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Modularity of osteoclast behaviour and "mode-specific" inhibition of osteoclast function.

This study is part of an attempt to understand the role of specific cellular activities in the bone resorptive process. Experiments were performed whereby known pharmacological agents were used to inhibit individual modes of osteoclastic activity, such as motility and secretion. The effects of such treatments on bone resorption were assessed by quantitative scanning electron microscopy. The compounds included colchicine, which was used to inhibit osteoclast motility; molybdate ions which were used to selectively inhibit the catalytic activity of secreted acid phosphatase, and omeprazole which was employed to inhibit the secretion of hydrogen ions. All compounds inhibited osteoclastic bone resorption, but singularly affected defined modes of activity. These findings suggest that each mode of osteoclastic activity is essential for the bone resorptive process, and that "mode-specific" inhibition may provide a means whereby excessive activity of the osteoclast can be regulated in disease.

Acid Phosphatase

The elastic modular changes of the rat uterine cervix under different physiological conditions.

In this paper, the elastic moduli of the rat uterine cervix were measured under different physiological conditions. It was found that the moduli significantly changed with the sex cycle, being higher in diestrus than in estrus, and highest in early pregnancy. The results suggest that active changes occur in the function of the uterine cervix under the modulation of hormones.

Animals

Selective immunoglobulin A deficiency associated with modular lymphoid hyperplasia.

Nodular lymphoid hyperplasia (NLH) has been firmly associated with syndromes of hypogammaglobulinemia but not with selective absence of IgA. We report the case of a 5-yr-old girl with the triad of selective IgA deficiency, NLH of the small bowel, and giardiasis. Results of an extensive immunologic investigation, including immunohistochemical examinations of small bowel biopsies, support the hypothesis that the basic defect responsible for IgA deficiency in this patient was the failure of precursor IgM-bearing lymphocytes to differentiate into IgA-producing plasma cells. Furthermore, the abundance of IgM-bearing cells in biopsy specimens demonstrates the existence of a compensatory mechanism in the intestine to substitute IgM for the absent IgA.

Child, Preschool

Modular structure of a chicken lysozyme silencer: involvement of an unusual thyroid hormone receptor binding site.

Silencer elements, by analogy to enhancer elements, function independently of their position and orientation. We show that the chicken lysozyme silencer S-2.4 kb has many other characteristics in common with enhancer elements. The silencer is comprised of modules that independently repress gene activity--repression being increased synergistically when different or identical modules are combined. Repression is effective both on a complete and on a minimal promoter consisting of a TATA box only. One silencer module is bound in vitro by a 75-93 kd protein, termed NeP1; the other can be bound either by the product of the oncogene v-erbA or by the thyroid hormone receptor. This erbA binding site is unusual in that the palindromic sequence is inverted.

Animals

A fully modular vector system for the optimization of gene expression in Escherichia coli.

The new expression vector system CYTEXP is designed to facilitate the optimization of both transcription and translation in Escherichia coli, while at the same time allowing the exchange of its major components using unique restriction sites. In vitro mutagenesis can be performed in situ using single-stranded DNA generated from the bacteriophage f1 ORI sequence. The basic vector pCYTEXP1 bears a synthetic copy of the intercistronic sequence that enhances the translation of the E. coli atpE gene. Reading frames can be inserted directly downstream of this sequence. The bacteriophage lambda promoters, the atpE sequence, the bacteriophage fd transcriptional terminator, the f1 ORI, and the amp antibiotic resistance gene are all borne on exchangeable "modules." Thus, both the efficiency and the conditions of expression of cloned genes can be readily optimized.

Antigens, Bacterial

MOL3D--a modular and interactive program for molecular modeling and conformational analysis: II. Extended modules.

The new release of MOL3D, a molecular modeling program written in FORTRAN, contains not only enhanced graphic capabilities, but also an improved module for intermolecular calculations that allows rigid and flexible docking. Various interfaces have been added to some well-known and widely diffused programs, such as MM2, AMBER and MOPAC, and to the Cambridge Crystallographic Database. Finally a graph manager and a samples database have been added, which allow efficient searches with various requirements concerning structural templates, pharmacophoric three-dimensional (3D) constraints, and the field of biological activity, if any.

Computer Graphics

Modular organization of ON and OFF responses in the cat lateral geniculate nucleus.

Multiunit mapping techniques were used to investigate whether or not units with ON- and OFF-center receptive fields occur in an orderly arrangement in the cat lateral geniculate nucleus. In the A layers, ON- and OFF-center sites were partially segregated in the dimension parallel to the laminae, with ON-center sites predominant at the dorsal surface of each layer and OFF-center sites relatively more numerous at the ventral surface of the layer. Microelectrode tracks were placed to traverse the visual field map in the nucleus parallel to projection lines, parallel to isoelevation lines and parallel to isoazimuth lines. The tracks placed parallel to projection lines contained long sequences of units of the same center sign, providing evidence that ON and OFF zones are organized in vertical modules which span much or all of the thickness of a layer. The tracks placed parallel to isoelevation and isoazimuth lines contained alternating clusters of ON- and OFF-center sites. These clusters were larger in the dimension representing isoelevation than in the dimension representing isoazimuth. Taken together, these results indicate that the cat lateral geniculate nucleus contains ON and OFF modules oriented perpendicular to the layers.

Action Potentials

Modular design of the Enterococcus hirae muramidase-2 and Streptococcus faecalis autolysin.

The mature forms of the extracellular muramidase-2 of Enterococcus hirae and Streptococcus faecalis autolysin have very similar primary structures. Each consists of an active-site-containing N-terminal domain fused to a multiple-repeat C-terminal domain. Polypeptide segments occurring at equivalent places in these two bacterial wall lytic enzymes have homologues in two phage lysozymes and in three functionally unrelated proteins, illustrating the principle that protein molecules frequently are constructed from modules that are linked in a single polypeptide chain.

Amino Acid Sequence

Modular organization of actin crosslinking proteins.

A family of actin-crosslinking proteins share a conserved 125 residue sequence that lies within a 250 residue actin-binding domain. This domain is combined with spacer segments consisting of a variable number of repeated alpha-helical or beta-sheet motifs and other functional domains, which generate proteins that differ in their ability to form actin bundles or networks and to associate with the plasma membrane. These functional domains are not in other actin-crosslinking proteins, one of which is elongation factor 1a (EF-1a) suggesting there are several pathways for the evolution of actin-crosslinking function.

Actinin

Crystallization of Escherichia coli catabolite gene activator protein with its DNA binding site. The use of modular DNA.

To obtain crystals of the Escherichia coli catabolite gene activator protein (CAP) complexed with its DNA-binding site, we have searched for crystallization conditions with 26 different DNA segments greater than or equal to 28 base-pairs in length that explore a variety of nucleotide sequences, lengths, and extended 5' or 3' termini. In addition to utilizing uninterrupted asymmetric lac site sequences, we devised a novel approach of synthesizing half-sites that allowed us to efficiently generate symmetric DNA segments with a wide variety of extended termini and lengths in the large size range (greater than or equal to 28 bp) required by this protein. We report three crystal forms that are suitable for X-ray analysis, one of which (crystal form III) gives measurable diffraction amplitudes to 3 A resolution. Additives such as calcium, n-octyl-beta-D-glucopyranoside and spermine produce modest improvements in the quality of diffraction from crystal form III. Adequate stabilization of crystal form III is unexpectedly complex, requiring a greater than tenfold reduction in the salt concentration followed by addition of 2-methyl-2,4-pentanediol and then an increase in the concentration of polyethylene glycol.

Base Sequence