Cadherin-6 mediates the heterotypic interactions between the hemopoietic osteoclast cell lineage and stromal cells in a murine model of osteoclast differentiation

Osteoclasts are multinucleated cells of hemopoietic origin that are responsible for bone resorption during physiological bone remodeling and in a variety of bone diseases. Osteoclast development requires direct heterotypic cell-cell interactions of the hemopoietic osteoclast precursors with the neighboring osteoblast/stromal cells. However, the molecular mechanisms underlying these heterotypic interactions are poorly understood. We isolated cadherin-6 isoform, denoted cadherin-6/2 from a cDNA library of human osteoclast-like cells. The isolated cadherin-6/2 is 3,423 bp in size consisting of an open reading frame of 2,115 bp, which encodes 705 amino acids. This isoform lacks 85 amino acids between positions 333 and 418 and contains 9 different amino acids in the extracellular domain compared with the previously described cadherin-6. The human osteoclast-like cells also expressed another isoform denoted cadherin-6/1 together with the cadherin-6. Introduction of cadherin-6/2 into L-cells that showed no cell-cell contact caused evident morphological changes accompanied with tight cell-cell association, indicating the cadherin-6/2 we isolated here is functional. Moreover, expression of dominant-negative or antisense cadherin-6/2 construct in bone marrow-derived mouse stromal ST2 cells, which express only cadherin-6/2, markedly impaired their ability to support osteoclast formation in a mouse coculture model of osteoclastogenesis. Our results suggest that cadherin-6 may be a contributory molecule to the heterotypic interactions between the hemopoietic osteoclast cell lineage and osteoblast/bone marrow stromal cells required for the osteoclast differentiation. Since both osteoclasts and osteoblasts/bone marrow stromal cells are the primary cells controlling physiological bone remodeling, expression of cadherin-6 isoforms in these two cell types of different origin suggests a critical role of these molecules in the relationship of osteoclast precursors and cells of osteoblastic lineage within the bone microenvironment.     

Designing Nanoscale Logic Circuits Based on Markov Random Fields

As devices and operating voltages are scaled down, future circuits will be plagued by higher soft error rates, reduced noise margins and defective devices. A key challenge for the future is retaining high reliability in the presence of faulty devices and noise. Probabilistic computing offers one possible approach. In this paper we describe our approach for mapping circuits onto CMOS using principles of probabilistic computation. In particular, we demonstrate how Markov random field elements may be built in CMOS and used to design combinational circuits running at ultra low supply voltages. We show that with our new design strategy, circuits can operate in highly noisy conditions and provide superior noise immunity, at reduced power dissipation. If extended to more complex circuits, our approach could lead to a paradigm shift in computing architecture without abandoning the dominant silicon CMOS technology.     

District sputum smear microscopy services in Malawi

SETTING: Government hospitals and health centres in 23 districts in Malawi. OBJECTIVE: To determine 1) the number and smear-positivity rate of sputum samples submitted at health centres and hospitals, and 2) the time for sputum samples to get from health centres to smear examination. DESIGN: Prospective data collection on sputum specimens coming from health centres to hospital laboratories, and over the equivalent time period, retrospective data collection from laboratory sputum registers. RESULTS: Information was collected over a period of 5.6 months during 1997. Of 21 527 patients submitting sputum samples, 16995 (79%) were from within the hospital and 4532 (21%) were from health centres. Of 15 833 new TB suspects, 12 804 (81%) submitted sputum within the hospital and 3029 (19%) were from health centres. The overall smear-positivity rate was 11.9%: the proportion of new suspects who were smear-positive was significantly higher in health centres (14.1%) compared with hospital-based patients (11.4%, P < 0.05); 27% of all sputum specimens from health centres took 8 days or longer to get to smear examination. Sputum smears were positive from 1-30 days between submission and laboratory examination. CONCLUSION: Fewer sputum samples are submitted at health centres compared with hospitals, and there may be long delays between sputum submission and smear examination. The precise reasons are unclear, but health centre staff need training about the importance of timely case finding procedures.     

Ordered intermetallic alloys: an assessment

The paper summarizes our present understanding, as established at a recent workshop, of two classes of intermetallic alloys: nickel and iron aluminides, which are currently used by industries; and advanced intermetallic alloys including silicides and Laves-phase alloys, which have a great potential to be developed as new high-temperature structural materials for future industrial use. The workshop emphasized close interaction and co-operation between basic research, applied research, and industrial development, and stressed discussion of critical scientific and technological issues. The current status of these intermetallic alloys was assessed, and the directions for future research and development, as well as emerging opportunities, were identified. The information presented in the text is summarized from the presentations at the workshop, and so no references are given to the published literature. However, an extensive bibliography is appended, in which further details may be found.     

Sexually transmitted disease acquisition among women infected with human immunodeficiency virus type 1

Recent evidence suggests that sexually transmitted diseases (STDs) enhance the transmission of human immunodeficiency virus (HIV) type 1. In 143 HIV-infected women enrolled in a university-based longitudinal HIV clinic over 16 months (mean), the STD point prevalence was examined at enrollment and the cumulative prevalence was calculated at follow-up. At enrollment, 35 women (25%) had > or = 1 STD. These included trichomoniasis in 16 women (11%); syphilis, 9 (6%); genital herpes, 8 (6%); gonorrhea, 5 (4%); chlamydia, 5 (4%); genital warts, 2 (1%); and pelvic inflammatory disease (PID), 1 (1%). STDs were found in 55 (42%) of the 125 patients who returned for at least one follow-up visit: trichomoniasis in 23 (18%); genital herpes, 20 (12%); gonorrhea, 9 (7%); syphilis, 7 (6%); genital warts, 7 (6%); chlamydia, 5 (4%); and PID, 4 (3%). Despite counseling at both enrollment and follow-up, these women had a very high cumulative prevalence of STDs, indicating persistent high-risk sexual behavior.     

Extracts of porcine pancreas prevent progression of hypercalcemia and cachexia and prolong survival in nude mice bearing a human squamous carcinoma

Porcine pancreatic extracts (PXs) have previously been shown to decrease blood ionized calcium in BALB/c mice (T. Yoneda, Y. Takaoka, and G. R. Mundy. FEBS Lett., 278: 171-174, 1991). In the present study, we show that the PX is effective in preventing progression of hypercalcemia and decreasing osteoclastic bone resorption associated with a human squamous carcinoma in nude mice. PX inhibited osteoclast-like cell formation in mouse bone marrow cultures and bone resorption in organ cultures of fetal rat long bones which had been stimulated by serum-free culture supernatants of this cancer. In addition, PX increased food intake, decreased weight loss, and prevented development of cachexia. In parallel with these effects, PX prolonged survival of tumor-bearing animals. PX might have therapeutic potential for management of hypercalcemia and cachexia associated with malignancy.