bluuebunny/crossref_metadata_2025 huggingface dataset:
Visuomotor system uses target features unavailable to conscious awareness
Authors: Binsted Gordon , Brownell Kyle , Vorontsova Zofia , Heath Matthew , Saucier Deborah
Published: July 2007

After lesions to primary visual cortex, patients lack conscious awareness of visual stimuli. Interestingly, however, some retain the ability to make accurate judgments about the visual world (i.e., so-called blindsight). Similarly, damage to inferior occipitotemporal regions of cortex (e.g., lateral occipital cortex) can result in an inability to perceive object properties while retaining the ability to act on them (i.e., visual form agnosia). In the present work, we demonstrate that the ability to interact with objects in the absence of conscious awareness is not isolated to those with restricted neuropathologic conditions. Specifically, neurologically intact individuals are able to program and execute goal-directed reaching movements to a target object without awareness of extrinsic target properties; they accurately tune the dynamics of their movement and modulate it online without conscious access to features of the goal object. Thus, the planning and execution of actions are not dependent on conscious awareness of the environment, suggesting that the phenomenon of blindsight (and agnosia) reflect normal conditions of the visual system.
Fasting-dependent glucose and lipid metabolic response through hepatic sirtuin 1
Authors: Rodgers Joseph T. , Puigserver Pere
Published: July 2007

In the fasted state, induction of hepatic glucose output and fatty acid oxidation is essential to sustain energetic balance. Production and oxidation of glucose and fatty acids by the liver are controlled through a complex network of transcriptional regulators. Among them, the transcriptional coactivator PGC-1α plays an important role in hepatic and systemic glucose and lipid metabolism. We have previously demonstrated that sirtuin 1 (SIRT1) regulates genes involved in gluconeogenesis through interaction and deacetylation of PGC-1α. Here, we show
in vivo
that hepatic SIRT1 is a factor in systemic and hepatic glucose, lipid, and cholesterol homeostasis. Knockdown of SIRT1 in liver caused mild hypoglycemia, increased systemic glucose and insulin sensitivity, and decreased glucose production. SIRT1 knockdown also decreased serum cholesterol and increased hepatic free fatty acid and cholesterol content. These metabolic phenotypes caused by SIRT1 knockdown tightly correlated with decreased expression of gluconeogenic, fatty acid oxidation and cholesterol degradation as well as efflux genes. Additionally, overexpression of SIRT1 reversed many of the changes caused by SIRT1 knockdown and depended on the presence of PGC-1α. Interestingly, most of the effects of SIRT1 were only apparent in the fasted state. Our results indicate that hepatic SIRT1 is an important factor in the regulation of glucose and lipid metabolism in response to nutrient deprivation. As these pathways are dysregulated in metabolic diseases, SIRT1 may be a potential therapeutic target to control hyperglycemia and hypercholesterolemia.
Rapid asymmetric evolution of a dual-coding tumor suppressor INK4a/ARF locus contradicts its function
Authors: Szklarczyk Radek , Heringa Jaap , Pond Sergei Kosakovsky , Nekrutenko Anton
Published: July 2007

INK4a/ARFtumor suppressor locus encodes two protein products, INK4a and ARF, essential for controlling tumorigenesis and mutated in more than half of human cancers. There is no resemblance between the two proteins: their coding regions are assembled by alternative splicing of two mutually exclusive 5′ exons into a constitutive one containing overlapping out-of-phase reading frames. We show that the dual-coding arrangement conflicts with the high cost of mutations withinINK4a/ARF. Unexpectedly, the locus evolves rapidly and asymmetrically, with ARF accumulating the majority of amino acid replacements. Rapid evolution drives both INK4a and ARF proteins out of sync with other members of the RB and p53 tumor suppressor pathways, both of which are controlled by the locus. Yet, the asymmetric behavior may be an intrinsic property of dual-coding exons: INK4a/ARF closely mimics the evolution of 90 newly identified genes with similar dual-coding structure. Thus, the strong link between mutations in INK4a/ARF and cancer may be a direct consequence of the architecture of the locus.
Identification of a locus control region for quadruplicated green-sensitive opsin genes in zebrafish
Authors: Tsujimura Taro , Chinen Akito , Kawamura Shoji
Published: July 2007

Duplication of opsin genes has a crucial role in the evolution of visual system. Zebrafish have four green-sensitive (RH2) opsin genes (
RH2–1
,
RH2–2
,
RH2–3
, and
RH2–4
) arrayed in tandem. They are expressed in the short member of the double cones (SDC) but differ in expression areas in the retina and absorption spectra of their encoding photopigments. The shortest and the second shortest wavelength subtypes,
RH2–1
and
RH2–2
, are expressed in the central-to-dorsal retina. The longer wavelength subtype,
RH2–3
, is expressed circumscribing the
RH2–1/RH2–2
area, and the longest subtype,
RH2–4
, is expressed further circumscribing the
RH2–3
area and mainly occupying the ventral retina. The present report shows that a 0.5-kb region located 15 kb upstream of the RH2 gene array is an essential regulator for their expression. When the 0.5-kb region was deleted from a P1-artificial chromosome (PAC) clone encompassing the four RH2 genes and when one of these genes was replaced with a reporter GFP gene, the GFP expression in SDCs was abolished in the zebrafish to which a series of the modified PAC clones were introduced. Transgenic studies also showed that the 0.5-kb region conferred the SDC-specific expression for promoters of a non-SDC (UV opsin) and a nonretinal (keratin 8) gene. Changing the location of the 0.5-kb region in the PAC clone conferred the highest expression for its proximal gene. The 0.5-kb region was thus designated as RH2-LCR analogous to the locus control region of the L-M opsin genes of primates.
Increased prostate cell proliferation and loss of cell differentiation in mice lacking prostate epithelial androgen receptor
Authors: Wu Chun-Te , Altuwaijri Saleh , Ricke William A. , Huang Shu-Pin , Yeh Shuyuan , Zhang Caixia , Niu Yuanjie , Tsai Meng-Ying , Chang Chawnshang
Published: July 2007

Developmental studies of the prostate have established that ductal morphogenesis, epithelial cytodifferentiation, and proliferation/apoptosis are regulated by androgens acting through stromal androgen receptor (AR). Here, we found mice lacking epithelial AR within the mature prostate (pes-ARKO) developed prostate tissue that was less differentiated and hyperproliferative relative to WT littermates. Epithelial AR protein was significantly decreased in 6-week-old mice and was nearly absent by ≥24 weeks of age. Circulating levels of testosterone, external genitalia, or fertility were not altered in pes-ARKO mice. A significant (
P
< 0.05) increase in bromo-deoxyuridine-positive epithelia was observed in ventral and dorsal-lateral prostates of pes-ARKO mice at 24 weeks of age. Less differentiation was observed as indicated by decreased epithelial height and glandular infolding through 24 weeks of age, differentiation markers probasin, PSP-94, and Nkx3.1 were sig nificantly decreased, and epithelial sloughing and luminal cell apoptosis increased from 6 to 32 weeks of age in pes-ARKO mice. Gain of function occurred by crossing pes-ARKO to the T857A transgenic mice containing constitutively activated AR. In T857A-pes-ARKO mice prostates were of normal size, contained glandular infoldings, and maintained high secretory epithelium, and the appropriate prostatic epithelial proliferation was restored. Collectively, these results suggest that prostatic epithelial AR plays an important role in the homeostasis of the prostate gland. These data support the hypothesis that epithelial AR controls prostate growth by suppressing epithelial proliferation in the mature gland.
Quantitative analysis of EGFRvIII cellular signaling networks reveals a combinatorial therapeutic strategy for glioblastoma
Authors: Huang Paul H. , Mukasa Akitake , Bonavia Rudy , Flynn Ryan A. , Brewer Zachary E. , Cavenee Webster K. , Furnari Frank B. , White Forest M.
Published: July 2007

Glioblastoma multiforme (GBM) is the most aggressive brain tumor in adults and remains incurable despite multimodal intensive treatment regimens. EGFRvIII is a truncated extracellular mutant of the EGF receptor (EGFR) commonly found in GBMs that confers enhanced tumorigenic behavior. To gain a molecular understanding of the mechanisms by which EGFRvIII acts, we have performed a large-scale analysis of EGFRvIII-activated phosphotyrosine-mediated signaling pathways and thereby have identified and quantified 99 phosphorylation sites on 69 proteins. Distinct signaling responses were observed as a function of titrated EGFRvIII receptor levels with the phosphatidylinositol 3-kinase pathway being dominant over the MAPK and STAT3 pathways at a high level of EGFRvIII expression. Within this data set, the activating phosphorylation site on the c-Met receptor was found to be highly responsive to EGFRvIII levels, indicating cross-activation of the c-Met receptor tyrosine kinase by EGFRvIII. To determine the significance of this finding, we devised a combined treatment regimen that used a c-Met kinase inhibitor and either an EGFR kinase inhibitor or cisplatin. This regimen resulted in enhanced cytotoxicity of EGFRvIII-expressing cells compared with treatment with either compound alone. These results suggest that the clinical use of c-Met kinase inhibitors in combination with either EGFR inhibitors or standard chemotherapeutics might represent a previously undescribed therapeutic approach to overcome the observed chemoresistance in patients with GBMs expressing EGFRvIII.
Phage escape libraries for checkmate analysis
Authors: Dickerson Tobin J. , McKenzie Kathleen M. , Hoyt Amanda S. , Wood Malcolm R. , Janda Kim D. , Brenner Sydney B. , Lerner Richard A.
Published: July 2007

Ligand-binding epitopes of proteins can mutate rapidly, as shown by viral mutations that lead to escape from neutralizing antibodies. We have undertaken to recreate
in vitro
the evolutionary competition between viral mutations that allow escape from antibody binding and host mutations that generate new neutralizing antibodies to the mutated viral antigen. To examine this vital race, we describe a phage-based method that allows rapid analysis of molecules that perturb the binding of proteins to their ligands. Because the system can amplify by replication, single-molecule sensitivity can be achieved. When combinatorial protein or small-molecule libraries are studied, large numbers of binding events can be analyzed simultaneously. Such libraries may be used in a sequential phage escape format, where cycles of phage binding and release of mutants are driven by antibodies or small molecules and the difficulty of escape increases at each cycle. Ultimately, the sequencing of the viral mutants allows annotation of the allowed trajectory of escape. Likewise, sequencing of the antibody perturbants charts the chemistry of the immune system response to the viral challenge. We have termed such analysis of competing mutations a “checkmate analysis.” When viral systems are studied, a checkmate analysis allows experimental evaluation of the evolutionary contest between viruses and the immune system and may predict which antibodies and small-molecule ligands should be generated in anticipation of viral mutations before these mutations create viral epidemics.
Metabolic plasticity during mammalian development is directionally dependent on early nutritional status
Authors: Gluckman Peter D. , Lillycrop Karen A. , Vickers Mark H. , Pleasants Anthony B. , Phillips Emma S. , Beedle Alan S. , Burdge Graham C. , Hanson Mark A.
Published: July 2007

Developmental plasticity in response to environmental cues can take the form of polyphenism, as for the discrete morphs of some insects, or of an apparently continuous spectrum of phenotype, as for most mammalian traits. The metabolic phenotype of adult rats, including the propensity to obesity, hyperinsulinemia, and hyperphagia, shows plasticity in response to prenatal nutrition and to neonatal administration of the adipokine leptin. Here, we report that the effects of neonatal leptin on hepatic gene expression and epigenetic status in adulthood are directionally dependent on the animal's nutritional status
in utero
. These results demonstrate that, during mammalian development, the direction of the response to one cue can be determined by previous exposure to another, suggesting the potential for a discontinuous distribution of environmentally induced phenotypes, analogous to the phenomenon of polyphenism.
Surgical interruption of pelvic nerve pathways in dysmenorrhea: a systematic review of effectiveness
Authors: LATTHE P.M. , PROCTOR M.L. , FARQUHAR C.M. , JOHNSON N. , KHAN K.S.
Published: July 2007

Objectives. To assess the effectiveness of surgical interruption of pelvic nerve pathways in primary and secondary dysmenorrhea. Data sources. The Cochrane Menstrual Disorders and Subfertility Group Trials Register (9 June 2004), CENTRAL (The Cochrane Library, Issue 2, 2004), MEDLINE (1966 to Nov. 2003), EMBASE (1980 to Nov. 2003), CINAHL (1982 to Oct. 2003), MetaRegister of Controlled Trials, the citation lists of review articles and included trials, and contact with the corresponding author of each included trial. Review methods. The inclusion criteria were randomized controlled trials of uterosacral nerve ablation or presacral neurectomy (both open and laparoscopic procedures) for the treatment of dysmenorrhea. The main outcome measures were pain relief and adverse effects. Two reviewers extracted data on characteristics of the study quality and the population, intervention, and outcome independently. Results. Nine randomized controlled trials were included in the systematic review. There were two trials with open presacral neurectomy; all other trials used laparoscopic techniques. For the treatment of primary dysmenorrhea, laparoscopic uterosacral nerve ablation at 12 months was better when compared to a control or no treatment (OR 6.12; 95% CI 1.78–21.03). The comparison of laparoscopic uterosacral nerve ablation with presacral neurectomy for primary dysmenorrhea showed that at 12 months follow‐up, presacral neurectomy was more effective (OR 0.10; 95% CI 0.03–0.32). In secondary dysmenorrhea, along with laparoscopic surgical treatment of endometriosis, the addition of laparoscopic uterosacral nerve ablation did not improve the pain relief (OR 0.77; 95% CI 0.43–1.39), while presacral neurectomy did (OR 3.14; 95% CI 1.59–6.21). Adverse events were more common for presacral neurectomy than procedures without presacral neurectomy (OR 14.6; 95% CI 5–42.5). Conclusion. The evidence for nerve interruption in the management of dysmenorrhea is limited. Methodologically sound and sufficiently powered randomized controlled trials are needed.
Qualitative Review of Serotonin Syndrome, Ecstasy (MDMA) and the use of Other Serotonergic Substances: Hierarchy of Risk
Authors: Silins Edmund , Copeland Jan , Dillon Paul
Published: July 2007

Growth of the antidepressant market and widespread use of the illicit drug ecstasy (methylenedioxymethamphetamine; MDMA) creates a need to delineate the potential harms associated with the concomitant use of ecstasy and serotonergic pharmaceutical drugs. One such harm is serotonin syndrome. The study aimed to synthesize the risk of serotonin syndrome associated with the concomitant use of ecstasy and other serotonergic substances in a clinically relevant hierarchy for psychiatrists and other medical practitioners. An extensive online database search was carried out of the literature on serotonin syndrome, in relation to illicit drugs and simultaneous use of other substances. Numerous licit and illicit substances implicated in serotonin syndrome, when used with ecstasy, have potential for increased toxicity and are presented in a resulting hierarchy of risk. Substances that inhibit serotonin re-uptake are less likely to lead to life-threatening elevations in serotonin when used with ecstasy. High doses or repeated use of stimulants such as methamphetamine and cocaine with ecstasy increase the risk of serotonin syndrome; as does the use of pharmaceutical amphetamine and ecstasy. Serotonin precursors also influence the course of serotonin syndrome when used with ecstasy. Substances that inhibit monoamine oxidase are most likely to lead to serious increases in serotonin when used with ecstasy. Findings highlight the importance of screening for the use of ecstasy and other serotonergic substances when prescribing antidepressant drugs.
Can educational experiments both test a theory and inform practice?
Authors: Marsden Emma
Published: July 2007

This article feeds into debate about the feasibility and usefulness of educational experiments by discussing methodological issues arising out of a study which sought causal links between teaching and learning of one aspect of French as a foreign language. The study involved two small‐scale experiments which tested a hypothesis regarding the learning of second language grammar within a particular theoretical, and its related pedagogical, framework (Input Processing and Processing Instruction respectively), and has been described in full elsewhere. The current article uses that example to suggest some circumstances (contextual, methodological and theoretical) within which educational experiments may be able to both test a learning theory and inform educational practice. It is argued that despite the complexities and limits of small‐scale educational experiments, an experimental design which combined a range of methods was able to generate new and useful (in a range of senses) substantive knowledge.
Book Review
Authors: Stojanovic-Birovljev Vesna
Published: July 2007

The Chest X-Ray: Differential Diagnosis in Conventional Radiology. Second edition. Edited by A. F. Burgener, M. Kormano and T. Pudas. Stuttgart, New York: Thieme Verlag, 2006. ISBN 1-58890-446-6 (TNP New York), ISBN 3-13-107612-7 (GTV Stuttgart). 208 pages, 329 figures, 29 tables pages. Price hardcover: EUR 79.95. USD 99.95
Book Review
Authors: Nakstad Per Hj.
Published: July 2007

MRI in Practice. Third edition. Edited by C. Westbrook, C. Kaut Roth and J. Talbot. Blackwell Publishing Ltd, Oxford, 2005. ISBN 9781405127875. 410 pages. Price paperback: USD 59.95, GBP 32.50
Book Review
Authors: Aaløkken Trond Mogens
Published: July 2007

Multidetector-Row CT of the Thorax. Edited by U. J. Schoepf. Springer-Verlag, Heidelberg, 2006. ISBN 3-540- 43774-6. 482 pages, 641 figures, 37 tables. Price hardcover: EUR 229
Book Review
Authors: Nakstad Per H.
Published: July 2007

Clinical 3T Magnetic Resonance. Edited by V. M. Runge, W. R. Nitz, S. H. Schmeets and S. O. Schoenberg. Stuttgart, New York: Georg Thieme Verlag, 2007. ISBN 978-3-13- 141101-3. 252 pages, 274 figures. Price paperback: EUR 39.95
A novel Crumbs3 isoform regulates cell division and ciliogenesis via importin β interactions
Authors: Fan Shuling , Fogg Vanessa , Wang Qian , Chen Xiao-Wei , Liu Chia-Jen , Margolis Ben
Published: July 2007

The Crumbs family of apical transmembrane proteins regulates apicobasal polarity via protein interactions with a conserved C-terminal sequence, ERLI. However, one of the mammalian Crumbs proteins, Crumbs3 (CRB3) has an alternate splice form with a novel C-terminal sequence ending in CLPI (CRB3-CLPI). We report that CRB3-CLPI localizes to the cilia membrane and a membrane compartment at the mitotic spindle poles. Knockdown of CRB3-CLPI leads to both a loss of cilia and a multinuclear phenotype associated with centrosomal and spindle abnormalities. Using protein purification, we find that CRB3-CLPI interacts with importin β-1 in a Ran-regulated fashion. Importin β-1 colocalizes with CRB3-CLPI during mitosis, and a dominant-negative form of importin β-1 closely phenocopies CRB3-CLPI knockdown. Knockdown of importin β-1 blocks targeting of CRB3-CLPI to the spindle poles. Our data suggest an expanded role for Crumbs proteins in polarized membrane targeting and cell division via unique interactions with importin proteins.
Cdc42 and noncanonical Wnt signal transduction pathways cooperate to promote cell polarity
Authors: Schlessinger Karni , McManus Edward J. , Hall Alan
Published: July 2007

Scratch-induced disruption of cultured monolayers induces polarity in front row cells that can be visualized by spatially localized polymerization of actin at the front of the cell and reorientation of the centrosome/Golgi to face the leading edge. We previously reported that centrosomal reorientation and microtubule polarization depend on a Cdc42-regulated signal transduction pathway involving activation of the Par6/aPKC complex followed by inhibition of GSK-3β and accumulation of the adenomatous polyposis coli (APC) protein at the plus ends of leading-edge microtubules. Using monolayers of primary rodent embryo fibroblasts, we show here that dishevelled (Dvl) and axin, two major components of the Wnt signaling pathway are required for centrosome reorientation and that Wnt5a is required for activation of this pathway. We conclude that disruption of cell–cell contacts leads to the activation of a noncanonical Wnt/dishevelled signal transduction pathway that cooperates with Cdc42/Par6/aPKC to promote polarized reorganization of the microtubule cytoskeleton.
Yeast peroxisomes multiply by growth and division
Authors: Motley Alison M. , Hettema Ewald H.
Published: July 2007

Peroxisomes can arise de novo from the endoplasmic reticulum (ER) via a maturation process. Peroxisomes can also multiply by fission. We have investigated how these modes of multiplication contribute to peroxisome numbers in Saccharomyces cerevisiae and the role of the dynamin-related proteins (Drps) in these processes. We have developed pulse-chase and mating assays to follow the fate of existing peroxisomes, de novo–formed peroxisomes, and ER-derived preperoxisomal structures. We find that in wild-type (WT) cells, peroxisomes multiply by fission and do not form de novo. A marker for the maturation pathway, Pex3-GFP, is delivered from the ER to existing peroxisomes. Strikingly, cells lacking peroxisomes as a result of a segregation defect do form peroxisomes de novo. This process is slower than peroxisome multiplication in WT cells and is Drp independent. In contrast, peroxisome fission is Drp dependent. Our results show that peroxisomes multiply by growth and division under our assay conditions. We conclude that the ER to peroxisome pathway functions to supply existing peroxisomes with essential membrane constituents.
Functional dissection of Rab GTPases involved in primary cilium formation
Authors: Yoshimura Shin-ichiro , Egerer Johannes , Fuchs Evelyn , Haas Alexander K. , Barr Francis A.
Published: July 2007

Primary cilia are sensory structures involved in morphogen signalling during development, liquid flow in the kidney, mechanosensation, sight, and smell (Badano, J.L., N. Mitsuma, P.L. Beales, and N. Katsanis. 2006. Annu. Rev. Genomics Hum. Genet. 7:125–148; Singla, V., and J.F. Reiter. 2006. Science. 313:629–633.). Mutations that affect primary cilia are responsible for several diseases, including neural tube defects, polycystic kidney disease, retinal degeneration, and cancers (Badano et al., 2006; Singla and Reiter, 2006). Primary cilia formation and function requires tight integration of the microtubule cytoskeleton with membrane trafficking (Singla and Reiter, 2006), and this is poorly understood. We show that the Rab GTPase membrane trafficking regulators Rab8a, -17, and -23, and their cognate GTPase-activating proteins (GAPs), XM_037557, TBC1D7, and EVI5like, are involved in primary cilia formation. However, other human Rabs and GAPs are not. Additionally, Rab8a specifically interacts with cenexin/ODF2, a basal body and microtubule binding protein required for cilium biogenesis (Ishikawa, H., A. Kubo, S. Tsukita, and S. Tsukita. 2005. Nat. Cell Biol. 7:517–524), and is the sole Rab enriched at primary cilia. These findings provide a basis for understanding how specific membrane trafficking pathways cooperate with the microtubule cytoskeleton to give rise to the primary cilia.
Organ-dependent in vivo priming of naive CD4+,but not CD8+,T cells by plasmacytoid dendritic cells
Authors: Sapoznikov Anita , Fischer Jens A.A. , Zaft Tami , Krauthgamer Rita , Dzionek Andrzej , Jung Steffen
Published: July 2007

Plasmacytoid dendritic cells (PDCs) play a pivotal role as cytokine-secreting accessory cells in the antimicrobial immune defense. In contrast, the capacity of PDCs to act as antigen-presenting cells in naive T cell priming remains unclear. By studying T cell responses in mice that lack conventional DCs (cDCs), and by the use of a PDC-specific antigen-targeting strategy, we show that PDCs can initiate productive naive CD4+ T cell responses in lymph nodes, but not in the spleen. PDC-triggered CD4+ T cell responses differed from cDC-driven responses in that they were not associated with concomitant CD8+ T cell priming. Our results establish PDCs as a bona fide DC subset that initiates unique CD4+ Th cell–dominated primary immune responses.
Repression of interleukin-4 in T helper type 1 cells by Runx/Cbfβ binding to the Il4 silencer
Authors: Naoe Yoshinori , Setoguchi Ruka , Akiyama Kaori , Muroi Sawako , Kuroda Masahiko , Hatam Farah , Littman Dan R. , Taniuchi Ichiro
Published: July 2007

Interferon γ (IFNγ) is the hallmark cytokine produced by T helper type 1 (Th1) cells, whereas interleukin (IL)-4 is the hallmark cytokine produced by Th2 cells. Although previous studies have revealed the roles of cytokine signaling and of transcription factors during differentiation of Th1 or Th2 cells, it is unclear how the exclusive expression pattern of each hallmark cytokine is established. The DNaseI hypersensitivity site IV within the mouse Il4 locus plays an important role in the repression of Il4 expression in Th1 cells, and it has been named the Il4 silencer. Using Cbfβ- or Runx3-deficient T cells, we show that loss of Runx complex function results in derepression of IL-4 in Th1 cells. Binding of Runx complexes to the Il4 silencer was detected in naive CD4+ T cells and Th1 cells, but not in Th2 cells. Furthermore, enforced expression of GATA-3 in Th1 cells inhibited binding of Runx complexes to the Il4 silencer. Interestingly, T cell–specific inactivation of the Cbfβ gene in mice led to elevated serum immunoglobulin E and airway infiltration. These results demonstrate critical roles of Runx complexes in regulating immune responses, at least in part, through the repression of the Il4 gene.
The SCFFBW7 ubiquitin ligase complex as a tumor suppressor in T cell leukemia
Authors: Thompson Benjamin J. , Buonamici Silvia , Sulis Maria Luisa , Palomero Teresa , Vilimas Tomas , Basso Giuseppe , Ferrando Adolfo , Aifantis Iannis
Published: July 2007

Recent studies have shown that activating mutations of NOTCH1 are responsible for the majority of T cell acute lymphoblastic leukemia (T-ALL) cases. Most of these mutations truncate its C-terminal domain, a region that is important for the NOTCH1 proteasome-mediated degradation. We report that the E3 ligase FBW7 targets NOTCH1 for ubiquitination and degradation. Our studies map in detail the amino acid degron sequence required for NOTCH1–FBW7 interaction. Furthermore, we identify inactivating FBW7 mutations in a large fraction of human T-ALL lines and primary leukemias. These mutations abrogate the binding of FBW7 not only to NOTCH1 but also to the two other characterized targets, c-Myc and cyclin E. The majority of the FBW7 mutations were present during relapse, and they were associated with NOTCH1 HD mutations. Interestingly, most of the T-ALL lines harboring FBW7 mutations were resistant to γ-secretase inhibitor treatment and this resistance appeared to be related to the stabilization of the c-Myc protein. Our data suggest that FBW7 is a novel tumor suppressor in T cell leukemia, and implicate the loss of FBW7 function as a potential mechanism of drug resistance in T-ALL.
The Hausdorff dimension of visible sets of planar continua
Authors: O’Neil Tacey
Published: July 2007

For a compact set

Γ
⊂

R

2

\Gamma \subset \mathbb {R}^2

and a point

x
x

, we define the visible part of

Γ
\Gamma

from

x
x

to be the set
\[

Γ
x

=
{
u
∈
Γ
:
[
x
,
u
]
∩
Γ
=
{
u
}
}
.

\Gamma _x=\{u\in \Gamma : [x,u]\cap \Gamma =\{u\}\}.

\]
(Here

[
x
,
u
]

[x,u]

denotes the closed line segment joining

x
x

to

u
u

.) In this paper, we use energies to show that if

Γ
\Gamma

is a compact connected set of Hausdorff dimension greater than one, then for (Lebesgue) almost every point

x
∈

R

2

x\in \mathbb {R}^2

, the Hausdorff dimension of

Γ
x

\Gamma _x

is strictly less than the Hausdorff dimension of

Γ
\Gamma

. In fact, for almost every

x
x

,
\[
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="dimension Subscript upper H Baseline left-parenthesis normal upper Gamma Subscript x Baseline right-parenthesis less-than-or-equal-to one half plus StartRoot dimension Subscript upper H Baseline left-parenthesis normal upper Gamma right-parenthesis minus three fourths EndRoot period">

dim
H

⁡
(

Γ
x

)
≤

1
2

+

dim
H

⁡
(
Γ
)
−

3
4

.

\dim _H (\Gamma _x)\leq \frac {1}{2}+\sqrt {\dim _H(\Gamma )-\frac {3}{4}}.

\]
We also give an estimate of the Hausdorff dimension of those points where the visible set has dimension greater than

σ
+

1
2

+

dim
H

⁡
(
Γ
)
−

3
4

\sigma +\frac {1}{2}+\sqrt {\dim _H (\Gamma )-\frac {3}{4}}

for some

σ
>
0

\sigma >0

.
Cadmium and mercury in Seine Estuary flounders and mussels: the results of two decades of monitoring
Authors: Nakhlé K. , Cossa D. , Claisse D. , Beliaeff B. , Simon S.
Published: July 2007

Nakhlé, K., Cossa, D., Claisse, D., Beliaeff, B., and Simon, S. 2007. Cadmium and mercury in Seine Estuary flounders and mussels: the results of two decades of monitoring. – ICES Journal of Marine Science, 64: 929–938. The flounder (Platichthys flesus) is a flatfish that inhabits marine coastal environments, especially estuaries. It is an alternative quantitative biological indicator to the common marine mussel (Mytilus spp.), which is currently used as a sentinel species to monitor chemical contamination in numerous monitoring programmes. Findings from two decades of monitoring cadmium (Cd) and mercury (Hg) using both sentinel species in the Seine Estuary (France) are reported. For comparison, time-series of water concentrations for the same two metals at the mouth of the River Seine are given. Cd concentrations in the liver of the fish and in the soft tissue of mussels show similar temporal trends, consistent with the major temporal variations of Cd concentrations recorded in river water and with changes in industrial discharge of Cd (phosphogypsum waste) within the Seine Estuary. On the other hand, Hg concentrations in the muscles of flounders show temporal variations with no link to that observed in mussels or fluvial Hg contributions, which are in fact nearly covariant. It is concluded that optimization of the use of flounders as sentinel organisms for monitoring temporal trends of metal contamination in estuarine environments requires in-depth knowledge of its ecology within the area studied. An adapted sampling strategy based on this knowledge should provide results that are easier to interpret.
Estimation of shrimp (Pandalus borealis) carapace length by image analysis
Authors: Harbitz Alf
Published: July 2007

Harbitz, A. 2007. Estimation of shrimp (Pandalus borealis) carapace length by image analysis. — ICES Journal of Marine Science, 64: 939–944. An image analysis technique was examined to assess its ability to estimate automatically the carapace length of shrimp (Pandalus borealis). Carapace length, pixel area, and weight were measured in a sample of 285 shrimp. An accurate slide calliper was used to measure the carapace length (13–30 mm) by an experienced operator with a precision (standard deviation) of ∼0.2 mm. A high-resolution still image camera was used to produce an 1810 × 1710 pixel colour image containing all 285 shrimp. The individual shrimp were segmented from the background by intensity thresholding. A linear model on a log-log scale of length in relation to pixel area yielded a precision of 0.43 mm. Despite differences in precision, the length frequency distributions based on manual and imaging techniques were similar. The central processing unit time spent by the image analysis program was <0.01 s per shrimp. This indicates the potential for precise, efficient, automatic processing of large numbers of shrimp lengths by, for example, video records of shrimp on a moving transport band.
Modelling stock–recruitment relationships to examine stock management policies
Authors: Kimoto A. , Mouri T. , Matsuishi T.
Published: July 2007

Kimoto, A., Mouri, T., and Matsuishi, T. 2007. Modelling stock–recruitment relationships to examine stock management policies. – ICES Journal of Marine Science, 64: 870–877. Simulation studies are used widely for fish stock management. In such studies, forecasting future recruitment, which can vary greatly between years, has become an essential part of evaluating management strategies. We propose a new forecasting algorithm to predict recruitment for short- or medium-term stochastic projections, using a stock–recruitment relationship. We address cases in which the spawning stock has dropped below previously observed levels, or in which predicted recruitment is situated close to the maximum observed level. The relative prediction error of seven existing algorithms was compared with that of the new model using leave-one-out cross-validation for 61 data sets from ICES, the Japanese Fisheries Agency, and PICES. The new algorithm had the smallest prediction error for 49 of the data sets, but was slightly biased by the precautionary treatment of predictions of high recruitment.
Relationships between fish larvae and siphonophores in the water column: effect of wind-induced turbulence and thermocline depth
Authors: Sanvicente-Añorve L. , Alatorre M. A. , Flores-Coto C. , Alba C.
Published: July 2007

Sanvicente-Añorve, L., Alatorre, M. A., Flores-Coto, C., and Alba, C. 2007. Relationships between fish larvae and siphonophores in the water column: effect of wind-induced turbulence and thermocline depth. – ICES Journal of Marine Science, 64: 878–888. The relationship between the abundance of fish larvae and siphonophores in relation to wind-induced turbulence and thickness of the mixed layer in the southern Gulf of Mexico were studied during two periods of different wind conditions: April (5.25 m s−1) and October (6.5 m s−1). The Spearman correlation between fish larvae and siphonophores revealed a random relationship in the 0–10 m layer during April and in the 0–20 m layer in October. This structure presumably persists while turbulent forces remain at sufficient strength. Positive patterns were observed deeper in the water column. Whereas thermocline position did not correspond with the depth separating random and positive relationships, low turbulence values did. Observations indicate that turbulent kinetic energy values above 4 × 10−4 J kg−1 might promote a random distribution between potential prey and predator zooplankton taxa. In surface waters, contact rates between siphonophores and fish larvae showed that turbulence enhances encounters 2.5 (1.2) times in April and 3.3 (1.3) times in October for prey velocities of 0.003 (0.011) m s−1. The positive relationship between fish larvae and siphonophores could be caused by a high degree of spatial overlap, enough food for both groups, and limited predation on larvae in the presence of alternative prey. Seasonal variability in the vertical structure of distribution patterns was attributed mainly to aggregative feeding behaviour of organisms and disruption of patches as a consequence of small-scale water turbulence.
Vertical distribution of Baltic sprat larvae: changes in patterns of diel migration?
Authors: Voss Rüdiger , Schmidt Jörn O. , Schnack Dietrich
Published: July 2007

Voss, R., Schmidt, J. O., and Schnack, D. 2007. Vertical distribution of Baltic sprat larvae: changes in patterns of diel migration? – ICES Journal of Marine Science, 64: 956–962. Ontogenetic and diurnal vertical migration patterns of Baltic sprat larvae were investigated for the periods 1989–1990 and 1998–2002. Comparison of the results led to the hypothesis that the diel vertical migration behaviour of sprat larvae >10 mm has changed. In 1989 and 1990, sprat larvae migrated to the surface at night, whereas they stayed 30–50 m deep by day. From 1998 to 2002, sprat larvae showed no signs of diel vertical migration, remaining in warmer, near-surface water by day and night. This behavioural change coincided with a more general change in the Baltic ecosystem, i.e. an increase in near-surface temperature and a general increase in abundance of the major prey organism (Acartia spp.) of Baltic sprat larvae, with more pronounced aggregation in surface waters.
Diel variation in the vertical distribution and schooling behaviour of sardine (Sardina pilchardus) off Portugal
Authors: Zwolinski Juan , Morais Alexandre , Marques Vitor , Stratoudakis Yorgos , Fernandes Paul G.
Published: July 2007

Zwolinski, J., Morais, A., Marques, V., Stratoudakis, Y., and Fernandes, P. G. 2007. Diel variation in the vertical distribution and schooling behaviour of sardine (Sardina pilchardus) off Portugal. – ICES Journal of Marine Science, 64: 963–972. Diel patterns in the schooling behaviour and vertical distribution of pelagic fish schools were studied by examining their echotraces from repeated acoustic survey transects at three inshore sites off the Portuguese coast. At two sites, sardine was the dominant pelagic species, and echotrace characteristics of fish schools were similar to those reported in the literature. At the third site, where there was a multispecies pelagic assemblage that included sardine, there was more variability in several of the school descriptors. At all sites, fish schools expanded after sunset, enlarging their cross-sectional area along the horizontal plane and reducing their mean internal acoustic density, while maintaining their overall mean abundance. Downward migration was rapid (within 1 h) after sunset and simultaneous with school expansion. School-like aggregations with total backscattering similar to daytime schools were present throughout the night, although the proportion of small schools and scattered fish appeared to increase at that time. At dawn, sardine rose back up the water column and rapidly reformed into the typical daytime schools. This pattern of diel vertical migration is opposite to that described for most clupeoids worldwide. The implications of this behaviour on abundance estimation by acoustic monitoring surveys for small pelagic fish are discussed.
Detecting sampling outliers and sampling heterogeneity when catch-at-length is estimated using the ratio estimator
Authors: Vigneau Joël , Mahévas Stéphanie
Published: July 2007

Vigneau, J., and Mahévas, S. 2007. Detecting sampling outliers and sampling heterogeneity when catch-at-length is estimated using the ratio estimator. – ICES Journal of Marine Science, 64: 1028–1032. Measuring fish on board fishing vessels or at fish markets to collect data for stock assessment purposes is one of the most straightforward actions carried out by fisheries scientists worldwide. However, such samples are not straightforward to handle and analyse because of their vector-type structure. A generic tool that allows investigation in any multinomial-like sampling scheme is provided, as long as the scheme is built on a ratio estimator, which is the case for most length sampling in the fisheries sector. The use of this tool is discussed using data obtained from two different sampling designs, one consisting of commercial market samples by category and the other on fishing activity or métier. The identification of outliers, misallocated samples, or potential bias as well as the analysis of heterogeneity within and between strata are discussed. The objective of such exploratory analyses is to help sampling coordinators design the best sampling scheme and improve the quality of input data for stock assessment models. The statistics described here are easy to implement and their use is recommended as a necessary stage before any use of sampling data at an international level.
Feeding ecology and abundance of two sympatric skates, the shortfin sand skate Psammobatis normani McEachran, and the smallthorn sand skate P. rudis Günther (Chondrichthyes, Rajidae), in the southwest Atlantic
Authors: Mabragaña Ezequiel , Giberto Diego A.
Published: July 2007

Mabragaña, E., and Giberto, D. A. 2007. Feeding ecology and abundance of two sympatric skates, the shortfin sand skate Psammobatis normani McEachran, and the smallthorn sand skate P. rudis Günther (Chondrichthyes, Rajidae), in the southwest Atlantic. – ICES Journal of Marine Science, 64: 1017–1027. The diet, feeding strategy, and abundance of Psammobatis normani and P. rudis in the southwest Atlantic was investigated to determine whether the species are segregated by habitat or dietary preference. The two coexist along the Argentine continental shelf, but there are differences in abundance. The most important prey for P. normani were crustaceans (mainly crabs and isopods) and, to a lesser extent, polychaetes, whereas P. rudis fed almost exclusively on crustaceans (mainly isopods, crabs, and gammarids), and fish and polychaetes contributed less to the diet. This suggests that P. normani and P. rudis are secondary consumers (trophic level <4). The two species fed on similar taxa, but in slightly different proportions according to region. However, an ANOSIM test failed to reveal significant differences in their diets. Circumstantial evidence of food competition is suggested, because the two species attain similar adult size and there are no notable morphological differences between them. Interspecific competition may be reduced by the use of distinct feeding behaviour and by the abundance of prey especially along shelf-break fronts. The use of standard ecological indices of similarity and multivariate techniques to calculate dietary overlap is evaluated.
Nerve Conduction Blockade in the Sciatic Nerve Prevents but Does Not Reverse the Activation of p38 Mitogen-activated Protein Kinase in Spinal Microglia in the Rat Spared Nerve Injury Model
Authors: Wen Yeong-Ray , Suter Marc R. , Kawasaki Yasuhiko , Huang Jin , Pertin Marie , Kohno Tatsuro , Berde Charles B. , Decosterd Isabelle , Ji Ru-Rong
Published: July 2007

Background

Current evidence indicates that p38 mitogen-activated protein kinase activation in spinal microglia contributes to the development of neuropathic pain. However, how nerve injury activates p38 in spinal microglia is incompletely unknown. Nerve injury-induced ectopic spontaneous activity is essential for the generation of neuropathic pain. The authors examined whether peripheral neural activity is necessary for p38 activation in spinal microglia.

Methods

To examine whether spinal microglia activation depends on peripheral activity in the rat spared nerve injury (SNI) model, the authors blocked conduction in the sciatic nerve before or 2 days after SNI. The block was produced by applying bupivacaine-loaded microspheres above the nerve injury site. The p38 activation was examined by p38 phosphorylation using a phosphorylated p38 antibody, and neuropathic pain-related behavior was evaluated before and after intrathecal infusion of a p38 inhibitor.

Results

Three days after SNI, there was a marked p38 activation in the medial two thirds of the dorsal horn, where the injured tibial and peroneal nerves terminated and where isolectin B4 staining was lost. Phosphorylated p38 was only colocalized with the microglial surface marker OX-42, indicating a microglial localization of phosphorylated p38 in the SNI model. Bupivacaine microspheres produced persistent block (loss of sensory and motor function) of the sciatic nerve for the whole period of the study (3 days). This blockade prevented but did not reverse p38 activation in spinal microglia. Intrathecal infusion of the p38 inhibitor FR167653 prevented and reversed mechanical allodynia on post-SNI day 3.

Conclusions

After nerve injury, activity in the peripheral nerve is required for the induction but not the maintenance of p38 activation in spinal microglia.
Assessment of the Accuracy of Procalcitonin to Diagnose Postoperative Infection after Cardiac Surgery
Authors: Jebali Mohamed Adel , Hausfater Pierre , Abbes Zoubeir , Aouni Zied , Riou Bruno , Ferjani Mustapha
Published: July 2007

Background

Cardiopulmonary bypass induces a nonspecific inflammatory response. Procalcitonin has been advocated as a specific biomarker for infection. The authors studied the accuracy of procalcitonin to diagnose postoperative infection after cardiac surgery and compared it with those of C-reactive protein, white blood cell count, and interleukins 6 and 8.

Methods

The authors prospectively included 100 patients scheduled to undergo elective cardiac procedures with cardiopulmonary bypass. Blood samples were taken before surgery and each day over the 7-day postoperative period, and measurement of procalcitonin, C-reactive protein, white blood cell count, and interleukins 6 and 8 were performed. Diagnosis of infection was performed by a blinded expert panel. Data are expressed as value [95% confidence interval].

Results

Infection was diagnosed in 16 patients. Procalcitonin was significantly higher in infected patients, with a peak reached on the third postoperative day. Only the areas under the receiver operating curve of procalcitonin (0.88 [0.71-0.95]) and C-reactive protein (0.72 [0.58-0.82]) were significantly different from the no-discrimination curve, and that of procalcitonin was significantly different from those of C-reactive protein, white blood cell count, and interleukins 6 and 8. A procalcitonin value greater than 1.5 ng/ml beyond the second day diagnosed postoperative infection with a sensitivity of 0.93 [0.70-0.99] and a specificity of 0.80 [0.70-0.87]. Procalcitonin was significantly higher in patients who died (27.5 [1.65-40.5] vs. 1.2 [0.7-1.5] ng/ml; P < 0.001).

Conclusion

Procalcitonin is a valuable marker of bacterial infections after cardiac surgery.
Cytotoxin-associated gene-A bearing strains of Helicobacter pylori and atrial fibrillation due to ischemic origin: is there a link?
Authors: Badran Hala Mahfouz , Mahfouz Magdi Elsayed
Published: July 2007

Background Helicobacter pylori CagA

strains could increase the risk for atrial fibrillation in patients with coronary artery disease

Methods

Serological status for H. pylori CagA using enzyme-linked immunosorbent assay, C-reactive protein, total leucocytic count and atrial size were determined in 185 coronary artery disease patients (with and without atrial fibrillation) and 80 healthy subjects (control).

Results CagA

strain showed a higher prevalence in the atrial fibrillation group. Atrial dimension and C-reactive protein (independent predictors of atrial fibrillation) were significantly increased in the CagA seropositive subgroup Conclus ons There is a strong liaison between H. pylori CagA infection and atrial fibrillation in coronary artery disease. Increased C reactive protein and atrial size in atrial fibrillation patients may reflect atrial inflammatory remodeling.