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Dirk Zahn

Publications and source records attributed to Dirk Zahn.

14 recordsLinked to original sources
PubMed2007

Control of channel shapes in a microporous manganese(II)-borophosphate framework by variation of size and shape of organic template cations.

The templated microporous compounds [H2(Templ.)][MnII{B2P3O12(OH)}], [templates: 1,3-diaminopropane, C3H10N2 (DAP); piperazine, C4H10N2 (PIP); 1,4-diazacyclo[2.2.2]octane, C6H12N2 (DABCO)] were prepared under mild hydrothermal conditions. The crystal structures (H2DAP-Mn: Pmc2(1) (no. 26), a=1259.43(5), b=949.86(5), c=1135.92(5) pm, Z=4; H2PIP-Mn: Ima2 (no. 46), a=1257.9(1), b=948.69(8), c=1158.19(8) pm, Z=4; H2DABCO-H2PIP-Mn: Ima2 (no. 46), a=1262.90(7), b=961.05(5), c=1151.42(7) pm, Z=4) are characterized by identical framework connectivities [MnII{B2P3O12(OH)}]2-, but vary in shapes (diameters) of the structural channels depending on the shapes of the templating molecule ions. The situation clearly reflects the directing effect of true templates during endotemplating reactions. The experimental results (preparation, chemical analyses, and X-ray refinements) are supported by detailed ab initio calculations (structure optimizations).

Journal Article↗
PubMed2006

Competing evaporation and condensation processes during the boiling of methane.

The atomistic mechanism of the boiling of methane is explored from molecular dynamics simulations. The liquid --> vapor transition is initiated by local density fluctuations resulting in a nanometer-sized domain that exhibits both liquid and vapor characteristics. Though the rates of evaporation and condensation events increase dramatically in this area, the overall balance exhibits only a marginal net rate of evaporation. Growth of the precritical domain leads to the nucleation of a vapor phase in which isolated methane molecules are confined by a liquid-vapor interface. After crossing the transition state, the system experiences progressive destabilization of the liquid phase and the evaporation processes clearly outnumber the condensation events.

Journal Article↗
PubMed2006

Mechanisms and nucleation characteristics of the pressure-induced B1-B2 transition in potassium halides: a question of ion hardness and softness.

The transformation of potassium bromide from the B1 to the high-pressure B2 structure type is investigated by means of molecular dynamics simulations and compared to previous studies of KF and KCl. The underlying simulation scheme is based on the transition path sampling approach, which allows an unbiased investigation of the phase transition and offers a unique perspective for studying the involved mechanisms at the atomistic level of detail. Our analysis reveals identical mechanisms for the overall transition in KF, KCl, and KBr, but rather dissimilar characteristics of the nucleation and growth of phases. The transformation of KCl may be initiated by both K+ and Cl- ion displacement, exhibiting no preference for either species. However, for KF and KBr, we identified a clear favoring of column-wise F- and K+ displacement, respectively. Such tendencies have important implications on the morphogenesis of the phase nuclei and account for the observation of short-ranged coexisting nucleation centers, resulting in the formation of nanosized twin domains separated by mirror planes on completion of the transition. On the basis of a systematic study of potassium halides, we present a conclusive explanation for the observed nucleation characteristics, which is expected to be of general relevance to pressure-induced phase transitions in ionic compounds.

Journal Article↗
PubMed2006

An atomistic simulation scheme for modeling crystal formation from solution.

We present an atomistic simulation scheme for investigating crystal growth from solution. Molecular-dynamics simulation studies of such processes typically suffer from considerable limitations concerning both system size and simulation times. In our method this time-length scale problem is circumvented by an iterative scheme which combines a Monte Carlo-type approach for the identification of ion adsorption sites and, after each growth step, structural optimization of the ion cluster and the solvent by means of molecular-dynamics simulation runs. An important approximation of our method is based on assuming full structural relaxation of the aggregates between each of the growth steps. This concept only holds for compounds of low solubility. To illustrate our method we studied CaF2 aggregate growth from aqueous solution, which may be taken as prototypes for compounds of very low solubility. The limitations of our simulation scheme are illustrated by the example of NaCl aggregation from aqueous solution, which corresponds to a solute/solvent combination of very high salt solubility.

Journal Article↗
PubMed2005

Unprejudiced identification of reaction mechanisms from biased transition path sampling.

A method for unprejudiced investigation of reaction mechanisms from molecular-dynamics simulations is presented. It combines the transition path sampling approach with a biasing strategy, which (a) allows optimization of transition paths crossing an energy minimum of the transition state surface. The bias is then used to (b) find reaction pathways, which follow different mechanistic routes. In the first step the manifold of similar trajectories that correspond to the same mechanism is reduced to a single characteristic dynamical path. Our method then allows a systematic search for further reaction mechanisms and the related energy barriers. It is illustrated at the example of a single particle in a two-dimensional potential and of the rather complex process of the pressure-induced insertion of a helium atom into a C60 buckyball molecule.

Journal Article↗
PubMed2005

Kisspeptin directly stimulates gonadotropin-releasing hormone release via G protein-coupled receptor 54.

We have recently described a molecular gatekeeper of the hypothalamic-pituitary-gonadal axis with the observation that G protein-coupled receptor 54 (GPR54) is required in mice and men for the pubertal onset of pulsatile luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion to occur. In the present study, we investigate the possible central mode of action of GPR54 and kisspeptin ligand. First, we show that GPR54 transcripts are colocalized with gonadotropin-releasing hormone (GnRH) neurons in the mouse hypothalamus, suggesting that kisspeptin, the GPR54 ligand, may act directly on these neurons. Next, we show that GnRH neurons seem anatomically normal in gpr54-/- mice, and that they show projections to the median eminence, which demonstrates that the hypogonadism in gpr54-/- mice is not due to an abnormal migration of GnRH neurons (as occurs with KAL1 mutations), but that it is more likely due to a lack of GnRH release or absence of GnRH neuron stimulation. We also show that levels of kisspeptin injected i.p., which stimulate robust LH and FSH release in wild-type mice, have no effect in gpr54-/- mice, and therefore that kisspeptin acts directly and uniquely by means of GPR54 signaling for this function. Finally, we demonstrate by direct measurement, that the central administration of kisspeptin intracerebroventricularly in sheep produces a dramatic release of GnRH into the cerebrospinal fluid, with a parallel rise in serum LH, demonstrating that a key action of kisspeptin on the hypothalamo-pituitary-gonadal axis occurs directly at the level of GnRH release. The localization and GnRH release effects of kisspeptin thus define GPR54 as a major control point in the reproductive axis and suggest kisspeptin to be a neurohormonal effector.

Animals↗
PubMed2005

The link between nutritional status and insulin sensitivity is dependent on the adipocyte-specific peroxisome proliferator-activated receptor-gamma2 isoform.

The nuclear receptor peroxisome proliferator-activated receptor-gamma (PPARgamma) is critically required for adipogenesis. PPARgamma exists as two isoforms, gamma1 and gamma2. PPARgamma2 is the more potent adipogenic isoform in vitro and is normally restricted to adipose tissues, where it is regulated more by nutritional state than PPARgamma1. To elucidate the relevance of the PPARgamma2 in vivo, we generated a mouse model in which the PPARgamma2 isoform was specifically disrupted. Despite similar weight, body composition, food intake, energy expenditure, and adipose tissue morphology, male mice lacking the gamma2 isoform were more insulin resistant than wild-type animals when fed a regular diet. These results indicate that insulin resistance associated with ablation of PPARgamma2 is not the result of lipodystrophy and suggests a specific role for PPARgamma2 in maintaining insulin sensitivity independently of its effects on adipogenesis. Furthermore, PPARgamma2 knockout mice fed a high-fat diet did not become more insulin resistant than those on a normal diet, despite a marked increase in their mean adipocyte cell size. These findings suggest that PPARgamma2 is required for the maintenance of normal insulin sensitivity in mice but also raises the intriguing notion that PPARgamma2 may be necessary for the adverse effects of a high-fat diet on carbohydrate metabolism.

Adipocytes↗
PubMed2004

How does water boil?

Insight into the boiling of water is obtained from molecular dynamics simulations. The process is initiated by the spontaneous formation of small vacuum cavities in liquid water. By themselves, these defects are very short lived. If, however, several cavities occur at close distances, they are likely to merge into larger vacuum holes. At the liquid-vapor interfaces, single or small groups of water molecules tend to leave the liquid surface. Once the system is propagated beyond the transition state, these evaporation events outnumber the competing reintegration into the hydrogen-bonded network.

Computer Simulation↗
PubMed2004

Nucleation and growth in pressure-induced phase transitions from molecular dynamics simulations: mechanism of the reconstructive transformation of NaCl to the CsCl-type structure.

We perform path sampling molecular dynamics on the pressure-induced reconstructive phase transition from NaCl to CsCl type structure. Unlike the molecular dynamics simulations prior to this work our approach does not drive the process by applying elevated pressure. As a consequence, we are able to observe nucleation events that initiate the successive transformation of the crystal. The competing phases are separated by an interface exhibiting a well-defined structure that propagates through the crystal during phase transition.

Journal Article↗
PubMed2004

Atomistic mechanism of NaCl nucleation from an aqueous solution.

Despite great technological relevance, the initial steps of nucleation and crystal growth from solution are still poorly understood. While experimentally difficult to access, simulations in principle may provide insight at the atomic level. However, in most cases the computational demand dramatically exceeds the scope of current hardware. Since crystallization usually occurs on time scales much larger than the few ns of a molecular dynamics simulation, special techniques for the study of rare events are of particular interest. In the present work the nucleation of sodium chloride aggregates from aqueous solution is investigated from path sampling molecular dynamics simulation. The introduced simulation schemes appear to be widely applicable.

Journal Article↗
PubMed2003

Stella is a maternal effect gene required for normal early development in mice.

stella is a novel gene specifically expressed in primordial germ cells, oocytes, preimplantation embryos, and pluripotent cells. It encodes a protein with a SAP-like domain and a splicing factor motif-like structure, suggesting possible roles in chromosomal organization or RNA processing. Here, we have investigated the effects of a targeted mutation of stella in mice. We show that while matings between heterozygous animals resulted in the birth of apparently normal stella null offspring, stella-deficient females displayed severely reduced fertility due to a lack of maternally inherited Stella-protein in their oocytes. Indeed, we demonstrate that embryos without Stella are compromised in preimplantation development and rarely reach the blastocyst stage. stella is thus one of few known mammalian maternal effect genes, as the phenotypic effect on embryonic development is mainly a consequence of the maternal stella mutant genotype. Furthermore, we show that STELLA that is expressed in human oocytes is also expressed in human pluripotent cells and in germ cell tumors. Interestingly, human chromosome 12p, which harbours STELLA, is consistently overrepresented in these tumors. These findings suggest a similar role for STELLA during early human development as in mice and a potential involvement in germ cell tumors.

Amino Acid Sequence↗
PubMed2003

The GPR54 gene as a regulator of puberty.

BACKGROUND: Puberty, a complex biologic process involving sexual development, accelerated linear growth, and adrenal maturation, is initiated when gonadotropin-releasing hormone begins to be secreted by the hypothalamus. We conducted studies in humans and mice to identify the genetic factors that determine the onset of puberty. METHODS: We used complementary genetic approaches in humans and in mice. A consanguineous family with members who lacked pubertal development (idiopathic hypogonadotropic hypogonadism) was examined for mutations in a candidate gene, GPR54, which encodes a G protein-coupled receptor. Functional differences between wild-type and mutant GPR54 were examined in vitro. In parallel, a Gpr54-deficient mouse model was created and phenotyped. Responsiveness to exogenous gonadotropin-releasing hormone was assessed in both the humans and the mice. RESULTS: Affected patients in the index pedigree were homozygous for an L148S mutation in GPR54, and an unrelated proband with idiopathic hypogonadotropic hypogonadism was determined to have two separate mutations, R331X and X399R. The in vitro transfection of COS-7 cells with mutant constructs demonstrated a significantly decreased accumulation of inositol phosphate. The patient carrying the compound heterozygous mutations (R331X and X399R) had attenuated secretion of endogenous gonadotropin-releasing hormone and a left-shifted dose-response curve for gonadotropin-releasing hormone as compared with six patients who had idiopathic hypogonadotropic hypogonadism without GPR54 mutations. The Gpr54-deficient mice had isolated hypogonadotropic hypogonadism (small testes in male mice and a delay in vaginal opening and an absence of follicular maturation in female mice), but they showed responsiveness to both exogenous gonadotropins and gonadotropin-releasing hormone and had normal levels of gonadotropin-releasing hormone in the hypothalamus. CONCLUSIONS: Mutations in GPR54, a G protein-coupled receptor gene, cause autosomal recessive idiopathic hypogonadotropic hypogonadism in humans and mice, suggesting that this receptor is essential for normal gonadotropin-releasing hormone physiology and for puberty.

Animals↗