bluuebunny/crossref_metadata_2025 huggingface dataset:
Women in the criminal justice system: The triumph of inertia
Authors: Player Elaine
Published: July 2013

This article explores why the government strategy for women offenders has failed to achieve its key objectives despite extensive agreement about the need and direction of change and the momentum generated by the Corston Report. It argues that although the women’s policy agenda is supported by equality and human rights legislation, the operational context of the criminal justice system inhibits its realization. The reforms recognize the need for differential treatment in the pursuit of gender equality and reflect principles of distributive and non-distributive justice that promote individual welfare and social inclusion. Paradoxically, they are advanced within a criminal justice system that is predominantly concerned with the distribution of just deserts and the management of criminal risk. The inherent contradictions reflect not only theoretical differences but distinct ideological constructs that shape the ways in which concepts of equality, rehabilitation and justice are interpreted and given practical effect. The agreed policy of equal justice for women requires a culture of rights that undermines the present concepts of desert and ‘less eligibility’ and replaces risk management with rehabilitative opportunities that provide a reparative approach to social harm.
The Artification of Tattoo: Transformations within a Cultural Field
Authors: Kosut Mary
Published: July 2013

Theorized as a Bourdieusian field, this article examines changes inside the tattoo world resulting in the valuation of certain tattoo practices as art and some actors taking ‘fine art’ positions within it. The category of tattoo art is distinct from tattoo because it positions the practice away from its traditional historic moorings as a lowbrow craft and occupation requiring a rudimentary level of technical skill. In contrast, tattoo art is created and evaluated within academic discourses and traditional fine art ideologies that stress innovation, creativity, and exclusivity. In addition to mastery of the medium, that is, applying the tattoo to skin, tattoo artists create original works that qualify as artistic by art world conventions. This process of artification has changed the symbolic meanings and valuation of a practice, imbuing tattoo art with cultural legitimacy from the inside.
Odanacatib in postmenopausal women with low bone mineral density: a review of current clinical evidence
Authors: Zerbini Cristiano A. F. , McClung Michael R.
Published: July 2013

Human bones are in a continuous process of remodeling that ensures renovation and maintenance of the skeletal mass. Bone remodeling has two phases that are normally coupled and balanced: bone resorption mediated by osteoclasts and bone formation mediated by osteoblasts. An increase in bone resorption over bone formation results in a progressive loss of bone mass and impairment of bone microarchitecture leading to osteoporosis and its associated fractures. Recent advances in the understanding of the molecular and cellular mechanisms involved in the remodeling process have allowed the development of new targets for osteoporosis treatment. Cathepsin K, a cysteine protease, is found in osteoclasts along the bone resorption surfaces and very efficiently degrades type I collagen, the major component of the organic bone matrix. Inhibition of cathepsin K reduces bone resorption but does not impair bone formation particularly at cortical sites. Odanacatib, a potent and highly selective cathepsin K inhibitor, showed prevention of bone loss without reduction of bone formation in preclinical and clinical trials (phase I and II). Odanacatib is currently in a phase III fracture outcome international trial for the treatment of postmenopausal osteoporosis.
A naturalistic comparison of the efficacy and safety of intramuscular olanzapine and intramuscular haloperidol in agitated elderly patients with schizophrenia
Authors: Suzuki Hidenobu , Gen Keishi , Takahashi Yuki
Published: July 2013

Objective:

This study was a comparative investigation of the clinical efficacy and safety of intramuscular (IM) olanzapine and IM haloperidol in agitated elderly patients with schizophrenia at 2 hours postdose.

Methods:

The subjects were 23 inpatients who had been diagnosed with schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). Their clinical symptoms were assessed using Positive and Negative Syndrome Scale Excited Component (PANSS-EC), PANSS and Agitation Calmness Evaluation Scale (ACES), and their safety were assessed using the Abnormal Involuntary Movement Scale (AIMS), Barnes Akathisia Rating Scale (BARS), Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) and laboratory tests.

Results:

The mean reduction from baseline on the PANSS-EC total score, the PANSS total score and the ACES score were significantly greater in the IM olanzapine injection group than in the IM haloperidol injection group. The mean changes from baseline on the AIMS score, the BARS score and the DIEPSS total score were significantly better in the IM olanzapine injection group than in the IM haloperidol injection group. No serious adverse events such as paralytic ileus, diabetic ketoacidosis, neuroleptic malignant syndrome or tardive dyskinesia occurred between the two groups.

Conclusion:

The results of this study suggest the possibility that agitated elderly patients may result in superior efficacy and safety after IM olanzapine without serious adverse events in comparison with IM haloperidol.
Young Adults’ Responses to Infant Names
Authors: Powell Darcey N , Karraker Katherine
Published: July 2013

AbstractMany parents in the United States devote a great deal of attention to selecting their children’s names. To better understand this process, 532 potential parents in the United States rated their liking and perceptions of infant names. Liking was related to characteristics of the names (such as popularity, defined as how frequently the names had been previously selected by parents) and to characteristics of the raters (such as their personality traits and gender). Ratings of the physical and behavioral traits of infants depicted through both a name and a photograph were related more strongly to ratings of the photograph alone than the name alone. These results suggest that parent preferences for certain names may account for changes in name popularity over time, and also suggest that the influence of names on adults’ perceptions of infants may be superseded by the influence of the infants’ physical appearance.
De-abbreviations: From Soviet Union to Contemporary Belarus
Authors: Astapova Anastasiya
Published: July 2013

AbstractThe article is dedicated to the study of ludic de-abbreviation, backronymization, or, alternatively, humorous decoding of the well-known abbreviations (which usually serve as names for political parties, countries, universities, and so on). A brief survey of the existing research is provided. Then, despite the fact that de-abbreviation was considered characteristic of the Soviet period, now almost extinct, the author focuses on a case study based on contemporary material, which proves that de-abbreviation is still popular and productive for name-giving. As soon as an abbreviation for the name of Belarusian president Alexander Lukashenko, used by the police for safety reasons, appeared in press (2012), it immediately caused dozens of ludic de-abbreviations suggesting alternative names for him. The article focuses on the mechanisms of these renaming de-abbreviations as well as the reasons that caused their peculiarities and multiplicity.
Staphylococcus aureus recognition by hematopoietic stem and progenitor cells via TLR2/MyD88/PGE2 stimulates granulopoiesis in wounds
Authors: Granick Jennifer L. , Falahee Patrick C. , Dahmubed Delsheen , Borjesson Dori L. , Miller Lloyd S. , Simon Scott I.
Published: July 2013

Key Points

HSPCs are recruited to S aureus–infected skin wounds, differentiate into neutrophils, and hasten resolution of infection. Bacterial sensing via TLR2 elicits PGE2 production in HSPCs that provides autocrine feedback to meet the demand for local granulopoiesis.
IκB-ζ controls the constitutive NF-κB target gene network and survival of ABC DLBCL
Authors: Nogai Hendrik , Wenzel Sören-Sebastian , Hailfinger Stephan , Grau Michael , Kaergel Eva , Seitz Volkhard , Wollert-Wulf Brigitte , Pfeifer Matthias , Wolf Annette , Frick Mareike , Dietze Kerstin , Madle Hannelore , Tzankov Alexander , Hummel Michael , Dörken Bernd , Scheidereit Claus , Janz Martin , Lenz Peter , Thome Margot , Lenz Georg
Published: July 2013

Key Points

IκB-ζ is essential for nuclear NF-κB activity in ABC DLBCL. ABC DLBCL survival depends on IκB-ζ signaling.
Bowel necrosis following endovascular revascularization for chronic mesenteric ischemia: a case report and review of the literature
Authors: Shirasu Takuro , Hosaka Akihiro , Okamoto Hiroyuki , Shigematsu Kunihiro , Takeda Yasushi , Miyata Tetsuro , Watanabe Toshiaki
Published: July 2013

Background

Endovascular revascularization has recently been established as a less invasive treatment method for chronic mesenteric ischemia. However, intestinal necrosis caused by distal embolization following this procedure has not been emphasized.

Case presentation

The present report describes a 59-year-old man who was treated with endovascular revascularization for chronic mesenteric ischemia. After the procedure, he was diagnosed with intestinal necrosis caused by distal embolization. Despite emergent bowel resection, he died on postoperative day 109.

Conclusion

Although endovascular revascularization for chronic mesenteric ischemia is less invasive and may be suitable for high-risk patients, attention should be paid to avoid embolic complications that can cause intestinal infarction possibly leading to a fatal condition.
High levels of soluble CD40 ligand and matrix metalloproteinase-9 in serum are associated with favorable clinical evolution in human visceral leishmaniasis
Authors: de Oliveira Fabrícia Alvisi , Vanessa Oliveira Silva Carla , Damascena Nayra Prata , Passos Rodrigo Oliveira , Duthie Malcolm S , Guderian Jeffrey A , Bhatia Ajay , de Moura Tatiana Rodrigues , Reed Steven G , de Almeida Roque Pacheco , de Jesus Amélia Ribeiro
Published: July 2013

Background

Soluble CD40 ligand (sCD40L) and matrix metalloproteinase 9 (MMP-9) are inflammation markers and have been poorly described in infectious disease. In this prospective study, we describe the sera kinetics of these two molecules in the course of treatment follow up in human visceral leishmaniasis (VL).

Methods

Sera from VL patients were collected before and during follow up of regular Antimony treatment. sCD40L and MMP-9 were measured by Luminex assay. Paired analysis by Wilcoxon signed test was used for comparison of values of the same subjects before and after initiation of treatment. Correlations between clinical data and parasite load with the serum levels of sCD40L and MMP-9 were performed by Spearman test. Tests were considered statistically significant if the probability of a type I error was less than 5% (p-value < 0.05).

Results

While sCD40L and MMP-9 were not observed in sera from non endemic controls which are at low risk ofLeishmania chagasiinfection, elevated levels were observed in sera from VL patients, and an increase in sCD40L and MMP-9 levels were detectable during the follow-up of VL patients undergoing antimony treatment. sCD40L levels were also high in individuals living in endemic settings at high risk of infection (endemic controls). Additionally, negative correlations were found between spleen sizes and MMP-9 before treatment and sCD40L at day 15 of treatment. Negative correlations were also found between parasite load with both sCD40L and MMP-9.

Conclusion

Serum sCD40L and MMP-9 are identified as new and simple biomarkers in two situations: (i) monitoring the success of therapy and (ii) predicting favorable clinical outcome of human VL.
Pseudomonas aeruginosa bacteremia in patients with liver cirrhosis: a comparison with bacteremia caused by Enterobacteriaceae
Authors: Bang Ji Hwan , Jung Younghee , Cheon Shinhye , Kim Chung Jong , Song Kyung Ho , Choe Pyeong Gyun , Park Wan Beom , Kim Eu Suk , Park Sang Won , Kim Hong Bin , Oh Myoung-don , Lee Hyo-Suk , Kim Nam Joong
Published: July 2013

Background

This study was performed to detect risk factors for Pseudomonas aeruginosa bacteremia in patients with liver cirrhosis.

Methods

A retrospective case–control study was designed to identify risk factors for P. aeruginosa bacteremia in cirrhotic patients. The cases were cirrhotic patients with P. aeruginosa bacteremia and the controls were cirrhotic patients with Enterobacteriaceae bacteremia.

Results

Sixty-one cases and the same number of controls were enrolled. In a multivariate analysis, younger age {adjusted odds ratio (aOR) per one year: 0.96, 95% confidence interval: 0.93 - 0.99}, nosocomial acquisition (aOR 3.87, 95% confidence interval: 1.50 - 9.94), preexisting biliary disease (aOR 4.79, 95% confidence interval: 1.92 - 10.47), and recent exposure to immunosuppressive agent (aOR 3.10, 95% confidence interval: 1.23 - 7.82) were associated with P. aeruginosa bacteremia. In the case group the frequency of appropriate initial antibiotic regimens was considerably lower than in the control group: 29.5% vs. 65.6% (P <0.01). However, thirty day mortality did not differ significantly between cases and controls (19.7% vs. 24.6%).

Conclusions

Nosocomial acquisition, preexisting biliary disease, and recent use of immunosuppressive agents are strong predictive factors for P. aeruginosa bacteremia in cirrhotic patients.
Comparison of T2 and T2
*-weighted MR molecular imaging of a mouse model of glioma
Authors: Blasiak Barbara , Barnes Samuel , Foniok Tadeusz , Rushforth David , Matyas John , Ponjevic Dragana , Weglarz Wladyslaw P , Tyson Randy , Iqbal Umar , Abulrob Abedelnasser , Sutherland Garnette R , Obenaus Andre , Tomanek Boguslaw
Published: July 2013

Background

Standard MRI has been used for high-grade gliomas detection, albeit with limited success as it does not provide sufficient specificity and sensitivity to detect complex tumor structure. Therefore targeted contrast agents based on iron oxide, that shorten mostly T2 relaxation time, have been recently applied. However pulse sequences for molecular imaging in animal models of gliomas have not been yet fully studied. The aim of this study was therefore to compare contrast-to-noise ratio (CNR) and explain its origin using spin-echo (SE), gradient echo (GE), GE with flow compensation (GEFC) as well as susceptibility weighted imaging (SWI) in T2 and T2* contrast-enhanced molecular MRI of glioma.

Methods

A mouse model was used. U87MGdEGFRvIII cells (U87MG), derived from a human tumor, were injected intracerebrally. A 9.4 T MRI system was used and MR imaging was performed on the 10 day after the inoculation of the tumor. The CNR was measured prior, 20 min, 2 hrs and 24 hrs post intravenous tail administration of glioma targeted paramagnetic nanoparticles (NPs) using SE, SWI, GE and GEFC pulse sequences.

Results

The results showed significant differences in CNR among all pulse sequences prior injection. GEFC provided higher CNR post contrast agent injection when compared to GE and SE. Post injection CNR was the highest with SWI and significantly different from any other pulse sequence.

Conclusions

Molecular MR imaging using targeted contrast agents can enhance the detection of glioma cells at 9.4 T if the optimal pulse sequence is used. Hence, the use of flow compensated pulse sequences, beside SWI, should to be considered in the molecular imaging studies.
The promoter of miR-663 is hypermethylated in Chinese pediatric acute myeloid leukemia (AML)
Authors: Yan-Fang Tao , Jian Ni , Jun Lu , Na Wang , Pei-Fang Xiao , Wen-Li Zhao , Dong Wu , Li Pang , Jian Wang , Xing Feng , Jian Pan
Published: July 2013

Background

There is growing evidence supporting a role for microRNAs (miRNA) as targets in aberrant mechanisms of DNA hypermethylation. Epigenetic silencing of tumor suppressor miRNAs, including miR-663, which has recently been reported to be inactivated by hypermethylation in several cancers, may play important roles in pediatric acute myeloid leukemia (AML). However, expression of miR-663 and its promoter methylation remain status unclear in childhood leukemia.

Methods

Promoter methylation status of miR-663 was investigated by methylation specific PCR (MSP) and bisulfate genomic sequencing (BGS). Transcriptional expression of miR-663 was evaluated by semi-quantitative and real-time PCR, and the relationship between expression of miR-663 and promoter methylation was confirmed using 5-aza-2’-deoxycytidine (5-Aza) demethylation reagent.

Results

MiR-663 was aberrantly methylated in 45.5% (5/11) leukemia cell lines; BGS showed that the promoter was significantly methylated in three AML cell lines; methylation of miR-663 was significantly higher in Chinese pediatric AML patients [41.4% (29/70)] compared to normal bone marrow (NBM) control samples [10.0% (3/30)]. These results were confirmed by both BGS and 5-Aza demethylation analysis. In addition, miR-663 transcript expression was significantly lower in AML patients, both with and without miR-663 methylation, compared to controls; however, there were no significant differences in clinical features or French-American-British (FAB) classification between patients with and without miR-663 methylation.

Conclusions

Expression of miR-663 was significantly lower in pediatric AML cells compared to NBM controls; furthermore, a high frequency of miR-663 promoter hypermethylation was observed in both AML cell lines and pediatric AML samples. Inactivation of miR-663 by promoter hypermethylation could be affected by 5-Aza demethylation. These findings suggest that hypermethylation of the miR-663 promoter may be an early event in the development of pediatric AML.
Use of emergency department services by women victims of violence in Lazio region, Italy
Authors: Farchi Sara , Polo Arianna , Asole Simona , Ruggieri Maria Pia , Di Lallo Domenico
Published: July 2013

Background

Violence against women is a significant health problem and a hidden phenomenon, in Italy that about 31% of the women have been victims of violence once in life. Aims of this study are to describe characteristics of women victims of violence (VV) attending the EDs in the Lazio region in 2008 and to illustrate the frequency and characteristics of previous ED visits.

Methods

Using the Emergency Information System, visits of women, (15–49 years), in the 60 EDs, for a violent trauma have been analysed. For each VV identified, we considered the last episode and searched for ED attendances in a six year period (2003–08) in order to identify other visits. We performed descriptive analyses of socio-demographic and clinical factors of VV and we analyzed the impact previous ED visits. We compared ED utilization of women VV with a random sample of women with the same age distribution who gave birth in 2008.

Results

In 2008, 7,725 ED attendances of women VV were found (1.1% of the ED visits) corresponding to 6,936 women (prevalence = 52.0x10,000). The mean number of ED visits for each woman in five years was 5.0 (1–190). Prevalent diagnoses were contusions (45.8%), neurotic disorders (5.4%) complications of medical care (6.3%). The women were young, approximately 70% were residents in Rome or the surrounding areas. Foreign women were three times more likely to visit the ED for intentional injuries than were Italian women (114.1 vs 44.4 per 10.000).

Conclusions

This study shows high prevalence of violence against women in Lazio region, Italy. Most of the women have been visited by the ED several times before the violent episode, often with traumas. ED medical and nursing staff should be prepared and trained to successfully manage victims of violence.
RETRACTED ARTICLE: Gastroprotective effect of desmosdumotin C isolated from Mitrella kentii against ethanol-induced gastric mucosal hemorrhage in rats: possible involvement of glutathione, heat-shock protein-70, sulfhydryl compounds, nitric oxide, and anti-Helicobacter pylori activity
Authors: Sidahmed Heyam Mohamed Ali , Azizan Ainnul Hamidah Syahadah , Mohan Syam , Abdulla Mahmood Ameen , Abdelwahab Siddig Ibrahim , Taha Manal Mohamed Elhassan , Hadi A Hamid A , Ketuly Kamal Aziz , Hashim Najihah Mohd , Loke Mun Fai , Vadivelu Jamuna
Published: July 2013

Background

Mitrella kentii (M. kentii) (Bl.) Miq, is a tree-climbing liana that belongs to the family Annonaceae. The plant is rich with isoquinoline alkaloids, terpenylated dihydrochalcones and benzoic acids and has been reported to possess anti-inflammatory activity. The purpose of this study is to assess the gastroprotective effects of desmosdumotin C (DES), a new isolated bioactive compound from M. kentii, on gastric ulcer models in rats.

Methods

DES was isolated from the bark of M. kentii. Experimental rats were orally pretreated with 5, 10 and 20 mg/kg of the isolated compound and were subsequently subjected to absolute ethanol-induced acute gastric ulcer. Gross evaluation, mucus content, gastric acidity and histological gastric lesions were assessed in vivo. The effects of DES on the anti-oxidant system, non-protein sulfhydryl (NP-SH) content, nitric oxide (NO)level, cyclooxygenase-2 (COX-2) enzyme activity, bcl-2-associated X (Bax) protein expression and Helicabacter pylori (H pylori) were also investigated.

Results

DES pre-treatment at the administered doses significantly attenuated ethanol-induced gastric ulcer; this was observed by decreased gastric ulcer area, reduced or absence of edema and leucocytes infiltration compared to the ulcer control group. It was found that DES maintained glutathione (GSH) level, decreased malondialdehyde (MDA) level, increased NP-SH content and NO level and inhibited COX-2 activity. The compound up regulated heat shock protein-70 (HSP-70) and down regulated Bax protein expression in the ulcerated tissue. DES showed interesting anti-H pylori effects. The efficacy of DES was accomplished safely without any signs of toxicity.

Conclusions

The current study reveals that DES demonstrated gastroprotective effects which could be attributed to its antioxidant effect, activation of HSP-70 protein, intervention with COX-2 inflammatory pathway and potent anti H pylori effect.
Bufalin, a component in Chansu, inhibits proliferation and invasion of hepatocellular carcinoma cells
Authors: Qiu Dong-Ze , Zhang Zhou-Ji , Wu Wei-Zhong , Yang Yun-Ke
Published: July 2013

Background

Hepatocellular carcinoma (HCC) is a common and aggressive cancer, and the treatment options are limited for patients with advanced HCC. Bufalin, the major digoxin-like component of the traditional Chinese medicine Chansu, exhibits significant anti-tumor activities in many tumor cell lines. In the present study, we investigated the effect of bufalin on the inhibition of an AKT-related signaling pathway, and examined the relationship between regulatory proteins and anti-tumor effects in hepatoma cells.

Methods

Proliferation, wound healing, transwell-migration/invasion and adhesion assays were performed in HCCLM3 and HepG2 cell lines. The protein levels of pAKT, AKT, pGSK3β, GSK3β, pβ-catenin, β-catenin, E-cadherin, MMP-9, and MMP-2 were measured by western blot analysis. E-Cadherin and β-catenin expression levels were also evaluated by immunofluorescence.

Results

Bufalin inhibited hepatoma cell proliferation, migration, invasion and adhesion. In addition, treatment with bufalin significantly decreased the levels of pAKT, pGSK3β, MMP-9, and MMP-2, while increasing the levels of GSK3β and E-cadherin and suppressing the nuclear translocation of β-catenin.

Conclusions

Bufalin is a potential anti-HCC therapeutic candidate through its inhibition of the AKT/GSK3β/β-catenin/E-cadherin signaling pathway. Further studies with bufalin are warranted in patients with HCC, especially those with the disease at advanced stages.
Interaction of nanoparticles with proteins: relation to bio-reactivity of the nanoparticle
Authors: Saptarshi Shruti R , Duschl Albert , Lopata Andreas L
Published: July 2013

Interaction of nanoparticles with proteins is the basis of nanoparticle bio-reactivity. This interaction gives rise to the formation of a dynamic nanoparticle-protein corona. The protein corona may influence cellular uptake, inflammation, accumulation, degradation and clearance of the nanoparticles. Furthermore, the nanoparticle surface can induce conformational changes in adsorbed protein molecules which may affect the overall bio-reactivity of the nanoparticle. In depth understanding of such interactions can be directed towards generating bio-compatible nanomaterials with controlled surface characteristics in a biological environment. The main aim of this review is to summarise current knowledge on factors that influence nanoparticle-protein interactions and their implications on cellular uptake.
Betaine supplement enhances skeletal muscle differentiation in murine myoblasts via IGF-1 signaling activation
Authors: Senesi Pamela , Luzi Livio , Montesano Anna , Mazzocchi Nausicaa , Terruzzi Ileana
Published: July 2013

Background

Betaine (BET) is a component of many foods, including spinach and wheat. It is an essential osmolyte and a source of methyl groups. Recent studies have hypothesized that BET might play a role in athletic performance. However, BET effects on skeletal muscle differentiation and hypertrophy are still poorly understood.

Methods

We examined BET action on neo myotubes maturation and on differentiation process, using C2C12 murine myoblastic cells. We used RT2-PCR array, Western blot and immunofluorescence analysis to study the BET effects on morphological features of C2C12 and on signaling pathways involved in muscle differentiation and hypertrophy.

Results

We performed a dose–response study, establishing that 10 mM BET was the dose able to stimulate morphological changes and hypertrophic process in neo myotubes. RT2-PCR array methodology was used to identify the expression profile of genes encoding proteins involved in IGF-1 pathway. A dose of 10 mM BET was found to promote IGF-1 receptor (IGF-1 R) expression. Western blot and immunofluorescence analysis, performed in neo myotubes, pointed out that 10 mM BET improved IGF-1 signaling, synthesis of Myosin Heavy Chain (MyHC) and neo myotubes length.

In addition, we investigated BET role on myoblasts proliferation and differentiation. During proliferation, BET did not modify C2C12 proliferative rate, but promoted myogenic induction, enhancing MyoD protein content and cellular elongation. During differentiation, BET caused an increase of muscle-specific markers and IGF-1 R protein levels.

Conclusions

Our findings provide the first evidence that BET could promote muscle fibers differentiation and increase myotubes size by IGF-1 pathway activation, suggesting that BET might represent a possible new drug/integrator strategy, not only in sport performance but also in clinical conditions characterized by muscle function impairment.
Integration-deficient lentivectors: an effective strategy to purify and differentiate human embryonic stem cell-derived hepatic progenitors
Authors: Yang Guanghua , Si-Tayeb Karim , Corbineau Sébastien , Vernet Rémi , Gayon Régis , Dianat Noushin , Martinet Clémence , Clay Denis , Goulinet-Mainot Sylvie , Tachdjian Gérard , Tachdjian Gérard , Burks Deborah , Vallier Ludovic , Bouillé Pascale , Dubart-Kupperschmitt Anne , Weber Anne
Published: July 2013

Background

Human pluripotent stem cells (hPSCs) hold great promise for applications in regenerative medicine. However, the safety of cell therapy using differentiated hPSC derivatives must be improved through methods that will permit the transplantation of homogenous populations of a specific cell type. To date, purification of progenitors and mature cells generated from either embryonic or induced pluripotent stem cells remains challenging with use of conventional methods.

Results

We used lentivectors encoding green fluorescent protein (GFP) driven by the liver-specific apoliprotein A-II (APOA-II) promoter to purify human hepatic progenitors. We evaluated both integrating and integration-defective lentivectors in combination with an HIV integrase inhibitor. A human embryonic stem cell line was differentiated into hepatic progenitors using a chemically defined protocol. Subsequently, cells were transduced and sorted at day 16 of differentiation to obtain a cell population enriched in hepatic progenitor cells. After sorting, more than 99% of these APOA-II-GFP-positive cells expressed hepatoblast markers such as α-fetoprotein and cytokeratin 19. When further cultured for 16 days, these cells underwent differentiation into more mature cells and exhibited hepatocyte properties such as albumin secretion. Moreover, they were devoid of vector DNA integration.

Conclusions

We have developed an effective strategy to purify human hepatic cells from cultures of differentiating hPSCs, producing a novel tool that could be used not only for cell therapy but also forin vitroapplications such as drug screening. The present strategy should also be suitable for the purification of a broad range of cell types derived from either pluripotent or adult stem cells.
Effects of ziprasidone and olanzapine on body composition and metabolic parameters: an open-label comparative pilot study
Authors: Park Subin , Yi Ki Kyoung , Kim Min-Seon , Hong Jin Pyo
Published: July 2013

Background

In contrast to olanzapine, ziprasidone has been reported to cause minimal or no weight gain. This study aimed to compare the effects of ziprasidone and olanzapine on weight, body composition, appetite, resting energy expenditure, substrate oxidation, and metabolic parameters in adults with schizophrenia or other psychotic disorders.

Methods

Twenty adults with schizophrenia or other psychotic disorders were randomized 1:1 to ziprasidone 20–160 mg/day or olanzapine 5–20 mg/day for 12 weeks. The mean doses during the 12-week study period were 109(range: 65–140) mg/day for ziprasidone and 11.6(range: 8.2–15.5) mg/day for olanzapine. Body weight, appetite, body composition, resting energy expenditure, and metabolic parameters were measured before and after drug treatment. Outcome measurements before and after medication were compared, and ziprasidone- and olanzapine-treated patients were compared.

Results

After 12 weeks, olanzapine-treated patients showed significant weight gain, particularly fat gain, with increased low density lipoprotein-cholesterol and decreased high density lipoprotein-cholesterol concentrations. In contrast, ziprasidone-treated patients showed no significant weight gain with increased high density lipoprotein-cholesterol concentration.

Conclusions

Ziprasidone was associated with a lower propensity for weight gain and central fat deposition than olanzapine. Studies in larger patient samples are required to confirm these results.
Comparative Survey of Entomophagy and Entomotherapeutic Practices in Six Tribes of Eastern Arunachal Pradesh (India)
Authors: Chakravorty Jharna , Ghosh Sampat , Meyer-Rochow V Benno
Published: July 2013

A consolidated list of edible insects used in the eastern part of Arunachal Pradesh (N.E. India) by Wangcho (Wancho) and Nocte tribes of the Tirap District and the Shingpo, Tangsa, Deori and Chakma of the Changlang District has been prepared. The list is based on thorough, semi-structured field-interviews with 20 informants of each tribal group. At least 51 insect species, belonging to 9 orders were considered edible. The largest number of the edible species belonged to the Coleoptera (14), followed by 10 each of the Orthoptera and Hymenoptera, 9 of the Hemiptera, 3 Lepidoptera, 2 Isoptera and one each of Ephemeroptera, Odonata and Mantodea. As far as therapeutic uses of insects are concerned, 4 species (Hemiptera) were mentioned by the Wangcho (Wancho). Food insects are chosen by members of the various tribes according to traditional beliefs, taste, regional and seasonal availability of the insects. Depending on the species, only certain, but sometimes all, developmental stages are consumed. Preparation of the food insects for consumption involves mainly roasting or boiling. With the degradation of natural resources, habitat loss, rapid population growth, and increasing ‘westernization’ , the traditional wisdom of North-East Indian tribals related to insect uses is at risk of being lost.
Coronary calcium scoring: are the results comparable to computed tomography coronary angiography for screening coronary artery disease in a South Asian population?
Authors: Bhulani Nizar , Khawaja Ali , Jafferani Asif , Baqir Maryam , Ebrahimi Ramin , Sajjad Zafar
Published: July 2013

Background

The need of having feasible screening tools like Coronary Calcium Scoring (CCS) and CT Coronary Artery (CTCA) for Coronary Artery Disease (CAD) has become paramount. We aimed to evaluate the accuracy of CCS in determining the degree of stenosis of coronary vessels as compared to that determined by CTCA in a South Asian population.

Methods

A retrospective study was conducted at The Aga Khan University Hospital. A total of 539 patient records were reviewed who had undergone CCS and CTCA between 2008 and 2010. Patient records were reviewed by comparing their CCS and CTCA results.

Results

About 268 out of 301 (89%) patients with a CCS of 0–9 were found to be free of stenosis on CTCA. On a CCS of 10–99, 110 out of 121 (91%) patients were either free of stenosis or had mild stenosis. About 66 out of 79 (84%) patients had moderate or severe stenosis with a calcium score of 100–400 while none of the patients were free of stenosis. Around 28 out of 38 (74%) patients with a CCS of more than 400 had severe stenosis. However, only 04 patients (11%) were found to have mild stenosis. Spearman’s rho revealed a correlation coefficient of 0.791 with a p-value of <0.001.

Conclusion

Our study reaffirms that in South Asian population, low CCS (<100) is associated with no or minimal stenosis while high CCS warrants further investigation; hence, making it a reliable tool for screening patients with CAD.
Willa Cather's Rewriting of the Historical Novel in Death Comes for the Archbishop
Authors: Lima Enrique
Published: July 2013

The historical novels of Sir Walter Scott, James Fenimore Cooper, and countless others have been interested primarily in exploiting the dramatic potential of historical events and the significant real and fictional personalities that took part in them. These writers are concerned mostly with the visible turbulence of history. Willa Cather, I argue, does something very different in Death Comes for the Archbishop: she portrays everyday life as embodying the long past that defines a culture. Cather renders the everyday as the mass of human experience that changes slowly over time and that provides the material basis for those instances of disorder that draw our attention by their intensity. In other words, Death Comes for the Archbishop is a novel of the history of what Fernand Braudel calls “the structures of everyday life.” But, in a contradictory fashion, Cather's novel also suggests that the deep past that makes the everyday historical is exactly what disqualifies native culture from history. This is the colonial paradox that most interests me in Cather's rethinking of the historical novel: Indian culture is excluded from the alternative space that Cather opens up for the quotidian precisely because it has the same historical structure as the quotidian.
Manufacturing Fictional Individuals: Victorian Social Statistics, the Novel, andGreat Expectations
Authors: Klotz Michael
Published: July 2013

This essay argues that the depiction of characters in Victorian realist fiction was shaped by an emerging cultural interest in the aggregation and analysis of statistical information about historical individuals and the subsequent production of the hypothetical persons of statistical discourse. Novelistic characters are frequently exposed in a double vision that draws attention to their individualized personhood and at the same time importantly locates them within a larger statistical population. In their description of characters, charting of individual fortunes, and imagining of possible contingencies, novelists drew from a wider fascination with the collection of social statistical information and the promise that this offered for envisioning possible dangers and picturing contingent versions of the self. I consider several examples of George Eliot's engagement with the logic of statistical analysis in Scenes of Clerical Life, Middlemarch, and Daniel Deronda. In the second half of this essay, I offer a rereading of Dickens's Great Expectations and argue that the International Statistical Congress of 1860, the Census of 1861, and the surrounding debates regarding the value of accumulating numerical information about the population provide a crucial context for Dickens's composition and structuring of the narrative.
Dreiser's Stamping Room: Becoming Media inAn American Tragedy
Authors: Marshall Kate
Published: July 2013

This essay makes the case for a reconsideration of Theodore Dreiser's An American Tragedy within the history of the modernist novel and its medial legacies by attending to the complex relationship enacted throughout the text between material forms and structures of interiority and identity. Although the mass media and other representational technologies such as cameras and film are notoriously complicit with the deterministic forces propelling An American Tragedy, I show that what counts as the “medial” in the novel appears instead in very different technologies: the stamping apparatus used in the novel's collar factory and the explicit figuring of architectural interiors as technologies of interiority. Both technologies show the process of identification central to the novel's narrative movement to be one of versioning, a media process encoded in the stamping technology and localized in hall ways that behave like characters. The factory tools and architectural spaces populating An American Tragedy, each rendered as a form of mediation, reveal Dreiser's text to hold a more important place in the formal history of the novel and of the novel's relationship to media than it has previously been afforded, especially as that story involves the blurry edges of the modern subject. It is precisely where the novel's naturalist concern with materiality confronts a modernist preoccupation with interiority that An American Tragedy provides a crucial glimpse into the kinds of persons and kinds of mediations developing in the early twentieth-century novel.
Functional validation of GWAS gene candidates for abnormal liver function during zebrafish liver development
Authors: Liu Leah Y. , Fox Caroline S. , North Trista E. , Goessling Wolfram
Published: July 2013

Genome-wide association studies (GWAS) have revealed numerous associations between many phenotypes and gene candidates. Frequently, however, further elucidation of gene function has not been achieved. A recent GWAS identified 69 candidate genes associated with elevated liver enzyme concentrations, which are clinical markers of liver disease. To investigate the role of these genes in liver homeostasis, we narrowed down this list to 12 genes based on zebrafish orthology, zebrafish liver expression and disease correlation. To assess the function of gene candidates during liver development, we assayed hepatic progenitors at 48 hours post fertilization (hpf) and hepatocytes at 72 hpf using in situ hybridization following morpholino knockdown in zebrafish embryos. Knockdown of three genes (pnpla3, pklr and mapk10) decreased expression of hepatic progenitor cells, whereas knockdown of eight genes (pnpla3, cpn1, trib1, fads2, slc2a2, pklr, mapk10 and samm50) decreased cell-specific hepatocyte expression. We then induced liver injury in zebrafish embryos using acetaminophen exposure and observed changes in liver toxicity incidence in morphants. Prioritization of GWAS candidates and morpholino knockdown expedites the study of newly identified genes impacting liver development and represents a feasible method for initial assessment of candidate genes to instruct further mechanistic analyses. Our analysis can be extended to GWAS for additional disease-associated phenotypes.
Kinesin-5 Kip1 is a bi-directional motor that stabilizes microtubules and tracks their plus-ends in vivo
Authors: Fridman Vladimir , Gerson-Gurwitz Adina , Shapira Ofer , Movshovich Natalia , Lakämper Stefan , Schmidt Christoph F. , Gheber Larisa
Published: July 2013

In this study, we examined the anaphase functions of S. cerevisiae kinesin-5 Kip1. We show that Kip1 is attached to the mitotic spindle midzone during late anaphase. This attachment is essential to stabilize interpolar microtubule (iMTs) plus-ends. By detailed examination of iMT dynamics we revealed that at the end of anaphase, iMTs depolymerize in two stages: during the first stage, one pair of anti-parallel iMTs depolymerizes at a velocity of 7.7 µm/min; during the second stage, ∼90 s later, the remaining pair of iMTs depolymerizes at a slower velocity of 5.4 µm/min. We show that upon the second depolymerization stage, which coincides with spindle breakdown, Kip1 follows the plus-ends of depolymerizing iMTs and translocates toward the spindle poles. This movement is independent of mitotic microtubule motor proteins or the major plus-end binding/tracking proteins. In addition, we show that Kip1 processively tracks the plus-ends of growing and shrinking MTs, both inside and outside the nucleus. The plus-end tracking activity of Kip1 requires its catalytic motor function, since a rigor mutant of Kip1 does not exhibit this activity. Finally, we show that Kip1 is a bi-directional motor: in vitro, at high ionic strength conditions, single Kip1 molecules move processively in the minus-end direction of the MTs, while in a multi-motor gliding assay, Kip1 is plus-end directed. The bi-directionality and plus-end tracking activity of Kip1, properties revealed here for the first time, allow Kip1 to perform its multiple functions in mitotic spindle dynamics and to partition the 2-micron plasmid.
Src mediates the mechanical activation of myogenesis by activating TNFα-converting enzyme
Authors: Niu Airu , Wen Yefei , Liu Huijie , Zhan Mei , Jin Bingwen , Li Yi-Ping
Published: July 2013

Mechanical stimulation affects many biological aspects in living cells through mechanotransduction. In myogenic precursor cells (MPCs), mechanical stimulation activates p38 mitogen-activated protein kinase (MAPK), a key regulator of myogenesis, via activating TNFα-converting enzyme (TACE, also known as ADAM17), to release autocrine TNFα. However, the signaling mechanism of mechanical activation of TACE is unknown. Because TACE possesses the structural features of substrates of the non-receptor tyrosine kinase Src, we tested the hypothesis that Src mediates mechanical activation of TACE in MPCs. We observed that mechanical stretch of C2C12 or primary rat myoblasts rapidly activates Src, which in turn interacts and colocalizes with TACE, resulting in tyrosine phosphorylation and activation of TACE. Particularly, Src activates TACE via the phosphorylation of amino acid residue Tyr702 in the intracellular tail of TACE, resulting in increased TNFα release and p38 activation. Src inhibition or deficiency blocks stretch activation of the TACE–p38-MAPK signaling, resulting in impaired myogenic gene expression. In response to functional overloading, Src and TACE are activated in mouse soleus muscle. Further, overloading-induced myogenesis and regeneration are impaired in the soleus of Src+/− mice. Therefore, Src mediates mechano-activation of TACE and myogenesis.
Promoter occupancy of MLL1 histone methyltransferase seems to specify the proliferative and apoptotic functions of E2F1 in a tumour microenvironment
Authors: Swarnalatha Manickavinayaham , Singh Anup Kumar , Kumar Vijay
Published: July 2013

The E2F family of transcription factors are considered versatile modulators poised at biological crossroads to execute diverse cellular functions. Despite extensive studies on E2F, the molecular mechanisms that control specific biological functions of E2F1 transcription factor is still not fully understood. Here we have addressed the molecular underpinnings of paradoxical functions of E2F1 in a tumour microenvironment using the ‘X15-myc’ oncomouse model of hepatocellular carcinoma. We observed that the HBx oncoprotein of hepatitis B virus regulates E2F1 functions by interfering with its binding to Skp2 E3 ubiquitin ligase. The HBx-Skp2 interaction led to the accumulation of transcriptionally active E2F1 and histone methyltransferase mixed lineage leukemia 1 (MLL1) protein. During early stages of hepatocarcinogenesis, the increased E2F1 activity promoted cellular proliferation by stimulating the genes involved in cell cycle control and replication. However, during the late stages, E2F1 triggered replicational stress-induced DNA damage and sensitized cells to apoptotic death in a p53-independent manner. Interestingly, the differential promoter occupancy of MLL1 during the early and late stages of tumour development seemed to specify the proliferative and apoptotic functions of E2F1 through its dynamic interaction with co-activator CBP or co-repressor Brg1. Thus, the temporally-regulated promoter occupancy of histone methyltransferase could be a novel regulatory mechanism associated with diverse cellular functions of E2F family of transcription factors.
Formin-mediated actin polymerization cooperates with Mushroom body defect (Mud)–Dynein during Frizzled–Dishevelled spindle orientation
Authors: Johnston Christopher A. , Manning Laurina , Lu Michelle S. , Golub Ognjen , Doe Chris Q. , Prehoda Kenneth E.
Published: July 2013

To position the mitotic spindle, cytoskeletal components must be coordinated to generate cortical forces on astral microtubules. Although the dynein motor is common to many spindle orientation systems, ‘accessory pathways’ are often also required. In this work, we identified an accessory spindle orientation pathway in Drosophila that functions with Dynein during planar cell polarity, downstream of the Frizzled (Fz) effector Dishevelled (Dsh). Dsh contains a PDZ ligand and a Dynein-recruiting DEP domain that are both required for spindle orientation. The Dsh PDZ ligand recruits Canoe/Afadin and ultimately leads to Rho GTPase signaling mediated through RhoGEF2. The formin Diaphanous (Dia) functions as the Rho effector in this pathway, inducing F-actin enrichment at sites of cortical Dsh. Chimeric protein experiments show that the Dia–actin accessory pathway can be replaced by an independent kinesin (Khc73) accessory pathway for Dsh-mediated spindle orientation. Our results define two ‘modular’ spindle orientation pathways and show an essential role for actin regulation in Dsh-mediated spindle orientation.