bluuebunny/crossref_metadata_2025 huggingface dataset:
Ordinal Linguistic Personification as a Variant of Synesthesia
Authors: Simner Julia , Holenstein Emma
Published: March 2007

This study examines the principles underlying ordinal linguistic personification (OLP): the involuntary and automatic tendency in certain individuals to attribute animate-like qualities such as personality and gender to sequential linguistic units (e.g., letters, numerals, days, months). This article aims to provide four types of evidence that OLP constitutes a form of synesthesia and is likely to have the same neurodevelopmental basis. We show that (a) OLP significantly co-occurs with other variants of synesthesia, (b) OLP associations (like those of synesthesia) are highly consistent over time (Experiment 1), (c) OLP associations (like those of synesthesia) have the characteristic of letter-to-word transference (i.e., they spread from initial letters throughout words) (Experiment 2), and (d) OLP associations (like those of synesthesia) are automatically generated and interfere in Stroop-type tasks (Experiment 3). We argue that these shared characteristics suggest a unified underlying behavior, and propose OLP as a subtype of synesthesia. In so doing, our study extends the range of reported phenomena that are known to be susceptible to cross-modal association.
Intercerebellar Coupling Contributes to Bimanual Coordination
Authors: Pollok Bettina , Butz Markus , Gross Joachim , Schnitzler Alfons
Published: March 2007

Compared to unimanual task execution, simultaneous bimanual tapping tasks are associated with a significantly reduced intertap variability. It has been suggested that this bimanual advantage is based on the integration of timing signals which otherwise control each hand independently. Although its functional and anatomic foundations are poorly understood, functional coupling between cerebellar hemispheres might be behind this process. Because the execution of fast alternating fingertaps increases intertap variability, it is hypothesized that intercerebellar coupling is reduced in such tasks. To shed light on the functional significance of intercerebellar coupling, 14 right-handed subjects performed unimanual right, bimanual simultaneous, and bimanual alternating synchronization tasks with respect to a regular auditory pacing signal. In all conditions, within-hand intertap interval was 500 msec. Continuous neuromagnetic activity, using a 122-channel wholehead neuromagnetometer and surface electromyograms of the first dorsal interosseus muscle of both hands, were recorded. For data analysis, we used the analysis tool Dynamic Imaging of Coherent Sources, which provides a tomographic map of cerebromuscular and cerebrocerebral coherence. Analysis revealed a bilateral cerebello-thalamo-cortical network oscillating at alpha (8–12 Hz) and beta (13–24 Hz) frequencies associated with bimanual synchronization. In line with our hypothesis, coupling between cerebellar hemispheres was restricted to simultaneous task execution. This result implies that intercerebellar coupling is key for the execution of simultaneous bimanual movements. Although the criticality of a specific magneto-encephalography pattern for behavioral changes should be interpreted with caution, data suggest that intercerebellar coupling possibly represents the functional foundation of the bimanual advantage.
Optimal Coding Predicts Attentional Modulation of Activity in Neural Systems
Authors: Jaramillo Santiago , Pearlmutter Barak A.
Published: March 2007

Neuronal activity in response to a fixed stimulus has been shown to change as a function of attentional state, implying that the neural code also changes with attention. We propose an information-theoretic account of such modulation: that the nervous system adapts to optimally encode sensory stimuli while taking into account the changing relevance of different features. We show using computer simulation that such modulation emerges in a coding system informed about the uneven relevance of the input features. We present a simple feedforward model that learns a covert attention mechanism, given input patterns and coding fidelity requirements. After optimization, the system gains the ability to reorganize its computational resources (and coding strategy) depending on the incoming attentional signal, without the need of multiplicative interaction or explicit gating mechanisms between units. The modulation of activity for different attentional states matches that observed in a variety of selective attention experiments. This model predicts that the shape of the attentional modulation function can be strongly stimulus dependent. The general principle presented here accounts for attentional modulation of neural activity without relying on special-purpose architectural mechanisms dedicated to attention. This principle applies to different attentional goals, and its implications are relevant for all modalities in which attentional phenomena are observed.
Efficient Computation Based on Stochastic Spikes
Authors: Ernst Udo , Rotermund David , Pawelzik Klaus
Published: March 2007

The speed and reliability of mammalian perception indicate that cortical computations can rely on very few action potentials per involved neuron. Together with the stochasticity of single-spike events in cortex, this appears to imply that large populations of redundant neurons are needed for rapid computations with action potentials. Here we demonstrate that very fast and precise computations can be realized also in small networks of stochastically spiking neurons. We present a generative network model for which we derive biologically plausible algorithms that perform spike-by-spike updates of the neuron's internal states and adaptation of its synaptic weights from maximizing the likelihood of the observed spike patterns. Paradigmatic computational tasks demonstrate the online performance and learning efficiency of our framework. The potential relevance of our approach as a model for cortical computation is discussed.
A Method to Correct the Thermal Dome Effect of Pyranometers in Selected Historical Solar Irradiance Measurements
Authors: Ji Qiang
Published: March 2007

In using pyranometers to measure solar irradiance, it is important to know the magnitudes and the consequences of the thermal effect, which is introduced by the glass domes of the instruments. Historically, the thermal dome effect was not monitored on a regular basis. Case studies show that, due to the thermal dome effect, the output of the pyranometers altered from less than 5 W m−2 in the nighttime to over 20 W m−2 around noontime during the Aerosol Recirculation and Rainfall Experiment (ARREX) in 1999 and the Southern African Fire–Atmosphere Research Initiative (SAFARI) in 2000 field campaigns, depending on sky conditions. A calibration and data processing procedure with the thermal dome effect incorporated has been tested to resolve the issue. It is demonstrated that the intrinsic calibration constants of the pyranometers can be obtained if two pyranometers are used side by side, and the thermal dome effect may be inferred whenever a pyranometer and a pyrgeometer are collocated.
Determining Weather Radar Antenna Pointing Using Signals Detected from the Sun at Low Antenna Elevations
Authors: Huuskonen Asko , Holleman Iwan
Published: March 2007

A method to determine the elevation and azimuth biases of the radar antenna using solar signals observed by a scanning radar is presented. Data recorded at low elevation angles where the atmospheric refraction has a significant effect on the propagation of the radio wave are used, and a method to take the effect of the refraction into account in the analysis is presented. A set of equations is given by which the refraction of the radio waves as a function of the relative humidity can easily be calculated. Also, a simplified model for the calculation of the atmospheric attenuation is presented. The consistency of the adopted models for the atmospheric refraction and atmospheric attenuation is confirmed by data collected at a single elevation pointing, but over a long observing time. Finally, the method is applied to datasets based on operational measurements at the Finnish Meteorological Institute (FMI) and Royal Netherlands Meteorological Institute (KNMI), and elevation and azimuth biases of the radars are shown.
SPARC: New Cloud, Snow, and Cloud Shadow Detection Scheme for Historical 1-km AVHHR Data over Canada
Authors: Khlopenkov Konstantin V. , Trishchenko Alexander P.
Published: March 2007

The identification of clear-sky and cloudy pixels is a key step in the processing of satellite observations. This is equally important for surface and cloud–atmosphere applications. In this paper, the Separation of Pixels Using Aggregated Rating over Canada (SPARC) algorithm is presented, a new method of pixel identification for image data from the Advanced Very High Resolution Radiometer (AVHRR) on board the NOAA satellites. The SPARC algorithm separates image pixels into clear-sky and cloudy categories based on a specially designed rating scheme. A mask depicting snow/ice and cloud shadows is also generated. The SPARC algorithm has been designed to work year-round (day and night) over the temperate and polar regions of North America, for current and historical AVHRR/NOAA High-Resolution Picture Transmission (HRPT) and Local Area Coverage (LAC) data with original 1-km spatial resolution. The algorithm was tested and applied to data from the AVHRR sensors flown on board NOAA-6 to NOAA-18. The method was employed in generating historical clear-sky composites for the 1982–2005 period at daily, 10-day, and monthly time scales at 1-km resolution for an area of 5700 km × 4800 km centered over Canada. This region also covers the northern part of the United States, including Alaska, as well as Greenland and the surrounding oceans.

The SPARC algorithm is designed to produce an aggregated rating that accumulates the results of several tests. The magnitude of the rating serves as an indicator of the probability for a pixel to belong to the clear-sky, partly cloudy, or overcast categories. The individual tests employ the spectral properties of five AVHRR channels, as well as surface skin temperature maps from the North American Regional Reanalysis (NARR) dataset. These temperature fields are available at 32 km × 32 km spatial resolution and at 3-h time intervals. Combining all test results into one final rating for each pixel is beneficial for the generation of multiscene clear-sky composites. The selection of the best pixel to be used in the final clear-sky product is based on the magnitude of the rating. This provides much-improved results relative to other approaches or “yes/no” decision methods.

The SPARC method has been compared to the results of supervised classification for a number of AVHRR scenes representing various seasons (snow-free summer, winter with snow/ice coverage, and transition seasons). The results show an overall agreement between the automated (SPARC) and the supervised classification at the level of 80% to 91%.
Directional Validation of Wave Predictions*
Authors: Rogers W. Erick , Wang David W. C.
Published: March 2007

A methodology for quantitative, directional validation of a long-term wave model hindcast is described and applied. Buoy observations are used as ground truth and the method does not require the application of a parametric model or data-adaptive method to the observations. Four frequency ranges, relative to the peak frequency, are considered. The validation of the hindcast does not suggest any systematic bias in predictions of directional spreading at or above the spectral peak. Idealized simulations are presented to aid in the interpretation of results.
Indirect Assessment of Cognitions of Child Sexual Abusers With the Implicit Association Test
Authors: Nunes Kevin L. , Firestone Philip , Baldwin Mark W.
Published: March 2007

The Implicit Association Test (IAT) is adapted to measure cognitions regarding self and children in 27 male child molesters and 29 male nonsexual offenders. As expected, child molesters view children as more sexually attractive than do nonsexual offenders. Among the child molesters, viewing children as more sexually attractive is associated with greater risk of sexual recidivism as measured by the Static-99. Viewing children as more powerful is associated with greater risk of sexual recidivism as measured by the Rapid Risk Assessment for Sexual Offense Recidivism. Although not all hypotheses are supported, this study demonstrates that the IAT has much promise as a tool with which to study cognitions associated with sexual abuse of children.
Managing Occupational Stress in a High-Risk Industry
Authors: Brough Paula , Williams Joanne
Published: March 2007

Occupational stress is an increasing health problem for the high-risk industries. The occupation of correctional officers has received relatively scant attention, contributing to a recent increase in formal occupational stress claims. This research evaluates the ability of the Job Demand-Control-Support (JDCS) model to predict strain in 132 Australian correctional officers. A specific measure of job demands predicts the psychological outcome (job satisfaction) to a greater extent than the generic (JDCS) demands measure. The ability of supervisor support to moderate the consequences of these job demands is also demonstrated and has implications for the training of correctional supervisors. Arguments for including sample-specific measures of job demands are discussed.
Validity of the Level of Service Inventory—Revised (LSI-R) Among African American and Hispanic Male Offenders
Authors: Schlager Melinda D. , Simourd David J.
Published: March 2007

The Level of Service Inventory—Revised (LSI-R) is a dynamic risk/needs assessment instrument that has been used extensively among a variety of offender samples. Validity research on the LSI-R, however, is based on samples consisting predominantly of Caucasian participants. The present study sought to examine the psychometric properties and validity of the instrument among a sample of African American and Hispanic male offenders. Participants were 446 male parolees residing in three halfway houses and one day reporting center. Three hundred and thirty-four offenders (75% of the sample) were of African American heritage and 112 (25%) were of Hispanic heritage. Analyses of the psychometric properties and validity of the LSI-R were conducted separately for each ethnic group. Results indicated the instrument had acceptable psychometric properties, but that the predictive validity results were lower than previous studies on the LSI-R. Results are discussed within the context of the invariance of risk variables and the applicability of the LSI-R to various offender groups.
Comparison of 3 Preventive Methods to Reduce the Recurrence of Ankle Inversion Sprains in Male Soccer Players
Authors: Mohammadi Farshid
Published: March 2007

Background

Ankle sprains are frequent injuries in soccer. Several strategies can be used to prevent further ankle sprains in athletes: the most common are proprioceptive training, strength training, and orthoses.

Objective

To investigate which of these 3 interventions is the most effective in preventing ankle sprains in athletes with previous ankle inversion sprain.

Study Design

Randomized controlled trial; Level of evidence, 1.

Methods and Measures

Eighty male soccer players (age, 24.6 ± 2.63 years; height, 175.60 ± 4.36 cm; weight, 64.26 ± 8.37 kg) in the first division of a men's league who had experienced previous ankle inversion sprain were randomly selected from an original population of 120 players. The subjects were individually and randomly assigned to 4 study groups: group 1 (n = 20) followed the proprioceptive program, group 2 (n = 20) followed the strength program, group 3 (n = 20) used orthoses, and group 4 (n = 20) was the control group. Data on the frequency of ankle sprain reinjury were collected at the end of the session.

Results

There were no significant differences among the groups in the number of exposures. The incidence of ankle sprains in players in the proprioception training group was significantly lower than in the control group (relative risk of injury, 0.13; 95% confidence interval, 0.003-0.93; P = .02). The findings with respect to the strength and orthotic groups in comparison with the control group were not significant (relative risk of injury, 0.5; 95% confidence interval, 0.11-1.87; P = .27 for strength; relative risk of injury, 0.25; 95% confidence interval, 0.03-1.25; P = .06 for orthotic group).

Conclusion

Proprioceptive training, compared with no intervention, was an effective strategy to reduce the rate of ankle sprains among male soccer players who suffered ankle sprain.
Philadelphia’s Trap of Grease
Authors: Hill Sarah
Published: March 2007

This essay contends that national energy policy both purposefully and indirectly disadvantages a Philadelphia-based initiative that would simultaneously foster energy self-reliance, help improve the city’s air quality, lower costs associated with wastewater treatment, and provide an alternative to imported petroleum-based vehicle fuel. Although some of the obstacles confronting this initiative are endemic to the character of Philadelphia’s fractured approach to urban management, this article suggests that a change in national energy policy could do much to enhance Philadelphia’s prospects to develop a commercial-scale biodiesel production facility that exploits a trap grease, an as yet virtually unutilized ingredient for making a biogenic fuel.
Broadcasting Behavior Change
Authors: Flores Alina L. , Prue Christine E. , Daniel Katherine Lyon
Published: March 2007

Awareness about folic acid's effectiveness in reducing the risk of certain birth defects has increased among women in the United States; however, few Hispanic women are consuming enough folic acid daily. A 1998 survey conducted by the Gallup Organization for the National March of Dimes Birth Defects Foundation found that English-speaking Hispanic women had lower folic acid awareness (53% vs. 72%) and lower daily consumption (29% vs. 33%) than non-Hispanic White women. In 1999, the Centers for Disease Control and Prevention (CDC) conducted baseline surveys with Spanish-speaking Hispanic women in selected U.S. markets to measure folic acid awareness, knowledge, and consumption. A Spanish-language public service announcement (PSA) volunteer campaign and a paid Spanish-language media and community education campaign were conducted in 2000 and 2002, respectively. Comparisons of postcampaign surveys indicate that the paid media campaign was significantly more effective than the PSA campaign in increasing folic acid awareness, knowledge, and consumption among Spanish-speaking Hispanic women.
Applying Projective Techniques to Formative Research in Health Communication Development
Authors: Wiehagen Theresa , Caito Nicole M. , Thompson Vetta Sanders , Casey Christopher M. , Weaver Nancy L. , Jupka Keri , Kreuter Matthew W.
Published: March 2007

This article describes a new approach to formative research in which projective techniques commonly used in psychological assessment were adapted for use in focus groups to help design colorectal-cancer screening materials for African American men and women. Participants (N = 20) were divided into six “design teams.” Each team was given a selection of design supplies and asked to create and discuss a visual layout for screening materials. Participants chose design elements that reflected visual preferences that they felt would connect meaningfully with other African Americans. The dynamics within the design teams were different than in traditional focus groups, with participants having more control over the group's direction. Using projective techniques helped draw out unique information from participants by allowing them to “project” their opinions onto objects. This approach may be a valuable tool for health-promotion and health-communication practitioners seeking insight on the implicit values of a priority population.
The Evolving Role of Health Educators in Advancing Patient Safety
Authors: Mercurio Annette
Published: March 2007

At least 1.5 million preventable injuries because of adverse drug events occur in the United States each year, according to an Institute of Medicine report. IOM and other organizations at the forefront of health care improvement emphasize that stronger partnerships between patients, their families, and health care providers are necessary to make health care safer. Health educators possess a skill set and an ethical framework that effectively equip them to advance patient and family-centered care and contribute in other significant ways to a safer health care system. Health educators in clinical settings are playing varied and significant roles in advancing patient safety. They are removing barriers to clear communication and forging partnerships between patients, their families, and staff. Health educators are leading patient safety culture change within their institutions and contributing to the shift from provider-centric to patient-centric systems. To expand their impact in improving patient safety, health educators in clinical settings are participating in public awareness campaigns. In seeking to enhance patient safety, health educators face a number of challenges. To successfully manage those, health educators must expand their knowledge, broaden connections, and engage patients and families in meaningful ways.
Crucial role of FLT3 ligand in immune reconstitution after bone marrow transplantation and high-dose chemotherapy
Authors: Buza-Vidas Natalija , Cheng Min , Duarte Sara , Nozad Hojjatollah , Jacobsen Sten Eirik W. , Sitnicka Ewa
Published: March 2007

Almost 5 decades after the first clinical transplantations, delayed immune reconstitution remains a considerable hurdle in bone marrow transplantation, and the mechanisms regulating immune reconstitution after transplantation remain to be established. Whereas adult fms-like tyrosine kinase 3 ligand–deficient (FL−/−) mice have reduced numbers of early B- and T-cell progenitors, they sustain close to normal levels of mature B and T cells. Herein, we demonstrate that adult bone marrow cells fail to reconstitute B-cell progenitors and conventional B cells in lethally irradiated FL−/− recipients, which also display delayed kinetics of T-cell reconstitution. Similarly, FL is essential for B-cell regeneration after chemotherapy-induced myeloablation. In contrast, fetal progenitors reconstitute B lymphopoiesis in FL−/− mice, albeit at reduced levels. A critical role of FL in adult B lymphopoiesis is further substantiated by an age-progressive decline in peripheral conventional B cells in FL−/− mice, whereas fetally and early postnatally derived B1 and marginal zone B cells are sustained in a FL-independent manner. Thus, FL plays a crucial role in sustaining conventional B lymphopoiesis in adult mice and, as a consequence, our findings implicate a critical role of FL in promoting immune reconstitution after myeloablation and bone marrow transplantation.
CpG oligodeoxynucleotide-enhanced humoral immune response and production of antibodies to prion protein PrPSc in mice immunized with 139A scrapie-associated fibrils
Authors: Spinner Daryl S , Kascsak Regina B , LaFauci Giuseppe , Meeker Harry C , Ye Xuemin , Flory Michael J , Kim Jae Il , Schuller-Levis Georgia B , Levis William R , Wisniewski Thomas , Carp Richard I , Kascsak Richard J
Published: March 2007

Prion diseases are characterized by conversion of the cellular prion protein (PrPC) to a protease-resistant conformer, the srapie form of PrP (PrPSc). Humoral immune responses to nondenatured forms of PrPSc have never been fully characterized. We investigated whether production of antibodies to PrPSc could occur in PrP null (Prnp−/−) mice and further, whether innate immune stimulation with the TLR9 agonist CpG oligodeoxynucleotide (ODN) 1826 could enhance this process. Whether such stimulation could raise anti-PrPSc antibody levels in wild-type (Prnp+/+) mice was also investigated. Prnp−/− and Prnp+/+ mice were immunized with nondenatured 139A scrapie-associated fibrils (SAF), with or without ODN 1826, and were tested for titers of PrP-specific antibodies. In Prnp−/− mice, inclusion of ODN 1826 in the immunization regime increased anti-PrP titers more than 13-fold after two immunizations and induced, among others, antibodies to an N-terminal epitope, which were only present in the immune repertoire of mice receiving ODN 1826. mAb 6D11, derived from such a mouse, reacts with the N-terminal epitope QWNK in native and denatured forms of PrPSc and recombinant PrP and exhibits a Kd in the 10−11 M range. In Prnp+/+ mice, ODN 1826 increased anti-PrP levels as much as 84% after a single immunization. Thus, ODN 1826 potentiates adaptive immune responses to PrPSc in 139A SAF-immunized mice. These results represent the first characterization of humoral immune responses to nondenatured, infectious PrPSc and suggest methods for optimizing the generation of mAbs to PrPSc, many of which could be used for diagnosis and treatment of prion diseases.
Pleiotropic Effects of PI‐3′ Kinase/Akt Signaling in Human Hepatoma Cell Proliferation and Drug‐Induced Apoptosis
Authors: ALEXIA CATHERINE , BRAS MARLÈNE , FALLOT GUILLAUME , VADROT NATHALIE , DANIEL FANNY , LASFER MALIKA , TAMOUZA HOUDA , GROYER ANDRÉ
Published: March 2007

Abstract:  IGF‐II and type I‐IGF receptor (IGF‐IR) gene expression is increased in primary liver tumors, and transgenic mice overexpressing IGF‐II in the liver develop hepatocellular carcinoma (HCC) spontaneously, suggesting that alterations of IGF‐IR signaling in vivo may play a role in the auto/paracrine control of hepatocarcinogenesis. We have addressed the contribution of PI‐3′K/Akt signaling on the proliferation of HepG2 human hepatoma cells and on their protection against doxorubicin‐induced apoptosis. Both basal HepG2 cell DNA replication and that stimulated by IGF‐IR signaling were inhibited by the specific PI‐3′K inhibitor Ly294002 (Ly). In the former case, PI‐3′K signaling overcame cell cycle arrest in G1 via increased cyclin D1 protein and decreased p27kip1 gene expression. Doxorubicin treatment induced apoptosis in HepG2 cells and was concomitant with the proteolytic cleavage of Akt‐1 and ‐2. Drug‐induced apoptosis was reversed by IGF‐I and this effect was (i) dependent on Akt‐1 and ‐2 phosphorylation and (ii) accompanied by the inhibition of initiator caspase‐9 activity, suggesting that IGF‐IR signaling interferes with mitochondria‐dependent apoptosis. Accordingly, Ly enhanced doxorubicin‐induced apoptosis and suppressed its reversal by IGF‐I. Altogether, the data emphasize the crucial role of PI‐3′K/Akt signaling (i) in basal as well as IGF‐IR‐stimulated HepG2 cell proliferation and (ii) in controlling both doxorubicin‐induced apoptosis (e.g., drug‐induced cleavage of Akt) and its reversal by IGF‐I (protection against apoptosis parallels the extent of Akt phosphorylation). They suggest that targeting Akt activity or downstream Akt effectors (e.g., GSK3‐beta, FOXO transcription factors) may help define novel therapeutic strategies of increased efficacy in the treatment of HCC‐bearing patients.
Magnetic Fields Protect from Apoptosis via Redox Alteration
Authors: DE NICOLA M. , CORDISCO S. , CERELLA C. , ALBERTINI M.C. , D'ALESSIO M. , ACCORSI A. , BERGAMASCHI A. , MAGRINI A. , GHIBELLI L.
Published: March 2007

Abstract:  Magnetic fields (MFs) are receiving much attention in basic research due to their emerging ability to alter intracellular signaling. We show here that static MFs with intensity of 6 mT significantly alter the intracellular redox balance of U937 cells. A strong increase of reactive oxygen species (ROS) and a decrease of glutathione (GSH) intracellular levels were found after 2 h of MF exposure and maintained thereafter. We found that also other types of MFs, such as extremely‐low‐frequency (ELF) MFs affect intracellular GSH starting from a threshold at 0.09 mT. We previously reported that static MFs in the intensity range of 0.3–60 mT reduce apoptosis induced by damaging agents (Fanelli et al., 1998).
Here, we show that ELF‐MFs are also able to protect U937 from apoptosis. Interestingly, this ability is limited to the ELF intensities able to alter redox equilibrium, indicating a link between MF's antiapoptotic effect and the MF alteration of intracellular redox balance. This suggests that MF‐produced redox alterations may be part of the signaling pathway leading to apoptosis antagonism. Thus, we tested whether MFs may still exert an antiapoptotic action in cells where the redox state was artificially altered in both directions, that is, by creating an oxidative (via GSH depletion with BSO) or a reducing (with DTT) cellular environment. In both instances, MFs fail to affect apoptosis. Thus, a correct intracellular redox state is required in order for MFs to exert their antiapoptotic effect.
The Cleavage Mode of Apoptotic Nuclear Vesiculation Is Related to Plasma Membrane Blebbing and Depends on Actin Reorganization
Authors: DE NICOLA M. , CERELLA C. , D'ALESSIO M. , COPPOLA S. , MAGRINI A. , BERGAMASCHI A. , GHIBELLI L.
Published: March 2007

Abstract:  In U937 monocytic cells induced to apoptosis, plasma membrane blebbing of different intensities appears, before the development of nuclear alterations; this latter phenomenon can occur through two major pathways, namely the cleavage and the budding mode (Dini et al., 1996). Strongly blebbing cells develop deep nuclear constrictions leading to nuclear fragmentation according to the cleavage mode, while cells with milder forms of blebbing, or no blebbing at all, undergo nuclear fragmentation along the budding mode. Compounds interfering with different cytoskeletal components affect blebbing, which is completely inhibited by the actin polymerization inhibitors, cytochalasins, while disturbance of tubulin network with taxol limits blebbing to milder forms. At the same time, the cytoskeletal poisons affect the type of nuclear fragmentation, abolishing the cleavage mode, shifting all events into the budding pathway. Adherent cells, which possess a more structured cytoskeleton, do not develop strong blebs and undergo nuclear fragmentation via budding. These observations suggest that the deep cytoskeletal movements that cause the strongest forms of plasma membrane blebbing strangle the nucleus, leading to the constrictions that later evolve into nuclear fragmentation by cleavage. The trigger for the cytoskeletal movements, known to be redox‐sensitive, is probably the apoptotic GSH extrusion.
Alterations in mRNA Expression of Apoptosis‐Related Genes BCL2, BAX, FAS, Caspase‐3, and the Novel Member BCL2L12 after Treatment of Human Leukemic Cell Line HL60 with the Antineoplastic Agent Etoposide
Authors: FLOROS KOSTAS V. , THOMADAKI HELLINIDA , FLOROU DIMITRA , TALIERI MAROULIO , SCORILAS ANDREAS
Published: March 2007

Abstract:  Apoptotic cell death is a highly regulated process, which plays a crucial role in many biological events. Etoposide is an antineoplastic drug, which targets the DNA unwinding enzyme, topoisomerase II. The aim of the present research approach to investigate the expression of the apoptosis‐related genes BCL2 (Bcl‐2), FAS, Caspase‐3, BAX and the new member BCL2L12, cloned by our group, along with treatment of HL‐60 leukemia cells with etoposide. The kinetics of apoptosis induction and cell toxicity was evaluated by DNA laddering and MTT method, respectively. The mRNA expression levels of the genes were analyzed by RT‐PCR using gene‐specific primers. β‐Actin was used as a control gene. An important downregulation of BCL2L12 was observed at 4 h of drug treatment, whereas BAX was upregulated at the same time point. No alteration in the expression pattern of the other apoptosis‐related genes was detected. Since, the main anticarcinogenic effect of etoposide is due to the induction of apoptosis, these changes observed in the mRNA expression levels of the genes may be an underlying mechanism.
Does Transduced p27 Induce Apoptosis in Human Tumor Cell Lines?
Authors: GRDIŠA MIRA , MIKECIN ANA‐MATEA , POZNIC MIROSLAV
Published: March 2007

Abstract:  p27 is a cyclin‐dependent kinase inhibitor involved in the negative regulation of G1 progression in response to a number of antiproliferative signals. In this study, we examined the transduction of full‐length Tat‐p27, pt‐mutated Tat‐p27, and N′‐ Tat‐p27 (truncated p27 on the C‐terminal end) fusion proteins into human tumor cell lines and whether these transduced proteins induced apoptosis in the cells. Protein transduction can be described as the direct uptake by the cell of exogenous proteins/peptides as a result of a specific property of the protein/peptide component. The basic domain of human immunodeficiency virus type 1 (HIV‐1) transactivator of transcription (Tat) protein possesses the ability to traverse biological membranes efficiently in a process termed protein transduction. Although the mechanism is unknown, transduction occurs in receptor/transporter‐independent manner that appears to target the lipid bilayer directly. Thus, HIV‐1 Tat proteins have tremendous potential to deliver large‐sized compounds into the cells. Transduction of TAT‐fusion proteins affected the proliferation of human tumor cell lines, depending on the type of protein and cell line. By Western blot analysis it was shown that some cell cycle regulatory proteins were affected, and that some proteins were responsible for the induction of apoptosis.
Caspase Activation and Extracellular Signal‐Regulated Kinase/Akt Inhibition Were Involved in Luteolin‐Induced Apoptosis in Lewis Lung Carcinoma Cells
Authors: KIM JIN‐HYUNG , LEE EUN‐OK , LEE HYO‐JUNG , KU JIN‐SOOK , LEE MIN‐HO , YANG DEOK‐CHUN , KIM SUNG‐HOON
Published: March 2007

Abstract: Luteolin was isolated fromScutellaria barbataD. Don (S. barbata). In the present study, we examined the underlying molecular mechanism of luteolin and its effect onin vivotumor growth of Lewis lung carcinoma (LLC) cells. Luteolin exhibited antiproliferative activity against LLC cells with IC50of 12 μM. Luteolin effectively increased Annexin‐V‐positive cells as well as sub G1DNA portion as seen on flow cytometric analysis. Western blotting has revealed that luteolin effectively activates caspase 9 and 3, cleaves poly (ADP‐ribose) polymerase (PARP), and increases the ratio of Bax/Bcl‐2. Furthermore, mitochondrial membrane potential was reduced by luteolin as seen on fluorescence microscopy. Luteolin downregulated the expression of extracellular signal‐regulated kinase (ERK) and Akt in a concentration‐dependent manner. In addition, luteolin significantly inhibited the growth of LLC cells implanted on the flank of mice to 40% and 60% of untreated control group values at 2 mg/kg and 10 mg/kg, respectively. Similarly, luteolin significantly reduced the expression of proliferating cell nuclear antigen (PCNA) as well as increased the expression of terminal deoxynucleotidyl transferase biotin‐dUTP nick end labeling (TUNEL) in tumor section of LLC‐bearing mice as determined by immunohistochemistry. Taken together, these results suggest that luteolin exerts antitumor activity by caspase activation and ERK/Akt inhibition.
Two Forms of the Nuclear Matrix–Bound p53 Protein in HEK293 Cells
Authors: LAPSHINA MARIA A. , PARKHOMENKO IGOR I. , TERENTIEV ALEXEI A.
Published: March 2007

Abstract:  Like many other transcription factors, the tumor suppressor protein p53 is bound to the nuclear matrix (NM). To study the interaction of p53 with the NM in more detail, we used alkaline and acidic extractions of NM proteins. It was found that there are two forms of p53, alkali‐ and acid‐soluble, in NM of HEK293 cells and only one alkali‐soluble form in NM of actinomycin D–treated MCF‐7 cells. We suggest that distinct forms of p53 differ either in interactions with NM proteins or in their charges.
Prevention of p53 Degradation in Human MCF‐7 Cells by Proteasome Inhibitors Does Not Mimic the Action of Roscovitine
Authors: RANFTLER CARMEN , GUEORGUIEVA MARIETA , WȨSIERSKA‐GA̧DEK JÒZEFA
Published: March 2007

Abstract:  We have recently observed activation of wild‐type (wt) p53 protein in human MCF‐7 breast cancer cells upon treatment with roscovitine (ROSC), a potent cyclin‐dependent kinase inhibitor. It has been previously suggested that ROSC repressed transcription of Mdm‐2, a negative p53 regulator, and that the lack of Mdm‐2 contributes to the ROSC‐induced upregulation of p53 protein. Therefore, we decided to see whether the prevention of p53 degradation by proteasome inhibitors will mimic the effects generated by ROSC. Exposure of human MCF‐7 cells to different proteasome inhibitors resulted in a time‐dependent increase of p53. However, unlike ROSC, they failed to modify p53 protein at Ser46 and to induce p53AIP1 protein. Moreover, whereas ROSC arrested MCF‐7 cells in the G2‐phase of the cell cycle, proteasome inhibitors blocked cells primarily in the S‐phase, presumably because of the prevention of cyclin degradation. Our results indicate that prevention of p53 degradation by proteasome inhibitors does not mimic the action of ROSC.
Signaling for Integrin α5/β1 Expression in Helicobacter pylori–Infected Gastric Epithelial AGS Cells
Authors: CHO SOON OK , KIM KYUNG HWAN , YOON JOO‐HEON , KIM HYEYOUNG
Published: March 2007

Abstract:  Integrin expression in cancer tissues demonstrates its possible contribution to tumor progression, invasion, and metastasis. Helicobacter pylori (H. pylori) infection is related to gastric cancer and gastric inflammation. H. pylori induced upregulation in expression of integrin in gastric epithelia cells. Reactive oxygen species (ROS) are considered as an important regulator in the pathogenesis of H. pylori–induced gastric ulceration and carcinogenesis. Integrin expression may be regulated by oxidant‐sensitive transcription factors, nuclear factor‐κB (NF‐κB) and activator protein‐1 (AP‐1). The present study aims to investigate whether H. pylori in a Korean isolate (HP99) induces the expression of integrin α5 and integrin β1, and whether H. pylori–induced expression of integrin α5 and integrin β1 are inhibited in the cells transfected with mutant genes for Ras (ras N‐17), c‐Jun (TAM‐67), and IκBα(MAD‐3) or treated with DPI, an inhibitor of NADPH oxidase. As a result, H. pylori induced the expression of integrin α5 and integrin β1 in gastric adenocarcinoma (AGS) cells time‐dependently
. Treatment of DPI or transfection with mutant genes for Ras (ras N‐17), c‐jun (TAM67), and IκBα(MAD3) inhibited H. pylori–induced expression of integrin α5 and integrin β1 in AGS cells. In conclusion, H. pylori activates Ras, NF‐κB, and AP‐1 and thus induces the expression of integrin α5 and integrin β1 in gastric epithelial cells. Inhibition of ROS production by DPI suppressed the expression of integrin α5 and integrin β1 in gastric epithelial cells. The results suggest the possible involvement of NADPH oxidase for ROS production in H. pylori–infected gastric epithelial cells.
The MAPK Pathway and HIF‐1 Are Involved in the Induction of the Human PAI‐1 Gene Expression by Insulin in the Human Hepatoma Cell Line HepG2
Authors: DIMOVA ELITSA Y. , KIETZMANN THOMAS
Published: March 2007

Abstract:  Enhanced levels of plasminogen activator inhibitor‐1 (PAI‐1) are considered to be a risk factor for pathological conditions associated with hypoxia or hyperinsulinemia. The expression of the PAI‐1 gene is increased by insulin in different cells, although, the molecular mechanisms behind insulin‐induced PAI‐1 expression are not fully known yet. Here, we show that insulin upregulates human PAI‐1 gene expression and promoter activity in HepG2 cells and that mutation of the hypoxia‐responsive element (HRE)–binding hypoxia‐inducible factor‐1 (HIF‐1) abolished the insulin effects. Mutation of E‐boxes E4 and E5 abolished the insulin‐dependent activation of the PAI‐1 promoter only under normoxia, but did not affect it under hypoxia. Furthermore, the insulin effect was associated with activation of HIF‐1α via mitogen‐activated protein kinases (MAPKs) but not PDK1 and PKB in HepG2 cells. Furthermore, mutation of a putative FoxO1 binding site which was supposed to be involved in insulin‐dependent PAI‐1 gene expression influenced the insulin‐dependent activation only under normoxia. Thus, insulin‐dependent PAI‐1 gene expression might be regulated by the action of both HIF‐1 and FoxO1 transcription factors.
Doxorubicin‐Induced MAPK Activation in Hepatocyte Cultures Is Independent of Oxidant Damage
Authors: NAVARRO ROSAURA , MARTÍNEZ ROSA , BUSNADIEGO IDOIA , RUIZ‐LARREA M. BEGOÑA , RUIZ‐SANZ JOSÉ IGNACIO
Published: March 2007

Abstract:  Doxorubicin (DOX) is a potent anticancer drug, whose clinical use is limited on account of its toxicity. DOX cytotoxic effects have been associated with reactive oxygen species (ROS) generated during drug metabolism. ROS induce signaling cascades leading to changes in the phosphorylation status of target proteins, which are keys for cell survival or apoptosis. The mitogen‐activated protein kinase (MAPK) cascades are routes activated in response to oxidative stress. In this work, the effects of DOX on cytotoxicity, indicators of oxidative stress (malondialdehyde ‐MDA‐ and GSH), and the phosphorylation status of extracellular signal‐regulated kinases (ERKs), c‐Jun N‐terminal kinases (JNKs), and p38 kinases were analyzed in primary cultures of rat hepatocytes. DOX (1–50 μM) did not modify lactate dehydrogenase (LDH
) release into the medium, the levels of MDA (determined by high‐performance liquid chromatography [HPLC]) or the intracellular GSH during the incubation time up to 6 h. GSH levels from mitochondria extracted by Percoll gradient from cultured hepatocytes were not modified by DOX, thus excluding its depletion or any impaired mitochondrial uptake. Characterization of proteins by Western blot analysis revealed that DOX increased phosphorylation of p38 kinases and JNK1 and JNK2 in a dose‐ and time‐dependent manner. DOX also increased ERK2 phosphorylation at latter time points. In conclusion, DOX triggers activation of ERK, JNK, and p38 kinases in primary cultures of rat hepatocytes independently of oxidant damage.
MAPKinase Gene Expression, as Determined by Microarray Analysis, Distinguishes Uncomplicated from Complicated Reconstitution after Major Surgical Trauma
Authors: SCHNEIDER E. MARION , WEISS MANFRED , DU WEIDONG , LEDER GERHARD , BUTTENSCHÖN KLAUS , LIENER ULRICH C. , BRÜCKNER UWE B.
Published: March 2007

Abstract:  Microarray expression analysis was performed in patients with major surgical trauma to identify signaling pathways which may be indicative for complicated versus uneventful reconstitution post trauma. In addition to a generalized upregulation of nonspecific stress response genes in all patients, a remarkable number of differences in gene expression patterns were found in individual patients. Some of the differing genes were associated with uncomplicated convalescence such as upregulation of both the ERK5 pathway (MAPK7 [mitogen‐activated protein kinase‐7]) and transcription factors which stimulate hematopoiesis and tissue reconstitution (MEF2, BMP‐2, TNFRSF11A [RANK], and RUNX‐1). Chemokine genes active in stem cell recruitment from the bone marrow as well as dendritic cell and natural killer (NK) cell maturation (SCYA14 [HCC‐1]), and activators of the lymphoid compartment (TNFRSF7 [CD27], CD3zeta and perforin [PRF1]) were increased. In contrast, all these transcripts were downregulated in complicated reconstitution and later development of septic shock. Moreover, p38 kinase (MAPK14), S100 molecules, and members of the lipoxygenase pathway were associated with a more eventful outcome. Microarray expression studies are a promising tool for screening and then selecting differentially regulated genes in favorable as compared to complicated reconstitution post trauma.
Chronic Tumor Necrosis Factor-α Treatment Causes Insulin Resistance via Insulin Receptor Substrate-1 Serine Phosphorylation and Suppressor of Cytokine Signaling-3 Induction in 3T3-L1 Adipocytes
Authors: Ishizuka Ken , Usui Isao , Kanatani Yukiko , Bukhari Agussalim , He Jianying , Fujisaka Shiho , Yamazaki Yu , Suzuki Hikari , Hiratani Kazuyuki , Ishiki Manabu , Iwata Minoru , Urakaze Masaharu , Haruta Tetsuro , Kobayashi Masashi
Published: March 2007

Serine phosphorylation of insulin receptor substrate (IRS)-1 and the induction of suppressor of cytokine signaling 3 (SOCS3) is recently well documented as the mechanisms for the insulin resistance. However, the relationship between these two mechanisms is not fully understood. In this study, we investigated the involvement of SOCS3 and IRS-1 serine phosphorylation in TNFα-induced insulin resistance in 3T3-L1 adipocytes. TNFα transiently stimulated serine phosphorylation of IRS-1 from 10 min to 1 h, whereas insulin-stimulated IRS-1 tyrosine phosphorylation was inhibited only after TNFα treatment longer than 4 h. These results suggest that serine phosphorylation of IRS-1 alone is not the major mechanism for the inhibited insulin signaling by TNFα. TNFα stimulation longer than 4 h enhanced the expression of SOCS3 and signal transducer and activator of transcription-3 phosphorylation, concomitantly with the production of IL-6. Anti-IL-6 neutralizing antibody ameliorated suppressed insulin signaling by 24 h TNFα treatment, when it partially decreased SOCS3 induction and signal transducer and activator of transcription-3 phosphorylation. These results suggest that SOCS3 induction is involved in inhibited insulin signaling by TNFα. However, low-level expression of SOCS3 by IL-6 or adenovirus vector did not affect insulin-stimulated IRS-1 tyrosine phosphorylation. Interestingly, when IRS-1 serine phosphorylation was enhanced by TNFα or anisomycin in the presence of low-level SOCS3, IRS-1 degradation was remarkably enhanced. Taken together, both IRS-1 serine phosphorylation and SOCS3 induction are necessary, but one of the pair is not sufficient for the inhibited insulin signaling. Chronic TNFα may inhibit insulin signaling effectively because it causes both IRS-1 serine phosphorylation and the following SOCS3 induction in 3T3-L1 adipocytes.
Comparison of the Diagnostic Accuracy of Brain Natriuretic Peptide (BNP) and the N-Terminal Part of the Propeptide of BNP Immunoassays in Chronic and Acute Heart Failure: A Systematic Review
Authors: Clerico Aldo , Fontana Marianna , Zyw Luc , Passino Claudio , Emdin Michele
Published: March 2007

Background: We used evidence-based laboratory medicine principles to compare the diagnostic accuracy of brain natriuretic peptide (BNP) and the N-terminal part of the propeptide of BNP (NT-proBNP) assays for the diagnosis of heart failure.

Methods: In May 2006, we performed a computerized literature search of the online National Library of Medicine to select studies specifically designed to compare the diagnostic accuracy of BNP and NT-proBNP assays. The comparison took into account the area under the curve and diagnostic odds ratio (DOR) derived from ROC analysis of original studies.

Results: Both BNP and NT-proBNP assays were found to be clinically useful for the diagnosis of heart failure. Metaanalysis of these data was difficult because of the heterogeneity of data regarding patient population, diagnostic criteria, end-points, and immunoassay methods for both BNP and NT-proBNP. Separate metaanalyses were performed for acute and chronic heart failure. In chronic heart failure, the diagnostic DOR for BNP (8.44, 95% CI 4.66–15.30) was not significantly different from that of NT-proBNP (23.36, 95% CI 9.38–58.19). In patients with acute heart failure, the mean DOR for BNP (16.46, 95% CI 10.65–25.43) was not significantly different from that of NT-proBNP (18.61, 95% CI 12.99–26.65).

Conclusion: Our results indicate that both BNP and NT-proBNP assays have a high degree of diagnostic accuracy and clinical relevance for both acute and chronic heart failure.