The connexin31 (Cx31) gene, a member of the connexin multigene family, is expressed in a characteristic spatiotemporal pattern during placental development in rodents. To elucidate the trophoblast-specific regulation of Cx31, we have isolated the rat Cx31 gene and performed structural and functional promoter analysis. The isolated Cx31 gene contains two exons separated by an intron of 2.6 kb. The first exon of the Cx31 gene is preceded by a TATA-less promoter region. Transcription is initiated in exon 1 from two transcription start sites producting transcripts of 105 and 139 bp. The 935 bp of the 5' flanking region of exon 1 comprises five putative binding sites for the GATA transcription factors as well as a NF-kappaB element, a CAAT-box and E-box/E-box-related sequences. For functional promoter analysis, the rat choriocarcinoma cell line Rcho-1 and the mouse keratinocyte cell line Hel37, which both express Cx31, were chosen. Only constructs including exon 1 and the complete intron showed high activity in transient transfection experiments in both cell lines. All deletion fragments of the putative promoter region, but which contain the entire intron sequence, did not reveal any obvious changes in luciferase activity. However, deletion of 1.1 kb of the intron sequence downstream of the splice donor site resulted in the loss of promoter activity. The intron exhibits no enhancer activity for the gene; however, the mRNA stability was increased in the presence of the intron sequence. These results indicate that parts of the intron sequence are critical for basic promoter function of the Cx31 gene.

Non-Fermi-liquid (NFL) effects in the temperature dependences of both the resistivity and specific heat have been investigated at hydrostatic tatic static pressures p≤1. 7GPa and magnetic fields B≤8T for "A-type" CeCu2Si2, some of its disordered derivatives and its homologue CeNi2Ge2. In dilute (La, Ce) Cu2. 2. Si2, the NFL phenomena hint at a quantum critical point of spin-glass type. In CeCu2Si2, NFL effects show up at the breakdown of phase A. However, the data cannot be explained consistently by the properties of a "nearly antiferromagnetic Fermi liquid". The origin of the NFL effects in CeNi2Ge2 is yet unclear. For this compound, a novel phase transition at T1=0. 9 K (p=1. 7GPa) and an incipient superconducting transition below T=0. 1 K (p=0) in a very clean sample are discovered.

In the alloy system CeCu2(Si1− xGex)2 phase A, i.e., antiferromagnetic order at x > 0, evolves from a heavy-fermion state at x = 0, where TA → 0 and non-Fermi-liquid effects are observed. Here, we present the results of specific-heat measurements on a CeCu2(Si0.9Ge0.1)2 polycrystal as a function of external magnetic field ( 0 ⩽ B ⩽ 8T) and hydrostatic pressure ( 0 ⩽ p ⩽ 1GPa). In this sample a magnetic (TA = 1.4K) and a superconducting (sc) phase (TC = 0.21K) have been observed at p = 0. Our finite-pressure results indicate a subtle difference between steric and chemical effects. At p = 1.0GPa superconductivity sets in at TC ⩽ 0.55K, while TA remains almost unchanged.

The interplay between superconductivity and magnetism in CeCu2Si2 has been investigated by means of microprobe, muon spin rotation and relaxation (mu SR), and specific-heat measurements on four slightly off-stoichiometric polycrystalline samples Ce1+xCu2+ySi2. Microprobe analysis reveals that within the errors (+/-3%) the main phases of all four samples exhibit the ideal stoichiometry 1:2:2 and their relative composition varies by less than 2%. Muon spin rotation and relaxation measurements, however, reveal pronounced differences in their ground states. The nonsuperconducting sample Ce0.99Cu2.02Si2 exhibits a phase transition at T-m=0.67 K to a magnetically ordered ground state of unknown structure, with a lower limit on the size of the frozen moments mu approximate to 0.2 mu(B). For T<T-m slow residual fluctuations of these moments at a rate nu approximate to 3 MHz are observed. In the three superconducting samples comparable magnetic behavior is found in reduced volume fractions. Paramagnetic and magnetic regions are distributed inhomogeneously in these samples, the relative volume fractions being strongly sample and temperature dependent. In all samples considerable volume fractions remain magnetic down to T=60 mK. The present data provide evidence that superconductivity sets in first in the paramagnetic regions, and, on further cooling, reduces the magnetically ordered volume fraction. Superconductivity and magnetic order do not appear to spatially coexist but compete in CeCu2Si2.

Gap junctions have been reported to play a pivotal role in coordinating embryonic development. Here we report the temporal and spatial pattern of connexin31 that has been found to be coexpressed with connexin43 in preimplantation rat embryos. Connexin31 and connexin43 transcripts are abundant in the zygote and degraded in the two- and four-cell stage to low levels for connexin31 and to undetectable ones for connexin43. The uncompacted eight-cell stage lacks the transcripts of both connexins. Reexpression of connexin43 and connexin31 mRNA is found from the compacted eight-cell stage onward. The connexin31 antigen, however, is already detected intracellularly at the uncompacted eight-cell stage. At the blastocyst stage, both connexins are coexpressed in the trophectoderm as well as in the inner cell mass. After implantation, compartmentalization of both connexins is observed. Connexin31 is now expressed exclusively by the cells of the ectoplacental cone and extraembryonic ectoderm, whereas connexin43 is restricted to the cells of the embryo proper. This compartmentalization in connexin expression between the derivatives of the inner cell mass and the trophectoderm may maintain the different developmental programs. THus, connexin31 seems not to be related to the first step in trophoblast lineage development and could serve as a compensatory channel during preimplantation development.

The effect of Si doping on the magnetic properties of the spin-Peierls SP system CuGeO3 was found to differ strongly between polycrystals PC’s and single crystals SC’s. In SC’s, the SP state is suppressed much more strongly, whereas the existence region of the antiferromagnetic AF state is enhanced. We investigated the origin of this difference by means of magnetic susceptibility, specific heat, thermal expansion, Raman scattering, elastic neutron scattering, and x-ray measurements on CuGe1xSixO3 samples prepared under different conditions. The partial oxygen pressure and the temperature during the synthesis were found to have a profound influence on the magnetic properties: preparation under reduced oxygen pressure leads to a stabilization of the AF state, whereas heating above the melting point results in a strong decrease of TSP in Si-doped samples. Therefore, both the AF stabilization and the TSP reduction observed in SC’s are not an intrinsic effect of Si doping PC samples, which can be prepared at lower temperatures and more oxidizing conditions, reflect much better the intrinsic properties of CuGe1xSixO3. We were able to prepare PC samples up to 50 at. % Si and found a continuous decrease of the one-dimensional character of the magnetic properties without pronounced changes in the structure. S0163-18299705321-6

The effect of Si doping on the magnetic properties of the spin-Peierls (SP) system CuGeO3 was found to differ strongly between polycrystals (PC's) and single crystals (SC's). In SC's, the SP state is suppressed much mon strongly, whereas the existence region of the antiferromagnetic (AF) state is enhanced. We investigated the origin of this difference by means of magnetic susceptibility, specific heat, thermal expansion, Raman scattering, elastic neutron scattering, and x-ray measurements on CuGe1-xSixO3 samples prepared under different conditions. The partial oxygen pressure and the temperature during the synthesis were found to have a profound influence on the magnetic properties: preparation under reduced oxygen pressure leads to a stabilization of the AF state, whereas heating above the melting point results in a strong decrease of T-SP in Si-doped samples. Therefore, both the AF stabilization and the TSP reduction observed in SC's are not an intrinsic effect of Si doping PC samples, which can be prepared at lower temperatures and more oxidizing conditions, reflect much better the intrinsic properties of CuGe1-xSixO3. We were able to prepare PC samples up to 50 at. % Si and found a continuous decrease of the one-dimensional character of the magnetic properties without pronounced changes in the structure.

We report low-temperature results of specific-heat and resistivity measurements on the heavy-fermion (HF) compounds CeCu2Si2 and CeNi2Ge2. "Non-Fermi-liquid" effects are observed which suggest the nearness of an antiferromagnetic quantum critical point (QCP) in either system. The observed deviations from the properties of a Landau Fermi liquid (FL) agree with theoretical predictions and point to an anomalous energy dependence of both the quasiparticle mass and the quasiparticle-quasiparticle scattering cross section. However, the complexity of the B-T phase diagram of CeCu2Si2 as well as the specific-heat results for CeNi2Ge2 measured at high pressure (1.7 GPa) indicate that the physics of HF metals is richer than anticipated in the theoretical models.

We analyze the T ln T dependence of the specific heat (C-p) in several Ce binaries and ternaries. We find that these systems can be directly compared by using a scaling law of the type: C-p/t = -D log t + ET0, where t = T/T-0, with the scaling temperature T-0 similar to T-K, D = 7.2 J/(mol K) and 0 < E < 0.14 J/(mol K-2). This general function describes those systems within the 0.005 < t < 0.5 range and accounts for nearly 1/2 of the expected entropy of the Ce-doublet.

We present a reinvestigation of the complex magnetic phase diagram of the heavy-fermion system Ce(Cu1-xNix)(2)Ge-2 by employing measurements of the specific heat, C(T), and thermal expansion, alpha(T), on high-quality single crystals with x = 0, 0.02, 0.05, 0.5 and 0.8 in magnetic fields B less than or equal to 8T. In addition to what was observed in polycrystalline samples multiple phase-transition anomalies could be resolved in these single crystals for x<0.5 and 1.5 K < T < T-N Sharp anomalies in C(T) and thermal hysteresis in a(T) give evidence that these transitions are of first order (x = 0.02, 0.05). Our findings demonstrate that the structure of the antiferromagnetically ordered state depends on subtle changes of the hybridization of the Ce-4f state to its local environment, while the interplay of Kondo- and RKKY-interaction, which determines the existence of a long-range ordered state is governed by volume and/or density-of-states effects.

Connexin31 (cx31) expression seems to play an important role during trophoblast development in rodents. During preimplantation cx31 is coexpressed with cx43 in the trophoblast cells as well as in the inner cell mass of the blastocyst. Following implantation, compartmentalization of both connexins occurs: cx31 is expressed in the proliferative and invasive trophoblast and cx43 in the embryo proper. Trophoblast differentiation into a functional placenta is indicated by a switch from cx31 to cx26 and cx43 [1]. Such a switch from cx31 to cx43 accompanied by a differentiation process can be induced in rat trophoblast cells by retinoic acid [2]. To further elucidate the trophoblast specific regulation properties of cx31, we have isolated the cx31 gene and performed structural and functional promoter analysis. The isolated rat cx31 gene contains two exons separated by an intron of 2.6 kb. Exon 1 comprises 105 and 139 bp, respectively due to two transcription start sites. Within 935 bp of the 5' flanking region of exon 1, four putative binding sites for GATA trancription factors, furthermore a NF-KB element, a CAAT-box and an E-box were identified. For functional promoter analysis two cell lines, rat choriocarcinoma cells and mouse keratinocyte cells, which both express cx31 were chosen. HeLa cells were used as a negative control. A construct including 880 bp of the promoter region, exon 1 and the intron linked to a luciferase reporter gene showed activity in transient transfection experiments in both cell lines. Deleting the 880 bp construct to 420 bp led to a decrease in promotor activity. Even without promotor the intron itself conferred the same basic activity as found for the 100 bp construct. Deletion of 2.3 kb from the 3' end of the intron resulted in a loss of promoter activity. Cell specific differences could be observed within the 5' region of the promoter. All constructs tested did not show any activity in HeLa cells. In conclusion an enhancer seems to be located between 880 bp and 420 bp in the promoter region and the intron plays a role in conferring activity.

Ce-based heavy-fermion superconductors (HFSC) exhibit magnetic phase diagrams differing from those of both the ideal Kondo lattice and substitutional alloys with intact Ce sublattice. While for the Ce-based HFSC (with well localized 4f shell) superconductivity and antiferromagnetic order seem to compete with each other, both phenomena typically coexist for U-based HFSC (with less localized 5f shell).

SUMMARY 1. Trophoblast invasion during embryo implantation in some aspects resembles tumour cell invasion but, unlike tumour cells, trophoblast cells are able to differentiate and establish a placenta. Because direct cell‐cell communication is believed to be involved in growth control and differentiation, we have investigated connexin (cx) gene expression during trophoblast development. 2. he‐implantation embryos expressed cx43 as well as ex31 proteins from the 8‐cell stage onwards. Following implantation, compartmentalization of both connexins occurred: cx31 expression was restricted to the invasive trophoblast cell population, whereas the embryo proper was characterized by cx43. Trophoblast differentiation was indicated by induction of cx26 in the labyrinth and cx43 in the spongiotrophoblast accompanied by a disappearance of cx31. Comparison with trophoblast cell lines revealed that rat trophoblast HRP‐1 cells express connexin43, while malignant choriocarcinoma cells express cx31. Treatment with retinoic acid led to a disappearance of cx31 in the choriocarcinoma. Both cell lines reduced their invasion properties after retinoic acid treatment, but growth retardation was only observed in the malignant trophoblast. 3. It seems that the cx31 channel is needed for trophoblast cell populations to maintain the highly proliferative properties but does not alter their invasion properties.

We have characterized the spatial and temporal expression pattern of six different connexin genes and E-cadherin during trophectoderm development in the rat. During the initial phase of trophoblast invasion at 6 days postcoitum (dpc), the trophoblast expressed E-cadherin but no connexin expression could be observed. With progressing invasion of the polar trophoblast into the maternal decidua, from 7 dpc onwards E-cadherin expression in the ectoplacental cone cells was lost and was now restricted to the extraembryonic ectoderm. In the ectoplacental cone and extraembryonic ectoderm instead connexin31 mRNA and protein could be found. This pattern was maintained up to day 10 postcoitum. The start of labyrinthine trophoblast differentiation from day 11 postcoitum onwards was characterized by persisting expression of E-cadherin in the extraembryonic ectoderm and its derivative, the chorionic plate. In addition to E-cadherin, from 10 dpc onwards, connexin26 started to be expressed in the chorionic plate, and both molecules remained coexpressed in the labyrinthine trophoblast of the mature placenta. During this differentiation process connexin31 remained expressed mainly in the proliferating spongiotrophoblast. From day 14 postcoitum onwards, the expression of connexin31 in the spongiotrophoblastic cells decreased, and in parallel they started to express connexin43. The trophoblastic giant cells, first characterized by connexin31, lost all of the investigated connexins during midgestation on day 12 postcoitum but started to express connexin43 from day 18 postcoitum onwards. Our studies suggest that loss of E-cadherin and induction of connexin31 expression is correlated with the proliferative and invasive stages of the ectoplacental cone, whereas appearance of connexin26, E-cadherin and connexin43 reflects the switch to the differentiated phenotypes of the mature placenta.

We present results of low-temperature calorimetric and resistive measurements on the isostructural heavy-fermion compounds and . `Non-Fermi-liquid' effects are established which suggest the nearness of an antiferromagnetic quantum critical point (QCP) in both systems. The observed deviations from the properties of a Landau Fermi liquid (FL) may be related to anomalous energy dependences of both the quasiparticle mass and the quasiparticle - quasiparticle scattering cross section. For , a moderately heavy FL can be recovered by application of moderate values of either magnetic field or hydrostatic pressure. For p = 1.7 GPa a novel, non-superconducting, phase transition has been discovered at .

We present the results of specific-heat and resistivity measurements as a function of temperature, magnetic field and hydrostatic pressure on the Kondo lattice CeNi2Ge2, the heavy-fermion superconductors CeCu2Si2 and UBe13 as well as the low-carrier-density system Yb4As3. "Non-Fermi-liquid" effects in the low-temperature normalstate properties of the three former systems are consistent with the existence of a "nearby" quantum critical point, presumably of antiferromagnetic type. Yb4As3, though showing the outward appearance of a Landau-type heavy-fermion metal, behaves very differently, i.e. as an extreme two-fluid system.

The controlled invasiveness of the trophoblast is based on the balance between invasive properties at implantation and the differentiation program of the developing placenta. During placental development in rats a switch of connexin gene expression has been observed in parallel to the switch from the invasive to the differentiated phenotype of trophoblast cells. To investigate the role of connexin expression for trophoblast invasion, proliferation, and differentiation, we studied one rat trophoblast (HRP-1) and one rat choriocarcinoma cell line (Rcho-1). The choriocarcinoma cells were characterized by expression of cx31 and a lack of E-cadherin, corresponding to the invasive trophoblastin vivo,whereas HRP-1 cells expressed cx43, normally found in the spongiotrophoblast and in late giant cells, and E-cadherin. Upon retinoic acid treatment, Rcho-1 cells irreversibly lost cx31 expression, accompanied by a loss of functional coupling. No changes in regard to connexin expression and cell–cell communication could be observed in HRP-1 cells. In addition, treatment of Rcho-1 cells with retinoic acid for 7 days upregulated expression of cx43 transcript, but no protein could be found. Proliferation was clearly reduced and the mean volume of cells doubled from Day 4 to Day 7 of retinoic acid treatment in Rcho-1 cells, while both parameters were not affected in HRP-1 cells. Both cell lines showed a similar invasion rate using a Matrigel invasion assay, and invasion was equally suppressed upon retinoic acid treatment. Thus the different connexin expression appears more likely to play a role in regulating proliferation and differentiation along the multilineage pathway than invasiveness of rat trophoblast cells.