bluuebunny/crossref_metadata_2025 huggingface dataset:
Plastic vasomotion entrainment
Authors: Sasaki Daichi , Imai Ken , Ikoma Yoko , Matsui Ko
Published: April 2024

The presence of global synchronization of vasomotion induced by oscillating visual stimuli was identified in the mouse brain. Endogenous autofluorescence was used and the vessel ‘shadow’ was quantified to evaluate the magnitude of the frequency-locked vasomotion. This method allows vasomotion to be easily quantified in non-transgenic wild-type mice using either the wide-field macro-zoom microscopy or the deep-brain fiber photometry methods. Vertical stripes horizontally oscillating at a low temporal frequency (0.25 Hz) were presented to the awake mouse, and oscillatory vasomotion locked to the temporal frequency of the visual stimulation was induced not only in the primary visual cortex but across a wide surface area of the cortex and the cerebellum. The visually induced vasomotion adapted to a wide range of stimulation parameters. Repeated trials of the visual stimulus presentations resulted in the plastic entrainment of vasomotion. Horizontally oscillating visual stimulus is known to induce horizontal optokinetic response (HOKR). The amplitude of the eye movement is known to increase with repeated training sessions, and the flocculus region of the cerebellum is known to be essential for this learning to occur. Here, we show a strong correlation between the average HOKR performance gain and the vasomotion entrainment magnitude in the cerebellar flocculus. Therefore, the plasticity of vasomotion and neuronal circuits appeared to occur in parallel. Efficient energy delivery by the entrained vasomotion may contribute to meeting the energy demand for increased coordinated neuronal activity and the subsequent neuronal circuit reorganization.
Transcending Boundaries: Evolving Transhumanist Technologies in International Business and Associated Consideration
Authors: Sharma Kavita , Makhija Tarun Kumar
Published: April 2024

The emergence of transhumanism – the belief in using technology to enhance the human body and experience – has the potential to profoundly disrupt international business landscapes. As genetic engineering, brain-computer interfaces, and human augmentation become increasingly sophisticated, the business world is poised to encounter unprecedented challenges and opportunities. These advancements not only reshape the structure of markets but also redefine the nature of human capital and work dynamics. This paper investigates the implications of these technologies on international business, while also exploring the potential for new markets, ethical considerations, and the complexities of managing a future workforce of augmented humans. This paper investigates the implications of these technologies on international business, while also exploring the potential for new markets, ethical considerations, and the complexities of managing a future workforce of augmented humans.
Investigating the Structure of Defects in Heterometallic Zeolitic Imidazolate Frameworks ZIF-8(Zn/Cd) and Its Interaction with CO2 Using First-Principle Calculations
Authors: Pambudi Fajar Inggit , Sutarno Sutarno , Hatmanto Adhi Dwi , Patmawati Mita , Utari Tika Dwi
Published: April 2024

Inducing defect in metal-organic frameworks (MOFs) is one of the strategies to modify the structure and properties of this functional material. Defect may occur in a pristine MOF due to missing organic linkers, metal centres and/or other structural behaviours. In this study, the structure of defects in multicomponent MOFs especially heterometallic MOFs of zeolitic imidazolate framework (ZIF-8(Zn/Cd)) was examined to unveil the possible preference defect formation due to missing 2-methylimidazolate (MeIm) and metal centres of Cd2+ and Zn2+. Assuming defect formation due to the reaction between ZIF-8(Zn/Cd) and water, MeIm linker removal is energetically lower than removing metal centres of either Cd2+ or Zn2+. But, the MeIm linker is easier to be removed when it is connected to Cd2+ (Cd-MeIm-Cd) than when it is connected to Zn2+ (Zn-MeIm-Zn). Defect in ZIF-8(Zn/Cd) affects the band gap energy to give slightly lower value than it in pristine ZIF-8(Zn/Cd). Non-covalent interaction (NCI) and interaction region indicator (IRI) analyses were also performed to indicate possible intermolecular forces such as van der Waals and attractive forces present in non-defective and defective ZIF-8(Zn/Cd). The presence of defects in mixed-metal ZIF-8(Zn/Cd) was also tested for its potential use on CO2 adsorption. The interaction energy of CO2 inside defective ZIF-8(Zn/Cd) indicates an exothermic behaviour where CO2 molecule has a preference to be adsorbed inside the framework. This is especially when the capping agents at the defective ZIF-8(Zn/Cd) sites are removed to give open metal sites. This study provides insight how defects in multicomponent MOFs might presence affecting the structural and properties changes. Copyright © 2024 by Authors, Published by BCREC Publishing Group. This is an open access article under the CC BY-SA License (https://creativecommons.org/licenses/by-sa/4.0).
Quantitative magnetic resonance imaging analyses and clinical significance of hyperintense white matter lesions in systemic lupus erythematosus patients
Authors: Appenzeller Simone , Vasconcelos Faria Andrea , Li Li Min , Costallat Lilian T. L. , Cendes Fernando
Published: December 2008

Objective

To analyze the clinical significance of hyperintense white matter (WM) lesions in both symptomatic and asymptomatic systemic lupus erythematosus (SLE) patients.

Methods

We studied 120 consecutive SLE patients and 44 healthy volunteers. Fluid attenuated inversion recovery and T2‐weighted magnetic resonance images (MRI) were used for visual and semiautomatic volumetric measurements.

Results

At baseline, 61 MRI were normal and 59 had hyperintense WM lesions. Mean volumes of WM lesions were 96.14 (SD = 85.14) mm3 in T2 weighted and 197.2 (161.13) mm3 in FLAIR images. The volume of WM lesions was associated with age (r = 0.45; p = 0.01), total corticosteroid dose (r = 0.53; p = 0.001), and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index scores (r = 0.55; p = 0.002). After a median follow‐up time of 24 months (SD = 2.3; range = 12–28 months), 20 patients had still normal MRIs, 30 patients had stable MRI findings, and 30 had new WM lesions. Predictors for new or increased WM lesions were past central nervous system manifestations (p = 0.001; OR = 12.2; 95% CI = 3.5–21.2), antiphospholipid antibodies (p = 0.003; OR = 6.9; 95% CI = 2.1–15.3); Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index scores (p = 0.002; OR = 7.2; 95% CI = 1.4–17.8) and higher dose of total corticosteroid dose (p = 0.01; OR = 2.4; 95% CI = 1.4–6.7).

Conclusion

Small hyperintense WM lesions in SLE are associated with central nervous system symptoms and antiphospholipid antibodies, and progress over time in patients with more severe SLE. Therefore, in the context of SLE, these lesions are likely consequences of central nervous system damage and not mere incidental finding. Ann Neurol 2008;64:635–643
Quantitative in vivo magnetic resonance imaging of multiple sclerosis at 7 Tesla with sensitivity to iron
Authors: Hammond Kathryn E. , Metcalf Meredith , Carvajal Lucas , Okuda Darin T. , Srinivasan Radhika , Vigneron Dan , Nelson Sarah J. , Pelletier Daniel
Published: December 2008

Objective

Magnetic resonance imaging at 7 Tesla produces high‐resolution gradient‐echo phase images of patients with multiple sclerosis (MS) that quantify the local field shifts from iron in the basal ganglia and lesions. Phase imaging is easily integrated into clinical examinations because it is a postprocessing technique and does not require additional scanning. The purpose of this study was to quantify local field shifts in MS and to investigate their relation to disease duration and disability status.

Methods

Thirty‐two subjects including 19 patients with MS and 13 age‐ and sex‐matched control subjects were scanned at a spatial resolution of up to 195 × 260μm. Data were postprocessed to produce anatomical quantitative phase images of local field shifts, as well as conventional magnitude images.

Results

The phase images showed an increased local field in the caudate, putamen, and globus pallidus of patients relative to control subjects (p < 0.01). The local field in the caudate was strongly correlated with disease duration (r2 = 0.77; p < 0.001). Phase images showed contrast in 74% of the 403 lesions, increasing the total lesion count by more than 30% and showing distinct peripheral rings and a close association with vasculature.

Interpretation

The increased field in the basal ganglia and correlation with disease duration suggest pathological iron content increases in MS. The peripheral phase rings are consistent with histological data demonstrating iron‐rich macrophages at the periphery of a subset of lesions. The clearly defined vessels penetrating MS lesions should increase our ability to detect focal vascular abnormalities specifically related to demyelinating processes. Ann Neurol 2008;64:707–713
Synthesis, characterization and catalytic studies of ruthenium(II) chalconate complexes
Authors: Muthukumar M. , Viswanathamurthi P.
Published: December 2008

Stable ruthenium(II) carbonyl complexes of the type [RuCl(CO)(EPh3)(B)(L)] (E = P or As; B = PPh3, AsPh3 or Py; L = 2′‐hydroxychalcones) were synthesized from the reaction of [RuHCl(CO)(EPh3)2(B)] (E = P or As; B = PPh3, AsPh3 or Py) with 2′‐hydroxychalcones in benzene under reflux. The new complexes were characterized by analytical and spectroscopic (IR, electronic 1H, 31P and 13C NMR) data. They were assigned an octahedral structure. The complexes exhibited catalytic activity for the oxidation of primary and secondary alcohols into their corresponding aldehydes and ketones in the presence of N‐methylmorpholine‐N‐oxide (NMO) as co‐oxidant and were also found to be efficient transfer hydrogenation catalysts. Copyright © 2008 John Wiley & Sons, Ltd.
Wood preservation by a mixed anhydride treatment: A 13C‐NMR investigation of simple models of polymeric wood constituents
Authors: Lyon F. , Thevenon M.‐F. , Pizzi A. , Tondi G. , Despres A. , Gril J. , Rigolet S.
Published: December 2008

The treatment of wood by a mixed aceto/oleic (or other fatty acid residue) anhydride promoted as a safe and environmentally friendly wood preservation system was examined quantitatively by liquid‐phase 13C‐NMR and solid‐phase magic angle spinning–DEC (proton decoupling) 13C‐NMR through of all its different stages to determine which reactions occurred with simple model compounds of the polymeric constituents of wood. The preparation of the mixed aceto/oleic anhydride under different conditions was also undertaken. The anhydride formed, but its percentage yield was only 30%. The mix composed of unreacted acetic anhydride, the mixed aceto/oleic anhydride, and a large proportion of free acetic and oleic acid, which are used for wood preservation, yielded the acetylation of the lignin model compound (1) by the reaction of the acetic anhydride with it and (2) by the reaction of the acetic part of the mixed anhydride. In this reaction, all of the mixed anhydride was consumed. The oleic part of the mixed anhydride was unable to form esters with either lignin or wood holocellulose as it was far less reactive than the acetic part. Some acetylation of holocellulose occurred, and some traces of its oleic acid ester also occurred under some conditions. This system of treatment through a mixed anhydride appeared to consist of just an acetylation with acetic anhydride mixed with some oleic acid as a water repellent, both of which are already known processes. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009
Development and validation of a model for prediction of mortality in patients with acute burn injury
Authors:   The Belgian Outcome in Burn Injury Study Group, Blot S
Published: December 2008

Background

The objective was to develop a user-friendly model to predict the probability of death from acute burns soon after injury, based on burned surface area, age and presence of inhalation injury.

Methods

This population-based cohort study included all burned patients admitted to one of the six Belgian burn centres. Data from 1999 to 2003 (5246 patients) were used to develop a mortality prediction model, and data from 2004 (981 patients) were used for validation.

Results

Mortality in the derivation cohort was 4·6 per cent. A mortality score (0–10 points) was devised: 0–4 points according to the percentage of burned surface area (less than 20, 20–39, 40–59, 60–79 or at least 80 per cent), 0–3 points according to age (under 50, 50–64, 65–79 or at least 80 years) and 3 points for the presence of an inhalation injury. Mortality in the validation cohort was 4·3 per cent. The model predicted 40 deaths, and 42 deaths were observed (P = 0·950). Receiver–operator characteristic curve analysis of the model for prediction of mortality demonstrated an area under the curve of 0·94 (95 per cent confidence interval 0·90 to 0·97).

Conclusion

An accurate model was developed to predict the probability of death from acute burn injury based on simple and objective clinical criteria.
Importance of routine cavity sampling in breast conservation surgery
Authors: Hewes J C , Imkampe A , Haji A , Bates T
Published: December 2008

Background

The role of cavity biopsy (CB) at the time of wide local excision (WLE) for primary breast cancer has not been evaluated fully. This study compared four groups of patients to determine the significance of margins and CB histology on tumour characteristics and outcome.

Methods

This was a retrospective study of patients undergoing WLE and CB in one institution over 21 years. Demographic data, tumour characteristics and survival information were obtained. Four subgroups of patients were compared according to their margin and cavity status (positive or negative).

Results

A total of 957 patients had WLE. The median 10-year survival was 85·6 per cent and breast cancer-specific survival was 92·4 per cent. Tumour size, grade, node and oestrogen receptor status were independent predictors of survival. There was poor concordance between positivity of resection margins and CB (32·0 per cent); a negative margin carried a 10·8 per cent risk of demonstrable residual disease. A positive CB, but not a positive margin, was associated with reduced overall survival and breast cancer-specific survival.

Conclusion

Cavity status was more significant with regard to survival than margin status. CB is important in identifying residual and multifocal disease, as margin and cavity positivity are often not concordant.
Dangerous halo after neoadjuvant chemotherapy and two-step hepatectomy for colorectal liver metastases
Authors: Mentha G , Terraz S , Morel P , Andres A , Giostra E , Roth A , Rubbia-Brandt L , Majno P
Published: December 2008

Background

Bilobar colorectal metastases are a therapeutic challenge and require a multidisciplinary approach. The aim of this study was to describe the clinical and histological outcomes of patients having neoadjuvant chemotherapy and two-step hepatectomy with right portal vein occlusion for advanced bilateral colorectal metastases.

Methods

A series of 23 consecutive patients treated with curative intent according to a standardized multidisciplinary management protocol was reviewed.

Results

Of 23 patients, 22 completed the programme. There was no mortality and no Clavien grade III morbidity. Median survival from the start of treatment was 45 months, and 1-, 3- and 5-year Kaplan–Meier estimates were 95, 73 and 27 per cent respectively. On histology at the first operation, ten patients had a dangerous halo of proliferating tumour cells infiltrating the surrounding liver parenchyma, of variable importance (six focal and four diffuse), regardless of the response to chemotherapy of the metastases. The dangerous halo increased in prevalence and importance (six focal and seven diffuse) between the first and second operation.

Conclusion

Neoadjuvant chemotherapy followed by two-step hepatectomy with right portal vein occlusion is feasible, safe and may be advantageous to the patient. The appearance of a dangerous halo around the liver metastases may require adaptation of the surgical technique to decrease the risk of local recurrence.
Prognostic significance of insulin-like growth factor II mRNA-binding protein 3 expression in gastric adenocarcinoma
Authors: Jeng Y-M , Wang T-H , Lu S-H , Yuan R-H , Hsu H-C
Published: December 2008

Background

Insulin-like growth factor II mRNA-binding protein (IMP) 3 is expressed in embryonic tissues and multiple cancers. The aim was to establish the prognostic value of IMP-3 expression in gastric adenocarcinoma.

Methods

IMP-3 expression in resected gastric adenocarcinomas was analysed by immunohistochemistry.

Results

IMP-3 was expressed in 183 (58·1 per cent) of 315 tumours. Expression was associated with older age (P < 0·001), larger tumour size (P = 0·009), deep tumour invasion (P < 0·001) and lymph node metastasis (P < 0·001). IMP-3-positive tumours were associated with poorer 5-year survival than negative tumours at all stages (stage I, 82 versus 97 per cent; stage II, 55 versus 78 per cent; stage III and IV, 11 versus 25 per cent; P = 0·005, P = 0·033 and P = 0·036 respectively). Multivariable analysis identified IMP-3 (hazard ratio (HR) 1·93), depth of tumour invasion (HR 3·69, 9·77 and 10·69 for pathological tumour stage (pT) 2, pT3 and pT4 respectively versus pT1), and lymph node metastasis (HR 1·57, 3·29 and 3·40 for pathological node stage (pN) 1, pN2 and pN3 respectively versus pN0) as independent prognostic factors.

Conclusion

IMP-3 expression correlates with the metastatic potential of gastric adenocarcinoma and is an independent prognostic factor.
Testing LED lighting for colour discrimination and colour rendering
Authors: Mahler Elodie , Ezrati Jean‐Jacques , Viénot Françoise
Published: December 2008

Light‐emitting diode (LED) technology offers the possibility of obtaining white light, despite narrow‐band spectra. In order to characterize the colour discrimination efficiency of various LED clusters, we designed a classification test, composed of 32 caps equally distributed along the hue circle at about 3 ΔE* ab‐unit intervals. Forty normal colour observers were screened under four different LED test light sources adjusted for best colour rendering, and under one control incandescent light of the same colour temperature. We used commercially available red, green, blue, and/or amber LED clusters. These yielded a poor colour rendering index (CRI). They also induced a significantly higher number of erroneous arrangements than did the control light. Errors are located around greenish‐blue and purplish‐red shades, parallel to the yellow‐axis direction, whereas when the distribution of light covers the full spectrum, the LED clusters achieve satisfactory colour discrimination efficiency. With respect to the lights we tested, the colour discrimination is correlated with the CIE CRIs as well as with a CRI based on our sample colours. We stress the fact that increasing the chroma of samples by lighting does not necessarily imply an improvement of colour discrimination. © 2008 Wiley Periodicals, Inc. Col Res Appl, 34, 8–17, 2009.
Cinematic‐film protection using metameric blacks
Authors: Rastar Amir
Published: December 2008

This article presents a new approach for security management in digital cinema applications. Metameric blacks are used as a new try for cinematic‐film protection procedures, which are used in theatre projection systems. The information given by the capturing device in production time decomposes to its base spectra and makes an unacceptable image quality for camcorders by adding a specific metameric black to it. This procedure takes place during the exhibition, and the camcorders take poor quality pictures although the image may not have any changes in its quality for the audience. This try tends to reach the goal of security management during the movie plays and may be a new method to keep the rights of producers against digital theft. © 2008 Wiley Periodicals, Inc. Col Res Appl, 34, 93–96, 2009.
Proposal for an indoor daylight illuminant
Authors: Gombos Katalin , Pointer Michael , Sik‐Lányi Cecília , Schanda János , Tarczali Tünde
Published: December 2008

Two indoor daylight illuminants are recommended for general colorimetric and graphic arts use. The daylight illuminants are derived using CIE standard illuminant D65 and illuminant D50 together with the average spectral transmission of a large number of window glass samples. We show that the average window glass filters not only the blue part of the spectrum but also the red part to such an extent that it has to be taken into consideration. Apart from some extreme glass types, the bulk of the window glasses now in use do not show a very large variation in their spectral transmittances, so that an average curve can adequately represent their filtering action. © 2008 Wiley Periodicals, Inc. Col Res Appl, 34, 18–25, 2009.
An evaluator's balancing act: Making decisions about methodological rigor
Authors: Braverman Marc T. , Arnold Mary E.
Published: December 2008

Methodological rigor consists of a series of elements that, in combination, determine the confidence with which conclusions can be drawn from the evaluation results. These elements include evaluation design, conceptualization of constructs, measurement strategies, time frames, program integrity, and others. The authors examine the factors that influence rigor‐related evaluation planning decisions and the relationship of rigor to evaluation use by the sponsoring organization. Rather than following generalized predetermined standards, decisions about rigor should be based on the specific organizational context, information needs for the evaluation, and anticipated benefits and costs of available methodological alternatives. Extension offers a rich organizational context for discussion because of the diversity and complexity of its funding, stakeholders, programs, and evaluations. Several roles are proposed through which evaluators can promote organizational learning with regard to the contribution of methodological rigor to sound evaluation practice. Two Extension evaluations are presented as examples; though they reflect differing levels of rigor, both were thoughtfully planned and resulted in strong use of findings. © Wiley Periodicals, Inc.
The value of evaluation in cooperative extension
Authors: Duttweiler Michael W.
Published: December 2008

The author considers whether current evaluation practice is of value to the Cooperative Extension System. Evaluation use and influence in Extension are characterized through literature review and examination of case examples informed by correspondence with study authors. The more than 675 evaluations examined consistently yielded specific and valuable program counsel applicable to Extension education practice. Nearly seven in ten studies addressed at least one aspect of program improvement. Beyond simply generating a supply of potentially useful findings, there was clear evidence of substantive program modification in response to program evaluation. Case examples indicated that evaluation studies have influenced Extension practice by helping to establish program direction, improving existing educational practice, informing public policy, establishing or sustaining program support, establishing a basis for resource allocation decisions, influencing relationships with stakeholders, and strengthening evaluation practice itself. The author concludes that evaluation practice is both dynamic and influential within the Cooperative Extension System. © Wiley Periodicals, Inc.
sup wit eval ext?
Authors: Patton Michael Quinn
Published: December 2008

Extension and evaluation share some similar challenges, including working with diverse stakeholders, parallel processes for focusing priorities, meeting common standards of excellence, and adapting to globalization, new technologies, and changing times. Evaluations of extension programs have helped clarify how change occurs, especially the relationship between knowledge change and behavior change, the importance of systems thinking, the purposes of evaluation (accountability versus improvement versus knowledge generation), the significance of process use, and the challenge of matching methods to evaluation questions, resources, and purposes to ensure methodological appropriateness. © Wiley Periodicals, Inc.
White‐matter lesions along the cholinergic tracts are related to cortical sources of EEG rhythms in amnesic mild cognitive impairment
Authors: Babiloni Claudio , Pievani Michela , Vecchio Fabrizio , Geroldi Cristina , Eusebi Fabrizio , Fracassi Claudia , Fletcher Evan , De Carli Charles , Boccardi Marina , Rossini Paolo Maria , Frisoni Giovanni B.
Published: December 2008

Does impairment of cholinergic systems represent an important factor in the development of amnesic mild cognitive impairment (aMCI), as a preclinical stage of Alzheimer's disease (AD)? Here we tested the hypothesis that electroencephalographic (EEG) rhythms, known to be modulated by the cholinergic system, may be particularly affected in aMCI patients with lesions along the cholinergic white‐matter tracts. Eyes‐closed resting EEG data were recorded in 28 healthy elderly (Nold) and 57 aMCI patients. Lesions along the cholinergic white‐matter tracts were detected with fluid‐attenuated inversion recovery sequences on magnetic resonance imaging. The estimation of the cholinergic lesion was performed with a validated semi‐automatic algorithm pipeline after registration to a stereotactic template, image integration with stereotactic masks of the cholinergic tracts, and normalization to intracranial volume. The aMCI patients were divided into two groups of high (MCI Ch+; N = 29; MMSE = 26.2) and low cholinergic damage (MCI Ch−; N = 28; MMSE = 26.6). EEG rhythms of interest were delta (2–4 Hz), theta (4–8 Hz), alpha 1 (8–10.5 Hz), alpha 2 (10.5–13 Hz), beta 1 (13–20 Hz), and beta 2 (20–30 Hz). Cortical EEG generators were estimated by LORETA software. As main results, (i) power of occipital, parietal, temporal, and limbic alpha 1 sources was maximum in Nold, intermediate in MCI Ch−, and low in MCI Ch+ patients; (ii) the same trend was true in theta sources. These results are consistent with the hypothesis that damage to the cholinergic system is associated with alterations of EEG sources in aMCI subjects. Hum Brain Mapp 2009. © 2008 Wiley‐Liss, Inc.
Mutation in the DNA‐binding domain of the EWS‐Oct‐4 oncogene results in dominant negative activity that interferes with EWS‐Oct‐4‐mediated transactivation
Authors: Kim Sol , Lee Jungwoon , Kim Ja Young , Lim Bobae , Shin Eung‐Kyun , Han Yong‐Mahn , Kim Sung‐Su , Song Jin‐Ho , Kim Jungho
Published: December 2008

The EWS‐Oct‐4 protein is a chimeric molecule in which the amino terminal domain (NTD) of the EWS becomes fused to the carboxy terminal domain (CTD) of the Oct‐4 transcription factor. It was identified in human bone and soft‐tissue tumors associated with t(6;22)(p21;q12). Using in vitro and in vivo systems, we found that the EWS‐Oct‐4 protein self‐associates. The major domains required for self‐association mapped to the EWS NTD (amino acids 70–163) and the POU DNA‐binding domain. EWS‐Oct‐4 protein also associated with EWS‐Oct‐4 (V351P), which contains a mutation in the POU DNA‐binding domain. Using electrophoretic mobility shift assays, we found that the EWS‐Oct‐4 (V351P) mutant interfered with wild‐type EWS‐Oct‐4 DNA‐binding activity. In addition, we found that EWS‐Oct‐4‐mediated transcriptional activation was inhibited by EWS‐Oct‐4 (V351P) protein in vivo. Thus, this mutation in the POU DNA‐binding domain results in a dominant negative protein. These findings suggest that the biological functions of the EWS‐Oct‐4 oncogene can be modulated by the dominant negative mutant EWS‐Oct‐4 (V351P). © 2008 Wiley‐Liss, Inc.
Actin and Vimentin proteins with N‐terminal deletion detected in tumor‐bearing rat livers induced by intraportal‐vein injection of Ha‐ras‐transfected rat liver cells
Authors: Nakamura Yasushi , Kominami Akari , Tsujimoto Yoshiyuki , Nakayama Yuko , Kitahashi Tsukasa , Yoshimoto Sonoko , Kubo Asuka , Watanabe Shinpei , Kageyama Minami , Yokoyama Meiko , Kido Yasuhiro , Kobayashi Yukiko , Kuwahata Masashi , Chang Chia‐Cheng , Upham Brad L. , Trosko James E. , Park Eun Young , Sato Kenji
Published: December 2008

The introduction of the tumorigenic v‐Ha‐ras oncogene‐transformed rat liver epithelial cells (WBras), which is deficient in gap junctional intercellular communication (GJIC), into F344 rats, induces significant formation of hepatocellular tumors. GJIC plays a major role in maintaining tissue homeostasis. Using this in vivo tumor model system, we used 2‐dimensional electrophoresis with isoelectric focusing in the first dimension and SDS‐PAGE in the second dimension to globally identify proteins that are uniquely expressed in the livers of WBras‐treated rats as compared to the sham control. Immunoblotting was used to identify Ras and Connexin43, which were the positive and negative marker proteins, respectively, of the introduced WBras cells. As predicted, immunoblotting indicated that the whole liver of tumor‐bearing animals exhibited a decreased level of Connexin43 and an increased level of Ras. Connexin43 and GJIC were expressed and functional in normal liver, but not in the tumor. In addition to these 2 markers, an additional 4 proteins exhibited decreased levels and 2 proteins exhibited increased levels in the livers of tumor‐bearing animals. N‐Terminal sequencing analysis was used to identify these proteins, which were glucose‐regulated protein 78, 2 isoforms of heat shock protein 60, and the β‐chain of ATP synthase for the down regulated proteins, and β‐Actin with a 46 amino acid deletion from its N‐terminus and Vimentin with a 71 amino acid deletion from its N‐terminus for the up regulated proteins. These data offer potentially new markers of liver tumorigenicity, particularly, Vimentin. © 2008 Wiley‐Liss, Inc.
Spleen tyrosine kinase as a novel candidate tumor suppressor gene for human oral squamous cell carcinoma
Authors: Ogane Satoru , Onda Takeshi , Takano Nobuo , Yajima Tetsuo , Uchiyama Takeshi , Shibahara Takahiko
Published: December 2008

We analyzed the mutational and methylation status of the spleen tyrosine kinase (Syk) gene and both mRNA and protein levels in primary oral squamous cell carcinoma (OSCC) and OSCC‐derived cell lines and examined the function of the Syk gene in OSCC‐derived cell lines in vitro. Using quantitative real‐time reverse transcription polymerase chain reaction, Western blotting and immunofluorescence on 7 OSCC‐derived cell lines and normal oral keratinocytes (NOKs), Syk mRNA and protein expression were commonly downregulated in all cell lines compared to the NOKs. Although no sequence variation in the coding region of the Syk gene was identified in these cell lines, we found frequent hypermethylation in the CpG island region. Syk expression was restored by experimental demethylation. In addition, using a wound healing assay and in vitro invasion assay, we performed functional analysis using Syk transfected into the OSCC‐derived cell lines, and they showed significant inhibition of motility and invasiveness. In clinical samples, high frequencies of Syk downregulation were detected by immunohistochemistry (33 of 53 [62%]). Furthermore, the Syk expression status was correlated significantly (p = 0.047) with tumor metastasis to cervical lymph nodes. These results suggest that the Syk gene is frequently inactivated during oral carcinogenesis and that an epigenetic mechanism may regulate loss of expression possibly leading to metastasis. © 2008 Wiley‐Liss, Inc.
Strain‐specific viral properties of variant Creutzfeldt–Jakob disease (vCJD) are encoded by the agent and not by host prion protein
Authors: Manuelidis Laura , Liu Ying , Mullins Brian
Published: December 2008

Human CJD, endemic sheep scrapie, epidemic bovine spongiform encephalopathy (BSE), and other transmissible spongiform encephalopathies (TSEs), are caused by a group of related but molecularly uncharacterized infectious agents. The UK‐BSE agent infected many species, including humans where it causes variant CJD (vCJD). As in most viral infections, different TSE disease phenotypes are determined by both the agent strain and the host species. TSE strains are most reliably classified by incubation time and regional neuropathology in mice expressing wild‐type (wt) prion protein (PrP). We compared vCJD to other human and animal derived TSE strains in both mice and neuronal cultures expressing wt murine PrP. Primary and serial passages of the human vCJD agent, as well as the highly selected mutant 263K sheep scrapie agent, revealed profound strain‐specific characteristics were encoded by the agent, not by host PrP. Prion theory posits that PrP converts itself into the infectious agent, and thus short incubations require identical PrP sequences in the donor and recipient host. However, wt PrP mice injected with human vCJD brain homogenates showed dramatically shorter primary incubation times than mice expressing only human PrP, a finding not in accord with a PrP species barrier. All mouse passage brains showed the vCJD agent derived from a stable BSE strain. Additionally, both vCJD brain and monotypic neuronal cultures produced a diagnostic 19 kDa PrP fragment previously observed only in BSE and vCJD primate brains. Monotypic cultures can be used to identify the intrinsic, strain‐determining molecules of TSE infectious particles. J. Cell. Biochem. 106: 220–231, 2009. © 2008 Wiley‐Liss, Inc.
Aberrant regulation and modification of heat shock factor 1 in senescent human diploid fibroblasts
Authors: Lee Yoon Kwang , Liu Diana J. , Lu Jiebo , Chen Kuang Yu , Liu Alice Y.‐C.
Published: December 2008

Induction of the heat shock response (HSR), determined by hsp70‐luciferase reporter and HSP70 protein expression, is attenuated as a function of age of the IMR‐90 human diploid fibroblasts. To better understand the underlying mechanism, we evaluated changes in the regulation and function of the HSF1 transcription factor. We show that the activation of HSF1 both in vivo and in vitro was decreased as a function of age, and this was attributable to a change in the regulation of HSF1 as the abundance of HSF1 protein and mRNA was unaffected. HSF1 was primarily cytosolic in young cells maintained at 37°C, and heat shock promoted its quantitative nuclear translocation and trimerization. In old cells, some HSF1 was nuclear sequestered at 37°C, and heat shock failed to promote the quantitative trimerization of HSF1. These changes in HSF1 could be reproduced by treating young cells with H2O2 to stunt them into premature senescence. Flow cytometry measurement of peroxide content showed higher levels in old cells and H2O2‐induced premature senescent cells as compared to young cells. Experiments using isoelectric focusing and Western blot showed age‐dependent changes in the mobility of HSF1 in a pattern consistent with its S‐glutathiolation and S‐nitrosylation; these changes could be mimicked by treating young cells with H2O2. Our results demonstrated dynamic age‐dependent changes in the regulation but not the amount of HSF1. These changes are likely mediated by oxidative events that promote reversible and irreversible modification of HSF1 including S‐glutathiolation and S‐nitrosylation. J. Cell. Biochem. 106: 267–278, 2009. © 2008 Wiley‐Liss, Inc.
Effects of MAPK signaling on 1,25‐dihydroxyvitamin D‐mediated CYP24 gene expression in the enterocyte‐like cell line, Caco‐2
Authors: Cui Min , Zhao Yan , Hance Kenneth W. , Shao Andrew , Wood Richard J. , Fleet James C.
Published: December 2008

We examined the role of the extracellular signal regulated kinases (ERK) in 1,25‐dihydroxyvitamin D (1,25(OH)2D3)‐induced gene expression in the differentiated Caco‐2 cells. 1,25(OH)2D3‐regulated expression of the 25‐hydroxyvitamin D, 24‐hydroxylase (CYP24) gene (both natural gene and promoter construct) was strongly modulated by altering ERK activity (i.e., reduced by MEK inhibitors and dominant negative (dn) ERK1 and ERK2, activated by epidermal growth factor) but ERK inhibition had no effect on 1,25(OH)2D3‐regulated expression of the transient receptor potential cation channel, subfamily V, member 6 (TRPV6). ERK5‐mediated phosphorylation of the transcription factor Ets‐1 enhanced 1,25(OH)2D3‐mediated CYP24 gene transcription in proliferating but not differentiated Caco‐2 cells due to reduced levels of ERK5 and Ets‐1 (total and phosphoprotein levels) in differentiated cells. MEK inhibition reduced 1,25(OH)2D3‐induced 3X‐VDRE promoter activity but had no impact on the association of vitamin D receptor (VDR) with chromatin suggesting a role for co‐activator recruitment in ERK‐modulation of vitamin D‐regulated CYP24 gene activation. Chromatin immunoprecipitation assays revealed that the ERK1/2 target, mediator 1 (MED1), is recruited to the CYP24, but not the TRPV6, promoter following 1,25(OH)2D3 treatment. MED1 phosphorylation was sensitive to activators and inhibitors of the ERK1/2 signaling and MED1 siRNA reduced 1,25(OH)2D3‐regulated human CYP24 promoter activity. This suggests ERK1/2 signaling enhances 1,25(OH)2D3 effects on the CYP24 promoter by MED1‐mediated events. Our data show that there are both promoter‐specific and cell stage‐specific roles for the ERK signaling pathway on 1,25(OH)2D3‐mediated gene induction in enterocyte‐like Caco‐2 cells. J. Cell. Physiol. 219: 132–142, 2009. © 2008 Wiley‐Liss, Inc.
Negative modulation of eNOS by laminin involving post‐translational phosphorylation
Authors: Kumar V.B. Sameer , Viji R.I. , Kiran M.S. , Sudhakaran P.R.
Published: December 2008

Nitric oxide (NO) regulates the vascular tone, and influences survival and apoptosis of endothelial cells (ECs). NO is produced by nitric oxide synthase (NOS) and eNOS is the constitutive enzyme in the endothelium. Though the extracellular matrix (ECM) has been reported to regulate various EC functions, the role of ECM in the regulation of eNOS is not clear. The present study was designed to analyze if laminin‐1 (Ln‐1), the major glycoprotein of the basement membrane, can regulate eNOS. The activity of eNOS was significantly low in ECs maintained on Ln‐1 as compared to those on Col I and polylysine. Reversal of the effect of Ln‐1 on treatment with inhibitor of p38 MAPK and changes in Thr and Ser phosphorylation in purified eNOS suggested that eNOS activity in cells maintained on Ln‐1 is negatively regulated by post‐translational phosphorylation at Ser and Thr residues by recruiting p38 MAPK pathway. Increase in eNOS activity and induction of apoptosis upon inhibition of p38 MAPK and reversal of this on inhibition of NOS by L‐NAME suggested that increased NO induced apoptosis in ECs maintained on Ln‐1 when p38 MAPK was inhibited. These results suggest that Ln contributes to survival of ECs by negatively modulating eNOS in a p38 MAPK dependent pathway. J. Cell. Physiol. 219: 123–131, 2009. © 2008 Wiley‐Liss, Inc.
Modulation of muscle rNav1.4 Na+ channel isoform by arachidonic acid and its non‐metabolized analog
Authors: Gu Hua , Fang Yan‐Jia , He Yan‐Lin , Sun Ji , Zhu Jian , Mei Yan‐Ai
Published: December 2008

Arachidonic acid (AA) and its metabolic products are important second messengers which exert many biological actions, including modulation of various ion channels. However, the blockage of muscle Na+ channel isoforms by AA has not been examined in detail. Here, we investigated the modulating effects of AA on muscle rNaV1.4 isoforms expressed in human embryonic kidney 293 cells. The results revealed that AA has both activation and inhibitory effects on rNaV1.4 currents depending on the depolarizing potential: AA increased the rNaV1.4 current evoked by a depolarization of −30 or −40 mV, but significantly decreased the rNaV1.4 current evoked by a depolarization of membrane potential over −10 mV. At concentrations of 1–500 µM, the inhibitory effect on the rNaV1.4 current induced by AA was dose‐dependent and reversible. In addition to modulating the amplitude of the rNaV1.4 current, AA significantly modulated the steady‐state activation and inactivation properties of rNaV1.4 channels. Furthermore, treatment with AA resulted in a fairly slow recovery of the rNaV1.4 channel from inactivation; however, the inhibitory effect of AA was not changed by repetitive pulses or by changing frequency. The effect of AA on rNaV1.4 currents was completely mimicked by ETYA, the non‐metabolized analog of AA. Our data demonstrated that AA, but not the metabolic products of AA, can voltage‐dependent modulate rNaV1.4 currents. J. Cell. Physiol. 219: 173–182, 2009. © 2008 Wiley‐Liss, Inc.
Nuclear matrix binding site in the Rad51 recombinase
Authors: Mladenov Emil V. , Kalev Peter S. , Anachkova Boyka B.
Published: December 2008

It has been shown that the key homologous recombination protein Rad51accumulates in DNA damage‐induced nuclear foci that are attached to the nuclear matrix. In the present communication we attempted to find whether Rad51 contains a functional domain responsible for nuclear matrix binding. By alignments of the sequences encoding nuclear matrix targeting signals of human nuclear matrix binding proteins with the whole length human Rad51sequence a putative nuclear matrix targeting signal was identified. To prove that it is responsible for the nuclear matrix association of Rad51 18 base pairs encoding a cluster of hydrophobic amino acids in the human Rad51 Flag‐tagged gene were deleted. The formation of damage‐induced Rad51 foci and their association with the nuclear matrix were monitored in HeLa cells transfected with the wild‐type and the mutated Rad51gene after treatment with mitomycin C. The results showed that while the wild‐type protein formed Rad51 foci attached to the nuclear matrix, the mutated Rad51 failed to form DNA damage‐induced nuclear foci. The loss of foci formation activity of the mutated protein was not due to impaired ability to bind double‐stranded DNA in an ATP‐dependant way in vitro and to bind chromatin in vivo. These data suggest that the assembly of Rad51 into nuclear foci is assisted by association with the nuclear matrix, which may support the spatial organization of the process of repair by homologous recombination. J. Cell. Physiol. 219: 202–208, 2009. © 2008 Wiley‐Liss, Inc.
The Ape‐1/Ref‐1 redox antagonist E3330 inhibits the growth of tumor endothelium and endothelial progenitor cells: Therapeutic implications in tumor angiogenesis
Authors: Zou Gang‐Ming , Karikari Collins , Kabe Yasuaki , Handa Hiroshi , Anders Robert A. , Maitra Anirban
Published: December 2008

The apurinic/apyrimidinic endonuclease 1/redox factor‐1 (Ape‐1/Ref‐1) is a multi‐functional protein, involved in DNA repair and the activation of redox‐sensitive transcription factors. The Ape‐1/Ref‐1 redox domain acts as a cytoprotective element in normal endothelial cells, mitigating the deleterious effects of apoptotic stimuli through induction of survival signals. We explored the role of the Ape‐1/Ref‐1 redox domain in the maintenance of tumor‐associated endothelium, and of endothelial progenitor cells (EPCs), which contribute to tumor angiogenesis. We demonstrate that E3330, a small molecule inhibitor of the Ape‐1/Ref‐1 redox domain, blocks the in vitro growth of pancreatic cancer‐associated endothelial cells (PCECs) and EPCs, which is recapitulated by stable expression of a dominant‐negative redox domain mutant. Further, E3330 blocks the differentiation of bone marrow‐derived mesenchymal stem cells (BMSCs) into CD31+ endothelial progeny. Exposure of PCECs to E3330 results in a reduction of H‐ras expression and intracellular nitric oxide (NO) levels, as well as decreased DNA‐binding activity of the hypoxia‐inducible transcription factor, HIF‐1α. E3330 also reduces secreted and intracellular vascular endothelial growth factor expression by pancreatic cancer cells, while concomitantly downregulating the cognate receptor Flk‐1/KDR on PCECs. Inhibition of the Ape‐1/Ref‐1 redox domain with E3330 or comparable angiogenesis inhibitors might be a potent therapeutic strategy in solid tumors. J. Cell. Physiol. 219: 209–218, 2009. © 2008 Wiley‐Liss, Inc.
Multicompartmental analysis of late contrast enhancement in areas of myocardial infarction supplied by chronically occluded coronary arteries
Authors: Mandry Damien , Lapicque Françoise , Odille Freddy , Djaballah Wassila , Codreanu Andrei , Escanyé Jean‐Marie , Felblinger Jacques , Karcher Gilles , Claudon Michel , Marie Pierre‐Yves
Published: December 2008

Purpose

To analyze the relationship between late contrast enhancement (LCE) and the interstitial distribution volume (VIn) of gadolinium (Gd) tracers in the myocardial infarction (MI) areas supplied by chronically occluded arteries from patients. In animal experimental models, LCE has already been shown to correspond to an enhanced VIn of Gd tracers and thus, to a decrease in the amount of intact cells.

Materials and Methods

A multicompartmental analysis was applied to serial MRI images encompassing both infarct and remote areas and recorded with a conventional two‐dimensional (2D) segmented inversion‐recovery gradient‐echo (IR‐GRE) sequence during a 15‐minute period following Gd‐diethylenetriamine pentaacetic acid (Gd‐DTPA) injection in 12 patients with Q‐wave MI supplied by chronically occluded coronary arteries.

Results

VIn from infarct tissue was: 1) higher than VIn from remote areas (in % of myocardial volume: 74 ± 16% vs. 20 ± 7%, P < 0.001); and 2) correlated with the quantification of LCE between infarct and noninfarct areas at the 15th minute (R2 = 0.63, P = 0.002). However, the difference in VIn between infarct and remote myocardium was a much better correlate of this quantified LCE (R2 = 0.85, P < 0.001).

Conclusion

Detection of LCE in the MI territories supplied by chronically occluded arteries relates to the difference in the VIn of tracers between the infarct and the noninfarct areas. J. Magn. Reson. Imaging 2009;29:78–85. © 2008 Wiley‐Liss, Inc.
Susceptibility compensated fMRI study using a tailored RF echo planar imaging sequence
Authors: Chung Jun‐Young , Yoon Hyo Woon , Kim Young‐Bo , Park Hyun Wook , Cho Zang‐Hee
Published: December 2008

Purpose

To implement a method using a tailored radiofrequency (TRF) pulse with a quadratic phase profile to recover susceptibility‐induced signal losses in gradient‐recalled echo‐planar images (EPI).

Materials and Methods

A functional magnetic resonance imaging (fMRI) experiment for compensation of susceptibility artifacts, known as the TRF pulse EPI sequence (TRF‐EPI), was used. TRF pulse compensates the susceptibility effect with a reduced signal‐to‐noise ratio (SNR) to one‐half when the maximum phase distribution is 2π. We demonstrate theoretically that the maximum phase distribution can also be reduced to π rather than 2π, improving the SNR accordingly. An analysis was conducted comparing this newly proposed strategy using a standard RF excitation with a linear phase distribution and a quadratic TRF excitation with a π phase distribution.

Results

Thorough experimental comparisons were also made between the TRF quadratic excitation with a π phase profile and conventional EPI with a standard excitation in human subjects during ventral brain activation.

Conclusion

With reduced maximum phase distribution in the TRF pulse, signals in the susceptibility‐affected areas, such as the orbitofrontal and inferior temporal cortex, were increased, suggesting that the technique could be a useful adjunct to fMRI. J. Magn. Reson. Imaging 2009;29:221–228. © 2008 Wiley‐Liss, Inc.