The extent of conformational change that calcium binding induces in EF-hand proteins is a key biochemical property specifying Ca(2+) sensor versus signal modulator function. To understand how differences in amino acid sequence lead to differences in the response to Ca(2+) binding, comparative analyses of sequence and structures, combined with model building, were used to develop hypotheses about which amino acid residues control Ca(2+)-induced conformational changes. These results were used to generate a first design of calbindomodulin (CBM-1), a calbindin D(9k) re-engineered with 15 mutations to respond to Ca(2+) binding with a conformational change similar to that of calmodulin. The gene for CBM-1 was synthesized, and the protein was expressed and purified. Remarkably, this protein did not exhibit any non-native-like molten globule properties despite the large number of mutations and the nonconservative nature of some of them. Ca(2+)-induced changes in CD intensity and in the binding of the hydrophobic probe, ANS, implied that CBM-1 does undergo Ca(2+) sensorlike conformational changes. The X-ray crystal structure of Ca(2+)-CBM-1 determined at 1.44 A resolution reveals the anticipated increase in hydrophobic surface area relative to the wild-type protein. A nascent calmodulin-like hydrophobic docking surface was also found, though it is occluded by the inter-EF-hand loop. The results from this first calbindomodulin design are discussed in terms of progress toward understanding the relationships between amino acid sequence, protein structure, and protein function for EF-hand CaBPs, as well as the additional mutations for the next CBM design.

EF-Hand Motif M. R. Nelson, M. R. NelsonSearch for more papers by this authorC. Weber, C. WeberSearch for more papers by this authorW. J. Chazin, W. J. Chazin Scripps Research Institute, La Jolla, CASearch for more papers by this author M. R. Nelson, M. R. NelsonSearch for more papers by this authorC. Weber, C. WeberSearch for more papers by this authorW. J. Chazin, W. J. Chazin Scripps Research Institute, La Jolla, CASearch for more papers by this author First published: 15 January 2002 https://doi.org/10.1002/047120918X.emb0448 Read the full textAbout ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Encyclopedia of Molecular BiologyBrowse other articles of this reference work:BROWSE BY TOPICBROWSE A-Z RelatedInformation

EDTA (Ethylenediamine-N,N,N′,N′-Tetraacetic Acid) C. Weber, C. WeberSearch for more papers by this authorM. R. Nelson, M. R. NelsonSearch for more papers by this authorW. J. Chazin, W. J. Chazin Scripps Research Institute, La Jolla, CASearch for more papers by this author C. Weber, C. WeberSearch for more papers by this authorM. R. Nelson, M. R. NelsonSearch for more papers by this authorW. J. Chazin, W. J. Chazin Scripps Research Institute, La Jolla, CASearch for more papers by this author First published: 15 January 2002 https://doi.org/10.1002/047120918X.emb0446 Read the full textAbout ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Encyclopedia of Molecular BiologyBrowse other articles of this reference work:BROWSE BY TOPICBROWSE A-Z RelatedInformation

A Monte Carlo simulation methodology was used to examine the effectiveness of five methods for handling missing data in items that comprise summated scales: listwise deletion, item mean substitution, person mean substitution, random number substitution, and regression imputation. Overall, regression imputation was the most effective method in reproducing psychometric properties of a summated scale and preserving statistical power to detect correlations between the summated scale and other variables. The item mean substitution method yielded biased estimates of the standard deviation of the summated scale. Although listwise deletion yielded relatively unbiased estimates of the psychometric properties of the summated scale, there were high levels of dispersion in the estimates around the true population values. Furthermore, listwise deletion led to severe reductions in statistical power to detect correlations between the summated scale and other variables.

Adefovir dipivoxil (bis-POM PMEA) is an adenine nucleotide analogue with activity against retroviruses and herpesviruses, and in vitro activity against hepatitis B virus (HBV). This study was conducted to evaluate its safety and antiviral activity in patients with chronic HBV infection. Twenty patients (13 co-infected with human immunodeficiency virus, HIV) were randomized in a phase I/II, double-blind, placebo-controlled study. Patients who had been hepatitis B surface antigen (HBsAg)/hepatitis B e antigen (HBeAg) positive for > or = 6 months, with elevated hepatic transaminases and serum HBV DNA > or = 50 pg ml-1, were randomized to adefovir dipivoxil 125 mg (n = 15) or placebo (n = 5) as a single, daily, oral dose for 28 days. Antiviral activity was assessed by changes in serum HBV DNA (using the Digene Hybrid Capture assay) and HBeAg/hepatitis B e antibody (HBeAb) status. HBV DNA levels fell rapidly by > 1 log10 in all active drug recipients (median fall 1.8 log10 pg ml-1) but increased by 0.01 log10 pg ml-1 in controls (P = 0.002). Reductions were sustained during treatment. HBV DNA returned to baseline over 1-6 weeks following discontinuation of active drug. HBeAg became transiently undetectable in one patient on treatment and, in another, sustained seroconversion to HBeAb occurred 12 weeks after treatment ended. Liver transaminase elevations > 300 U l-1 were observed in three patients during therapy (leading to protocol-specified treatment discontinuation or dose reduction) and in four patients during follow-up. On-treatment transaminase elevations were associated with HIV status, occurring in three of six HIV-uninfected patients compared with none of nine who were HIV infected. In addition, a slower return to baseline of serum HBV DNA levels was observed in the non-HIV-infected patients. Treatment for chronic hepatitis B as a once-daily oral dose was well tolerated and associated with significant and sustained reductions in serum HBV DNA levels during treatment. Transaminase elevations, which may be related to the therapeutic effect, were observed during and after treatment. Further studies are warranted to investigate the safety, and optimum dose and duration, of adefovir dipivoxil treatment for chronic hepatitis B.

Calcium sensor proteins translate transient increases in intracellular calcium levels into metabolic or mechanical responses, by undergoing dramatic conformational changes upon Ca 2+ binding. A detailed analysis of the calcium binding‐induced conformational changes in the representative calcium sensors calmodulin (CaM) and troponin C was performed to obtain insights into the underlying molecular basis for their response to the binding of calcium. Distance difference matrices, analysis of interresidue contacts, comparisons of interhelical angles, and inspection of structures using molecular graphics were used to make unbiased comparisons of the various structures. The calcium‐induced conformational changes in these proteins are dominated by reorganization of the packing of the four helices within each domain. Comparison of the closed and open conformations confirms that calcium binding causes opening within each of the EF‐hands. A secondary analysis of the conformation of the C‐terminal domin of CaM (CaM‐C) clearly shows that CaM‐C occupies a closed conformation in the absence of calcium that is distinct from the semi‐open conformation observed in the C‐terminal EF‐hand domains of myosin light chains. These studies provide insight into the structural basis for these changes and into the differential response to calcium binding of various members of the EF‐hand calcium‐binding protein family. Factors contributing to the stability of the Ca 2+ ‐loaded open conformation are discussed, including a new hypothesis that critical hydrophobic interactions stabilize the open conformation in Ca2+ sensors, but are absent in “non‐sensor” proteins that remain closed upon Ca 2+ binding. A role for methionine residues in stabilizing the open conformation is also proposed.

A regional management plan was designed and implemented for a multivirus, multivector, disease complex in tomatoes in the Del Fuerte Valley, Sinaloa, Mexico. The viruses include tobacco etch and cucumber mosaic with aphid vectors, a geminivirus complex with whitefly vectors, tomato spotted wilt with thrips vectors, and tomato mosaic with no known vector. Although the viruses and their vectors are biologically diverse, all are transmitted by flying insects, with the exception of tomato mosaic, and ail except tomato mosaic are known to have alternate hosts among weeds and other crop plants in the area. Because of these similarities, we developed a risk-assessment process based on general virus infection hazards rather than specific viruses. The risk assessment helped to focus on actions that could be taken both locally and regionally to reduce early and damaging infections. Risk assessment and virus disease-incidence data were collected from 53 fields during 1990-1991 and 60 fields during 1991-1992. A geostatistical analysis of risk and incidence showed that both were spatially dependent variables with a variogram range of 20 to 25 km. Moving spatial averages (computed by kriging) indicated Chat the area east of Los Mochis was higher in risk and incidence than the area near Guasave during both seasons. Qualitative observations consistent with observed patterns of incidence suggest there are underlying landscape features more conducive to endemic plant virus diseases in the Los Mochis area than in the Guasave area.

view Abstract Citations (14) References (12) Co-Reads Similar Papers Volume Content Graphics Metrics Export Citation NASA/ADS Mass transfer in DQ Herculis. Nelson, M. R. Abstract New observations of the 279rn binary period and 71s sinusoidal period are presented. From these and other data we derive an upper and lower bound and an estimate for the mass transfer rate. Luminosity of the system based on the value of the mass transfer rate is discussed. Subject headings: stars: eclipsing binaries - stars: individual - stars: mass loss - stars: novae Publication: The Astrophysical Journal Pub Date: October 1976 DOI: 10.1086/154705 Bibcode: 1976ApJ...209..168N full text sources ADS | data products SIMBAD (1)

The 1975 observations show a dramatic change in the UBV light curves of the eclipsing binary DQ Her (nova 1934). Since 1954, the B light outside eclipse has dimmed approximately 0.5 mag and the light at primary minimum has dimmed approximately 1.3 mag. Simple analysis of the light curves allows one to conclude that (1) the eclipsed light has fallen approximately 20 percent while the light which is constant with orbital phase has dropped approximately 75 percent; (2) the time over which most of the change in the eclipsed light occurred is less than approximately 0.7 years; (3) light loss at mid-eclipse is approximately 0.94; and (4) the mass of the secondary star is less than 0.4 M/sub solar mass/. The changes provide indirect evidence that the mass transfer rate is not constant in time. Near-infrared data are also presented which show a reversal of the trend seen in the UBV light curves of greater eclipse depth with longer wavelength.