Quantum Critical Point in the Itinerant Ferromagnet Ni_{1-x}Rh_{x}.

We report a chemical substitution-induced ferromagnetic quantum critical point in polycrystalline Ni_{1-x}Rh_{x} alloys. Through magnetization and muon spin relaxation measurements, we show that the ferromagnetic ordering temperature is suppressed continuously to zero at x_{crit}=0.375 while the magnetic volume fraction remains 100% up to x_{crit}, pointing to a second order transition. Non-Fermi liquid behavior is observed close to x_{crit}, where the electronic specific heat C_{el}/T diverges logarithmically, while immediately above x_{crit} the volume thermal expansion coefficient α_{V}/T and the Grüneisen ratio Γ=α_{V}/C_{el} both diverge logarithmically in the low temperature limit, further indication of a ferromagnetic quantum critical point in Ni_{1-x}Rh_{x}.

Antiadhesive phthalides from Apium graveolens fruits against uropathogenic E. coli.

ETHNOPHARMACOLOGICAL RELEVANCE: Fruits of Apium graveolens (celery) are used traditionally in Persian and European medicine for the treatment of uncomplicated urinary tract infections. AIM OF THE STUDY: The study aimed at identifying potential antiadhesive compounds from celery extracts to provide strategies for improved standardization of the herbal material. MATERIALS AND METHODS: Decoction, hydroalcoholic and acetone extracts were prepared from celery fruits. Bioassay-guided fractionation was performed by Fast Centrifugal Partition Chromatography and preparative HPLC, followed by LC-MS and NMR investigations for structure elucidation. The antiadhesive activity of extracts, fractions and purified compounds was assessed by flow cytometry, evaluating the adhesion of fluorescent-labelled uropathogenic bacteria (UPEC NU14) to T24 bladder cells; mannose served as positive control. Influence of the extract on gene expression of selected adhesins and fitness genes was monitored by qPCR. RESULTS: Concentration-dependent antiadhesive activity was found for the hydroalcoholic and even more for the acetone extract AE (IC50 85 µg/mL) from celery fruits. Bioassay-guided fractionation revealed the presence of the phthalides senkyunolide (1, inactive) and sedanenolide (2, IC50 790 µM). 2 is assessed as the main antiadhesive compound, which accounts for 4.0% in the water extract, for 18% in the hydroethanolic extract and for 71% in AE. Additionally a similar phthalide, Z-ligustilide (5), was shown to exert an IC50 of 611 µM. Furthermore, AE caused a significant upregulation of fimH and sfaG in free floating, non-attached UPEC and significantly down-regulated these genes in adherent bacteria. CONCLUSIONS: Phthalides were identified as the main active compounds in polar and semi-polar extracts, which exert strong antiadhesive activity against uropathogenic E. coli. The current findings support the traditional use in phytotherapy for urinary tract infections and provide a base for standardization of the herbal material.

Magnetic and Structural Quantum Phase Transitions in CeCu_{6-x}Au_{x} are Independent.

The heavy-fermion compound CeCu_{6-x}Au_{x} has become a model system for unconventional magnetic quantum criticality. For small Au concentrations 0≤x<0.16, the compound undergoes a structural transition from orthorhombic to monoclinic crystal symmetry at a temperature T_{s} with T_{s}→0 for x≈0.15. Antiferromagnetic order sets in close to x≈0.1. To shed light on the interplay between quantum-critical magnetic and structural fluctuations we performed neutron-scattering and thermodynamic measurements on samples with 0≤x≤0.3. The resulting phase diagram shows that the antiferromagnetic and monoclinic phase coexist in a tiny Au concentration range between x≈0.1 and 0.15. The application of hydrostatic and chemical pressure allows us to clearly separate the transitions from each other and to explore a possible effect of the structural transition on the magnetic quantum-critical behavior. Our measurements demonstrate that at low temperatures the unconventional quantum criticality exclusively arises from magnetic fluctuations and is not affected by the monoclinic distortion.

Entropy Evolution in the Magnetic Phases of Partially Frustrated CePdAl.

In the heavy-fermion metal CePdAl, long-range antiferromagnetic order coexists with geometric frustration of one-third of the Ce moments. At low temperatures, the Kondo effect tends to screen the frustrated moments. We use magnetic fields B to suppress the Kondo screening and study the magnetic phase diagram and the evolution of the entropy with B employing thermodynamic probes. We estimate the frustration by introducing a definition of the frustration parameter based on the enhanced entropy, a fundamental feature of frustrated systems. In the field range where the Kondo screening is suppressed, the liberated moments tend to maximize the magnetic entropy and strongly enhance the frustration. Based on our experiments, this field range may be a promising candidate to search for a quantum spin liquid.

Pauli-limited multiband superconductivity in KFe2As2.

The upper critical field H(c2)(T) of the multiband superconductor KFe2As2 has been studied via low-temperature thermal expansion and magnetostriction measurements. We present compelling evidence for Pauli-limiting effects dominating H(c2)(T) for H || a, as revealed by a crossover from second- to first-order phase transitions to the superconducting state in the magnetostriction measurements down to 50 mK. Corresponding features were absent for H || c. To our knowledge, this crossover constitutes the first confirmation of Pauli limiting of the H(c2)(T) of a multiband superconductor. The results are supported by modeling Pauli limits for single-band and multiband cases.

Evolution of the magnetic structure in CeCu(5.5)Au(0.5) under pressure towards quantum criticality.

In the prototypical heavy-fermion system CeCu(6-x)Au(x), a magnetic quantum critical point can be tuned by Au concentration x, hydrostatic pressure p, or magnetic field B. A striking equivalence of the tuning behavior with x or p had been found with respect to thermodynamic and transport properties. By means of elastic neutron scattering on single crystalline CeCu(5.5)Au(0.5), we demonstrate this x-p equivalence on a microscopic level by showing that the magnetic ordering wave vector q(m) can be tuned accordingly. At ambient pressure,CeCu(5.5)Au(0.5) orders at q(m)≈(0.59 0 0). Upon applying p=4.1 kbar, q(m)≈(0.61 0 0.21) is found corresponding to CeCu(5.6)Au(0.4) at ambient pressure. The transition seems to occur in a first-order fashion and to be governed by slight changes in the nesting properties of the Fermi surface.

Towards the identification of a quantum critical line in the (p, B) phase diagram of CeCoIn5 with thermal-expansion measurements.

The low-temperature thermal expansion of CeCoIn(5) single crystals measured parallel and perpendicular to magnetic fields B oriented along the c axis yields the volume thermal-expansion coefficient ß. Considerable deviations of ß(T) from Fermi-liquid behavior occur already within the superconducting region of the (B, T) phase diagram and become maximal at the upper critical field B(c2)(0). However, ß(T) and the Grüneisen parameter Γ are incompatible with a quantum critical point at B(c2)(0), but allow for a quantum criticality shielded by superconductivity and extending to negative pressures for B

Importance of in-plane anisotropy in the quasi-two-dimensional antiferromagnet BaNi2V2O8.

The phase diagram of the quasi-two-dimensional antiferromagnet BaNi(2)V(2)O(8) is studied by specific heat, thermal expansion, magnetostriction, and magnetization for magnetic fields applied perpendicular to c. At micro(o)H* approximately 1.5 T, a crossover to a high-field state, where T(N)(H) increases linearly, arises from a competition of intrinsic and field-induced in-plane anisotropies. The pressure dependences of T(N) and H* are interpreted using the picture of a pressure-induced in-plane anisotropy. Even at zero field and ambient pressure, in-plane anisotropy cannot be neglected, which implies deviations from pure Berezinskii-Kosterlitz-Thouless behavior.

The internalized interleukin-1 activation complex in fibroblasts localizes to the Golgi apparatus.

In order to investigate binding and internalization of interleukin-1 (IL-1) by confocal laser scanning microscopy, we established a model system comprising an IL-1 receptor type I (IL-1R1) overexpressing transfectant of the murine fibrosarcoma cell line L929 (L929R1) and an N-terminal FLAG-tagged human recombinant IL-1 alpha (FLAG-IL-1 alpha). The function of the transfected receptors was shown by their IL-1-induced association with a kinase activity. The biological activity of the purified FLAG-IL-1 alpha was comparable to the unmodified molecule. L929RI cells were exposed to saturating concentrations of FLAG-IL-1 alpha. Two-color fluorescence analysis revealed increasing cell surface binding of FLAG-IL-1 alpha to the receptor over 30 min. This was followed by internalization and accumulation of the ligand/receptor complex at the Golgi apparatus. After 3 hr the receptor signal significantly decreased and patches of FLAG-epitopes reappeared on the cell surface, no longer colocalized with IL-1R1. Thus, in this model, the previously assumed nuclear accumulation of IL-1 was not detected but rather localization of the internalized IL-1/IL-1R1-complex to the Golgi apparatus was found. Direct effects of IL-1 on the nucleus or the nuclear membrane therefore are unlikely.

Increased poly(ADP-ribosyl)ation in intact cells by cisplatin treatment.

Cisplatin (DDP) is a clinically important antitumor drug that induces the formation of DNA-DNA and DNA-protein crosslinks. We have studied whether poly(ADP-ribosyl)ation, a post-translational modification of nuclear proteins that is drastically increased by the presence of DNA strand breaks and plays a role in DNA repair, is induced following DDP treatment of cell cultures. By using an immunofluorescence technique for the in situ detection of poly(ADP-ribose) in intact cells, we found spotty nuclear signals after DDP treatment of O-342 rat ovarian tumor cells or CV-1 monkey cells, but not in untreated control cells, nor in DDP-treated cells postincubated with the ADP-ribosylation inhibitor 3-aminobenzamide. Our results thus provide direct evidence for an involvement of poly(ADP-ribosyl)ation in the cell's response to DDP treatment and, more generally, illustrate the versatility of this rapid in situ method for the detection of increased poly(ADP-ribosyl)ation in living cells.

Gastroenteropancreatic neuroendocrine tumours contain a common set of synaptic vesicle proteins and amino acid neurotransmitters.

Human neuroendocrine tumours of the gastroenteropancreatic system contain major integral membrane proteins of small synaptic vesicles of neurons, together with characteristic membrane polypeptides of large dense-core vesicles of neurons and neuroendocrine cells. The membrane polypeptides characteristic for small synaptic and large dense-core vesicles are detected in pheochromocytomas (n = 6), functional (n = 6) and non-functional (n = 6) foregut, and midgut carcinoids (n = 17). All gastroenteropancreatic tumours contain large amounts of amino acid neurotransmitters, i.e. glycine and glutamate. gamma-Aminobutyric acid, however, is only found in some foregut carcinoids. Thus, neuroendocrine gastroenteropancreatic tumours possess a vesicle type with a content and membrane composition similar to small synaptic vesicles of neurons.

Poly(ADP-ribose) polymerase activity in mononuclear leukocytes of 13 mammalian species correlates with species-specific life span.

Poly(ADP-ribosyl)ation is a eukaryotic posttranslational modification of proteins that is strongly induced by the presence of DNA strand breaks and plays a role in DNA repair and the recovery of cells from DNA damage. We compared poly(ADP-ribose) polymerase (PARP; EC 2.4.2.30) activities in Percoll gradient-purified, permeabilized mononuclear leukocytes from mammalian species of different maximal life span. Saturating concentrations of a double-stranded octameric oligonucleotide were applied to provide a direct and maximal stimulation of PARP. Our results on 132 individuals from 13 different species yield a strong positive correlation between PARP activity and life span (r = 0.84; P << 0.001), with human cells displaying approximately 5 times the activity of rat cells. Intraspecies comparisons with both rat and human cells from donors of all age groups revealed some decline of PARP activity with advancing age, but it was only weakly correlated. No significant polymer degradation was detectable under our assay conditions, ruling out any interference by poly(ADP-ribose) glycohydrolase activity. By Western blot analysis of mononuclear leukocytes from 11 species, using a crossreactive antiserum directed against the extremely well-conserved NAD-binding domain, no correlation between the amount of PARP protein and the species' life spans was found, suggesting a greater specific enzyme activity in longer-lived species. We propose that a higher poly(ADP-ribosyl)ation capacity in cells from long-lived species might contribute to the efficient maintenance of genome integrity and stability over their longer life span.

Poly(ADP-ribosyl)ation: its role in inducible DNA amplification, and its correlation with the longevity of mammalian species.

In this paper, we review our recent work on poly(ADP-ribosyl)ation and its relationships with DNA amplification and with the life span of different mammalian species. Poly(ADP-ribosyl)ation is a eukaryotic posttranslational protein modification catalyzed by poly(ADP-ribose) polymerase (PARP; EC 2.4.2.30). This enzyme is strongly activated by DNA strand breaks and apparently plays a role in DNA repair and other cellular responses to DNA damage. Our data from two different cell culture systems for inducible DNA amplification strongly suggest that poly(ADP-ribosyl)ation acts as a negative regulatory factor in the DNA amplification induced by carcinogens. Furthermore, we could show a strong positive correlation between directly stimulated PARP activities in mononuclear leukocytes of 13 mammalian species and the species' maximal life spans. The hypothesis is raised that a higher poly(ADP-ribosyl)ation capacity of long-lived species might contribute to the efficient maintenance of genome integrity and stability over their longer life span. Finally, we could show that the selectively overexpressed PARP DNA-binding domain efficiently inhibits poly(ADP-ribosyl)ation in a transdominant manner. This molecular genetic approach should permit further interventional studies on biological role(s) of poly(ADP-ribosyl)ation without application of low-molecular-weight PARP inhibitors, thus avoiding any of their possible side effects.

Direct stimulation of poly(ADP ribose) polymerase in permeabilized cells by double-stranded DNA oligomers.

Poly(ADP ribosyl)ation, a post-translational modification of nuclear proteins catalyzed by poly (ADP ribose) polymerase, is an immediate response of most eukaryotic cells to DNA strand breaks and has been implicated in DNA repair and other cellular phenomena associated with DNA strand breakage. Poly(ADP ribose) polymerase activity levels have been frequently assayed by incubating permeabilized cells with radioactively labeled NAD+ as substrate. In such assays enzyme activation has routinely been achieved indirectly by prior exposure of living cells to carcinogens or by adding DNase I to permeabilized cells, thereby introducing strand breaks in chromosomal DNA. Here we show that, as an alternative method, the direct activation of purified poly(ADP ribose) polymerase by double-stranded oligonucleotides (N. A. Berger and S. I. Petzold, 1985, Biochemistry 24, 4352-4355) can be adopted for permeabilized cell systems. The inclusion of a palindromic decameric deoxynucleotide in the reaction buffer stimulated the enzyme activity in permeabilized Molt-3 human lymphoma cells up to 30-fold (at 50 micrograms/ml [corrected] oligonucleotide concentration) in a concentration-dependent manner. The activating effect of oligonucleotides was also evident when ethanol-fixed HeLa cells were postincubated with NAD+ to allow poly(ADP ribose) synthesis to occur in situ, which was detected as specific anti-poly (ADP ribose) immunofluorescence. We conclude that double-stranded oligonucleotides can be conveniently used as chemically and stoichiometrically well-defined poly (ADP ribose) polymerase activators in permeabilized or ethanol-fixed mammalian cells.

Steroidogenic capabilities of the early mouse embryo.

Preimplantation embryos from ICR albino mice were used to determine progesterone and estradiol-17beta production during incubation in BMOC-2. Following culture of 40 embryos/culture at either the morula, early blastocyst or late blastocyst stages, progesterone and estradiol-17beta contents were 192 +/- 27 and 82 +/- 22 pg, 289 +/- 50 and 147 +/- 46 pg and 157 +/- 28 and 88 +/- 23 pg, respectively, for incubated samples and 306 +/- 68 and 89 +/- 40 pg, 404 +/- 63 and 125 +/- 44 pg, and 241 +/- 54 and 86 +/- 39 pg, respectively for control samples. Although, there were significant stage of development and treatments effects (p less than 0.05) for progesterone, production of this steroid was not evident. These data suggest that the early preimplantation mouse embryo does not produce progesterone or estradiol-17beta in a defined culture system.