Unconventional short-range structural fluctuations in cuprate superconductors.

The interplay between structural and electronic degrees of freedom in complex materials is the subject of extensive debate in physics and materials science. Particularly interesting questions pertain to the nature and extent of pre-transitional short-range order in diverse systems ranging from shape-memory alloys to unconventional superconductors, and how this microstructure affects macroscopic properties. Here we use neutron and X-ray diffuse scattering to uncover universal structural fluctuations in La2-xSrxCuO4 and Tl2Ba2CuO6+δ, two cuprate superconductors with distinct point disorder effects and with optimal superconducting transition temperatures that differ by more than a factor of two. The fluctuations are present in wide doping and temperature ranges, including compositions that maintain high average structural symmetry, and they exhibit unusual, yet simple scaling behaviour. The scaling regime is robust and universal, similar to the well-known critical fluctuations close to second-order phase transitions, but with a distinctly different physical origin. We relate this behaviour to pre-transitional phenomena in a broad class of systems with structural and magnetic transitions, and propose an explanation based on rare structural fluctuations caused by intrinsic nanoscale inhomogeneity. We also uncover parallels with superconducting fluctuations, which indicates that the underlying inhomogeneity plays an important role in cuprate physics.

Enhanced superconductivity and ferroelectric quantum criticality in plastically deformed strontium titanate.

The properties of quantum materials are commonly tuned using experimental variables such as pressure, magnetic field and doping. Here we explore a different approach using irreversible, plastic deformation of single crystals. We show that compressive plastic deformation induces low-dimensional superconductivity well above the superconducting transition temperature (Tc) of undeformed SrTiO3, with evidence of possible superconducting correlations at temperatures two orders of magnitude above the bulk Tc. The enhanced superconductivity is correlated with the appearance of self-organized dislocation structures, as revealed by diffuse neutron and X-ray scattering. We also observe deformation-induced signatures of quantum-critical ferroelectric fluctuations and inhomogeneous ferroelectric order using Raman scattering. Our results suggest that strain surrounding the self-organized dislocation structures induces local ferroelectricity and quantum-critical dynamics that strongly influence Tc, consistent with a theory of superconductivity enhanced by soft polar fluctuations. Our results demonstrate the potential of plastic deformation and dislocation engineering for the manipulation of electronic properties of quantum materials.

The HER tyrosine kinase inhibitor CI1033 enhances cytotoxicity of 7-ethyl-10-hydroxycamptothecin and topotecan by inhibiting breast cancer resistance protein-mediated drug efflux.

Because the activities of HER family members are elevated and/or aberrant in a variety of human neoplasms, these cell surface receptors are receiving increasing attention as potential therapeutic targets. In the present study, we examined the effect of combining the HER family tyrosine kinase inhibitor CI1033 (PD 183805) with the topoisomerase (topo) I poison 7-ethyl-10-hydroxycamptothecin (SN-38), the active metabolite of irinotecan, in a number of different cell lines. Colony-forming assays revealed that the antiproliferative effects of simultaneous treatment with CI1033 and SN-38 were synergistic in T98G glioblastoma cells and HCT8 colorectal carcinoma cells, whereas sequential treatments were additive at best. In additional studies examining the mechanistic basis for these findings in T98G cells, immunoblotting revealed that the inhibitory effects of CI1033 on epidermal growth factor receptor autophosphorylation were unaffected by SN-38. Likewise, CI1033 had no effect on topo I polypeptide levels, localization, or activity. Nonetheless, CI1033 markedly enhanced the number of covalent topo I-DNA complexes stabilized by SN-38 or the related agent topotecan (TPT). Analysis of intracellular SN-38 levels by high-performance liquid chromatography and intracellular TPT levels by flow microfluorometry revealed that CI1033 increased the steady-state accumulation of SN-38 and TPT by 9.4 +/- 1.9- and 1.8 +/- 0.2-fold, respectively. Further evaluation revealed that the initial rate of TPT uptake was unaffected by CI1033, whereas the rate of efflux was markedly diminished. Additional studies demonstrated that T98G and HCT8 cells express the breast cancer resistance protein (BCRP), a recently cloned ATP binding cassette transporter. Moreover, CI1033 enhanced the uptake and cytotoxicity of SN-38 and TPT in cells transfected with BCRP but not empty vector. Conversely, CI1033 accumulation was diminished in cells expressing BCRP, suggesting that CI1033 is a substrate for this efflux pump. These results indicate that CI1033 can modulate the accumulation and subsequent cytotoxicity of two widely used topo I poisons in cells that have no history of previous exposure to these agents.

Submerged permanent teeth: literature review and case report.

Submerged permanent teeth pose a diagnostic as well as a treatment planning dilemma. Teeth with delayed eruption, arrested eruption, and paradoxical movement all can appear to be submerged teeth. While orthodontics may seem like the simplest solution, it often has the most frustrating results. A multidisciplinary approach often is required, utilizing surgical, orthodontic, and prosthetic components.

A single nucleotide substitution converts potato spindle tuber viroid (PSTVd) from a noninfectious to an infectious RNA for nicotiana tabacum.

Mechanical inoculation of Nicotiana tabacum with the PSTVd isolate KF 440-2 from the host plant tomato resulted in the de novo emergence, replication, and accumulation of a new "tobacco variant," designated PSTVd NT. It produces no symptoms in tobacco but, like PSTV KF 440-2, severe ones in tomato. The sequence analysis of PSTVd NT revealed a single nucleotide substitution from C-->U at position 259. Autonomous viroid replication was also induced in tobacco by genomic integration of oligomeric cDNA copies of PSTVd KF 440-2. Although these cDNAs contained the original tomato-specific C259, the circular PSTVd RNA subsequently accumulating in tobacco also exhibited the C259-->U259 substitution. In the secondary structure of PSTVd, nucleotide 259 is part of an internal loop analogous to loop E of eukaryotic 5S rRNA and presumed to be the only bulged extrahelical nucleotide of this loop. The C259 in PSTVd KF 440-2 and in practically all other isolates and the U259 in PSTVd NT of the loop E-like structure might be involved in protein binding and in viroid processing. The new variant PSTVd NT is genetically stable in both tobacco and tomato.

In vitro-generated 'inverse' chimeric Coleus blumei viroids evolve in vivo into infectious RNA replicons.

The three Coleus blumei viroids (CbVd) CbVd 1-RL, CbVd 2-RL and CbVd 3-RL occur naturally in plants of Coleus blumei cultivar (cv.) 'Ruhm von Luxemburg'. CbVd 2-RL is a viroid chimera made up of the right half of CbVd 1-RL and the left half of CbVd 3-RL. Using the cDNAs of the left half of CbVd 1-RL and the right half of CbVd 3-RL, 'inverse' viroid chimeras (CbVd-Ch1 and CbVd-Ch2) were constructed in vitro as dimeric cDNA units. The in vitro-generated cDNA-transcripts of CbVd-Ch1 and CbVd-Ch2 were used to inoculate plants of Coleus blumei cv. 'Ruhm von Luxemburg' harbouring CbVd 1-RL and CbVd 3-RL, leading to the emergence of new viroid-like RNA replicons, named CbVd A-1 and CbVd A-2, that hitherto have not been found in Coleus plants. The sequences of CbVd A-1 and CbVd A-2 are not identical to the corresponding sequences of the cDNA-transcripts of CbVd-Ch1 and CbVd-Ch2, but show a deletion of a segment at the border of the two original halves as well as two U to A transitions. When the cDNA-transcripts of CbVd-Ch1 and CbVd-Ch2 were used to inoculate plants of Coleus blumei cv. 'Scarlet Dragonfly' that were either viroid-free or infected with CbVd 1-RL and CbVd 3-RL, no new viroid-like RNAs emerged. However, the cDNA-transcripts of CbVd A-1 and CbVd A-2 are infectious by mechanical inoculation of viroid-free plants of cv. 'Scarlet Dragonfly', thus proving their viroid nature.

The molecular structure of Iresine viroid, a new viroid species from Iresine herbstii ('beefsteak plant').

A viroid was isolated from Iresine herbstii plants using the bidirectional PAGE method for analysis of small circular RNA molecules. The viroid was transmitted to viroid-free Iresine herbstii plants of the cultivar 'Aureoreticulata' by mechanical inoculation. Infected plants did not develop any symptoms. The new viroid species has been named Iresine viroid (IrVd). It is a member of the potato spindle tuber viroid group and consists of 370 nucleotides, 227 G+C, 143 A+U (GC content, 61.4%). The most stable rod-like secondary structure of this viroid has 86 G:C, 34 A:U and 12 G:U base pairs with a minimum free energy of -153.4 kcal/mol (-641.2 kJ/mol). The sequence and the position of the terminal conserved region (TCR) within the rod-like secondary structure of IrVd differ from the other known TCRs. The structure of the left terminal domain of IrVd may reflect the result of an intramolecular RNA recombination event.

Secondary structure probing of potato spindle tuber viroid (PSTVd) and sequence comparison with other small pathogenic RNA replicons provides evidence for central non-canonical base-pairs, large A-rich loops, and a terminal branch.

Using PCR and in vitro transcription, linear (non-circular) unit-length (+)strand RNA molecules of a lethal PSTVd variant were produced which are able to initiate typical disease symptoms when inoculated into tomato. Non-denaturing gel electrophoresis shows that these transcripts can adopt the same two conformations as circular PSTVd molecules, namely a fast migrating rod-like and a slowly migrating cruciform structure. The rod-like conformer of two end-labelled transcripts was probed with nucleases and dimethyl sulphate, revealing that in solution its right part is identical to computer prediction. In the left part, however, three unique features could be substantiated. (1) In the central region a UV-cross-linkable loop is closed and thus contains non-canonical base-pairs ("loop E structure"). (2) Three large "pre-melting loops" are present at 25 degrees to 37 degrees C. The structure of the leftmost one, which is A-rich and conserved in most viroids, correlates with pathogenicity. (3) Two small stem-loops instead of an unbranched structure are found at the left terminus. These hairpins can form in all "large" viroids (approximately 300 nucleotides or longer), thus placing the dodecamer conserved among these viroids, GGUUCCUGUGGU, within the upper helix and the branch junction. A large viroid from Iresine lacks one of these hairpins, whereas all "small" viroids (approximately 300 nucleotides or smaller) lack both. In several plant virus satellite RNAs and the newt satellite RNA, the motif GAUUU(U) and dodecamer remnants appear in an equivalent structure comprising two or three hairpins. Using lead- and terbium-induced cleavage of the RNA, metal binding sites were found, mostly in loops. Thus, probing of PSTVd RNA and comparison with other.

Viroids proper can be distinguished from hammerhead viroids and satellite RNAs through their dinucleotide composition.

G + C-rich viroids proper exhibit a unique dinucleotide composition in that AU and UA are much less frequent than expected. Thus, evaluation of the dinucleotide pattern allows a quick discrimination between viroids proper and similar RNAs from plants, such as hammerhead-containing viroids, satellite RNAs, and defective interfering RNAs. In addition to sequence alignment, this method might be useful for the classification of a newly found small RNA replicon.

A new sequence variant of Coleus blumei viroid 1 from the Coleus blumei cultivar "Rainbow Gold'.

A viroid was isolated from symptomless Coleus blumei cultivar (cv.) 'Rainbow Gold' plants using the bidirectional PAGE method for analysis of small circular RNA molecules. The viriod was transmitted to viroid-free plants of Coleus blumei cv. 'Scarlet Dragonfly' by mechanical inoculation. Cloning and sequencing revealed that the viriod from the Coleus cv. 'Rainbow Gold' is closely related to the Coleus blumei viriod 1-BvA (CbVd 1-BvA) isolated from the Coleus cv. 'Bienvenue'. Therefore, new viroid sequence variant has been named Coleus blumei viriod 1-RG (CbVd 1-RG). Coleus blumei viriod 1-RG consists of 251 nucleotides, 140 G + C, 111 A + U with a GC content of 55.4%. The most stable rod-like secondary structure of this viroid has 53 G:C, 29 A:U and 5 G:U base pairs with a minimum free energy (at 25 degrees C) of -81.2 kcal/mol (-339.4 kJ/mol). The right terminal domain shows a high sequence similarity to the corresponding domain of hop latent viroid (HLVd).

A viroid from Brunfelsia undulata closely related to the Columnea latent viroid.

A viroid was isolated from symptomless Brunfelsia undulata plants using the bidirectional PAGE method for analysis of small circular RNA molecules. The viroid was transmitted to tomato by mechanical inoculation. Infected tomato plants developed symptoms similar to those caused by intermediate strains of potato spindle tuber viroid (PSTVd). Cloning and sequencing revealed that the viroid from Brunfelsia undulata is closely related to the Columnea latent viroid (CLVd). Therefore, the new viroid sequence variant has been named CLVd-B. The Brunfelsia viroid CLVd-B consists of 373 nucleotides, 215 G + C, 158 A + U with a GC content of 57.6%. The most stable rod-like secondary structure of this viroid has 80 G:C, 39 A:U and 11 G:U base pairs with a minimum free energy of -157.2 kcal/mol (-657.1 kJ/mol). The sequence similarity of the right terminal domain of CLVd-B and of tomato apical stunt viroid (TASVd) is higher than the sequence similarity of these domains comparing CLVd and TASVd.

A new sequence variant of Coleus blumei viroid 3 from the Coleus blumei cultivar 'Fairway Ruby'.

A viroid was isolated from symptomless Coleus blumei cultivar (cv) 'Fairway Ruby' plants using the bidirectional PAGE method for analysis of small circular RNA molecules. The viroid was transmitted to viroid-free plants of Coleus blumei cv. 'Scarlet Dragonfly' by mechanical inoculation. Cloning and sequencing revealed that the viroid from the Coleus cv. 'Fairway Ruby' is closely related to the Coleus blumei viroid 3-Bv (CbVd 3-Bv) isolated from the Coleus cv. 'Bienvenue'. Therefore, the new viroid sequence variant has been named Coleus blumei viroid 3-FR (CbVd 3-FR). Coleus blumei viroid 3-FR consists of 364 nucleotides, 202 G + C, 162 A + U with a GC content of 55.5%. The most stable rod-like secondary structure of this viroid has 82 G:C, 50 A:U and 10 G:U base pairs with a minimum free energy of -670.5 kJ/mol (-160.4 kcal/mol). Due to mutations that increase the stability of the rod-like secondary structure, CbVd 3-FR has a lower minimum free energy than CbVd 3-Bv (-598.2 kJ/mol; -143.1 kcal/mol). A base-exchange in the upper strand of the central domain of CbVd 3-FR may stabilize the basal helix of hairpin I.

A viroid from Solanum pseudocapsicum closely related to the tomato apical stunt viroid.

A viroid was isolated from symptomless Solanum pseudocapsicum cultivar (cv) 'New Patterson' plants using the bidirectional PAGE method for analysis of small circular RNA molecules. The viroid was transmitted to tomato by mechanical inoculation. Infected tomato plants developed symptoms similar to those caused by potato spindle tuber viroid (PSTVd). Cloning and sequencing revealed that the viroid from Solanum pseudocapsicum is closely related to the tomato apical stunt viroid (TASVd). Therefore, the new viroid sequence variant has been named TASVd-S. The circular RNA of TASVd-S consists of 360 nucleotides which can potentially form a rod-like structure with a high degree of base-pairing like all the other known viroids. The nucleotide composition is 99 G, 72 A, 101 C and 88 U, corresponding to 200 G + C, 160 A + U with a GC content of 55.6%. In total 71% of the residues are base-paired and the basepaired residues consist of 73 G:C (57%), 43 A:U (34%) and 11 G:U (9%) base pairs. The most stable rod-like secondary structure of this viroid has 80 G:C, 39 A:U and 11 G:U base pairs with a minimum free energy of -147.5 kcal/mol (-616.6 kJ/mol). The sequence similarity of the left terminal (T1) domain of TASVd-S and the T1 domain of tomato planta macho viroid (TPMVd) is higher than the sequence similarity of these domains of TASVd-S and TASV-d.

[The effect of the time of day on the renal excretion of several minerals in cattle]. / Der Einfluss der Tageszeit auf die renale Ausscheidung einiger Mineralstoffe bei Rindern.

Urine of 17 cows was totally collected with a permanent bladder catheter for 3-5 days. The quantities of excreted calcium, magnesium, sodium, potassium, and inorganic phosphorus were evaluated. In a second experiment 448 urine samples, spontaneously excreted at different times of day, were analysed concerning the concentrations of the specified minerals and of creatinine. In order to avoid a possible misinterpretation the relations of the concentrations of the minerals and of creatinine concentration in each sample were computed. In both experiments it is shown that excretion of potassium and magnesium doesn't considerably differ at different times of day. Calcium, sodium and inorganic phosphorus, however, show maxima of excretion in the middle of each day and minima at midnight. Possible reasons for this phenomena and the meaning for use in diagnosis are discussed.