------------------------------ Date: Mon, 02 Jan 95 22:33:55 MST From: mednews@stat.com (HICNet Medical News) To: hicnews Subject: Structure and Hydration of DNA Essential for Gene Expression Message-ID: <9y8Byc11w165w@stat.com> Structure and Hydration of DNA Essential for Control of Gene Expression Research from The Weizman Institute of Science May 1994 No 31 Although proteins that regulate gene expression have been intensively investigated, structural chemists still have much to learn about the mechanisms by which these factors are targeted to the genes they control and thereby enable cells to function. Scientists at the Weizmann Institute, working in collaboration with Yale University researchers, have shown that a novel recognition mechanism may enable DNA transcription factors to recognize their regulatory sites. This discovery is of critical importance because faulty gene regulation underlies a wide variety of development and metabolic diseases, as well as malignancies. The researchers found that flexing of the DNA control site makes possible the snug intermeshing of the protein and DNA molecules and that water molecules deeply seated in the double-helix groove of the DNA stabilize the complex. According to Weizmann Institute Prof., Zippora Shakked (Dept. of Structural Biology), a major participant in this study, one of the best-studied control proteins, the trp repressor, supervises the operation of genes in E. coli that enable the bacterium to produce the amino acid tryptophan. When too much tryptophan is present in the cell, the amino acid binds to the trp repressor protein, which interacts with the DNA regulatory site, thereby halting operation of these genes. In 1988, Prof. Paul B. Sigler and his colleagues at Yale University were the first to determine the structure of the trp repressor/DNA complex by high-resolution X-ray crystallography. However, they were unable to see any of the normally observed atom-to-atom interactions that would have explained why the protein is attracted to and binds the DNA. In order to shed light on this question, Shakked joined forces with her departmental colleagues - graduate student Gali Guzikevich-Guerstein, Prof. Dov Rabinovich, and Dr. Felix Frolow - and Prof. Sigler and his associate at Yale, Dr. Andrzej Joachimiak. The collaborators carried out an X-ray study of the DNA control segment in the absence of the repressor protein an investigation that is usually more complicated than that involving the protein/DNA complex, due to the difficulties of crystallizing DNA and determining its structure. The DNA structural group at the Weizmann Institute has had many years' experience carrying out such X-ray studies. The Weizmann structural chemists obtained X-ray data for the DNA control site in its unbound form and compared that structure with the bound DNA in the complex. They discovered that the native DNA is flexed by nearly 15 degrees when it binds to the protein, and that water molecules present deep in the groove of the DNA double helix provide the chemical "glue" that makes repressor binding possible. They also found that prime recognition was based on the overall structure of the protein and DNA surfaces, with flexibility of the DNA allowing it to take on a structure which complements that of the protein. This first analytical comparison of bound and naked DNA fragments was vital to this study because it is impossible to know from a bound DNA what its structure is in the unbound state. Shakked is now applying her comparative approach for studying the binding of regulatory proteins to genes present in mammalian cells, some of which are involved in malignant processes. This investigation was reported in a recent issue of Nature. It was supported by the U.S.-Israel Binational Science Foundation, the Israel Science Foundation (Israel Academy of Sciences and Humanities), the Helen and Milton Kimmelman Center for Macromolecular Structure and Assembly, and the U.S. National Institutes of Health. Prof. Zippora Shakked holds the Helena Rubinstein Chair of Structural Biology; and Prof. Dov Rabinovich, the William and Lee Abramowitz Chair of Macromolecular Biophysics. ------------------------------ Date: Mon, 02 Jan 95 22:34:57 MST From: mednews@stat.com (HICNet Medical News) To: hicnews Subject: Dental Implants Show Promise for Adolescents Message-ID: Dental Implants Show Promise for Adolescents From the National Institute of Dental Research September 1994 Preliminary results of an NIDR study suggest that dental implants can improve the quality of life for adolescents. Findings from the study were presented at this year's IADR/AADR meeting in Seattle. Since the early 1980s, dental implants have been used to treat adults who have lost their teeth to disease or have never developed teeth. Many researchers thought that implants could benefit adolescents, but there were concerns. "A major consideration about placing implants in adolescents had been that the patient would outgrow the implant structure," said Dr. George McCarthy, a dentist who is part of the NIDR implant team. "We have found that the implant is anchored in the bone so well that it moves with the jaw during growth." NlDR's implant team-Dr. Albert Guckes, a prosthodontist now at the University of North Carolina School of Dentistry, Dr. McCarthy, and Dr. Jaime Brahim, an oral surgeon- placed 114 implants in the jaws of 26 adolescents with ectodermal dysplasias (ED), a group of congenital diseases that can result in the absence of teeth, hair, and sweat glands. The patients, 18 boys and 8 girls, were an average of 15 years of age when they joined the study. The youngest patient was 12 and the oldest was 20. The dental researchers used titanium endosseous screw implants, which can each hold one or more prosthetic teeth. Two surgical procedures are required to place the implants. First, the oral surgeon cuts through the top of the gum tissue to expose the jawbone. Small holes are drilled into the bone, and a screw implant is placed in each hole. The gums are closed and allowed to heal. During the following three to six months, the implants are osseointegrated. In the study, 93 of 100 implants evaluated so far were successfully osseointegrated. "This is the most essential part of the process," said Dr. McCarthy. "If the implant isn't anchored in the jaw, then we can't continue." In the second surgery, an incision is made to expose the implants and a small post is put on top of each one. Attaching the prosthetic teeth to the posts is the final phase of the implant process. Two months after the prosthetic teeth are placed, the patients return for their first follow-up appointment. All patients are followed for five years. The NIDR researchers are currently placing implants in children ages 7-11 years old. They will follow these children over the next few years to determine if the implants affect craniofacial growth. ------------------------------ Date: Mon, 02 Jan 95 22:38:19 MST From: mednews@stat.com (HICNet Medical News) To: hicnews Subject: New Listserv: Culture and Nursing Message-ID: Dear Colleague, You are invited to join CULTURE-AND-NURSING, a new list sponsered by the School of Nursing at the University of California - San Francisco. This list was created for nurses and other health care professionals interested in topics relating to culture and health. (We apologize ahead of time for duplicate postings to other lists). We are seeking to create an on-line community which encourages the exchange of ideas in this exciting new field. This list will allow participants to address areas of cultural competence, theory, practice, research, and experience in an open and unmoderated forum. It will give list members the chance to discuss some of the political, economic, and demographic issues affecting health care today. It will also be an opportunity to meet others working in the field of cross cultural and transcultural nursing. To subscribe to CULTURE-AND-NURSING, send the following command in the BODY of the mail message (leave the subject header blank) to: majordomo@itssrv1.ucsf.edu subscribe CULTURE-AND-NURSING This list uses Brent Chapman's "Majordomo" mailing list manager. Although similar to listserv and listproc programs, there are a few differences. To receive the command list, send the following command to the list server (at majordomo@itssrv1.ucsf.edu): help If you have any questions, please send them to: Chuck Pitkofsky, MS, RN list manager chuckp@itsa.ucsf.edu phone: 415-546-7822 FAX: 415-546-7823 ------------------------------ End of HICNet Medical News Digest V08 Issue #02 *********************************************** --- Editor, HICNet Medical Newsletter Internet: david@stat.com FAX: +1 (602) 451-1165 Bitnet : ATW1H@ASUACAD