bluuebunny/crossref_metadata_2025 huggingface dataset:
Tight associations between transcription promoter type and epigenetic variation in histone positioning and modification
Authors: Nozaki Tadasu , Yachie Nozomu , Ogawa Ryu , Kratz Anton , Saito Rintaro , Tomita Masaru
Published: August 2011

Background

Transcription promoters are fundamental genomic cis-elements controlling gene expression. They can be classified into two types by the degree of imprecision of their transcription start sites: peak promoters, which initiate transcription from a narrow genomic region; and broad promoters, which initiate transcription from a wide-ranging region. Eukaryotic transcription initiation is suggested to be associated with the genomic positions and modifications of nucleosomes. For instance, it has been recently shown that histone with H3K9 acetylation (H3K9ac) is more likely to be distributed around broad promoters rather than peak promoters; it can thus be inferred that there is an association between histone H3K9 and promoter architecture.

Results

Here, we performed a systematic analysis of transcription promoters and gene expression, as well as of epigenetic histone behaviors, including genomic position, stability within the chromatin, and several modifications. We found that, in humans, broad promoters, but not peak promoters, generally had significant associations with nucleosome positioning and modification. Specifically, around broad promoters histones were highly distributed and aligned in an orderly fashion. This feature was more evident with histones that were methylated or acetylated; moreover, the nucleosome positions around the broad promoters were more stable than those around the peak ones. More strikingly, the overall expression levels of genes associated with broad promoters (but not peak promoters) with modified histones were significantly higher than the levels of genes associated with broad promoters with unmodified histones.

Conclusion

These results shed light on how epigenetic regulatory networks of histone modifications are associated with promoter architecture.
LeukoCatch, a quick and efficient tool for the preparation of leukocyte extracts from blood
Authors: Okuzaki Daisuke , Kimura Shoichi , Yabuta Norikazu , Ohmine Toshinari , Nojima Hiroshi
Published: August 2011

Background

Whole-protein extracts from peripheral blood leukocytes are ideal for basic and clinical research. However, lack of a simple preparation technique has limited the use of such extracts. The aim of this study is to develop a simple and easy system that can selectively obtain leukocyte extracts without hemoglobin.

Methods

A filter that captures the leukocytes but not RBCs was set at the bottom of a 10-mL medical syringe by sandwiching it between plastic stoppers. The capturing efficiency of leukocytes with this tool, called LeukoCatch, was examined using human macrophage cells (MONO-MAC-6). The abilities of LeukoCatch system to capture the leukocyte proteins and to remove the hemoglobin from RBCs were tested by western blot analysis using human blood samples.

Results

This study presents the development of LeukoCatch, a novel tool that allows the preparation of leukocyte extracts from blood samples within 3 min without centrifugation. Tissue-cultured human macrophage cells were tested to determine the optimal filter numbers and pass-through frequencies of LeukoCatch, which was then applied to 2-mL blood samples. Samples were passed 2~5 times through a LeukoCatch equipped with 5 filters, washed twice with phosphate-buffered saline for red cell removal, and leukocyte proteins were extracted with 0.5 mL of elution buffer. Western blot analysis of the purified extract indicated that more than 90% of hemoglobin was removed by the LeukoCatch and that the protein recovery rate of leukocytes was at least 4 times better than that of the conventional centrifugation method.

Conclusion

We conclude that LeukoCatch is useful not only for diagnosis at the bedside but also for basic research using blood samples or tissue culture cells.
Feasibility and acceptability of ACT for the community case management of malaria in urban settings in five African sites
Authors: Akweongo Patricia , Agyei-Baffour Peter , Sudhakar Morankar , Simwaka Bertha N , Konaté Amadou T , Adongo Philip B , Browne Edmund NL , Tegegn Ayalew , Ali Doreen , Traoré Abdoulaye , Amuyunzu-Nyamongo Mary , Pagnoni Franco , Barnish Guy
Published: August 2011

Background

The community case management of malaria (CCMm) is now an established route for distribution of artemisinin-based combination therapy (ACT) in rural areas, but the feasibility and acceptability of the approach through community medicine distributors (CMD) in urban areas has not been explored. It is estimated that in 15 years time 50% of the African population will live in urban areas and transmission of the malaria parasite occurs in these densely populated areas.

Methods

Pre- and post-implementation studies were conducted in five African cities: Ghana, Burkina Faso, Ethiopia and Malawi. CMDs were trained to educate caregivers, diagnose and treat malaria cases in < 5-year olds with ACT. Household surveys, focus group discussions and in-depth interviews were used to evaluate impact.

Results

Qualitative findings: In all sites, interviews revealed that caregivers' knowledge of malaria signs and symptoms improved after the intervention. Preference for CMDs as preferred providers for malaria increased in all sites.

Quantitative findings: 9001 children with an episode of fever were treated by 199 CMDs in the five study sites. Results from the CHWs registers show that of these, 6974 were treated with an ACT and 6933 (99%) were prescribed the correct dose for their age. Fifty-four percent of the 3,025 children for which information about the promptness of treatment was available were treated within 24 hours from the onset of symptoms.

From the household survey 3700 children were identified who had an episode of fever during the preceding two weeks. 1480 (40%) of them sought treatment from a CMD and 1213 of them (82%) had received an ACT. Of these, 1123 (92.6%) were administered the ACT for the correct number of doses and days; 773 of the 1118 (69.1%) children for which information about the promptness of treatment was available were treated within 24 hours from onset of symptoms, and 768 (68.7%) were treated promptly and correctly.

Conclusions

The concept of CCMm in an urban environment was positive, and caregivers were generally satisfied with the services. Quality of services delivered by CMDs and adherence by caregivers are similar to those seen in rural CCMm settings. The proportion of cases seen by CMDs, however, tended to be lower than was generally seen in rural CCMm. Urban CCMm is feasible, but it struggles against other sources of established healthcare providers. Innovation is required by everyone to make it viable.
Biodistribution and blood clearance of plasmid DNA administered in arginine peptide complexes
Authors: Woo Jung Gyu , Kim Na Young , Yang Jai Myung , Shin Sungho
Published: August 2011

Background

Peptide/DNA complexes have great potential as non-viral methods for gene delivery. Despite promising results for peptide-mediated gene delivery technology, an effective systemic peptide-based gene delivery system has not yet been developed.

Methods

This study used pCMV-Luc as a model gene to investigate the biodistribution and the in vivo efficacy of arginine peptide-mediated gene delivery by polymerase chain reaction (PCR).

Results

Plasmid DNA was detected in all organs tested 1 h after intraperitoneal administration of arginine/DNA complexes, indicating that the arginine/DNA complexes disseminated widely through the body. The plasmid was primarily detected in the spleen, kidney, and diaphragm 24 h post administration. The mRNA expression of plasmid DNA was noted in the spleen, kidney, and diaphragm for up to 2 weeks, and in the other major organs, for at least 1 week. Blood clearance studies showed that injected DNA was found in the blood as long as 6 h after injection.

Conclusions

Taken together, our results demonstrated that arginine/DNA complexes are stable in blood and are effective for in vivo gene delivery. These findings suggest that intraperitoneal administration of arginine/DNA complexes is a promising tool in gene therapy.
Optical properties of as-grown and annealed InAs quantum dots on InGaAs cross-hatch patterns
Authors: Himwas Chalermchai , Panyakeow Somsak , Kanjanachuchai Songphol
Published: August 2011

InAs quantum dots (QDs) grown on InGaAs cross-hatch pattern (CHP) by molecular beam epitaxy are characterized by photoluminescence (PL) at 20 K. In contrast to QDs grown on flat GaAs substrates, those grown on CHPs exhibit rich optical features which comprise as many as five ground-state emissions from [1-10]- and [110]-aligned QDs, two wetting layers (WLs), and the CHP. When subject to in situ annealing at 700°C, the PL signals rapidly degrades due to the deterioration of the CHP which sets the upper limit of overgrowth temperature. Ex situ hydrogen annealing at a much lower temperature of 350°C, however, results in an overall PL intensity increase with a significant narrowing and a small blueshift of the high-energy WL emission due to hydrogen bonding which neutralizes defects and relieves associated strains.
Integrated postdischarge transitional care in a hospitalist system to improve discharge outcome: an experimental study
Authors: Shu Chin-Chung , Hsu Nin-Chieh , Lin Yu-Feng , Wang Jann-Yuan , Lin Jou-Wei , Ko Wen-Je
Published: August 2011

Background

The postdischarge period is a vulnerable time for patients, with high rates of adverse events that may cause unnecessary readmissions, especially in the elderly. Because postdischarge care continuity is often interrupted after hospitalist care, close follow-up may decrease patient readmission. In this study, we aimed to investigate the impact of a quality improvement program, integrated postdischarge transitional care (PDTC), in Taiwan's hospitalist system.

Methods

From December 2009 to May 2010, patients admitted to the hospitalist ward of a medical center in Taiwan and later discharged alive to home care were included. Efforts to improve the quality of interventions in the PDTC program, including a disease-specific care plan, telephone monitoring, hotline counseling and referral to a hospitalist-run clinic, were implemented in the latter four months in the intervention group, while the control group was recruited during the first two months of the study period. The primary end point was unplanned readmission or death within 30 days after discharge.

Results

There were 94 and 219 patients in the control and intervention groups, respectively. Both groups had similar characteristics at the time of admission and at discharge. In the intervention group, 18 patients with worsening disease-specific indicators recorded during telephone monitoring and 21 patients with new or worsening symptoms recorded during hotline counseling had higher rates of unplanned readmission than those without worsening disease-specific indicators (P= 0.031) and worsening symptoms (P= 0.019), respectively. Patients who received PDTC had lower rates of readmission and death than the control group within 30 days after discharge (15% vs. 25%;P= 0.021). Nonuse of a hospitalist-run clinic and presence of underlying malignancy were other independent risk factors for readmission and death within 30 days after discharge.

Conclusion

Integrated PDTC using disease-specific care, telephone monitoring, hotline counseling and a hospitalist-run clinic can reduce rates of postdischarge readmission and death.
Sliding and pressure evaluation on conventional and V-shaped seats of reclining wheelchairs for stroke patients with flaccid hemiplegia: a crossover trial
Authors: Huang Hsiu-Chen , Yeh Cheng-Hsin , Chen Chi-Myn , Lin Yu-Sheng , Chung Kao-Chi
Published: August 2011

Background

Reclining wheelchairs are commonly used to transport elderly stroke patients in Taiwan. However, there is concern that the patient's body in the wheelchair often slides forward when they return to a seated position, increasing the sitting pressure. Therefore, a novel reclining wheelchair with an ergonomic "V-Seat" was designed to prevent forward sliding and pressure sores. The use of these reclining chairs by stroke patients has not yet been studied. Thus, we investigated the effects of V-shaped and conventional seats in reclining wheelchairs on the extent of forward sliding and on the sitting pressure of stroke patients with flaccid hemiplegia and of able-bodied elders.

Methods

We recruited 13 able-bodied elders and 11 stroke patients with flaccid hemiplegia and performed 5 reclining cycles in both types of wheelchair. The amount of sliding along the backrest (BS) plane and the seat (SS) plane, the mean sitting pressure (MP), and the sacral peak pressure (SPP) of the subjects were recorded. We used the Wilcoxon signed-rank test to compare the BS, SS, MP, and SPP in wheelchairs with conventional and V-shaped seats, and we used the Wilcoxon rank sum test to compare the differences in BS and SS between stroke patients and able-bodied elders in both types of reclining wheelchair.

Results

The BS, SS, and SPP of stroke patients were significantly lower in the wheelchairs with V-shaped seats than in conventional wheelchairs in most comparisons; however, the BS of able-bodied elders was higher in V-shaped seats than in conventional seats. The SS and SPP of stroke patients were significantly higher than those of able-bodied elders in both types of reclining wheelchair, and the BS of stroke patients was significantly higher than that of able-bodied elders only in conventional reclining wheelchairs.

Conclusions

The use of V-shaped seats in reclining wheelchairs can help reduce the forward sliding and sacral peak pressure of stroke patients with flaccid hemiplegia. The back displacement of able-bodied subjects when using both conventional and V-shape seats in reclining positions differs from the back displacement of stroke patients with flaccid hemiplegia when using such seats. These results are of paramount value and should be considered when prescribing the use of reclining wheelchairs to subjects with flaccid hemiplegia.
SUrgical versus PERcutaneous Bypass: SUPERB-trial; Heparin-bonded endoluminal versus surgical femoro-popliteal bypass: study protocol for a randomized controlled trial
Authors: Lensvelt Mare MA , Holewijn Suzanne , Fritschy Wilbert M , Wikkeling Otmar RM , van Walraven Laurens A , Wallis de Vries Bas M , Zeebregts Clark J , Reijnen Michel MPJ
Published: August 2011

Background

Endovascular treatment options for the superficial femoral artery are evolving rapidly. For long lesions, the venous femoropopliteal bypass considered to be superior above the prosthetic bypass. An endoluminal bypass, however, may provide equal patency rates compared to the prosthetic above knee bypass. The introduction of heparin-bonded endografts may further improve patency rates. The SUrgical versus PERcutaneous Bypass (SuperB) study is designed to assess whether a heparin-bonded endoluminal bypass provides equal patency rates compared to the venous bypass and to prove that it is associated with improved quality of life, related to a decreased complication rate, or not.

Methods/design

Two-hundred-twenty-two patients with peripheral arterial occlusive disease, category 3-6 according to Rutherford, will be randomized in two treatment arms; 1. the surgical femoro-popliteal bypass, venous whenever possible, and 2. the heparin-bonded endoluminal bypass. The power analysis was based on a non-inferiority principle, with an effect size of 90% and 10% margins (alpha 5%, power 80%). Patients will be recruited from 5 teaching hospitals in the Netherlands during a 2-year period. The primary endpoint is primary patency and quality of life evaluated by the RAND-36 questionnaire and the Walking Impairment Questionnaire. Secondary endpoints include secondary patency, freedom-from-TLR and complications.

Discussion

The SuperB trial is a multicentre randomized controlled trial designed to show non-inferiority in patency rates of the heparin-bonded endograft compared to the surgical bypass for treatment of long SFA lesions, and to prove a better quality of life using the heparin bonded-endograft compared to surgically treatment, related to a reduction in complications.

Trial Registration

Clinicaltrials: NCT01220245
Mechanisms of increased risk of tumorigenesis in Atm and Brca1 double heterozygosity
Authors: Wang Jufang , Su Fengtao , Smilenov Lubomir B , Zhou Libin , Hu Wentao , Ding Nan , Zhou Guangming
Published: August 2011

Background

Both epidemiological and experimental studies suggest that heterozygosity for a single gene is linked with tumorigenesis and heterozygosity for two genes increases the risk of tumor incidence. Our previous work has demonstrated thatAtm/Brca1double heterozygosity leads to higher cell transformation rate than single heterozygosity. However, the underlying mechanisms have not been fully understood yet. In the present study, a series of pathways were investigated to clarify the possible mechanisms of increased risk of tumorigenesis inAtmandBrca1heterozygosity.

Methods

Wild type cells,AtmorBrca1single heterozygous cells, andAtm/Brca1double heterozygous cells were used to investigate DNA damage and repair, cell cycle, micronuclei, and cell transformation after photon irradiation.

Results

Remarkable high transformation frequency was confirmed inAtm/Brca1double heterozygous cells compared to wild type cells. It was observed that delayed DNA damage recognition, disturbed cell cycle checkpoint, incomplete DNA repair, and increased genomic instability were involved in the biological networks. Haploinsufficiency of either ATM or BRCA1 negatively impacts these pathways.

Conclusions

The quantity of critical proteins such as ATM and BRCA1 plays an important role in determination of the fate of cells exposed to ionizing radiation and double heterozygosity increases the risk of tumorigenesis. These findings also benefit understanding of the individual susceptibility to tumor initiation.
Limb salvage after gas gangrene: a case report and review of the literature
Authors: Aggelidakis John , Lasithiotakis Konstantinos , Topalidou Anastasia , Koutroumpas John , Kouvidis Georgios , Katonis Paulos
Published: August 2011

Gas gangrene is a necrotic infection of soft tissue associated with high mortality, often necessitating amputation in order to control the infection. Herein we present a case of gas gangrene of the arm in an intravenous drug user with a history of intramuscular injections with normal saline in the shoulder used to provoke pain for recovery after drug induced coma. The patient was early treated with surgery and antibiotics rendering possible the preservation of the limb and some of its function. Additionally, a review of the literature regarding case reports of limb salvage after gas gangrene is presented.
Prolapsed sigmoid intussusception per anus in an elderly man: a case report
Authors: Teyha Penn S , Chandika Alphonce , Kotecha Vihar R
Published: August 2011

Background

Intussusception in pediatrics is widely documented and well described. On the basis of the literature, however, adult intussusception is a rare entity with a prevalence of from 1% to 5%. The majority of adult patients with intussusception have an underlying pathology that needs to be identified by performing a proper physical examination and a wide array of investigations.

Case presentation

We present a case of a 66-year-old African man who presented to our emergency department with a mass protruding per anus with obstipation. During laparotomy, we found that the sigmoid colon had intussuscepted into the rectum and out from the anus. Other abdominal viscera were normal and without any obvious mesenteric lymphadenopathy. Sigmoid colectomy and spectacle colostomy were performed. Grossly, the excised bowel looked normal, but the histologic results showed features of necrosis and chronic inflammation.

Conclusion

While 70% to 90% of cases of adult intussusception have an identifiable cause or lesion, most pediatric intussusceptions are idiopathic. The presentation in an adult described herein was of an uncommon idiopathic type with no identifiable cause found on the basis of the history, physical examination, or histological findings.
Melatonin Controls Photoperiodic Changes in Tanycyte Vimentin and Neural Cell Adhesion Molecule Expression in the Djungarian Hamster (Phodopus sungorus)
Authors: Bolborea Matei , Laran-Chich Marie-Pierre , Rasri Kamontip , Hildebrandt Herbert , Govitrapong Piyarat , Simonneaux Valérie , Pévet Paul , Steinlechner Stephan , Klosen Paul
Published: August 2011

The Djungarian hamster displays photoperiodic variations in gonadal size synchronized to the seasons by the nightly secretion of the pineal hormone melatonin. In short photoperiod (SP), the gonads regress in size, and circulating sex steroids levels decline. Thus, the brain is subject to seasonal variations of both melatonin and sex steroids. Tanycytes are specialized glial cells located in the ependymal lining of the third ventricle. They send processes either to the meninges or to blood vessels of the medio-basal hypothalamus. Furthermore, they are known to locally modulate GnRH release in the median eminence and to display seasonal structural changes. Seasonal changes in tanycyte morphology might be mediated either through melatonin or sex steroids. Therefore, we analyzed the effects of photoperiod, melatonin, and sex steroids 1) on tanycyte vimentin expression by immunohistochemistry and 2) on the expression of the neural cell adhesion molecule (NCAM) and polysialic acid as markers of brain plasticity. Vimentin immunostaining was reduced in tanycyte cell bodies and processes in SP. Similarly, tanycytes and their processes contained lower amounts of NCAM in SP. These changes induced by SP exposure could not be restored to long photoperiod (LP) levels by testosterone supplementation. Likewise, castration in LP did not affect tanycyte vimentin or NCAM expression. By contrast, late afternoon melatonin injections mimicking a SP-like melatonin peak in LP hamsters reduced vimentin and NCAM expression. Thus, the seasonal changes in vimentin and NCAM expression in tanycytes are regulated by melatonin independently of seasonal sex steroid changes.
Micro-RNA378 (miR-378) Regulates Ovarian Estradiol Production by Targeting Aromatase
Authors: Xu Shengyu , Linher-Melville Katja , Yang Burton B. , Wu De , Li Julang
Published: August 2011

Estradiol is a steroid hormone that not only plays an important role in ovarian follicular development but also is associated with many reproductive disorders. Owing to the importance of aromatase in the production of estradiol, the regulation of aromatase gene expression at the transcriptional level has been an extensive area of study for over two decades. However, its regulation at the posttranscriptional level has remained unclear. Here, we show that micro-RNA378 (miR-378) is spatiotemporally expressed in porcine granulosa cells, the cells that generate estradiol in the ovary during follicular development, in an inverse manner compared with the expression of aromatase. In vitro overexpression and inhibition experiments revealed that aromatase expression, and therefore estradiol production, by granulosa cells, is posttranscriptionally down-regulated by miR-378. Furthermore, site-directed mutation studies identified two binding sites in the 3′-untranslated region (3′-UTR) of the aromatase coding sequence that are critical for the action of miR-378. Interestingly, overexpression of the aromatase 3′-UTR enhanced aromatase expression at the protein level in granulosa cells, possibly mediated by the binding of miR-378 within this region, thereby reducing the binding of this micro-RNA to the endogenous aromatase 3′-UTR.
GH, But Not GHRH, Plays a Role in the Development of Experimental Autoimmune Encephalomyelitis
Authors: Shohreh Rugia , Pardo Carlos A. , Guaraldi Federica , Schally Andrew V. , Salvatori Roberto
Published: August 2011

GH has been suggested to influence the function of the immune system in several species. Experimental autoimmune encephalomyelitis (EAE) (an animal model for multiple sclerosis) has been reported not to occur in GH-deficient (GHD) mice. The aim of this study was to elucidate the effects of GH and GHRH replacement on development of EAE in a mouse model of isolated GHD due to removal of the GHRH gene [GHRH knockout (GHRHKO)]. We studied two groups of adult female mice: 12 GH-sufficient animals (control) and 36 GHRHKO animals. All mice were immunized with myelin oligodendrocyte glycoprotein peptide, a peptide known to induce EAE. GHRHKO mice were left untreated or were treated for 4 wk with daily sc injections of recombinant GH or of a GHRH super agonist JI-38 (JI38-GHD). Evaluation of EAE symptoms was carried out daily, and T-proliferative assay and histopathological analysis of the spinal cord were performed. GHRHKO mice were less prone to develop EAE when compared with control mice. GH (but not JI-38) restored the original susceptibility of mice to the disease, despite lack of complete serum IGF-I normalization. GH treatment was also associated with a markedly increase in spleen size and T-cell proliferation specific to myelin oligodendrocyte glycoprotein peptide. GH (but not GHRH) plays an important role in the development of EAE.
Detection of synthetic glucocorticoids by liquid chromatography-tandem mass spectrometry in patients being investigated for Cushing's syndrome
Authors: Djedovic N K , Rainbow S J
Published: August 2011

Background

We report a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the detection of four commonly prescribed steroid drugs (prednisolone, dexamethasone, betamethasone and beclomethasone dipropionate) while simultaneously measuring 24-h urine free cortisol and cortisone in patients.

Methods

Two hundred and fifty microlitre aliquots of urine were spiked with internal standard and extracted with dichloromethane. The MS instrument was operated with positive electrospray and multiple reaction monitoring. Two transitions were monitored for each analyte of interest and the ratio of the intensities of the product ion fragments was established.

Results

The LC-MS/MS method for the measurement of urine free cortisol and cortisone was established. The assay was linear up to 788 nmol/L for cortisol and 777 nmol/L for cortisone, with a limit of quantitation of 5.0 nmol/L for both. Analysis time per sample was seven minutes. Transitions for four synthetic glucocorticoids were included, and they were identified based on the ratio of the intensities of product ion fragments. Analysis of 219 samples collected from 154 patients (55 male and 99 female) revealed the presence of prednisolone in five samples from three patients. Dexamethasone was detected in samples from four patients, and betamethasone was detected in one sample.

Conclusion

This is the first LC-MS/MS method in routine use to combine quantification of urinary cortisol and cortisone and detection of synthetic glucocorticoids in patients being investigated for Cushing's syndrome. Since the most common quoted cause of Cushing's syndrome is steroid treatment, this is a valuable diagnostic tool.
Ball milling effect on structural and magnetic properties of Ni–Mn–Ga ferromagnetic nanoparticles
Authors: Vallal Peruman Kaliyan , Mahendran Manickam
Published: August 2011

The off-stoichiometric Ni2MnGa ferromagnetic alloys are one of the active materials that are of great interest when they are ball milled into nanopowder. These powders are prospective materials for nanosystem applications. However, the properties of the nano-crystalline Ni–Mn–Ga alloys depend strongly on their structure and internal stress, which develop during the milling process. Ni–Mn–Ga nanoparticles were prepared by ball-milling method, and characterized by X-ray diffraction (XRD) and vibrating sample magnetometer (VSM) techniques. The powders are found to be a disordered mixture structure of austenite and martensite. We calculated that an average internal stress is 0.28 to 2.05 MPa stored in the distorted lattice due to milling. Reduction in particle sizes is accompanied by increase of the lattice strain level when the milling time increases. The VSM reveals that magnetic saturation and coercivity decrease with increase of the milling duration. This phenomenon causes deterioration in the hard magnetic properties.
Research on Export Pricing: Still Moving toward Maturity
Authors: Tan Qun , Sousa Carlos M.P.
Published: August 2011

Over the past four decades, there has been a considerable number of studies that have examined the determinants and outcomes of export pricing. However, despite this large volume of studies, the knowledge of the determinants and consequences of export pricing is characterized by a fragmented, diverse, and inconsistent collection of findings that hinders scholarship and practical advancement in the field. A major reason for this absence of clear insights is the lack of synthesis and assimilation of the fragmented knowledge. To address this gap in the literature, the authors review and evaluate 98 articles published between 1971 and 2010. The results indicate that although significant progress has been made in recent years, research on export pricing is still characterized by the lack of a strong theoretical basis, the failure to agree on the relevant determinants of export pricing, and some weakness in research designs and analytical techniques, which may explain the many contradictory and confusing findings in the literature. On the basis of these findings, the authors discuss several implications, and consider directions for further research.
Consumer World-Mindedness and Attitudes toward Product Positioning in Advertising: An Examination of Global versus Foreign versus Local Positioning
Authors: Nijssen Edwin J. , Douglas Susan P.
Published: August 2011

In recent years, increasing interest has emerged in examining global consumer culture and its impact on consumer product preferences and choices, lifestyles, and exposure to mass media from other countries. In turn, this has sparked interest in concepts such as consumer world-mindedness and its impact on attitudes and behavior. The current research examines differences in consumer response to advertisements reflecting a global consumer culture positioning (GCCP) versus a foreign consumer culture positioning (FCCP) or a local consumer culture positioning (LCCP) and the relationship with consumer world-mindedness. In Studies 1 and 2, the authors examine the impact of world-mindedness, while controlling for ethnocentric attitudes. In Study 3, they examine the interactions of world-mindedness, international travel, and preference for authenticity. The authors develop several hypotheses and examine them using two surveys of 90 (Study 1) and 100 consumers (Studies 2 and 3) in the Netherlands. The results demonstrate, for example, that advertisements for brands with FCCP and GCCP are nomologically different and evaluated differently.
The Trade-off between Customer and Technology Orientations: Impact on Innovation Capabilities and Export Performance
Authors: Hortinha Paula , Lages Carmen , Lages Luis Filipe
Published: August 2011

Technological exporters are constantly challenged by the trade-off between two types of strategic orientations: customer and technology. Nonetheless, research directly addressing this topic is scarce, and few recommendations exist about the best orientation to emphasize. Using two respondents in the same firm, the export manager and the research-and-development manager, the authors find that customer orientation is as important as technological orientation in the development of exploratory innovation capabilities. However, when past performance is poor, customer orientation has a greater role. Exporters with poor past performance may achieve higher export performance levels by focusing more on customers than on technology. Conversely, firms performing well may risk export performance if they ignore technology orientation. These firms also need to maintain high levels of customer orientation.
Representation of Vestibular and Visual Cues to Self-Motion in Ventral Intraparietal Cortex
Authors: Chen Aihua , DeAngelis Gregory C. , Angelaki Dora E.
Published: August 2011

Convergence of vestibular and visual motion information is important for self-motion perception. One cortical area that combines vestibular and optic flow signals is the ventral intraparietal area (VIP). We characterized unisensory and multisensory responses of macaque VIP neurons to translations and rotations in three dimensions. Approximately one-half of VIP cells show significant directional selectivity in response to optic flow, one-half show tuning to vestibular stimuli, and one-third show multisensory responses. Visual and vestibular direction preferences of multisensory VIP neurons could be congruent or opposite. When visual and vestibular stimuli were combined, VIP responses could be dominated by either input, unlike the medial superior temporal area (MSTd) where optic flow tuning typically dominates or the visual posterior sylvian area (VPS) where vestibular tuning dominates. Optic flow selectivity in VIP was weaker than in MSTd but stronger than in VPS. In contrast, vestibular tuning for translation was strongest in VPS, intermediate in VIP, and weakest in MSTd. To characterize response dynamics, direction–time data were fit with a spatiotemporal model in which temporal responses were modeled as weighted sums of velocity, acceleration, and position components. Vestibular responses in VIP reflected balanced contributions of velocity and acceleration, whereas visual responses were dominated by velocity. Timing of vestibular responses in VIP was significantly faster than in MSTd, whereas timing of optic flow responses did not differ significantly among areas. These findings suggest that VIP may be proximal to MSTd in terms of vestibular processing but hierarchically similar to MSTd in terms of optic flow processing.
The Control of Mimicry by Eye Contact Is Mediated by Medial Prefrontal Cortex
Authors: Wang Yin , Ramsey Richard , de C. Hamilton Antonia F.
Published: August 2011

Spontaneous mimicry of other people's actions serves an important social function, enhancing affiliation and social interaction. This mimicry can be subtly modulated by different social contexts. We recently found behavioral evidence that direct eye gaze rapidly and specifically enhances mimicry of intransitive hand movements (Wang et al., 2011). Based on past findings linking medial prefrontal cortex (mPFC) to both eye contact and the control of mimicry, we hypothesized that mPFC might be the neural origin of this behavioral effect. The present study aimed to test this hypothesis. During functional magnetic resonance imaging (fMRI) scanning, 20 human participants performed a simple mimicry or no-mimicry task, as previously described (Wang et al., 2011), with direct gaze present on half of the trials. As predicted, fMRI results showed that performing the task activated mirror systems, while direct gaze and inhibition of the natural tendency to mimic both engaged mPFC. Critically, we found an interaction between mimicry and eye contact in mPFC, superior temporal sulcus (STS) and inferior frontal gyrus. We then used dynamic causal modeling to contrast 12 possible models of information processing in this network. Results supported a model in which eye contact controls mimicry by modulating the connection strength from mPFC to STS. This suggests that mPFC is the originator of the gaze–mimicry interaction and that it modulates sensory input to the mirror system. Thus, our results demonstrate how different components of the social brain work together to on-line control mimicry according to the social context.
Aminopyridines Correct Early Dysfunction and Delay Neurodegeneration in a Mouse Model of Spinocerebellar Ataxia Type 1
Authors: Hourez Raphael , Servais Laurent , Orduz David , Gall David , Millard Isabelle , de Kerchove d'Exaerde Alban , Cheron Guy , Orr Harry T. , Pandolfo Massimo , Schiffmann Serge N.
Published: August 2011

The contribution of neuronal dysfunction to neurodegeneration is studied in a mouse model of spinocerebellar ataxia type 1 (SCA1) displaying impaired motor performance ahead of loss or atrophy of cerebellar Purkinje cells. Presymptomatic SCA1 mice show a reduction in the firing rate of Purkinje cells (bothin vivoand in slices) associated with a reduction in the efficiency of the main glutamatergic synapse onto Purkinje cells and with increased A-type potassium current. The A-type potassium channel Kv4.3 appears to be internalized in response to glutamatergic stimulation in Purkinje cells and accumulates in presymptomatic SCA1 mice. SCA1 mice are treated with aminopyridines, acting as potassium channel blockers to test whether the treatment could improve neuronal dysfunction, motor behavior, and neurodegeneration. In acutely treated young SCA1 mice, aminopyridines normalize the firing rate of Purkinje cells and the motor behavior of the animals. In chronically treated old SCA1 mice, 3,4-diaminopyridine improves the firing rate of Purkinje cells, the motor behavior of the animals, and partially protects against cell atrophy. Chronic treatment with 3,4-diaminopyridine is associated with increased cerebellar levels of BDNF, suggesting that partial protection against atrophy of Purkinje cells is possibly provided by an increased production of growth factors secondary to the reincrease in electrical activity. Our data suggest that aminopyridines might have symptomatic and/or neuroprotective beneficial effects in SCA1, that reduction in the firing rate of Purkinje cells can cause cerebellar ataxia, and that treatment of early neuronal dysfunction is relevant in neurodegenerative disorders such as SCA1.
Regulator of G-Protein Signaling-10 Negatively Regulates NF-κB in Microglia and Neuroprotects Dopaminergic Neurons in Hemiparkinsonian Rats
Authors: Lee Jae-Kyung , Chung Jaegwon , McAlpine Fiona E. , Tansey Malú G.
Published: August 2011

Microglia are the brain-resident macrophages responsible for immune surveillance that become activated in response to injury, infection, environmental toxins, and other stimuli that threaten neuronal survival. Previous work from our group demonstrated that mice deficient in Regulator of G-protein Signaling 10 (RGS10), a microglia-enriched GTPase activating protein (GAP) for G-protein α subunits, displayed increased microglial burden in the CNS at birth and developed a parkinsonian phenotype after exposure to chronic systemic inflammation, implicating a neuroprotective role for RGS10 in the nigrostriatal pathway. While it is known that RGS10 is expressed in both microglia and certain subsets of neurons, it is not known whether RGS10 functions similarly in both cells types. In this study we sought to delineate the specific role of RGS10 in microglia and identify the molecular pathway(s) required for RGS10 to exert its actions in microglia. Here, we identify RGS10 as a negative regulator of the nuclear factor κB(NF-κB) pathway in microglia and demonstrate that the proinflammatory and cytotoxic phenotype of Rgs10-null microglia can be reversed by lentiviral-mediated restoration of RGS10 expression.In vivogene transfer of RGS10 into the substantia nigra pars compacta (SNpc) of rats reduced microgliosis and protected against 6-OHDA neurotoxin-induced death of dopaminergic (DA) neurons. Together, our findings suggest that modulation of RGS10 activity in microglia may afford therapeutic benefit in the treatment of chronic neuroinflammatory conditions as well as neuroprotection against inflammation-related degeneration in Parkinson's disease (PD), the second most common neurodegenerative disorder affecting individuals over age 65.
The Phase of Ongoing Oscillations Mediates the Causal Relation between Brain Excitation and Visual Perception
Authors: Dugué Laura , Marque Philippe , VanRullen Rufin
Published: August 2011

Why does neuronal activity in sensory brain areas sometimes give rise to perception, and sometimes not? Although neuronal noise is often invoked as the key factor, a portion of this variability could also be due to the history and current state of the brain affecting cortical excitability. Here we directly test this idea by examining whether the phase of prestimulus oscillatory activity is causally linked with modulations of cortical excitability and with visual perception. Transcranial magnetic stimulation (TMS) was applied over human visual cortex to induce illusory perceptions (phosphenes) while electroencephalograms (EEGs) were simultaneously recorded. Subjects reported the presence or absence of an induced phosphene following a single pulse of TMS at perceptual threshold. The phase of ongoing alpha (∼10 Hz) oscillations within 400 ms before the pulse significantly covaried with the perceptual outcome. This effect was observed in occipital regions around the site of TMS, as well as in a distant frontocentral region. In both regions, we found a systematic relationship between prepulse EEG phase and perceptual performance: phosphene probability changed by ∼15% between opposite phases. In summary, we provide direct evidence for a chain of causal relations between the phase of ongoing oscillations, neuronal excitability, and visual perception: ongoing oscillations create periodic “windows of excitability,” with sensory perception being more likely to occur at specific phases.
Fasting and 17β-Estradiol Differentially Modulate the M-Current in Neuropeptide Y Neurons
Authors: Roepke Troy A. , Qiu Jian , Smith Arik W. , Rønnekleiv Oline K. , Kelly Martin J.
Published: August 2011

Multiple K+conductances are targets for many peripheral and central signals involved in the control of energy homeostasis. Potential K+channel targets are the KCNQ subunits that form the channels underlying the M-current, a subthreshold, non-inactivating K+current that is a common target for G-protein-coupled receptors. Whole-cell recordings were made from GFP (Renilla)-tagged neuropeptide Y (NPY) neurons from the arcuate nucleus of the hypothalamus using protocols to isolate and characterize the M-current in these orexigenic neurons. We recorded robust K+currents in the voltage range of the M-current, which were inhibited by the selective KCNQ channel blocker 10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone dihydrochloride (XE991) (40 μm), in both intact males and ovariectomized, 17β-estradiol (E2)-treated females. Since NPY neurons are orexigenic and are active during fasting, the M-current was measured in fed and fasted male mice. Fasting attenuated the XE991-sensitive current by threefold, which correlated with decreased expression of the KCNQ2 and KCNQ3 subunits as measured with quantitative real-time PCR. Furthermore, E2 treatment augmented the XE991-sensitive M-current by threefold in ovariectomized (vs oil-treated) female mice. E2 treatment increased the expression of the KCNQ5 subunit in females but not KCNQ2 or KCNQ3 subunits. Fasting in females abrogated the effects of E2 on M-current activity, at least in part, by decreasing KCNQ2 and KCNQ3 expression. In summary, these data suggest that the M-current plays a pivotal role in the modulation of NPY neuronal excitability and may be an important cellular target for neurotransmitter and hormonal signals in the control of energy homeostasis in both males and females.
Early Prenatal Stress Epigenetically Programs Dysmasculinization in Second-Generation Offspring via the Paternal Lineage
Authors: Morgan Christopher P. , Bale Tracy L.
Published: August 2011

Studies have linked sex-biased neurodevelopmental disorders, including autism and schizophrenia, with fetal antecedents such as prenatal stress. Further, these outcomes can persist into subsequent generations, raising the possibility that aspects of heritability in these diseases involve epigenetic mechanisms. Utilizing a mouse model in which we previously identified a period in early gestation when stress results in dysmasculinized and stress-sensitive male offspring, we have examined programming effects in second-generation offspring of prenatally stressed (F2-S) or control (F2-C) sires. Examination of gene expression patterns during the perinatal sensitive period, when organizational gonadal hormones establish the sexually dimorphic brain, confirmed dysmasculinization in F2-S males, where genes important in neurodevelopment showed a female-like pattern. Analyses of the epigenomic miRNA environment detected significant reductions in miR-322, miR-574, and miR-873 in the F2-S male brain, levels that were again more similar to those of control females. Increased expression of a common gene target for these three miRNAs, β-glycan, was confirmed in these males. These developmental effects were associated with the transmission of a stress-sensitive phenotype and shortened anogenital distance in adult F2-S males. As confirmation that the miRNA environment is responsive to organizational testosterone, neonatal males administered the aromatase inhibitor formestane exhibited dramatic changes in brain miRNA patterns, suggesting that miRNAs may serve a previously unappreciated role in organizing the sexually dimorphic brain. Overall, these data support the existence of a sensitive period of early gestation when epigenetic programming of the male germline can occur, permitting transmission of specific phenotypes into subsequent generations.
Spinal Synthesis of Estrogen and Concomitant Signaling by Membrane Estrogen Receptors Regulate Spinal κ- and μ-Opioid Receptor Heterodimerization and Female-Specific Spinal Morphine Antinociception
Authors: Liu Nai-Jiang , Chakrabarti Sumita , Schnell Stephen , Wessendorf Martin , Gintzler Alan R.
Published: August 2011

We previously demonstrated that the spinal cord κ-opioid receptor (KOR) and μ-opioid receptor (MOR) form heterodimers (KOR/MOR). KOR/MOR formation and the associated KOR dependency of spinal morphine antinociception are most robust during proestrus. Using Sprague Dawley rats, we now demonstrate that (1) spinal synthesis of estrogen is critical to these processes, and (2) blockade of either estrogen receptor (ER) α-, β-, or G-protein-coupled ER1 or progesterone receptor (PR) substantially reduces KOR/MOR and eliminates mediation by KOR of spinal morphine antinociception. Effects of blocking ERs were manifest within 15 min, whereas those of PR blockade were manifest after 18 h, indicating the requirement for rapid signaling by estrogen and transcriptional effects of progesterone. Individual or combined blockade of ERs produced the same magnitude of effect, suggesting that they work in tandem as part of a macromolecular complex to regulate KOR/MOR formation. Consistent with this inference, we found that KOR and MOR were coexpressed with ERα and G-protein-coupled ER1 in the spinal dorsal horn. Reduction of KOR/MOR by ER or PR blockade or spinal aromatase inhibition shifts spinal morphine antinociception from KOR dependent to KOR independent. This indicates a sex steroid-dependent plasticity of spinal KOR functionality, which could explain the greater analgesic potency of KOR agonists in women versus men. We suggest that KOR/MOR is a molecular switch that shifts the function of KOR and thereby endogenous dynorphin from pronociceptive to antinociceptive. KOR/MOR could thus serve as a novel molecular target for pain management in women.