bluuebunny/crossref_metadata_2025 huggingface dataset:
Tiger Girls on the Soccer Field
Authors: Friedman Hilary Levey
Published: November 2013

Scholar Hilary Levey Friedman investigates how parental decisions result in different classed forms of femininity for girls who learn to be either “graceful girls” through dance, “aggressive girls” through soccer, or “pink warrior girls” through chess. She finds that parents higher up in the hierarchy of the middle class promote a more aggressive femininity, and we see this with both soccer and chess.
Inequality and the Growth of Bad Jobs
Authors: Vidal Matt
Published: November 2013

The share of jobs that are low-skill declined by 15% from 1960 to 2005, yet low-wage jobs have made up an increasing share of total job growth over that period. Scholar Matt Vidal discusses how the manufacturing-based, nationally bound economy of the postwar years allowed employers to pay decent wages for low-skill jobs, but in today’s postindustrial, internationalized economy, wage-based competition has returned with a vengeance.
Therapeutic Approaches to Skeletal Muscle Repair and Healing
Authors: Danna Natalie R. , Beutel Bryan G. , Campbell Kirk A. , Bosco Joseph A.
Published: November 2013

Context:

Skeletal muscle is comprised of a highly organized network of cells, neurovascular structures, and connective tissue. Muscle injury is typically followed by a well-orchestrated healing response that consists of the following phases: inflammation, regeneration, and fibrosis. This review presents the mechanisms of action and evidence supporting the effectiveness of various traditional and novel therapies at each phase of the skeletal muscle healing process.

Evidence Acquisition:

Relevant published articles were identified using MEDLINE (1978-2013).

Study Design:

Clinical review.

Level of Evidence:

Level 3.

Results:

To facilitate muscle healing, surgical techniques involving direct suture repair, as well as the implantation of innovative biologic scaffolds, have been developed. Nonsteroidal anti-inflammatory drugs may be potentially supplanted by nitric oxide and curcumin in modulating the inflammatory pathway. Studies in muscle regeneration have identified stem cells, myogenic factors, and β-agonists capable of enhancing the regenerative capabilities of injured tissue. Furthermore, transforming growth factor-β1 (TGF-β1) and, more recently, myostatin and the rennin-angiotensin system have been implicated in fibrous tissue formation; several antifibrotic agents have demonstrated the ability to disrupt these systems.

Conclusion:

Effective repair of skeletal muscle after severe injury is unlikely to be achieved with a single intervention. For full functional recovery of muscle there is a need to control inflammation, stimulate regeneration, and limit fibrosis.

Strength-of-Recommendation Taxonomy (SORT):

B
Add-on clinical effects of simvastatin and ondansetron in patients with schizophrenia stabilized on antipsychotic treatment: pilot study
Authors: Chaudhry Imran B. , Husain Nusrat , Drake Richard , Dunn Graham , Husain M. Omair , Kazmi Ajmal , Hamirani Munir M. , Rahman Raza , Stirling John , Deakin William
Published: November 2013

Objectives:

There is some evidence that anti-inflammatory treatment may have beneficial effects in schizophrenia and major depression. Statins are cholesterol-lowering agents but have been found to be anti-inflammatory and also decrease C-reactive protein (CRP). Ondansetron is a serotonin (5-HT3) receptor antagonist widely used to prevent nausea and vomiting in patients receiving chemotherapy for cancer. Small studies have suggested that adjunctive ondansetron is efficacious against schizophrenia symptoms. We carried out a feasibility study in schizophrenia patients (within 5 years of first diagnosis) to explore the adjunctive use of simvastatin and ondansetron on positive, negative and general psychopathology.

Methods:

This was a 12-week rater-blind placebo-controlled study. A total of 36 patients with DSM-IV diagnosis of schizophrenia were recruited, 12 in each arm. Patients were assessed at baseline and at 12 weeks using Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression (CGI) scale, Global Assessment of Functioning (GAF) and Abnormal Involuntary Movement Scale (AIMS).

Results:

Both simvastatin and ondansetron provide some evidence of a reduction in symptoms compared with treatment as usual (TAU) on PANSS total score, although this was not statistically significant. In the secondary analyses, no significant differences were seen on CGI, GAF and AIMS.

Conclusions:

Anti-inflammatory treatments have been shown to have some beneficial effects in schizophrenia. Both simvastatin and ondansetron provide some evidence of a reduction in symptoms compared with TAU. This study has led to a larger Stanley Medical Research Institute (SMRI)-funded, double-blind, randomized control trial.
Religion and media: A critical review of recent developments
Authors: Morgan David
Published: November 2013

This article considers recent changes in the definition of religion and of media as the basis for framing the study of their relation to one another and recent research in the intersection they have come to form over the last two decades or so. The history, materiality, and reception of each have colored scholarly work, and made ethnography, practice, material culture, and embodiment key aspects of scholarship. A new paradigm for some scholars for studying mediation is aesthetics—no longer understood as the “philosophy of the beautiful,” but as the study of perception in the mediated practices that make up lived religion.
Altered distribution and function of natural killer cells in murine and human Niemann-Pick disease type C1
Authors: Speak Anneliese O. , te Vruchte Danielle , Davis Lianne C. , Morgan Anthony J. , Smith David A. , Yanjanin Nicole M. , Simmons Louise , Hartung Ralf , Runz Heiko , Mengel Eugen , Beck Michael , Imrie Jackie , Jacklin Elizabeth , Wraith James E. , Hendriksz Christian , Lachmann Robin , Cognet Celine , Sidhu Rohini , Fujiwara Hideji , Ory Daniel S. , Galione Antony , Porter Forbes D. , Vivier Eric , Platt Frances M.
Published: November 2013

Key Points

Lysosomal storage affects NK-cell frequency, development, and function. Lysosomal calcium is important for NK-cell degranulation.
How I treat ALL in Down's syndrome: pathobiology and management
Authors: Izraeli Shai , Vora Ajay , Zwaan C. Michel , Whitlock James
Published: November 2013

Children with Down syndrome are at high risk for developing B-cell precursor acute lymphoblastic leukemia (DS-ALL) associated with poor outcome due to both a high relapse rate and increased treatment-related mortality (TRM) from infections. Biologically, these heterogeneous leukemias are characterized by under-representation of the common cytogenetic subgroups of childhood ALL and overrepresentation of CRLF2-IL7R-JAK-STAT activating genetic aberrations. Although relapse is the major determinant of poor outcomes in this population, de-escalation of chemotherapy intensity might be feasible in the 10% to 15% DS-ALL patients with ETV6-RUNX1 or high hyperdipoidy in whom TRM is the major limiting event. As infection-associated TRM occurs during all treatment phases, including the maintenance period, increased surveillance and supportive care is required throughout therapy. Improvement in outcome will require better understanding of the causes of treatment failure and TRM, incorporation of new therapies targeting the unique biological properties of DS-ALL, and enhanced supportive care measures to reduce the risk of infection-related TRM. To facilitate these goals, an international collaboration plans to establish a prospective DS-ALL registry and develop specific supportive care recommendations for this at-risk population.
Effects of weight loss on asthma control in obese patients with severe asthma
Authors: Dias-Júnior Sérvulo Azevedo , Reis Monica , de Carvalho-Pinto Regina Maria , Stelmach Rafael , Halpern Alfredo , Cukier Alberto
Published: November 2013

Studies on the effects of weight loss in patients with asthma are scarce. No studies have been performed in patients with severe asthma. Therefore, the aim of the present study was to assess the impact of weight loss in patients with severe asthma associated with obesity.

This was an open, prospective, randomised study of two parallel groups, in patients with severe uncontrolled asthma and moderate obesity. The primary outcome was the level of asthma control 6 months after initiation of the weight reduction programme, quantified using the Asthma Control Questionnaire (ACQ). We evaluated clinical parameters, lung function, markers of airway inflammation and circulating cytokines.

22 patients were randomised to undergo treatment for obesity and 11 to the control group. The weight reduction programme was associated with significant improvements in asthma control (mean±seACQ score 3.02±0.19 to 2.25±0.28 in the treatment groupversus2.91±0.25 to 2.90±0.16 in the controls, p=0.001). This improvement was not accompanied by changes in markers of airway inflammation or bronchial reactivity, but by an increase in forced vital capacity.

Our results suggest that weight reduction in obese patients with severe asthma improves asthma outcomes by mechanisms not related to airway inflammation.
Role of activin-A in cigarette smoke-induced inflammation and COPD
Authors: Verhamme Fien M. , Bracke Ken R. , Amatngalim Gimano D. , Verleden Geert M. , Van Pottelberge Geert R. , Hiemstra Pieter S. , Joos Guy F. , Brusselle Guy G.
Published: November 2013

Activin-A is a pleiotropic cytokine belonging to the transforming growth factor-β superfamily and has been implicated in asthma and pulmonary fibrosis. However, the role of activin-A and its endogenous inhibitor, follistatin, in the pathogenesis of chronic obstructive pulmonary disease (COPD) is unknown.

We first quantified activin-A and follistatin in the lungs of air- or cigarette smoke-exposed mice and in the lungs of patients with COPD by immunohistochemistry, ELISA and quantitative real-time PCR. We subsequently studied the effect of cigarette smoke on primary human bronchial epithelial cellsin vitro. Next, activin-A signalling was antagonisedin vivoby administration of follistatin in mice exposed to air or cigarette smoke for 4 weeks.

Protein levels of activin-A were increased in the airway epithelium of patients with COPD compared with never-smokers and smokers. Cigarette smoke-exposed human bronchial epithelial cells expressed higher levels of activin-A and lower levels of follistatin. Both mRNA and protein levels of activin-A were increased in the lungs of cigarette smoke-exposed mice, whereas follistatin levels were reduced upon cigarette smoke exposure. Importantly, administration of follistatin attenuated the cigarette smoke-induced increase of inflammatory cells and mediators in the bronchoalveolar lavage fluid in mice.

These results suggest that an imbalance between activin-A and follistatin contributes to the pathogenesis of cigarette smoke-induced inflammation and COPD.
Bronchial valve treatment for pulmonary air leak after anatomical lung resection for cancer
Authors: Dooms Christophe A. , Decaluwe Herbert , Yserbyt Jonas , De Leyn Paul , Van Raemdonck Dirk , Ninane Vincent
Published: November 2013

A persistent post-operative pulmonary expiratory air leak after an anatomical pulmonary resection is usually managed conservatively, but can be associated with significant morbidity and increased costs. The use of bronchial valves is a minimally invasive method that may be an effective and safe treatment in this setting.

In a prospective study, the clinical efficacy of intrabronchial valve treatment in patients with a prolonged persistent pulmonary air leak after anatomical surgical resection for cancer was investigated.

10 out of 277 patients with anatomical pulmonary resection for cancer were included, and 90% were scheduled for valve treatment. We demonstrated an air leak cessation at a median of 2 days after valve placement, which resulted in chest tube removal at a median of 4 days after valve placement. Elective removal of the intrabronchial valves could be safely planned 3 weeks after valve implantation. Lung function alteration associated with airway occlusion by valves was limited.

Intrabronchial valve treatment with the aid of a digital thoracic drainage system is an effective and safe therapy for patients with a prolonged pulmonary air leak after anatomical lung resection for cancer.
Asthma affects time to pregnancy and fertility: a register-based twin study
Authors: Gade Elisabeth J. , Thomsen Simon F. , Lindenberg Svend , Kyvik Kirsten O. , Lieberoth Sofie , Backer Vibeke
Published: November 2013

Coexistence of infertility and asthma has been observed clinically. Therefore, we investigated the association between asthma and delayed pregnancy in a nationwide population-based cohort of twins.

A cohort of 15 250 twins living in Denmark (aged 12–41 years) participated in a questionnaire study including questions about the presence of asthma and fertility. Differences in time to pregnancy and pregnancy outcome were analysed in subjects with asthma, allergy and in healthy individuals using multiple regression analysis.

Asthma was associated with an increased time to pregnancy, the percentage of asthmatics with a time to pregnancy >1 year was 27%versus21.6% for non-asthmatics (OR (95% CI) 1.31 (1.1–1.6); p=0.009). The association remained significant after adjustment for age, age at menarche, body mass index and socioeconomic status (OR (95% CI) 1.25 (1.0–1.6); p=0.05), and was more pronounced in those >30 years of age (32.2%versus24.9%, OR (95% CI) 1.44 (1.1–1.9); p=0.04). Untreated asthmatics had a significant increased risk of prolonged time to pregnancy compared to healthy individuals (OR (95% CI) 1.79 (1.20–2.66); p=0.004), while asthmatics receiving any kind of treatment for asthma tended to have a shorter time to pregnancy than untreated asthmatics (OR 1.40; p=0.134).

Asthma prolongs time to pregnancy. The negative effect of asthma on fertility increases with age and with disease intensity, indicating that a systemic disease characterised by systemic inflammation also can involve reproductive processes.
Genome-wide identification of Thellungiella salsuginea microRNAs with putative roles in the salt stress response
Authors: Zhang Quan , Zhao Chuanzhi , Li Ming , Sun Wei , Liu Yan , Xia Han , Sun Mingnan , Li Aiqin , Li Changsheng , Zhao Shuzhen , Hou Lei , Picimbon Jean-François , Wang Xingjun , Zhao Yanxiu
Published: November 2013

Background

MicroRNAs are key regulators of plant growth and development with important roles in environmental adaptation. The microRNAs from the halophyte species Thellungiella salsuginea (salt cress), which exhibits extreme salt stress tolerance, remain to be investigated. The sequenced genome of T. salsuginea and the availability of high-throughput sequencing technology enabled us to discover the conserved and novel miRNAs in this plant species. It is interesting to identify the microRNAs from T. salsuginea genome wide and study their roles in salt stress response.

Results

In this study, two T. salsuginea small RNA libraries were constructed and sequenced using Solexa technology. We identified 109 miRNAs that had previously been reported in other plant species. A total of 137 novel miRNA candidates were identified, among which the miR* sequence of 26 miRNAs was detected. In addition, 143 and 425 target mRNAs were predicted for the previously identified and Thellungiella-specific miRNAs, respectively. A quarter of these putative targets encode transcription factors. Furthermore, numerous signaling factor encoding genes, defense-related genes, and transporter encoding genes were amongst the identified targets, some of which were shown to be important for salt tolerance. Cleavage sites of seven target genes were validated by 5’ RACE, and some of the miRNAs were confirmed by qRT-PCR analysis. The expression levels of 26 known miRNAs in the roots and leaves of plants subjected to NaCl treatment were determined by Affymetrix microarray analysis. The expression of most tested miRNA families was up- or down-regulated upon NaCl treatment. Differential response patterns between the leaves and roots were observed for these miRNAs.

Conclusions

Our results indicated that diverse set of miRNAs of T. salsuginea were responsive to salt stress and could play an important role in the salt stress response.
External ocular surface bacterial isolates and their antimicrobial susceptibility patterns among pre-operative cataract patients at Mulago National Hospital in Kampala, Uganda
Authors: Mshangila Barnabas , Paddy Musana , Kajumbula Henry , Ateenyi-Agaba Charles , Kahwa Binta , Seni Jeremiah
Published: November 2013

Background

Endophthalmitis is a severe complication of cataract surgery which leads to high ocular morbidity and visual loss even with antibiotic treatment. Bacterial ocular floras are the implicated causative agents. This study was undertaken to evaluate the external ocular surface bacterial isolates and their antimicrobial susceptibility patterns among pre-operative cataract patients at Mulago National Hospital.

Methods

This cross sectional study enrolled consecutively 131 patients scheduled for routine cataract surgery in the Department of Ophthalmology at Mulago National Hospital in Kampala, Uganda. Eyelid margin and conjunctival swabs were collected and processed using standard microbiological procedures to identify bacterial isolates and their respective antimicrobial susceptibility patterns.

Results

Of 131 patients involved (mean age 63.3 ± 14.5 years), 54.2% (71/131) were females. The eyelid margin and conjunctival samples were culture positive in 59.5% (78/138) and 45.8% (60/138) respectively. The most common organisms identified were Coagulase-negative Staphylococci (CoNS) [65.9% (91/138)] and Staphylococcus aureus [21.0% (29/138)]. CoNS showed the highest resistance to tetracycline (58.2%, 53/91) and erythromycin (38.5%, 35/91), whereas in S. aureus the resistance to tetracycline and erythromycin were 55.2% (16/29) and 31.0% (9/29) respectively. Methicillin resistant CoNS (MRS) and Methicillin resistance S. aureus (MRSA) were 31.9% (29/91) and 27.6% (8/29) respectively. There were low resistance rates for CoNS, S. aureus and other bacterial isolates to ciprofloxacin (11.1%-24.2%), gentamicin (5.6-31.0%), tobramycin (17.2% -25.3%) and vancomycin (0.0%).

Conclusion

CoNS and S. aureus are the most common bacterial isolates found on the external ocular surface of the pre-operative cataract patients. Ciprofloxacin, gentamicin, tobramycin and vancomycin showed the lowest resistance rates to all bacterial isolates, therefore may be used to reduce bacteria load in the conjunctiva sac among cataract patients prior to surgery.
Predictors of the resumption of menses in adolescent anorexia nervosa
Authors: Dempfle Astrid , Herpertz-Dahlmann Beate , Timmesfeld Nina , Schwarte Reinhild , Egberts Karin M , Pfeiffer Ernst , Fleischhaker Christian , Wewetzer Christoph , Bühren Katharina
Published: November 2013

Background

The resumption of menses is an important indicator of recovery in anorexia nervosa (AN). Patients with early-onset AN are at particularly great risk of suffering from the long-term physical and psychological consequences of persistent gonadal dysfunction. However, the clinical variables that predict the recovery of menstrual function during weight gain in AN remain poorly understood. The aim of this study was to investigate the impact of several clinical parameters on the resumption of menses in first-onset adolescent AN in a large, well-characterized, homogenous sample that was followed-up for 12 months.

Methods

A total of 172 female adolescent patients with first-onset AN according to DSM-IV criteria were recruited for inclusion in a randomized, multi-center, German clinical trial. Menstrual status and clinical variables (i.e., premorbid body mass index (BMI), age at onset, duration of illness, duration of hospital treatment, achievement of target weight at discharge, and BMI) were assessed at the time of admission to or discharge from hospital treatment and at a 12-month follow-up. Based on German reference data, we calculated the percentage of expected body weight (%EBW), BMI percentile, and BMI standard deviation score (BMI-SDS) for all time points to investigate the relationship between different weight measurements and resumption of menses.

Results

Forty-seven percent of the patients spontaneously began menstruating during the follow-up period. %EBW at the 12-month follow-up was strongly correlated with the resumption of menses. The absence of menarche before admission, a higher premorbid BMI, discharge below target weight, and a longer duration of hospital treatment were the most relevant prognostic factors for continued amenorrhea.

Conclusions

The recovery of menstrual function in adolescent patients with AN should be a major treatment goal to prevent severe long-term physical and psychological sequelae. Patients with premenarchal onset of AN are at particular risk for protracted amenorrhea despite weight rehabilitation. Reaching and maintaining a target weight between the 15th and 20th BMI percentile is favorable for the resumption of menses within 12 months. Whether patients with a higher premorbid BMI may benefit from a higher target weight needs to be investigated in further studies.
Large-scale cell production of stem cells for clinical application using the automated cell processing machine
Authors: Kami Daisuke , Watakabe Keizo , Yamazaki-Inoue Mayu , Minami Kahori , Kitani Tomoya , Itakura Yoko , Toyoda Masashi , Sakurai Takashi , Umezawa Akihiro , Gojo Satoshi
Published: November 2013

Background

Cell-based regeneration therapies have great potential for application in new areas in clinical medicine, although some obstacles still remain to be overcome for a wide range of clinical applications. One major impediment is the difficulty in large-scale production of cells of interest with reproducibility. Current protocols of cell therapy require a time-consuming and laborious manual process. To solve this problem, we focused on the robotics of an automated and high-throughput cell culture system. Automated robotic cultivation of stem or progenitor cells in clinical trials has not been reported till date. The system AutoCulture® used in this study can automatically replace the culture medium, centrifuge cells, split cells, and take photographs for morphological assessment. We examined the feasibility of this system in a clinical setting.

Results

We observed similar characteristics by both the culture methods in terms of the growth rate, gene expression profile, cell surface profile by fluorescence-activated cell sorting, surface glycan profile, and genomic DNA stability. These results indicate that AutoCulture® is a feasible method for the cultivation of human cells for regenerative medicine.

Conclusions

An automated cell-processing machine will play important roles in cell therapy and have widespread use from application in multicenter trials to provision of off-the-shelf cell products.
Si-RNA mediated knockdown of CELF1 gene suppressed the proliferation of human lung cancer cells
Authors: Wu Li-Na , Xue Yi-Jun , Zhang Li-Jian , Ma Xue-Mei , Chen Jin-Feng
Published: November 2013

Background

Lung cancer is the leading cause of cancer-related death in the world, with metastasis as the main reason for the mortality. CELF1 is an RNA-binding protein controlling the post-transcriptional regulation of genes related to cell survival. As yet, there is little knowledge of CELF1 expression and biological function in lung cancer. This study investigated the expression levels of CELF1 in lung cancer tissues and the biological function of CELF1 in lung cancer cells.

Methods

CELF1 mRNA expression was determined in lung cancer and normal tissues, and the relationship between the expression level of CELF1 and clinicopathological parameters was evaluated. The biological function of CELF1 in A549 and H1299 lung cancer cell lines growth was examined.

Results

The expression of CELF1 was higher in human lung cancer tissues compared with the normal lung tissue. Lentiviral-mediated transfection of CELF1 siRNA effectively silenced the expression of CELF1 in both A549 and H1299 cells. Moreover, CELF1 knockdown markedly reduced the survival rate of lung cancer cells. Colony formation assays revealed a reduction in the number and size of lung cancer cell colonies from CELF1 knockdown.

Conclusion

These results indicated that CELF1 may have significant roles in the progression of lung cancer, and suggested that siRNA mediated silencing of CELF1 could be an effective tool in lung cancer treatment.
Geographic information systems and logistic regression for high-resolution malaria risk mapping in a rural settlement of the southern Brazilian Amazon
Authors: de Oliveira Elaine Cristina , dos Santos Emerson Soares , Zeilhofer Peter , Souza-Santos Reinaldo , Atanaka-Santos Marina
Published: November 2013

Background

In Brazil, 99% of the cases of malaria are concentrated in the Amazon region, with high level of transmission. The objectives of the study were to use geographic information systems (GIS) analysis and logistic regression as a tool to identify and analyse the relative likelihood and its socio-environmental determinants of malaria infection in the Vale do Amanhecer rural settlement, Brazil.

Methods

A GIS database of georeferenced malaria cases, recorded in 2005, and multiple explanatory data layers was built, based on a multispectral Landsat 5 TM image, digital map of the settlement blocks and a SRTM digital elevation model. Satellite imagery was used to map the spatial patterns of land use and cover (LUC) and to derive spectral indices of vegetation density (NDVI) and soil/vegetation humidity (VSHI). An Euclidian distance operator was applied to measure proximity of domiciles to potential mosquito breeding habitats and gold mining areas. The malaria risk model was generated by multiple logistic regression, in which environmental factors were considered as independent variables and the number of cases, binarized by a threshold value was the dependent variable.

Results

Out of a total of 336 cases of malaria, 133 positive slides were from inhabitants at Road 08, which corresponds to 37.60% of the notifications. The southern region of the settlement presented 276 cases and a greater number of domiciles in which more than ten cases/home were notified. From these, 102 (30.36%) cases were caused by Plasmodium falciparum and 174 (51.79%) cases by Plasmodium vivax. Malaria risk is the highest in the south of the settlement, associated with proximity to gold mining sites, intense land use, high levels of soil/vegetation humidity and low vegetation density.

Conclusions

Mid-resolution, remote sensing data and GIS-derived distance measures can be successfully combined with digital maps of the housing location of (non-) infected inhabitants to predict relative likelihood of disease infection through the analysis by logistic regression. Obtained findings on the relation between malaria cases and environmental factors should be applied in the future for land use planning in rural settlements in the Southern Amazon to minimize risks of disease transmission.
Expression analysis and in silico characterization of intronic long noncoding RNAs in renal cell carcinoma: emerging functional associations
Authors: Fachel Angela A , Tahira Ana C , Vilella-Arias Santiago A , Maracaja-Coutinho Vinicius , Gimba Etel RP , Vignal Giselle M , Campos Franz S , Reis Eduardo M , Verjovski-Almeida Sergio
Published: November 2013

Background

Intronic and intergenic long noncoding RNAs (lncRNAs) are emerging gene expression regulators. The molecular pathogenesis of renal cell carcinoma (RCC) is still poorly understood, and in particular, limited studies are available for intronic lncRNAs expressed in RCC.

Methods

Microarray experiments were performed with custom-designed arrays enriched with probes for lncRNAs mapping to intronic genomic regions. Samples from 18 primary RCC tumors and 11 nontumor adjacent matched tissues were analyzed. Meta-analyses were performed with microarray expression data from three additional human tissues (normal liver, prostate tumor and kidney nontumor samples), and with large-scale public data for epigenetic regulatory marks and for evolutionarily conserved sequences.

Results

A signature of 29 intronic lncRNAs differentially expressed between RCC and nontumor samples was obtained (false discovery rate (FDR) <5%). A signature of 26 intronic lncRNAs significantly correlated with the RCC five-year patient survival outcome was identified (FDR <5%, p-value ≤0.01). We identified 4303 intronic antisense lncRNAs expressed in RCC, of which 22% were significantly (p <0.05)ciscorrelated with the expression of the mRNA in the samelocusacross RCC and three other human tissues. Gene Ontology (GO) analysis of thoselocipointed to 'regulation of biological processes’ as the main enriched category. A module map analysis of the protein-coding genes significantly (p <0.05)transcorrelated with the 20% most abundant lncRNAs, identified 51 enriched GO terms (p <0.05). We determined that 60% of the expressed lncRNAs are evolutionarily conserved. At the genomiclocicontaining the intronic RCC-expressed lncRNAs, a strong association (p <0.001) was found between their transcription start sites and genomic marks such as CpG islands, RNA Pol II binding and histones methylation and acetylation.

Conclusion

Intronic antisense lncRNAs are widely expressed in RCC tumors. Some of them are significantly altered in RCC in comparison with nontumor samples. The majority of these lncRNAs is evolutionarily conserved and possibly modulated by epigenetic modifications. Our data suggest that these RCC lncRNAs may contribute to the complex network of regulatory RNAs playing a role in renal cell malignant transformation.
Surface-enhanced Raman scattering of suspended monolayer graphene
Authors: Huang Cheng-Wen , Lin Bing-Jie , Lin Hsing-Ying , Huang Chen-Han , Shih Fu-Yu , Wang Wei-Hua , Liu Chih-Yi , Chui Hsiang-Chen
Published: November 2013

The interactions between phonons and electrons induced by the dopants or the substrate of graphene in spectroscopic investigation reveal a rich source of interesting physics. Raman spectra and surface-enhanced Raman spectra of supported and suspended monolayer graphenes were measured and analyzed systemically with different approaches. The weak Raman signals are greatly enhanced by the ability of surface-enhanced Raman spectroscopy which has attracted considerable interests. The technique is regarded as wonderful and useful tool, but the dopants that are produced by depositing metallic nanoparticles may affect the electron scattering processes of graphene. Therefore, the doping and substrate influences on graphene are also important issues to be investigated. In this work, the peak positions of G peak and 2D peak, the I
2D/I
G ratios, and enhancements of G and 2D bands with suspended and supported graphene flakes were measured and analyzed. The peak shifts of G and 2D bands between the Raman and SERS signals demonstrate the doping effect induced by silver nanoparticles by n-doping. The I
2D/I
G ratio can provide a more sensitive method to carry out the doping effect on the graphene surface than the peak shifts of G and 2D bands. The enhancements of 2D band of suspended and supported graphenes reached 138, and those of G band reached at least 169. Their good enhancements are helpful to measure the optical properties of graphene. The different substrates that covered the graphene surface with doping effect are more sensitive to the enhancements of G band with respect to 2D band. It provides us a new method to distinguish the substrate and doping effect on graphene.

PACS

78.67.Wj (optical properties of graphene); 74.25.nd (Raman and optical spectroscopy); 63.22.Rc (phonons in graphene)
Characterization of single 1.8-nm Au nanoparticle attachments on AFM tips for single sub-4-nm object pickup
Authors: Cheng Hui-Wen , Chang Yuan-Chih , Tang Song-Nien , Yuan Chi-Tsu , Tang Jau , Tseng Fan-Gang
Published: November 2013

This paper presents a novel method for the attachment of a 1.8-nm Au nanoparticle (Au-NP) to the tip of an atomic force microscopy (AFM) probe through the application of a current-limited bias voltage. The resulting probe is capable of picking up individual objects at the sub-4-nm scale. We also discuss the mechanisms involved in the attachment of the Au-NP to the very apex of an AFM probe tip. The Au-NP-modified AFM tips were used to pick up individual 4-nm quantum dots (QDs) using a chemically functionalized method. Single QD blinking was reduced considerably on the Au-NP-modified AFM tip. The resulting AFM tips present an excellent platform for the manipulation of single protein molecules in the study of single protein-protein interactions.
Dual-acting stapled peptides target both HIV-1 entry and assembly
Authors: Zhang Hongtao , Curreli Francesca , Waheed Abdul A , Mercredi Peter Y , Mehta Mansi , Bhargava Pallavi , Scacalossi Daniel , Tong Xiaohe , Lee Shawn , Cooper Alan , Summers Michael F , Freed Eric O , Debnath Asim K
Published: November 2013

Background

Previously, we reported the conversion of the 12-mer linear and cell-impermeable peptide CAI to a cell-penetrating peptide NYAD-1 by using an i,i + 4 hydrocarbon stapling technique and confirmed its binding to the C-terminal domain (CTD) of the HIV-1 capsid (CA) protein with an improved affinity (Kd ~ 1 μM) compared to CAI (Kd ~ 15 μM). NYAD-1 disrupts the formation of both immature- and mature-like virus particles in in vitro and cell-based assembly assays. In addition, it displays potent anti-HIV-1 activity in cell culture against a range of laboratory-adapted and primary HIV-1 isolates.

Results

In this report, we expanded the study to i,i + 7 hydrocarbon-stapled peptides to delineate their mechanism of action and antiviral activity. We identified three potent inhibitors, NYAD-36, -66 and -67, which showed strong binding to CA in NMR and isothermal titration calorimetry (ITC) studies and disrupted the formation of mature-like particles. They showed typical α-helical structures and penetrated cells; however, the cell penetration was not as efficient as observed with the i,i + 4 peptides. Unlike NYAD-1, the i,i + 7 peptides did not have any effect on virus release; however, they impaired Gag precursor processing. HIV-1 particles produced in the presence of these peptides displayed impaired infectivity. Consistent with an effect on virus entry, selection for viral resistance led to the emergence of two mutations in the gp120 subunit of the viral envelope (Env) glycoprotein, V120Q and A327P, located in the conserved region 1 (C1) and the base of the V3 loop, respectively.

Conclusion

The i,i + 7 stapled peptides derived from CAI unexpectedly target both CA and the V3 loop of gp120. This dual-targeted activity is dependent on their ability to penetrate cells as well as their net charge. This mechanistic revelation will be useful in further modifying these peptides as potent anti-HIV-1 agents.
Drug development for exceptionally rare metabolic diseases: challenging but not impossible
Authors: Putzeist Michelle , Mantel-Teeuwisse Aukje K , Wied Christine C Gispen-de , Hoes Arno W , Leufkens Hubert GM , de Vrueh Remco LA
Published: November 2013

Background

We studied to what extent the level of scientific knowledge on exceptionally rare metabolic inherited diseases and their potential orphan medicinal products is associated with sponsors deciding to apply for an orphan designation at the US Food and Drug Administration (FDA) or the European Medicines Agency (EMA).

Methods

All metabolic diseases with a genetic cause and prevalence of less than 10 patients per 1 million of the population were selected from the ‘Orphanet database of Rare diseases’. The outcome of interest was the application for an orphan designation at FDA or EMA. The level of publicly available knowledge of the disease and drug candidate before an orphan designation application was defined as whether the physiological function corresponding with the pathologic gene and initiation of the pathophysiological pathway was known, whether an appropriate animal study was identified for the disease, whether preclinical proof of concept was ascertained and the availability of data in humans. Other determinants included in the study were metabolic disease class, the prevalence of the disease, prognosis and time of first description of the disease in the literature. Univariate relative risks (RRs) and 95% confidence intervals (CIs) of an orphan designation application were calculated for each of these determinants. In addition, a multivariate Cox regression analysis was conducted (Forward LR).

Results

In total, 166 rare metabolic genetic diseases were identified and included in the analysis. For only 42 (25%) of the diseases an orphan designation application was submitted at either FDA or EMA before January 2012. The multivariate analysis identified preclinical proof of concept of a potential medicinal product as major knowledge related determinant associated with an orphan designation application (RRadj 3.9, 95% CI 1.9-8.3) and confirmed that prevalence of the disease is also associated with filing an application for an orphan designation (RRadj 2.8, 95% CI 1.4-5.4).

Conclusion

For only one out of four known exceptionally rare metabolic inherited diseases sponsors applied for an orphan designation at FDA or EMA. These applications were found to be associated with the prevalence of the rare disease and the level of available scientific knowledge on the proof of concept linking possible drug candidates to the disease of interest.
Histological assessments of intestinal immuno-morphology of tiger grouper juvenile, Epinephelus fuscoguttatus
Authors: Firdaus-Nawi Mohd , Zamri-Saad Mohd , Nik-Haiha Nik Yusoff , Zuki Md Abu Bakar , Effendy Abd Wahid Mohd
Published: November 2013

Histological assessments on the intestinal morphology and immunity of tiger grouper juveniles, Epinephelus fuscoguttatus help in determining the earliest age to start an oral vaccination. This study describes the morphological development of the intestinal immunity of tiger grouper of various ages. Clinically healthy tiger groupers were selected and divided into 4 groups of 20 fish per group. Groups 1, 2, 3 and 4 consisted of juveniles of 30, 60, 90 and 120 days old, respectively. The whole intestine was collected and divided into three regions, the anterior, mid and posterior intestine and fixed in 10% buffered formalin before slides were prepared for microscopic examinations. It was found that the histological structures of the anterior intestine were for absorption of nutrient from digested food particles. The significantly (p < 0.05) higher number and length of the intestinal villi and smaller gap between villi were observed in the anterior intestine, which were structures for absorption. Structures of the posterior intestine were for immunity especially the adaptive immunity with included significantly (p < 0.05) higher numbers of the lymphoid and goblet cells, and significantly (p < 0.05) thicker lamina propria, which were structures for immunity. The mid intestine was the transition structure that involved in both absorption and innate immunity. The results also revealed that leukocytes existed in the lamina propria of 30-days old tiger groupers, an indication that the immune system was present at that particular age.
The effect of temperature on the viability of human mesenchymal stem cells
Authors: Reissis Yannis , García-Gareta Elena , Korda Michelle , Blunn Gordon W , Hua Jia
Published: November 2013

Introduction

Impaction allograft with cement is a common technique used in revision hip surgeries for the last 20 years. However, its clinical results are inconsistent. Recent studies have shown that mesenchymal stem cells (MSCs) seeded onto allograft can enhance bone formation. This in vitro study investigates whether the increase in temperature related to the polymerisation of bone cement will affect the viability of human MSCs.

Methods

The viability of human MSCs was measured after incubating them at temperatures of 38°C, 48°C and 58°C; durations 45 seconds, 80 seconds and 150 seconds. A control group was kept at 37°C and 5% carbon dioxide for the duration of the investigation (7 days). During the course of the study the human MSCs were analysed for cell metabolic activity using the alamarBlue™ assay, cell viability using both Trypan Blue dye exclusion and calcein staining under fluorescent microscopy, and necrosis and apoptosis using Annexin V and propidium iodide for flow cytometric analysis. A one-way analysis of variance with a priori Dunnett’s test was used to indicate the differences between the treatment groups, when analysed against the control. This identified conditions with a significant difference in cell metabolic activity (alamarBlue™) and cell viability (Trypan Blue).

Results

Results showed that cell metabolism was not severely affected up to 48°C/150 seconds, while cells in the 58°C group died. Similar results were shown using Trypan Blue and calcein analysis for cell viability. No significant difference in apoptosis and necrosis of the cells was observed when human MSCs treated at 48°C/150 seconds were compared with the control group.

Conclusions

The study suggests that human MSCs seeded onto allograft can be exposed to temperatures up to 48°C for 150 seconds. Exposure to this temperature for this time period is unlikely to occur during impaction allograft surgery when cement is used. Therefore, in many situations, the addition of human MSCs to cemented impaction grafting may be carried out without detrimental effects to the cells. Furthermore, previous studies have shown that this can enhance new bone formation and repair the defects in revision situations.
Virus-specific CD4 and CD8 T cell responses in the absence of Th1-associated transcription factors
Authors: Mollo Sarah B , Ingram Jennifer T , Kress Robert L , Zajac Allan J , Harrington Laurie E
Published: November 2013

Effector and memory CD4 and CD8 T cell responses are critical for the control of many intracellular pathogens. The development of these populations is governed by transcription factors that molecularly control their differentiation, function, and maintenance. Two transcription factors known to be involved in these processes are Tbet and STAT4. Although Tbet has been shown to regulate CD8 T cell fate decisions and effector CD4 T cell choices, the contribution of STAT4 is less well understood. To address this, we examined the impact of STAT4 on T cell responses in the presence or absence of Tbet, following LCMV infection by using mice lacking Tbet, STAT4, or both transcription factors. STAT4 was not required for Tbet or Eomes expression; however, virus-specific effector CD8 T cells are skewed toward a memory-precursor phenotype in the absence of STAT4. This altered proportion of memory precursors did not result in an increase in memory CD8 T cells after the resolution of the infection. We also demonstrate that virus-specific effector and memory CD4 T cells formed independently of Tbet and STAT4, although a slight reduction in the number of antigen-specific CD4 T cells was apparent in mice lacking both transcription factors. Collectively, we have discovered distinct roles for Tbet and STAT4 in shaping the phenotype and function of virus-specific T cell responses.
Κοραϊκά παραλειπόμενα [Β']
Authors: Φραγκίσκος Εμμ. Ν.
Published: November 2013

no abstract
Ρήγας και γαλλική Encyclopédie. Μία ακόμη χρησιμοποίηση της στα 1797
Authors: Καραμπερόπουλος Δημήτριος Απ.
Published: November 2013

no abstract
Case Report: Pregnancy in a patient with recurrent glioblastoma
Authors: Flechl Birgit , Hassler Marco Ronald , Kopetzky Gerhard , Balcke Peter , Kurz Christine , Marosi Christine
Published: November 2013

We report the case of a woman with relapsed glioblastoma multiforme (GBM) who recently gave birth. She announced her pregnancy shortly after the sixth cycle of a dense regimen of temozolomide, prescribed for treating the first recurrence of glioblastoma. Three years ago, in April 2008, she had undergone gross total resection of a glioblastoma multiforme in the postcentral region of the right hemisphere and had subsequently received treatment according to the actual standard therapy consisting of radiotherapy up to 60 Gy with concomitant and adjuvant temozolomide. The complete amount of temozolomide given before this pregnancy was 20.9 mg/m2. Nevertheless, she delivered a 1890 g child by caesarean section in the 32/6 week of pregnancy. The child showed no anomalies and is developing normally under close surveillance by paediatricians.
No psychological effect of color context in a low level vision task
Authors: Pedley Adam , Wade Alex R
Published: November 2013

Background: A remarkable series of recent papers have shown that colour can influence performance in cognitive tasks. In particular, they suggest that viewing a participant number printed in red ink or other red ancillary stimulus elements improves performance in tasks requiring local processing and impedes performance in tasks requiring global processing whilst the reverse is true for the colour blue. The tasks in these experiments require high level cognitive processing such as analogy solving or remote association tests and the chromatic effect on local vs. global processing is presumed to involve widespread activation of the autonomic nervous system. If this is the case, we might expect to see similar effects on all local vs. global task comparisons. To test this hypothesis, we asked whether chromatic cues also influence performance in tasks involving low level visual feature integration.

Methods: Subjects performed either local (contrast detection) or global (form detection) tasks on achromatic dynamic Glass pattern stimuli. Coloured instructions, target frames and fixation points were used to attempt to bias performance to different task types. Based on previous literature, we hypothesised that red cues would improve performance in the (local) contrast detection task but would impede performance in the (global) form detection task. 

Results: A two-way, repeated measures, analysis of covariance (2×2 ANCOVA) with gender as a covariate, revealed no influence of colour on either task, F(1,29) = 0.289, p = 0.595, partial η2 = 0.002. Additional analysis revealed no significant differences in only the first attempts of the tasks or in the improvement in performance between trials.

Discussion: We conclude that motivational processes elicited by colour perception do not influence neuronal signal processing in the early visual system, in stark contrast to their putative effects on processing in higher areas.
A new Cocconeis (Bacillariophyceae) from Moorea Island, Society Archipelago, South Pacific Ocean with distinctive valvocopula morphology and linking system
Authors: Riaux-Gobin Catherine , Romero Oscar E. , Coste Michel , Galzin René
Published: November 2013

The study of coral reef diatoms on Moorea Island in the Society Archipelago, South Pacific Ocean revealed a strong representation of the Achnanthales, with many taxa of Cocconeis. One of these Cocconeis, examined by light and scanning electron microscopy, shows a sternum valve (SV) with a close resemblance to the Cocconeis scutellum lineage, whereas the raphe valve (RV) and the valvocopula system are different from that of C. scutellum, therefore a new name has been given to it, Cocconeis spina-christi sp. nov. This new taxon has several remarkable features: 1) the RV stria density is, on average, twice as high as that of the SV; 2) the RV valvocopula extended and structurally complex, has large marginal fenestrae, irregular digitiform fimbriae and one longer spine-like fimbria at each apex; and 3) an anchor system between the valvocopula of each valve is observed, consisting of a rounded papilla with transverse furrows lying on each basal RV valvocopula fimbria and fitting into a rounded concavity – or cupule – in the corresponding marginal edge of the SV valvocopula. Such an anchor system between valvocopulae seems a characteristic common to several Cocconeis species bearing fimbriae on each valvocopula. The definition and limit of the concept of varieties in the C. scutellum lineage is also addressed.