bluuebunny/crossref_metadata_2025 huggingface dataset:
Electronic energy delocalization and dissipation in single- and double-stranded DNA
Authors: Buchvarov Ivan , Wang Qiang , Raytchev Milen , Trifonov Anton , Fiebig Torsten
Published: March 2007

The mechanism that nature applies to dissipate excess energy from solar UV light absorption in DNA is fundamental, because its efficiency determines the vulnerability of all genetic material to photodamage and subsequent mutations. Using femtosecond time-resolved broadband spectroscopy, we have traced the electronic excitation in both time and space along the base stack in a series of single-stranded and double-stranded DNA oligonucleotides. The obtained results demonstrate not only the presence of delocalized electronic domains (excitons) as a result of UV light absorption, but also reveal the spatial extent of the excitons.
Folding free-energy landscape of villin headpiece subdomain from molecular dynamics simulations
Authors: Lei Hongxing , Wu Chun , Liu Haiguang , Duan Yong
Published: March 2007

High-accuracy
ab initio
folding has remained an elusive objective despite decades of effort. To explore the folding landscape of villin headpiece subdomain HP35, we conducted two sets of replica exchange molecular dynamics for 200 ns each and three sets of conventional microsecond-long molecular dynamics simulations, using AMBER FF03 force field and a generalized-Born solvation model. The protein folded consistently to the native state; the lowest C
α
-rmsd from the x-ray structure was 0.46 Å, and the C
α
- rmsd of the center of the most populated cluster was 1.78 Å at 300 K.
ab initio
simulations have previously not reached this level. The folding landscape of HP35 can be partitioned into the native, denatured, and two intermediate-state regions. The native state is separated from the major folding intermediate state by a small barrier, whereas a large barrier exists between the major folding intermediate and the denatured states. The melting temperature
T
m
= 339 K extracted from the heat-capacity profile was in close agreement with the experimentally derived
T
m
= 342 K. A comprehensive picture of the kinetics and thermodynamics of HP35 folding emerges when the results from replica exchange and conventional molecular dynamics simulations are combined.
Role for CD47-SIRPα signaling in xenograft rejection by macrophages
Authors: Ide Kentaro , Wang Hui , Tahara Hiroyuki , Liu Jianxiang , Wang Xiaoying , Asahara Toshimasa , Sykes Megan , Yang Yong-Guang , Ohdan Hideki
Published: March 2007

We have previously proven that human macrophages can phagocytose porcine cells even in the absence of Ab or complement opsonization, indicating that macrophages present a pivotal immunological obstacle to xenotransplantation. A recent report indicates that the signal regulatory protein (SIRP)α is a critical immune inhibitory receptor on macrophages, and its interaction with CD47, a ligand for SIRPα, prevents autologous phagocytosis. Considering the limited compatibility (73%) in amino acid sequences between pig and human CD47, we hypothesized that the interspecies incompatibility of CD47 may contribute to the rejection of xenogeneic cells by macrophages. In the present study, we have demonstrated that porcine CD47 does not induce SIRPα tyrosine phosphorylation in human macrophage-like cell line, and soluble human CD47-Fc fusion protein inhibits the phagocytic activity of human macrophages toward porcine cells. In addition, we have verified that manipulation of porcine cells for expression of human CD47 radically reduces the susceptibility of the cells to phagocytosis by human macrophages. These results indicate that the interspecies incompatibility of CD47 significantly contributes to the rejection of xenogeneic cells by macrophages. Genetic induction of human CD47 on porcine cells could provide inhibitory signaling to SIRPα on human macrophages, providing a novel approach to preventing macrophage-mediated xenograft rejection.
Homogenization of regional river dynamics by dams and global biodiversity implications
Authors: Poff N. LeRoy , Olden Julian D. , Merritt David M. , Pepin David M.
Published: March 2007

Global biodiversity in river and riparian ecosystems is generated and maintained by geographic variation in stream processes and fluvial disturbance regimes, which largely reflect regional differences in climate and geology. Extensive construction of dams by humans has greatly dampened the seasonal and interannual streamflow variability of rivers, thereby altering natural dynamics in ecologically important flows on continental to global scales. The cumulative effects of modification to regional-scale environmental templates caused by dams is largely unexplored but of critical conservation importance. Here, we use 186 long-term streamflow records on intermediate-sized rivers across the continental United States to show that dams have homogenized the flow regimes on third- through seventh-order rivers in 16 historically distinctive hydrologic regions over the course of the 20th century. This regional homogenization occurs chiefly through modification of the magnitude and timing of ecologically critical high and low flows. For 317 undammed reference rivers, no evidence for homogenization was found, despite documented changes in regional precipitation over this period. With an estimated average density of one dam every 48 km of third- through seventh-order river channel in the United States, dams arguably have a continental scale effect of homogenizing regionally distinct environmental templates, thereby creating conditions that favor the spread of cosmopolitan, nonindigenous species at the expense of locally adapted native biota. Quantitative analyses such as ours provide the basis for conservation and management actions aimed at restoring and maintaining native biodiversity and ecosystem function and resilience for regionally distinct ecosystems at continental to global scales.
Collective neuronal growth and self organization of axons
Authors: de Gennes P.-G.
Published: March 2007

I describe an assembly of neurons that synthesizes a chemorepellant molecule and transfers this molecule to the growth cones by axonal transport. From the growth cone, the repellant diffuses in nearby regions, achieving a certain concentration profile, δ, with a gradient. The growth cone migrates preferentially toward the regions of low δ. I show that this process self-consistently generates a profile of finite width, with a relatively sharp front of neuronal growth.
Differential responses of hippocampal subfields to cortical up–down states
Authors: Hahn Thomas T. G. , Sakmann Bert , Mehta Mayank R.
Published: March 2007

The connectivity of the hippocampal trisynaptic circuit, formed by the dentate gyrus, the CA3 and the CA1 region, is well characterized anatomically and functionally
in vitro
. The functional connectivity of this circuit
in vivo
remains to be understood. Toward this goal, we investigated the influence of the spontaneous, synchronized oscillations in the neocortical local field potential, reflecting up–down states (UDS) of cortical neurons, on the hippocampus. We simultaneously measured the extracellular local field potential in association cortex and the membrane potential of identified hippocampal excitatory neurons in anesthetized mice. Dentate gyrus granule cells showed clear UDS modulation that was phase locked to cortical UDS with a short delay. In contrast, CA3 pyramidal neurons showed mixed UDS modulation, such that some cells were depolarized during the cortical up state and others were hyperpolarized. CA1 pyramidal neurons, located farther downstream, showed consistent UDS modulation, such that when the cortical and dentate gyrus neurons were depolarized, the CA1 pyramidal cells were hyperpolarized. These results demonstrate the differential functional connectivity between neocortex and hippocampal subfields during UDS oscillations.
A genomic screen for activators of the antioxidant response element
Authors: Liu Yanxia , Kern Jonathan T. , Walker John R. , Johnson Jeffrey A. , Schultz Peter G. , Luesch Hendrik
Published: March 2007

The antioxidant response element (ARE) is a cis-acting regulatory enhancer element found in the 5′ flanking region of many phase II detoxification enzymes. Up-regulation of ARE-dependent target genes is known to have neuroprotective effects; yet, the mechanism of activation is largely unknown. By screening an arrayed collection of ≈15,000 full-length expression cDNAs in the human neuroblastoma cell line IMR-32 with an ARE-luciferase reporter, we have identified several cDNAs not previously associated with ARE activation. A subset of cDNAs, encoding sequestosome 1 (SQSTM1) and dipeptidylpeptidase 3 (DPP3), activated the ARE in primary mouse-derived cortical neurons. Overexpression of SQSTM1 and DPP3 in IMR-32 cells stimulated NF-E2-related factor 2 (NRF2) nuclear translocation and led to increased levels of NAD(P)H:quinone oxidoreductase 1, a protein which is transcriptionally regulated by the ARE. When transfected into IMR-32 neuroblastoma cells that were depleted of transcription factor NRF2 by RNA interference, SQSTM1 and DPP3 were unable to activate the ARE or induce NAD(P)H:quinone oxidoreductase 1 expression, indicating that the ARE activation upon ectopic expression of these cDNAs is mediated by NRF2. Studies with pharmacological inhibitors indicated that 1-phosphatidylinositol 3-kinase and protein kinase C signaling are essential for activity. Overexpression of these cDNAs conferred partial resistance to hydrogen peroxide or rotenone-induced toxicity, consistent with the induction of antioxidant and phase II detoxification enzymes, which can protect from oxidative stress. This work and other such studies may provide mechanisms for activating the ARE in the absence of general oxidative stress and a yet-unexploited therapeutic approach to degenerative diseases and aging.
Identification of prothymosin-α1, the necrosis–apoptosis switch molecule in cortical neuronal cultures
Authors: Ueda Hiroshi , Fujita Ryousuke , Yoshida Akira , Matsunaga Hayato , Ueda Mutsumi
Published: March 2007

We initially identified a nuclear protein, prothymosin-α1 (ProTα), as a key protein inhibiting necrosis by subjecting conditioned media from serum-free cultures of cortical neurons to a few chromatography steps. ProTα inhibited necrosis of cultured neurons by preventing rapid loss of cellular adenosine triphosphate levels by reversing the decreased membrane localization of glucose transporters but caused apoptosis through up-regulation of proapoptotic Bcl2-family proteins. The apoptosis caused by ProTα was further inhibited by growth factors, including brain-derived neurotrophic factor. The ProTα-induced cell death mode switch from necrosis to apoptosis was also reproduced in experimental ischemia-reperfusion culture experiments, although the apoptosis level was markedly reduced, possibly because of the presence of growth factors in the reperfused serum. Knock down of PKCβII expression prevented this cell death mode switch. Collectively, these results suggest that ProTα is an extracellular signal protein that acts as a cell death mode switch and could be a promising candidate for preventing brain strokes with the help of known apoptosis inhibitors.
Critical requirement for cell cycle inhibitors in sustaining nonproliferative states
Authors: Pajalunga Deborah , Mazzola Alessia , Salzano Anna Maria , Biferi Maria Grazia , De Luca Gabriele , Crescenzi Marco
Published: March 2007

In adult vertebrates, most cells are not in the cell cycle at any one time. Physiological nonproliferation states encompass reversible quiescence and permanent postmitotic conditions such as terminal differentiation and replicative senescence. Although these states appear to be attained and maintained quite differently, they might share a core proliferation-restricting mechanism. Unexpectedly, we found that all sorts of nonproliferating cells can be mitotically reactivated by the sole suppression of histotype-specific cyclin-dependent kinase (cdk) inhibitors (CKIs) in the absence of exogenous mitogens. RNA interference–mediated suppression of appropriate CKIs efficiently triggered DNA synthesis and mitosis in established and primary terminally differentiated skeletal muscle cells (myotubes), quiescent human fibroblasts, and senescent human embryo kidney cells. In serum-starved fibroblasts and myotubes alike, cell cycle reactivation was critically mediated by the derepression of cyclin D–cdk4/6 complexes. Thus, both temporary and permanent growth arrest must be actively maintained by the constant expression of CKIs, whereas the cell cycle–driving cyclins are always present or can be readily elicited. In principle, our findings could find wide application in biotechnology and tissue repair whenever cell proliferation is limiting.
The Par polarity complex regulates Rap1- and chemokine-induced T cell polarization
Authors: Gérard Audrey , Mertens Alexander E.E. , van der Kammen Rob A. , Collard John G.
Published: March 2007

Cell polarization is required for virtually all functions of T cells, including transendothelial migration in response to chemokines. However, the molecular pathways that establish T cell polarity are poorly understood. We show that the activation of the partitioning defective (Par) polarity complex is a key event during Rap1- and chemokine-induced T cell polarization. Intracellular localization and activation of the Par complex are initiated by Rap1 and require Cdc42 activity. The Rac activator Tiam1 associates with both Rap1 and components of the Par complex, and thereby may function to connect the Par polarity complex to Rap1 and to regulate the Rac-mediated actin remodelling required for T cell polarization. Consistent with these findings, Tiam1-deficient T cells are impaired in Rap1- and chemokine-induced polarization and chemotaxis. Our studies implicate Tiam1 and the Par polarity complex in polarization of T cells, and provide a mechanism by which chemokines and Rap1 regulate T cell polarization and chemotaxis.
A CDK-related kinase regulates the length and assembly of flagella in Chlamydomonas
Authors: Tam Lai-Wa , Wilson Nedra F. , Lefebvre Paul A.
Published: March 2007

Little is known about how cells regulate the size of their organelles. In this study, we find that proper flagellar length control in Chlamydomonas reinhardtii requires the activity of a new member of the cyclin-dependent kinase (CDK) family, which is encoded by the LF2 (long flagella 2) gene. This novel CDK contains all of the important residues that are essential for kinase activity but lacks the cyclin-binding motif PSTAIRE. Analysis of genetic lesions in a series of lf2 mutant alleles and site-directed mutagenesis of LF2p reveals that improper flagellar length and defective flagellar assembly correlate with the extent of disruption of conserved kinase structures or residues by mutations. LF2p appears to interact with both LF1p and LF3p in the cytoplasm, as indicated by immunofluorescence localization, sucrose density gradients, cell fractionation, and yeast two-hybrid experiments. We propose that LF2p is the catalytic subunit of a regulatory kinase complex that controls flagellar length and flagellar assembly.
Syk, c-Src, the αvβ3 integrin, and ITAM immunoreceptors, in concert, regulate osteoclastic bone resorption
Authors: Zou Wei , Kitaura Hideki , Reeve Jennifer , Long Fanxin , Tybulewicz Victor L.J. , Shattil Sanford J. , Ginsberg Mark H. , Ross F. Patrick , Teitelbaum Steven L.
Published: March 2007

In this study, we establish that the tyrosine kinase Syk is essential for osteoclast function in vitro and in vivo. Syk−/− osteoclasts fail to organize their cytoskeleton, and, as such, their bone-resorptive capacity is arrested. This defect results in increased skeletal mass in Syk−/− embryos and dampened basal and stimulated bone resorption in chimeric mice whose osteoclasts lack the kinase. The skeletal impact of Syk deficiency reflects diminished activity of the mature osteoclast and not impaired differentiation. Syk regulates bone resorption by its inclusion with the αvβ3 integrin and c-Src in a signaling complex, which is generated only when αvβ3 is activated. Upon integrin occupancy, c-Src phosphorylates Syk. αvβ3-induced phosphorylation of Syk and the latter's capacity to associate with c-Src is mediated by the immunoreceptor tyrosine-based activation motif (ITAM) proteins Dap12 and FcRγ. Thus, in conjunction with ITAM-bearing proteins, Syk, c-Src, and αvβ3 represent an essential signaling complex in the bone-resorbing osteoclast, and, therefore, each is a candidate therapeutic target.
IL-31–IL-31R interactions negatively regulate type 2 inflammation in the lung
Authors: Perrigoue Jacqueline G. , Li Ji , Zaph Colby , Goldschmidt Michael , Scott Phillip , de Sauvage Frederic J. , Pearce Edward J. , Ghilardi Nico , Artis David
Published: March 2007

Interleukin (IL) 31Rα (glycoprotein 130–like monocyte receptor and glycoprotein 130–like receptor) heterodimerizes with oncostatin M receptor β to bind IL-31, a cytokine expressed preferentially by CD4+ T helper type 2 (Th2) cells. However, the functions of IL-31–IL-31R signaling in immune regulation remain unknown. Here, we identify a novel role for IL-31R in limiting type 2 inflammation in the lung. After intravenous injection of Schistosoma mansoni eggs, IL-31Rα−/− mice developed severe pulmonary inflammation, characterized by an increase in the area of granulomatous inflammation, increased numbers of resistin-like molecule α+ cells, and enhanced collagen deposition compared to WT counterparts. In vitro, macrophages generated from IL-31Rα−/− mice promoted enhanced ovalbumin-specific CD4+ T cell proliferation and purified naive CD4+ T cells from IL-31Rα−/− mice exhibited enhanced proliferation and expression of Th2 cytokines, identifying a T cell– and macrophage-intrinsic regulatory function for IL-31R signaling. In contrast, the generation of CD4+ T cell–mediated Th1 responses were normal in IL-31Rα−/− mice, suggesting that the regulatory role of IL-31R signaling is limited to type 2 responses. Together, these data implicate IL-31R signaling as a novel negative regulatory pathway that specifically limits type 2 inflammation.
A novel pathway down-modulating T cell activation involves HPK-1–dependent recruitment of 14-3-3 proteins on SLP-76
Authors: Bartolo Vincenzo Di , Montagne Benjamin , Salek Mogjiborahman , Jungwirth Britta , Carrette Florent , Fourtane Julien , Sol-Foulon Nathalie , Michel Frédérique , Schwartz Olivier , Lehmann Wolf D. , Acuto Oreste
Published: March 2007

The SH2 domain–containing leukocyte protein of 76 kD (SLP-76) is a pivotal element of the signaling machinery controlling T cell receptor (TCR)-mediated activation. Here, we identify 14-3-3ε and ζ proteins as SLP-76 binding partners. This interaction was induced by TCR ligation and required phosphorylation of SLP-76 at serine 376. Ribonucleic acid interference and in vitro phosphorylation experiments showed that serine 376 is the target of the hematopoietic progenitor kinase 1 (HPK-1). Interestingly, either S376A mutation or HPK-1 knockdown resulted in increased TCR-induced tyrosine phosphorylation of SLP-76 and phospholipase C-γ1. Moreover, an SLP-76–S376A mutant induced higher interleukin 2 gene transcription than wild-type SLP-76. These data reveal a novel negative feedback loop involving HPK-1–dependent serine phosphorylation of SLP-76 and 14-3-3 protein recruitment, which tunes T cell activation.
Oncogenic signaling: new insights and controversies from chronic myeloid leukemia
Authors: Van Etten Richard A.
Published: March 2007

Chronic myeloid leukemia (CML), which is caused by the BCR–ABL fusion tyrosine kinase, is one of the most intensively studied human cancers. ABL kinase inhibitors have been spectacularly successful in treating CML, but disease persistence and acquired drug resistance can prevent eradication and cure of the leukemia. The development of better therapies will depend on a full understanding of signaling pathways in CML, facilitated by model studies using mutant mice.
Structural Determinants of the Closed KCa3.1 Channel Pore in Relation to Channel Gating: Results from a Substituted Cysteine Accessibility Analysis
Authors: Klein Hélène , Garneau Line , Banderali Umberto , Simoes Manuel , Parent Lucie , Sauvé Rémy
Published: March 2007

In this work we address the question of the KCa3.1 channel pore structure in the closed configuration in relation to the contribution of the C-terminal end of the S6 segments to the Ca2+-dependent gating process. Our results based on SCAM (substituted cysteine accessibility method) experiments first demonstrate that the S6 transmembrane segment of the open KCa3.1 channel contains two distinct functional domains delimited by V282 with MTSEA and MTSET binding leading to a total channel inhibition at positions V275, T278, and V282 and to a steep channel activation at positions A283 and A286. The rates of modification by MTSEA (diameter 4.6 Å) of the 275C (central cavity) and 286C residues (S6 C-terminal end) for the closed channel configuration were found to differ by less than sevenfold, whereas experiments performed with the larger MTSET reagent (diameter 5.8 Å) resulted in modification rates 103–104 faster for cysteines at 286 compared with 275. Consistent with these results, the modification rates of the cavity lining 275C residue by MTSEA, Et-Hg+, and Ag+ appeared poorly state dependent, whereas modification rates by MTSET were 103 faster for the open than the closed configuration. A SCAM analysis of the channel inner vestibule in the closed state revealed in addition that cysteine residues at 286 were accessible to MTS reagents as large as MTS-PtrEA, a result supported by the observation that binding of MTSET to cysteines at positions 283 or 286 could neither sterically nor electrostatically block the access of MTSEA to the closed channel cavity (275C). It follows that the closed KCa3.1 structure can hardly be accountable by an inverted teepee-like structure as described for KcsA, but is better represented by a narrow passage centered at V282 (equivalent to V474 in Shaker) connecting the channel central cavity to the cytosolic medium. This passage would not be however restrictive to the diffusion of small reagents such as MTSEA, Et-Hg+, and Ag+, arguing against the C-terminal end of S6 forming an obstructive barrier to the diffusion of K+ ions for the closed channel configuration.
Author's version vs. publisher's version: an analysis of the copy‐editing function
Authors: WATES Edward , CAMPBELL Robert
Published: March 2007

This report describes an informal study carried out by Blackwell Publishing to assess whether the copy‐editing and proof‐correction process alone results in a significant difference between the author's version and the publisher's version of an article accepted for publication. One hundred and eighty‐nine articles were reviewed from 23 journals. The results indicate that a substantial number of changes are made. It is suggested that copy‐editing has an equal role to play in both the printed and online environments, and that in the latter it contributes substantially to the accuracy of the electronic version. Copy‐editing is therefore an important function within the publisher's overall responsibility towards the integrity of the article of record.
Researchers' use and perceptions of discovery services
Authors: JUBB Michael , LOOK Hugh , SPARKS Sue
Published: March 2007

This article describes a study investigating how academic researchers in the UK use discovery services to find different kinds of information resources relevant to their research. The study shows that they use a very wide range of services, from Google to highly specialized databases, to find information relevant to different stages in their research. Researchers treat searching an integral part of the research process; their central concern is that they might miss something, and they tend to refine down from a large set of search results. Most are confident in their skills, though librarians see them as conservative in the tools they use and unsophisticated in their methods. Finally, we point to some gaps in provision as reported by researchers.
Sopungyangjae‐Tang Inhibits Development of Dermatitis in Nc/Nga Mice
Authors: Pokharel Yuba Raj , Lim Sung Chul , Kim Sang Chan , Heo Tae-Hwe , Choi Hoo Kyun , Kang Keon Wook
Published: March 2007

Sopungyangjae‐Tang (SYT) is a traditional Korean decoction used for the treatment of dermatitis. The aim of this study was to confirm whether or not SYT has a preventive effect on the development of atopic dermatitis in dinitrochlorobenzene‐applied Nc/Nga mice. SYT was administered orally to Nc/Nga mice, which led to the remarkable suppression of the development of dermatitis, as determined by a histological examination and the serum IgE levels. Moreover, SYT inhibited the production of thymus‐ and activation‐regulated chemokine (TARC) and its mRNA expression in a keratinocyte cell line, HaCaT, which had been stimulated with tumor necrosis factor‐α (TNF‐α) and interferon‐γ (IFN‐γ). Activation of the nuclear factor‐κB (NF‐κB) or activator protein‐1 (AP‐1) is one of the key steps in the signaling pathways mediating induction of TARC. In this study, SYT selectively suppressed NF‐κB activation, which may be essential for TARC expression in TNF‐α/IFN‐γ treated keratinocytes. The inhibitory effect of SYT on NF‐κB activation and TARC production might be associated with the anti‐dermatitic effects of SYT.
Intramuscular Neurilemoma of the Lower Limb
Authors: Bombaci Hasan , Kilicoglu Gamze , Gorgec Mucahit
Published: March 2007

Objectives:

Neurilemoma (schwannoma) is a benign tumor of peripheral nerves, usually arising from spinal nerve roots or larger peripheral nerves. We report a case of intramuscular neurilemoma in the quadriceps femoris muscle, which is a rare site for this tumor. Diagnostic appearance and differential diagnosis are discussed.
An Older Female With Chronic Fluctuating Weakness
Authors: Holt Anthony E , Mitchell Christopher W , Maccarino Sue , Bertorini Tulio E
Published: March 2007

Educational Objectives:

To discuss a case of fluctuating and slowly progressive weakness in an older female.

Key Questions:

1) What is the differential diagnosis of longstanding fluctuating weakness? 2) How would one approach diagnostic testing for such a patient? 3) What is the treatment for this patient?
A Randomized, Placebo-Controlled Trial of Creatine in Children With Spinal Muscular Atrophy
Authors: Wong Brenda L , Hynan Linda S , Iannaccone Susan T
Published: March 2007

Objective:

To determine whether oral creatine produces positive changes in any of 4 outcomes in children with spinal muscular atrophy (SMA).

Methods:

The authors conducted a randomized, double-blind, placebo-controlled trial on 55 patients aged 2-18 years with SMA. Patients aged younger than 5 years received 2 g/day of creatine/placebo for 6 months. Patients aged 5 years and older received 5 g/day. The primary outcome measure was the Gross Motor Function Measure (GMFM). Secondary outcome measures were Quantitative Muscle Testing (QMT), Parent Questionnaire for the PedsQL™ Neuromuscular Module (QOL), and Pulmonary Function Tests (PFT).

Results:

Forty of the 55 patients completed the protocol. There was no significant difference in the 4 outcome measures between creatine and placebo groups.

Conclusions:

Under the experimental conditions of our study, creatine supplementation for 6 months did not improve motor function, muscle strength, pulmonary function, or quality of life in children with SMA,
Opposing effects on muscarinic acetylcholine receptors in the piriform cortex of odor-trained rats
Authors: Saar Drorit , Dadon Moran , Leibovich Marcela , Sharabani Hagar , Grossman Yoram , Heldman Eliahu
Published: March 2007

We combined pharmacological studies and electrophysiological recordings to investigate modifications in muscarinic acetylcholine (ACh) receptors (mAChR) in the rat olfactory (piriform) cortex, following odor-discrimination rule learning. Rats were trained to discriminate between positive and negative cues in pairs of odors, until they reached a phase of high capability to learn unfamiliar odors, using the same paradigm (“rule learning”). It has been reported that at 1–3 d after the acquisition of odor-discrimination rule learning, pyramidal neurons in the rat piriform cortex show enhanced excitability, due to a reduction in the spike-activated potassium current IAHP, which is modulated by ACh. Further, ACh and its analog, carbachol (CCh), lost the ability to reduce the IAHPin neurons from trained rats. Here we show that the reduced sensitivity to CCh in the piriform cortex results from a decrease in the number of mAChRs, as well as a reduction in the affinity of the receptors to CCh. Also, it has been reported that 3–8 d after the acquisition of odor-discrimination rule learning, synaptic transmission in the piriform cortex is enhanced, and paired-pulse facilitation (PPF) in response to twin stimulations is reduced. Here, intracellular recordings from pyramidal neurons show that CCh increases PPF in the piriform cortex from odor-trained rats more than in control rats, suggesting enhanced effect of ACh in inhibiting presynaptic glutamate release after odor training.
Role of matrix metalloproteinases in the acquisition and reconsolidation of cocaine-induced conditioned place preference
Authors: Brown Travis E. , Forquer Melissa R. , Cocking Davelle L. , Jansen Heiko T. , Harding Joseph W. , Sorg Barbara A.
Published: March 2007

Persistent drug seeking/taking behavior involves the consolidation of memory. With each drug use, the memory may be reactivated and reconsolidated to maintain the original memory. During reactivation, the memory may become labile and susceptible to disruption; thus, molecules involved in plasticity should influence acquisition and/or reconsolidation. Recently, matrix metalloproteinases (MMPs) have been shown to influence neuronal plasticity, presumably by their regulation of extracellular matrix (ECM) molecules involved in synaptic reorganization during learning. We hypothesized that inhibition of MMP activity would impair the acquisition and/or reconsolidation of cocaine-conditioned place preference (CPP) in rats. Intracerebral ventricular (i.c.v.) microinjection of a broad spectrum MMP inhibitor, FN-439, prior to cocaine training suppressed acquisition of CPP and attenuated cocaine-primed reinstatement in extinguished animals. In a separate experiment, the cocaine memory was reactivated on two consecutive days with a cocaine priming injection. On these two days, artificial cerebral spinal fluid (aCSF) or FN-439 was administered either 30 min prior to or 1 min after cocaine-primed reinstatement sessions. Infusion of FN-439 partially impaired retrieval of the cocaine-associated context when given 30 min prior to cocaine. In both groups, however, FN-439 suppressed reinstatement compared with controls on the third consecutive test for cocaine-primed reinstatement, when no FN-439 was given. Control experiments demonstrated that two injections of FN-439 + cocaine given in the home cage, or of FN-439 + saline priming injections in the CPP chambers did not disrupt subsequent cocaine-primed reinstatement. These results show for the first time that (1) MMPs play a critical role in acquisition and reconsolidation of cocaine-induced CPP, and (2) rats demonstrate apparent disruption of reconsolidation by an MMP inhibitor after extinction and while they are under the influence of cocaine during reinstatement.
Reduced protein expression of metastasis‐related genes (nm23, KISS1, KAI1 and p53) in lymph node and liver metastases of gastric cancer
Authors: Guan‐zhen Yu , Ying Chen , Can‐rong Ni , Guo‐dong Wang , Jian‐xin Qian , Jie‐jun Wang
Published: March 2007

Purpose:  Metastasis remains an incurable common complication in patients with gastric cancer. A variety of theories have been proposed to explain the inefficiency of the metastatic process. To compare protein expression of metastasis‐related genes (nm23, KISS1, KAI1 and p53) between primary tumours and metastatic tumours may be useful in illustrating these theories.

Methods:  Metastasis‐related tissue microarrays (including normal tissues, primary tumours, nodal metastases and liver metastases) were constructed. The protein expression of nm23, KISS1, KAI1 and p53 in lymph node and liver metastases from advanced gastric cancer specimens was mainly examined by immunohistochemical staining in relation to primary tumours.

Results:  Immunohistochemical staining showed reduced protein expression of nm23, KISS1 and KAI1 in lymph node and liver metastases compared with primary tumours. Results for p53 were to the contrary.

Conclusions:  Our investigations revealed a tendency of reduced protein expression of metastasis suppressor genes nm23, KISS1 and KAI1 in gastric cancer with the progress of metastasis. This means that the progression theory is an important determinant of metastatic efficiency.
Neuromyelitis optica following CMV primo‐infection
Authors: Tran C. , Du Pasquier R. A. , Cavassini M. , Guex‐Crosier Y. , Meuli R. , Ciuffreda D. , Waeber G.
Published: March 2007

We report the case of an acute optic neuromyelitis with rhabdomyolysis in a 34‐year‐old immunocompetent transsexual patient following a recent cytomegalovirus (CMV) infection. The combination of optic neuropathy and myelopathy is recognized as Devic's syndrome. Clinical presentation was unusual as the recent CMV infection induced rhabdomyolysis and was the suspected trigger of neuromyelitis.
A genetic association study of 5‐HTT LPR and GNβ3 C825T polymorphisms with irritable bowel syndrome
Authors: Saito Y. A. , Locke G. R. , Zimmerman J. M. , Holtmann G. , Slusser J. P. , De Andrade M. , Petersen G. M. , Talley N. J.
Published: March 2007

Abstract  A pharmacogenetic study suggests the 5‐HTT LPR polymorphism predicts response to alosetron, and another study describes a possible association of the GNβ3 C825T polymorphism with IBS in patients with dyspepsia. We performed a case–control association study to determine whether these polymorphisms are associated with irritable bowel syndrome (IBS). The study aim was to compare allele and genotype frequencies between cases and controls for the 5‐HTT LPR and the GNβ3 C825T polymorphism. Cases were 50 GI outpatients; controls were 53 General Medicine outpatients matched to cases for age, gender and race at a major medical centre. Participants completed a questionnaire and donated blood. DNA was genotyped using polymerase chain reaction based assays. Eighty‐two per cent of cases met Rome II criteria for IBS: 12% constipation‐, 46% diarrhoea‐, and 42% mixed‐IBS. Genotype and allele frequencies for both polymorphisms did not differ between cases and controls. However, the allele frequency of the short (S) allele of the 5‐HTT LPR polymorphism was greater in those with mixed‐IBS compared with controls (68%vs 45%, P < 0.05). This study suggests that the 5‐HTT LPR polymorphism may be associated with mixed‐IBS, but not IBS overall. No association was observed for the GNβ3 C825T polymorphism with IBS overall or subtypes.
Autonomic nervous system response to a solid meal and water loading in healthy children: its relation to gastric myoelectrical activity
Authors: Friesen C. A. , Lin Z. , Schurman J. V. , Andre L. , Mc Callum R. W.
Published: March 2007

Abstract  The aim of this study was to investigate the correlation of gastric myoelectrical and autonomic activities in healthy children. Simultaneous recordings of electrogastrography (EGG) and electrocardiogram (ECG) were performed in healthy children before and after a solid meal and water loading respectively. The autonomic activity was assessed by spectral analysis of the heart rate variability (HRV). The solid meal resulted in an increase in EGG‐dominant frequency (2.92 cpm vs 3.16 cpm, P < 0.05), dominant power (46.9 dB vs 53.7 dB, P < 0.05) and percentage normal slow waves (81.9%vs 89.0%, P < 0.05), while only dominant power increased following water loading. Power in the low‐frequency band of HRV (LF) was significantly increased and power in the high‐frequency band of HRV (HF) significantly decreased following the solid meal. Postprandial LF was positively and HF negatively correlated with the postprandial increase in EGG‐dominant power. Water loading was not associated with any significant changes in HRV parameters. These results suggest that both vagal and sympathetic pathways are involved in modulation of gastric myoelectrical activity.
Sphincter of Oddi function in the Australian brush‐tailed possum is inhibited by intragastric ethanol
Authors: Sonoda Y. , Kawamoto M. , Woods C. N. , Schloithe A. C. , Carati C. J. , Toouli J. , Saccone G. T. P.
Published: March 2007

Abstract The role of sphincter of Oddi (SO) function in alcoholic acute pancreatitis (AP) is unclear. We aimed to compare the effect of i.v. and intragastric (IG) ethanol on SO function (i.e.trans‐sphincteric flow; TSF) and investigate possible neural mechanisms. The involvement of gastric mucosal damage was also investigated by pretreatment with pantoprazole. In anaesthetized Australian possums, blood pressure (BP), TSF and blood ethanol concentrations were measured after i.v. or IG ethanol. Possums were subjected to acute vagotomy, atropine,l‐nitro arginine methyl ester(l‐NAME) or pantoprazole pretreatment prior to IG ethanol. BP was not significantly altered by ethanol. Ethanol decreased TSF in a dose and route‐dependent manner. The lowest dose of IG ethanol reduced TSF but this response was not duplicated by i.v. ethanol producing the same blood ethanol concentrations. Acute vagotomy, atropine orl‐NAME pretreatment blocked the ethanol‐induced decrease in TSF and simultaneously suppressed the blood ethanol concentration. Pantoprazole pretreatment reduced the TSF response and blood ethanol concentrations implicating mechanisms induced by gastric mucosal damage. We conclude that ethanol (and/or its metabolites) reduces TSF via humoral and neural mechanisms involving vagal pathways, muscarinic receptors and nitric oxide. Reduced TSF could contribute to the onset of AP.
The cell‐cycle promoter cdc2aAt from Arabidopsis thaliana is induced in the lateral roots of the actinorhizal tree Allocasuarina verticillata during the early stages of the symbiotic interaction with Frankia
Authors: Ourèye Sy Mame , Hocher Valérie , Gherbi Hassen , Laplaze Laurent , Auguy Florence , Bogusz Didier , Franche Claudine
Published: March 2007

The symbiosis between the actinorhizal tree Allocasuarina verticillata and the actinomycete Frankia leads to the formation of root nodules inside which bacteria fix atmospheric nitrogen. Actinorhizal nodule organogenesis starts with the induction of cell divisions in the root cortex and in the pericycle cells opposite protoxylem poles near Frankia‐infected root hairs. To study the ability of Frankia to induce progression through the cell cycle, we monitored the expression of the β‐glucuronidase (gus) gene driven by the promoter from cdc2aAt, an Arabidopsis cyclin‐dependent kinase gene that displays competence for cell division, during plant growth and nodule ontogenesis. In non‐symbiotic tissues, the gus gene was mainly expressed in primary and secondary meristems of roots and shoots. Auxins and cytokinins were found to induce reporter gene activity in the root system of whole plants, showing that the promoter cdc2aAt displayed the same regulation by hormones in Allocasuarina as that reported in Arabidopsis. In transgenic nodules, gus expression was found to be restricted to the phellogen. During the early stages of the interaction between Frankia and the plant root system, cdc2aAt was strongly induced in the lateral roots surrounded by hyphae of the actinomycete. Histochemical analysis of β‐glucuronidase activity revealed that cells from the pericycle opposite protoxylem poles were very deeply stained. These data indicate that upon Frankia infection, cells from the lateral roots, and notably pericycle cells that can give rise to a nodule or a root primordium, prepare to re‐enter the cell cycle.
Transfusion of red blood cells: no impact on length of hospital stay in moderately anaemic parturients
Authors: Palo R. , Ahonen J. , Salo H. , Salmenperä M. , Krusius T. , Mäki T.
Published: March 2007

Background:  In a search for information to improve decision making on red blood cell (RBC) transfusion, we examined the impact of RBC transfusion on the length of hospital stay for delivery in moderately anaemic women (haemoglobin, 7–10 g/dl).

Methods:  This was a retrospective, observational study covering 2 years (2002 and 2003), and included major blood‐transfusing hospitals from four university and five central hospital districts managing 67.5% of Finnish in‐hospital deliveries. The impact of the transfusion of 1–2 RBC units vs. no transfusion on the length of hospital stay was evaluated for three different haemoglobin levels: 7–7.9, 8–8.9 and 9–10 g/dl.

Results:  Of the 1954 moderately anaemic mothers in hospital for delivery, 13.3% were transfused with RBC. The mean length of hospital stay was 5.2 days vs. the average Finnish hospital delivery stay of 3.5 days. No differences in stay were found between patients with comparable anaemia transfused with 1–2 RBC units or none (at the three haemoglobin levels: P= 0.50, P= 0.07 and P= 0.54, respectively). The final haemoglobin value was higher (P < 0.001) in transfused patients.

Conclusion:  The duration of admission for delivery in moderately anaemic parturients was longer than the average length of hospital stay in Finnish parturients. However, 1–2 RBC units had no impact on the length of stay, suggesting that unnecessary RBCs are transfused after delivery. Thus, transfusion practices in obstetrics are not always optimal.
Long‐term outcome of elderly patients requiring intensive care admission for abdominal pathologies: survival and quality of life*
Authors: Merlani P. , Chenaud C. , Mariotti N. , Ricou B.
Published: March 2007

Background:  Medical developments have allowed the management of patients aged over 70 years with severe abdominal pathologies requiring intensive care unit (ICU) admission. These patients require enhanced life support and present a high ICU mortality. We investigated the outcome and quality of life (QOL) of elderly patients 2 years after their ICU stay for abdominal pathologies.

Methods:  Patients aged 70 years or over with abdominal pathologies, admitted to our ICU over a period of 2 years, were included. Two years following their ICU stay, a letter informed the patients about the present study. Consent to participate was obtained by telephone. QOL was assessed by the Euro‐QOL and Short Form‐36 questionnaires. Other patient‐centered outcomes were evaluated.

Results:  Overall, 2780 patients were admitted to the ICU during the study period; 141 (5%) patients were eligible; 112 of the 141 (79%) survived their ICU stay, 95 (67%) survived their hospital stay and 52 (37%) were alive 2 years after their ICU stay; 36 of the 52 survivors (69%) answered the questionnaire. Their QOL 2 years after their ICU stay was decreased in comparison with an age‐matched population. Eighty‐one per cent of patients lived at home and 57% were totally independent. They perceived their ICU stay as positive and 75% stated that they would agree to go through intensive care again. Factors associated with 2‐year survival were the absence of co‐morbidity, absence of malignancy and a lower Simplified Acute Physiology II score on ICU admission.

Conclusions:  A high mortality rate and a decrease in QOL were observed in elderly patients with severe abdominal pathologies. Nonetheless, these patients were able to adapt well to their physical disabilities.
Low concentrations of inhaled nitric oxide do not improve oxygenation in patients with very severe chronic obstructive pulmonary disease
Authors: Melsom M. N. , Flatebø T. , Nicolaysen G.
Published: March 2007

Background:  Chronic obstructive pulmonary disease (COPD) is characterized by airway narrowing that is most frequently inhomogeneously distributed. Ventilation/perfusion (V̇/Q̇) mismatch may explain much of the hypoxemia in patients with advanced disease. A potential treatment strategy would be to redistribute blood flow to well‐ventilated lung regions in order to decrease V̇/Q̇ mismatch. It has been suggested that inhaled nitric oxide (iNO) in physiologic concentrations (∼ 100 p.p.b.) could act as a local vasodilating agent in well‐ventilated lung regions. To test this, we included 10 volunteer patients with very severe COPD in this study.

Methods:  NO was mixed with O2 and N2 and administered through a face mask. The partial pressure of inspired oxygen (Pio2) did not change by more than ± 0.5 kPa from the room air value. NO was given in 15‐min periods at concentrations of ∼ 0, ∼ 40, ∼ 400, ∼ 4000 and ∼ 40,000 p.p.b. (random order). During each NO exposure, arterial blood gases, methemoglobin and systemic blood pressure were measured every fifth minute.

Results:  None of the patients reported subjective effects of the different gas mixtures. The partial pressure of oxygen in arterial blood (Pao2) did not change by more than ± 1.2 kPa from the baseline value, and there was no correlation between the change in Pao2 and iNO concentration. No significant changes were found in blood pressure or methemoglobin during iNO.

Conclusion:  No significant effect of iNO at concentrations up to 40,000 p.p.b. in inspired gas was found on arterial blood gases. This indicates that neither low nor high concentrations of iNO improve oxygenation in patients with very severe COPD.
Mycological evaluation of bronchoalveolar lavage in cats with respiratory signs from Rio de Janeiro, Brazil
Authors: Leme L. R. P. , Schubach T. M. P. , Santos I. B. , Figueiredo F. B. , Pereira S. A. , Reis R. S. , Mello M. F. V. , Ferreira A. M. R. , Quintella L. P. , Schubach A. O.
Published: March 2007

Twenty‐three cats with respiratory signs who had domiciliary contact with cats with sporotrichosis were studied. Sneezing was the predominant extracutaneous sign. Twelve cats had no skin lesions and 11 had ulcerated skin lesions. Mycological culture of material obtained from the nasal cavity, oral cavity, bronchoalveolar lavage (BAL) and skin lesions, when present, was performed for all cats. In the case of autopsy, lung fragments were cultured.Sporothrix schenckiiwas isolated from four of the 12 cats without skin lesions: BAL (one cat) and oral and/or nasal cavity (three cats). The latter three animals developed nasal and distant skin lesions within the following 2–4 weeks. The cat withS. schenckiiisolated from BAL did not develop skin lesions or lower respiratory tract symptoms during the 6 months of follow‐up.S. schenckiiwas isolated from one or more biological samples of all 11 cats with skin lesions: oral cavity (five), nasal cavity (eight), BAL fluid (four), skin lesions (eight), and blood culture (one). No yeast‐like structures were observed upon BAL cytology in any of the 23 cats. The results suggest thatS. schenckiican cause infection of skin contiguous to the natural facial orifices through colonisation of the mucosal surfaces of the upper airways.
Rhinocerebral mucormycosis: the disease spectrum in 27 patients
Authors: Mohindra Sandeep , Mohindra Satyawati , Gupta Rahul , Bakshi Jaimanti , Gupta Sunil Kumar
Published: March 2007

The variable forms of clinical complaints, findings and time interval of presentation in 27 cases of mucormycosis have been described, which were encountered over a span of 8 years. The previous concept about this fungal infection attacking chronic, debilitated, immunocompromised patients does not appear to hold true. Seven of the 27 patients (22.2%) did not reveal any predisposing factors and their outcome of 42.9% survival seems to be poorer than the total outcome (66.7%). ‘Chronic form’ of disease presentation, the definition of which is still not delineated, was encountered in four patients (14.8%). Again, the outcome was not significantly different from the total survival. Burr‐hole tap of an intracranial abscess revealing mucor in a 2‐month‐old infant has been described. Even in the present era, extranasal exenteration of sinuses along with disfiguring orbital exenteration is required to ensure satisfactory surgical debridement. Control of the underlying predisposing illness, along with the aggressive surgical debridement and the parenteral administration of amphotericin B, remains the treatment essentials even today.