Estrogens exert their physiological effects on target tissues by interacting with the estrogen receptors, ERalpha and ERbeta. Estrogen replacement is one the most common and effective strategies used to prevent osteoporosis in postmenopausal women. Whereas it was thought that estrogens work exclusively by inhibiting bone resorption, our previous results show that 17beta-estradiol (E2) increases mouse bone morphogenetic protein (BMP)-2 mRNA, suggesting that estrogens may also enhance bone formation. In this study, we used quantitative real-time RT-PCR analysis to demonstrate that estrogens increase BMP-2 mRNA in mouse mesenchymal stem cells. The selective ER modulators, tamoxifen, raloxifene, and ICI-182,780 (ICI), failed to enhance BMP-2 mRNA, whereas ICI inhibited E2 stimulation of expression. To investigate if estrogens increase BMP-2 expression by transcriptional mechanisms and if the response is mediated by ERalpha and/or ERbeta, we studied the effects of estrogens on BMP-2 promoter activity in transient transfected C3H10T1/2 cells. E2 produced a dose-dependent induction of the mouse -2712 BMP-2 promoter activity in cells cotransfected with ERalpha and ERbeta. At a dose of 10 nM E2, ERalpha induced mouse BMP-2 promoter activity 9-fold, whereas a 3-fold increase was observed in cells cotransfected with ERbeta. Tamoxifen and raloxifene were weak activators of the mouse BMP-2 promoter via ERalpha, but not via ERbeta. ICI blocked the activation of BMP-2 promoter activity by E2 acting via both ERalpha and ERbeta, indicating that mouse BMP-2 promoter activation is ER dependent. In contrast to E2 and selective ER modulators, the phytoestrogen, genistein was more effective at activating the mouse BMP-2 promoter with ERbeta, compared with ERalpha. Using a deletion series of the BMP-2 promoter, we determined that AP-1 or Sp1 sites are not required for E2 activation. A mutation in a sequence at -415 to -402 (5'-GGGCCActcTGACCC-3') that resembles the classical estrogen-responsive element abolished the activation of the BMP-2 promoter in response to E2. Our studies demonstrate that E2 activation of mouse BMP-2 gene transcription requires ERalpha or ERbeta acting via a variant estrogen-responsive element binding site in the promoter, with ERalpha being the more efficacious regulator. Estrogenic compounds may enhance bone formation by increasing the transcription of the BMP-2 gene.
Argon is an extremely chemically inert element. HArF is presently the only experimentally known neutral molecule containing a chemically bound argon atom. Ab initio calculations at the MP2 and CCSD(T) levels presented here suggest, however, the existence of whole families of additional molecules. Explicitly predicted are FArCCH, with an argon-carbon bond, and FArSiF(3), with an argon-silicon bond. These metastable compounds are found to be protected from decomposition by relatively high energy barriers. Other organo-argon and organo-silicon molecules derived from the above should be equally stable. The results may open the way to a substantial field of ``argon chemistry.'' (C) 2003 American Institute of Physics.
In a previous communication (Kindt et al., 2001) we reported preliminary results of Brownian dynamics simulation and analytical theory which address the packaging and ejection forces involving DNA in bacteriophage capsids. In the present work we provide a systematic formulation of the underlying theory, featuring the energetic and structural aspects of the strongly confined DNA. The free energy of the DNA chain is expressed as a sum of contributions from its encapsidated and released portions, each expressed as a sum of bending and interstrand energies but subjected to different boundary conditions. The equilibrium structure and energy of the capsid-confined and free chain portions are determined, for each ejected length, by variational minimization of the free energy with respect to their shape profiles and interaxial spacings. Numerical results are derived for a model system mimicking the lambda-phage. We find that the fully encapsidated genome is highly compressed and strongly bent, forming a spool-like condensate, storing enormous elastic energy. The elastic stress is rapidly released during the first stage of DNA injection, indicating the large force (tens of pico Newtons) needed to complete the (inverse) loading process. The second injection stage sets in when similar to1/3 of the genome has been released, and the interaxial distance has nearly reached its equilibrium value (corresponding to that of a relaxed torus in solution); concomitantly the encapsidated genome begins a gradual morphological transformation from a spool to a torus. We also calculate the loading force, the average pressure on the capsid's walls, and the anisotropic pressure profile within the capsid. The results are interpreted in terms of the (competing) bending and interaction components of the packing energy, and are shown to be in good agreement with available experimental data.
L Khriachtchev, H Tanskanen, A Cohen, RB Gerber, J Lundell, M Pettersson, H Kiljunen, and M Rasanen. 2003. “A gate to organokrypton chemistry: HKrCCH.” JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 125, Pp. 6876-6877.
Experimental and computational studies demonstrating that the conduction of compressed, two-dimensional arrays of hexagonally ordered Ag quantum dots (QDs) may be varied through the influence of applied electric fields are reported and discussed. Monolayers of Ag QDs are incorporated into three-terminal (gated) devices, in which temperature, source-drain voltage (V-sd), gating voltage (V-g), compression of the array, and QD size distribution may all be varied. Experimental and computational results are compared in an effort to construct a physical picture of the system. Current vs V-sd plots at low temperatures exhibit systematic nonlinearities that change over to an ohmic-like behavior at higher temperatures and/or higher V-sd. The voltage-induced transition is discussed as a transition of the conducting states from domain localized to delocalized. Such a transition was previously observed in the temperature dependence of the resistance. The computational model reveals that this transition is also highly sensitive to both the compression of the array and the size-distribution of the dots. We calculate the influence of V-g on the conductivity of the QD array, using the same computational model. In both the experiment and the model, we find a significant voltage gating effect and we observe hole-type conductivity of the array. Overall, the results demonstrate that low-temperature transport measurements provide a spectroscopic-like probe of the electronic states of the QD lattice. The theoretical approach further suggests that quite different gating behavior can be observed for electrodes with a different Fermi energy than the gold electrodes used in the experiment.
We reconsider the Born-Oppenheimer-Huang treatment of systems of electrons and nuclei for the case of their interaction with time-dependent fields. Initially, we present a framework in which all expressions derived are formally exact since no truncations are introduced. The objective is to explore the general structure of the equations under the most unrestricted conditions, including the possibility that the electronic basis is dependent both on the nuclear coordinates and on time. We then derive an application of the theory applicable to cases of interaction with strong time-dependent fields. The method truncates the electronic basis only after the time-dependent interaction is taken into account in the electronic wave functions. This leads to theory which is similar to a Born-Oppenheimer-type truncation within the interaction picture. (C) 2003 American Institute of Physics.
BACKGROUND: Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene containing a premature termination signal cause a deficiency or absence of functional chloride-channel activity. Aminoglycoside antibiotics can suppress premature termination codons, thus permitting translation to continue to the normal end of the transcript. We assessed whether topical administration of gentamicin to the nasal epithelium of patients with cystic fibrosis could result in the expression of functional CFTR channels.
METHODS: In a double-blind, placebo-controlled, crossover trial, patients with stop mutations in CFTR or patients homozygous for the DeltaF508 mutation received two drops containing gentamicin (0.3 percent, or 3 mg per milliliter) or placebo in each nostril three times daily for two consecutive periods of 14 days. Nasal potential difference was measured at base line and after each treatment period. Nasal epithelial cells were obtained before and after gentamicin treatment from patients carrying stop mutations, and the C-terminal of surface CFTR was stained.
RESULTS: Gentamicin treatment caused a significant reduction in basal potential difference in the 19 patients carrying stop mutations (from -45+/-8 to -34+/-11 mV, P=0.005) and a significant response to chloride-free isoproterenol solution (from 0+/-3.6 to -5+/-2.7 mV, P<0.001). This effect of gentamicin on nasal potential difference occurred both in patients who were homozygous for stop mutations and in those who were heterozygous, but not in patients who were homozygous for DeltaF508. After gentamicin treatment, a significant increase in peripheral and surface staining for CFTR was observed in the nasal epithelial cells of patients carrying stop mutations.
CONCLUSIONS: In patients with cystic fibrosis who have premature stop codons, gentamicin can cause translational "read through," resulting in the expression of full-length CFTR protein at the apical cell membrane, and thus can correct the typical electrophysiological abnormalities caused by CFTR dysfunction.
This issue of 'Zion' is dedicated to Ben-Zion Dinur (1884-1973) on the 30th anniversary of his death. Dinur was one of the creators of the Jerusalem school in the study of Jewish history and among the founders of the Israeli Historical Society and of 'Zion,' of which he was an editor for forty years. This article reviews Dinur's life and work in the fields of historical research, education, and public affairs and evaluates his achievements.
Generation of axisymmetric stable, long plasma channels with temperatures of 8 eV and electron densities ∼ 10[sup 19] cm[sup -3] by a high-current evaporating-wall capillary discharge with prepulse ablative plasma is reported. Results of spectroscopic measurements of the temperature and electron density of plasma produced in a polyethylene capillary are presented. The discharge provides a convenient source of dense highly ionized plasmas for laser-plasma interaction studies. [ABSTRACT FROM AUTHOR]
Stephen W Scherer, Joseph Cheung, Jeffrey R MacDonald, Lucy R Osborne, Kazuhiko Nakabayashi, Jo-Anne Herbrick, Andrew R Carson, Layla Parker-Katiraee, Jennifer Skaug, Razi Khaja, Junjun Zhang, Alexander K Hudek, Martin Li, May Haddad, Gavin E Duggan, Bridget A Fernandez, Emiko Kanematsu, Simone Gentles, Constantine C Christopoulos, Sanaa Choufani, Dorota Kwasnicka, Xiangqun H Zheng, Zhongwu Lai, Deborah Nusskern, Qing Zhang, Zhiping Gu, Fu Lu, Susan Zeesman, Malgorzata J Nowaczyk, Ikuko Teshima, David Chitayat, Cheryl Shuman, Rosanna Weksberg, Elaine H Zackai, Theresa A Grebe, Sarah R Cox, Susan J Kirkpatrick, Nazneen Rahman, Jan M Friedman, Henry HQ Heng, Pier Giuseppe Pelicci, Francesco Lo-Coco, Elena Belloni, Lisa G Shaffer, Barbara Pober, Cynthia C Morton, James F Gusella, Gail AP Bruns, Bruce R Korf, Bradley J Quade, Azra H Ligon, Heather Ferguson, Anne W Higgins, Natalia T Leach, Steven R Herrick, Emmanuelle Lemyre, Chantal G Farra, Hyung-Goo Kim, Anne M Summers, Karen W Gripp, Wendy Roberts, Peter Szatmari, Elizabeth JT Winsor, Karl-Heinz Grzeschik, Ahmed Teebi, Berge A Minassian, Juha Kere, Lluis Armengol, Miguel Angel Pujana, Xavier Estivill, Michael D Wilson, Ben F Koop, Sabrina Tosi, Gudrun E Moore, Andrew P Boright, Eitan Zlotorynski, Batsheva Kerem, Peter M Kroisel, Erwin Petek, David G Oscier, Sarah J Mould, Hartmut Döhner, Konstanze Döhner, Johanna M Rommens, John B Vincent, Craig J Venter, Peter W Li, Richard J Mural, Mark D Adams, and Lap-Chee Tsui. 2003. “Human chromosome 7: DNA sequence and biology..” Science, 300, 5620, Pp. 767-72. Abstract
DNA sequence and annotation of the entire human chromosome 7, encompassing nearly 158 million nucleotides of DNA and 1917 gene structures, are presented. To generate a higher order description, additional structural features such as imprinted genes, fragile sites, and segmental duplications were integrated at the level of the DNA sequence with medical genetic data, including 440 chromosome rearrangement breakpoints associated with disease. This approach enabled the discovery of candidate genes for developmental diseases including autism.
In part I, we proposed and investigated a hybrid pulse position modulation/ultrashort light pulse code-division multiple-access (PPM/ULP-CDMA) system for ultrafast optical communication networks. In this scheme, the large bandwidth of a ULP is efficiently utilized by virtue of the very high time resolution of a time-space processor. More detailed analysis and discussion on the receiver scheme using the time-space processor is now presented; nonideal performance of the time-space processor, including the reference pulse realization problem, as well as amplifier and detector noise, are taken into account. Discussions on physically achievable ranges of the system parameters that determine the performance of the proposed PPM/ULP-CDMA system are also made based upon current, state of the art technology. As remedies to overcome the physical limitations on the system parameters, two modified modulation/demodulation schemes are proposed and investigated to enhance the performance of the hybrid PPM/ULP-CDMA system.
Elevated fasting plasma total homocysteine concentration (tHcy) and lower vitamin status are associated with atherosclerotic states. Silent brain ischemic lesions and brain atrophy, prevailing in the elderly, are affected by tHcy and vitamin status. The study was performed on 56 outpatients who had undergone brain computed tomography (CT) before the onset of the study. According to brain CT evaluation, three groups were set: minor brain ischemia, brain atrophy and control. Brain CT, tHcy, plasma pyridoxal phosphate (PLP), vitamin B12, folic acid and cognitive and functional capacities were measured or evaluated in all of the subjects. Plasma vitamin score for three vitamins was calculated. In subjects with minor brain ischemic lesions (n = 21), tHcy was higher by 5.6 μM, whereas vitamin score and cognitive function were lower than in controls (n = 24). In subjects with brain atrophy (n = 11), plasma PLP and cognitive function were lower. Particular attention should be paid to tHcy mon
Collisions of the gaseous hydroxyl (OH) radical and ozone (O-3) with the surfaces of sodium chloride or iodide solutions, as well as with the surface of neat water, were investigated by molecular dynamics simulations. The principal intent was to answer atmospherically relevant questions concerning the trapping and accommodation of the OH and O-3 species at the surface and their uptake into the bulk solution. Although trapping is substantial for both species, OH adsorbs and absorbs significantly better than O-3. Most of the trapped O-3 molecules desorb from the surface within 50 ps, whereas a significant fraction of OH radicals remains at the interface for time intervals exceeding 100 ps. The aqueous surface has also an orientational effect on the OH species, favoring geometries with the H atom pointing toward the aqueous bulk. The effect of the dissolved salt on the trapping efficiency is minor; therefore, most likely, atomic ions solvated in aqueous aerosols do not act as strong scavengers of reactive gases in the atmosphere. However, frequent and relatively long contacts between the adsorbed molecules and halide anions do occur, allowing for heterogeneous atmospheric chemistry in the interfacial layer.
