bluuebunny/crossref_metadata_2025 huggingface dataset:
Crystallographic features and cleavage nanomorphology of chlinochlore: Specific applications
Authors: Valdrè Giovanni , Malferrari Daniele , Brigatti Maria Franca
Published: May 2009

Natural and synthetic micas have been used widely as substrates to study biological systems; but, as in the case of negatively charged DNA, anionic charge repulsion may render micas a less than ideal templating surface for many biological systems. The purpose of this study was to investigate the potential for the chlorite clinoclore, which contains a positively charged interlayer octahedral sheet, to serve as a substrate for DNA adsorption. The relationships between clinochlore cleavage characteristics, in terms of nano-morphology, and surface potential are investigated, as are its average crystal chemistry and topology. That the structural features of clinochlore can be used successfully to condense, order, and self assemble complex biomolecules, such as DNA is also proven.

A natural IIb-4 clinochlore [<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:c="http://cambridge.org/core/content" xmlns:core="http://cambridge.org/core" xmlns:m="http://cambridge.org/core/metadata" xmlns:cup="http://contentservices.cambridge.org" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:mnf="http://cambridge.org/core/manifest">C1¯\$\end{document} symmetry, unit-cell parameters a = 0.53301(4); b = 0.92511(6); c = 1.4348(1) (nm); α = 90.420(3); β = 97.509(3); γ = 89.996(4) (°)] with chemical composition <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:c="http://cambridge.org/core/content" xmlns:core="http://cambridge.org/core" xmlns:m="http://cambridge.org/core/metadata" xmlns:cup="http://contentservices.cambridge.org" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:mnf="http://cambridge.org/core/manifest">(Mg1.701Fe0.2452+Ti0.004Al0.998Cr0.0523+)Mg3(Si2.939Al1.015Fe0.0463+)O10(OH7.913F0.087)\$\end{document} was selected. The octahedral sites of the silicate layer ( = 0.2080 nm and  = 0.2081 nm) are equal and occupied by Mg, whereas the octahedral sites in the interlayer M(3) and M(4) ( = 0.2088 nm and  = 0.1939 nm) show different sizes and are mostly completely occupied by divalent (Mg2+ and Fe2+) and trivalent (Al3+) cations, respectively.

The clinochlore cleaved surface is present in two forms: (1) the stripe type (0.40 nm in height, up to several micrometers long and ranging from some nanometers to a few microns in lateral size); and (2) the triangular type (0.40 nm in height). Both features may result either from interlayer sheets whose cleavage weak directions are related to the different M(3) and M(4) site occupancy, or from weak interlayer bonding along specific directions to the 2:1 layer underneath. The cleaved surface, particularly at the cleaved edges, presents high DNA affinity, which is directly related to an average positive surface and ledge potential.
The role of clay minerals in the preservation of organic matter in sediments of Qinghai Lake, NW China
Authors: Yu Bingsong , Dong Hailiang , Jiang Hongchen , LV Guo , Eberl Dennis , Li Shanying , Kim Jinwook
Published: May 2009

The role of saline lake sediments in preserving organic matter has long been recognized. In order to further understand the preservation mechanisms, the role of clay minerals was studied. Three sediment cores, 25, 57, and 500 cm long, were collected from Qinghai Lake, NW China, and dissected into multiple subsamples. Multiple techniques were employed, including density fractionation, X-ray diffraction, scanning and transmission electron microscopy (SEM and TEM), total organic carbon (TOC) and carbon compound analyses, and surface area determination. The sediments were oxic near the water-sediment interface, but became anoxic at depth. The clay mineral content was as much as 36.8%, consisting mostly of illite, chlorite, and halloysite. The TEM observations revealed that organic matter occurred primarily as organic matter-clay mineral aggregates. The TOC and clay mineral abundances are greatest in the mid-density fraction, with a positive correlation between the TOC and mineral surface area. The TOC of the bulk sediments ranges from 1 to 3% with the non-hydrocarbon fraction being predominant, followed by bitumen, saturated hydrocarbon, aromatic hydrocarbons, and chloroform-soluble bitumen. The bimodal distribution of carbon compounds of the saturated hydrocarbon fraction suggests that organic matter in the sediments was derived from two sources: terrestrial plants and microorganisms/algae. Depth-related systematic changes in the distribution patterns of the carbon compounds suggest that the oxidizing conditions and microbial abundance near the water-sediment interface promote degradation of labile organic matter, probably in adsorbed form. The reducing conditions and small microbial biomass deeper in the sediments favor preservation of organic matter, because of the less labile nature of organic matter, probably occurring within clay mineral-organic matter aggregates that are inaccessible to microorganisms. These results have important implications for our understanding of mechanisms of organic matter preservation in saline lake sediments.
Polarized ATR-FTIR investigation of Fe reduction in the Uley nontronites
Authors: Bzdek Bryan R. , McGuire Molly M.
Published: May 2009

Reduction of structural Fe in smectites affects the surface chemical behavior of the clay, but the underlying mechanism and changes in clay structure are still in need of investigation, particularly with respect to changes in the tetrahedral sheet. The purpose of this study was to probe changes in the tetrahedral sheet that occur when structural Fe is reduced in the Uley nontronites, NAu-1 and NAu-2, using polarized attenuated total internal reflection Fourier-transform infrared spectroscopy. Despite the differences in their structures — NAu-2 has tetrahedral Fe3+while NAu-1 does not — the changes observed in the Si-O stretching region were quite similar. Reduction results in a shift of the in-plane Si-O stretching modes to lower frequencies, while the out-of-plane Si-O stretch shifts to higher frequencies. The magnitude of these shifts is greater in NAu-2 than in NAu-1, but the crystallinity of the tetrahedral silicate sheet of NAu-2 is preserved upon reduction. In both nontronites, the orientation of the out-of-plane Si-O bond changes and becomes completely perpendicular to the basal (001) surface of the clay, indicating the formation of trioctahedral domains wherein the individual tetrahedra reorient relative to the plane of the clay layer.
Simultaneous incorporation of Cr, Zn, Cd, and Pb in the goethite structure
Authors: Kaur Navdeep , Gräfe Markus , Singh Balwant , Kennedy Brendan
Published: May 2009

In order to improve our understanding of how the goethite crystal structure is affected by the incorporation of metals (and by variations in the amount of the incorporation), and to review any possible synergistic and antagonistic effects of co-metals, the present investigation focused on the incorporation of multiple (di-, tri-, and tetra-) metals, i.e. Cr, Zn, Cd, and Pb, in the goethite crystallographic structure. A series of single- and multi-metal M-Cr/Zn/Cd/Pb-substituted goethites with M/(M+Fe) molar ratios = 0.10 were prepared. The general sequence of metal entry in single-metal substituted goethites was Zn = Cr > Cd > Pb and in multi-metal-substituted goethites was Zn > Cr ⩾ Cd > Pb. Simultaneous incorporation of Cr, Zn, Cd, and Pb up to 10.5 mole % was achieved in goethite. Synchrotron X-ray diffraction and extended X-ray absorption fine structure (EXAFS) techniques were employed to assess the structural characteristics of the synthesis products. Rietveld refinement of XRD data showed small changes in unit-cell parameters and Fe/M-Fe/M distances due to M substitution(s). A typical goethite-like crystalline structure remained intact, however. The unit-cell parameters were mutually, linearly correlated, though Fe/M-Fe/M distances were not, indicating that complex changes occurred at the local scale. In single-metal substituted goethites, incorporation of Cr reduced the unit-cell volume by 0.13% while that of Zn, Cd, and Pb increased it by 1.09, 3.58, and 0.56%, respectively. The changes in multi-metal-substituted goethites appeared to be the complex combination of that of the individually incorporated metals. The X-ray absorption near edge structure study of Pb-substituted goethites showed that the majority of associated Pb was Pb2+, while Pb4+ was preferred over Pb2+ in the bulk structure. Measurements by EXAFS at the Fe K-edge indicated that the Fe polyhedra contracted in the presence of Cd2+ and Pb2+, providing room for the substitution of larger cations. Measurements by EXAFS at the Cr and Cd K-edges indicated symmetric Cr/Cd polyhedra with single Cr/Cd-O distances and, at Fe and Zn K-edges and the Pb LIII-edge, indicated asymmetric polyhedra with two sets of Fe/Zn/Pb-O distances. The Zn octahedra were possibly Zn(OH)4O2, which enlarged the metal-metal corner-sharing distance to 3.86 Å. This configuration of ligands around the Zn2+ cation might occur to balance local charges. Symmetric polyhedra appeared to reduce steric strains in the structure, compared to the asymmetric polyhedra. The result was that Cr enhanced the incorporation of Zn, Cd, and Pb, while the converse was true for Zn.
Anisotropy of magnetic susceptibility study of kaolinite matrix subjected to biaxial tests
Authors: Sengupta Aniruddha
Published: May 2009

The potential for structural failure of consolidated clay materials, which is of great importance in many applications, typically are assessed by measuring the localized strain bands that develop under anisotropic load stress. Most methods are precluded from providing a full understanding of the strain anisotropy because they only give two-dimensional information about the stressed clay blocks. The purpose of the present study was to investigate three-dimensional strain localization in a kaolinite matrix, caused by strain anisotropy due to a biaxial plane-strain test, using a relatively new method known as Anisotropy of Magnetic Susceptibility (AMS). This method involves induction of magnetism in an oriented sample in different directions and measurement of the induced magnetization in each direction. The AMS analyses were performed on core samples from different parts of the deformed kaolinite matrix. The degree of magnetic anisotropy (P′), which is a measure of the intensity of magnetic fabric and a gauge of strain intensity, was shown to be greater in cores containing shear bands than in those containing none. A threshold value for P′ for the deformed kaolinite matrix was identified, above which shear bands may develop. The comparison of the shape parameter (T), obtained from undeformed and deformed samples, illustrated a superimposition of prolate strain over the original oblate fabric of the kaolinite matrix. The orientation of the principal strain axis revealed that reorientation or rotation of the principal axis occurred along the shear bands.
Melt synthesis and characterization of synthetic Mn-rich tainiolite
Authors: Baumgartner Alexander , Butterhof Christian , Koch Sebastian , Mariychuk Ruslan , Breu Josef
Published: May 2009

Large transition-metal contents add desirable physical properties, such as redox reactivity, magnetism, and electric or ionic conductivity to micas and make them interesting for a variety of materials-science applications. A Mn- and F-rich tainiolite mica,

, was synthesized by a high-temperature melt-synthesis technique. Subsequent annealing for 10 days led to a single-phase and coarsegrained material. Single-crystal X-ray diffraction studies were performed and characteristic geometric parameters were compared to the analogous ferrous compound, synthetic Fe-rich tainiolite,

. Both tainiolite structures are outside the compositional stability limits for the 2:1 layer structure, and incorporating the relatively large cation Mn2+ requires significant structural adjustments in both the octahedral and tetrahedral sheets. As expected, increasing the ionic radius of the octahedral cation from 0.78 Å (VIFe2+) to 0.83 Å (VIMn2+) reduces the octahedral flattening angle from <Ψ> = 57.05° to <Ψ> = 56.4°, the smallest value ever observed for a tetrasilicic mica. However, even this small <Ψ> value is insufficient to match the lateral sizes of the tetrahedral and octahedral sheets and, in addition, unusual structural adjustments in the tetrahedral sheet are required. The average tetrahedral bond length  is much greater (1.643 Å) than the average value observed for tetrasilicic micas (1.607 Å,) and a significant difference between the apical (1.605 Å) and the basal bond lengths (1.656 Å) and an enlarged basal flattening angle (τbas = 106.29°) are noted. These parameters indicate: (1) that the 2:1 layer might be more flexible than previously thought, to allow matching of the lateral dimensions of the tetrahedral and octahedral sheets; and (2) that many other compositions that appear interesting from a materials-science point of view might be accessible.
Anesthesia and Cognitive Performance in Children: No Evidence for a Causal Relationship
Authors: Bartels Meike , Althoff Robert R. , Boomsma Dorret I.
Published: May 2009

Recent findings of an association between anesthesia administration in the first three years of life and later learning disabilities have created concerns that anesthesia has neurotoxic effects on synaptogenesis, causing later learning problems. An alternative hypothesis is that those children who are likely to undergo surgery early in life have significant medical problems that are associated with a vulnerability to learning disabilities. These two hypotheses were evaluated in a monozygotic concordant–discordant twin design. Data on anesthesia administration and learning abilities and disabilities were available for 1,143 monozygotic twin pairs (56% female) from the Netherlands Twin Registry. Parents of the twins reported on anesthesia use before age 3 and again between ages 3 and 12 years. Near age 12, educational achievement and cognitive problems were assessed with standardized tests and teacher ratings. Results showed that twins who were exposed to anesthesia before age 3 had significantly lower educational achievement scores and significantly more cognitive problems than twins not exposed to anesthesia. However, there was one important exception: the unexposed co-twin from discordant pairs did not differ from their exposed co-twin. Thus, there is no evidence for a causal relationship between anesthesia administration and later learning-related outcomes in this sample. Rather, there is evidence for early anesthesia being a marker of an individual's vulnerability for later learning problems, regardless of their exposure to anesthesia.
Polymorphisms in the FGF2 Gene and Risk of Serous Ovarian Cancer: Results From the Ovarian Cancer Association Consortium
Authors: Johnatty Sharon E. , Beesley Jonathan , Chen Xiaoqing , Spurdle Amanda B. , DeFazio Anna , Webb Penelope M. ,   Australian Ovarian Cancer Study Group,   Australian Cancer Study (Ovarian Cancer), Goode Ellen L. , Rider David N. , Vierkant Robert A. , Anderson Stephanie , Wu Anna H. , Pike Malcolm , Van Den Berg David , Moysich Kirsten , Ness Roberta , Doherty Jennifer , Rossing Mary-Anne , Pearce Celeste Leigh , Chenevix-Trench Georgia
Published: May 2009

Fibroblast growth factor (FGF)-2 (basic) is a potent angiogenic molecule involved in tumor progression, and is one of several growth factors with a central role in ovarian carcinogenesis. We hypothesized that common single nucleotide polymorphisms (SNPs) in the FGF2 gene may alter angiogenic potential and thereby susceptibility to ovarian cancer. We analyzed 25 FGF2 tgSNPs using five independent study populations from the United States and Australia. Analysis was restricted to non-Hispanic White women with serous ovarian carcinoma (1269 cases and 2829 controls). There were no statistically significant associations between any FGF2 SNPs and ovarian cancer risk. There were two nominally statistically significant associations between heterozygosity for two FGF2 SNPs (rs308379 and rs308447; p < .05) and serous ovarian cancer risk in the combined dataset, but rare homozygous estimates did not achieve statistical significance, nor were they consistent with the log additive model of inheritance. Overall genetic variation in FGF2 does not appear to play a role in susceptibility to ovarian cancer.
Genetic Variation in Female BMI Increases with Number of Children Born but Failure to Replicate Association betweenGNβ3Variants and Increased BMI in Parous Females
Authors: Cornes Belinda K. , Medland Sarah E. , Lind Penelope A. , Nyholt Dale R. , Montgomery Grant W. , Martin Nicholas G.
Published: May 2009

Objective:As post-pregnancy weight retention in women is a risk factor for obesity later in life, we assessed the changes in magnitude of genetic and environmental variation in BMI due to parity in an Australian female sample, comprising 11,915 female twins and their sisters.Results:Total variance of BMI increased with parity, primarily driven by an increase in nonadditive genetic variance. This finding was of particular interest given Gutersohn et al's (2000) report of recessive association between post-partum weight retention and the 825T allele of theGNβ3gene (rs5443) at 12p13.31. Hence, we attempted to replicate this association and test an additional three SNPs also located near or onGNβ3(rs10744716 (upstream), rs5442 (exon 10), rs5446 (exon 11)) in a sample of 3131 females and 1693 males from 2585 twin families. No association was found between these SNPs among females, even when allowing for a genotype by parity effect. However, a significant association was observed among males for rs10744716 (χ22= 10.22,p= 0.006; effect size = 0.47kg/m2), representing a novel association between a region upstream ofGNβ3and male BMI.
Concordant Symptomatic Intracranial Aneurysm in a Monozygotic Twin: A Case Report and Review of the Literature
Authors: ter Laan Mark , Kerstjens-Frederikse Wilhelmina S. , Metzemaekers Jan D. M. , van Dijk J. Marc C. , Groen Rob J. M.
Published: May 2009

The development of an intracranial aneurysm (IA) is a multifactorial process, involving genetic and environmental factors. The presence of IA or aneurysmal subarachnoid hemorrhage (aSAH) in twins is particularly interesting, since both genetic and environmental factors can be studied. It also raises the question of whether, when one twin is affected, the other asymptomatic twin should be examined for an IA. We report on a monozygotic (MZ) twin-pair with aSAH in both twins and we review all reported cases of IA in MZ twins. Including our case, we found only 14 MZ twin-pairs in which both twins harbored an IA, suggesting a heavy underreporting in the medical literature. In this small group, a high concordance was noted in the sites of IAs. In MZ twins, the preferred sites for IAs are the branching arteries, while aneurysms arising from fusion arteries are rare. These sites differ from the preferential sites seen in series of familial IAs and series of sporadic IAs. We therefore hypothesize that the twinning process might play a significant role in the development of IAs in MZ twins. To further explore and substantiate this, the large twin registries should be studied. Although IAs in MZ twins with a negative family history for IAs should not be regarded as familial IAs, screening of the asymptomatic twin should be seriously considered if one MZ twin presents with an aSAH or an IA, because of the high fatality rates reported in asymptomatic (and not screened) MZ twin-halves.
The Establishment of the GENEQOL Consortium to Investigate the Genetic Disposition of Patient-Reported Quality-of-Life Outcomes
Authors: Sprangers Mirjam A. G. , Sloan Jeff A. , Veenhoven Ruut , Cleeland Charles S. , Halyard Michele Y. , Abertnethy Amy P. , Baas Frank , Barsevick Andrea M. , Bartels Meike , Boomsma Dorret I. , Chauhan Cynthia , Dueck Amylou C. , Frost Marlene H. , Hall Per , Klepstad Pål , Martin Nicholas G. , Miaskowski Christine , Mosing Miriam , Movsas Benjamin , Van Noorden Cornelis J. F. , Patrick Donald L. , Pedersen Nancy L. , Ropka Mary E. , Shi Quiling , Shinozaki Gen , Singh Jasvinder A. , Yang Ping , Zwinderman Ailko H.
Published: May 2009

To our knowledge, no comprehensive, interdisciplinary initiatives have been taken to examine the role of genetic variants on patient-reported quality-of-life outcomes. The overall objective of this paper is to describe the establishment of an international and interdisciplinary consortium, the GENEQOL Consortium, which intends to investigate the genetic disposition of patient-reported quality-of-life outcomes. We have identified five primary patient-reported quality-of-life outcomes as initial targets: negative psychological affect, positive psychological affect, self-rated physical health, pain, and fatigue. The first tangible objective of the GENEQOL Consortium is to develop a list of potential biological pathways, genes and genetic variants involved in these quality-of-life outcomes, by reviewing current genetic knowledge. The second objective is to design a research agenda to investigate and validate those genes and genetic variants of patient-reported quality-of-life outcomes, by creating large datasets. During its first meeting, the Consortium has discussed draft summary documents addressing these questions for each patient-reported quality-of-life outcome. A summary of the primary pathways and robust findings of the genetic variants involved is presented here. The research agenda outlines possible research objectives and approaches to examine these and new quality-of-life domains. Intriguing questions arising from this endeavor are discussed. Insight into the genetic versus environmental components of patient-reported quality-of-life outcomes will ultimately allow us to explore new pathways for improving patient care. If we can identify patients who are susceptible to poor quality of life, we will be able to better target specific clinical interventions to enhance their quality of life and treatment outcomes.
Growth Charts of Length and Height from Birth to Six Years of Age in Japanese Triplets
Authors: Yokoyama Yoshie , Sugimoto Masako , Silventoinen Karri , Pitkäniemi Janne , Kaprio Jaakko
Published: May 2009

We analyzed the characteristics associated with the growth in length and height of Japanese triplets from birth to 6 years of age and present the growth charts for them. The study included 354 mothers and their 1,061 triplet children, who were born between 1978 and 2006. Data were collected through a mailed questionnaire sent to the mothers asking for information recorded in medical records. For these births, data on triplets' length and height growth, gestational age, sex, parity, and maternal age at delivery were obtained from records in the Maternal and Child Health Handbooks, which is provided by the authorities after a report of pregnancy. Birth length showed the strongest contribution to height of triplets from 1 to 6 years of age. In addition, birthweight was also a significant contributing factor to height from 1 to 3 years of age. Compared to the 50th percentile of the growth standard for the general population of Japan, the length and height deficit of the triplets was approximately 15% at birth (male, –7.0 cm; female, –7.0 cm), decreased within the first year of age, and fluctuated between 2 and 5% until 6 years of age (male, –3.7 cm; female, –3.3 cm). In conclusion, triplets have lower birth length and subsequent height than singletons. In spite of the catch-up growth during the first year of life, they are behind singletons even in mid-childhood. This study provides height growth curves for triplets.
Dimeric/oligomeric DNA methyltransferases: an unfinished story
Authors: Malygin Ernst G. , Evdokimov Alexey A. , Hattman Stanley
Published: May 2009

DNA methyltransferases (MTases) are enzymes that carry out post-replicative sequence-specific modifications. The initial experimental data on the structure and kinetic characteristics of the EcoRI MTase led to the paradigm that type II systems comprise dimeric endonucleases and monomeric MTases. In retrospect, this was logical because, while the biological substrate of the restriction endonuclease is two-fold symmetrical, the in vivo substrate for the MTase is generally hemi-methylated and, hence, inherently asymmetric. Thus, the paradigm was extended to include all DNA MTases except the more complex bifunctional type I and type III enzymes. Nevertheless, a gradual enlightenment grew over the last decade that has changed the accepted view on the structure of DNA MTases. These results necessitate a more complex view of the structure and function of these important enzymes.
Advanced glycation end product accumulation in rho0 cells without a functional respiratory chain
Authors: Nass Norbert , Kukat Alexandra , Seibel Peter , Brömme Hans-Jürgen , Schinzel Reinhard , Silber Rolf-Edgar , Simm Andreas
Published: May 2009

Advanced glycation end products (AGEs) accumulate during ageing with reactive oxygen species from the mitochondrial respiratory chain discussed as a driving force. To determine the role of mitochondrial activity for AGE formation, a rho0 derivative of the 143B.TK- osteosarcoma cell line lacking the respiratory chain, was analysed. These cells exhibit decreased superoxide formation but unchanged mitochondrial SOD expression as well as unchanged antioxidative free sulfhydryl (SH) levels. Whereas total protein content shows no differences in AGE levels, cell fractionation and Western blotting demonstrates some changes in the AGE pattern. Thus, the absence of functional respiration has only a negligible impact on AGE accumulation.
MUC1 traverses apical recycling endosomes along the biosynthetic pathway in polarized MDCK cells
Authors: Mattila Polly E. , Kinlough Carol L. , Bruns Jennifer R. , Weisz Ora A. , Hughey Rebecca P.
Published: May 2009

MUC1 is a heavily glycosylated transmembrane protein localized at the apical surface of polarized epithelial cells. Here, we examined the biosynthetic route of newly synthesized MUC1 in polarized Madin-Darby canine kidney (MDCK) cells. Apically and basolaterally destined cargo are sorted at the trans-Golgi network into distinct vesicles, and proteins with lipid raft-dependent apical targeting signals and glycan-dependent apical targeting signals appear to specifically transit apical early endosomes (AEEs) and apical recycling endosomes (AREs), respectively. Using metabolic labeling we found that MUC1 is efficiently targeted to the apical surface of polarized MDCK cells with a t
1/2 of 45 min. Apical delivery was not altered by inactivation of AEEs by treatment with hydrogen peroxide and diaminobenzidine treatment after apical loading of endosomes with horseradish peroxidase-conjugated wheat germ agglutinin. However, expression of a GFP-tagged myosin Vb tail fragment (GFP-MyoVbT) that disrupts export from the ARE significantly reduced MUC1 apical expression. Moreover, MUC1 expressed for brief periods in MDCK cells co-localized with GFP-MyoVbT. We conclude that MUC1 traffics to the apical surface via AREs in polarized renal epithelial cells.
Challenges to our current view on chloroplasts
Authors: Reski Ralf
Published: May 2009

Chloroplasts are the co-evolution product of three different genetic compartments. This review compiles reports about bacteria and various photosynthetically active eukaryotes that challenge our current view on the structure of chloroplasts. It highlights their structurally dynamic nature and their differences in various groups of the Archaeplastida. Based on these reports, it argues in favor of an evolutionary view on bacterial as well as on plastid cell biology.
The do's and don'ts of p53 isoforms
Authors: Jänicke Reiner U. , Graupner Vilma , Budach Wilfried , Essmann Frank
Published: May 2009

Upon DNA damage and other stresses, the transcription factor p53 elicits numerous responses including DNA repair, cell cycle arrest and apoptosis, properties that make p53 the prototype tumor suppressor. In addition, p53 also transactivates genes whose products act in an anti-apoptotic manner providing strong evidence that p53 exhibits both tumor suppressive and tumorigenic functions. Although several events were postulated to contribute to the p53-mediated decision process, the precise mechanism(s) that governs p53 activities is still elusive. Recently, it was found that the p53 gene allows expression of at least nine different isoforms that arise from multiple splicing events and the usage of alternative promoters. Several of these isoforms were shown to critically interfere with the function of the full-length p53 mainly by acting in a dominant-negative manner. However, an isoform-dependent selective activation of p53 target genes was also observed. Furthermore, certain p53 isoforms are aberrantly expressed in various tumors strongly implying their involvement in tumorigenic events. Thus, p53 isoforms may represent crucial determinants in p53-mediated decision processes whose precise functions (their do's and don'ts) are only beginning to emerge.
Analytical role in clinical toxicology: impact on the diagnosis and treatment of poisoned patients1
Authors: Hallbach Jürgen , Degel Fritz , Desel Herbert , Felgenhauer Norbert
Published: May 2009

Acute poisoning is a medical emergency situation and requires urgent but adequate medical intervention. The outcome depends on accurate primary care, the correct identification of poison(s) and adequate therapeutic decisions. The present paper reviews the literature concerning the role of analytical toxicology in emergency medicine with particular focus on the last few years. This study is mainly based on a PubMed search: “clinical toxicology review (urine, serum)”. Many acutely poisoned patients are treated with no laboratory support other than general clinical chemistry, haemostaseology and haematology. Emergency toxicological analyses that could influence immediate patient management, if offered on the basis of 24-h availability, are most often restricted to ethanol, oximetry and drugs of abuse in urine. Despite paracetamol (acetaminophen) being the top entry on all hit lists of poison control centres worldwide with few exceptions, the availability of its determination in blood on an urgent basis is not standard even at hospitals with large accident and emergency departments. Therefore, recommendations regarding the assays and methods that should be provided locally and at regional centres were provided for the US and UK, and should be adapted for Germany. Emergency toxicological analyses that could influence immediate patient management are relatively few in number and are remarkably similar worldwide. Recommendations for the US and UK are compared in the present paper together with suggestions for Germany. The first group of these assays should be provided locally by larger hospitals with emergency and intensive care units with a turnaround time (TAT) of <1 h. Other assays (second group) and a systematic toxicological analysis that can help improve patient management after a period of primary stabilisation of vital functions and general supportive therapy can be provided from regional centres with a TAT of 4 h. The need for such centres and the repertoire of tests and methods that should be available will be adapted and discussed. It is well known that comprehensive toxicological analysis incorporating various methods can identify much more substances than are clinically suspected. At the same time, this information might have no clinical utility owing to the time required for sampling, transportation, analysis and reporting, or because the toxicological report might be inconsequential. This has contributed to a range of clinical opinions and practices, from a minimalist approach to a “shotgun” approach of broad-based laboratory testing. The present review should help to understand and discuss the pros and cons of both approaches.
Limits for the determination of guiding values from intra-laboratory data basis, demonstrated by prostate specific antigen (PSA)1
Authors: Gurr Eberhard , Krönig Friedrich , Golbeck Anja , Arzideh Farhad
Published: May 2009

The German guidelines for early detection of prostate cancer propose the use of digital rectal palpation and prostate specific antigen (PSA). PSA levels above 4 μg/L are considered to be suspect. However, method comparison of six different assays resulted in differences up to 20% in the range of 4 μg/L, although all assays used the Stanford 90/10 (WHO 96/670) calibration. Interpretation of PSA levels therefore has to take into consideration assay-specific characteristics, using assay-specific local reference ranges. However, the estimation of reference ranges by, e.g., analysis of frequency distribution failed with regard to the high prevalence of benign prostate hyperplasia. PSA velocity is proposed for early detection. Interpretation of PSA velocity especially at low PSA levels has to take into consideration analytical imprecision and biological variation.
A Retrograde Neuronal Survival Response: Target-Derived Neurotrophins Regulate MEF2D and bcl-w
Authors: Pazyra-Murphy Maria F. , Hans Aymeric , Courchesne Stephanie L. , Karch Christoph , Cosker Katharina E. , Heerssen Heather M. , Watson Fiona L. , Kim Taekyung , Greenberg Michael E. , Segal Rosalind A.
Published: May 2009

Survival and maturation of dorsal root ganglia sensory neurons during development depend on target-derived neurotrophins. These target-derived signals must be transmitted across long distances to alter gene expression. Here, we address the possibility that long-range retrograde signals initiated by target-derived neurotrophins activate a specialized transcriptional program. The transcription factor MEF2D is expressed in sensory neurons; we show that expression of this factor is induced in response to target-derived neurotrophins that stimulate the distal axons. We demonstrate that MEF2D regulates expression of an anti-apoptoticbcl-2family member,bcl-w. Expression ofmef2dandbcl-wis stimulated in response to activation of a Trk-dependent ERK5/MEF2 pathway, and our data indicate that this pathway promotes sensory neuron survival. We find thatmef2dandbcl-ware members of a larger set of retrograde response genes, which are preferentially induced by neurotrophin stimulation of distal axons. Thus, activation of an ERK5/MEF2D transcriptional program establishes and maintains the cellular constituents of functional sensory circuits.
Connectivity Patterns Revealed by Mapping of Active Inputs on Dendrites of Thalamorecipient Neurons in the Auditory Cortex
Authors: Richardson Robert J. , Blundon Jay A. , Bayazitov Ildar T. , Zakharenko Stanislav S.
Published: May 2009

Despite being substantially outnumbered by intracortical inputs on thalamorecipient neurons, thalamocortical projections efficiently deliver acoustic information to the auditory cortex. We hypothesized that thalamic projections may achieve effectiveness by forming synapses at optimal locations on dendritic trees of cortical neurons. Using two-photon calcium imaging in dendritic spines, we constructed maps of active thalamic and intracortical inputs on dendritic trees of thalamorecipient cortical neurons in mouse thalamocortical slices. These maps revealed that thalamic projections synapse preferentially on stubby dendritic spines within 100 μm of the soma, whereas the locations and morphology of spines that receive intracortical projections have a less-defined pattern. Using two-photon photolysis of caged glutamate, we found that activation of stubby dendritic spines located perisomatically generated larger postsynaptic potentials in the soma of thalamorecipient neurons than did activation of remote dendritic spines or spines of other morphological types. These results suggest a novel mechanism of reliability of thalamic projections: the positioning of crucial afferent inputs at optimal synaptic locations.
Equalization of Ocular Dominance Columns Induced by an Activity-Dependent Learning Rule and the Maturation of Inhibition
Authors: Toyoizumi Taro , Miller Kenneth D.
Published: May 2009

Early in development, the cat primary visual cortex (V1) is dominated by inputs driven by the contralateral eye. The pattern then reorganizes into ocular dominance columns that are roughly equally distributed between inputs serving the two eyes. This reorganization does not occur if the eyes are kept closed. The mechanism of this equalization is unknown. It has been argued that it is unlikely to involve Hebbian activity-dependent learning rules, on the assumption that these would favor an initially dominant eye. The reorganization occurs at the onset of the critical period (CP) for monocular deprivation (MD), the period when MD can cause a shift of cortical innervation in favor of the nondeprived eye. In mice, the CP is opened by the maturation of cortical inhibition, which does not occur if the eyes are kept closed. Here we show how these observations can be united: under Hebbian rules of activity-dependent synaptic modification, strengthening of intracortical inhibition can lead to equalization of the two eyes' inputs. Furthermore, when the effects of homeostatic synaptic plasticity or certain other mechanisms are incorporated, activity-dependent learning can also explain how MD causes a shift toward the open eye during the CP despite the drive by inhibition toward equalization of the two eyes' inputs. Thus, assuming similar mechanisms underlie the onset of the CP in cats as in mice, this and activity-dependent learning rules can explain the interocular equalization observed in cat V1 and its failure to occur without visual experience.
Multisensory Integration in the Superior Colliculus Requires Synergy among Corticocollicular Inputs
Authors: Alvarado Juan Carlos , Stanford Terrence R. , Rowland Benjamin A. , Vaughan J. William , Stein Barry E.
Published: May 2009

Influences from the visual (AEV), auditory (FAES), and somatosensory (SIV) divisions of the cat anterior ectosylvian sulcus (AES) play a critical role in rendering superior colliculus (SC) neurons capable of multisensory integration. However, it is not known whether this is accomplished via their independent sensory-specific action or via some cross-modal cooperative action that emerges as a consequence of their convergence on SC neurons. Using visual–auditory SC neurons as a model, we examined how selective and combined deactivation of FAES and AEV affected SC multisensory (visual–auditory) and unisensory (visual–visual) integration capabilities. As noted earlier, multisensory integration yielded SC responses that were significantly greater than those evoked by the most effective individual component stimulus. This multisensory “response enhancement” was more evident when the component stimuli were weakly effective. Conversely, unisensory integration was dominated by the lack of response enhancement. During cryogenic deactivation of FAES and/or AEV, the unisensory responses of SC neurons were only modestly affected; however, their multisensory response enhancement showed a significant downward shift and was eliminated. The shift was similar in magnitude for deactivation of either AES subregion and, in general, only marginally greater when both were deactivated simultaneously. These data reveal that SC multisensory integration is dependent on the cooperative action of distinct subsets of unisensory corticofugal afferents, afferents whose sensory combination matches the multisensory profile of their midbrain target neurons, and whose functional synergy is specific to rendering SC neurons capable of synthesizing information from those particular senses.
Membrane Resonance in Bursting Pacemaker Neurons of an Oscillatory Network Is Correlated with Network Frequency
Authors: Tohidi Vahid , Nadim Farzan
Published: May 2009

Network oscillations typically span a limited range of frequency. In pacemaker-driven networks, including many central pattern generators (CPGs), this frequency range is determined by the properties of bursting pacemaker neurons and their synaptic connections; thus, factors that affect the burst frequency of pacemaker neurons should play a role in determining the network frequency. We examine the role of membrane resonance of pacemaker neurons on the network frequency in the crab pyloric CPG. The pyloric oscillations (frequency of ∼1 Hz) are generated by a group of pacemaker neurons: the anterior burster (AB) and the pyloric dilator (PD). We examine the impedance profiles of the AB and PD neurons in response to sinusoidal current injections with varying frequency and find that both neuron types exhibit membrane resonance, i.e., demonstrate maximal impedance at a given preferred frequency. The membrane resonance frequencies of the AB and PD neurons fall within the range of the pyloric network oscillation frequency. Experiments with pharmacological blockers and computational modeling show that both calcium currentsICaand the hyperpolarization-activated inward currentIhare important in producing the membrane resonance in these neurons. We then demonstrate that both the membrane resonance frequency of the PD neuron and its suprathreshold bursting frequency can be shifted in the same direction by either direct current injection or by using the dynamic-clamp technique to inject artificial conductances forIhorICa. Together, these results suggest that membrane resonance of pacemaker neurons can be strongly correlated with the CPG oscillation frequency.
Central Opioid Inhibition of Neuroendocrine Stress Responses in Pregnancy in the Rat Is Induced by the Neurosteroid Allopregnanolone
Authors: Brunton Paula J. , McKay Ailsa J. , Ochędalski Tomasz , Piastowska Agnieszka , Rębas Elżbieta , Lachowicz Agnieszka , Russell John A.
Published: May 2009

The hypothalamus–pituitary–adrenal (HPA) axis is the major neuroendocrine stress response system. Corticotropin-releasing hormone (CRH) neurons in the parvocellular paraventricular nucleus (pPVN) play a key role in coordinating responses of this system to stressors. The cytokine interleukin-1β (IL-1β), mimicking infection, robustly activates these CRH neurons via a noradrenergic input arising from the nucleus tractus solitarii (NTS). In late pregnancy, HPA axis responses to stressors, including IL-1β, are attenuated by a central opioid mechanism that auto-inhibits noradrenaline release in the PVN. Here we show that the neuroactive progesterone metabolite allopregnanolone induces these changes in HPA responsiveness to IL-1β in pregnancy. In late pregnancy, inhibition of 5α-reductase (an allopregnanolone-synthesizing enzyme) with finasteride restored HPA axis responses (rapidly increased pPVN CRH mRNA expression, ACTH, and corticosterone secretion) to IL-1β. Conversely, allopregnanolone reduced HPA responses in virgin rats. In late pregnancy, activity of the allopregnanolone-synthesizing enzymes (5α-reductase and 3α-hydroxysteroid dehydrogenase) was increased in the hypothalamus as was mRNA expression in the NTS and PVN. Naloxone, an opioid antagonist, restores HPA axis responses to IL-1β in pregnancy but had no additional effect after finasteride, indicating a causal connection between allopregnanolone and the endogenous opioid mechanism. Indeed, allopregnanolone induced opioid inhibition over HPA responses to IL-1β in virgin rats. Furthermore, in virgin rats, allopregnanolone treatment increased, whereas in pregnant rats finasteride decreased proenkephalin-A mRNA expression in the NTS. Thus, in pregnancy, allopregnanolone induces opioid inhibition over HPA axis responses to immune challenge. This novel opioid-mediated mechanism of allopregnanolone action may alter regulation of other brain systems in pregnancy.
Reggies/Flotillins Regulate Retinal Axon Regeneration in the Zebrafish Optic Nerve and Differentiation of Hippocampal and N2a Neurons
Authors: Munderloh Christina , Solis Gonzalo P. , Bodrikov Vsevolod , Jaeger Friederike A. , Wiechers Marianne , Málaga-Trillo Edward , Stuermer Claudia A. O.
Published: May 2009

The reggies/flotillins—proteins upregulated during axon regeneration in retinal ganglion cells (RGCs)—are scaffolding proteins of microdomains and involved in neuronal differentiation. Here, we show that reggies regulate axon regeneration in zebrafish (ZF) after optic nerve section (ONS)in vivoas well as axon/neurite extension in hippocampal and N2a neuronsin vitrothrough signal transduction molecules modulating actin dynamics. ZF reggie-1a, -2a, and -2b downregulation by reggie-specific morpholino (Mo) antisense oligonucleotides directly after ONS significantly reduced ZF RGC axon regeneration: RGC axons from reggie Mo retinas were markedly reduced. Moreover, the number of axon-regenerating RGCs, identified by insertion of A488-coupled dextran, decreased by 69% in retinas 7 d after Mo application. At 10 and 14 d, RGCs decreased by 53 and 33%, respectively, in correlation with the gradual inactivation of the Mos. siRNA-mediated knockdown of reggie-1 and -2 inhibited the differentiation and axon/neurite extension in hippocampal and N2a neurons. N2a cells had significantly shorter filopodia, more cells had lamellipodia and fewer neurites, defects which were rescued by a reggie-1 construct without siRNA-binding sites. Furthermore, reggie knockdown strongly perturbed the balanced activation of the Rho family GTPases Rac1, RhoA, and cdc42, influenced the phosphorylation of cortactin and cofilin, the formation of the N-WASP, cortactin and Arp3 complex, and affected p38, Ras, ERK1/2 (extracellular signal-regulated kinases 1 and 2), and focal adhesion kinase activation. Thus, as suggested by their prominent re-expression after lesion, the reggies represent neuron-intrinsic factors for axon outgrowth and regeneration, being crucial for the coordinated assembly of signaling complexes regulating cytoskeletal remodeling.
Inactivation of Ras by p120GAP via Focal Adhesion Kinase Dephosphorylation Mediates RGMa-Induced Growth Cone Collapse
Authors: Endo Mitsuharu , Yamashita Toshihide
Published: May 2009

The repulsive guidance molecule RGMa performs several functions in the developing and adult CNSs. RGMa, through its receptor neogenin, induces growth cone collapse and neurite outgrowth inhibition. Here, we demonstrate that RGMa binding to neogenin leads to the inactivation of Ras, which is required for the RGMa-mediated repulsive function in cortical neurons. This signal transduction is mediated by the Ras-specific GTPase-activating protein (GAP) p120GAP. The SH2 domain of p120GAP interacts with focal adhesion kinase (FAK), which is phosphorylated at Tyr-397. When the cells are stimulated with RGMa, FAK undergoes dephosphorylation at Tyr-397 and is dissociated from p120GAP, and this dissociation is followed by an increase in the interaction between p120GAP and GTP-Ras. In addition, the knockdown of p120GAP prevents RGMa-induced growth cone collapse and neurite outgrowth inhibition. Furthermore, RGMa stimulation induces Akt inactivation through p120GAP, and the expression of the constitutively active Akt prevents RGMa-induced growth cone collapse. Thus, RGMa binding to neogenin regulates p120GAP activity through FAK Tyr-397 dephosphorylation, leading to the inactivation of Ras and its downstream effector Akt, and this signal transduction plays a role in the RGMa-mediated repulsive function.