Osteoclasts are specialized cells derived from the monocyte/macrophage haematopoietic lineage that develop and adhere to bone matrix, then secrete acid and lytic enzymes that degrade it in a specialized, extracellular compartment. Discovery of the RANK signalling pathway in the osteoclast has provided insight into the mechanisms of osteoclastogenesis and activation of bone resorption, and how hormonal signals impact bone structure and mass. Further study of this pathway is providing the molecular basis for developing therapeutics to treat osteoporosis and other diseases of bone loss.

Osteoclast differentiation and activation

Bevacizumab plus Irinotecan,Fluorouracil,and Leucovorin for Metastatic Colorectal Cancer

We describe the design, construction, and performance of the Sloan Digital Sky Survey telescope located at Apache Point Observatory. The telescope is a modified two-corrector Ritchey-Chretien design with a 2.5 m, f/2.25 primary, a 1.08 m secondary, a Gascoigne astigmatism corrector, and one of a pair of interchangeable highly aspheric correctors near the focal plane, one for imaging and the other for spectroscopy. The final focal ratio is f/5. The telescope is instrumented by a wide-area, multiband CCD camera and a pair of fiber-fed double spectrographs. Novel features of the telescope include the following: (1) A 3° diameter (0.65 m) focal plane that has excellent image quality and small geometric distortions over a wide wavelength range (3000-10,600 A) in the imaging mode, and good image quality combined with very small lateral and longitudinal color errors in the spectroscopic mode. The unusual requirement of very low distortion is set by the demands of time-delay-and-integrate (TDI) imaging. (2) Very high precision motion to support open-loop TDI observations. (3) A unique wind baffle/enclosure construction to maximize image quality and minimize construction costs. The telescope had first light in 1998 May and began regular survey operations in 2000.

https://iopscience.iop.org/article/10.1086/500975/pdf

The 2.5 m Telescope of the Sloan Digital Sky Survey

Catalytic protein subunits of telomerase from the ciliate Euplotes aediculatus and the yeast Saccharomyces cerevisiae contain reverse transcriptase motifs. Here the homologous genes from the fission yeast Schizosaccharomyces pombe and human are identified. Disruption of the S. pombe gene resulted in telomere shortening and senescence, and expression of mRNA from the human gene correlated with telomerase activity in cell lines. Sequence comparisons placed the telomerase proteins in the reverse transcriptase family but revealed hallmarks that distinguish them from retroviral and retrotransposon relatives. Thus, the proposed telomerase catalytic subunits are phylogenetically conserved and represent a deep branch in the evolution of reverse transcriptases.

https://science.sciencemag.org/content/sci/277/5328/955.full.pdf

Telomerase catalytic subunit homologs from fission yeast and human

Telomere Shortening and Tumor Formation by Mouse Cells Lacking Telomerase RNA

A receptor that mediates osteoprotegerin ligand (OPGL)-induced osteoclast differentiation and activation has been identified via genomic analysis of a primary osteoclast precursor cell cDNA library and is identical to the tumor necrosis factor receptor (TNFR) family member RANK. The RANK mRNA was highly expressed by isolated bone marrow-derived osteoclast progenitors and by mature osteoclasts in vivo. Recombinant OPGL binds specifically to RANK expressed by transfected cell lines and purified osteoclast progenitors. Transgenic mice expressing a soluble RANK-Fc fusion protein have severe osteopetrosis because of a reduction in osteoclasts, similar to OPG transgenic mice. Recombinant RANK-Fc binds with high affinity to OPGL in vitro and blocks osteoclast differentiation and activation in vitro and in vivo. Furthermore, polyclonal Ab against the RANK extracellular domain promotes osteoclastogenesis in bone marrow cultures suggesting that RANK activation mediates the effects of OPGL on the osteoclast pathway. These data indicate that OPGL-induced osteoclastogenesis is directly mediated through RANK on osteoclast precursor cells.

https://www.pnas.org/content/pnas/96/7/3540.full.pdf

Tumor necrosis factor receptor family member RANK mediates osteoclast differentiation and activation induced by osteoprotegerin ligand

Handbook of optics

The telomerase ribonucleoprotein catalyzes the addition of new telomeres onto chromosome ends A gene encoding a mammalian telomerase homolog called TP1 (telomerase-associated protein 1) was identified and cloned TP1 exhibited extensive amino acid similarity to the Tetrahymena telomerase protein p80 and was shown to interact specifically with mammalian telomerase RNA Antiserum to TP1 immunoprecipitated telomerase activity from cell extracts, suggesting that TP1 is associated with telomerase in vivo The identification of TP1 suggests that telomerase-associated proteins are conserved from ciliates to humans

http://science.sciencemag.org/content/sci/275/5302/973.full.pdf

A mammalian telomerase-associated protein.

We have cloned and characterized a human gene encoding TP2 (telomerase-associated protein 2), a protein with similarity to reverse transcriptases and the catalytic telomerase subunits from Saccharomyces cerevisiae and Euplotes aediculatus. Indirect immunofluorescence revealed that TP2 was localized to the nucleus. Using antibodies to endogenous and epitope-tagged TP2, we found that TP2 was associated specifically with human telomerase activity and the recently identified telomerase-associated protein TP1. Mutation of conserved residues within the reverse transcriptase domain of TP2 severely reduced associated telomerase activity. These results suggest that telomerase is an evolutionarily conserved multisubunit complex composed of both structural and catalytic subunits.

/pdf/human-telomerase-contains-evolutionarily-conserved-catalytic-eguoc229vf.pdf

Michael Bass

Papers

Tumor necrosis factor receptor family member RANK mediates osteoclast differentiation and activation induced by osteoprotegerin ligand

Handbook of optics

A mammalian telomerase-associated protein.

Human telomerase contains evolutionarily conserved catalytic and structural subunits

Laser materials processing