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- Vallet-Erdtmann, V, et al.
(författare)
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The testicular form of hormone-sensitive lipase HSLtes confers rescue of male infertility in HSL-deficient mice
- 2004
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 279:41, s. 42875-42880
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Tidskriftsartikel (refereegranskat)abstract
- Inactivation of the hormone-sensitive lipase gene (HSL) confers male sterility with a major defect in spermatogenesis. Several forms of HSL are expressed in testis. HSLtes mRNA and protein are found in early and elongated spermatids, respectively. The other forms are expressed in diploid germ cells and interstitial cells of the testis. To determine whether the absence of the testis-specific form of HSL, HSLtes, was responsible for the infertility in HSL-null mice, we generated transgenic mice expressing HSLtes under the control of its own promoter. The transgenic animals were crossed with HSL-null mice to produce mice deficient in HSL in non-gonadal tissues but expressing HSLtes in haploid germ cells. Cholesteryl ester hydrolase activity was almost completely blunted in HSL-deficient testis. Mice with one allele of the transgene showed an increase in enzymatic activity and a small elevation in the production of spermatozoa. The few fertile hemizygous male mice produced litters of very small to small size. The presence of the two alleles led to a doubling in cholesteryl ester hydrolase activity, which represented 25% of the wild type values associated with a qualitatively normal spermatogenesis and a partial restoration of sperm reserves. The fertility of these mice was totally restored with normal litter sizes. In line with the importance of the esterase activity, HSLtes transgene expression reversed the cholesteryl ester accumulation observed in HSL-null mice. Therefore, expression of HSLtes and cognate cholesteryl ester hydrolase activity leads to a rescue of the infertility observed in HSL-deficient male mice.
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| 2. |
- Vallet, V., et al.
(författare)
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Solvent effects on uranium(VI) fluoride and hydroxide complexes studied by EXAFS and quantum chemistry
- 2001
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Ingår i: Inorganic Chemistry. - : American Chemical Society (ACS). - 0020-1669 .- 1520-510X. ; 40:14, s. 3516-3525
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Tidskriftsartikel (refereegranskat)abstract
- The structures of the complexes UO2Fn(H2O)(5-n)(2-n), n = 3-5, have been studied by EXAFS. All have pentagonal bipyramid geometry with U-F of and U-H2O distances equal to 2.26 and 2.48 Angstrom, respectively. On the other hand the complex UO2(OH)(4)(2-) has a square bipyramid geometry both in the solid state and in solution. The structures of hydroxide and fluoride complexes have also been investigated with wave function based and DFT methods in order to explore the possible reasons for the observed structural differences. These studies include models that describe the solvent by using a discrete second coordination sphere, a model with a spherical, or shape-adapted cavity in a conductor-like polarizable continuum medium (CPCM), or a combination of the two. Solvent effects were shown to give the main contribution to the observed structure variations between the uranium(VI) tetrahydroxide and the tetrafluoride complexes. Without a solvent model both UO2(OH)(4)(H2O)(2-) and UO2F4(H2O)(2-) have the same square bipyramid geometry, with the water molecule located at a distance of more than 4 Angstrom from uranium and with a charge distribution that is very near identical in the two complexes. Of the models tested, only the CPCM ones are able to describe the experimentally observed square and pentagonal bipyramid geometry in the tetrahydroxide and tetrafluoride complexes. The geometry and the relative energy of different isomers of UO2F3(H2O)(2)(-) are very similar, indicating that they are present in comparable amounts in solution. All calculated bond distances are in good agreement with the experimental observations, provided that a proper model of the solvent is used.
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| 3. |
- Vallet, V., et al.
(författare)
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The mechanism for water exchange in UO2(H2O)(5) (2+) and UO2(oxalate)(2)(H2O) (2-), as studied by quantum chemical methods
- 2001
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 123:48, s. 11999-12008
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Tidskriftsartikel (refereegranskat)abstract
- The mechanisms for the exchange of water between [UO2(H2O)(5)](2+), [UO2(oxalate)(2)(H2O)](2-), and water solvent along dissociative (D), associative (A) and interchange (1) pathways have been investigated with quantum chemical methods. The choice of exchange mechanism is based on the computed activation energy and the geometry of the identified transition states and intermediates. These quantities were calculated both in the gas phase and with a polarizable continuum model for the solvent. There is a significant and predictable difference between the activation energy of the gas phase and solvent models: the energy barrier for the D-mechanism increases in the solvent as compared to the gas phase, while it decreases for the A- and I-mechanisms. The calculated activation energy, AW, for the water exchange in [UO2(H2O)(5)](2+) is 74, 19, and 21 kJ/mol, respectively, for the D-, A-, and I-mechanisms in the solvent, as compared to the experimental value DeltaH(double dagger) = 26 +/- 1 kJ/mol. This indicates that the D-mechanism for this system can be ruled out. The energy barrier between the intermediates and the transition states is small, indicating a lifetime for the intermediate approximate to 10(-10) s, making it very difficult to distinguish between the A- and I-mechanisms experimentally. There is no direct experimental information on the rate and mechanism of water exchange in [UO2(oxalate)(2)(H2O)](2-)containing two bidentate oxalate ions. The activation energy and the geometry of transition states and intermediates along the D-, A-, and I-pathways were calculated both in the gas phase and in a water solvent model, using a single-point MP2 calculation with the gas phase geometry. The activation energy, AW, in the solvent for the D-, A-, and I-mechanisms is 56, 12, and 53 kJ/mol, respectively. This indicates that the water exchange follows an associative reaction mechanism. The geometry of the A- and I-transition states for both [UO2(H2O)(5)](2+) and [UO2(oxalate)(2)(H2O)](2-) indicates that the entering/leaving water molecules are located outside the plane formed by the spectator ligands.
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