bluuebunny/crossref_metadata_2025 huggingface dataset:
IWASAWA TYPE FORMULA FOR COVERS OF A LINK IN A RATIONAL HOMOLOGY SPHERE
Authors: KADOKAMI TERUHISA , MIZUSAWA YASUSHI
Published: October 2008

Based on the analogy between links and primes, we present an analogue of the Iwasawa's class number formula in a Zp-extension for the p-homology groups of pn-fold cyclic covers of a link in a rational homology 3-sphere. We also describe the associated Iwasawa invariants precisely for some examples and discuss analogies with the number field case.
THE EFFECT OF POPULATION CONTEXTS ON CLASSIFIER PERFORMANCE
Authors: CHOUDHARY ASHISH , HUA JIANPING , BITTNER MICHAEL L. , DOUGHERTY EDWARD R.
Published: October 2008

Classifying a patient based on disease type, treatment prognosis, survivability, or other such criteria has become a major focus of genomics and proteomics. From the perspective of the general population of a particular kind of cell, one would like a classifier that applies to the whole population; however, it is often the case that the population is sufficiently structurally diverse that a satisfactory classifier cannot be designed from available sample data. In such a circumstance, it can be useful to identify cellular contexts within which a disease can be reliably diagnosed, which in effect means that one would like to find classifiers that apply to different sub-populations within the overall population. Using a model-based approach, this paper quantifies the effect of contexts on classification performance as a function of the classifier used and the sample size. The advantage of a model-based approach is that we can vary the contextual confusion as a function of the model parameters, thereby allowing us to compare the classification performance in terms of the degree of discriminatory confusion caused by the contexts. We consider five popular classifiers: linear discriminant analysis, three nearest neighbor, linear support vector machine, polynomial support vector machine, and Boosting. We contrast the case where classification is done with a single classifier without discriminating between the contexts to the case where there are context markers that facilitate context separation before classifier design. We observe that little can be done if there is high contextual confusion, but when the contextual confusion is low, context separation can be beneficial, the benefit depending on the classifier.
NUTRIENT-PHYTOPLANKTON-ZOOPLANKTON DYNAMICS IN THE PRESENCE OF ADDITIONAL FOOD SOURCE — A MATHEMATICAL STUDY
Authors: CHAKRABORTY SUBHENDU , CHATTOPADHYAY JOYDEV
Published: October 2008

In the present paper we propose four nutrient-phytoplankton-zooplankton models with and without additional food source. Each of the models is incorporated with the influence of toxin released by phytoplankton population. Existence and local stability analysis are performed for each of the models. Extensive numerical experiments are performed to observe the global dynamics of the model system. Our observations indicate that the chance of extinction of population decreases due to additional food source even if in the presence of toxin released by phytoplankton.
ASSESSING THE SUITABILITY OF STERILE INSECT TECHNIQUE APPLIED TOAEDES AEGYPTI
Authors: FERREIRA CLAUDIA PIO , YANG HYUN MO , ESTEVA LOURDES
Published: October 2008

The efficacy of biological control of Aedes aegypti mosquitoes using Sterile Insect Technique (SIT) is analyzed. This approach has shown to be very efficient on agricultural plagues and has become an alternative control strategy to the usual technique of insecticide application, which promotes resistance against chemical controls and is harmful to other species that live in the same mosquito habitat. By using a discrete cellular automata approach we have shown that in the case of Aedes aegypti, the spatially heterogeneous distribution of oviposition containers and the mosquito behavior, especially with respect to mating, make the application of STI difficult or impracticable.
DYNAMIC BEHAVIORS OF A KIND OF PREDATOR–PREY SYSTEM WITH IVLEV'S AND BEDDINGTON–DEANGELIS' FUNCTIONAL RESPONSE AND IMPULSIVE RELEASE
Authors: GUO HONGJIAN , SONG XINYU , CHEN LANSUN
Published: October 2008

A kind of one-prey two-predator system with Ivlev's and Beddington–DeAngelis' functional response and impulsive release at fixed moments is presented. It is shown that the system has a prey-free periodic solution. By using the Floquet theory and small amplitude perturbation skills, it is proved that the prey-free periodic solution of the system is locally asymptotically stable when the period of impulsive release is less than a critical value. Furthermore, permanence of the system is investigated and the condition of permanence is obtained. Finally, numerical simulations show that the system has complex properties which include periodic solution, period-doubling bifurcation, chaos, chaotic windows, half-period bifurcation. A brief discussion on our results and their relation between the continuous system and the impulsive system are given. The results obtained in this paper are confirmed by numerical simulations.
AN ARCHITECTURE FOR UNDERSTANDING INTENT USING A NOVEL HIDDEN MARKOV FORMULATION
Authors: KELLEY RICHARD , KING CHRISTOPHER , TAVAKKOLI ALIREZA , NICOLESCU MIRCEA , NICOLESCU MONICA , BEBIS GEORGE
Published: October 2008

Understanding intent is an important aspect of communication among people and is an essential component of the human cognitive system. This capability is particularly relevant to situations that involve collaboration among multiple agents or detection of situations that can pose a particular threat. In this paper, we propose an approach that allows a physical robot to detect the intent of others based on experience acquired through its own sensory–motor capabilities, then use this experience while taking the perspective of the agent whose intent should be recognized. Our method uses a novel formulation of hidden Markov models (HMMs) designed to model a robot's experience and interaction with the world when performing various actions. The robot's capability to observe and analyze the current scene employs a novel vision-based technique for target detection and tracking, using a nonparametric recursive modeling approach. We validate this architecture with a physically embedded robot, detecting the intent of several people performing various activities.
Use of Nuclear Data Sensitivity and Uncertainty Analysis for the Design Preparation of the HCLL Breeder Blanket Mockup Experiment for ITER
Authors: Kodeli I.
Published: October 2008

An experiment on a mockup of the test blanket module based on helium-cooled lithium lead (HCLL) concept will be performed in 2008 in the Frascati Neutron Generator (FNG) in order to study neutronics characteristics of the module and the accuracy of the computational tools. With the objective to prepare and optimise the design of the mockup in the sense to provide maximum information on the state-of-the-art of the cross-section data the mockup was pre-analysed using the deterministic codes for the sensitivity/uncertainty analysis. The neutron fluxes and tritium production rate (TPR), their sensitivity to the underlying basic cross-sections, as well as the corresponding uncertainties were calculated using the deterministic transport codes (DOORS package), the sensitivity/uncertainty code package SUSD3D, and the VITAMINJ/ COVA covariance matrix libraries. The cross-section reactions with largest contribution to the uncertainty of the calculated TPR were identified to be (n,2n) and (n,3n) reactions on lead. The conclusions of this work support the main benchmark design and suggest some modifications and improvements. In particular this study recommends the use, as far as possible, of both natural and enriched lithium pellets for the TRP measurements. The combined use is expected to provide additional and complementary information on the sensitive cross-sections.
Giardiasis: Conceptos modernos sobre su control y tratamiento
Authors: Thompson R.C. Andrew
Published: October 2008

Giardia es el patógeno protozoario entérico más corriente en humanos, animales domésticos y animales salvajes. El riesgo máximo de las consecuencias clínicas de la infección por Giardia recae en los niños, particularmente los que habitan en países en vías de desarrollo, en asentamientos comunitarios en condiciones desventajosas. Los estudios de epidemiología molecular han contribuido a aclarar las fuentes de infección y la significación de los reservorios animales para la salud pública. Aunque en la actualidad se conocen aspectos de la patogénesis de la infección por Giardia, estamos todavía muy lejos de poder comprender los factores que predisponen a la enfermedad clínica. Existe la disponibilidad de fármacos eficaces para tratar las infecciones por Giardia, pero sólo pueden actuar como coadyuvantes de los abordajes de salud pública tradicionales en los entornos endémicos donde los niños están frecuentemente infectados.
The Quest for the Optimal Assessment of Global Cardiovascular Risk: Are Traditional Risk Factors and Metabolic Syndrome Partners in Crime?
Authors: Arsenault Benoit J. , Pibarot Philippe , Després Jean-Pierre
Published: October 2008

Global risk calculators such as the Framingham risk score generally take into account traditional risk factors such as age, sex, blood pressure, smoking status, total cholesterol and high-density lipoprotein cholesterol levels, and the presence of diabetes which are recommended to be used in clinical practice to estimate patients’ cardiovascular disease (CVD) risk. Over the last decades, the prevalence of obesity has dramatically increased all over the world. The deleterious form of obesity, visceral obesity, is the most prevalent form of the so-called metabolic syndrome, a constellation of risk factors associated with perturbations of the lipoprotein-lipid profile and of the plasma glucose-insulin homeostasis also likely to be associated with increased blood pressure and a proinflammatory and prothrombotic state. To this date, metabolic syndrome is still in need of a place in global CVD risk prediction. As the metabolic syndrome is not likely to replace currently used global risk scoring algorithms, both traditional risk factors and emerging metabolic markers associated with the metabolic syndrome should be incorporated in future risk scoring systems to be developed in order to adapt CVD risk prediction tools to the epidemic of obesity which has direct consequences on the daily life of health professionals.
Single-Center Experience of Therapeutic Management of Hepatic Artery Stenosis after Orthotopic Liver Transplantation
Authors: Chen G.-H. , Wang G.-Y. , Yang Y. , Li H. , Lu M.-Q. , Cai C.-J. , Wang G.-S. , Xu C. , Yi S.-H. , Zhang J.-F. , Fu B.-S.
Published: October 2008

Background/Aims: Hepatic artery stenosis (HAS) is a potentially life-threatening complication of liver transplantation because the associated mortality and morbidity rates are high. Surgical reconstruction was recommended as first choice of treatment and interventional radiologic techniques have been introduced recently. However, the mid- or long-term outcomes of HAS were unclear. The purpose of this study was to evaluate the efficacy of interventional therapy and clinical outcomes of HAS following liver transplantation. Methods: A retrospective analysis was performed for 20 cases of HAS documented by angiography from October 2003 to August 2007 at the authors’ institution. All patients underwent transluminal interventional therapy including percutaneous transluminal angioplasty and endovascular stent placement. The technical results, hepatic artery patency and clinical outcome were reviewed. Results: All patients were treated with interventional management. Technical and immediate success was 100%. Of 8 patients with early HAS (within 1 month of transplantation), 1 underwent retransplantation due to deterioration of liver function. One died of acute liver failure waiting for retransplantation. Of 12 patients with late HAS (after 1 month of liver transplantation), 1 died of severe sepsis 38 days after transplantation. Five patients underwent late retransplantation due to ischemic-type biliary strictures or recurrent attacks of cholangitis. One of these patients died 11 days after retransplantation. The median follow-up of all 20 patients was 14.4 months after liver transplantation. The Kaplan-Meier curve of patency showed that cumulated primary patency of hepatic artery interventional treatment at 3, 6 and 12 months was 94, 87 and 79%, respectively. Two patients died of causes unrelated to HAS. Three patients developed recurrent HAS and were successfully treated with second interventional therapy. Eight patients (40%) developed ischemic-type biliary strictures and 7 underwent endoscopic treatment or percutaneous transhepatic cholangiodrainage. Graft function in 5 patients improved. The Kaplan-Meier curve of survival showed that the 1- and 2-year cumulated survival rates of early and late HAS were 87.5 and 43.8% and 81.5 and 61.1%, respectively. There was no significant difference in 1- and 2-year survival rates between early and late HAS (log-rank test, p = 0.928). Conclusion: Interventional therapy is an effective treatment for both early and late HAS with excellent short- and mid-term outcomes, while without irreversible graft dysfunction resulted from HAS. However, the patients have a high incidence of ischemic-type biliary lesions.
Efficacy of Short-Term Cyclosporine Treatment to Control Psoriasis-Related Events during Efalizumab Therapy
Authors: Costanzo Antonio , Talamonti Marina , Spallone Giulia , Botti Elisabetta , Chimenti Maria Sole , Papoutsaki Marina , Chimenti Sergio
Published: October 2008

Efalizumab is a recombinant humanized anti-CD11a monoclonal antibody that blocks the activation, adhesion and trafficking of T cells and has been approved for the treatment of moderate-to-severe plaque psoriasis. To document management of the fluctuations in symptom control that patients with psoriasis sometimes experience during treatment, we performed a retrospective analysis of our experience using cyclosporine as an intercurrent treatment to control psoriasis-related adverse events (AEs) in 10 patients who had received continuous efalizumab therapy for 20–200 weeks prior to recurrence of symptoms. Combination therapy with cyclosporine and efalizumab was generally well tolerated and controlled the relapse effectively. There were no reports of severe AEs during combination treatment, and no clinically significant changes were noted in clinical and laboratory values. Although mild, localized psoriasis recurred in most of these patients after cyclosporine termination, no patient experienced rebound or psoriasis flare and all continued with long-term efalizumab treatment.
Dispute Settlement Under the UN Convention on the Law of the Sea: Survey for 2007
Authors: Churchill Robin
Published: October 2008

This is the fourth of a projected series of annual surveys reviewing dispute settlement under the UN Convention on the Law of the Sea. 2007 was the busiest year for dispute settlement in the law of the sea for some time. The main developments under Part XV of the UN Convention on the Law of the Sea were the award of the arbitral tribunal in the Guyana/Suriname Case and two prompt-release-of-vessel judgments by the International Tribunal for the Law of the Sea. Outside the framework of the Convention, the International Court of Justice gave judgments in two maritime boundary cases—one on the merits (Nicaragua v. Honduras) and the other on jurisdiction (Nicaragua v. Colombia).
The European Community, the European Court of Justice and the Law of the Sea
Authors: Boelaert-Suominen Sonja
Published: October 2008

The European Community has gradually increased its focus on marine and maritime affairs, starting with the Community's Fishery Policy in the 1970s and culminating recently in the 2007 Blue Book on an Integrated Maritime Policy of the European Union. The Community's increased clout over marine and maritime matters has been reflected also in the case law of the European Court of Justice. From the outset the Court has given great impetus to the Community's efforts to assert its external competence in matters related to fisheries and conservation of biological resources of the sea. Even so, the Court has thus far only occasionally been confronted with public international law questions pertaining to the law of the sea. However, the few cases in which the Court has addressed such issues are worthy of note. For example, the Court has ruled on whether Member States should be allowed to rely on the international law of the sea in order to derogate from obligations under Community law; whether Member States should be allowed to prefer the dispute settlement provisions set out in the 1982 United Nations Convention on the Law of the Sea over the Community's own dispute settlement system; and on whether private parties may invoke arguments derived from the customary or conventional international law of the sea to challenge the validity of Community legislation pertaining to marine and maritime matters. The resulting judgments of the European Court of Justice have often turned out to be landmark cases, although some of them have tended to divide academic opinion.
A highly sensitive, PCR-based method for the detection of Plasmodium falciparum clones in microtiter plates
Authors: Maher Steven P , Balu Bharath , Shoue Doug A , Weissenbach Matthew E , Adams John H
Published: October 2008

Background

Cloning of parasites by limiting dilution is an essential and rate-limiting step in many aspects of malaria research including genomic and genetic manipulation studies. The standard Giemsa-stained blood smears to detect parasites is time-consuming, whereas the more sensitive parasite lactate dehydrogenase assay involves multiple steps and requires fresh reagents. A simple PCR-based method was therefore tested for parasite detection that can be adapted to high throughput studies.

Methods

Approximately 1 μL of packed erythrocytes from each well of a microtiter cloning plate was directly used as template DNA for a PCR reaction with primers for the parasite 18s rRNA gene. Positive wells containing parasites were identified after rapid separation of PCR products by gel electrophoresis.

Results

The PCR-based method can consistently detect a parasitaemia as low as 0.0005%, which is equivalent to 30 parasite genomes in a single well of a 96-well plate. Parasite clones were easily detected from cloning plates using this method and a comparison of PCR results with Giemsa-stained blood smears showed that PCR not only detected all the positive wells identified in smears, but also detected wells not identified otherwise, thereby confirming its sensitivity.

Conclusion

The PCR-based method reported here is a simple, sensitive and efficient method for detecting parasite clones in culture. This method requires very little manual labor and can be completely automated for high throughput studies. The method is sensitive enough to detect parasites a week before they can be seen in Giemsa smears and is highly effective in identifying slow growing parasite clones.
The perspectives of injection drug users regarding safer injecting education delivered through a supervised injecting facility
Authors: Fast Danya , Small Will , Wood Evan , Kerr Thomas
Published: October 2008

Background

Unsafe injection practices are prevalent among injection drug users (IDU) and have resulted in numerous forms of drug-related harm including HIV/HCV transmission and other bacterial and viral infections. North America's first supervised injection facility (SIF) was established in Vancouver in order to address injection-related harms among IDU. This study sought to examine injection drug users' experiences receiving safer injecting education in the context of a SIF.

Methods

Semi-structured qualitative interviews were conducted with 50 individuals recruited from a cohort of SIF users known as the Scientific Evaluation of Supervised Injection (SEOSI) cohort. Audio recorded interviews elicited IDU perspectives regarding the provision of safer injecting education within the context of a SIF. Interviews were transcribed verbatim and a thematic analysis was conducted.

Results

Participant narratives indicate that significant gaps in knowledge regarding safer injecting practices exist among local IDU, and that these knowledge deficits result in unsafe injecting practices and negative health outcomes. However, IDU perspectives reveal that the SIF allows clients to identify and address these gaps in knowledge through a number of mechanisms that are unique to this facility, including targeted educational messaging that occurs as a part of the drug use cycle and not outside of it, in situ demonstration of safer injecting techniques that takes place the moment a client is experiencing difficulties, and enhanced opportunities to seek help from 'expert' healthcare professionals. Importantly, study participants indicated that the overall environment of the SIF promotes the adoption of safer injecting practices over time, both within and outside of the facility.

Conclusion

We conclude that the SIF has been particularly effective in transmitting educational messages targeting unsafe and unhygienic injection practices to a population of active IDU. Consistent with previous work, results of this study indicate that SIFs represent a unique 'micro-environment' that can facilitate the reduction of numerous drug related harms.
Memory-enhancing treatments reverse the impairment of inhibitory avoidance retention in sepsis-surviving rats
Authors: Tuon Lisiane , Comim Clarissa M , Petronilho Fabrícia , Barichello Tatiana , Izquierdo Ivan , Quevedo João , Dal-Pizzol Felipe
Published: October 2008

Introduction

Survivors from sepsis have presented with long-term cognitive impairment, including alterations in memory, attention, concentration, and global loss of cognitive function. Thus, we evaluated the effects of memory enhancers in sepsis-surviving rats.

Methods

The rats underwent cecal ligation and perforation (CLP) (sepsis group) with 'basic support' (saline at 50 mL/kg immediately and 12 hours after CLP plus ceftriaxone at 30 mg/kg and clindamycin at 25 mg/kg 6, 12, and 18 hours after CLP) or sham-operated (control group). After 10 or 30 days, rats were submitted to an inhibitory avoidance task. After task training, animals received injections of saline, epinephrine, naloxone, dexamethasone, or glucose. Twenty-four hours afterwards, animals were submitted to the inhibitory avoidance test.

Results

We demonstrated that memory enhancers reversed impairment in the sepsis group 10 and 30 days after sepsis induction. This effect was of lower magnitude when compared with sham animals 10 days, but not 30 days, after sepsis.

Conclusions

Using different pharmacologic approaches, we conclude that the adrenergic memory formation pathways are responsive in sepsis-surviving animals.
A dual role for caveolin-1 in the regulation of fibronectin matrix assembly by uPAR
Authors: Monaghan-Benson Elizabeth , Mastick Cynthia Corley , McKeown-Longo Paula J.
Published: October 2008

The relationship between the plasminogen activator system and integrin function is well documented but incompletely understood. The mechanism of uPAR-mediated signaling across the membrane and the molecular basis of uPAR-dependent activation of integrins remain important issues. The present study was undertaken to identify the molecular intermediates involved in the uPAR signaling pathway controlling α5β1-integrin activation and fibronectin polymerization. Disruption of lipid rafts with MβCD or depletion of caveolin-1 by siRNA led to the inhibition of uPAR-dependent integrin activation and stimulation of fibronectin polymerization in human dermal fibroblasts. The data indicate a dual role for caveolin-1 in the uPAR signaling pathway, leading to integrin activation. Caveolin-1 functions initially as a membrane adaptor or scaffold to mediate uPAR-dependent activation of Src and EGFR. Subsequently, in its phosphorylated form, caveolin-1 acts as an accessory molecule to direct trafficking of activated EGFR to focal adhesions. These studies provide a novel paradigm for the regulation of crosstalk among integrins, growth-factor receptors and uPAR.
Involvement of endothelial ephrin-B2 in adhesion and transmigration of EphB-receptor-expressing monocytes
Authors: Pfaff Dennis , Héroult Mélanie , Riedel Maria , Reiss Yvonne , Kirmse Robert , Ludwig Thomas , Korff Thomas , Hecker Markus , Augustin Hellmut G.
Published: October 2008

The vascular endothelium is a crucial interface that controls the recruitment of circulating leukocytes. Based on the luminal expression of the ephrin-B2 ligand by endothelial cells (ECs) and the expression of EphB receptors (EphBRs) by circulating monocytes, we hypothesized that EphBR-ephrinB interactions are involved in monocyte adhesion. Adhesion experiments with monocytic cells were performed on ECs that overexpressed either full-length ephrin-B2 or cytoplasmically truncated ephrin-B2 (ΔC-ephrin-B2). Atomic force microscopy confirmed similar adhesive strengths of EphBR-expressing J774 cells to ECs that either overexpressed full-length ephrin-B2 or truncated ΔC-ephrin-B2 (1-minute interaction). Yet, adhesion experiments under static or flow conditions for 30 minutes demonstrated the preferential adhesion of monocytic cells to ECs that overexpressed full-length ephrin-B2 but not to ΔC-ephrin-B2 or to ECs that had been mock transduced. Adhesion was blocked by ephrin-B2-specific and EphBR-specific antibodies. Correspondingly, adhesion of EphB4-receptor-overexpressing monocytes to ephrin-B2-positive ECs was further augmented. Trafficking experiments of cell-surface molecules revealed that, prior to internalization, the resulting EphB4-receptor–ephrin-B2 complex translocated from the luminal surface to inter-endothelial junctions. Lastly, full-length ephrin-B2 in ECs was also involved in monocyte transmigration. Collectively, our study identifies a role of EphBR-ephrinB interactions as a new step in the cascade of events leading to monocyte adhesion and transmigration through the vascular endothelium.
The role of Delta-like 1 shedding in muscle cell self-renewal and differentiation
Authors: Sun Danqiong , Li Hui , Zolkiewska Anna
Published: October 2008

Myogenic cells have the ability to adopt two divergent fates upon exit from the cell cycle: differentiation or self-renewal. The Notch signaling pathway is a well-known negative regulator of myogenic differentiation. Using mouse primary myoblasts cultured in vitro or C2C12 myogenic cells, we found that Notch activity is essential for maintaining the expression of Pax7, a transcription factor associated with the self-renewal lineage, in quiescent undifferentiated myoblasts after they exit the cell cycle. Stimulation of the Notch pathway by expression of a constitutively active Notch-1, or co-culture of myogenic cells with CHO cells transfected with Delta like-1 (DLL1), increases the level of Pax7. DLL1, a ligand for Notch receptor, is shed by ADAM metalloproteases in a pool of Pax7+ C2C12 reserve cells, but it remains intact in differentiated myotubes. DLL1 shedding changes the receptor/ligand ratio and modulates the level of Notch signaling. Inhibition of DLL1 cleavage by a soluble, dominant-negative mutant form of ADAM12 leads to elevation of Notch signaling, inhibition of differentiation, and expansion of the pool of self-renewing Pax7+/MyoD– cells. These results suggest that ADAM-mediated shedding of DLL1 in a subset of cells during myogenic differentiation in vitro contributes to downregulation of Notch signaling in neighboring cells and facilitates their progression into differentiation. We propose that the proteolytic processing of DLL1 helps achieve an asymmetry in Notch signaling in initially equivalent myogenic cells and helps sustain the balance between differentiation and self-renewal.
Ncd motor binding and transport in the spindle
Authors: Hallen Mark A. , Liang Zhang-Yi , Endow Sharyn A.
Published: October 2008

The Ncd kinesin-14 motor is required for meiotic spindle assembly in Drosophila oocytes and produces force in mitotic spindles that opposes other motors. Despite extensive studies, the way the motor binds to the spindle to perform its functions is not well understood. By analyzing Ncd deleted for the conserved head or the positively charged tail, we found that the tail is essential for binding to spindles and centrosomes, but both the head and tail are needed for normal spindle assembly and function. Fluorescence photobleaching assays to analyze binding interactions with the spindle yielded data for headless and full-length Ncd that did not fit well to previous recovery models. We report a new model that accounts for Ncd transport towards the equator revealed by fluorescence flow analysis of early mitotic spindles and gives rate constants that confirm the dominant role the Ncd tail plays in binding to the spindle. By contrast, the head binds weakly to spindles based on analysis of the tailless fluorescence recovery data. Minus-end Ncd thus binds tightly to spindles and is transported in early metaphase towards microtubule plus-ends, the opposite direction to that in which the motor moves, to produce force in the spindle later in mitosis.
First Detection of a Silicic Acid Complex with a Catechol Derivative under Natural Conditions
Authors: Bai Shuqin , Tsuji Yutaka , Okaue Yoshihiro , Yokoyama Takushi
Published: October 2008

The formation of silicic acid–tiron complexes was predicted based on the increase in the solubility of amorphous silica in aqueous tiron solution near neutral pH compared with aqueous sodium chloride solutions of the same pH. A 6-coordinated silicic acid–tiron complex was detected by 29Si NMR and the composition was determined to be 1:3 (Si:tiron) by ESI mass spectroscopy.
Gene expression studies with microarrays and SAGE: biological and analytical principles1
Authors: Müller Holger , Neumaier Michael , Hoffmann Georg
Published: October 2008

The present article continues a series of publications and internet presentations (www.dgkl.de/bioninformatik) on analytical and postanalytical aspects of gene expression studies. We present a critical laboratory diagnostics view on the two most important analytical techniques for genome-wide expression profiles, i.e., DNA microarrays (biochips) and Serial Analysis of Gene Expression (SAGE). A gene expression profile is a list of mRNA species (transcripts) with corresponding quantities in a given tissue. Of the 10–20 pg total RNA per cell, mRNA constitutes only 1–5% and is dispersed among about 30,000 individual transcripts. Therefore, most of them are present in extremely low amounts reaching one molecule per cell, whereas a few show 10,000-fold higher concentrations. The analytical challenge of whole genome expression profiling is therefore substantial.

Both techniques have specific strengths and weaknesses: Microarray experiments yield semi-quantitative results with less effort in a relatively short time, but they can analyze only known gene products. SAGE is extremely costly, time-consuming and difficult to interpret, but it counts well-defined sequence tags and detects – at least in principle – any mRNA in the sample. Due to the large number of hardly standardized preanalytical and analytical procedures, both techniques suffer from accuracy and precision problems and may lead to contradictory conclusions. A signal highly expressed with microarrays may be undetectable with SAGE and vice versa. High throughput sequencing techniques could help to close the gap between both techniques.
Rapid Changes in Thalamic Firing Synchrony during Repetitive Whisker Stimulation
Authors: Temereanca Simona , Brown Emery N. , Simons Daniel J.
Published: October 2008

Thalamic firing synchrony is thought to ensure selective transmission of relevant sensory information to the recipient cortical neurons by rendering them more responsive to temporally correlated input spikes. However, direct evidence for a synchrony code in the thalamus is limited. Here, we directly measure thalamic firing synchrony and its stimulus-induced modulation over time, using simultaneous single unit recordings from individual thalamic barreloids in the rat somatosensory whisker/barrel system. Employing whisker deflections varying in velocity or frequency and a cross-correlation approach, we find systematic changes in both time course and strength of thalamic firing synchrony as a function of stimulus parameters and sensory adaptation. Synchrony develops faster and is greater with higher velocity deflections. Greater firing synchrony reflects stimulus-dependent increases in instantaneous firing rates, greater spike time precision relative to stimulus onset as well as common input that likely arises from divergent trigeminothalamic and corticothalamic neurons. With adaptation, synchrony decreases and takes longer to develop but is more dependent on the cells' common inputs. Rapid, sharp increases in thalamic synchrony mirroring quick increases in whisker velocity occur also during ongoing random, high-frequency whisker vibrations. Together, results demonstrate millisecond by millisecond changes in thalamic near-synchronous firing during complex patterns of ongoing vibrissa movements that may ensure transmission of preferred sensory information in local thalamocortical circuits during whisking and active touch.
Opposite Effects of Zinc on Human and Rat P2X2Receptors
Authors: Tittle Rachel K. , Hume Richard I.
Published: October 2008

P2X2receptors from rats show potentiation when a submaximal concentration of ATP is combined with zinc in the range of 10–100 μm. Alignment of the amino acid sequences of human P2X2(hP2X2) and rat P2X2(rP2X2) indicated that only one of two histidines essential for zinc potentiation in rP2X2is present at the homologous position in hP2X2(H132), with the position homologous to rat H213 instead having an arginine (R225). When expressed inXenopusoocytes, mouse P2X2aand P2X2breceptors showed zinc potentiation indistinguishable from rat P2X2a, but hP2X2breceptors were inhibited by zinc. The extent of zinc inhibition of hP2X2bvaried with the ATP concentration, with an IC50of 8.4 μmzinc when ATP was applied at 10% of maximal and 87 μmzinc when ATP was applied at 99% of maximal. Site-directed mutagenesis showed that none of the nine histidines in the extracellular domain of hP2X2bwere required for zinc inhibition, although inhibition was attenuated in the H204A and H209A mutations. Mutating R225 to a cysteine was sufficient to confer zinc potentiation onto hP2X2b, and zinc potentiation was absent in the hP2X2bH132A/R225C double mutant. This suggests that zinc potentiation in the mutant hP2X2buses the same mechanism as zinc potentiation in wild-type rP2X2a. Because of the species-specific modulation by zinc, evidence for anin vivorole of P2X2receptors based on studies conducted on genetically modified mice needs to be viewed with caution when extrapolations are made to the function of the human nervous system.
Double Dissociation of the Effects of Medial and Orbital Prefrontal Cortical Lesions on Attentional and Affective Shifts in Mice
Authors: Bissonette Gregory B. , Martins Gabriela J. , Franz Theresa M. , Harper Elizabeth S. , Schoenbaum Geoffrey , Powell Elizabeth M.
Published: October 2008

Many neuropsychiatric diseases are associated with cognitive rigidity linked to prefrontal dysfunction. For example, schizophrenia and Parkinson's disease are associated with performance deficits on the Wisconsin Card Sorting Test, which evaluates attentional set shifting. Although the genetic underpinnings of these disorders can be reproduced in mice, there are few models for testing the functional consequences. Here, we demonstrate that an analog of the Wisconsin Card Sorting Test, developed in marmosets and recently adapted to rats, is a behavioral model of prefrontal function in mice. Systematic analysis demonstrated that formation of the attentional set in mice is dependent on the number of problem sets. We found that mice, like rats and primates, exhibit both affective and attentional sets, and these functions are disrupted by neurotoxic damage to orbitofrontal and medial prefrontal cortical areas, respectively. These data are identical to studies in rats and similar to the deficits reported after prefrontal damage in a comparable task in marmosets. These results provide a behavioral model to assess prefrontal function in mice.
Conditional Deletion of theItgb4Integrin Gene in Schwann Cells Leads to Delayed Peripheral Nerve Regeneration
Authors: Van der Zee Catharina E. E. M. , Kreft Maaike , Beckers Gaby , Kuipers Arthur , Sonnenberg Arnoud
Published: October 2008

Several different integrins participate in the complex interactions that promote repair of the peripheral nervous system. The role of the integrin α6β4 in peripheral nerve regeneration was investigated in mice by cre-mediated deletion of theItgb4(β4) gene in Schwann cells. After a crush lesion of the sciatic nerve, the recovery of motor, but not that of sensory, nerve function in β4−/−mice was delayed. Immunostaining of neurofilament-200 showed that there also is a significant reduction in the number of newly outgrowing nerve sprouts in β4−/−mice. Morphometric quantitative measurements revealed that fewer axons are myelinated in the nonlesioned β4−/−nerves. After a sciatic nerve crush lesion, β4−/−mice did not only have fewer myelinated axons compared with lesioned wild-type nerve, but their axons also showed a higherg-ratio and a thinner myelin sheath, pointing at reduced myelination. This study revealed that the β4 protein remains expressed in the early stages of peripheral regeneration, albeit at levels lower than those before the lesion was inflicted, and showed that laminin deposition is not altered in the absence of β4. These results together demonstrate that integrin α6β4 plays an essential role in axonal regeneration and subsequent myelination.
Mechanisms Underlying the Transformation of Disparity Signals from V1 to V2 in the Macaque
Authors: Tanabe Seiji , Cumming Bruce G.
Published: October 2008

Stereo vision relies on cortical signals that encode binocular disparity. In V1, the disparity energy model explains many features of binocular interaction, but it overestimates the responses to anticorrelated images. Combining the outputs of two, or more, energy model-like subunits [two-subunit (2SU) model] can resolve this discrepancy and provides an alternative explanation for disparity signals previously thought to indicate phase disparity between the receptive fields (RFs) of each eye. The 2SU model naturally explains how “near/far” (odd-symmetric) tuning becomes dominant in extrastriate cortex. To compare the energy and the 2SU models, we used a broadband compound grating and applied a common interocular phase difference to all spatial frequency components (a stimulus phase disparity), combined with a common spatial displacement (a stimulus position disparity). This produces binocular images that never occur in natural viewing, for which the 2SU model and the energy model make distinctively different predictions. Responses of neurons recorded from both V1 and V2 of awake rhesus macaques systematically deviated from the predictions of the energy model, in accordance with the 2SU model. These deviations correlated with the symmetry of the tuning curve, indicating that the 2SU mechanism is exploited to produce odd symmetry. Nonetheless, individual subunits also contain RF phase disparity that contributes to odd symmetry. The results suggest that neurons in V2 probably inherit phase disparity signals from V1 neurons, but systematically combine input from V1 neurons with different position disparities, in a way that elaborates odd-symmetric tuning and extends the range of disparities encoded by single neurons.
Cholinergic Augmentation Modulates Visual Task Performance in Sleep-Deprived Young Adults
Authors: Chuah Lisa Y. M. , Chee Michael W. L.
Published: October 2008

Using 24 h of total sleep deprivation to perturb normal cognitive function, we conducted a double-blind, placebo-controlled crossover study to evaluate the effect of the acetylcholinesterase inhibitor, donepezil, on behavioral performance and task-related brain activation in 28 healthy, young, adult volunteers. The behavioral tasks involved the parametric manipulation of visual short-term memory load and perceptual load in separate experiments indirectly evaluating attention. Sleep deprivation significantly reduced posterior cortical activation (intraparietal sulcus and extrastriate cortex) at all levels of visual memory as well as perceptual load. Donepezil modulated an individual's performance in both tasks in accordance to whether accuracy declined after sleep deprivation without treatment. Critically, there were significant correlations between donepezil-induced increases in neural activation in the posterior cortical areas and improvement in accuracy. Reduced visual short-term memory after sleep deprivation may thus originate from a decline in visual attention and/or visual processing. Cholinergic augmentation can alleviate these deficits in individuals vulnerable to the effects of sleep deprivation, but it may have neutral or negative effects on those resistant to sleep deprivation.
Proceedings of the Thirty-Fourth Meeting of the Israel Society of Ecology and Environmental Quality Sciences (Iseeqs)
Authors: ARNON A. , UNGAR E.D. , SVORAY T. , PEREVOLOTSKY A.
Published: October 2008

Spatio-temporal dynamics of the association between woody and herbaceous vegetation in a grazed, semi-arid ecosystem
Codon Signature Extremes In Eukaryote genomes
Authors: Karlin Samuel , Carmelli Dorit
Published: October 2008

Twenty-one complete eukaryotic genomes are compared for codon signature biases. The codon signature refers to the dinucleotide relative abundance values at codon sites {1, 2}, {2, 3}, and {3, 4} (4 = 1 of the next codon site). The genomes under study include human, mouse, chicken, three invertebrates, one plant species, eight fungi, and six protists. The dinucleotide CpG is significantly underrepresented at all contiguous codon sites and drastically suppressed in noncoding regions in mammalian species, in yeast-like genomes, in the dicotArabidopsis thaliana, but not in the filamentous fungiNeurospora crassaandAsperigillus fumigatus, and in the protistEntamoeba histolytica.The dinucleotide TpA, probably due to DNA structural weaknesses, is underrepresented genome-wide and significantly underrepresented in the codon signature for all contiguous codon sites in mammals, inverterbrates, plants, and fungi, but somewhat restricted to codon sites {1, 2} among protists helping in avoidance of stop codons. The amino acid Ser, not of abundance in bacterial genomes, generally ranks among the two most used amino acids among eukaryotes ostensibly resulting from greater activity in the nucleus. The observed differences are linked to specifics of methylation, context-dependent mutation, DNA repair, and replication. For example, the amino acid Leu is broadly abundant in all life domains generally resulting from extra occurrences of the codon TTR, R purine. The malarial protistPlasmodium falciparumshows many codon signature extremes.
On the Origin of Cells and Viruses: A Comparative-Genomic Perspective
Authors: Koonin Eugene V.
Published: October 2008

It is proposed that the pre-cellular stage of biological evolution, including the Last Universal Common Ancestor (LUCA) of modern cellular life forms, occurred within networks of inorganic compartments that hosted a diverse mix of virus-like genetic elements. This viral model of cellular origin recapitulates the early ideas of J.B.S. Haldane, sketched in his 1928 essay on the origin of life. However, unlike in Haldane's day, there is substantial empirical support for this scenario from three major lines of evidence provided by comparative genomics: (i) the lack of homology among the core components of the DNA replication systems between the two primary lines of descent of cellular life forms, archaea and bacteria, (ii) the similar lack of homology between the enzymes of lipid biosynthesis in conjunction with distinct membrane chemistries in archaea and bacteria, and (iii) the spread of several viral hallmark genes, which encode proteins with key functions in viral replication and morphogenesis, among numerous and extremely diverse groups of viruses, in contrast to their absence in cellular life forms. Under the viral model of pre-cellular evolution, the key elements of cells including the replication apparatus, membranes, molecular complexes involved in membrane transport and translocation, and others originated as components of virus-like entities. This model alleviates, at least in part, the challenge of the emergence of the immensely complex organization of modern cells.
Retrotransposons: Metaparasites and Agents of Genome Evolution
Authors: Sabot François , Kalendar Ruslan , Jääskeläinen Marko , Wei Chang , Tanskanen Jaakko , Schulman Alan H.
Published: October 2008

Transposable elements comprise the bulk of higher plant genomes. The majority of these elements are the Class I LTR retrotransposons, which transpose via an RNA intermediate in a "Copy-and-Paste" mechanism. Because retrotransposons use cellular resources and their own enzymes to replicate independently of the genome as a whole, and have thereby become in many cases more predominant than the cellular genes, they have been considered "selfish DNA" and nuclear parasites. They are thought to share many features of the internal life cycle of retroviruses such as HIV (lentiviruses). However, whereas at least some of the retroviruses arriving in an organism during an infection must be functional in order for the infection to proceed, some LTR retrotransposon families appear to completely lack active members even though they remain mobile. Furthermore, the process of retrotransposition is inherently error-prone and mutagenic, giving rise to "pseudospecies," or clusters of imperfect copies. The non-autonomous retrotransposons are able to cis- and trans-parasitize host retrotransposons to gain mobility, much as do defective interfering particles of RNA viruses. Hence, a complex dynamic is set up, whereby the impact of retrotransposons on genomes can be under selection on the organismal level; the impact of non-autonomous retrotransposons on autonomous ones can likewise be under selection if there is selection on the autonomous elements themselves. We are exploring the retrotransposon life cycle and the causes and possible consequences of non-autonomy at each stage regarding genome evolution.
Genomic Organization and Molecular Evolution of the Genes for Neuroglobin and Cytoglobin in the Hypoxiatolerant Israeli Mole Rat, Spalax Carmeli
Authors: Gerlach Frank , Avivi Aaron , Joel Alma , Burmester Thorsten , Nevo Eviatar , Hankeln Thomas
Published: October 2008

The genes for the two respiratory proteins neuroglobin (Ngb) and cytoglobin (Cygb) in the subterranean Israeli mole rat Spalax carmeli have been sequenced and compared to other mammals including human. Coding regions of both Spalax genes are highly conserved on the nucleotide and amino acid level. The ratios of non-synonymous to synonymous nucleotide substitutions suggest strong purifying selection acting on Ngb and Cygb in all mammals. Thus, there appears to be no special sequence level adaptation in the two respiratory proteins within the hypoxia-tolerant mole rat. On the genomic level, Spalax Ngb and Cygb gene regions revealed the conserved 4-exon-3-intron structure and conserved CpG-rich islands in the 5' region. The Spalax Cygb gene promoter contains a conserved hypoxia-responsive transcription factor binding site, indicating a possible up-regulation of Cygb under oxygen deprivation. In Cygb intron 1, we observed a stretch of highly conserved putatively non-coding sequence of yet unknown (regulatory?) importance. In the Spalax Ngb gene, we note the presence of candidate hypoxia-responsive elements, which are not conserved in Ngb of hypoxia-sensitive mammals. Both globin gene regions harbor Spalax-specific simple sequence regions, which might be of adaptive value. We conclude that adaptations for hypoxia in mole rats are most likely to be found in regulatory functions rather than in protein structure.