Defective microtubule-dependent podosome organization in osteoclasts leads to increased bone density in Pyk2−/− mice

The protein tyrosine kinase Pyk2 is highly expressed in osteoclasts, where it is primarily localized in podosomes. Deletion of Pyk2 in mice leads to mild osteopetrosis due to impairment in osteoclast function. Pyk2-null osteoclasts were unable to transform podosome clusters into a podosome belt at the cell periphery; instead of a sealing zone only small actin rings were formed, resulting in impaired bone resorption. Furthermore, in Pyk2-null osteoclasts, Rho activity was enhanced while microtubule acetylation and stability were significantly reduced. Rescue experiments by ectopic expression of wild-type or a variety of Pyk2 mutants in osteoclasts from Pyk2−/− mice have shown that the FAT domain of Pyk2 is essential for podosome belt and sealing zone formation as well as for bone resorption. These experiments underscore an important role of Pyk2 in microtubule-dependent podosome organization, bone resorption, and other osteoclast functions

Cathepsin K-deficient osteocytes prevent lactation-induced bone loss and parathyroid hormone suppression

Lactation induces bone loss to provide sufficient calcium in the milk, a process that involves osteoclastic bone resorption but also osteocytes and perilacunar resorption. The exact mechanisms by which osteocytes contribute to bone loss remain elusive. Osteocytes express genes required in osteoclasts for bone resorption, including cathepsin K (Ctsk), and lactation elevates their expression. We show that Ctsk deletion in osteocytes prevented the increase in osteocyte lacunar area seen during lactation, as well as the effects of lactation to increase osteoclast numbers and decrease trabecular bone volume, cortical thickness, and mechanical properties. In addition, we show that Ctsk deletion in osteocytes increased bone parathyroid hormone-related peptide (PTHrP) and prevented the decrease in serum parathyroid hormone (PTH) induced by lactation, but amplified the increase in serum 1,25-dyhydroxyvitamin D [1,25(OH)(2)D]. The net result of these changes is to maintain serum and milk calcium levels in the normal range, ensuring normal offspring skeletal development. Our studies confirm the fundamental role of osteocytic perilacunar remodeling in physiological states of lactation and provide genetic evidence that osteocyte-derived Ctsk contributes not only to osteocyte perilacunar remodeling, but also to the regulation of PTH, PTHrP, 1,25(OH)(2)D, osteoclastogenesis, and bone loss in response to the high calcium demand associated with lactation

Zfp521 controls bone mass by HDAC3-dependent attenuation of Runx2 activity

Zfp521 regulates osteoblast development during lineage commitment and osteoblast maturation by suppressing Runx2 transcriptional activity

Beyond the “Code”: A Guide to the Description and Documentation of Biodiversity in Ciliated Protists (Alveolata, Ciliophora)

Recent advances in molecular technology have revolutionized research on allaspects of the biology of organisms, including ciliates, and created unprece-dented opportunities for pursuing a more integrative approach to investigationsof biodiversity. However, this goal is complicated by large gaps and inconsis-tencies that still exist in the foundation of basic information about biodiversityof ciliates. The present paper reviews issues relating to the taxonomy of cili-ates and presents specific recommendations for best practice in the observa-tion and documentation of their biodiversity. This effort stems from aworkshop that explored ways to implement six Grand Challenges proposed bythe International Research Coordination Network for Biodiversity of Ciliates(IRCN-BC). As part of its commitment to strengthening the knowledge basethat supports research on biodiversity of ciliates, the IRCN-BC proposes topopulate The Ciliate Guide, an online database, with biodiversity-related dataand metadata to create a resource that will facilitate accurate taxonomic identi-fications and promote sharing of data

Comment letters to the National Commission on Commission on Fraudulent Financial Reporting, 1987 (Treadway Commission) Vol. 1

https://egrove.olemiss.edu/aicpa_sop/1661/thumbnail.jp