bluuebunny/crossref_metadata_2025 huggingface dataset:
Formation and reactivation of the Cambrian Kanmantoo Trough, SE Australia: implications for early Palaeozoic tectonics at eastern Gondwana’s plate margin
Authors: FLÖTTMANN T. , HAINES P. , JAGO J. , JAMES P. , BELPERIO A. , GUM J.
Published: December 2007

The Kanmantoo Group is a thick and largely metamorphosed sedimentary succession that filled an isolated arcuate Cambrian basin (Kanmantoo Trough) which formed within continental Gondwana, and now lies on the southern margin of the present Australian continent. Kanmantoo Group sediments unconformably overlie Neoproterozoic and older Cambrian rocks. We consider that the geometry of the southern part of this trough was influenced by strike-slip movement along an intra-continental tear fault. To the north, the basin changes to a style dominated by orthogonal extension and eventually tapers and dies out normal to the tear fault. Balanced sections show that the kinematic style and strain distribution developed during early Palaeozoic inversion was controlled by the specific architecture of the Kanmantoo Trough. Early Palaeozoic tear faulting could have linked contrasting subduction polarities along the then contiguous palaeo-Pacific margin of Gondwana. The Kanmantoo Trough is considered to have formed at a passive margin related to east-directed subduction in what is now the Australian continent. In contrast, west-directed subduction formed an active margin at contiguous parts of current Antarctica. Kanmantoo Group sediments were derived from the south by erosion of a Grenvillean province mixed with sediments eroded from the emergent active margin of Gondwana. The inception, localization and sedimentation in the Kanmantoo Trough reflects a complex interaction of tectonic processes along the encroaching Ross–Delamerian Orogen.
Addiction and the Brain Antireward System
Authors: Koob George F. , Le Moal Michel
Published: December 2007

A neurobiological model of the brain emotional systems has been proposed to explain the persistent changes in motivation that are associated with vulnerability to relapse in addiction, and this model may generalize to other psychopathology associated with dysregulated motivational systems. In this framework, addiction is conceptualized as a cycle of decreased function of brain reward systems and recruitment of antireward systems that progressively worsen, resulting in the compulsive use of drugs. Counteradaptive processes, such as opponent process, that are part of the normal homeostatic limitation of reward function fail to return within the normal homeostatic range and are hypothesized to repeatedly drive the allostatic state. Excessive drug taking thus results in not only the short-term amelioration of the reward deficit but also suppression of the antireward system. However, in the long term, there is worsening of the underlying neurochemical dysregulations that ultimately form an allostatic state (decreased dopamine and opioid peptide function, increased corticotropin-releasing factor activity). This allostatic state is hypothesized to be reflected in a chronic deviation of reward set point that is fueled not only by dysregulation of reward circuits per se but also by recruitment of brain and hormonal stress responses. Vulnerability to addiction may involve genetic comorbidity and developmental factors at the molecular, cellular, or neurocircuitry levels that sensitize the brain antireward systems.
Targeting of the molecular chaperone oxygen-regulated protein 150 (ORP150) to mitochondria and its induction by cellular stress
Authors: Arrington David D. , Schnellmann Rick G.
Published: December 2007

Oxygen-regulated protein 150 (ORP150) is an inducible endoplasmic reticulum (ER) chaperone molecule that is upregulated after numerous cellular insults and has a cytoprotective role in renal, neural, and cardiac models of ischemia-reperfusion injury. ORP150 also has been shown to play a role in cellular Ca2+homeostasis, and in turn, regulating calpain activity. In this study, we identified ORP150 in whole rat renal cortical mitochondria and matrix fractions, demonstrated the targeting of an ORP150-GFP construct to the mitochondria of NIH-3T3 cells, and showed that the NH2-terminal 13 amino acids of ORP150 are sufficient for this translocation. ORP150 expression was found to be regulated by the anti-C/enhancer-binding protein homologous protein (CHOP)/GADD153 transcription factor and ORP150 levels increased in the mitochondria and ER of COS-7 cells after diverse stresses, including hypoxia, serum starvation, prolyl hydroxylase inhibition with dimethyloxaloylglycine, and exposure to tunicamycin, ethidium, bromide, and 2-deoxyglucose. Induction of the mitochondrial specific stress response in COS-7 cells through expression of an ornithine transcarbamylase mutant (ΔOTC) increased mitochondrial ORP150 levels and mitochondrial calpain activity. To determine whether mitochondrial ORP150 and mitochondrial calpain 10 interact, rat cortical mitochondria exposed to Ca2+resulted in ORP150 cleavage in a calpain inhibitor-dependent manner, revealing that ORP150 is a substrate and may be regulated by calpain 10. These data reveal a novel cellular localization for ORP150 and that mitochondrial ORP150 is upregulated by CHOP/GADD153 in response to mitochondrial and ER stress. Our data also reveal that ORP150 is a substrate for mitochondrial calpain 10.
Food deprivation-induced changes in body fat mobilization after neonatal monosodium glutamate treatment
Authors: Leitner Claudia , Bartness Timothy J.
Published: December 2007

The reversal of obesity is a difficult feat at best and is a growing problem as the obesity epidemic increases worldwide. Considerable focus has been made on the arcuate nucleus (Arc) in the control of body and lipid mass and food intake. To test the role of the Arc in body fat mobilization, we compared the effects of food deprivation on white adipose tissue (WAT) mass in adult Siberian hamsters by making exocytotic lesions of the Arc via neonatal subcutaneous injections of monosodium glutamate (MSG). MSG-treated hamsters had significantly increased body mass, total and individual WAT pad masses, and serum leptin concentrations compared with their vehicle-injected counterparts. MSG produced marked reductions in Arc Nissl staining, tyrosine hydroxylase-immunoreactive (ir) neurons, and neuropeptide Y (NPY)- and agouti-related protein (AgRP)-ir fibers compared with controls. MSG significantly decreased hypothalamic paraventricular nucleus (PVN) NPY- and AgRP fiber-ir compared with controls, likely because of Arc projections to this nucleus. MSG treatment also reduced area postrema (AP) tyrosine hydroxylase (TH)-ir fibers compared with controls. MSG treatment did not, however, block food deprivation-induced decreases in WAT pad mass compared with controls. Thus, despite considerable damage to the Arc and some of its projections to the PVN, as well as the AP, body fat was mobilized apparently normally, bringing into question the necessity of these structures for food deprivation-induced lipid mobilization. These data support recent evidence that chronically decerebrate rats, in which the forebrain is surgically isolated from the caudal brainstem, show normal food deprivation responses, including lipid mobilization.
Adult Nasolacrimal Sac Mucocele
Authors: Xiao M.Y. , Tang L.S. , Zhu H. , Li Y.J. , Li H.L. , Wu X.R.
Published: December 2007

Adult nasolacrimal sac mucocele is an uncommon mass arising in the medial canthal region of the orbit. Twenty-one cases with lacrimal sac mucocele were reviewed retrospectively. We gathered information about the clinical characteristics, natural history, mechanism for mucocele formation and optimal management of this disorder. The results show that the medial canthal mass was confirmed to be dacryocystocele-associated with distal nasolacrimal duct obstruction and proximal obstruction at the junction of the common canaliculus and sac. The interventional procedure of polyurethane stent placement is a practicable and simplified treatment for lacrimal sac mucocele.
N-Terminal-pro-B Type Natriuretic Peptide as a Useful Tool to Evaluate Pulmonary Hypertension and Cardiac Function in CDH Infants
Authors: Baptista Maria J. , Rocha Gustavo , Clemente Fátima , Azevedo Luís F. , Tibboel Dick , Leite-Moreira Adelino F. , Guimarães Hercília , Areias José C. , Correia-Pinto Jorge
Published: December 2007

Objective: In congenital diaphragmatic hernia (CDH) the severity of pulmonary hypertension (PH) is considered, by several authors, determinant of clinical outcome. Plasmatic N-terminal-pro-B type natriuretic peptide (NT-proBNP) might be useful in diagnosis and management of PH in newborns, although its interest in CDH infants remains to be defined. Early NT-proBNP levels were assessed in CDH infants and correlated with cardiovascular echocardiographic parameters. Patients and Methods: 28 newborns, CDH and age-matched controls were enrolled in a prospective study. Clinical condition, NT-proBNP plasmatic levels, echo parameters of PH and biventricular function were assessed at 24 h after delivery as well as survival outcome. Results: Estimated mean pulmonary pressure and NT-proBNP were significantly higher in CDH than control infants. NT-proBNP significantly correlated with estimated pulmonary artery pressure, right ventricular Tei index, and tricuspid E/A ratio. Additionally, we found that CDH infants with NT-proBNP >11,500 pg/ml experienced a worse prognosis. Conclusions: We demonstrated that PH is associated with NT-proBNP elevation and diastolic impairment in CDH infants. Early elevations in NT-proBNP levels seem to alert for a subset of CDH infants with worse prognosis.
Impact and Management of Skin Toxicity Associated with Anti-Epidermal Growth Factor Receptor Therapy: Survey Results
Authors: Boone Susan L. , Rademaker Alfred , Liu Dachao , Pfeiffer Carmen , Mauro David J. , Lacouture Mario E.
Published: December 2007

Biologic agents targeting the epidermal growth factor receptor (EGFR) have emerged as a robust treatment option for various solid tumors. Despite lower systemic side effects than conventional chemotherapy, the majority of patients treated with these agents experience cutaneous toxicities, including papulopustular rashes, hair and nail changes, xerosis and pruritus, which have a significant impact on health and quality of life. Currently no consensus or management guidelines exist for these untoward events. Therefore, a retrospective survey was carried out across 110 oncology practioners in the US that were administering EGFR inhibitors. Providers were queried on the impact and management of these untoward events in their practices. Responses suggest that combination therapies (topical and oral) were more effective than either therapy alone, and also lead to a more rapid resolution of the papulopustular rash. Providers also reported that patients frequently complained of physical symptoms associated with the rash (itching and pain), and that they had a positive perception when being treated for their cutaneous side effects. The survey results support that attentive cutaneous care is important in patients treated with EGFR inhibitors, and that proactive/combined interventions may enhance quality of life and optimize consistent drug administration.
`It's like Maintaining a Hedge'
Authors: Blakeley Georgina , Evans Brendan
Published: December 2007

Since participation at the local level is frequently urged as a solution to political disengagement (Stoker, 2006), it is important to acknowledge the structural obstacles to the ready imposition of the participatory project. This article argues that this focus upon popular democratic participation in urban affairs neglects the realities of political and social life, particularly for poorer areas of cities, and the structural constraints that greatly limit the opportunities for residents to engage actively within their community. From this perspective, the miracle is how much participation occurs rather than how little.
Histories of Violent Victimization Among Women Who Reported Unwanted Sex in Marriages and Intimate Relationships
Authors: Basile Kathleen C.
Published: December 2007

This article summarizes results of semistructured telephone interviews with 41 women about experiences with various forms of violent victimization. Women who reported an incident or incidents of unwanted sex in their intimate partner relationships were recruited from a national telephone poll and interviewed about other types of victimization, such as childhood maltreatment, unwanted sex by a date or acquaintance, and nonsexual violence by a husband or partner. Results suggest that women who report unwanted sex by a husband or partner have commonly experienced various other forms of abuse in their lives. The author discusses implications of the findings for prevention of unwanted sex in intimate relationships.
The Role of School Principals in Enhancing Teacher Professionalism
Authors: Rizvi Meher
Published: December 2007

Following the initiation of educational reforms, this article reports on the different models of leadership that have emerged as being important for developing teacher professionalism in government primary schools in Karachi, Pakistan. The evidence from the case studies, reported in this article, illustrates that even within formalized government primary school structures, such as those in Pakistan, principals can make a shift from traditional leadership styles to more contemporary approaches designed to enhance teacher professionalism. The first section of the article presents the literature review and the background analysis. In the second part, information about the research project and the development of the four cases is provided. The third section utilizes the findings from the four case studies to discuss the central roles played by the school principals in enhancing teacher professionalism and the key leadership models that have emerged as important as a result of performing these roles. Finally, the article argues that the principals require training for high quality leadership in similar types of schools in Karachi.
Organizational Communication and Job Satisfaction in Australian Catholic Primary Schools
Authors: De Nobile John J. , McCormick John
Published: December 2007

Job satisfaction has been associated with a variety of behaviours relating to communication. However, very little research has been conducted in primary schools encompassing job satisfaction and a range of communication variables. This study investigated the relationships between aspects of organizational communication and facets of job satisfaction. The participants were 356 staff members from 52 primary schools of six Catholic education systems in New South Wales, Australia. The participants completed a survey consisting of the Organizational Communication in Primary Schools Questionnaire and the Teacher Job Satisfaction Questionnaire (TJSQ). Ten organizational communication factors and nine job satisfaction factors were identified. Multiple regression analyses identified several organizational communication factors that were predictors of job satisfaction. The results suggest implications for policy and practice with regard to communication in these schools.
High frequency of CD4+FoxP3+ cells in HTLV-1 infection: inverse correlation with HTLV-1–specific CTL response
Authors: Toulza Frederic , Heaps Adrian , Tanaka Yuetsu , Taylor Graham P. , Bangham Charles R. M.
Published: December 2007

Evidence from population genetics, gene expression microarrays, and assays of ex vivo T-cell function indicates that the cytotoxic T lymphocyte (CTL) response to human T-lymphotropic virus type 1 (HTLV-1) controls the level of HTLV-1 expression and the proviral load. The rate at which CTLs kill autologous HTLV-1–infected lymphocytes differs significantly among infected people, but the reasons for such variation are unknown. Here, we demonstrate a strong negative cor-relation between the frequency of CD4+FoxP3+ Tax− regulatory T cells (Tregs) in the circulation and the rate of CTL-mediated lysis of autologous HTLV-1–infected cells ex vivo. We propose that the frequency of CD4+FoxP3+ Tax− Tregs is one of the chief determinants of the efficiency of T cell–mediated immune control of HTLV-1.
Sequencing analysis of 20,000 full-length cDNA clones from cassava reveals lineage specific expansions in gene families related to stress response
Authors: Sakurai Tetsuya , Plata Germán , Rodríguez-Zapata Fausto , Seki Motoaki , Salcedo Andrés , Toyoda Atsushi , Ishiwata Atsushi , Tohme Joe , Sakaki Yoshiyuki , Shinozaki Kazuo , Ishitani Manabu
Published: December 2007

Background

Cassava, an allotetraploid known for its remarkable tolerance to abiotic stresses is an important source of energy for humans and animals and a raw material for many industrial processes. A full-length cDNA library of cassava plants under normal, heat, drought, aluminum and post harvest physiological deterioration conditions was built; 19968 clones were sequence-characterized using expressed sequence tags (ESTs).

Results

The ESTs were assembled into 6355 contigs and 9026 singletons that were further grouped into 10577 scaffolds; we found 4621 new cassava sequences and 1521 sequences with no significant similarity to plant protein databases. Transcripts of 7796 distinct genes were captured and we were able to assign a functional classification to 78% of them while finding more than half of the enzymes annotated in metabolic pathways in Arabidopsis. The annotation of sequences that were not paired to transcripts of other species included many stress-related functional categories showing that our library is enriched with stress-induced genes. Finally, we detected 230 putative gene duplications that include key enzymes in reactive oxygen species signaling pathways and could play a role in cassava stress response features.

Conclusion

The cassava full-length cDNA library here presented contains transcripts of genes involved in stress response as well as genes important for different areas of cassava research. This library will be an important resource for gene discovery, characterization and cloning; in the near future it will aid the annotation of the cassava genome.
Reconciling the Roles of Orbitofrontal Cortex in Reversal Learning and the Encoding of Outcome Expectancies
Authors: SCHOENBAUM GEOFFREY , SADDORIS MICHAEL P. , STALNAKER THOMAS A.
Published: December 2007

Abstract:Damage to orbitofrontal cortex (OFC) has long been associated with decision‐making deficits. Such deficits are epitomized by impairments in reversal learning. Historically, reversal learning deficits have been linked to a response inhibition function or to the rapid reversal of associative encoding in OFC neurons. However here we will suggest that OFC supports reversal learning not because its encoding is particularly flexible—indeed it actually is not—but rather because output from OFC is critical for flexible associative encoding downstream in basolateral amygdala (ABL). Consistent with this argument, we will show that reversal performance is actually inversely related to the flexibility of associative encoding in OFC (i.e., the better the reversal performance, the less flexible the encoding). Further, we will demonstrate that associative correlates in ABL are more flexible during reversal learning than in OFC, become less flexible after damage to OFC, and are required for the expression of the reversal deficit caused by OFC lesions. We will propose that OFC facilitates associative flexibility in downstream regions, such as ABL, for the same reason that it is critical for outcome‐guided behavior in a variety of setting—namely that processing in OFC signals the value of expected outcomes. In addition to their role in guiding behavior, these outcome expectancies permit the rapid recognition of unexpected outcomes, thereby driving new learning.
Neuronal Mechanisms in Prefrontal Cortex Underlying Adaptive Choice Behavior
Authors: WALLIS JONATHAN D.
Published: December 2007

Abstract: This chapter aims to address two questions relating to the role of the prefrontal cortex (PFC) in reward‐guided choice behavior. First, do PFC neurons encode rewards per se, or are they encoding behavioral sequelae of reward? To address this, we recorded simultaneously from multiple PFC subregions, with the rationale that neuronal selectivity that directly encoded the reward outcome should occur before selectivity that reflected reward‐related sequelae. Our results indicate that neurons in the orbitofrontal cortex (OFC) encode reward information before neurons in the dorsolateral PFC (DLPFC). Furthermore, whereas DLPFC neurons encoded both the upcoming response as well as the expected reward, OFC neurons encoded the reward alone. Our interpretation of these results is that the OFC encodes the reward and passes this information to the DLPFC, which uses it to determine the behavioral response. The second question is whether the encoding is specific to the reward outcome or reflective of a more abstract value signal that could facilitate decision making. We examined this by determining whether the PFC encodes other types of information relevant to decision making, such as probability of success and effort. We found that many PFC neurons encoded at least one of these variables, but neurons in the OFC and the medial PFC (MPFC) encoded combinations of the variables indicative of encoding an abstract value signal. This signal could provide decision making with flexibility and a capacity to deal with novelty, which are two of the hallmark features of prefrontal function. Future research will focus on delineating the differential contributions of the OFC and the MPFC to decision making.
What Can an Orbitofrontal Cortex‐Endowed Animal Do with Smells?
Authors: GOTTFRIED JAY A.
Published: December 2007

Abstract: It is widely presumed that odor quality is a direct outcome of odorant molecular structure, but increasing evidence suggests that learning, experience, and context play important roles in human olfactory perception. Such data suggest that a given set of olfactory receptors activated by an odorant does not map directly onto a given odor percept. Rather, odor perception may rely on more synthetic, or integrative, mechanisms subserved by higher‐order brain regions. Results presented here explore the specific role of human orbitofrontal cortex (OFC) in the formation and modulation of odor quality coding. Combining olfactory psychophysical techniques and functional imaging approaches, we have found that sensory‐specific information about an odorant is not static or fixed within human olfactory OFC, but is highly malleable and can be rapidly updated by perceptual experience. Critically, the magnitude of OFC activation predicts subsequent behavioral improvement in olfactory perception. Our findings highlight the pivotal role of OFC in linking olfactory sensation, perception, and experience. It is worth considering that many of the current proposed functions attributed to the (distinctively mammalian) OFC are an extension of mechanisms that originally evolved to mediate response flexibility between chemosensory signals and appropriate behavioral actions.
The Orbitofrontal Cortex, Impulsivity, and Addiction
Authors: WINSTANLEY CATHARINE A.
Published: December 2007

Abstract:  The association between impulsivity and addiction is currently a topic of intense research interest. Investigations into the neurobiological basis of aspects of impulse control have revealed some striking parallels between the brain circuitry and neurochemical systems implicated in drug dependence and impulsive behavior. Both processes are heavily regulated by limbic corticostriatal circuits including the orbitofrontal cortex (OFC) and nucleus accumbens (NAC), and are modulated by dopamine (DA) and serotonin (5‐HT). Hypoactivity within the OFC has been observed in recently abstinent cocaine users, and this is thought to contribute to the cognitive deficits associated with drug abuse, including impairments in impulse control. However, the neurobiological mechanisms underlying these functional and behavioral deficits are unclear. In parallel to observations made in the NAC, recent data indicate that chronic cocaine use also induces the transcription factor ΔFosB in the OFC and that this plays a role in the cognitive sequelae of chronic cocaine administration. In particular, ΔFosB appears to be involved in the development of tolerance to the disruptive effects of acute cocaine on impulsivity and motivation observed after repeated cocaine administration. Increased ΔFosB also contributes to increased impulsivity during withdrawal from the drug. Both effects could be attributed to the up‐regulation of local inhibitory processes in the OFC after over‐expression of ΔFosB and chronic cocaine treatment. Through integrating what is known of the interaction between addictive drugs and impulsivity at the neural, neurochemical, and molecular level, novel insight may be obtained into the multi‐faceted regulation of the addicted state.
Role of Orbitofrontal Cortex Connections in Emotion
Authors: REMPEL‐CLOWER NANCY L.
Published: December 2007

Abstract: The orbitofrontal cortex is extensively connected with diverse neural areas that underlie its participation in emotional function. It receives extensive sensory input and sends output to areas important for emotional processing and expression, including medial temporal cortical areas, hypothalamic and brain stem autonomic areas, and the amygdala. In the rat, the functional relationship between the orbitofrontal cortex and amygdala has been investigated in numerous recent studies. Clearer understanding of the complex connections between the rat orbitofrontal cortex and the amygdala is fundamental to elucidating the functional contributions of these pathways. Recent work shows that, as in the primate, the subdivisions of the rat orbitofrontal cortex issue different patterns of projections to the amygdala, with intriguing variations in the relative distribution of projections to the sensory‐related basal areas compared with output areas, such as the central nucleus. Notably, as has been observed in the monkey, the rat orbitofrontal cortex targets the intercalated nuclei, which contain GABAergic interneurons and provide local inhibitory influences within the amygdala. The complex connections between the orbitofrontal cortex and the amygdala, as well as other areas involved in emotion, suggest important implications for the role of the orbitofrontal cortex in anxiety disorders, in which emotional expression is not appropriate to the situation.
AML1-ETO reprograms hematopoietic cell fate by downregulatingsclexpression
Authors: Yeh Jing-Ruey J. , Munson Kathleen M. , Chao Yvonne L. , Peterson Quinn P. , MacRae Calum A. , Peterson Randall T.
Published: December 2007

AML1-ETO is one of the most common chromosomal translocation products associated with acute myelogenous leukemia (AML). Patients carrying the AML1-ETO fusion gene exhibit an accumulation of granulocyte precursors in the bone marrow and the blood. Here, we describe a transgenic zebrafish line that enables inducible expression of the human AML1-ETO oncogene. Induced AML1-ETO expression in embryonic zebrafish causes a phenotype that recapitulates some aspects of human AML. Using this highly tractable model, we show that AML1-ETO redirects myeloerythroid progenitor cells that are developmentally programmed to adopt the erythroid cell fate into the granulocytic cell fate. This fate change is characterized by a loss of gata1 expression and an increase in pu.1expression in myeloerythroid progenitor cells. Moreover, we identify scl as an early and essential mediator of the effect of AML1-ETO on hematopoietic cell fate. AML1-ETO quickly shuts off scl expression,and restoration of scl expression rescues the effects of AML1-ETO on myeloerythroid progenitor cell fate. These results demonstrate that scl is an important mediator of the ability of AML1-ETO to reprogram hematopoietic cell fate decisions, suggesting that scl may be an important contributor to AML1-ETO-associated leukemia. In addition, treatment of AML1-ETO transgenic zebrafish embryos with a histone deacetylase inhibitor,Trichostatin A, restores scl and gata1 expression, and ameliorates the accumulation of granulocytic cells caused by AML1-ETO. Thus,this zebrafish model facilitates in vivo dissection of AML1-ETO-mediated signaling, and will enable large-scale chemical screens to identify suppressors of the in vivo effects of AML1-ETO.
Phosphorylation of vascular endothelial cadherin controls lymphocyte emigration
Authors: Turowski Patric , Martinelli Roberta , Crawford Rebecca , Wateridge David , Papageorgiou Anna-Pia , Lampugnani Maria Grazia , Gamp Alexander C. , Vestweber Dietmar , Adamson Peter , Dejana Elisabetta , Greenwood John
Published: December 2007

Lymphocytes emigrate from the circulation to target tissues through the microvascular endothelial cell (EC) barrier. During paracellular transmigration cell-cell junctions have been proposed to disengage and provide homophilic and heterophilic interaction surfaces in a zip-like process. However, it is not known whether ECs modulate junction proteins during this process. Here we show that tyrosine phosphorylation of adherens junction vascular endothelial cadherin (VEC) is required for successful transendothelial lymphocyte migration. We found that adhesion of lymphocytes or activation of the endothelial intercellular adhesion molecule 1 (ICAM1) led to tyrosine phosphorylation of VEC. Substitution of tyrosine for phenylalanine in VEC at positions 645, 731 or 733 produced ECs that were significantly less permissive to lymphocyte migration. We also found that these same tyrosine residues are involved in ICAM1-dependent changes of VEC phosphorylation. ICAM1 activation enhanced transendothelial permeability, suggesting the occurrence of junction disassembly. In agreement, the expression of VEC mutated at Y645F, Y731F or Y733F predominantly affected lymphocyte transmigration in paracellular areas. Taken together, these results demonstrate that phosphorylation of adherens junctions constitutes a molecular endpoint of lymphocyte-induced vascular EC signaling and may be exploited as a new target of anti-inflammatory therapies.
A genome-wide approach identifies distinct but overlapping subsets of cellular mRNAs associated with Staufen1- and Staufen2-containing ribonucleoprotein complexes
Authors: Furic Luc , Maher-Laporte Marjolaine , DesGroseillers Luc
Published: December 2007

Messenger RNAs are associated with multiple RNA-binding proteins to form ribonucleoprotein (mRNP) complexes. These proteins are important regulators of the fate of their target mRNAs. In human cells, Staufen1 and Staufen2 proteins, coded by two different genes, are double-stranded RNA-binding proteins involved in several cellular functions including mRNA localization, translation, and decay. Although 51% identical, these proteins are nevertheless found in different RNA particles. In addition, differential splicing events generate Staufen2 isoforms that only differ at their N-terminal extremities. In this paper, we used a genome-wide approach to identify and compare the mRNA targets of mammalian Staufen proteins. The mRNA content of Staufen mRNPs was identified by probing DNA microarrays with probes derived from mRNAs isolated from immunopurified Staufen-containing complexes following transfection of HEK293T cells with Stau155-HA, Stau259-HA, or Stau262-HA expressors. Our results indicate that 7% and 11% of the cellular RNAs expressed in HEK293T cells are found in Stau1- and in Stau2-containing mRNPs, respectively. A comparison of Stau1- and Stau2-containing mRNAs identifies a relatively low percentage of common mRNAs; the percentage of common mRNAs highly increases when mRNAs in Stau259-HA- and Stau262-containing mRNPs are compared. There is a predominance of mRNAs involved in cell metabolism, transport, transcription, regulation of cell processes, and catalytic activity. All these subsets of mRNAs are mostly distinct from those associated with FMRP or IMP, although some mRNAs overlap. Consistent with a model of post-transcriptionnal gene regulation, our results show that Stau1- and Stau2-mRNPs associate with distinct but overlapping sets of cellular mRNAs.
A-to-I editing sites are a genomically encoded G: Implications for the evolutionary significance and identification of novel editing sites
Authors: Tian Nan , Wu Xiaojie , Zhang Yaozhou , Jin Yongfeng
Published: December 2007

Ribonucleic acid (RNA) editing can extend transcriptomic and proteomic diversity by changing the identity of a particular codon. Genetic recoding as a result of adenosine-to-inosine (A-to-I) RNA editing can alter highly conserved or invariant coding positions in proteins. Interestingly, examples exist in which A-to-I editing sites in one species are fixed genomically as a G in a closely related species. Phylogenetic analysis indicates that G-to-A mutations at the DNA level may be corrected by post-transcriptional A-to-I RNA editing, while in turn, the edited I (G) may be hardwired into the genome, resulting in an A-to-G mutation. We propose a model in which nuclear A-to-I RNA editing acts as an evolutionary intermediate of genetic variation. We not only provide information on the mechanism behind the evolutionary acquisition of an A-to-I RNA editing site but also demonstrate how to predict nuclear A-to-I editing sites by identifying positions where an RNA editing event would maintain the conservation of a protein relative to its homologs in other species. We identified a novel edited site in the fourth exon of the cacophony transcript coding calcium channel α1 and verified it experimentally.
Puf1p acts in combination with other yeast Puf proteins to control mRNA stability
Authors: Ulbricht Randi J. , Olivas Wendy M.
Published: December 2007

The eukaryotic Puf proteins bind 3′ untranslated region (UTR) sequence elements to regulate the stability and translation of their target transcripts, and such regulatory events are critical for cell growth and development. Several global genome analyses have identified hundreds of potential mRNA targets of theSaccharomyces cerevisiaePuf proteins; however, only three mRNA targets for these proteins have been characterized thus far. After direct testing of nearly 40 candidate mRNAs, we established two of these as true mRNA targets of Puf-mediated decay in yeast,HXK1andTIF1. In a novel finding, multiple Puf proteins, including Puf1p, regulate both of these mRNAs in combination.TIF1mRNA decay can be stimulated individually by Puf1p and Puf5p, but the combination of both proteins is required for full regulation. This Puf-mediated decay requires the presence of two UGUA binding sites within theTIF13′ UTR, with one site regulated by Puf5p and the other by both Puf1p and Puf5p. Alteration of the UGUA site in thetif13′ UTR to more closely resemble the Puf3p binding site broadens the specificity to include regulation by Puf3p. The stability of the endogenously transcribedHXK1mRNA, cellular levels of Hxk1 protein activity, andHXK13′ UTR-directed decay are affected by Puf1p and Puf5p as well as Puf4p. Together these results identify the first mRNA targets of Puf1p-mediated decay, describe similar yet distinct combinatorial control of two new target mRNAs by the yeast Puf proteins, and suggest the importance of direct testing to evaluate RNA-regulatory mechanisms.
An intact unfolded protein response in Trpt1 knockout mice reveals phylogenic divergence in pathways for RNA ligation
Authors: Harding Heather P. , Lackey Jeremy G. , Hsu Hao-Chi , Zhang Yuhong , Deng Jing , Xu Rui-Ming , Damha Masad J. , Ron David
Published: December 2007

Unconventional mRNA splicing by an endoplasmic reticulum stress-inducible endoribonuclease, IRE1, is conserved in all known eukaryotes. It controls the expression of a transcription factor, Hac1p/XBP-1, that regulates gene expression in the unfolded protein response. In yeast, the RNA fragments generated by Ire1p are ligated by tRNA ligase (Trl1p) in a process that leaves a 2′-PO42− at the splice junction, which is subsequently removed by an essential 2′-phosphotransferase, Tpt1p. However, animals, unlike yeast, have two RNA ligation/repair pathways that could potentially rejoin the cleaved Xbp-1 mRNA fragments. We report that inactivation of the Trpt1 gene, encoding the only known mammalian homolog of Tpt1p, eliminates all detectable 2′-phosphotransferase activity from cultured mouse cells but has no measurable effect on spliced Xbp-1 translation. Furthermore, the relative translation rates of tyrosine-rich proteins is unaffected by the Trpt1 genotype, suggesting that the pool of (normally spliced) tRNATyr is fully functional in the Trpt1−/− mouse cells. These observations argue against the presence of a 2′-PO42− at the splice junction of ligated RNA molecules in Trpt1−/− cells, and suggest that Xbp-1 and tRNA ligation proceed by distinct pathways in yeast and mammals.
A Robust Optimization Perspective on Stochastic Programming
Authors: Chen Xin , Sim Melvyn , Sun Peng
Published: December 2007

In this paper, we introduce an approach for constructing uncertainty sets for robust optimization using new deviation measures for random variables termed the forward and backward deviations. These deviation measures capture distributional asymmetry and lead to better approximations of chance constraints. Using a linear decision rule, we also propose a tractable approximation approach for solving a class of multistage chance-constrained stochastic linear optimization problems. An attractive feature of the framework is that we convert the original model into a second-order cone program, which is computationally tractable both in theory and in practice. We demonstrate the framework through an application of a project management problem with uncertain activity completion time.
Sipuleucel-T: A Vaccine for Metastatic, Asymptomatic, Androgen-Independent Prostate Cancer
Authors: Patel Punam H , Kockler Denise R
Published: December 2007

Objective:

To review the design, efficacy, safety, dosing, therapeutic, and pharmacoeconomic considerations of sipuleucel-T, an investigational, autologous, dendritic, cell-based prostate cancer vaccine.

Data Sources:

English-language literature searches of MEDLINE (1966–September 2007) and the Cochrane Database (2007, Issue 3) were performed using the terms sipuleucel-T, APC8015, and prostate cancer vaccine. Other data sources were identified from bibliographies of selected articles and from press releases.

Study Selection and Data Extraction:

All published articles or abstracts on human studies of sipuleucel-T for androgen-independent prostate cancer (AIPC) were reviewed for inclusion. Manufacturer Web sites, Food and Drug Administration (FDA) documents, and the clinical trials registry were used to obtain information regarding ongoing clinical trials.

Data Synthesis:

AIPC is an incurable disease with a median survival rate of 18–20 months. Docetaxel-based chemotherapy is currently the only FDA-approved treatment for AIPC with a survival benefit (2.4 mo). Sipuleucel-T is a novel active cellular immunotherapy under investigation for the treatment of metastatic, asymptomatic AIPC. In clinical trials, the primary endpoint of time to disease progression was not met; however, an underpowered analysts of data suggests that sipuleucel-T prolongs survival by a median of 4.5 months compared with placebo. Sipuleucel-T has been relatively well tolerated, although a possible increased risk of cerebrovascular events may exist. In May 2007, the FDA did not approve the biologics license application for sipuleucel-T since the primary endpoint of the Phase 3 trials was not met. However, its approval will be reconsidered by the FDA once interim survival results from an ongoing Phase 3 trial, IMPACT, are determined. These data are anticipated to be released in the fourth quarter of 2008.

Conclusions:

Metastatic AIPC Is an incurable disease that currently has limited treatment options. Approval of sipuleucel-T hinges on results from the IMPACT trial. If improved survival is shown, sipuleucel-T may become the first approved active cellular immunotherapy for treating metastatic, asymptomatic AIPC.
Enhancing Mitigation in Augmented Cognition
Authors: Fuchs Sven , Hale Kelly S. , Stanney Kay M. , Juhnke Joseph , Schmorrow Dylan D.
Published: December 2007

In augmented cognition (AugCog), mitigation strategies are used as real-time intervention techniques that are triggered by the outcome of cognitive state assessment and context to significantly improve human-systems performance. Yet, no common ground has been established regarding best practices and what aspects to consider during implementation. This paper discusses mitigation strategies currently used in AugCog systems and provides insights into their strengths and weaknesses. An event-based conceptual framework is introduced that aids real-time mitigation strategy selection by linking system events to real-time cognitive state indicators, which together determine when, what, and how to mitigate. Insights from the implementation of this framework in an AugCog system designed to optimize situation awareness are presented, which support the architecture of the framework and identify further challenges to mitigation. Future work should focus on further validating the proposed framework and leveraging techniques from other domains (e.g., film, theater) to create more effective mitigation concepts in AugCog systems.
Jellyfish sting. A case report
Authors: Tamás Ildikó , Veres Imre , Remenyik Éva
Published: December 2007

A medúzacsípés Magyarországon ritka. A tengerparti turizmus által azonban ezen epizoonózis is jelentőséghez juthat, különösen differenciáldiagnosztikai szempontból. – Egy tízéves nőbeteg jobb lábszárát 2005 augusztusában az Adrián való fürdőzés során medúza csípte meg. Az érintkezést követően pár perccel ez említett területen csalánkiütések jelentek meg, az egész végtag égett, erősen fájt. Néhány óra múlva hőemelkedése, általános rossz közérzete volt, majd a bőrtünetek lividdé váltak. Helyileg azonnal ecetes borogatással, majd antibiotikus kenőccsel kezelték, kalciumtartalmú pezsgőtablettát kapott. – Az általános tünetek másnapra megszűntek, a bőrtünetek fokozatosan javultak. Lokális antibiotikum, majd antihisztamin mellett négy hét múlva vált tünetmentessé. Három hónap múlva a korábbi csípés helyén viszkető, fokozatosan erősödő hyperaemiás papulák jelentkeztek. A biopszia hisztológiai vizsgálata jelentős vascularis érintettséget, eozinofíliát mutatott. Lokális okkluzív szteroidkezelésre a gyulladásos tünetek visszafejlődtek, a terület hypopigmentatióval gyógyult. – A különböző mérges medúzafajokkal történő érintkezés után bőrtünetek gyakran előfordulnak, de hónapokkal a kontaktus után, annak helyén jelentkező vascularis érintettség irodalmi ritkaság. – A cikk az esetismertetés mellett áttekinti a medúzacsípés által okozott gyakoribb bőr- és szisztémás tüneteket, részletesen tárgyalja a bőrgyógyászati differenciáldiagnosztikát, valamint ismerteti a mérges medúzafajokat, azok földrajzi elterjedését, az elsősegélyt, a kezelést és a prevenciós lehetőségeket.
Sensitivity Analysis of Geomechanical Behavior on Time-Lapse Seismic Velocity Modeling
Authors: Vidal-Gilbert S. , Tisseau E.
Published: December 2007

The petroelastic model identifies how the dynamic elastic properties (P and S velocities and density) change during reservoir production. This forms the basis of time-lapse seismic feasibility studies. To provide accurate and meaningful predictions, the model requires appropriate input from reservoir engineering (pore pressure and saturation variations) and geomechanics (stress and strain variations). In stress sensitive reservoirs, a geomechanical simulation coupled with the conventional reservoir simulation provides the updated vertical deformation and the mean effective stress field in and around the reservoir. The key objective of this work is to identify how the combined reservoir and geomechanical effects will influence predictions of the petroelastic model.

A methodology integrating reservoir engineering, geomechanics and rock physics is applied on a 3D synthetic case. The first task of this study consists in modeling deformation and stresses induced by reservoir exploitation in the reservoir and in its surrounding formations. For this, the pore pressure issued from the reservoir simulation is used as a load in the geomechanical simulation. Then, a sensitivity analysis of some mechanical parameters (Young's modulus contrast, Poisson's ratio, initial effective stress ratio, plasticity behavior) is performed with a 3D model including the reservoir and the rocks around. The results of these geomechanical modelings are analyzed considering the compaction effect, the stress arching effect and the mean effective stress value in and above the reservoir. Then, the mean effective stress issued from each geomechanical simulation allows updating seismic velocities and the time shifts associated to seismic horizons, using Hertz-Mindlin's model. Last, this approach, considering the geomechanical aspect, is improved by the contribution of the fluid substitution on the petroelastic model, taking the saturation effects into account. The geomechanical approach is compared with some classical non-geomechanical approaches commonly used.

In this work, it is demonstrated that the geomechanical approach influences the results in and around the reservoir. The time-shift values of the seismic horizons issued from this approach would be detectable on 4D seismic data and in this case study the effect is much stronger than the saturation effect alone.
Method for Conditioning the Reservoir Model on 3D and 4D Elastic Inversion Data Applied to a Fluvial Reservoir in the North Sea
Authors: Andersen T. , Zachariassen E. , Høye T. , Meisingset H. C. , Otterlei C. , van Wijngaarden A. J. , Hatland K. , Mangerøy G. , Liestol F. M.
Published: December 2007

A work flow to improve the modeling of a fluvial reservoir is presented. Modeling of fluvial reservoirs can be very uncertain when only conditioned to well data. By utilising 3D and 4D seismic inversion data to condition the geological model, the uncertainty in the facies distribution is reduced. Cross plot of 3D elastic inversion data predicts facies better than acoustic impedance data or Vp/Vs data individually. By including 4D elastic inversion data, the correlation between the classified facies from seismic and the facies zonation in the wells, is further improved. A sand probability cube is computed from 3D and 4D elastic inversion data, and used to condition the geological model of the fluvial reservoir. Upscaling and flow simulation are carried out on a set of realisations. This results in a range of simulated production profiles. The dynamic information in the 4D seismic is then used to rank the realisations by comparing the real 4D data with forward modelled elastic parameters from the flow simulation model.

The described work flow is a new way of integrating different types of data in the modeling process in order to reduce uncertainties. The method is applied to the fluvial Ness reservoir in the Oseberg field in the North Sea.