bluuebunny/crossref_metadata_2025 huggingface dataset:
Facioscapulohumeral muscular dystrophy and Charcot-Marie-Tooth neuropathy 1A - evidence for “double trouble” overlapping syndromes
Authors: Schreiber Olivia , Schneiderat Peter , Kress Wolfram , Rautenstrauss Bernd , Senderek Jan , Schoser Benedikt , Walter Maggie C
Published: September 2013

Background

We report on a patient with genetically confirmed overlapping diagnoses of CMT1A and FSHD. This case adds to the increasing number of unique patients presenting with atypical phenotypes, particularly in FSHD. Even if a mutation in one disease gene has been found, further genetic testing might be warranted in cases with unusual clinical presentation.

Case presentation

The reported 53 years old male patient suffered from walking difficulties and foot deformities first noticed at age 20. Later on, he developed scapuloperoneal and truncal muscle weakness, along with atrophy of the intrinsic hand and foot muscles, pes cavus, claw toes and a distal symmetric hypoesthesia. Motor nerve conduction velocities were reduced to 20 m/s in the upper extremities, and not educible in the lower extremities, sensory nerve conduction velocities were not attainable. Electromyography showed both, myopathic and neurogenic changes. A muscle biopsy taken from the tibialis anterior muscle showed a mild myopathy with some neurogenic findings and hypertrophic type 1 fibers. Whole-body muscle MRI revealed severe changes in the lower leg muscles, tibialis anterior and gastrocnemius muscles were highly replaced by fatty tissue. Additionally, fatty degeneration of shoulder girdle and straight back muscles, and atrophy of dorsal upper leg muscles were seen. Taken together, the presenting features suggested both, a neuropathy and a myopathy. Patient’s family history suggested an autosomal dominant inheritance.

Molecular testing revealed both, a hereditary motor and sensory neuropathy type 1A (HMSN1A, also called Charcot-Marie-Tooth neuropathy 1A, CMT1A) due to a PMP22 gene duplication and facioscapulohumeral muscular dystrophy (FSHD) due to a partial deletion of the D4Z4 locus (19 kb).

Conclusion

Molecular testing in hereditary neuromuscular disorders has led to the identification of an increasing number of atypical phenotypes. Nevertheless, finding the right diagnosis is crucial for the patient in order to obtain adequate medical care and appropriate genetic counseling, especially in the background of arising curative therapies.
Evaluation of IScore validity in a Greek cohort of patients with type 2 diabetes
Authors: Dragoumanos Vasileios , Tzirogiannis Konstantinos N , Panoutsopoulos Georgios I , Krikonis Konstantinos , Fousteris Evangelos , Vourvou Maria , Elesnitsalis Georgios , Melas Nikolaos , Kourentzi Kalliopi T , Melidonis Andreas
Published: September 2013

Background

Diabetes constitutes a risk factor for stroke that also aggravates stroke prognosis. Several prognostic models have been developed for the evaluation of neurologic status, severity, short-term functional outcome and mortality of stroke patients. IScore is a novel tool recently developed in order to predict mortality rates within 30 days and 1 year after ischemic stroke and diabetes is not included in the scoring scale of IScore. The aim of the present study was to evaluate and compare IScore validity in ischemic stroke patients with and without diabetes.

Methods

This prospective study included 312 consecutive Caucasian patients with type 2 diabetes and 222 Caucasian patients without diabetes admitted for ischemic stroke in a tertiary Greek hospital. Thirty-day and 1-year IScores were individually calculated for each patient and actual mortality was monitored at the same time intervals. IScore’s predictive ability and calibration was evaluated and compared for ischemic stroke patients with and without diabetes. The performance of IScore for predicting 30 and 1-year mortality between patients with and without diabetes was assessed by determining the calibration and discrimination of the score. The area under the receiver operating characteristic curve was used to evaluate the discriminative ability of IScore for patients with and without diabetes, whereas the calibration of IScore was assessed by the Hosmer–Lemeshow goodness-of fit statistic.

Results

Baseline population characteristics and mortality rates did not differ significantly for both cohorts. IScore values were significantly higher for patients with diabetes at 30 days and 1 year after ischemic stroke and patients with diabetes presented more frequently with lacunar strokes. Based on ROC curves analysis IScore’s predictive ability for 30 day mortality was excellent, without statistically significant difference, for both cohorts. Predictive ability for 1 year mortality was also excellent for both groups with significantly better ability for patients with diabetes especially at high score values. Calibration of the model was good for both groups of patients.

Conclusions

IScore accurately predicts mortality in acute ischemic stroke Caucasian patients with and without diabetes with higher efficacy in predicting 1 year mortality in patients with diabetes especially with high scores.
Preventing academic difficulties in preterm children: a randomised controlled trial of an adaptive working memory training intervention – IMPRINT study
Authors: Pascoe Leona , Roberts Gehan , Doyle Lex W , Lee Katherine J , Thompson Deanne K , Seal Marc L , Josev Elisha K , Nosarti Chiara , Gathercole Susan , Anderson Peter J
Published: September 2013

Background

Very preterm children exhibit difficulties in working memory, a key cognitive ability vital to learning information and the development of academic skills. Previous research suggests that an adaptive working memory training intervention (Cogmed) may improve working memory and other cognitive and behavioural domains, although further randomised controlled trials employing long-term outcomes are needed, and with populations at risk for working memory deficits, such as children born preterm.

In a cohort of extremely preterm (<28 weeks’ gestation)/extremely low birthweight (<1000 g) 7-year-olds, we will assess the effectiveness of Cogmed in improving academic functioning 2 years’ post-intervention. Secondary objectives are to assess the effectiveness of Cogmed in improving working memory and attention 2 weeks’, 12 months’ and 24 months’ post-intervention, and to investigate training related neuroplasticity in working memory neural networks 2 weeks’ post-intervention.

Methods/Design

This double-blind, placebo-controlled, randomised controlled trial aims to recruit 126 extremely preterm/extremely low birthweight 7-year-old children. Children attending mainstream school without major intellectual, sensory or physical impairments will be eligible. Participating children will undergo an extensive baseline cognitive assessment before being randomised to either an adaptive or placebo (non-adaptive) version of Cogmed. Cogmed is a computerised working memory training program consisting of 25 sessions completed over a 5 to 7 week period. Each training session takes approximately 35 minutes and will be completed in the child’s home. Structural, diffusion and functional Magnetic Resonance Imaging, which is optional for participants, will be completed prior to and 2 weeks following the training period. Follow-up assessments focusing on academic skills (primary outcome), working memory and attention (secondary outcomes) will be conducted at 2 weeks’, 12 months’ and 24 months’ post-intervention.

Discussion

To our knowledge, this study will be the first randomised controlled trial to (a) assess the effectiveness of Cogmed in school-aged extremely preterm/extremely low birthweight children, while incorporating advanced imaging techniques to investigate neural changes associated with adaptive working memory training, and (b) employ long-term follow-up to assess the potential benefit of improved working memory on academic functioning. If effective, Cogmed would serve as a valuable, available intervention for improving developmental outcomes for this population.

Trial registration

Australian New Zealand Clinical Trials RegistryACTRN12612000124831.
Altered expression of caveolin 2 and 3 in smooth muscle of rat urinary bladder by 17β-estradiol
Authors: Kim Sun-Ouck , Song Seung Hee , Lee Seung-Chul , Cho Kyung Aa , Park Jong Sung , Kwon Dongdeuk , Park Kwangsung
Published: September 2013

Background

The purpose of this study was to investigate the effect of estrogen alteration on the expression of caveolin 2 and 3 in rat smooth muscle of urinary bladder.

Methods

Female Sprague–Dawley rats were divided into three groups: control, bilateral ovariectomy (Ovx), and bilateral ovariectomy followed by subcutaneous injections of 17β-estradiol (Ovx?+?Est). After 4 weeks, urodynamic measurements were taken to ascertain the contraction interval and contraction pressure. The expression and cellular localization of caveolin 2 and 3 were determined by Western blot and immunohistochemistry in rat urinary bladder smooth muscle.

Results

In cystometrograms, the contraction interval (min) was significantly lower in the Ovx group (3.1?±?1.5) than in the control group (5.6?±?1.2), but was increased after estrogen treatment (9.3?±?1.0). Conversely, the average contraction pressure (mmHg) was higher in the Ovx group (26.2?±?2.3) than in the control group (21.9?±?3.1), and was decreased after estrogen treatment (23.8?±?3.5). Caveolin 2 and 3 expression was localized in the cell membrane of the smooth muscle. The protein expression of both caveolin 2 and 3 was significantly lower after ovariectomy and was restored to the control levels after 17β-estradiol treatment.

Conclusions

Hormonal alteration causes a significant change in the expression of caveolin 2 and 3 in smooth muscle of rat urinary bladder. These findings suggest that these molecules might have functional roles in the detrusor overactivity that occurs in association with hormonal alteration.
The antiproliferative effect of Moringa oleifera crude aqueous leaf extract on cancerous human alveolar epithelial cells
Authors: Tiloke Charlette , Phulukdaree Alisa , Chuturgoon Anil A
Published: September 2013

Background

The incidence of lung cancer is expected to increase due to increases in exposure to airborne pollutants and cigarette smoke. Moringa oleifera (MO), a medicinal plant found mainly in Asia and South Africa is used in the traditional treatment of various ailments including cancer. This study investigated the antiproliferative effect of MO leaf extract (MOE) in cancerous A549 lung cells.

Methods

A crude aqueous leaf extract was prepared and the cells were treated with 166.7 μg/ml MOE (IC50) for 24 h and assayed for oxidative stress (TBARS and Glutathione assays), DNA fragmentation (comet assay) and caspase (3/7 and 9) activity. In addition, the expression of Nrf2, p53, Smac/DIABLO and PARP-1 was determined by Western blotting. The mRNA expression of Nrf2 and p53 was assessed using qPCR.

Results

A significant increase in reactive oxygen species with a concomitant decrease in intracellular glutathione levels (p < 0.001) in MOE treated A549 cells was observed. MOE showed a significant reduction in Nrf2 protein expression (1.89-fold, p < 0.05) and mRNA expression (1.44-fold). A higher level of DNA fragmentation (p < 0.0001) was seen in the MOE treated cells. MOE’s pro-apoptotic action was confirmed by the significant increase in p53 protein expression (1.02-fold, p < 0.05), p53 mRNA expression (1.59-fold), caspase-9 (1.28-fold, p < 0.05), caspase-3/7 (1.52-fold) activities and an enhanced expression of Smac/DIABLO. MOE also caused the cleavage and activation of PARP-1 into 89 KDa and 24 KDa fragments (p < 0.0001).

Conclusion

MOE exerts antiproliferative effects in A549 lung cells by increasing oxidative stress, DNA fragmentation and inducing apoptosis.
A study on relapse/re-infection rate of Plasmodium vivax malaria and identification of the predominant genotypes of P. vivax in two endemic districts of Nepal
Authors: Manandhar Sulochana , Bhusal Chop L , Ghimire Umesh , Singh Shankar P , Karmacharya Dibesh B , Dixit Sameer M
Published: September 2013

Background

Malaria is a major public health problem in Nepal inflicted primarily by the parasite Plasmodium vivax, - the only species responsible for relapse cases in Nepal. Knowledge on its relapse rate is important for successful malaria control, but is lacking in Nepal. The information on circulating predominant genotypes of P. vivax is equally relevant for high endemic districts of Nepal to understand the transmission dynamics of the parasite and to uncover the coverage and efficacy of potential vaccine beforehand.

Methods

A prospective observational study with a six months follow-up period was conducted from August 2010 to May 2011 in four health centres of Kailali and Kanchanpur districts of Nepal to access the relapse/re-infection rate of P. vivax. The prevalence and heterogeneity of its genotypes were identified by PCR-RFLP assay targeting central repeat region of circumsporozoite protein (Pvcsp).

Results

In total, 137 cases microscopically suspected to have P. vivax infection were enrolled in the study. Of these, 23 cases (17%) were detected for the relapse/ re-infection-during a six-month period, with a high proportion being male cases of age group 11–20 years. For genotyping, 100 whole blood samples were analysed, of which 95% of the parasite isolates were found to be of VK210 genotype. The minor genotype VK247 existed either in isolation or as mixed infection with VK210 in rest of the samples.

Conclusions

The relapse/re-infection rate of 17% was determined for P. vivax in Kailali and Kanchanpur districts of Nepal. A heterogeneous Pvcsp genotypic distribution of P. vivax was detected with VK210 being a predominant type, suggesting a complex transmission dynamics of the parasite. Expanding such study in other endemic regions of Nepal would help provide a complete picture on relapse/re-infection rate and parasite genotypic variability that can help in effective control and management of malaria in Nepal.
Apolipoprotein M T-778C polymorphism is associated with serum lipid levels and the risk of coronary artery disease in the Chinese population: a meta-analysis
Authors: Zhang Zhi , Chu Guang , Yin Rui-Xing
Published: September 2013

Background

The apolipoprotein M (APOM) T-778C gene polymorphism has been associated with serum lipid levels and the risk of coronary artery disease (CAD), but the results are inconclusive. The purpose of this meta-analysis was to detect the association between the APOM T-778C polymorphism and serum lipid levels and the risk of CAD in the Chinese population.

Methods

Databases of MEDLINE, EMBASE, the Cochrane Library and CNKI were systematically searched. Data were extracted using standardized methods. The association was assessed by mean difference (MD) with 95% confidence intervals (CI) or odds ratio (OR) with 95% CI.

Results

Ten studies with 4,413 patients were included in this meta-analysis. Pooled effects indicated that CT+CC group had higher levels of total cholesterol (TC) (MD:-0.36, 95% CI: -0.53 – -0.19, P < 0.0001) and low-density lipoprotein cholesterol (LDL-C) (MD: -0.08, 95% CI: -0.16 – -0.01, P = 0.03) than TT group. There was no difference in the levels of triglyceride (MD: 0.06, 95% CI: -0.04 – 0.15, P = 0.22) and high-density lipoprotein cholesterol (MD: 0.00, 95% CI: -0.03–0.03, P = 0.93) between TT and CT+CC groups. Pooled effects showed that CAD group had higher CT+CC genotype frequency than control group (OR: 1.97, 95% CI: 1.62–2.39, P < 0.00001; heterogeneity test x
2 = 2.96, P = 0.71, I
2 = 0%).

Conclusions

The results of the current meta-analysis show that the CT+CC group has higher levels of TC and LDL-C than the TT group. Moreover, there is also a prominent association between APOM T-778C polymorphism and the risk of CAD in the Chinese population, the CT+CC genotype is associated with increased risk of CAD.
Role of conserved cis-regulatory elements in the post-transcriptional regulation of the human MECP2 gene involved in autism
Authors: Bagga Joetsaroop S , D’Antonio Lawrence A
Published: September 2013

Background

The MECP2 gene codes for methyl CpG binding protein 2 which regulates activities of other genes in the early development of the brain. Mutations in this gene have been associated with Rett syndrome, a form of autism. The purpose of this study was to investigate the role of evolutionarily conserved cis-elements in regulating the post-transcriptional expression of the MECP2 gene and to explore their possible correlations with a mutation that is known to cause mental retardation.

Results

A bioinformatics approach was used to map evolutionarily conserved cis-regulatory elements in the transcribed regions of the human MECP2 gene and its mammalian orthologs. Cis-regulatory motifs including G-quadruplexes, microRNA target sites, and AU-rich elements have gained significant importance because of their role in key biological processes and as therapeutic targets. We discovered in the 5′-UTR (untranslated region) of MECP2 mRNA a highly conserved G-quadruplex which overlapped a known deletion in Rett syndrome patients with decreased levels of MeCP2 protein. We believe that this 5′-UTR G-quadruplex could be involved in regulating MECP2 translation. We mapped additional evolutionarily conserved G-quadruplexes, microRNA target sites, and AU-rich elements in the key sections of both untranslated regions. Our studies suggest the regulation of translation, mRNA turnover, and development-related alternative MECP2 polyadenylation, putatively involving interactions of conserved cis-regulatory elements with their respective trans factors and complex interactions among the trans factors themselves. We discovered highly conserved G-quadruplex motifs that were more prevalent near alternative splice sites as compared to the constitutive sites of the MECP2 gene. We also identified a pair of overlapping G-quadruplexes at an alternative 5′ splice site that could potentially regulate alternative splicing in a negative as well as a positive way in the MECP2 pre-mRNAs.

Conclusions

A Rett syndrome mutation with decreased protein expression was found to be associated with a conserved G-quadruplex. Our studies suggest that MECP2 post-transcriptional gene expression could be regulated by several evolutionarily conserved cis-elements like G-quadruplex motifs, microRNA target sites, and AU-rich elements. This phylogenetic analysis has provided some interesting and valuable insights into the regulation of the MECP2 gene involved in autism.
Linkages between HIV-1 specificity for CCR5 or CXCR4 and in vitrousage of alternative coreceptors during progressive HIV-1 subtype C infection
Authors: Cashin Kieran , Jakobsen Martin R , Sterjovski Jasminka , Roche Michael , Ellett Anne , Flynn Jacqueline K , Borm Katharina , Gouillou Maelenn , Churchill Melissa J , Gorry Paul R
Published: September 2013

Background

Human immunodeficiency virus type 1 (HIV-1) subtype C (C-HIV) is spreading rapidly and is now responsible for >50% of HIV-1 infections worldwide, and >95% of infections in southern Africa and central Asia. These regions are burdened with the overwhelming majority of HIV-1 infections, yet we know very little about the pathogenesis of C-HIV. In addition to CCR5 and CXCR4, the HIV-1 envelope glycoproteins (Env) may engage a variety of alternative coreceptors for entry into transfected cells. Whilst alternative coreceptors do not appear to have a broad role in mediating the entry of HIV-1 into primary cells, characterizing patterns of alternative coreceptor usage in vitro can provide valuable insights into mechanisms of Env-coreceptor engagement that may be important for HIV-1 pathogenesis.

Results

Here, we characterized the ability of luciferase reporter viruses pseudotyped with HIV-1 Envs (n = 300) cloned sequentially from plasma of 21 antiretroviral therapy (ART)-naïve subjects experiencing progression from chronic to advanced C-HIV infection over an approximately 3-year period, who either exclusively maintained CCR5-using (R5) variants (n = 20 subjects) or who experienced a coreceptor switch to CXCR4-using (X4) variants (n = 1 subject), to utilize alternative coreceptors for entry. At a population level, CCR5 usage by R5 C-HIV Envs was strongly linked to usage of FPRL1, CCR3 and CCR8 as alternative coreceptors, with the linkages to FPRL1 and CCR3 usage becoming statistically more robust as infection progressed from chronic to advanced stages of disease. In contrast, acquisition of an X4 Env phenotype at advanced infection was accompanied by a dramatic loss of FPRL1 usage. Env mutagenesis studies confirmed a direct link between CCR5 and FPRL1 usage, and showed that the V3 loop crown, but not other V3 determinants of CCR5-specificity, was the principal Env determinant governing the ability of R5 C-HIV Envs from one particular subject to engage FPRL1.

Conclusions

Our results suggest that, in the absence of coreceptor switching, the ability of R5 C-HIV viruses to engage certain alternative coreceptors in vitro, in particular FPRL1, may reflect an altered use of CCR5 that is selected for during progressive C-HIV infection, and which may contribute to C-HIV pathogenicity.
Live attenuated rubella vectors expressing SIV and HIV vaccine antigens replicate and elicit durable immune responses in rhesus macaques
Authors: Virnik Konstantin , Hockenbury Max , Ni Yisheng , Beren Joel , Pavlakis George N , Felber Barbara K , Berkower Ira
Published: September 2013

Background

Live attenuated viruses are among our most potent and effective vaccines. For human immunodeficiency virus, however, a live attenuated strain could present substantial safety concerns. We have used the live attenuated rubella vaccine strain RA27/3 as a vector to express SIV and HIV vaccine antigens because its safety and immunogenicity have been demonstrated in millions of children. One dose protects for life against rubella infection. In previous studies, rubella vectors replicated to high titers in cell culture while stably expressing SIV and HIV antigens. Their viabilityin vivo, however, as well as immunogenicity and antibody persistence, were unknown.

Results

This paper reports the first successful trial of rubella vectors in rhesus macaques, in combination with DNA vaccines in a prime and boost strategy. The vectors grew robustlyin vivo, and the protein inserts were highly immunogenic. Antibody titers elicited by the SIV Gag vector were greater than or equal to those elicited by natural SIV infection. The antibodies were long lasting, and they were boosted by a second dose of replication-competent rubella vectors given six months later, indicating the induction of memory B cells.

Conclusions

Rubella vectors can serve as a vaccine platform for safe delivery and expression of SIV and HIV antigens. By presenting these antigens in the context of an acute infection, at a high level and for a prolonged duration, these vectors can stimulate a strong and persistent immune response, including maturation of memory B cells. Rhesus macaques will provide an ideal animal model for demonstrating immunogenicity of novel vectors and protection against SIV or SHIV challenge.
Design and evaluation of a unique RT-qPCR assay for diagnostic quality control assessment that is applicable to pathogen detection in three species of salmonid fish
Authors: Sepúlveda Dagoberto , Bohle Harry , Labra Álvaro , Grothusen Horst , Marshall Sergio H
Published: September 2013

Background

The detection of pathogens at early stages of infection is a key point for disease control in aquaculture. Therefore, accurate diagnostic procedures are a must. Real-time PCR has been a mainstay in diagnostics over the years due to its speed, specificity, sensitivity, reproducibility and throughput; as such, real-time PCR is a target for improvement. Nevertheless, to validate a novel diagnostic tool, correct setup of the assay, including proper endogenous controls to evaluate the quantity and quality of the samples and to detect possible sample degradation, is compulsory. This work aims to design a unique RT-qPCR assay for pathogen detection in the three salmonid species reared in Chile. The assay uses elongation factor 1 alpha as the single endogenous control, thus avoiding the need for multiple endogenous controls, as well as multiple validations and non-comparable quality control parameters.

Results

The in vivo and in vitro analyses of samples from Salmo salar, Oncorhynchus mykiss and Oncorhynchus kisutch showed that when primers were accurately selected to target conserved regions of the elongation factor 1 alpha (ELF1α) gene, a single novel RT-qPCR assay yielding similar and reproducible Ct values between the three species could be designed. The opposite occurred when an assay originally designed for Salmo salar was tested in samples from the two species of the genus Oncorhynchus.

Conclusions

Here, we report the design and evaluation of an accurate trans-species RT-qPCR assay that uses the elongation factor 1 alpha (ELF1α) gene as an endogenous control and is applicable for diagnostic purposes in samples obtained from the three salmonid species reared in Chile.
Quantitative analysis of tumor shrinkage due to chemotherapy and its implication for radiation treatment planning in limited-stage small-cell lung cancer
Authors: Xia Bing , Wang Jia-Zhou , Liu Qi , Cheng Jing-Yi , Zhu Zheng-Fei , Fu Xiao-Long
Published: September 2013

Background

The optimal timing of chemoradiotherapy in limited-stage small-cell lung cancer (LS-SCLC) hasn’t been established, although evidence from studies supported that patients can benefit from early radiation therapy. The purpose of this study was to quantify tumor shrinkage in response to induction chemotherapy (IC), evaluate the impact of tumor shrinkage on radiation dosimetric parameters and determine its implication for the timing of radiation therapy for patients with LS-SCLC.

Methods

Twenty patients with LS-SCLC who were treated with IC followed by concomitant radiation therapy were investigated retrospectively. Ten patients received 1 cycle of IC, and 10 patients received 2 cycles of IC. Pre-IC CT imaging was coregistered with a simulation CT, and virtual radiation plans were created for pre- and post-IC thoracic disease in each case. The changes in the gross target volume (GTV), planning target volume (PTV) and dosimetric factors associated with the lungs, esophagus and heart were analyzed.

Results

The mean GTV and PTV for all of the patients decreased by 60.9% and 40.2%, respectively, which resulted in a significant reduction in the radiation exposure to the lungs, esophagus and heart. Changes in the PTV and radiation exposure of normal tissue were not significantly affected by the number of chemotherapy cycles delivered, although patients who received 2 cycles of IC had a greater decrease in GTV than those who received only 1 cycle of IC (69.6% vs. 52.1%, p = 0.273).

Conclusions

Our data showed that targeting the tumor post-IC may reduce the radiation dose to normal tissue in patients with LS-SCLC. However, the benefit to the normal tissue was not increased by an additional cycle of IC. These findings suggest that the first cycle of chemotherapy is very important for tumor shrinkage and that initiating thoracic radiation therapy at the second cycle of chemotherapy may be a reasonable strategy for timing of radiation therapy in LS-SCLC treatment.
Impact of osmotic stress and ethanol inhibition in yeast cells on process oscillation associated with continuous very-high-gravity ethanol fermentation
Authors: Wang Liang , Zhao Xin-Qing , Xue Chuang , Bai Feng-Wu
Published: September 2013

Background

VHG fermentation is a promising process engineering strategy aiming at improving ethanol titer, and thus saving energy consumption for ethanol distillation and distillage treatment. However, sustained process oscillation was observed during continuous VHG ethanol fermentation, which significantly affected ethanol fermentation performance of the system.

Results

Sustained process oscillation was investigated in continuous VHG ethanol fermentation, and stresses exerted on yeast cells by osmotic pressure from unfermented sugars and ethanol inhibition developed within the fermentation system were postulated to be major factors triggering this phenomenon. In this article, steady state was established for continuous ethanol fermentation with LG medium containing 120 g/L glucose, and then 160 g/L non-fermentable xylose was supplemented into the LG medium to simulate the osmotic stress on yeast cells under the VHG fermentation condition, but the fermentation process was still at steady state, indicating that the impact of osmotic stress on yeast cells was not the main reason for the process oscillation. However, when 30 g/L ethanol was supplemented into the LG medium to simulate the ethanol inhibition in yeast cells under the VHG fermentation condition, process oscillation was triggered, which was augmented with extended oscillation period and exaggerated oscillation amplitude as ethanol supplementation was increased to 50 g/L, but the process oscillation was gradually attenuated when the ethanol supplementations were stopped, and the steady state was restored. Furthermore, gas stripping was incorporated into the continuous VHG fermentation system to in situ remove ethanol produced by Saccharomyces cerevisiae, and the process oscillation was also attenuated, but restored after the gas stripping was interrupted.

Conclusions

Experimental results indicated that ethanol inhibition rather than osmotic stress on yeast cells is one of the main factors triggering the process oscillation under the VHG fermentation condition, and in the meantime gas stripping was validated to be an effective strategy for attenuating the process oscillation.
Engineering xylose metabolism in triacylglycerol-producing Rhodococcus opacusfor lignocellulosic fuel production
Authors: Kurosawa Kazuhiko , Wewetzer Sandra J , Sinskey Anthony J
Published: September 2013

Background

There has been a great deal of interest in fuel productions from lignocellulosic biomass to minimize the conflict between food and fuel use. The bioconversion of xylose, which is the second most abundant sugar present after glucose in lignocellulosic biomass, is important for the development of cost effective bioprocesses to fuels. Rhodococcus opacus PD630, an oleaginous bacterium, accumulates large amounts of triacylglycerols (TAGs), which can be processed into advanced liquid fuels. However, R. opacus PD630 does not metabolize xylose.

Results

We generated DNA libraries from a Streptomyces bacterium capable of utilizing xylose and introduced them into R. opacus PD630. Xsp8, one of the engineered strains, was capable of growing on up to 180 g L-1 of xylose. Xsp8 grown in batch-cultures derived from unbleached kraft hardwood pulp hydrolysate containing 70 g L-1 total sugars was able to completely and simultaneously utilize xylose and glucose present in the lignocellulosic feedstock, and yielded 11.0 g L-1 of TAGs as fatty acids, corresponding to 45.8% of the cell dry weight. The yield of total fatty acids per gram of sugars consumed was 0.178 g, which consisted primarily of palmitic acid and oleic acid. The engineered strain Xsp8 was introduced with two heterologous genes from Streptomyces: xylA, encoding xylose isomerase, and xylB, encoding xylulokinase. We further demonstrated that in addition to the introduction and the concomitant expression of heterologous xylA and xylB genes, there is another molecular target in the R. opacus genome which fully enables the functionality of xylA and xylB genes to generate the robust xylose-fermenting strain capable of efficiently producing TAGs at high xylose concentrations.

Conclusion

We successfully engineered a R. opacus strain that is capable of completely utilizing high concentrations of xylose or mixed xylose/glucose simultaneously, and substantiated its suitability for TAG production. This study demonstrates that the engineered strain possesses a key trait of converters for lipid-based fuels production from lignocellulosic biomass.
Thermo-mechanical properties of silicon carbide filled chopped glass fiber reinforced epoxy composites
Authors: Agarwal Gaurav , Patnaik Amar , Sharma Rajesh Kumar
Published: September 2013

The effect of addition of silicon carbide (SiC) filler in different weight percentages on physical properties, mechanical properties, and thermal properties of chopped glass fiber-reinforced epoxy composites has been investigated. Physical and mechanical properties, i.e., hardness, tensile strength, flexural strength, interlaminar shear strength, and impact strength, are determined with the change in filler content to notice the behavior of composite material subjected to loading. Thermo-mechanical properties of the material are measured with the help of a dynamic mechanical analyzer. The result shows that the physical and mechanical properties of SiC-filled glass fiber-reinforced epoxy composites are better than unfilled glass fiber-reinforced epoxy composites. Viscoelastic analysis for different compositions indicate that adding too much SiC content results in degradation in energy absorption capacity of the material and hence overall performance of the composites, whereas adding too much (more than 10 wt.%) SiC content increases the elastic behavior of the composite.
The use of Hand-Held XRF for investigating the composition and corrosion of Roman copper-alloyed artefacts
Authors: Fernandes Ricardo , van Os Bertil JH , Huisman Hans DJ
Published: September 2013

The study of archaeological artefacts using deployed in situ analytical instruments presents some obvious advantages. Including, obtaining an immediate feedback that can be used to redefine in real-time fieldwork strategies. Ideally analytical field instruments should also have characteristics that limit damage to the studied artefact.

Here, we present a case study on the use of a Hand Held XRF (HH XRF) device employed to define the composition of copper-alloyed artefacts retrieved from the Roman military site of Fectio in the vicinity of Vechten (The Netherlands). The goals of the study were to establish artefact preservation status, to investigate artefact elemental composition, and to compare the composition of artefact corrosion layer and uncorroded core.

The results showed that the objects were in an overall good preservation state. Decuprification and dezincification represented the probable main corrosion processes resulting in the formation of smooth corrosion layers or patinas. The major elemental composition of the artefacts’ uncorroded cores showed a wide-range variability most likely associated with recycling practices of scrap metal during the 3rd century CE.
Expression of PIK3CA, PTEN mRNA and PIK3CA mutations in primary breast cancer: association with lymph node metastases
Authors: Palimaru Irina , Brügmann Anja , Wium-Andersen Marie Kim , Nexo Ebba , Sorensen Boe Sandahl
Published: September 2013

Purpose

High activity of the intracellular phosphatidylinositol-3 kinase (PI3K) pathway is common in breast cancer. Here, we explore differences in expression of important PI3K pathway regulators: the activator, phosphatidylinositol-3-kinase catalytic subunit alpha (PIK3CA), and the tumour suppressor, phosphatase and tensin homolog (PTEN), in breast carcinoma tissue and normal breast tissue. Furthermore, we examine whether expression of PIK3CA and PTEN mRNA and occurrence of PIK3CA mutations are associated with lymph node metastases in patients with primary breast cancer.

Methods

Paired tissue samples of breast carcinoma and normal breast tissue were obtained from 175 breast cancer patients at the time of primary surgery, of these 105 patients were lymph node positive. Expression of PIK3CA and PTEN mRNA was quantified with Quantitative Real Time PCR. Somatic mutations in exon 9 and exon 20 of the PIK3CA gene were identified by genotyping.

Results

Both PIK3CA and PTEN mRNA expression was significantly increased in breast carcinoma tissue compared to normal breast tissue (p = 2 × 10-11) and (p < 0.001), respectively. PIK3CA mutations were present in 68 out of 175 patients (39%), but were not associated with PIK3CA expression (p = 0.59). Expression of PIK3CA and PTEN mRNA, and PIK3CA mutations in breast carcinomas were not associated with presence of lymph node metastases.

Conclusions

The expression of PTEN and PIK3CA mRNA is increased in breast carcinoma tissue compared to normal breast tissue, and PIK3CA mutations are frequent in primary breast carcinoma, however these factors were not associated with lymph node metastases.
RETRACTED ARTICLE: Propylthiouracil prevents cutaneous and pulmonary fibrosis in the reactive oxygen species murine model of systemic sclerosis
Authors: Bagnato Gianluca , Bitto Alessandra , Irrera Natasha , Pizzino Gabriele , Sangari Donatella , Cinquegrani Maurizio , Roberts William Neal , Atteritano Marco , Altavilla Domenica , Squadrito Francesco , Bagnato Gianfilippo , Saitta Antonino
Published: September 2013

Introduction

Recent advances suggest that the cellular redox state may play a significantrole in the progression of fibrosis in systemic sclerosis (SSc). Another,and as yet poorly accounted for, feature of SSc is its overlap with thyroidabnormalities. Previous reports demonstrate that hypothyroidism reducesoxidant stress. The aim of this study was therefore to evaluate the effectof propylthiouracil (PTU), and of the hypothyroidism induced by it, on thedevelopment of cutaneous and pulmonary fibrosis in the oxidant stress murinemodel of SSc.

Methods

Chronic oxidant stress SSc was induced in BALB/c mice by daily subcutaneousinjections of hypochlorous acid (HOCl) for 6 weeks. Mice (n = 25)were randomized into three arms: HOCl (n = 10), HOCl plus PTU(n = 10) or vehicle alone (n = 5). PTU administrationwas initiated 30 minutes after HOCl subcutaneous injection and continueddaily for 6 weeks. Skin and lung fibrosis were evaluated by histologicmethods. Immunohistochemical staining for alpha-smooth muscle actin(α-SMA) in cutaneous and pulmonary tissues was performed to evaluatemyofibroblast differentiation. Lung and skin concentrations of vascularendothelial growth factor (VEGF), extracellular signal-related kinase (ERK),rat sarcoma protein (Ras), Ras homolog gene family (Rho), and transforminggrowth factor (TGF) β were analyzed by Western blot.

Results

Injections of HOCl induced cutaneous and lung fibrosis in BALB/c mice. PTUtreatment prevented both dermal and pulmonary fibrosis. Myofibroblastdifferentiation was also inhibited by PTU in the skin and lung. The increasein cutaneous and pulmonary expression of VEGF, ERK, Ras, and Rho in micetreated with HOCl was significantly prevented in mice co-administered////with PTU.

Conclusions

PTU, probably through its direct effect on reactive oxygen species orindirectly through thyroid function inhibition, prevents the development ofcutaneous and pulmonary fibrosis by blocking the activation of the Ras-ERKpathway in the oxidant-stress animal model of SSc.
An organ culture system to model early degenerative changes of the intervertebral disc II: profiling global gene expression changes
Authors: Markova Dessislava Z , Kepler Christopher K , Addya Sankar , Murray Hallie B , Vaccaro Alexander R , Shapiro Irving M , Greg Anderson D , Albert Todd J , Risbud Makarand V
Published: September 2013

Introduction

Despite many advances in our understanding of the molecular basis of disc degeneration, there remains a paucity of preclinical models which can be used to study the biochemical and molecular events that drive disc degeneration, and the effects of potential therapeutic interventions. The goal of this study is to characterize global gene expression changes in a disc organ culture system that mimics early nontraumatic disc degeneration.

Methods

To mimic a degenerative insult, rat intervertebral discs were cultured in the presence of TNF-α, IL-1β and serum-limiting conditions. Gene expression analysis was performed using a microarray to identify differential gene expression between experimental and control groups. Differential pattern of gene expression was confirmed using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) or Western blot.

Results

Treatment resulted in significant changes in expression of more than 1,000 genes affecting many aspects of cell function including cellular movement, the cell cycle, cellular development, and cell death and proliferation. Many of the most highly upregulated and downregulated genes have known functions in disc degeneration and extracellular matrix hemostasis. Construction of gene networks based on known cellular pathways and expression data from our analysis demonstrated that the network associated with cell death, cell cycle regulation and DNA replication and repair was most heavily affected in this model of disc degeneration.

Conclusions

This rat organ culture model uses cytokine exposure to induce wide gene expression changes with the most affected genes having known reported functions in disc degeneration. We propose that this model is a valuable tool to study the etiology of disc degeneration and evaluate potential therapeutic treatments.
Differential Transform – Pade Technique for Treating Non-linear Singular Boundary Value Problems Arising in the Applied Sciences
Authors: Ravi Kanth A. S. V. , Aruna K.
Published: September 2013

This paper applies differential transform – Pade technique for treating non-linear singular boundary value problems arising in various physical problems of science and engineering. Comparisons are made between the results of the proposed method, and the exact solutions. The results show that the proposed method is an attractive method for solving non-linear singular boundary value problems.
Wavelet-Galerkin Method for the Solution of Shear Wave Equation
Authors: Saha Ray S. , Dandapat A.
Published: September 2013

Wavelet function generates significant interest from both theoretical and applied research given in the last ten years. In the present paper, the Daubechies family of wavelets will be considered due to their useful properties, since the contribution of compactly supported wavelet by Daubechies and multi resolution analysis based on Fast Fourier Transform (FWT) algorithm by Beylkin, wavelet based solution of ordinary and partial differential equations gained momentum in attractive way. Advantages of Wavelet-Galerkin method over finite difference or element method have led to tremendous application in science and engineering.

In this paper, the Daubechies families of wavelets have been applied to solve differential equations. Solution obtained with the Daubechies' 6 Wavelet filter coefficients has been compared with exact solution. The good agreement of the result with the exact solution proves the accuracy and efficiency of Wavelet-Galerkin method.
Exact Solutions for Pattern Formation in a Reaction-Diffusion System
Authors: Lin Yezhi , Liu Yinping , Li Zhibin
Published: September 2013

Reaction-diffusion equations are ubiquitous as models of pattern formation in chemistry and biology. In this paper, the invariant subspace method is used to investigate exact solutions and the corresponding patterns in a reaction-diffusion system. Several forms of the exact solutions of the one-dimensional reaction-diffusion system are presented, including complexions. Furthermore, we show several patterns the two-dimensional reaction-diffusion system, involving stripes, spots and transitions between them. Additionally, we discuss the relations between patterns and exact solutions.
Kindermedienwelten als Forschungsgegenstand. Projekte des Instituts für angewandte Kindermedienforschung der Hochschule der Medien Stuttgart (HdM) / Children Media World as a research focus. The Institute for applied Children Media Research of the Stuttgart Media University and its projects / Les mondes des médias des enfants comme objet de recherche : Les projets de l’Institut für angewandte Kindermedienforschung der Hochschule der Medien Stuttgart (HdM) (Institut de recherche appliquée des médias des enfants de l’université des médias de Stuttgart)
Authors: Stang Richard , Nagl Manfred
Published: September 2013

Die Bedeutung der Medien im Alltag hat in den letzten Jahren durch den immensen technologischen Wandel zugenommen. Medien sind heute elementarer Bestandteil des Alltags und dies gilt in besonderem Maße für den Kinderalltag. Gleichzeitig ist es durch die enorme Ausdifferenzierung des Medienangebots für Eltern und pädagogische Kräfte kaum mehr möglich, einen Überblick über den Medienkonsum der Kinder zu behalten. Das Institut für angewandte Kindermedienforschung (IfaK) fungiert als Kompetenzzentrum in Anbetracht dieser Herausforderungen. Die enge Zusammenarbeit mit Bibliotheken eröffnete vielfältige Optionen, medienpädagogische Arbeit zu initiieren und zu unterstützen. Im Rahmen des Forschungsschwerpunkts „KinderMedienWelten“ bereitet das IfaK die Geschichte der Kindermedien auf. Die Schwerpunkte der Arbeit werden in diesem Beitrag vorgestellt.
Lernwelten gestalten. Forschung zur Relevanz des Raumes bei der Gestaltung von Lernlandschaften / Creating learning environments. Research on the relevance of space on the designing of learning landscapes / Conception de mondes d’apprentissage. Recherche sur la pertinence de l’espace dans la création de paysages d’apprentissage
Authors: Stang Richard
Published: September 2013

Die sich verändernde Bildungslandschaft und der Bedarf an veränderten Lernarrangements schaffen große Herausforderungen bei der Gestaltung einer Lerninfrastruktur, um unter der Perspektive des lebenslangen Lernens unterschiedlichste Lernzugänge zu ermöglichen. Es müssen nicht nur didaktisch-methodische Konzepte gestaltet werden, sondern in verstärktem Maße sind es die Verknüpfung virtueller und realer Lerninfrastrukturen sowie die Gestaltung von realen Lernsettings, die zum Lernen anregen aber auch Unterstützungsstrukturen für die Lernenden bereit halten. Der Forschungsschwerpunkt „Lernwelten“ an der Hochschule der Medien beschäftigt sich mit den Fragen, die sich aus diesen Herausforderungen ergeben und dies unter den Perspektiven: didaktischmethodische Lehr-/Lernsettings, organisatorische Gestaltungskonzepte, bauliche Gestaltung von realen Lernräumen und Gestaltung virtueller Lernräume. Der Beitrag zeigt anhand der Projekte „LearnerLab“ und „Innovative Bildungsräume gestalten/Lernzentren“ wie in diesem Zusammenhang Entwicklungsforschung realisiert wird.
Digitale Persönlichkeiten als interdisziplinärer Forschungsgegenstand / Digital personalities as a topic for interdisciplinary research / Personnalités numériques comme objet de recherche interdisciplinaire
Authors: Ebner Tamara , Kölzer Anna , Scharfen Jana , Spitzer Sarah , Trost Kai Erik , Wilczek Stephan
Published: September 2013

Der Beitrag stellt die unterschiedlichen Perspektiven auf das Forschungsfeld „Digitale Persönlichkeiten“ dar. Unter diesem werden Untersuchungen zur Selbstdarstellung und öffentlichen Wahrnehmung/Auswertung von Profilen in „Sozialen Online Netzwerken“ verstanden, ein Forschungsfeld, das in unterschiedlichen Wissenschaftsdisziplinen mit verschiedenen Schwerpunkten bearbeitet wird. Die Autoren fassen die wesentlichen Aspekte der einzelnen Disziplinen zusammen und zeigen Potenziale der interdisziplinären Forschung auf.
Qualitätsmanagement und Organisationsentwicklung – Forschung für Bibliotheken und Hochschulen / Quality management and organizational development – research for libraries and institutions of higher education / Gestion de la qualité et développement organisationnel – recherche destinée aux bibliothèques et aux écoles supérieures
Authors: Vonhof Cornelia , Bertele Maria , Bauknecht Cornelius
Published: September 2013

Das Institut für Qualitätsmanagement und Organisationsentwicklung in Bibliotheken und Hochschulen (IQO) an der Hochschule der Medien Stuttgart stellt die beiden Institutionen ins Zentrum seiner Forschungsarbeit, die die Verbreitung von Qualitätsmanagement als ganzheitlichem Managementansatz im öffentlichen Sektor in den letzten Jahren aktiv vorangebracht haben. Ausgehend von einem ganzheitlichen Qualitätsverständnis werden am IQO Management- und Steuerungsinstrumente entwickelt, die Veränderungsprozesse in Bibliotheken und Hochschulen anstoßen und unterstützen.