which also blocks c-KIT's lysosomal degradation. In this paranuclear compartment, c-KIT interacts directly with both the BH3 and the evolutionarily conserved domain (ECD) of Beclin 1, decreasing its binding to VPS34 and increasing its binding to BCL2, resulting in suppression of autophagy. Indeed, silencing of c-KIT induces autophagy and apoptosis in MCPyV-positive MCC cell lines. It is noteworthy that the positive feedback loop of LT and c-KIT also applies in the reverse direction, as LT is degraded via autophagy. This notion explains why an autophagy-inducing peptide efficiently induces apoptosis-independent cell death and inhibits tumor growth of MCC xenografts in mice. In conclusion, we identified a novel mechanism of MCPyV LT to suppress autophagy through sequestering and stabilizing c-KIT in the paranuclear compartment, which is mandatory to maintain the oncogenic phenotype of MCC cells. Autophagy-inducing agents therefore represent a therapeutic strategy for patients with advanced MCPyV-associated MCC. Citation Format: Hao Shi, Yajie Yang, Catharina Larsson, Weng-Onn Lui. Paranuclear retention of c-KIT by Merkel cell polyomavirus large T-antigen suppresses autophagy through interaction with Beclin 1 essential for Merkel cell carcinoma cell survival [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1375
Cooling tower performance : a critical evaluation of the Merkel assumptions
No full textCITATION: Kloppers, J. C. & Kroger, D. G. 2004. Cooling tower performance : a critical evaluation of the Merkel assumptions. R&D Journal, 20(1):24-29.The original publication is available at https://www.saimeche.org.za/page/RDJournalThe simpltfying assamptions made by Merkel ure
critically evaluated by comparing the Merkel analysis
to the more rigoroas Poppe analysis of cooling
tower performnnce. It is shown that the uccaracy of
the Merkel method can be greatly improved, under
certain cooling tower operating conditions, to predict
cooling tower performance within very close
tolerance of the performance predicted by the Poppe
method, It is shown under which tower operating
conditions the thermal tower performance, according
to the Merkel method, is likely to diffe, from
the performance predicted by the Poppe method.Publisher's versio
Merkel cell carcinoma of the auriche.
No full textAbstract: Merkel cell carcinoma is a rare malignant tumor of the skin. The face and extremities are the most common locations. We present a case of Merkel cell carcinoma of the auricle in a 93-year-old man subsequently treated with surgery and radiotherapy. The clinical features, prognosis, and treatment of the Merkel cell carcinoma are discussed. (c) 2005 Elsevier Inc. All rights reserve
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