bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the predictive value of the evoked potentials score in MS within an appropriate patient population: a hint for an early identification of benign MS?
Authors: Margaritella Nicolò , Mendozzi Laura , Garegnani Massimo , Nemni Raffaello , Colicino Elena , Gilardi Elisabetta , Pugnetti Luigi
Published: August 2012

Background

The prognostic value of evoked potentials (EPs) in multiple sclerosis (MS) has not been fully established. The correlations between the Expanded Disability Status Scale (EDSS) at First Neurological Evaluation (FNE) and the duration of the disease, as well as between EDSS and EPs, have influenced the outcome of most previous studies. To overcome this confounding relations, we propose to test the prognostic value of EPs within an appropriate patient population which should be based on patients with low EDSS at FNE and short disease duration.

Methods

We retrospectively selected a sample of 143 early relapsing remitting MS (RRMS) patients with an EDSS < 3.5 from a larger database spanning 20 years. By means of bivariate logistic regressions, the best predictors of worsening were selected among several demographic and clinical variables. The best multivariate logistic model was statistically validated and prospectively applied to 50 patients examined during 2009–2011.

Results

The Evoked Potentials score (EP score) and the Time to EDSS 2.0 (TT2) were the best predictors of worsening in our sample (Odds Ratio 1.10 and 0.82 respectively, p=0.001). Low EP score (below 15–20 points), short TT2 (lower than 3–5 years) and their interaction resulted to be the most useful for the identification of worsening patterns. Moreover, in patients with an EP score at FNE below 6 points and a TT2 greater than 3 years the probability of worsening was 10% after 4–5 years and rapidly decreased thereafter.

Conclusions

In an appropriate population of early RRMS patients, the EP score at FNE is a good predictor of disability at low values as well as in combination with a rapid buildup of disability. Interestingly, an EP score at FNE under the median together with a clinical stability lasting more than 3 years turned out to be a protective pattern. This finding may contribute to an early identification of benign patients, well before the term required to diagnose Benign MS (BMS).
Production of medium-chain-length polyhydroxyalkanoates by sequential feeding of xylose and octanoic acid in engineered Pseudomonas putida KT2440
Authors: Le Meur Sylvaine , Zinn Manfred , Egli Thomas , Thöny-Meyer Linda , Ren Qun
Published: August 2012

Background

Pseudomonas putida KT2440 is able to synthesize large amounts of medium-chain-length polyhydroxyalkanoates (mcl-PHAs). To reduce the substrate cost, which represents nearly 50% of the total PHA production cost, xylose, a hemicellulose derivate, was tested as the growth carbon source in an engineered P. putida KT2440 strain.

Results

The genes encoding xylose isomerase (XylA) and xylulokinase (XylB) from Escherichia coli W3110 were introduced into P. putida KT2440. The recombinant KT2440 exhibited a XylA activity of 1.47 U and a XylB activity of 0.97 U when grown on a defined medium supplemented with xylose. The cells reached a maximum specific growth rate of 0.24 h-1 and a final cell dry weight (CDW) of 2.5 g L-1 with a maximal yield of 0.5 g CDW g-1 xylose. Since no mcl-PHA was accumulated from xylose, mcl-PHA production can be controlled by the addition of fatty acids leading to tailor-made PHA compositions. Sequential feeding strategy was applied using xylose as the growth substrate and octanoic acid as the precursor for mcl-PHA production. In this way, up to 20% w w-1 of mcl-PHA was obtained. A yield of 0.37 g mcl-PHA per g octanoic acid was achieved under the employed conditions.

Conclusions

Sequential feeding of relatively cheap carbohydrates and expensive fatty acids is a practical way to achieve more cost-effective mcl-PHA production. This study is the first reported attempt to produce mcl-PHA by using xylose as the growth substrate. Further process optimizations to achieve higher cell density and higher productivity of mcl-PHA should be investigated. These scientific exercises will undoubtedly contribute to the economic feasibility of mcl-PHA production from renewable feedstock.
Analysis of in vitro secretion profiles from adipose-derived cell populations
Authors: Blaber Sinead P , Webster Rebecca A , Hill Cameron J , Breen Edmond J , Kuah Donald , Vesey Graham , Herbert Benjamin R
Published: August 2012

Background

Adipose tissue is an attractive source of cells for therapeutic purposes because of the ease of harvest and the high frequency of mesenchymal stem cells (MSCs). Whilst it is clear that MSCs have significant therapeutic potential via their ability to secrete immuno-modulatory and trophic cytokines, the therapeutic use of mixed cell populations from the adipose stromal vascular fraction (SVF) is becoming increasingly common.

Methods

In this study we have measured a panel of 27 cytokines and growth factors secreted by various combinations of human adipose-derived cell populations. These were 1. co-culture of freshly isolated SVF with adipocytes, 2. freshly isolated SVF cultured alone, 3. freshly isolated adipocytes alone and 4. adherent adipose-derived mesenchymal stem cells (ADSCs) at passage 2. In addition, we produced an ‘in silico’ dataset by combining the individual secretion profiles obtained from culturing the SVF with that of the adipocytes. This was compared to the secretion profile of co-cultured SVF and adipocytes. Two-tailed t-tests were performed on the secretion profiles obtained from the SVF, adipocytes, ADSCs and the ‘in silico’ dataset and compared to the secretion profiles obtained from the co-culture of the SVF with adipocytes. A p-value of < 0.05 was considered statistically different. To assess the overall changes that may occur as a result of co-culture we compared the proteomes of SVF and SVF co-cultured with adipocytes using iTRAQ quantitative mass spectrometry.

Results

A co-culture of SVF and adipocytes results in a distinct secretion profile when compared to all other adipose-derived cell populations studied. This illustrates that cellular crosstalk during co-culture of the SVF with adipocytes modulates the production of cytokines by one or more cell types. No biologically relevant differences were detected in the proteomes of SVF cultured alone or co-cultured with adipocytes.

Conclusions

The use of mixed adipose cell populations does not appear to induce cellular stress and results in enhanced secretion profiles. Given the importance of secreted cytokines in cell therapy, the use of a mixed cell population such as the SVF with adipocytes may be considered as an alternative to MSCs or fresh SVF alone.
Treatment of central giant cell lesions using bisphosphonates with intralesional corticosteroid injections
Authors: da Silva Newton Guerreiro , Carreira Aline Semblano Dias , Pedreira Erick Nelo , Tuji Fabrício Mesquita , Ortega Karem López , de Jesus Viana Pinheiro João
Published: August 2012

Central giant cell lesions are benign intraosseous proliferative lesions that have considerable local aggressiveness. Nonsurgical treatment methods, such as intralesional corticosteroid injections, systemic calcitonin and interferon have been reported. Recently, bisphosphonates have been used to treat central giant cell lesions. A case of a 36-year-old male with a central giant cell lesion crossing the mandibular midline was treated with intralesional corticosteroids combined with alendronate sodium for the control of systemic bone resorption. The steroid injections and the use of bisphosphonates were stopped after seven months when further needle penetration into the lesion was not possible due to new bone formation. After two years, the bony architecture was near normal, and only minimal radiolucency was present around the root apices of the involved teeth. The patient was followed up for four years, and panoramic radiography showed areas of new bone formation. Thus far, neither recurrence nor side effects of the medication have been detected.
Effect of hypoxia on equine mesenchymal stem cells derived from bone marrow and adipose tissue
Authors: Ranera Beatriz , Remacha Ana Rosa , Álvarez-Arguedas Samuel , Romero Antonio , Vázquez Francisco José , Zaragoza Pilar , Martín-Burriel Inmaculada , Rodellar Clementina
Published: August 2012

Background

Mesenchymal stem cells (MSCs) derived from bone marrow (BM-MSCs) and adipose tissue (AT-MSCs) are being applied to equine cell therapy. The physiological environment in which MSCs reside is hypoxic and does not resemble the oxygen level typically used inin vitroculture (20% O2). This work compares the growth kinetics, viability, cell cycle, phenotype and expression of pluripotency markers in both equine BM-MSCs and AT-MSCs at 5% and 20% O2.

Results

At the conclusion of culture, fewer BM-MSCs were obtained in hypoxia than in normoxia as a result of significantly reduced cell division. Hypoxic AT-MSCs proliferated less than normoxic AT-MSCs because of a significantly higher presence of non-viable cells during culture. Flow cytometry analysis revealed that the immunophenotype of both MSCs was maintained in both oxygen conditions. Gene expression analysis using RT-qPCR showed that statistically significant differences were only found forCD49din BM-MSCs andCD44in AT-MSCs. Similar gene expression patterns were observed at both 5% and 20% O2for the remaining surface markers. Equine MSCs expressed the embryonic markersNANOG,OCT4andSOX2in both oxygen conditions. Additionally, hypoxic cells tended to display higher expression, which might indicate that hypoxia retains equine MSCs in an undifferentiated state.

Conclusions

Hypoxia attenuates the proliferative capacity of equine MSCs, but does not affect the phenotype and seems to keep them more undifferentiated than normoxic MSCs.
TEG® and ROTEM® in trauma: similar test but different results?
Authors: Sankarankutty Ajith , Nascimento Bartolomeu , Teodoro da Luz Luis , Rizoli Sandro
Published: August 2012

Introduction

Transfusion in trauma is often empiric or based on traditional lab tests. Viscoelastic tests such as thromboelastography (TEG
®
) and rotational thromboelastometry (ROTEM
®
) have been proposed as superior to traditional lab tests. Due to the similarities between the two tests, general opinion seems to consider them equivalent with interchangeable interpretations. However, it is not clear whether the results can be similarly interpreted. This review evaluates the comparability between TEG and ROTEM and performs a descriptive review of the parameters utilized in each test in adult trauma patients.

Methods

PUBMED database was reviewed using the keywords “thromboelastography” and “compare”, between 2000 and 2011. Original studies directly comparing TEG
®
with ROTEM
®
in any area were retrieved. To verify the individual test parameter used in studies involving trauma patients, we further performed a review using the keywords “thromboelastography” and “trauma” in the PUBMED database.

Results

Only 4 studies directly compared TEG
®
with ROTEM
®
. One in liver transplantation found that transfusion practice could differ depending on the device in use. Another in cardiac surgery concluded that all measurements are not completely interchangeable. The third article using commercially available plasma detected clinically significant differences in the results from the two devices. The fourth one was a head-to-head comparison of the technical aspects. The 24 articles reporting the use of viscoelastic tests in trauma patients, presented considerable heterogeneity.

Conclusion

Both tests are potentially useful as means to rapidly diagnose coagulopathy, guide transfusion and determine outcome in trauma patients. Differences in the activators utilized in each device limit the direct comparability. Standardization and robust clinical trials comparing the two technologies are needed before these tests can be widely recommended for clinical use in trauma.
Twelve year experience of laparoscopic gastric plication in morbid obesity: development of the technique and patient outcomes
Authors: Talebpour Mohammad , Motamedi Seyed Mohammad Kalantar , Talebpour Atieh , Vahidi Hamed
Published: August 2012

Background

Laparoscopic Gastric Plication (LGP) is a new restrictive bariatric surgery, previously introduced by the author. The aim of this study is to explain the modifications and to present the 12-year experience, regarding early and long term results, complications and cost.

Methods

We used LGP for morbid obesity during the past 12 years. Anterior plication (10 cases), one-row bilateral plication while right gastroepiploic artery included (42 cases), and excluded from the plication (104 cases) and two-row plication (644 cases). The gastric greater curvature was plicated using 2/0 prolen from fundus at the level of diaphragm preserving the His angle to just proximal to the pylorus. The anatomic and functional volume of stomach was 50cc and 25cc respectively in two-row method. Ordered postop visits also included evaluation of weight loss, complications, change of diet and control of exercise.

Results

LGP was performed in 800 cases (mean age: 27.5, range: 12 to 65 years, nine under 18). Female to male ratio was 81% to 19% and average BMI was 42.1 (35-59). The mean excess weight loss (EWL) was 70% (40% to 100%) after 24 months and 55% (28% to 100%) after 5 years following surgery. 134 cases (16.7%) did not completed long term follow-up. The average time of follow up was 5 years (1 month to 12 years). 5.5% and 31% of cases complained from weight regain respectively during 4 and 12 years after LGP. The mean time of operation was 72 (49–152) minutes and average hospitalization time was 72 hours (24 hours to 45 days). The cost of operation was 2000 $ less than gastric banding or sleeve and 2500 $ less than gastric bypass. Eight patients out of 800 cases (1%) required reoperation due to complications like: micro perforation, obstruction and vomiting following adhesion of His angle. Other complications included hepatitis pneumonia, self-limiting intra-abdominal bleeding and hypocalcaemia.

Conclusion

The percentage of EWL in this technique is comparable to other restrictive methods. The technique is safe with 1.6% complication (1% reoperated), and 31% regain during 12 years. The cost of operation is less than the other methods.
A systematic review of genetic skeletal disorders reported in Chinese biomedical journals between 1978 and 2012
Authors: Cui Yazhou , Zhao Heng , Liu Zhenxing , Liu Chao , Luan Jing , Zhou Xiaoyan , Han Jinxiang
Published: August 2012

Little information is available on the prevalence, geographic distribution and mutation spectrum of genetic skeletal disorders (GSDs) in China. This study systematically reviewed GSDs as defined in “Nosology and Classification of genetic skeletal disorders (2010 version)” using Chinese biomedical literature published over the past 34 years from 1978 to 2012. In total, 16,099 GSDs have been reported. The most frequently reported disorders were Marfan syndrome, osteogenesis imperfecta, fibrous dysplasia, mucopolysaccharidosis, multiple cartilaginous exostoses, neurofibromatosis type 1 (NF1), osteopetrosis, achondroplasia, enchondromatosis (Ollier), and osteopoikilosis, accounting for 76.5% (12,312 cases) of the total cases. Five groups (group 8, 12, 14, 18, 21) defined by “Nosology and Classification of genetic skeletal disorders” have not been reported in the Chinese biomedical literature. Gene mutation testing was performed in only a minor portion of the 16,099 cases of GSDs (187 cases, 1.16%). In total, 37 genes for 41 different GSDs were reported in Chinese biomedical literature, including 43 novel mutations. This review revealed a significant imbalance in rare disease identification in terms of geographic regions and hospital levels, suggesting the need to create a national multi-level network to meet the specific challenge of care for rare diseases in China.
Cohesin is required for expression of the estrogen receptor-alpha (ESR1) gene
Authors: Prenzel Tanja , Kramer Frank , Bedi Upasana , Nagarajan Sankari , Beissbarth Tim , Johnsen Steven A
Published: August 2012

Background

In conjunction with posttranslational chromatin modifications, proper arrangement of higher order chromatin structure appears to be important for controlling transcription in the nucleus. Recent genome-wide studies have shown that the Estrogen Receptor-alpha (ERα), encoded by the ESR1 gene, nucleates tissue-specific long-range chromosomal interactions in collaboration with the cohesin complex. Furthermore, the Mediator complex not only regulates ERα activity, but also interacts with the cohesin complex to facilitate long-range chromosomal interactions. However, whether the cohesin and Mediator complexes function together to contribute to estrogen-regulated gene transcription remains unknown.

Results

In this study we show that depletion of the cohesin subunit SMC3 or the Mediator subunit MED12 significantly impairs the ERα-regulated transcriptome. Surprisingly, SMC3 depletion appears to elicit this effect indirectly by rapidly decreasing ESR1 transcription and ERα protein levels. Moreover, we provide evidence that both SMC3 and MED12 colocalize on the ESR1 gene and are mutually required for their own occupancy as well as for RNAPII occupancy across the ESR1 gene. Finally, we show that extended proteasome inhibition decreases the mRNA expression of cohesin subunits which accompanies a decrease in ESR1 mRNA and ERα protein levels as well as estrogen-regulated transcription.

Conclusions

These results identify the ESR1 gene as a cohesin/Mediator-dependent gene and indicate that this regulation may potentially be exploited for the treatment of estrogen-dependent breast cancer.
Implementation of a neonatal pain management module in the computerized physician order entry system
Authors: Mazars Nathalie , Milési Christophe , Carbajal Ricardo , Mesnage Renault , Combes Clémentine , Novais Aline Rideau Batista , Cambonie Gilles
Published: August 2012

Background

Despite the recommended guidelines, the neonatal management of pain and discomfort often remains inadequate. The purpose of the present study was to determine whether adding a pain and discomfort module to a computerized physician order entry (CPOE) system would improve pain and discomfort evaluation in premature newborns under invasive ventilation.

Methods

All newborns <37 weeks gestational age (GA) and requiring invasive ventilation were included in a prospective study during two 6-month periods: before and after the inclusion of the pain and discomfort evaluation module. The main outcome measure was the percentage of patients having at least one assessment of pain and discomfort per day of invasive ventilation using the COMFORT scale.

Results

A total of 122 patients were included: 53 before and 69 after the incorporation of the module. The mean age was 30 (3) weeks GA. After the module was included, the percentage of patients who benefited from at least one pain and discomfort assessment per day increased from 64% to 88% (p < 0.01), and the mean number (SD) of scores recorded per day increased from 1 (1) to 3 (1) (p < 0.01). When the score was not within the established range, the nursing staff adapted analgesia/sedation doses more frequently after module inclusion (53% vs. 34%,p < 0.001). Despite higher mean doses of midazolam after module introduction [47 (45) vs. 31 (18) μg/kg/hr,p < 0.05], the durations of invasive ventilation and hospital stay, and the number of nosocomial infections, were not significantly modified.

Conclusions

Adding a pain and discomfort tool to the CPOE system was a simple and effective way to improve the systematic evaluation of premature newborns who required ventilatory assistance.
The role of BCL11B in hematological malignancy
Authors: Huang Xin , Du Xin , Li Yangqiu
Published: August 2012

The B-cell leukemia/lymphoma 11B (BCL11B) gene is a member of the BCL family which plays a crucial role in the development, proliferation, differentiation and subsequent survival of T cells. BCL11B gene alterations are related to malignant T cell transformation that occurs in hematological malignancies. Remarkably, the BCL11B gene is responsible for the regulation of the apoptotic process and cell proliferation. This review summarizes current data and knowledge concerning the alteration of BCL11B in hematological malignancies and its role as a potential target for therapies directed against T cell malignancies.
The active electrosensory range ofGymnotus omarorum
Authors: Pereira Ana Carolina , Aguilera Pedro , Caputi Angel A.
Published: August 2012

This article reports a biophysical and behavioral assessment of the active electrolocation range of Gymnotus omarorum. Physical measurements show that the stimulus field of a point on the sensory mosaic (i.e. the potential positions in which an object may cause a significant departure of the transcutaneous field from basal in the absence of an object) consists of relatively extended volumes surrounding this point. The shape of this stimulus field is dependent on the position of the point on the receptive mosaic and the size of the object. Although the limit of stimulus fields is difficult to assess (it depends on receptor threshold), departure from the basal field decays rapidly, vanishing at about 1.5 diameters for conductive spheres. This short range was predictable from earlier theoretical constructs and experimental data. Here, we addressed the contribution of three different but synergetic mechanisms by which electrosensory signals attenuate with object distance. Using novelty responses as an indicator of object detection we confirmed that the active electrosensory detection range is very short. Behavioral data also indicate that the ability to precisely locate a small object of edible size decays even more rapidly than the ability to detect it. The role of active electroreception is discussed in the context of the fish's habitat.
Resolvins D1, D2, and Other Mediators of Self-Limited Resolution of Inflammation in Human Blood following n-3 Fatty Acid Supplementation
Authors: Mas Emilie , Croft Kevin D , Zahra Paul , Barden Anne , Mori Trevor A
Published: August 2012

BACKGROUND

Resolvins and protectins are families of local lipid mediators generated from the n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) during self-limited resolution of inflammation. We aimed to develop a liquid chromatography–tandem mass spectrometry (LC-MS/MS) assay to measure these lipid mediators in human blood following n-3 fatty acid supplementation and to determine whether the blood collection method affects their measured concentration.

METHODS

Blood samples from 20 healthy volunteers enrolled in an n-3 fatty acid supplementation trial were collected in EDTA, heparin, or citrate, or prepared as serum after volunteers had undergone 3 weeks of supplementation. Plasma or serum was purified by solid-phase chromatography and analyzed with LC-MS/MS.

RESULTS

The assay identified 18R/S-hydroxy-5Z,8Z,11Z,14Z,16E-eicosapentaenoic acid (18R/S-HEPE); 17S-hydroxy-4Z,7Z,10Z,13Z,15E,19Z-docosahexaenoic acid (17R/S-HDHA); 7S,8R,17S-trihydroxy-4Z,9E,11E,13Z,15E,19Z-docosahexaenoic acid (RvD1); 7S,8R,17R-trihydroxy-4Z,9E,11E,13Z,15E19Z-docosahexaenoicacid (17R-RvD1); 7S,16R,17S-trihydroxy-4Z,8E,10Z,12E,14E,19Z-docosahexaenoic acid (RvD2); 10S,17S-dihydroxy-4Z,7Z,11E,13Z,15E,19Z-docosahexaenoicacid (10S,17S-DiHDHA); and 10R,17S-dihydroxy-4Z,7Z,11E,13E,15Z,19Z-docosahexaenoic acid (protectin D1, PD1). The limits of detection and quantification were 3 pg and 6 pg on-column, respectively. The pathway precursors 18R/S-HEPE and 17R/S-HDHA, but not the resolvins, were lower in serum compared with plasma. After n-3 fatty acid supplementation, mean (SD) EDTA plasma concentrations were: 18R/S-HEPE 386 (56) pg/mL, 17R/S-HDHA 365 (65) pg/mL, RvD2 26 (4) pg/mL, RvD1 31 (5) pg/mL, and 17R-RvD 161 (7) pg/mL. 10S,17S-DiHDHA and PD1 concentrations were below the limit of quantification.

CONCLUSIONS

This is the first study reporting 17R/S-HDHA, RvD1, and RvD2 concentrations measured in human blood following oral n-3 fatty acid supplementation. The concentrations of the antiinflammatory lipid mediators RvD1 and RvD2 were within the biological range known to have antiinflammatory and proresolving activities in isolated human leukocytes and in in vivo studies in mice.
Compressed Transformation of Korean Film Industry from Old to New Regime
Authors: Noh Kwang Woo
Published: August 2012

Korean film business was constructed during the Japanese Occupation era (1910 1945). Under the situation that Japanese immigrants owned all theaters, Koreans managed to produce local films based on a distinct culture and history. From the Sino-Japanese War (1937) to the end of World War II, Korean local films fell into war propaganda film and were even suspended. From the end of WWII to the Korean War (1950 1953), the base of the Korean film business was almost destroyed. From 1954 to 1973, the Korean film business developed rapidly and was so prosperous that this era was called the South Korean Golden Age. But the establishment of Park Chung-hee's military dictatorship regime (1973) tightened its control of society including the film business. Besides, the nationwide spread of television made Korean film business stagnate from the 1970s to the mid 1980s.
Collecting the Ashes of Time: The Temporality and Materiality of Industrial Ruins in Wang Bing's West of the Tracks
Authors: Zhang Ling
Published: August 2012

The enigmatic and evocative characteristics of ruins (for example, ruined monuments, gardens, tombs, or steles) and the visual representations of ruins by painting, photography, and cinema, have been explored and elucidated by philosophers, theorists, art historians, and film scholars over decades or even centuries. The romantic tendency to aestheticize ruins in terms of their innate beauty as objects of venerable decay (Schonle, 2006: 649-669; Makarius, 2004: 81, 84, 108) has been contested by Walter Benjamin (Benjamin, 1977) in the modern period, since war catastrophes and human disasters which have resulted in vast ruins in the 20th Century make the aesthetic appreciation of ruins problematic.
Beyond South of the Border: A Textual Analysis of the Taiwanese Blockbuster Cape No.7
Authors: Su Chiaoning
Published: August 2012

Cape No. 7 (2008) was the most extraordinary cultural phenomenon to sweep Taiwan in 2008. From its debut on Aug. 22, 2008 to its close on Dec. 12, 2008, Cape No.7, a locally produced low-budget movie, not only achieved the longest theatrical release in Taiwanese cinematic history, stretching to 16 weeks, but also earned US$ 15.5 million in box office sales, becoming Taiwan's second highest-grossing movie of all time, trailing only to Titanic (Li, 2008).
Spectatorships, Pleasures, and Social Uses of Cinema: A Tentative Study of the Reception of Cape No 7
Authors: Shiau Hong-Chi
Published: August 2012

Cape No. 7 seems to have a simple storyline despite the large number of characters: essentially the story involves a Mandarin-speaking fashion model from Japan assigned the difficult task of managing a hastily assembled band comprising seven untrained locals. Not only in the movie, is the journey to success of the band a "miracle," but the marketing of the movie itself is a miracle as well1. The unusual music-comedy genre, strong character development, and localized humor are all important to the content of the movie (Hu, 2008; Cape No. 7 official site). The characterization in the film is especially impressive, as the characters are presented as rounded individuals with multi-faceted personalities.
Beyond Fuller and M.A.S.H.: Korean War Representations in Film, Genre, and Comic Strip
Authors: Williams Tony
Published: August 2012

Like that popular definition of the Korean War, most Hollywood representations appear to be as "forgotten" as the still relevant implications of the actual conflict. Exceptions do exist such as the early 50s films of Samuel Fuller - The Steel Helmet (1950) and Fixed Bayonets (1951 -- as well as M*A*S*H. (1970) that led to the popular CBS television series version that ran from 1972-1983. However, these films generally received attention as works of film "auteurs," while Altman's M*A*S*H received acclaim more as an allegory of the Vietnam War that was occurring at the time of production than a representation of the earlier conflict. However, cinematic representations of Korea were scarce in comparison to earlier and later representations of conflict.
Music and Meaning in the Independence-Era Malaysian Films of P. Ramlee
Authors: McGraw Andrew Clay , Suriyanti Azmi Azti Nezia
Published: August 2012

Independence-era Malaysia boasted a robust film industry that produced hundreds of films per year between the late 1950s and early 1960s. The multiinstrumentalist, singer, composer, actor, and director P. Ramlee was the most productive and popular figure in this scene. Today Ramlee is lauded as one of Malaysia's and Singapore's most important cultural figures. In this article we argue that Ramee's film music served to score the topography of ethnic relations in independence-era Malaysia. In Ramlee's films, which featured almost exclusively Malay casts and cultural contexts, inter-ethnic relations were heard more often than seen. Ramlee's music stood in a complex if sometimes contradictory relationship to the representation of modern Malay culture and class in his films. While upper class Westernized Malay characters were inevitably portrayed as betraying traditional values, Westernized Malay music (and vice versa) served as the soundtrack for modern, working class Malaysians rooted in traditional cultural mores.
Revisiting the Tale of Obasute in the Japanese Imagination
Authors: Lee Wood-hung , Shaw Yomei
Published: August 2012

In 1983, Japanese director Imamura Shôhei's film The Ballad of Narayama (Narayama bushikô1) gained international recognition by winning the Palme d'Or prize at the Cannes Film Festival. The film was based on a well-known Japanese novel of the same name, written by Fukasawa Shichirô in 1956,2 depicting a rural village where an elderly woman, Orin, stoically prepares to make her final journey to a sacred mountaintop where she will await death, after the village custom. The earthy realism of the film's portrayal of the harsh world of the farming village both shocked and touched critics (Kehr, 1997: 85-86; Lardeau, 1997: 157-158; Tesson, 1997: 159-163). Imamura's film was not, however, the first to adapt Fukasawa's novel for the screen. Earlier, in 1958, Kinoshita Keisuke had also directed a film3 based on the same novel, in a very different style which incorporated elements of traditional Japanese theatre.
Paired-Pulse Plasticity in the Strength and Latency of Light-Evoked Lateral Inhibition to Retinal Bipolar Cell Terminals
Authors: Vickers Evan , Kim Mean-Hwan , Vigh Jozsef , von Gersdorff Henrique
Published: August 2012

Synapses in the inner plexiform layer of the retina undergo short-term plasticity that may mediate different forms of adaptation to regularities in light stimuli. Using patch-clamp recordings from axotomized goldfish Mb bipolar cell (BC) terminals with paired-pulse light stimulation, we isolated and quantified the short-term plasticity of GABAergic lateral IPSCs (L-IPSCs). Bright light stimulation evoked ON and OFF L-IPSCs in axotomized BCs, which had distinct onset latencies (∼50–80 and ∼70–150 ms, respectively) that depended on background light adaptation. We observed plasticity in both the synaptic strength and latency of the L-IPSCs. With paired light stimulation, latencies of ON L-IPSCs increased at paired-pulse intervals (PPIs) of 50 and 300 ms, whereas OFF L-IPSC latencies decreased at the 300 ms PPI. ON L-IPSCs showed paired-pulse depression at intervals <1 s, whereas OFF L-IPSCs showed depression at intervals ≤1 s and amplitude facilitation at longer intervals (1–2 s). This biphasic form of L-IPSC plasticity may underlie adaptation and sensitization to surround temporal contrast over multiple timescales. Block of retinal signaling at GABAARs and AMPARs differentially affected ON and OFF L-IPSCs, confirming that these two types of feedback inhibition are mediated by distinct and convergent retinal pathways with different mechanisms of plasticity. We propose that these plastic changes in the strength and timing of L-IPSCs help to dynamically shape the time course of glutamate release from ON-type BC terminals. Short-term plasticity of L-IPSCs may thus influence the strength, timing, and spatial extent of amacrine and ganglion cell inhibitory surrounds.
A GABAergic Inhibitory Neural Circuit Regulates Visual Reversal Learning inDrosophila
Authors: Ren Qingzhong , Li Hao , Wu Yanying , Ren Jing , Guo Aike
Published: August 2012

Inflexible cognition and behavior are prominent features of prefrontal cortex damage and several neuropsychiatric disorders. The ability to flexibly adapt cognitive processing and behavior to dynamically changing environmental contingencies has been studied using the reversal learning paradigm in mammals, but the complexity of the brain circuits precludes a detailed analysis of the underlying neural mechanism. Here we study the neural circuitry mechanism supporting flexible behavior in a genetically tractable model organism,Drosophila melanogaster. Combining quantitative behavior analysis and genetic manipulation, we found that inhibition from a single pair of giant GABAergic neurons, the anterior paired lateral (APL) neurons, onto the mushroom bodies (MBs) selectively facilitates behavioral flexibility during visual reversal learning. This effect was mediated by ionotropic GABAAreceptors in the MB. Moreover, flies with perturbed MB output recapitulated the poor reversal performance of flies with dysfunctional APL neurons. Importantly, we observed that flies with dysfunctional APL–MB circuit performed normally in simple forms of visual learning, including initial learning, extinction, and differential conditioning. Finally, we showed that acute disruption of the APL–MB circuit is sufficient to impair visual reversal learning. Together, these data suggest that the APL–MB circuit plays an essential role in the resolution of conflicting reinforcement contingencies and reveals an inhibitory neural mechanism underlying flexible behavior inDrosophila.
Molecular and Functional Interaction between Protocadherin-γC5 and GABAAReceptors
Authors: Li Yanfang , Xiao Haiyan , Chiou Tzu-Ting , Jin Hongbing , Bonhomme Bevan , Miralles Celia P. , Pinal Noelia , Ali Rashid , Chen Weisheng V. , Maniatis Tom , De Blas Angel L.
Published: August 2012

We have found that the γ2 subunit of the GABAAreceptor (γ2-GABAAR) specifically interacts with protocadherin-γC5 (Pcdh-γC5) in the rat brain. The interaction occurs between the large intracellular loop of the γ2-GABAAR and the cytoplasmic domain of Pcdh-γC5. In brain extracts, Pcdh-γC5 coimmunoprecipitates with GABAARs. In cotransfected HEK293 cells, Pcdh-γC5 promotes the transfer of γ2-GABAAR to the cell surface. We have previously shown that, in cultured hippocampal neurons, endogenous Pcdh-γC5 forms clusters, some of which associate with GABAergic synapses. Overexpression of Pcdh-γC5 in hippocampal neurons increases the density of γ2-GABAAR clusters but has no significant effect on the number of GABAergic contacts that these neurons receive, indicating that Pcdh-γC5 is not synaptogenic. Deletion of the cytoplasmic domain of Pcdh-γC5 enhanced its surface expression but decreased the association with both γ2-GABAAR clusters and presynaptic GABAergic contacts. Cultured hippocampal neurons from the Pcdh-γ triple C-type isoform knock-out (TCKO) mouse (Pcdhgtcko/tcko) showed plenty of GABAergic synaptic contacts, although their density was reduced compared with sister cultures from wild-type and heterozygous mice. Knocking down Pcdh-γC5 expression with shRNA decreased γ2-GABAAR cluster density and GABAergic innervation. The results indicate that, although Pcdh-γC5 is not essential for GABAergic synapse formation or GABAAR clustering, (1) Pcdh-γC5 regulates the surface expression of GABAARs viacis-cytoplasmic interaction with γ2-GABAAR, and (2) Pcdh-γC5 plays a role in the stabilization and maintenance of some GABAergic synapses.
Microglia Proliferation Is Controlled by P2X7 Receptors in a Pannexin-1-Independent Manner during Early Embryonic Spinal Cord Invasion
Authors: Rigato Chiara , Swinnen Nina , Buckinx Roeland , Couillin Isabelle , Mangin Jean-Marie , Rigo Jean-Michel , Legendre Pascal , Le Corronc Hervé
Published: August 2012

Microglia are known to invade the mammalian spinal cord (SC) at an early embryonic stage. While the mechanisms underlying this early colonization of the nervous system are still unknown, we recently found that it is associated, at least partially, with the ability of microglia to proliferate at the onset of motoneuron developmental cell death and of synaptogenesis in mouse embryo (E13.5).In vitrostudies have shown that the proliferation and activation of adult microglia can be influenced by the purinergic ionotropic receptor P2X7 via a coupling with Pannexin-1. By performing patch-clamp recordingsin situusing a whole-mouse embryonic SC preparation, we show here that embryonic microglia already express functional P2X7R. P2X7R activation evoked a biphasic current in embryonic microglia, which is supposed to reflect large plasma membrane pore opening. However, although embryonic microglia express pannexin-1, this biphasic current was still recorded in microglia of pannexin-1 knock-out embryos, indicating that it rather reflected P2X7R intrinsic pore dilatation. More important, we found that proliferation of embryonic SC microglia, but not their activation state, depends almost entirely on P2X7R by comparing wild-type and P2X7R−/− embryos. Absence of P2X7R led also to a decrease in microglia density. Pannexin-1−/− embryos did not exhibit any difference in microglial proliferation, showing that the control of embryonic microglial proliferation by P2X7R does not depend on pannexin-1 expression. These results reveal a developmental role of P2X7R by controlling embryonic SC microglia proliferation at a critical developmental state in the SC of mouse embryos.
Social, Communication, and Cortical Structural Impairments in Epac2-Deficient Mice
Authors: Srivastava Deepak P. , Jones Kelly A. , Woolfrey Kevin M. , Burgdorf Jeffrey , Russell Theron A. , Kalmbach Abigail , Lee Hyerin , Yang Connie , Bradberry Mazdak M. , Wokosin David , Moskal Joseph R. , Casanova Manuel F. , Waters Jack , Penzes Peter
Published: August 2012

Deficits in social and communication behaviors are common features of a number of neurodevelopmental disorders. However, the molecular and cellular substrates of these higher order brain functions are not well understood. Here we report that specific alterations in social and communication behaviors in mice occur as a result of loss of theEPAC2gene, which encodes a protein kinase A-independent cAMP target. Epac2-deficient mice exhibited robust deficits in social interactions and ultrasonic vocalizations, but displayed normal olfaction, working and reference memory, motor abilities, anxiety, and repetitive behaviors. Epac2-deficient mice displayed abnormal columnar organization in the anterior cingulate cortex, a region implicated in social behavior in humans, but not in somatosensory cortex.In vivotwo-photon imaging revealed reduced dendritic spine motility and density on cortical neurons in Epac2-deficient mice, indicating deficits at the synaptic level. Together, these findings provide novel insight into the molecular and cellular substrates of social and communication behavior.
Recurrent Interactions between the Input and Output of a Songbird Cortico-Basal Ganglia Pathway Are Implicated in Vocal Sequence Variability
Authors: Hamaguchi Kosuke , Mooney Richard
Published: August 2012

Complex brain functions, such as the capacity to learn and modulate vocal sequences, depend on activity propagation in highly distributed neural networks. To explore the synaptic basis of activity propagation in such networks, we made dualin vivointracellular recordings in anesthetized zebra finches from the input (nucleus HVC, used here as a proper name) and output [lateral magnocellular nucleus of the anterior nidopallium (LMAN)] neurons of a songbird cortico-basal ganglia (BG) pathway necessary to the learning and modulation of vocal motor sequences. These recordings reveal evidence of bidirectional interactions, rather than only feedforward propagation of activity from HVC to LMAN, as had been previously supposed. A combination of dual and triple recording configurations and pharmacological manipulations was used to map out circuitry by which activity propagates from LMAN to HVC. These experiments indicate that activity travels to HVC through at least two independent ipsilateral pathways, one of which involves fast signaling through a midbrain dopaminergic cell group, reminiscent of recurrent mesocortical loops described in mammals. We then usedin vivopharmacological manipulations to establish that augmented LMAN activity is sufficient to restore high levels of sequence variability in adult birds, suggesting that recurrent interactions through highly distributed forebrain–midbrain pathways can modulate learned vocal sequences.
Clinically Relevant Hormone Treatments Fail to Induce Spinogenesis in Prefrontal Cortex of Aged Female Rhesus Monkeys
Authors: Ohm Daniel T. , Bloss Erik B. , Janssen William G. , Dietz Karen C. , Wadsworth Shannon , Lou Wendy , Gee Nancy A. , Lasley Bill L. , Rapp Peter R. , Morrison John H.
Published: August 2012

Preclinical animal models have provided strong evidence that estrogen (E) therapy (ET) enhances cognition and induces spinogenesis in neuronal circuits. However, clinical studies have been inconsistent, with some studies revealing adverse effects of ET, including an increased risk of dementia. In an effort to bridge this disconnect between the preclinical and clinical data, we have developed a nonhuman primate (NHP) model of ET combined with high-resolution dendritic spine analysis of dorsolateral prefrontal cortical (dlPFC) neurons. Previously, we reported cyclic ET in aged, ovariectomized NHPs increased spine density on dlPFC neurons. Here, we report that monkeys treated with cyclic E treatment paired with cyclic progesterone (P), continuous E combined with P (either cyclic or continuous), or unopposed continuous E failed to increase spines on dlPFC neurons. Given that the most prevalent form of ET prescribed to women is a combined and continuous E and P, these data bring into convergence the human neuropsychological findings and preclinical neurobiological evidence that standard hormone therapy in women is unlikely to yield the synaptic benefit presumed to underlie the cognitive enhancement reported in animal models.
Arf6-GEF BRAG1 Regulates JNK-Mediated Synaptic Removal of GluA1-Containing AMPA Receptors: A New Mechanism for Nonsyndromic X-Linked Mental Disorder
Authors: Myers Kenneth R. , Wang Guangfu , Sheng Yanghui , Conger Kathryn K. , Casanova James E. , Zhu J. Julius
Published: August 2012

Activity-dependent modifications of excitatory synapses contribute to synaptic maturation and plasticity, and are critical for learning and memory. Consequently, impairments in synapse formation or synaptic transmission are thought to be responsible for several types of mental disabilities. BRAG1 is a guanine nucleotide exchange factor for the small GTP-binding protein Arf6 that localizes to the postsynaptic density of excitatory synapses. Mutations in BRAG1 have been identified in families with X-linked intellectual disability (XLID). These mutations mapped to either the catalytic domain or an IQ-like motif; however, the pathophysiological basis of these mutations remains unknown. Here, we show that the BRAG1 IQ motif binds apo-calmodulin (CaM), and that calcium-induced CaM release triggers a reversible conformational change in human BRAG1. We demonstrate that BRAG1 activity, stimulated by activation of NMDA-sensitive glutamate receptors, depresses AMPA receptor (AMPA-R)-mediated transmission via JNK-mediated synaptic removal of GluA1-containing AMPA-Rs in rat hippocampal neurons. Importantly, a BRAG1 mutant that fails to activate Arf6 also fails to depress AMPA-R signaling, indicating that Arf6 activity is necessary for this process. Conversely, a mutation in the BRAG1 IQ-like motif that impairs CaM binding results in hyperactivation of Arf6 signaling and constitutive depression of AMPA transmission. Our findings reveal a role for BRAG1 in response to neuronal activity with possible clinical relevance to nonsyndromic XLID.
Teneurin-4 Is a Novel Regulator of Oligodendrocyte Differentiation and Myelination of Small-Diameter Axons in the CNS
Authors: Suzuki Nobuharu , Fukushi Masaya , Kosaki Keisuke , Doyle Andrew D. , de Vega Susana , Yoshizaki Keigo , Akazawa Chihiro , Arikawa-Hirasawa Eri , Yamada Yoshihiko
Published: August 2012

Myelination is essential for proper functioning of the CNS. In this study, we have identified a mouse mutation, designatedfurue, which causes tremors and hypomyelination in the CNS, particularly in the spinal cord, but not in the sciatic nerve of the PNS. In the spinal cord of thefuruemice, myelination of small-diameter axons was dramatically reduced, and differentiation of oligodendrocytes, the myelin-forming cells in the CNS, was inhibited. We subsequently found that thefuruemutation was associated with a transgene insertion into the teneurin-4 (Ten-4, Ten-m4/Odz4) gene, encoding a transmembrane protein of unknown function. Ten-4 was strongly expressed in the spinal cord of wild-type mice and was induced during normal oligodendrocyte differentiation. In contrast, in thefuruemice, the expression of Ten-4 was absent. Differentiation and cellular process formation of oligodendrocytes were inhibited in primary cell culture from thefuruemice. Cell differentiation and process formation were also inhibited in the oligodendrocyte progenitor cell line CG-4 after suppression of Ten-4 expression by shRNA. Furthermore, Ten-4 positively regulated focal adhesion kinase, an essential signaling molecule for oligodendrocyte process formation and myelination of small-diameter axons. These findings suggest that Ten-4 is a novel regulator of oligodendrocyte differentiation and that it plays a critical role in the myelination of small-diameter axons in the CNS.
Presynaptic But Not Postsynaptic GABA Signaling at Unitary Mossy Fiber Synapses
Authors: Cabezas Carolina , Irinopoulou Theano , Gauvain Grégory , Poncer Jean Christophe
Published: August 2012

Dentate gyrus granule cells have been suggested to corelease GABA and glutamate both in juvenile animals and under pathological conditions in adults. Although mossy fiber terminals (MFTs) are known to express glutamic acid decarboxylase (GAD) in early postnatal development, the functional role of GABA synthesis in MFTs remains controversial, and direct evidence for synaptic GABA release from MFTs is missing. Here, using GAD67-GFP transgenic mice, we show that GAD67 is expressed only in a population of immature granule cells in juvenile animals. We demonstrate that GABA can be released from these cells and modulate mossy fiber excitability through activation of GABAB autoreceptors. However, unitary postsynaptic currents generated by individual, GAD67-expressing granule cells are purely glutamatergic in all postsynaptic cell types tested. Thus GAD67 expression does not endow dentate gyrus granule cells with a full GABAergic phenotype and GABA primarily instructs the pre- rather than the postsynaptic element.