bluuebunny/crossref_metadata_2025 huggingface dataset:
On a Generalized 2 + 1 Dispersive Water Wave Hierarchy
Authors: Gordoa Pilar R. , Joshi Nalini , Pickering Andrew
Published: September 2006

We present a generalized non-isospectral dispersive water wave hierarchy in 2+1 dimensions. We characterize our entire hierarchy and its underlying linear problem using a single equation together with its corresponding non-isospectral scattering problem. This then allows a straightforward construction of linear problems for the entire generalized 2 + 1 hierarchy. Reductions of this hierarchy then yield new integrable hierarchies in 1+1 dimensions, and also new integrable hierarchies of ordinary differential equations, all together with their underlying linear problems. In particular, we obtain a generalized

P_{IV} − P_{II}

hierarchy; this includes as special cases both a hierarchy of ODEs having the fourth Painlevé equation as first member, and also a hierarchy of ODEs having the second Painlevé equation as first member. All of these hierarchies of ordinary differential equations, as well as their underlying linear problems, are new; both the

P_{IV}

hierarchy and the

P_{II}

hierarchy obtained here are different from those which have previously been given.
Fixed Points in Topological *-Algebras of Unbounded Operators
Authors: Bagarello Fabio
Published: September 2006

We discuss some results concerning fixed point equations in the setting of topological *-algebras of unbounded operators. In particular, an existence result is obtained for what we have called
weak τ strict contractions
, and some continuity properties of these maps are discussed. We also discuss possible applications of our procedure to quantum mechanical systems.
A Class of Polynomials from Banach Spaces into Banach Algebras
Authors: Lourenço Mary L. , Moraes Luiza A.
Published: September 2006

Let

E

be a complex Banach space and

F

be a complex Banach algebra. We will be interested in the subspace

ℙ_f({}^n E,F)

of

P({}^n E,F)

generated by the collection of functions

\varphi^n(n\in ℕ, \varphi \in L(E,F))

where

\varphi^n(x) = (\varphi (x))^n

for each

x\in E

.
Fourier Transforms on the Quantum $\textit{SU}(1,1)$ Group
Authors: Koelink Erik , Stokman Jasper V.
Published: September 2006

The main goal is to interpret the Askey–Wilson function and the corresponding transform pair on the quantum

\textit{SU}(1,1)

group. A weight on the

\mathrm C^∗

-algebra of continuous functions vanishing at infinity on the quantum

\textit{SU}(1,1)

group is studied, which is left and right invariant in a weak sense with respect to a product defined using Wall functions. The Haar weight restricted to certain subalgebras are explicitly determined in terms of an infinitely supported Jackson integral and in terms of an infinitely supported Askey–Wilson type measure. For the evaluation the spectral analysis of explicit unbounded doubly infinite Jacobi matrices and some new summation formulas for basic hypergeometric series are needed. The spherical functions are calculated in terms of Askey–Wilson functions and big

q

-Jacobi functions. The corresponding spherical Fourier transforms are identified with special cases of the big

q

-Jacobi function transform and of the Askey–Wilson function transform.
Metathesis of 1‐Octene in Ionic Liquids and Other Solvents: Effects of Substrate Solubility, Solvent Polarity and Impurities
Authors: Stark Annegret , Ajam Mariam , Green Mike , Raubenheimer Helgard G. , Ranwell Alta , Ondruschka Bernd
Published: September 2006

With the self‐metathesis of 1‐octene to 7‐tetradecene catalyzed by Grubbs 1st generation [benzylidene‐bis(tricyclohexylphosphine)dichlororuthenium, (1)] precursor at low concentrations (0.02 mol %) as basis, the effects of the solubility of the substrate in ionic liquids, the solvent polarity, as well as the influence of various impurities stemming from the preparation of ionic liquids have been investigated. The solubility of the substrate in the ionic liquid has little effect on the conversion, and the reaction is not mass‐transfer limited. While a higher polarity of an organic solvent increases the rate, it is independent of the polarity excerted by the cation of an ionic liquid. Of paramount importance for reproducible results is the purity of ionic liquids. An extensive study shows that catalyst deactivation by impurities increases in the order of water<halide<1‐methylimidazole. In the presence of water or 1‐methylimidazole impurities, the Grubbs‐Hoveyda precursor (3) is superior to both the 1st (1) and 2nd (2) generation Grubbs complexes. Under impurity‐free conditions or in the presence of chloride, the performance of 2 is equivalent to that of 3.
Automated detection of tunneling nanotubes in 3D images
Authors: Hodneland Erlend , Lundervold Arvid , Gurke Steffen , Tai Xue‐Cheng , Rustom Amin , Gerdes Hans‐Hermann
Published: September 2006

Background:

This paper presents an automated method for the identification of thin membrane tubes in 3D fluorescence images. These tubes, referred to as tunneling nanotubes (TNTs), are newly discovered intercellular structures that connect living cells through a membrane continuity. TNTs are 50–200 nm in diameter, crossing from one cell to another at their nearest distance. In microscopic images, they are seen as straight lines. It now emerges that the TNTs represent the underlying structure of a new type of cell‐to‐cell communication.

Methods:

Our approach for the identification of TNTs is based on a combination of biological cell markers and known image processing techniques. Watershed segmentation and edge detectors are used to find cell borders, TNTs, and image artifacts. Mathematical morphology is employed at several stages of the processing chain. Two image channels are used for the calculations to improve classification of watershed regions into cells and background. One image channel displays cell borders and TNTs, the second is used for cell classification and displays the cytoplasmic compartments of the cells. The method for cell segmentation is 3D, and the TNT detection incorporates 3D information using various 2D projections.

Results:

The TNT‐ and cell‐detection were applied to numerous 3D stacks of images. A success rate of 67% was obtained compared with manual identification of the TNTs. The digitalized results were used to achieve statistical information of selected properties of TNTs.

Conclusion:

To further explore these structures, automated detection and quantification is desirable. Consequently, this automated recognition tool will be useful in biological studies on cell‐to‐cell communication where TNT quantification is essential. © 2006 International Society for Analytical Cytology
A modern biomaterial for adhesion prevention
Authors: diZerega Gere S. , Cortese Stephanie , Rodgers Kathleen E. , Block Kathleen M. , Falcone Samuel J. , Juarez Thomas G. , Berg Richard
Published: September 2006

A biomaterial composed of carboxymethylcellulose, poly(ethylene oxide), and calcium can be prepared in a variety of ways to reduce fibrin deposition and adhesion formation. This biomaterial platform can be formulated into a flowable gel with tissue adherence appropriate for use in minimally invasive surgery. The device remains at the site of placement even in gravitationally dependent areas. A peridural formulation was shown in preclinical studies to be safe and effective in reducing adhesions to dura following spinal surgery. A peritoneal formulation used on pelvic organs following peritoneal cavity surgery was also shown to be safe and effective. A clinical feasibility study showed that patients with severe back pain and lower extremity weakness treated with the peridural formulation, applied over their nerve roots following laminectomy or laminotomy, experienced significantly reduced symptoms when compared with surgery‐only controls. The peritoneal formulation was shown in two multicenter feasibility studies of women undergoing pelvic surgery to significantly reduce adhesion formation when compared with surgery‐only controls. Confirmation of the feasibility studies awaits results from pivotal clinical trials. These formulations were safe, effective, and easy to use. This biomaterial provided a benefit to patients undergoing surgery where postsurgical adhesion formation is a concern. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2006
Ganglionary mechanisms of spasticity and ileus in cerebral hemorrhage: an experimental study
Authors: Aydin Mehmet Dumlu , Erdogan Ali Riza , Cevli Salih Cenap , Gundogdu Cemal , Dane Senol , Diyarbakirli Semih
Published: September 2006

Objective

The effects of retrograde neuronal death is well determined in dorsal root ganglia (DRG) after peripheral nerve injury, but the effects of intracerebral hemorrhage on the DRG has not been well known. In this study, it was investigated if hemorrhagic lesions of sensory–motor cortex cause neurodegeneration on DRG.

Materials and Methods

This study was conducted on 23 male hybrid rabbits. Three of 23 animals were examined as control. Left parietal burr‐hole surgery was applied to remaining 20 animals and autolog blood of 0.25 ml injected into left sensory–motor region under general anesthesia. All rabbits were followed‐up for two months and sacrificed. L5 DRG's were observed histopathologically. The results were analyzed with Mann–Whitney U‐test.

Results

Right spastic hemiplegia developed only in 16 operated animals and 10 of them were developed ileus. The number of degenerated neurons in DRG was higher in the plegic side than in the non‐plegic side (p < 0.001). But, the difference between the non‐plegic side of the study group and control group did not meaningful (p > 0.05).

Conclusion

Intracerebral hemorrhages affecting the sensory–motor cortex may result in neurodegeneration in DRG. Sensitive reflex arches of striated muscles and bowels may be disturbed due to DRG degeneration and results in spasticity and/or ileus.
Superficial Acral Fibromyxoma of the Distal Phalanx of the Thumb
Authors: ABOU-NUKTA F. , FIEDLER P. , PARKASH V. , ARONS J.
Published: September 2006

Superficial acral fibromyxoma is an uncommon benign tumour which was first described recently ( Fetsch et al., 2001 , Human Pathology 32: 704–714). It has been reported several times since, suggesting it is more common than initially thought.
A One-Stage Shoulder Arthrodesis and Brooks Seddon Pectoralis Major to Biceps Tendon Transfer for Upper Brachial Plexus Injuries
Authors: SOLOMONS M. , CVITANICH M.
Published: September 2006

Reconstructive procedures to optimise the function of patients with upper brachial plexus injuries are well described. From 1999 to 2005, nine patients underwent a single stage Brooks Seddon pectoralis major to biceps tendon transfer with a glenohumeral arthrodesis for restoration of elbow flexion and shoulder stability. All of these patients had sustained traumatic upper trunk brachial plexus injuries which had not responded to nerve repair, grafting or neurotisation or had a delayed presentation. Results were assessed using a goniometer and the Medical Research Council strength grading. At follow-up of 28.5 months, the average arc of elbow flexion was 103° and eight had good elbow flexion power. There was one failure. We had two complications, both related to humerus fractures below the arthrodesis plate. Both united with conservative treatment. Our experience has given encouraging results with a high level of patient satisfaction. Our indications, operative technique and results are presented.
The Ghost of the Literary in Recent Theories of Text and Performance
Authors: Erickson Jon
Published: September 2006

In Book 3 of Plato's Republic, Socrates refers to the beginning of the Iliad in order to take Homer to task for switching from a purely narrative voice to actually “speaking” in the voice of a character—the Trojan priest Chryses—who is attempting to get Agamemnon to return his daughter. Socrates then demonstrates in his own third-person narrative of that same story how it could have been told without the imitation provided by the priest's speech. Socrates also makes the point that it is in tragic drama where the opposite condition obtains: tragic drama is comprised entirely of direct, imitative speech instead of a distanced, third-person narration. The distinction being made between diegesis (narrative) and mimesis (imitation) marks the beginning of the concept of theatricality, a concept still hotly debated today. Interestingly enough, as is often the case with concepts, it is born in a negative fashion, from antitheatrical criticism.
Optical transfer cavity stabilization using current-modulated injection-locked diode lasers
Authors: Bohlouli-Zanjani P. , Afrousheh K. , Martin J. D. D.
Published: September 2006

It is demonstrated that rf current modulation of a frequency stabilized injection-locked diode laser allows the stabilization of an optical cavity to adjustable lengths, by variation of the rf frequency. This transfer cavity may be used to stabilize another laser at an arbitrary wavelength, in the absence of atomic or molecular transitions suitable for stabilization. Implementation involves equipment and techniques commonly used in laser cooling and trapping laboratories and does not require electro- or acousto-optic modulators. With this technique we stabilize a transfer cavity using a rf current-modulated diode laser which is injection locked to a 780nm reference diode laser. The reference laser is stabilized using polarization spectroscopy in a Rb cell. A Ti:sapphire ring laser at 960nm is locked to this transfer cavity and may be precisely scanned by varying the rf modulation frequency. We demonstrate the suitability of this system for the excitation of laser cooled Rb atoms to Rydberg states.
Cytoskeletal polymer networks: The molecular structure of cross-linkers determines macroscopic properties
Authors: Wagner B. , Tharmann R. , Haase I. , Fischer M. , Bausch A. R.
Published: September 2006

In living cells the mechanical properties of the actin cytoskeleton are defined by the local activation of different actin cross-linking proteins. These proteins consist of actin-binding domains that are separated and geometrically organized by different numbers of rod domains. The detailed molecular structure of the cross-linking molecules determines the structural and mechanical properties of actin networks
in vivo
. In this study, we systematically investigate the impact of the length of the spacing unit between two actin-binding domains on
in vitro
actin networks. Such synthetic cross-linkers reveal that the shorter the constructs are, the greater the elastic modulus changes in the linear response regime. Because the same binding domains are used in all constructs, only the differences in the number of rod domains determine their mechanical effectiveness. Structural rearrangements of the networks show that bundling propensity is highest for the shortest construct. The nonlinear mechanical response is affected by the molecular structure of the cross-linker molecules, and the observed critical strains and fracture stress increase proportional to the length of the spacing unit.
Small molecules that bind the inner core of gp41 and inhibit HIV envelope-mediated fusion
Authors: Frey Gary , Rits-Volloch Sophia , Zhang X.-Q. , Schooley Robert T. , Chen Bing , Harrison Stephen C.
Published: September 2006

HIV-1 enters cells by membrane fusion, mediated by the trimeric viral envelope glycoprotein gp160, which is processed by a single proteolytic cleavage into stably associated gp120 and gp41. The gp120/gp41 trimer can be triggered to undergo an irreversible conformational change. Using a protein-based assay designed to mimic the gp41 conformational change, we screened for small molecules that prevent the formation of postfusion gp41. Several compounds were identified. One set of structurally related molecules inhibited formation of a postfusion-like assembly with an IC
50
of ≈5 μM. The compounds also inhibited envelope-mediated membrane fusion in both cell–cell fusion and viral infectivity assays. Thus, our screen identifies effective fusion inhibitors. Tested against a panel of envelope proteins from primary HIV-1 isolates, the compounds inhibited fusion across a broad range of clades, including both M and T tropic strains. They bind in a highly conserved, hydrophobic pocket on the inner core of the gp41 trimer, a region previously identified as a potential inhibitor site.
The effect of anticipation and the specificity of sex differences for amygdala and hippocampus function in emotional memory
Authors: Mackiewicz Kristen L. , Sarinopoulos Issidoros , Cleven Krystal L. , Nitschke Jack B.
Published: September 2006

Prior research has shown memory is enhanced for emotional events. Key brain areas involved in emotional memory are the amygdala and hippocampus, which are also recruited during aversion and its anticipation. This study investigated whether anticipatory processes signaling an upcoming aversive event contribute to emotional memory. In an event-related functional MRI paradigm, 40 healthy participants viewed aversive and neutral pictures preceded by predictive warning cues. Participants completed a surprise recognition task directly after functional MRI scanning or 2 weeks later. In anticipation of aversive pictures, bilateral dorsal amygdala and anterior hippocampus activations were associated with better immediate recognition memory. Similar associations with memory were observed for activation of those areas in response to aversive pictures. Anticipatory activation predicted immediate memory over and above these associations for picture viewing. Bilateral ventral amygdala activations in response to aversive pictures predicted delayed memory only. We found that previously reported sex differences of memory associations with left amygdala for women and with right amygdala for men were confined to the ventral amygdala during picture viewing and delayed memory. Results support an established animal model elucidating the functional neuroanatomy of the amygdala and hippocampus in emotional memory, highlight the importance of anticipatory processes in such memory for aversive events, and extend neuroanatomical evidence of sex differences for emotional memory.
Solution structure of the complex between poxvirus-encoded CC chemokine inhibitor vCCI and human MIP-1β
Authors: Zhang Li , DeRider Michele , McCornack Melissa A. , Jao Shu-chuan , Isern Nancy , Ness Traci , Moyer Richard , LiWang Patricia J.
Published: September 2006

Chemokines (chemotactic cytokines) comprise a large family of proteins that recruit and activate leukocytes, giving chemokines a major role in both immune response and inflammation-related diseases. The poxvirus-encoded viral CC chemokine inhibitor (vCCI) binds to many CC chemokines with high affinity, acting as a potent inhibitor of chemokine action. We have used heteronuclear multidimensional NMR to determine the structure of an orthopoxvirus vCCI in complex with a human CC chemokine, MIP-1β (macrophage inflammatory protein 1β). vCCI binds to the chemokine with 1:1 stoichiometry, forming a complex of 311 aa. vCCI uses residues from its β-sheet II to interact with a surface of MIP-1β that includes residues adjacent to its N terminus, as well as residues in the 20′s region and the 40′s loop. This structure reveals the strategy used by vCCI to tightly bind numerous chemokines while retaining selectivity for the CC chemokine subfamily.
Alternative inclusion of fibroblast growth factor receptor 2 exon IIIc in Dunning prostate tumors reveals unexpected epithelial mesenchymal plasticity
Authors: Oltean Sebastian , Sorg Brian S. , Albrecht Todd , Bonano Vivian I. , Brazas Robert M. , Dewhirst Mark W. , Garcia-Blanco Mariano A.
Published: September 2006

In epithelial cells, alternative splicing of fibroblast growth factor receptor 2 (FGFR2) transcripts leads to the expression of the FGFR2(IIIb) isoform, whereas in mesenchymal cells, the same process results in the synthesis of FGFR2(IIIc). Expression of the FGFR2(IIIc) isoform during prostate tumor progression suggests a disruption of the epithelial character of these tumors. To visualize the use of FGFR2 exon IIIc in prostate AT3 tumors in syngeneic rats, we constructed minigene constructs that report on alternative splicing. Imaging these alternative splicing decisions revealed unexpected mesenchymal–epithelial transitions in these primary tumors. These transitions were observed more frequently where tumor cells were in contact with stroma. Indeed, these transitions were frequently observed among lung micrometastases in the organ parenchyma and immediately adjacent to blood vessels. Our data suggest an unforeseen relationship between epithelial mesenchymal plasticity and malignant fitness.
A tropomyosin-related kinase B ligand is required for ERK activation, long-term synaptic facilitation, and long-term memory in
Aplysia
Authors: Sharma Shiv K. , Sherff Carolyn M. , Stough Shara , Hsuan Vickie , Carew Thomas J.
Published: September 2006

BDNF, which acts through tropomyosin-related kinase B (TrkB) receptors during mammalian development, also enhances long-term synaptic facilitation (LTF) in adult
Aplysia
. Because LTF is a substrate for long-term memory (LTM) in
Aplysia
, we examined the requirement of a secreted TrkB ligand in LTM formation at molecular, synaptic, and behavioral levels. Using an extracellular fusion protein that sequesters secreted TrkB ligands, we show that TrkB function is required for serotonin-induced activation of extracellular signal-regulated kinase, tail nerve shock-induced LTF in the CNS, and tail shock-induced LTM but is not necessary for short-term synaptic facilitation or short-term memory. These results show that a secreted growth factor, acting through a TrkB signaling cascade, is critical for the induction of long-lasting plasticity and memory formation in
Aplysia
.
Reconstitution of full-round uridine-deletion RNA editing with three recombinant proteins
Authors: Kang Xuedong , Gao Guanghan , Rogers Kestrel , Falick Arnold M. , Zhou Sharleen , Simpson Larry
Published: September 2006

Uridine (U)-insertion/deletion RNA editing in trypanosome mitochondria involves an initial cleavage of the preedited mRNA at specific sites determined by the annealing of partially complementary guide RNAs. An involvement of two RNase III-containing core editing complex (L-complex) proteins, MP90 (KREPB1) and MP61 (KREPB3) in, respectively, U-deletion and U-insertion editing, has been suggested, but these putative enzymes have not been characterized or expressed in active form. Recombinant MP90 proteins from
Trypanosoma brucei
and
Leishmania major
were expressed in insect cells and cytosol of
Leishmania tarentolae
, respectively. These proteins were active in specifically cleaving a model U-deletion site and not a U-insertion site. Deletion or mutation of the RNase III motif abolished this activity. Full-round guide RNA (gRNA)-mediated
in vitro
U-deletion editing was reconstituted by a mixture of recombinant MP90 and recombinant RNA editing exonuclease I from
L. major
, and recombinant RNA editing RNA ligase 1 from
L. tarentolae
. MP90 is designated REN1, for RNA-editing nuclease 1.
Identification of DNMT1 (DNA methyltransferase 1) hypomorphs in somatic knockouts suggests an essential role for DNMT1 in cell survival
Authors: Egger Gerda , Jeong Shinwu , Escobar Sonia G. , Cortez Connie C. , Li Tony W. H. , Saito Yoshimasa , Yoo Christine B. , Jones Peter A. , Liang Gangning
Published: September 2006

Previous studies have shown that DNA methyltransferase (Dnmt) 1 is required for maintenance of bulk DNA methylation and is essential for mouse development. However, somatic disruption of
DNMT1
in the human cancer cell line HCT116 was not lethal and caused only minor decreases in methylation. Here, we report the identification of a truncated DNMT1 protein, which was generated by the disruption of
DNMT1
in HCT116 cells. The truncated protein, which had parts of the regulatory N-terminal domain deleted but preserved the catalytic C-terminal domain, was present at different levels in all
DNMT1
single-knockout and
DNMT1
/
DNMT3b
double-knockout cell lines tested and retained hemimethylase activity. DNMT1 RNAi resulted in decreased cell viability in WT and knockout cells and further loss of DNA methylation in
DNMT1
knockout cells. Furthermore, we observed a delay in methylation after replication and an increase in hemimethylation of specific CpG sites in cells expressing the truncated protein. Remethylation studies after drug-induced hypomethylation suggest a putative role of DNMT1 in the
de novo
methylation of a subtelomeric repeat,
D4Z4
, which is lost in cells lacking full-length DNMT1. Our data suggest that DNMT1 might be essential for maintenance of DNA methylation, proliferation, and survival of cancer cells.
AL-57, a ligand-mimetic antibody to integrin LFA-1, reveals chemokine-induced affinity up-regulation in lymphocytes
Authors: Shimaoka Motomu , Kim Minsoo , Cohen Edward H. , Yang Wei , Astrof Nathan , Peer Dan , Salas Azucena , Ferrand Audrey , Springer Timothy A.
Published: September 2006

Affinity of integrin lymphocyte function-associated antigen 1 (LFA-1) is enhanced by conformational changes from the low-affinity closed form to the high-affinity (HA) open form of the ligand-binding inserted (I) domain as shown by work with purified I domains. However, affinity up-regulation of LFA-1 on the cell surface by physiological agonists such as chemokines has yet to be demonstrated by monovalent reagents. We characterize a mAb, AL-57 (activated LFA-1 clone 57), that has been developed by phage display that selectively targets the HA open conformation of the LFA-1 I domain. AL-57 discriminates among low-affinity, intermediate-affinity, and HA states of LFA-1. Furthermore, AL-57 functions as a ligand mimetic that binds only upon activation and requires Mg2+for binding. Compared with the natural ligand intercellular adhesion molecule-1, AL-57 shows a tighter binding to the open I domain and a 250-fold slower off rate. Monovalent Fab AL-57 demonstrates affinity increases on a subset (≈10%) of lymphocyte cell surface LFA-1 molecules upon stimulation with CXCL-12 (CXC chemokine ligand 12). Affinity up-regulation correlates with global conformational changes of LFA-1 to the extended form. Affinity increase stimulated by CXCL-12 is transient and peaks 2 to 5 min after stimulation.
Influenza A virus NS1 protein binds p85β and activates phosphatidylinositol-3-kinase signaling
Authors: Hale Benjamin G. , Jackson David , Chen Yun-Hsiang , Lamb Robert A. , Randall Richard E.
Published: September 2006

Influenza A virus NS1 is a multifunctional protein, and in virus-infected cells NS1 modulates a number of host-cell processes by interacting with cellular factors. Here, we report that NS1 binds directly to p85β, a regulatory subunit of phosphatidylinositol-3-kinase (PI3K), but not to the related p85α subunit. Activation of PI3K in influenza virus-infected cells depended on genome replication, and showed kinetics that correlated with NS1 expression. Additionally, it was found that expression of NS1 alone was sufficient to constitutively activate PI3K, causing the phosphorylation of a downstream mediator of PI3K signal transduction, Akt. Mutational analysis of a potential SH2-binding motif within NS1 indicated that the highly conserved tyrosine at residue 89 is important for both the interaction with p85β, and the activation of PI3K. A mutant influenza virus (A/Udorn/72) expressing NS1 with the Y89F amino acid substitution exhibited a small-plaque phenotype, and grew more slowly in tissue culture than WT virus. These data suggest that activation of PI3K signaling in influenza A virus-infected cells is important for efficient virus replication.
Repeated 100 Hz TENS for the Treatment of Chronic Inflammatory Hyperalgesia and Suppression of Spinal Release of Substance P in Monoarthritic Rats
Authors: Liu Hong-Xiang , Tian Jin-Bin , Luo Fei , Jiang Yu-Hui , Deng Zu-Guo , Xiong Liang , Liu Cheng , Wang Jin-Shu , Han Ji-Sheng
Published: September 2006

Transcutaneous electrical nerve stimulation (TENS) has been shown to be an effective measure for pain relief. The aim of the present study was to determine the optimal intensity and interval of repeated 100 Hz TENS for the treatment of chronic inflammatory hyperalgesia in a monoarthritic pain model of the rat, and to assess the changes of the spinal substance P (SP) release in response to TENS treatment. A reliable, reproducible chronic monoarthritic pain model was produced by intra‐articular injection of complete Freund′s adjuvant (CFA) at single ankle joint. The efficacy of 100 Hz TENS treatments with different frequencies and intensities was compared. In the acute period (within 3 weeks) of monoarthritis, twice‐a‐week schedule of TENS reduced the swelling of the inflamed ankle significantly. In the stable period (4–9 weeks), however, once‐a‐week schedule produced a significantly better therapeutic effect on both inflammation and arthritic hyperalgesia than that of twice‐ or five‐times‐a‐week schedule. Using three levels of intensity of TENS, we found that the weaker (1‐1‐2 mA) stimulation produced significantly better therapeutic effects. Repeated TENS produced a reduction of SP content in spinal perfusate in parallel with the progressive reduction of the arthritic pain scores. Our results suggest that (i) consecutive TENS treatments produced cumulative effect for chronic hyperalgesia, (ii) for chronic inflammatory hyperalgesia, a weaker intensity and more sparsely arranged treatment schedule may produce better therapeutic effect and (iii) a decrease in SP release may serve as one of the possible neurochemical mechanisms underlying the therapeutic effects of multiple TENS treatments on chronic inflammatory hyperalgesia.
Safety of Traditional Arab Herbal Medicine
Authors: Saad Bashar , Azaizeh Hassan , Abu-Hijleh Ghassan , Said Omar
Published: September 2006

Herbal remedies are widely used for the treatment and prevention of various diseases and often contain highly active pharmacological compounds. Many medicinal herbs and pharmaceutical drugs are therapeutic at one dose and toxic at another. Toxicity related to traditional medicines is becoming more widely recognized as these remedies become popular in the Mediterranean region as well as worldwide. Most reports concerning the toxic effects of herbal medicines are associated with hepatotoxicity although reports of other toxic effects including kidney, nervous system, blood, cardiovascular and dermatologic effects, mutagenicity and carcinogenicity have also been published in the medical literature. This article presents a systematic review on safety of traditional Arab medicine and the contribution of Arab scholars to toxicology. Use of modern cell biological, biochemical, in vitro and in vivo techniques for the evaluation of medicinal plants safety is also discussed.
Comparative genomics modeling of the NRSF/REST repressor network: From single conserved sites to genome-wide repertoire
Authors: Mortazavi Ali , Thompson Evonne Chen Leeper , Garcia Sarah T. , Myers Richard M. , Wold Barbara
Published: September 2006

We constructed and applied an open source informatic framework called Cistematic in an effort to predict the target gene repertoire for transcription factors with large binding sites. Cistematic uses two different evolutionary conservation-filtering algorithms in conjunction with several analysis modules. Beginning with a single conserved and biologically tested site for the neuronal repressor NRSF/REST, Cistematic generated a refined PSFM (position specific frequency matrix) based on conserved site occurrences in mouse, human, and dog genomes. Predictions from this model were validated by chromatin immunoprecipitation (ChIP) followed by quantitative PCR. The combination of transfection assays and ChIP enrichment data provided an objective basis for setting a threshold for membership and rank-ordering a final gene cohort model consisting of 842 high-confidence sites in the human genome associated with 733 genes. Statistically significant enrichment of NRSE-associated genes was found for neuron-specific Gene Ontology (GO) terms and neuronal mRNA expression profiles. A more extensive evolutionary survey showed that NRSE sites matching the PSFM model exist in roughly similar numbers in all fully sequenced vertebrate genomes but are notably absent from invertebrate and protochordate genomes, as is NRSF itself. Some NRSF/REST sites reside in repeats, which suggests a mechanism for both ancient and modern dispersal of NRSEs through vertebrate genomes. Multiple predicted sites are located near neuronal microRNA and splicing-factor genes, and these tested positive for NRSF/REST occupancy in vivo. The resulting network model integrates post-transcriptional and translational controllers, including candidate feedback loops on NRSF and its corepressor, CoREST.
Doubling genome size without polyploidization: Dynamics of retrotransposition-driven genomic expansions in Oryza australiensis, a wild relative of rice
Authors: Piegu Benoit , Guyot Romain , Picault Nathalie , Roulin Anne , Saniyal Abhijit , Kim Hyeran , Collura Kristi , Brar Darshan S. , Jackson Scott , Wing Rod A. , Panaud Olivier
Published: September 2006

Retrotransposons are the main components of eukaryotic genomes, representing up to 80% of some large plant genomes. These mobile elements transpose via a “copy and paste” mechanism, thus increasing their copy number while active. Their accumulation is now accepted as the main factor of genome size increase in higher eukaryotes, besides polyploidy. However, the dynamics of this process are poorly understood. In this study, we show that Oryza australiensis, a wild relative of the Asian cultivated rice O. sativa, has undergone recent bursts of three LTR-retrotransposon families. This genome has accumulated more than 90,000 retrotransposon copies during the last three million years, leading to a rapid twofold increase of its size. In addition, phenetic analyses of these retrotransposons clearly confirm that the genomic bursts occurred posterior to the radiation of the species. This provides direct evidence of retrotransposon-mediated variation of genome size within a plant genus.
Genomic organization of the Drosophila telomere retrotransposable elements
Authors: George Janet A. , DeBaryshe P. Gregory , Traverse Karen L. , Celniker Susan E. , Pardue Mary-Lou
Published: September 2006

The emerging sequence of the heterochromatic portion of the Drosophila melanogaster genome, with the most recent update of euchromatic sequence, gives the first genome-wide view of the chromosomal distribution of the telomeric retrotransposons, HeT-A, TART, and Tahre. As expected, these elements are entirely excluded from euchromatin, although sequence fragments of HeT-A and TART 3 untranslated regions are found in nontelomeric heterochromatin on the Y chromosome. The proximal ends of HeT-A/TART arrays appear to be a transition zone because only here do other transposable elements mix in the array. The sharp distinction between the distribution of telomeric elements and that of other transposable elements suggests that chromatin structure is important in telomere element localization. Measurements reported here show (1) D. melanogaster telomeres are very long, in the size range reported for inbred mouse strains (averaging 46 kb per chromosome end in Drosophila stock 2057). As in organisms with telomerase, their length varies depending on genotype. There is also slight under-replication in polytene nuclei. (2) Surprisingly, the relationship between the number of HeT-A and TART elements is not stochastic but is strongly correlated across stocks, supporting the idea that the two elements are interdependent. Although currently assembled portions of the HeT-A/TART arrays are from the most-proximal part of long arrays, ~61% of the total HeT-A sequence in these regions consists of intact, potentially active elements with little evidence of sequence decay, making it likely that the content of the telomere arrays turns over more extensively than has been thought.
Identifying gene regulatory elements by genomic microarray mapping of DNaseI hypersensitive sites
Authors: Follows George A. , Dhami Pawan , Göttgens Berthold , Bruce Alexander W. , Campbell Peter J. , Dillon Shane C. , Smith Aileen M. , Koch Christoph , Donaldson Ian J. , Scott Mike A. , Dunham Ian , Janes Mary E. , Vetrie David , Green Anthony R.
Published: September 2006

The identification of cis-regulatory elements is central to understanding gene transcription. Hypersensitivity of cis-regulatory elements to digestion with DNaseI remains the gold-standard approach to locating such elements. Traditional methods used to identify DNaseI hypersensitive sites are cumbersome and can only be applied to short stretches of DNA at defined locations. Here we report the development of a novel genomic array-based approach to DNaseI hypersensitive site mapping (ADHM) that permits precise, large-scale identification of such sites from as few as 5 million cells. Using ADHM we identified all previously recognized hematopoietic regulatory elements across 200 kb of the mouse T-cell acute lymphocytic leukemia-1 (Tal1) locus, and, in addition, identified two novel elements within the locus, which show transcriptional regulatory activity. We further validated the ADHM protocol by mapping the DNaseI hypersensitive sites across 250 kb of the human TAL1 locus in CD34+ primary stem/progenitor cells and K562 cells and by mapping the previously known DNaseI hypersensitive sites across 240 kb of the human α-globin locus in K562 cells. ADHM provides a powerful approach to identifying DNaseI hypersensitive sites across large genomic regions.
Large-scale intron conservation and order-of-magnitude variation in intron loss/gain rates in apicomplexan evolution
Authors: Roy Scott William , Penny David
Published: September 2006

The age of modern introns and the evolutionary forces controlling intron loss and gain remain matters of much debate. In the case of the apicomplexan malaria parasite Plasmodium falciparum, previous studies have shown that while the positions of two thirds of P. falciparum introns are not shared with surveyed non-apicomplexans (leaving open the possibility that they were relatively recently gained), 99.1% are shared with Plasmodium yoelii, which diverged from P. falciparum at least 100 Mya. We show here that 60.6% of P. falciparum intron positions in conserved regions are shared with the distantly related apicomplexan Theileria parva, whereas only 18.2% of introns in the more intron-rich T. parva are shared with P. falciparum. Comparison of 3305 pairs of orthologous genes between T. parva and Theileria annulata showed that 7089/7111 (99.7%) introns in conserved regions are shared between species. These levels of conservation imply significant differences in rates of intron loss and gain through apicomplexan history. Because transposable elements (TEs) and/or (often TE-encoded) reverse transcriptase are implicated in models of intron loss and gain, the observed low rates of intron loss and gain in recent Plasmodium and Theileria evolution are consistent with the lack of known TE in those groups. We suggest that intron loss/gain in some eukaryotic lineages may be concentrated in relatively short episodes coincident with occasional TE invasions.
Mapping of the juxtacentromeric heterochromatin-euchromatin frontier of human chromosome 21
Authors: Grunau Christoph , Buard Jérome , Brun Marie-Elisabeth , De Sario Albertina
Published: September 2006

Euchromatin and heterochromatin are functional compartments of the genome. However, little is known about the structure and the precise location of the heterochromatin–euchromatin boundaries in higher eukaryotes. Constitutive heterochromatin in centromeric regions is associated with (1) specific histone methylation patterns, (2) high levels of DNA methylation, (3) low recombination frequency, and (4) the repression of transcription. All of this contrasts with the permissive structure of euchromatin found along chromosome arms. On the sequence level, the transition between these two domains consists most often of patchworks of segmental duplications. We present here a comprehensive analysis of gene expression, DNA methylation in CpG islands, distribution of histone isoforms, and recombination activity for the juxtacentromeric (or pericentromeric) region of the long arm of human chromosome 21. We demonstrate that most HapMap data are reliable within this region. We show that high linkage disequilibrium between pairs of SNPs extends 719–737 kb from the centromeric α-satellite. In the same region we find a peak of histone isoforms H3K9Me3 and H3K27Me (715–822 kb distal to the α-satellite). In normal somatic cells, CpG islands proximal to this peak are highly methylated, whereas distal CpG islands are not or very little methylated. This methylation profile undergoes dramatic changes in cancer cells and during spermatogenesis. As a consequence, transcription from heterochromatic genes is activated in the testis, and aberrant gene activation can occur during neoplastic transformation. Our data indicate that the frontier between the juxtacentromeric heterochromatic domain and euchromatic domain of the long arm of chromosome 21 is marked by a heterochromatic peak located ~750 kb distal to the α-satellite.
Pathogen-Induced Arabidopsis WRKY7 Is a Transcriptional Repressor and Enhances Plant Susceptibility to Pseudomonas syringae
Authors: Kim Kang-Chang , Fan Baofang , Chen Zhixiang
Published: September 2006

The Arabidopsis (Arabidopsis thaliana) WRKY7 gene is induced by pathogen infection and salicylic acid (SA) treatment and may therefore play a role in plant defense responses. Here, we show that WRKY7 is localized in the nucleus, recognizes DNA molecules with the W-box (TTGAC) elements, and functions as a transcriptional repressor in plant cells. To study its biological functions directly, we have characterized both loss-of-function T-DNA insertion and RNAi mutants and gain-of-function transgenic overexpression plants for WRKY7 in Arabidopsis. The T-DNA insertion and RNAi mutant plants displayed enhanced resistance to a virulent strain of the bacterial pathogen Pseudomonas syringae as measured by significant decrease in both bacterial growth and symptom development as compared to those in wild-type plants. The enhanced resistance in the loss-of-function mutants was associated with increased induction of SA-regulated Pathogenesis-Related 1 (PR1) by the bacterial pathogen. Transgenic plants that constitutively overexpress WRKY7 have altered leaf growth and morphology strikingly similar to those observed in the previously isolated eds8 mutant plants. Like eds8 mutant plants, WRKY7-overexpressing plants supported more growth of P. syringae and developed more severe disease symptoms than wild-type plants. The enhanced susceptibility of both the WRKY7-overexpressing plants and the eds8 mutant correlated with reduced expression of defense-related genes, including PR1, but significantly increased accumulation of SA after pathogen infection, probably due to reduced negative feedback of SA synthesis. Thus, pathogen-induced WRKY7 transcription factor play a negative role in defense responses to P. syringae.
Consistency of Polyamine Profiles and Expression of Arginine Decarboxylase in Mitosis during Zygotic Embryogenesis of Scots Pine
Authors: Vuosku Jaana , Jokela Anne , Läärä Esa , Sääskilahti Mira , Muilu Riina , Sutela Suvi , Altabella Teresa , Sarjala Tytti , Häggman Hely
Published: September 2006

In this study, we show that both arginine decarboxylase (ADC) protein and mRNA transcript are present at different phases of mitosis in Scots pine (Pinus sylvestris) zygotic embryogenesis. We also examined the consistency of polyamine (PA) profiles with the effective temperature sum, the latter indicating the developmental stage of the embryos. PA metabolism was analyzed by fitting statistical regression models to the data of free and soluble conjugated PAs, to the enzyme activities of ADC and ornithine decarboxylase (ODC), as well as to the gene expression of ADC. According to the fitted models, PAs typically had the tendency to increase at the early stages but decrease at the late stages of embryogenesis. Only the free putrescine fraction remained stable during embryo development. The PA biosynthesis strongly preferred the ADC pathway. Both ADC gene expression and ADC enzyme activity were substantially higher than putative ODC gene expression or ODC enzyme activity, respectively. ADC gene expression and enzyme activity increased during embryogenesis, which suggests the involvement of transcriptional regulation in the expression of ADC. Both ADC mRNA and ADC protein localized in dividing cells of embryo meristems and more specifically within the mitotic spindle apparatus and close to the chromosomes, respectively. The results suggest the essential role of ADC in the mitosis of plant cells.
Isolation ofmtpimProvesTnt1a Useful Reverse Genetics Tool inMedicago truncatulaand Uncovers New Aspects ofAP1-Like Functions in Legumes
Authors: Benlloch Reyes , d'Erfurth Isabelle , Ferrandiz Cristina , Cosson Viviane , Beltrán José Pío , Cañas Luis Antonio , Kondorosi Adam , Madueño Francisco , Ratet Pascal
Published: September 2006

Comparative studies help shed light on how the huge diversity in plant forms found in nature has been produced. We use legume species to study developmental differences in inflorescence architecture and flower ontogeny with classical models such as Arabidopsis thaliana or Antirrhinum  majus. Whereas genetic control of these processes has been analyzed mostly in pea (Pisum sativum), Medicago truncatula is emerging as a promising alternative system for these studies due to the availability of a range of genetic tools. To assess the use of the retrotransposon Tnt1 for reverse genetics in M. truncatula, we screened a small Tnt1-mutagenized population using degenerate primers for MADS-box genes, known controllers of plant development. We describe here the characterization of mtpim, a new mutant caused by the insertion of Tnt1 in a homolog to the PROLIFERATING INFLORESCENCE MERISTEM (PIM)/APETALA1 (AP1)/SQUAMOSA genes. mtpim shows flower-to-inflorescence conversion and altered flowers with sepals transformed into leaves, indicating that MtPIM controls floral meristem identity and flower development. Although more extreme, this phenotype resembles the pea pim mutants, supporting the idea that M. truncatula could be used to complement analysis of reproductive development already initiated in pea. In fact, our study reveals aspects not shown by analysis of pea mutants: that the mutation in the AP1 homolog interferes with the specification of floral organs from common primordia and causes conversion of sepals into leaves, in addition to true conversion of flowers into inflorescences. The isolation of mtpim represents a proof of concept demonstrating that Tnt1 populations can be efficiently used in reverse genetics screenings in M. truncatula.
Identification of Drought Tolerance Determinants by Genetic Analysis of Root Response to Drought Stress and Abscisic Acid
Authors: Xiong Liming , Wang Rui-Gang , Mao Guohong , Koczan Jessica M.
Published: September 2006

Drought stress is a common adverse environmental condition that seriously affects crop productivity worldwide. Due to the complexity of drought as a stress signal, deciphering drought tolerance mechanisms has remained a major challenge to plant biologists. To develop new approaches to study plant drought tolerance, we searched for phenotypes conferred by drought stress and identified the inhibition of lateral root development by drought stress as an adaptive response to the stress. This drought response is partly mediated by the phytohormone abscisic acid. Genetic screens using Arabidopsis (Arabidopsis thaliana) were devised, and drought inhibition of lateral root growth (dig) mutants with altered responses to drought or abscisic acid in lateral root development were isolated. Characterization of these dig mutants revealed that they also exhibit altered drought stress tolerance, indicating that this root response to drought stress is intimately linked to drought adaptation of the entire plant and can be used as a trait to access the elusive drought tolerance machinery. Our study also revealed that multiple mechanisms coexist and together contribute to whole-plant drought tolerance.