δ-EF1 is a negative regulator of Ihh in the developing growth plate

Hedgehog protein IHH expression is regulated by transcription factor δ-EF1 to control endochondral bone formatio

Serum haptoglobin and C-reactive protein in human skeletal fluorosis

Circulating levels of haptoglobin and C-reactive protein were studied in patients of skeletal fluorosis and compared with two types of controls. The first type of control included normal healthy individuals consuming water containing permissible levels of fluoride (up to 1 mg/L). The second type of control included individuals consuming water contaminated with fluoride (1.2-14.5 mg/L) but not exhibiting clinical manifestations of skeletal fluorosis. A significant increase in the levels of haptoglobin (p < 0.01) and C-reactive protein (p < 0.01) as well as a raised erythrocyte sedimentation rate were seen in patients of skeletal fluorosis as compared to both types of controls. The present study suggests the possibility of a subclinical inflammatory reaction occurring in patients with skeletal fluorosis

Prospects of zona pellucida glycoproteins as immunogens for contraceptive vaccine

The zona pellucida (ZP) surrounding a mammalian oocyte mediates the initial recognition and binding of spermatozoon to oocyte in a relatively species-specific manner and plays an important role in the subsequent activation events during the fertilization process. The ZP comprises three biochemically and immunologically distinct glycoproteins termed ZP1, ZP2 and ZP3. The critical role of ZP glycoproteins in reproduction together with their tissue-specific nature have led to their being considered as potential candidate antigens for immunocontraception. Immunization of females with ZP glycoproteins leads to a block of fertility in several animal models. However, it is invariably associated with either a transient or an irreversible alteration in the cyclicity, hormonal profile and follicular development in the ovary. To overcome these problems, attempts are being made to delineate relevant 'B'cell epitopes on ZP proteins so as to design immunocontraceptive vaccines based on synthetic peptides devoid of oophoritogenic 'T' cell epitopes. Monoclonal antibodies capable of inhibiting the gamete interaction are being employed to delineate such regions. Additionally, DNA-recombinant technology has made it feasible to obtain, in reasonably large quantities, the ZP glycoproteins from human and non-human primates. Availability of sequence information of these zona proteins and the availability of recombinant antigens (devoid of other ovarian-associated proteins) will further help in understanding more precisely their functions during fertilization and make it feasible to undertake immunization studies to determine their prospects as immunogens for fertility regulation

Transcriptional profile of GTP-mediated differentiation of C2C12 skeletal muscle cells

Several purine receptors have been localised on skeletal muscle membranes. Previous data support the hypothesis that extracellular guanosine 5′-triphosphate (GTP) is an important regulatory factor in the development and function of muscle tissue. We have previously described specific extracellular binding sites for GTP on the plasma membrane of mouse skeletal muscle (C2C12) cells. Extracellular GTP induces an increase in intracellular Ca2+ concentrations that results in membrane hyperpolarisation through Ca2+-activated K+ channels, as has been demonstrated by patch-clamp experiments. This GTP-evoked increase in intracellular Ca2+ is due to release of Ca2+ from intracellular inositol-1,4,5-trisphosphate-sensitive stores. This enhances the expression of the myosin heavy chain in these C2C12 myoblasts and commits them to fuse into multinucleated myotubes, probably via a phosphoinositide-3-kinase-dependent signal-transduction mechanism. To define the signalling of extracellular GTP as an enhancer or modulator of myogenesis, we investigated whether the gene-expression profile of differentiated C2C12 cells (4 and 24 h in culture) is affected by extracellular GTP. To investigate the nuclear activity and target genes modulated by GTP, transcriptional profile analysis and real-time PCR were used. We demonstrate that in the early stages of differentiation, GTP up-regulates genes involved in different pathways associated with myogenic processes, including cytoskeleton structure, the respiratory chain, myogenesis, chromatin reorganisation, cell adhesion, and the Jak/Stat pathway, and down-regulates the mitogen-activated protein kinase pathway. GTP also increases the expression of three genes involved in myogenesis, Pp3ca, Gsk3b, and Pax7. Our data suggests that in the myogenic C2C12 cell line, extracellular GTP acts as a differentiative factor in the induction and sustaining of myogenesis