bluuebunny/crossref_metadata_2025 huggingface dataset:
Perceptual Completion of a Sound with a Short Silent Gap
Authors: Remijn Gerard B , Nakajima Yoshitaka , Tanaka Shunsuke
Published: May 2007

Listeners reported the perceptual completion of a sound in stimuli consisting of two crossing frequency glides of unequal duration that shared a short silent gap (40 ms or less) at their crossing point. Even though both glides shared the gap, it was consistently perceived only in the shorter glide, whereas the longer glide could be perceptually completed. Studies on perceptual completion in the auditory domain reported so far have shown that completion of a sound with a gap occurs only if the gap is filled with energy from another sound. In the stimuli used here, however, no such substitute energy was present in the gap, showing evidence for perceptual completion of a sound without local stimulation (‘modal’ completion). Perceptual completion of the long glide occurred under both monaural and dichotic presentation of the gap-sharing glides; it therefore involves central stages of auditory processing. The inclusion of the gap in the short glide, rather than in both the long and the short glide, is explained in terms of auditory event and stream formation.
Alarin is a vasoactive peptide
Authors: Santic Radmila , Schmidhuber Sabine M. , Lang Roland , Rauch Isabella , Voglas Elena , Eberhard Nicole , Bauer Johann W. , Brain Susan D. , Kofler Barbara
Published: May 2007

Galanin-like peptide (GALP) is a hypothalamic neuropeptide belonging to the galanin family of peptides. The GALP gene is characterized by extensive differential splicing in a variety of murine tissues. One splice variant excludes exon 3 and results in a frame shift leading to a novel peptide sequence and a stop codon after 49 aa. In this peptide, which we termed alarin, the signal sequence of the GALP precursor peptide and the first 5 aa of the mature GALP are followed by 20 aa without homology to any other murine protein. Alarin mRNA was detected in murine brain, thymus, and skin. In accordance with its vascular localization, the peptide exhibited potent and dose-dependent vasoconstrictor and anti-edema activity in the cutaneous microvasculature, as was also observed with other members of the galanin peptide family. However, in contrast to galanin peptides in general, the physiological effects of alarin do not appear to be mediated via the known galanin receptors. Alarin adds another facet to the surprisingly high-functional redundancy of the galanin family of peptides.
A unique T cell receptor discovered in marsupials
Authors: Parra Zuly E. , Baker Michelle L. , Schwarz Ryan S. , Deakin Janine E. , Lindblad-Toh Kerstin , Miller Robert D.
Published: May 2007

T cells recognize antigens by using T cell receptors (TCRs) encoded by gene segments, called variable (V), diversity (D), and joining (J), that undergo somatic recombination to create diverse binding specificities. Four TCR chains (α, β, γ, and δ) have been identified to date, and, as T cells develop in the thymus, they express exclusively either an αβTCR or a γδTCR heterodimer. Here, we show that marsupials have an additional TCR (TCRμ) that has V, D, and J that are either somatically recombined, as in conventional TCRs, or are already prejoined in the germ-line DNA in a manner consistent with their creation by retrotransposition. TCRμ does not have a known homolog in eutherian mammals but has features analogous to a recently described TCRδ isoform in sharks. TCRμ is expressed in at least two mRNA isoforms that appear capable of encoding a full-length protein, both of which are transcribed in the thymus and spleen. One contains two variable domains: a somatically recombined V and a prejoined V. This appears to be the dominant isoform in peripheral lymphoid tissue. The other isoform contains only the prejoined V and is structurally more similar to conventional TCR chains, however invariant. Unlike other TCRs, TCRμ uses prejoined gene segments and is likely present in all marsupials. Its similarity to a TCR isoform in sharks suggests that it, or something similar, may be present in other vertebrate lineages and, therefore, may represent an ancient receptor system.
Thehoteimutation of medaka in the anti-Müllerian hormone receptor causes the dysregulation of germ cell and sexual development
Authors: Morinaga Chikako , Saito Daisuke , Nakamura Shuhei , Sasaki Takashi , Asakawa Shuichi , Shimizu Nobuyoshi , Mitani Hiroshi , Furutani-Seiki Makoto , Tanaka Minoru , Kondoh Hisato
Published: May 2007

We previously performed mutant screens in the medaka for defects in gonadal development and identified a mutant of interest in this regard, which was designated ashotei(hot). This mutant manifests a number of remarkable phenotypic abnormalities including: (i) excessive proliferation of germ cells that initiates at around the hatching stage regardless of the genetic sex of the fish; (ii) initiation of premature meiosis in phenotypically malehothomozygotes; (iii) one-half of thehot-homozygous XY fish undergo sex reversal, which accompanies the expression of the female-characteristicaromatasegene in the somatic cells of the gonad; and (iv) in phenotypically female homozygotes, follicular development is arrested at an early stage. We have also performed genetic mapping, chromosome walking, and candidate gene sequencing analysis ofhotand demonstrate that the underlying mutation occurs in the recently identified medaka anti-Müllerian hormone (Amh) receptor type II (amhrII) gene. Moreover, this gene was found to be responsible for each of thehotphenotypes, as anamhrIItransgene rescues these abnormalities. In addition, theamhrIIgene is expressed in the somatic cells of the gonads of both sexes. The phenotypes of thehothomozygotes indicate that there are multiple regulatory functions of the AMH/AMHRII signaling system in the development of the gonad, including the sex-dependent regulation of germ cell proliferation and follicular development. These presumably represent the basic roles of Amh, which precede Müllerian duct evolution during phylogeny.
Inhibition of ubiquitin-mediated degradation of MOAP-1 by apoptotic stimuli promotes Bax function in mitochondria
Authors: Fu Nai Yang , Sukumaran Sunil K. , Yu Victor C.
Published: May 2007

The multidomain proapoptotic protein Bax of the Bcl-2 family is a central regulator for controlling the release of apoptogenic factors from mitochondria. Recent evidence suggests that the Bax-associating protein MOAP-1 may act as an effector for promoting Bax function in mitochondria. Here, we report that MOAP-1 protein is rapidly up-regulated by multiple apoptotic stimuli in mammalian cells. MOAP-1 is a short-lived protein (
t
1/2
≈ 25 min) that is constitutively degraded by the ubiquitin-proteasome system. Induction of MOAP-1 by apoptotic stimuli ensues through inhibition of its polyubiquitination process. Elevation of MOAP-1 levels sensitizes cells to apoptotic stimuli and promotes recombinant Bax-mediated cytochrome
c
release from isolated mitochondria. Mitochondria depleted of short-lived proteins by cycloheximide (CHX) become resistant to Bax-mediated cytochrome
c
release. Remarkably, incubation of these mitochondria with
in vitro
-translated MOAP-1 effectively restores the cytochrome
c
releasing effect of recombinant Bax. We propose that apoptotic stimuli can facilitate the proapoptotic function of Bax in mitochondria through stabilization of MOAP-1.
Small-molecule activators of RNase L with broad-spectrum antiviral activity
Authors: Thakur Chandar S. , Jha Babal Kant , Dong Beihua , Das Gupta Jaydip , Silverman Kenneth M. , Mao Hongxia , Sawai Hiro , Nakamura Akiko O. , Banerjee Amiya K. , Gudkov Andrei , Silverman Robert H.
Published: May 2007

RNase L, a principal mediator of innate immunity to viral infections in higher
vertebrates, is required for a complete IFN antiviral response against certain
RNA stranded viruses. dsRNA produced during viral infections activates
IFN-inducible synthetases that produce 5′-phosphorylated, 2′,5′-oligoadenylates
(2-5A) from ATP. 2-5A activates RNase L in a wide range of different mammalian
cell types, thus blocking viral replication. However, 2-5A has unfavorable
pharmacologic properties; it is rapidly degraded, does not transit cell
membranes, and leads to apoptosis. To obtain activators of RNase L with improved
drug-like properties, high-throughput screening was performed on chemical
libraries by using fluorescence resonance energy transfer. Seven compounds were
obtained that activated RNase L at micromolar concentrations, and
structure–activity relationship studies resulted in identification of an
additional four active compounds. Two lead compounds were shown to have a
similar mechanistic path toward RNase L activation as the natural activator
2-5A. The compounds bound to the 2-5A-binding domain of RNase L (as determined
by surface plasmon resonance and confirmed by computational docking), and the
compounds induced RNase L dimerization and activation. Interestingly, the
low-molecular-weight activators of RNase L had broad-spectrum antiviral activity
against diverse types of RNA viruses, including the human pathogen human
parainfluenza virus type 3, yet these compounds by themselves were not cytotoxic
at the effective concentrations. Therefore, these RNase L activators are
prototypes for a previously uncharacterized class of broad-spectrum antiviral
agents.
Sumoylation of nucleophosmin/B23 regulates its subcellular localization, mediating cell proliferation and survival
Authors: Liu Xia , Liu Zhixue , Jang Sung-Wuk , Ma Zhiyong , Shinmura Kazuya , Kang Sumin , Dong Shaozhong , Chen Jing , Fukasawa Kenji , Ye Keqiang
Published: May 2007

Nucleophosmin/B23 is a major multifunctional nucleolar phosphoprotein that plays a critical role in ribosome biogenesis and cell proliferation. Arf tumor suppressor binds B23 and enhances its sumoylation. However, the biological effects of this event remain unknown. Here we show that B23 is sumoylated on both Lysine 230 and 263 residues, but the latter is the major one. Mutation of K263, but not K230, into R abolishes its centrosomal and nucleolar residency. Moreover, Rb binds to wild-type B23, but fails to interact with K263R. Sumoylation enhances B23 binding to Rb. Consequently, B23 potently stimulates E2F1-mediated transcriptional activity, which is abolished in B23 K263R. Further, K263R mutation makes B23 vulnerable to caspase-3 cleavage and sensitizes cells to apoptosis. Surprisingly, K230R mutant strongly binds to phosphatidylinositol-3,4,5-trisphosphate and suppresses DNA fragmentation. Thus, B23 sumoylation regulates its subcellular localization, cell proliferation, and survival activities.
A high-throughput siRNA library screen identifies osteogenic suppressors in human mesenchymal stem cells
Authors: Zhao Yuanxiang , Ding Sheng
Published: May 2007

Tissue-specific (or adult) stem/progenitor cells are regarded as the source for normal tissue homeostasis and tissue repair. They also provide tremendous promise for regenerative medicine because of their capacity to proliferate and differentiate into a variety of mature cell types. Human mesenchymal stem cells (hMSCs) can differentiate into osteocytes, adipocytes, chondrocytes, muscle cells, and neurons. However, the molecular mechanisms underlying these differentiation processes are poorly understood. We screened a synthetic siRNA library targeting 5,000 human genes to identify the endogenous repressors of osteogenic specification, which when silenced could initiate differentiation of hMSCs into osteoblasts. This screen yielded 53 candidate suppressors, and 12 of those were further confirmed for their dynamic roles in suppressing osteogenic specification in hMSCs. Furthermore, cAMP was identified to play opposing roles in osteogenesis vs. adipogenesis. This study provides a basis for further elucidation of the genetic network controlling osteogenesis and, potentially, the molecular rationale for treating bone diseases.
Stepwise proteolysis liberates tau fragments that nucleate the Alzheimer-like aggregation of full-length tau in a neuronal cell model
Authors: Wang Y. P. , Biernat J. , Pickhardt M. , Mandelkow E. , Mandelkow E.-M.
Published: May 2007

Tau is a highly soluble protein, yet it aggregates abnormally in Alzheimer's disease. Here, we address the question of proteolytic processing of tau and the nucleation of aggregates by tau fragments. We show in neuronal cell models that fragments of the repeat domain of tau containing mutations of FTDP17 (frontotemporal dementia with parkinsonism linked to chromosome 17), produced by endogenous proteases, can induce the aggregation of full-length tau. Fragments are generated by successive cleavages, first N-terminally between K257 and S258, then C-terminally around residues 353–364; conversely, when the N-terminal cleavage is inhibited, no fragmentation and aggregation takes place. The C-terminal truncation and the coaggregation of fragments with full-length tau depends on the propensity for β-structure. The aggregation is modulated by phosphorylation but does not depend on it. Aggregation but not fragmentation as such is toxic to cells; conversely, toxicity can be prevented by inhibiting either aggregation or proteolysis. The results reveal a novel pathway of abnormal tau aggregation in neuronal cells.
Bacteriorhodopsin photocycle at cryogenic temperatures reveals distributed barriers of conformational substates
Authors: Dioumaev Andrei K. , Lanyi Janos K.
Published: May 2007

The time course of thermal reactions after illumination of 100% humidified bacteriorhodopsin films was followed with FTIR spectroscopy between 125 and 195 K. We monitored the conversion of the initial photoproduct, K, to the next, L intermediate, and a shunt reaction of the L state directly back to the initial BR state. Both reactions can be described by either multiexponential kinetics, which would lead to apparent end-state mixtures that contain increasing amounts of the product, i.e., L or BR, with increasing temperature, or distributed kinetics. Conventional kinetic schemes that could account for the partial conversion require reversible reactions, branching, or parallel cycles. These possibilities were tested by producing K or L and monitoring their interconversion at a single temperature and by shifting the temperature upward or downward after an initial incubation and after their redistribution. The results are inconsistent with any conventional scheme. Instead, we attribute the partial conversions to the other alternative, distributed kinetics, observed previously in myoglobin, which arise from an ensemble of frozen conformational substates at the cryogenic temperatures. In this case, the time course of the reactions reflects the progressive depletion of distinct microscopic substates in the order of their increasing activation barriers, with a distribution width for K to L reaction of ≈7 kJ/mol.
An essential role for the SHIP2-dependent negative feedback loop in neuritogenesis of nerve growth factor–stimulated PC12 cells
Authors: Aoki Kazuhiro , Nakamura Takeshi , Inoue Takanari , Meyer Tobias , Matsuda Michiyuki
Published: May 2007

The local accumulation of phosphatidylinositol (3,4,5) trisphosphate (PIP3) and resulting activation of Rac1/Cdc42 play a critical role in nerve growth factor (NGF)–induced neurite outgrowth. To further explore the mechanism, we visualized PIP3, phosphatidylinositol (3,4) bisphosphate, and Rac1/Cdc42 activities by fluorescence resonance energy transfer (FRET) imaging in NGF-stimulated PC12 cells. Based on the obtained FRET images, and with the help of in silico kinetic reaction model, we predicted that PI-5-phosphatase negatively regulates PIP3 upon NGF stimulation. In agreement with this model, depletion of Src homology 2 domain–containing inositol polyphosphate 5-phosphatase 2 (SHIP2) markedly potentiated NGF-induced Rac1/Cdc42 activation and PIP3 accumulation and considerably increased the number and the length of neurites in phosphate and tensin homologue–depleted PC12 cells. Further refinement of the computational model predicted Rac1 regulation of PI3-kinase and SHIP2, which was also validated experimentally. We propose that the SHIP2-mediated negative feedback on PIP3 coordinately works with the PI3-kinase–mediated positive feedback to form an initial protrusive pattern and, later, to punctuate the PIP3 accumulation to maintain proper neurite outgrowth.
Ubiquitination differentially regulates clathrin-dependent internalization of protease-activated receptor-1
Authors: Wolfe Breann L. , Marchese Adriano , Trejo JoAnn
Published: May 2007

Protease-activated receptor-1 (PAR1), a G protein–coupled receptor (GPCR) for thrombin, is irreversibly activated by proteolysis. Consequently, PAR1 trafficking is critical for the fidelity of thrombin signaling. PAR1 displays constitutive and agonist-induced internalization, which are clathrin and dynamin dependent but are independent of arrestins. The clathrin adaptor AP2 (adaptor protein complex-2) is critical for constitutive but not for activated PAR1 internalization. In this study, we show that ubiquitination negatively regulates PAR1 constitutive internalization and specifies a distinct clathrin adaptor requirement for activated receptor internalization. PAR1 is basally ubiquitinated and deubiquitinated after activation. A PAR1 lysineless mutant signaled normally but was not ubiquitinated. Constitutive internalization of ubiquitin (Ub)-deficient PAR1 was markedly increased and inhibited by the fusion of Ub to the cytoplasmic tail. Ub-deficient PAR1 constitutive internalization was AP2 dependent like the wild-type receptor. However, unlike wild-type PAR1, AP2 was required for the internalization of activated Ub-deficient receptor, suggesting that the internalization of ubiquitinated PAR1 requires different endocytic machinery. These studies reveal a novel function for ubiquitination in the regulation of GPCR internalization.
Tumor suppressor p53 Arg72Pro polymorphism and longevity, cancer survival, and risk of cancer in the general population
Authors: Ørsted David Dynnes , Bojesen Stig Egil , Tybjærg-Hansen Anne , Nordestgaard Børge Grønne
Published: May 2007

p53 is an important tumor suppressor, normally preventing cancer development via apoptosis. A genomic Arg72Pro substitution in the p53 protein has important influence on cell death via apoptosis, which could be beneficial. We therefore tested the hypotheses that this polymorphism influences longevity, survival after a cancer diagnosis, and risk of cancer in the general population. We examined a cohort of 9,219 participants ages 20–95 from the Danish general population with 100% follow-up. The overall 12-yr survival was increased in p53 Arg/Pro heterozygotes with 3% (P = 0.003) and in Pro/Pro homozygotes with 6% (P = 0.002) versus Arg/Arg homozygotes, corresponding to an increase in median survival of 3 yr for Pro/Pro versus Arg/Arg homozygotes. We also demonstrated an increased survival after the development of cancer, or even after the development of other life-threatening diseases, for Pro/Pro versus Arg/Arg homozygotes. The Arg72Pro substitution did not associate with decreased risk of cancer. In conclusion, in this large cohort from the general population, we show that a well-known functional single nucleotide polymorphism in the tumor suppressor p53 protein leads to increased longevity, but not to decreased risk of cancer. The increased longevity may be due to increased survival after a diagnosis of cancer or other life-threatening diseases.
Tumoricidal activity of TLR7/8-activated inflammatory dendritic cells
Authors: Stary Georg , Bangert Christine , Tauber Martina , Strohal Robert , Kopp Tamara , Stingl Georg
Published: May 2007

Imiquimod (IMQ), a synthetic agonist to Toll-like receptor (TLR) 7, is being successfully used for the treatment of certain skin neoplasms, but the exact mechanisms by which this compound induces tumor regression are not yet understood. While treating basal cell carcinoma (BCC) patients with topical IMQ, we detected, by immunohistochemistry, sizable numbers of both myeloid dendritic cells (mDCs) and plasmacytoid DCs (pDCs) within the inflammatory infiltrate. Surprisingly, peritumoral mDCs stained positive for perforin and granzyme B, whereas infiltrating pDCs expressed tumor necrosis factor–related apoptosis-inducing ligand (TRAIL). The biological relevance of this observation can be deduced from our further findings that peripheral blood–derived CD11c+ mDCs acquired antiperforin and anti–granzyme B reactivity upon TLR7/8 stimulation and could use these molecules to effectively lyse major histocompatibility complex (MHC) class Ilo cancer cell lines. The same activation protocol led pDCs to kill MHC class I–bearing Jurkat cells in a TRAIL-dependent fashion. While suggesting that mDCs and pDCs are directly involved in the IMQ-induced destruction of BCC lesions, our data also add a new facet to the functional spectrum of DCs, ascribing to them a major role not only in the initiation but also in the effector phase of the immune response.
Streptomyces turgidiscabies Secretes a Novel Virulence Protein, Nec1, Which Facilitates Infection
Authors: Joshi Madhumita , Rong Xin , Moll Simon , Kers Johan , Franco Christopher , Loria Rosemary
Published: May 2007

Emergence of new, economically important plant-pathogenic species in the mostly saprophytic genus Streptomyces involves acquisition of a large, mobile pathogenicity island (PAI). Biosynthetic genes for a phytotoxin, thaxtomin A, are contained on this PAI. The Nec1 protein has necrogenic activity on excised potato tuber tissue, and the encoding gene is highly conserved in plant-pathogenic Streptomyces spp. The G+C content of nec1 indicates lateral transfer from an unrelated taxon; however, the nucleic acid and protein databases have not yielded homologs. Data presented in this article demonstrate that the Nec1 protein is necrogenic when expressed in Escherichia coli and that an active 16-kDa form of Nec1 is secreted from the plant pathogen Streptomyces turgidiscabies. Deletion analysis of nec1 demonstrated that the 151-amino-acid C-terminal region of the Nec1 protein is sufficient to confer necrogenic activity. Analysis of nec1 transcriptional start sites indicates that two mRNA species are produced and that the site of transcription initiation is influenced by glucose. S. turgidiscabies containing a nec1 deletion was greatly compromised in virulence on Arabidopsis thaliana, Nicotiana tabacum, and Raphanus sativus seedlings. The wild-type strain, S. turgidiscabies Car8, aggressively colonized and infected the root meristem of radish, whereas the Δnec1 mutant Car811 did not. Taken together, these data suggest that Nec1 is a secreted virulence protein with a conserved plant cell target that acts early in plant infection.
Components of Arabidopsis Defense- and Ethylene-Signaling Pathways Regulate Susceptibility to Cauliflower mosaic virus by Restricting Long-Distance Movement
Authors: Love Andrew J. , Laval Valérie , Geri Chiara , Laird Janet , Tomos A. Deri , Hooks Mark A. , Milner Joel J.
Published: May 2007

We analyzed the susceptibility of Arabidopsis mutants with defects in salicylic acid (SA) and jasmonic acid (JA)/ethylene (ET) signaling to infection by Cauliflower mosaic virus (CaMV). Mutants cpr1-1 and cpr5-2, in which SA-dependent defense signaling is activated constitutively, were substantially more resistant than the wild type to systemic infection, implicating SA signaling in defense against CaMV. However, SA-deficient NahG, sid2-2, eds5-1, and pad4-1 did not show enhanced susceptibility. A cpr5 eds5 double mutant also was resistant, suggesting that resistance in cpr5 may function partially independently of SA. Treatment of cpr5 and cpr5 eds5, but not cpr1, with salicyl-hydroxamic acid, an inhibitor of alternative oxidase, partially restored susceptibility to wild-type levels. Mutants etr1-1, etr1-3, and ein2-1, and two mutants with lesions in ET/JA-mediated defense, eds4 and eds8, also showed reduced virus susceptibility, demonstrating that ET-dependent responses also play a role in susceptibility. We used a green fluorescent protein (GFP)-expressing CaMV recombinant to monitor virus movement. In mutants with reduced susceptibility, cpr1-1, cpr5-2, and etr1-1, CaMV-GFP formed local lesions similar to the wild type, but systemic spread was almost completely absent in cpr1 and cpr5 and was substantially reduced in etr1-1. Thus, mutations with enhanced systemic acquired resistance or compromised ET signaling show diminished long-distance virus movement.
Mutation of Lon Protease Differentially Affects the Expression of Pseudomonas syringae Type III Secretion System Genes in Rich and Minimal Media and Reduces Pathogenicity
Authors: Lan Lefu , Deng Xin , Xiao Yanmei , Zhou Jian-Min , Tang Xiaoyan
Published: May 2007

The bacterial Lon protease participates in a variety of biological processes. In Pseudomonas syringae, mutation of lon is known to activate hrpL and a few hrpL-regulated genes in rich medium. The elevated expression of hrpL and hrpL-regulated genes results from increased stability of HrpR, the transcriptional activator of hrpL, in the lon mutant. Here, we conducted a microarray analysis to identify genes that are differentially expressed in a lon¯ mutant of P. syringae pv. tomato DC3000 grown in the rich medium King's B (KB). Most genes induced in the lon¯ mutant belong to the HrpL regulon or are related to transcription, protein synthesis, and energy metabolism. A major group of genes reduced in the lon¯ mutant are related to cell wall biogenesis. The HrpL-regulated genes exhibit different induction patterns in the lon¯ mutant, suggesting that additional regulators other than HrpL are likely to be involved in regulation of these genes. Compared with the wild-type bacteria, lon¯ mutants of P. syringae pv. tomato DC3000 and P. syringae pv. phaseolicola NPS3121 strains exhibit elevated hrpL expression in KB medium, but reduced hrpL expression in minimal medium (MM). The reduced hrpL RNA is correlated with reduced hrpR and hrpS RNAs, suggesting that the Lon-mediated regulation of hrpL involves different mechanisms in KB and MM. The lon¯ mutation also reduced bacterial pathogenicity.
Is Catalase Activity One of the Factors Associated with Maize Resistance to Aspergillus flavus?
Authors: Magbanua Zenaida V. , De Moraes Consuelo M. , Brooks T. D. , Williams W. Paul , Luthe Dawn S.
Published: May 2007

Plant responses to biotic and abiotic stresses are usually accompanied by the release of reactive oxygen species including hydrogen peroxide. Hydrogen peroxide plays a direct role in defense and is involved in many signal transduction pathways that lead to the proliferation of other defenses. Because catalase helps to maintain reactive oxygen homeostasis during biotic and abiotic stress, its activity was measured in various cob tissues during maize ear development. Catalase activity was determined in immature and mature embryos, pericarp, and rachis tissues of maize lines that are resistant and susceptible to Aspergillus flavus infection. The effect of fungal inoculation on catalase activity was also measured. Over two years of field experimentation, a correlation was observed between resistance and the level of catalase-specific activity in immature embryos, which was significantly higher in resistant lines (P < 0.0001). Furthermore, catalase activity in the resistant lines was significantly higher in immature embryos from inoculated ears (P = 0.0199). No correlation was observed between resistance and catalase activity in other ear tissues. Levels of hydrogen peroxide, the catalase substrate, and salicylic acid in the embryo were also determined. The resistant lines showed lower levels of H2O2 (P < 0.0001) and higher levels of salicylic acid (P < 0.0001) as compared with the susceptible lines. Catalase 3 was sequenced from the aflatoxin-resistant (Mp313E) and -susceptible (SC212m) inbreds. The predicted amino acid sequence indicated that there was a 20-aa deletion in the resistant inbred that might affect enzymatic activity. Unlike many plant-pathogen interactions, it appears that lowering H2O2 levels helps to prevent A. flavus infection and subsequent aflatoxin accumulation.
Velocity model updating in prestack Kirchhoff time migration for PS converted waves: Part II – Application
Authors: Dai Hengchang , Li Xiang‐Yang
Published: May 2007

We have developed a practical approach for updating the velocity of PS converted waves based on the inverse normal‐moveout common‐image‐point gather obtained from prestack Kirchhoff time migration. We have integrated all the steps involved in updating the migration velocity model into an interactive tool and have applied this approach to a real seismic data set from the Alba Field in the North Sea. Based on experience in handling the real data, we discuss various practical aspects of updating the velocity model, including: what kind of initial velocity model should be used; which parameters in the velocity model should be updated; and how to update them. Application of prestack Kirchhoff time migration to the data set using the updated velocity model produces an improved image of the Alba Field.
Tropical montane forest ecotones: climate gradients, natural disturbance, and vegetation zonation in the Cordillera Central, Dominican Republic
Authors: Martin Patrick H. , Sherman Ruth E. , Fahey Timothy J.
Published: May 2007

Aim We examined relationships between climate–disturbance gradients and patterns of vegetation zonation and ecotones on a subtropical mountain range.

Location The study was conducted on the windward slopes of the Cordillera Central, Dominican Republic, where cloud forest appears to shift in a narrow ecotone to monodominant forest ofPinus occidentalis.

Methods Climate, disturbance and vegetation data were collected over the elevation range 1100–3100 m and in 50 paired plots along the ecotone. Aerial photographs were georeferenced to a high‐resolution digital elevation model in order to enable the analysis of landscape‐scale patterns of the ecotone.

Results A Shipley–Keddy test detected discrete compositional ecotones at 2200 and 2500 m; the distributions of tree species at lower elevations were continuous. The elevation of the ecotone determined with aerial photographs was fairly consistent, namely ± 164 m (SD) over its 124‐km length, but it exhibited significant landscape variation, occurring at a lower elevation in a partially leeward, western zone. The ecotone also occurred significantly lower on ridges than it did in drainage gullies. Ecotone forest structure and composition differed markedly between paired plots. In pine paired plots, the canopy height was 1.7 times higher and the basal area of non‐pine species was 6 times lower than in the cloud forest directly below. Fire evidence was ubiquitous in the pine forest but rare in the abutting cloud forest. Mesoclimate changed discontinuously around the elevation of the ecotone: humidity and cloud formation decreased markedly, and frost frequency increased exponentially.

Main conclusions The discreteness of the ecotone was produced primarily by fire. The elevational consistency of the ecotone, however, resulted from the overarching influence of mesoclimate on the elevational patterns of fire occurrence. Declining temperature and precipitation combine with the trade‐wind inversion to create a narrow zone where high‐elevation fires extinguish, enabling fire‐sensitive and fire‐tolerant taxa to abut. Once established, mesotopography and contrasting vegetation physiognomy probably reinforce this boundary through feedbacks on microenvironment and fire likelihood. The prominence of the pine in this study – and of temperate and fire‐tolerant taxa in subtropical montane forests in general – highlights the importance of climate‐disturbance–biogeography interactions in ecotone formation, particularly where fire mediates a dynamic between climate and vegetation.
Serum alcohol dehydrogenase: a sensitive biomarker of ongoing graft function after liver transplantation
Authors: Shimojima Naoki , Shimazu Motohide , Kikuchi Haruhito , Kawachi Shigeyuki , Tanabe Minoru , Hoshino Ken , Wakabayashi Go , Morikawa Yasuhide , Kitajima Masaki
Published: May 2007

Abstract:  Alcohol dehydrogenase (ADH) is an enzyme specifically located in the cytoplasm of hepatocytes. The purpose of this study was to assess the potential usefulness of serum ADH activity as a biomarker of graft function following liver transplantation. Blood samples were obtained from 26 patients who underwent living‐donor liver transplantation. In patients without any post‐operative complication, serum ADH activity normalized at 2.9 ± 1.2 d. Values of serum ADH activity were remarkably elevated in patients with vascular complications, whereas they were only slightly elevated or remained within the reference range in patients with acute cellular rejections. In vascular complications, serum ADH activity peaked prior to elevation of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and once the cause of damage was resolved, the values returned to reference range more quickly than did ALT and AST. In conclusion, monitoring serum ADH activity in addition to ALT and AST may provide more sensitive ongoing graft status and valuable information for the differential diagnosis of vascular complications and acute cellular rejection.
Prevalence of depression among adults in Oyo State, Nigeria: A comparative study of rural and urban communities
Authors: Amoran Olorunfemi , Lawoyin Taiwo , Lasebikan Victor
Published: May 2007

Objective:  This study was designed to assess the current prevalence of depression in Oyo State, Nigeria and the rural–urban variation in prevalence.

Setting:  This is a two‐phase community‐based cross‐sectional study. The urban areas selected for the study are the Ibadan North‐West and Egbeda local government areas. The rural area selected was the Saki‐East local government area.

Participants:  A total of 1105 participants were recruited into the study. Multistage sampling technique was used to obtain a representative sample of the participants from the communities in Oyo State. The study was conducted using an interviewer‐administered structured questionnaire, and the general health questionnaire (GHQ 12) as a screening tool. The second phase of the interview was conducted only for those participants with a score of more than 3 using the GHQ 12. These participants were then clinically examined using the Structured Clinical Interview DSM IV for assessment of clinical depression.

Main outcome measure:  Prevalence of depression.

Results:  A total of 721 (65.2%) were from urban communities, while 384 (34.8%) were from the rural community. The overall prevalence of depression was found to be 5.2%. Depression was more prevalent among women than men (5.7% vs 4.8%, χ

2
 = 0.36 P = 0.55), and among adolescents (9.6%, P = 0.04). Furthermore, depression was more common in the rural areas than in the urban areas (7.3% vs 4.2%, χ2 = 4.94 P = 0.02).

Conclusion:  Depression is more common in rural than urban areas in the Nigerian population. Mental health education for adolescents and secondary school students should be encouraged in rural communities.
Regulation of hepatocyte apoptosis by oxidative stress
Authors: Singh Rajat , Czaja Mark J
Published: May 2007

Oxidative stress has been implicated as the mechanism of hepatocyte injury from numerous agents. Although reactive oxygen species injure cells by the modification of critical cellular macromolecules, recent studies have demonstrated the mechanistic involvement of oxidant stress‐induced alterations in signal transduction cascades. Studies in menadione‐treated hepatocytes have demonstrated differential effects of mitogen‐activated protein kinase activation on hepatocyte death from acute oxidative stress. Activation of the extracellular signal‐regulated kinase pathway 1/2 (ERK1/2) confers hepatocyte resistance to death whereas sustained c‐Jun N‐terminal kinase (JNK)/c‐Jun/AP‐1 activation promotes apoptosis. Redundant protective signals such as the protein kinase C/protein kinase D pathways also downregulate the JNK/c‐Jun/AP‐1 cascade and provide resistance to cell death. Although ERK1/2 overactivation also acts as a protective response to chronic oxidative stress, enhanced activation of this kinase sensitizes hepatocytes to death from free fatty acids in this setting. The outcome from challenge with an oxidative stress, therefore, depends on the integration of a series of signaling cascades that both protect against and promote hepatocyte apoptosis.
Regulation of macrophage activation in alcoholic liver disease
Authors: Thakur Varsha , McMullen Megan R , Pritchard Michele T , Nagy Laura E
Published: May 2007

Chronic ethanol feeding sensitizes Kupffer cells to activation by lipopolysaccharide (LPS), leading to increased production of tumor necrosis factor α (TNFα). The regulation of TNFα synthesis is controlled by both transcriptional and post‐transcriptional mechanisms via the integration of complex signal transduction pathways activated in response to LPS exposure. Recent data has shown that increased LPS‐stimulated phosphorylation of extracellular signal‐regulated kinase pathway 1/2 (ERK1/2) is one of the important molecular targets of chronic ethanol in Kupffer cells. This increased activation of ERK1/2 after chronic ethanol is associated with increased expression of Egr‐1, a transcription factor required for enhanced LPS‐stimulated TNFα mRNA expression after chronic ethanol exposure. egr‐1 null mice are protected from the development of fatty liver injury in response to chronic ethanol feeding, identifying an essential role for Egr‐1 in the development of chronic ethanol‐induced liver injury. Here we review recent studies aimed at understanding the mechanisms by which chronic ethanol enhances the LPS→ERK1/2→Egr‐1→ΤNFα pathway in Kupffer cells. These studies identify a critical role for nicotinamide adenine dinucleotide phosphate (NADPH) oxidase‐derived reactive oxygen species in the activation of ERK1/2 and subsequent production of TNFα in Kupffer cells after chronic ethanol feeding.
Role of oxidative stress and Kupffer cells in hepatic fibrosis
Authors: Kawada Norifumi , Otogawa Kohji
Published: May 2007

Although non‐alcoholic steatohepatitis (NASH) has become a common disease worldwide, its pathogenesis remains unclear. Establishment of a proper animal model is a prerequisite for analyzing the molecular mechanism of this disease. A NASH model has been developed using rabbits fed a high‐fat diet. These rabbits developed prominent fatty changes in hepatocytes. Hepatic fibrosis was seen around hepatocytes and the portal vein area. Apoptotic hepatocytes, which were rare in the intact liver, appeared in the liver of high‐fat diet‐fed rabbits. It is speculated that Kupffer cells/macrophages may play an important role in triggering the generation of oxidative stress in this model. Thus, this rabbit model is proposed for use in the molecular analysis of human NASH.
Role of retinoic acid receptor in steatohepatitis‐related tumor formation
Authors: Shiota Goshi
Published: May 2007

Retinoic acid (RA) appears to play an important role in the pathophysiology of liver disease. However, this role remains to be clarified in detail. To explore the role of RA in the liver, transgenic mice that express RA receptor (RAR) α−dominant negative form in hepatocytes under the control of albumin promoter and enhancer, were developed. At 4 months of age the RAR α– dominant negative form transgenic mice developed microvesicular steatosis and spotty focal necrosis. The enzymes that are involved in mitochondrial β‐oxidation of fatty acids, including very‐long‐acyl‐CoA dehydrogenase, long‐acyl‐CoA dehydrogenase, and 3‐hydroxyacyl‐CoA dehydrogenase, were downregulated; in contrast, the enzymes that are involved in peroxisomal β‐oxidation, including acyl‐CoA oxidase and bifunctional enzyme, were upregulated. Expression of cytochrome p4504a10, cytochrome p4504a12, and cytochrome p4504a14 was increased, suggesting that ω‐oxidation of fatty acids in microsomes was accelerated. In addition, formation of H2O2 and 8‐hydroxy‐2′‐deoxyguanosine was increased. After 12 monthsof age, these mice developed hepatocellular carcinomaand adenoma of the liver. The incidence of tumor formation increased with age. Expression of β‐catenin and cyclin D1 was enhanced and the TCF‐4/β‐catenin complex was increased, whereas the RARα/β‐catenin complex was decreased. Feeding on a high‐RA diet reversed histological and biochemical abnormalities and inhibited the occurrence of liver tumors. These results suggest that hepatic loss of RA function leads to the development of steatohepatitis and liver tumors. In conclusion, RA plays an important role in preventing hepatocarcinogenesis in association with fatty acid metabolism and Wnt signaling.
Central role of mitochondria in metabolic regulation of liver pathophysiology
Authors: Sato Nobuhiro
Published: May 2007

Mitochondria play a central role in cellular energy metabolism. Oxidative phosphorylation occurs in the electron transport system of the inner mitochondrial membrane. Cytochrome aa3, b and c1 are encoded by mitochondrial DNA whereas cytochrome c is encoded by the nuclear gene, and these mitochondrial‐DNA dependent cytochromes are decreased and electron transport at complex II, III and IV is disturbed in liver carcinomas and during carcinogenesis. The more the decreased cytochrome and oxidase activity are seen, the more significant is the increase in reactive oxygen species (ROS) production. ROS produced in mitochondria may be the main cause of nuclear‐gene mutation in carcinogenesis. The mitochondrial dysfunction and overproduction of ROS plays a key role in progression of chronic hepatitis C and ethanol‐induced liver injury. Ethanol also causes bacterial translocation in the intestine and the resulting lipopolysaccharides (LPS) activates Kupffer cells to produce pro‐inflammatory cytokines. We suspect that non‐alcoholic steatohepatitis (NASH) also is the result of increased ROS production in Kupffer cells and hepatocytes.
A transition care programme which improves diabetes control and reduces hospital admission rates in young adults with Type 1 diabetes aged 15–25 years
Authors: Holmes‐Walker D. J. , Llewellyn A. C. , Farrell K.
Published: May 2007

Aims  To determine if a transition support programme for young adults with diabetes could maintain attendance at a specialist clinic, improve diabetes control and reduce acute hospital admissions with diabetic ketoacidosis (DKA) in 15–25‐year‐olds with Type 1 diabetes.

Methods  A transition coordinator/diabetes educator arranged booking and rebooking of appointments for a young adult diabetes clinic based in an adult hospital between July 2001 and March 2006. An after‐hours phone support service was initiated. Data collected included source of referral, frequency of clinic attendance and HbA1c at each visit. Numbers of admissions and readmissions with DKA, length of stay and HbA1c on admission were recorded.

Results  One hundred and ninety‐one young adults were referred. HbA1c at initial referral was 9.3 ± 2.17%. HbA1c significantly improved to 8.8 ± 1.9% (P < 0.001) after a median of five visits with a statistically significant fall in HbA1c of 0.13% per visit (P = 0.01). The greatest improvements were seen in those with starting HbA1c > 11% (−2.5 ± 2.3%, P < 0.001). Eighty‐two percent had attended appointments in the last 6 months. There was a significant reduction in DKA admissions falling by 1/3 (P = 0.05), and in readmissions a significant reduction in length of stay (−3.6 days, P = 0.02), over 3.5 years.

Conclusions  If young adults are appropriately supported in adult services, clinic attendance is maintained, diabetes control is improved and hospital admission rates with DKA are reduced. The cost savings from reduced admissions covered the costs of the programme.
Reduced peripheral blood mitochondrial DNA content is not a risk factor for Type 2 diabetes
Authors: Singh R. , Hattersley A. T. , Harries L. W.
Published: May 2007

Aims  Mitochondrial depletion in pancreatic beta cells is known to reduce glucose stimulated insulin secretion. We aimed to determine whether the offspring of patients with early onset Type 2 diabetes had reduced peripheral blood mitochondrial content relative to control subjects and whether this could lead to a predisposition to type 2 diabetes in later life.

Methods  We measured the levels of mitochondria relative to a single copy genomic target by real time polymerase chain reaction in a series of peripheral blood samples taken from the offspring of Caucasian patients with Type 2 diabetes and matched controls. Measures of insulin sensitivity and beta cell function were also taken.

Results  In contrast with previous studies, mitochondrial DNA content was not decreased in the offspring of patients with Type 2 diabetes relative to matched controls in our cohort. Conversely, we noted a small proliferation in mitochondrial numbers in our case subjects. In agreement with these findings, no correlations with either insulin sensitivity or beta cell function were noted.

Conclusions  Our results indicate that reduced mitochondrial DNA content in peripheral blood is not a risk factor for the development of Type 2 diabetes in the offspring of patients with early onset Type 2 diabetes.
The Centrality of Gender and Ethnic Identities across Individuals and Contexts
Authors: Turner Kelly L. , Brown Christia Spears
Published: May 2007

This study examined (1) whether 5‐ to 12‐year‐old children consider gender and ethnicity to be central and important components of their identity, (2) whether the relative centrality of these identity components differs across children, and (3) how the centrality of children's gender and ethnic identities is affected by a dynamic situational context of inclusion and exclusion. Results indicate that although gender and ethnicity are not the most important aspects of elementary schoolchildren's self‐concepts, both gender and ethnic identities differ among European‐American and ethnic minority group children, and those differences are greater in older children. In addition, children's gender identity is context‐dependent, but the exact nature of this flexibility is contingent on the existing centrality of their identity.
Thyrotoxicosis Presenting With Headache
Authors: Stone J , Foulkes A , Adamson K , Stevenson L , Salman R Al-Shahi
Published: May 2007

We report three cases of thyrotoxicosis who presented acutely with headache to our neurology service in a 1-year period. In two of these patients there was a pre-existing or subsequent history of migraine. With hindsight, there were other clinical features of thyrotoxicosis but this diagnosis had been missed in primary care. Severe headache can be a striking presenting feature of thyrotoxicosis, but these cases provide reassurance to the clinician that when this does occur, other clinical features of hyperthyroidism are usually present.
Founder Effect of the 669insA Mutation in BSCL2 Gene Causing Berardinelli‐Seip Congenital Lipodystrophy in a Cluster from Brazil
Authors: Gomes K. B. , Pardini V. C. , Ferreira A. C. S. , Fonseca C. G. , Fernandes A. P.
Published: May 2007

Congenital generalized lipodystrophy (CGL) or Berardinelli‐Seip Syndrome (BSCL) is a rare autosomal recessive disease characterized by a nearly‐complete absence of adipose tissue from birth and severe metabolic alterations. The 669insA mutation in exon 4 of the BSCL2 gene was identified as the major genetic alteration leading to BSCL in a group of 22 patients from the northeastern Brazilian state of Rio Grande do Norte. Aiming to investigate the causes of the high frequency of BSCL in this region, a molecular genetic study was conducted using eight microsatelite markers located in chromosome 11. Additional investigations concerning the proportion of expected homozygous and heterozygous individuals, genetic diversity, fixation index and coefficient of endogamy were undertaken, and indicated significant differences by comparing the allelic and haplotypic frequencies observed for the BSCL affected families and the control group. It was concluded that a founder effect, genetic drift and consanguineous marriages have significantly affected the structure of this population, resulting in the highest frequency of BSCL in Brazil.