Biological stenciling of mineralization in the skeleton: Local enzymatic removal of inhibitors in the extracellular matrix.

Biomineralization is remarkably diverse and provides myriad functions across many organismal systems. Biomineralization processes typically produce hardened, hierarchically organized structures usually having nanostructured mineral assemblies that are formed through inorganic-organic (usually protein) interactions. Calcium­carbonate biomineral predominates in structures of small invertebrate organisms abundant in marine environments, particularly in shells (remarkably it is also found in the inner ear otoconia of vertebrates), whereas calcium-phosphate biomineral predominates in the skeletons and dentitions of both marine and terrestrial vertebrates, including humans. Reconciliation of the interplay between organic moieties and inorganic crystals in bones and teeth is a cornerstone of biomineralization research. Key molecular determinants of skeletal and dental mineralization have been identified in health and disease, and in pathologic ectopic calcification, ranging from small molecules such as pyrophosphate, to small membrane-bounded matrix vesicles shed from cells, and to noncollagenous extracellular matrix proteins such as osteopontin and their derived bioactive peptides. Beyond partly knowing the regulatory role of the direct actions of inhibitors on vertebrate mineralization, more recently the importance of their enzymatic removal from the extracellular matrix has become increasingly understood. Great progress has been made in deciphering the relationship between mineralization inhibitors and the enzymes that degrade them, and how adverse changes in this physiologic pathway (such as gene mutations causing disease) result in mineralization defects. Two examples of this are rare skeletal diseases having osteomalacia/odontomalacia (soft bones and teeth) - namely hypophosphatasia (HPP) and X-linked hypophosphatemia (XLH) - where inactivating mutations occur in the gene for the enzymes tissue-nonspecific alkaline phosphatase (TNAP, TNSALP, ALPL) and phosphate-regulating endopeptidase homolog X-linked (PHEX), respectively. Here, we review and provide a concept for how existing and new information now comes together to describe the dual nature of regulation of mineralization - through systemic mineral ion homeostasis involving circulating factors, coupled with molecular determinants operating at the local level in the extracellular matrix. For the local mineralization events in the extracellular matrix, we present a focused concept in skeletal mineralization biology called the Stenciling Principle - a principle (building upon seminal work by Neuman and Fleisch) describing how the action of enzymes to remove tissue-resident inhibitors defines with precision the location and progression of mineralization.

Integration of basic sciences in health's courses.

Concepts from disciplines such as Biochemistry, Genetics, Cellular and Molecular Biology are essential to the understanding and treatment of an elevated number of illnesses, but often they are studied separately, with no integration between them. This article proposes a model for basic sciences integration based on problem-based learning (PBL) and compares failure rate, global final grade, approved student final grade, grade distribution and students' satisfaction with teacher conduction between integrated curriculum and traditional learning in health courses from Anhembi Morumbi University-a private institution from Brazil. Comparison between integrated and traditional curriculum was based on students' records obtained from first-year health sciences students. A total of 1,697 records from 2005 to 2007 (nonintegrated curriculum) and 785 records from 2008 (integrated curriculum) were selected for this study and they were necessary to get information about students' grades. Moreover, a questionnaire was applied in order to cover student's satisfaction with teacher conduction. The data presented in this study indicated that the integrated curriculum based on PBL was related to an improvement in student's grades and satisfaction compared with traditional teaching. We believe that the effectiveness in health education will be a combination of "classical" presentation of contents associated to actively involved students in the educational process and methodology based on problems in order to create the stimulus for the undergraduates continue to integrate basic and clinical investigation.