bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract PR6: Resistance to EGFR inhibition via the emergence of EGFRvIII-independent tumor growth-promoting mechanisms in glioblastoma
Authors: Wykosky Jill , Mukasa Akitake , Chin Lynda , Cavenee Webster , Furnari Frank
Published: June 2012

A major hurdle in the clinical success of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) for the treatment of glioblastoma multiforme (GBM) is the occurrence of resistance, the mechanisms for which remain largely unknown. Amplification of EGFR and/or expression of its constitutively active mutant, EGFRvIII, are among the most frequently found molecular alterations in GBMs. Recently, we have shown that U373 cells engineered to express doxycycline (dox)-repressible EGFRvIII were dependent upon the expression of this receptor not only for tumor initiation, but also for maintenance and progression of tumors in a xenograft mouse model. Interestingly, following a period of growth stasis in vivo due to silencing of EGFRvIII, some tumors regained the ability to grow rapidly, which is strikingly similar to the clinical scenario of resistance. These aggressive breakthrough tumors, termed “escapers,” remained silenced for EGFRvIII and employed distinctly different signaling pathways when collectively compared to the initial EGFRvIII-dependent tumors. Escapers exhibited elevated activity of components of the MAPK signaling pathway, and cell lines established from the tumors were significantly more sensitive to inhibition of Mek than cells derived from EGFRvIII-dependent tumors. Removal of dox and reexpression of EGFRvIII in escapers markedly suppressed tumor growth, suggesting that the unique signaling pathway preferences of escapers are not compatible with those pathways preferentially utilized by EGFRvIII. Genes were identified by microarray analysis that were specifically expressed at higher levels in the escapers. These genes represent candidates for involvement in the process of overcoming EGFRvIII-dependence and, thus, may also contribute to resistance to EGFR inhibition. Significantly, escaper cells that reexpressed EGFRvIII were resistant to the in vitro growth- inhibitory effects of the TKI gefitinib as measured by colony formation in soft agar. Thus, the emergence of EGFRvIII-independent tumor growth-promoting mechanisms in escapers is characterized by a switch in pathway signaling preferences and upregulation of novel genes, and confers resistance to EGFR inhibition. The genes and pathways identified may shed light on novel mechanisms of TKI resistance and point towards potential targets for the development of agents that could be used in combination with TKIs to circumvent resistance while improving clinical response.

Citation Information: Clin Cancer Res 2010;16(14 Suppl):PR6.
Calciolangbeinite, K2Ca2(SO4)3, a new mineral from the Tolbachik volcano, Kamchatka, Russia
Authors: Pekov I. V. , Zelenski M. E. , Zubkova N. V. , Yapaskurt V. O. , Chukanov N. V. , Belakovskiy D. I. , Pushcharovsky D. Y.
Published: July 2012

The new mineral calciolangbeinite, ideally K2Ca2(SO4)3, is the Ca-dominant analogue of langbeinite. It occurs in sublimates at the Yadovitaya fumarole on the Second scoria cone of the Northern Breakthrough of the Great Tolbachik Fissure eruption, Tolbachik volcano, Kamchatka, Russia. The mineral is associated with langbeinite, piypite, hematite, rutile, pseudobrookite, orthoclase, lyonsite, lammerite, cyanochroite and chlorothionite. Calciolangbeinite occurs as tetrahedral to pseudooctahedral crystals, which are bounded by {111} and {11}, and as anhedral grains up to 1 mm in size, aggregated into clusters up to 2 mm across, and forming crusts covering areas of up to 1.5x1.5 cm on the surface of volcanic scoria. Late-stage calciolangbeinite occurs in complex epitaxial intergrowths with langbeinite. Calciolangbeinite is transparent and colourless with white streak and vitreous lustre. Its Mohs' hardness is 3–3½. It is brittle, has a conchoidal fracture and no obvious cleavage. The measured and calculated densities are Dmeas = 2.68(2) and Dcalc = 2.74 g cm–3, respectively. Calciolangbeinite is optically isotropic with n = 1.527(2). The chemical composition of the holotype specimen is Na2O 0.38, K2O 21.85, MgO 6.52, CaO 16.00, MnO 0.27, FeO 0.08, Al2O3 0.09, SO3 55.14, total 100.63 wt.%. The empirical formula, calculated on the basis of twelve oxygen atoms per formula unit, is K2.01(Ca1.24Mg0.70Na0.05Mn0.02Fe0.01Al0.01)S 2.03S3.00O12. Calciolangbeinite is cubic, space group P213, a = 10.1887(4) Å, V = 1057.68(4) Å3 and Z = 4. The strongest reflections in the X-ray powder pattern [listed as (d, Å (I)(hkl)] are 5.84(8)(111); 4.54(9)(120); 4.15(27)(211); 3.218 (100) (310, 130); 2.838 (8) (230, 320), 2.736 (37) (231, 321), 2.006 (11) (431, 341) , 1.658(8)(611,532,352). The crystal structure was refined from single-crystal X-ray diffraction data to R = 0.0447. The structure is based on the langbeinite-type three-dimensional complex framework, which is made up of (Ca,Mg)O6 octahedra (Ca and Mg are disordered) and SO4 tetrahedra. Potassium atoms occupy two sites in voids in the framework; K(1) cations are located in ninefold polyhedra whereas K(2) cations are sited in significantly distorted octahedra. Calciolangbeinite and langbeinite are isostructural and form a solid-solution series.
Computational identification and analysis of novel sugarcane microRNAs
Authors: Thiebaut Flávia , Grativol Clícia , Carnavale-Bottino Mariana , Rojas Cristian Antonio , Tanurdzic Milos , Farinelli Laurent , Martienssen Robert A , Hemerly Adriana Silva , Ferreira Paulo Cavalcanti Gomes
Published: July 2012

Background

MicroRNA-regulation of gene expression plays a key role in the development and response to biotic and abiotic stresses. Deep sequencing analyses accelerate the process of small RNA discovery in many plants and expand our understanding of miRNA-regulated processes. We therefore undertook small RNA sequencing of sugarcane miRNAs in order to understand their complexity and to explore their role in sugarcane biology.

Results

A bioinformatics search was carried out to discover novel miRNAs that can be regulated in sugarcane plants submitted to drought and salt stresses, and under pathogen infection. By means of the presence of miRNA precursors in the related sorghum genome, we identified 623 candidates of new mature miRNAs in sugarcane. Of these, 44 were classified as high confidence miRNAs. The biological function of the new miRNAs candidates was assessed by analyzing their putative targets. The set of bona fide sugarcane miRNA includes those likely targeting serine/threonine kinases, Myb and zinc finger proteins. Additionally, a MADS-box transcription factor and an RPP2B protein, which act in development and disease resistant processes, could be regulated by cleavage (21-nt-species) and DNA methylation (24-nt-species), respectively.

Conclusions

A large scale investigation of sRNA in sugarcane using a computational approach has identified a substantial number of new miRNAs and provides detailed genotype-tissue-culture miRNA expression profiles. Comparative analysis between monocots was valuable to clarify aspects about conservation of miRNA and their targets in a plant whose genome has not yet been sequenced. Our findings contribute to knowledge of miRNA roles in regulatory pathways in the complex, polyploidy sugarcane genome.
Somato-dendritic morphology and dendritic signal transfer properties differentiate between fore- and hindlimb innervating motoneurons in the frog Rana esculenta
Authors: Stelescu András , Sümegi János , Wéber Ildikó , Birinyi András , Wolf Ervin
Published: June 2012

Background

The location specific motor pattern generation properties of the spinal cord along its rostro-caudal axis have been demonstrated. However, it is still unclear that these differences are due to the different spinal interneuronal networks underlying locomotions or there are also segmental differences in motoneurons innervating different limbs. Frogs use their fore- and hindlimbs differently during jumping and swimming. Therefore we hypothesized that limb innervating motoneurons, located in the cervical and lumbar spinal cord, are different in their morphology and dendritic signal transfer properties. The test of this hypothesis what we report here.

Results

Discriminant analysis classified segmental origin of the intracellularly labeled and three-dimensionally reconstructed motoneurons 100% correctly based on twelve morphological variables. Somata of lumbar motoneurons were rounder; the dendrites had bigger total length, more branches with higher branching orders and different spatial distributions of branch points. The ventro-medial extent of cervical dendrites was bigger than in lumbar motoneurons. Computational models of the motoneurons showed that dendritic signal transfer properties were also different in the two groups of motoneurons. Whether log attenuations were higher or lower in cervical than in lumbar motoneurons depended on the proximity of dendritic input to the soma. To investigate dendritic voltage and current transfer properties imposed by dendritic architecture rather than by neuronal size we used standardized distributions of transfer variables. We introduced a novel combination of cluster analysis and homogeneity indexes to quantify segmental segregation tendencies of motoneurons based on their dendritic transfer properties. A segregation tendency of cervical and lumbar motoneurons was detected by the rates of steady-state and transient voltage-amplitude transfers from dendrites to soma at all levels of synaptic background activities, modeled by varying the specific dendritic membrane resistance. On the other hand no segregation was observed by the steady-state current transfer except under high background activity.

Conclusions

We found size-dependent and size-independent differences in morphology and electrical structure of the limb moving motoneurons based on their spinal segmental location in frogs. Location specificity of locomotor networks is therefore partly due to segmental differences in motoneurons driving fore-, and hindlimbs.
Capsule endoscopy with flexible spectral imaging color enhancement reduces the bile pigment effect and improves the detectability of small bowel lesions
Authors: Sakai Eiji , Endo Hiroki , Kato Shingo , Matsuura Tetsuya , Tomeno Wataru , Taniguchi Leo , Uchiyama Takashi , Hata Yasuo , Yamada Eiji , Ohkubo Hidenori , Higrashi Takuma , Hosono Kunihiro , Takahashi Hirokazu , Nakajima Atsushi
Published: July 2012

Background

Capsule endoscopy with flexible spectral imaging color enhancement (CE-FICE) has been reported to improve the visualization and detection of small-bowel lesions, however, its clinical usefulness is still not established. Therefore, we conducted a study to evaluate whether CE-FICE contributes to improve the detectability of small-bowel lesions by CE trainees.

Methods

Four gastroenterology trainees without prior CE experience were asked to read and interpret 12 CE videos. Each of the videos was read by conventional visualization method and under three different FICE settings. To evaluate whether the lesion recognition ability of the CE trainees could be improved by the FICE technology, the lesion detection rate under each of the three FICE settings was compared with that by conventional CE. CE trainees tend to miss small-bowel lesions in bile-pigment-positive condition, therefore we evaluated whether CE-FICE contributes to reducing the bile-pigment effect. The bile-pigment condition was determined by the color values around the small-bowel lesions according to the results of the receiver-operating-characteristic analysis. Moreover, we also evaluated whether poor bowel preparion might affect the accuracy of lesion recognition by CE-FICE.

Results

Of a total of 60 angioectasias, CE trainees identified 26 by conventional CE, 40 under FICE setting 1, 38 under FICE setting 2, and 31 under FICE setting 3. Of a total of 82 erosions/ulcerations, CE trainees identified 38 by conventional CE, 62 under FICE setting 1, 60 under FICE setting 2, and 20 under FICE setting 3. Compared with conventional CE, FICE settings 1 and 2 significantly improved the detectability of angioectasia (P = 0.0017 and P = 0.014, respectively) and erosions/ulcerations (P = 0.0012 and P = 0.0094, respectively). Although the detectability of small-bowel lesions by conventional CE (P = 0.020) and under FICE setting 2 (P = 0.0023) was reduced by the presence of bile-pigments, that under FICE setting 1 was not affected (P = 0.59). Our results also revealed that in poor bowel visibility conditions, CE-FICE yielded a high rate of false-positive findings.

Conclusions

CE-FICE may reduce the bile-pigment effect and improve the detectability of small-bowel lesions by CE trainees; the reliability of CE-FICE may be improved by good bowel preparation.
Acute and acute-on-chronic kidney injury of patients with decompensated heart failure: impact on outcomes
Authors: Zhou Qiugen , Zhao Chunmei , Xie Di , Xu Dingli , Bin Jianping , Chen Pingyan , Liang Min , Zhang Xun , Hou Fanfan
Published: July 2012

Background

Acute worsening of renal function, an independent risk factor for adverse outcomes in acute decompensated heart failure (ADHF), occurs as a consequence of new onset kidney injury (AKI) or acute deterioration of pre-existed chronic kidney disease (CKD) (acute-on-chronic kidney injury, ACKI). However, the possible difference in prognostic implication between AKI and ACKI has not been well established.

Methods

We studied all consecutive patients hospitalized with ADHF from 2003 through 2010 in Nanfang Hospital. We classified patients as with or without pre-existed CKD based on the mean estimated glomerular filtration rate (eGFR) over a six-month period before hospitalization. AKI and ACKI were defined by RIFLE criteria according to the increase of the index serum creatinine.

Results

A total of 1,005 patients were enrolled. The incidence of ACKI was higher than that of AKI. The proportion of patients with diuretic resistance was higher among patients with pre-existed CKD than among those without CKD (16.9% vs. 9.9%, P = 0.002). Compared with AKI, ACKI was associated with higher risk for in-hospital mortality, long hospital stay, and failure in renal function recovery. Pre-existed CKD and development of acute worsening of renal function during hospitalization were the independent risk factors for in-hospital death after adjustment by the other risk factors. The RIFLE classification predicted all-cause and cardiac mortality in both AKI and ACKI.

Conclusions

Patients with ACKI were at greatest risk of adverse short-term outcomes in ADHF. Monitoring eGFR and identifying CKD should not be ignored in patients with cardiovascular disease.
Retrospective analysis of changes in the anterior corneal surface after Q value guided LASIK and LASEK in high myopic astigmatism for 3 years
Authors: Huang Hui , Yang Jianguo , Bao Huijing , Chen Shaorong , Xia Beibei , Zou Jun
Published: June 2012

Background

To compare the corneal high-order aberrations (HOAs), asphericity and regularity after Q-value guided laser in situ keratomileusis (LASIK) and laser epithelial keratomileusis (LASEK) in high myopic astigmatism.

Methods

In this retrospectively comparative study, we measured the corneal HOAs, asphericity indices (Q values) and corneal regularity indices preoperatively and 36 months postoperatively in 70 eyes (35 patients) with Q-value guided surgeries. All the patients with high myopic astigmatism were divided into two groups which included 34 eyes underwent LASIK and 36 eyes underwent LASEK procedures. The main impact factors of the high-order aberrations were also analyzed.

Results

In the two groups, the efficacy index was more than 1.00 and safety index approached 1.00 at year 3 postoperatively. Statistically significant (P < 0.05) increased in Q values and main corneal HOAs (spherical aberrations and coma) following Q-value guided LASIK and LASEK procedures. Spherical aberrations increased more in the LASEK group and there was statistically difference compared to the LASIK group (P < 0.05). LASEK had better effects in correcting corneal astigmatism (P < 0.05). All the corneal regularity indices after surgeries increased and there was no significant difference (P = 0.707, P = 0.8 and P = 0.224, respectively) between the two groups. The main impact factors of spherical aberration included the optic zone size, changes of Q value, surgical procedure and the corrected refraction.

Conclusions

In high myopic astigmatism, Q-value guided ablation showed good safety, efficacy and predictability. Q value, regularity indices, spherical aberration and coma increased in both LASIK and LASEK procedures. Astigmatism could be corrected more effectively by LASEK but greater spherical aberration could be created. The difference might be related to the different healing mechanisms. Optic zone size and the corrected refraction might be the main influence factors on the anterior corneal high order aberrations.
Effect of communicating genetic and phenotypic risk for type 2 diabetes in combination with lifestyle advice on objectively measured physical activity: protocol of a randomised controlled trial
Authors: Godino Job G , van Sluijs Esther MF , Marteau Theresa M , Sutton Stephen , Sharp Stephen J , Griffin Simon J
Published: June 2012

Background

Type 2 diabetes (T2D) is associated with increased risk of morbidity and premature mortality. Among those at high risk, incidence can be halved through healthy changes in behaviour. Information about genetic and phenotypic risk of T2D is now widely available. Whether such information motivates behaviour change is unknown. We aim to assess the effects of communicating genetic and phenotypic risk of T2D on risk-reducing health behaviours, anxiety, and other cognitive and emotional theory-based antecedents of behaviour change.

Methods

In a parallel group, open randomised controlled trial, approximately 580 adults born between 1950 and 1975 will be recruited from the on-going population-based, observational Fenland Study (Cambridgeshire, UK). Eligible participants will have undergone clinical, anthropometric, and psychosocial measurements, been genotyped for 23 single-nucleotide polymorphisms associated with T2D, and worn a combined heart rate monitor and accelerometer (Actiheart®) continuously for six days and nights to assess physical activity. Participants are randomised to receive either standard lifestyle advice alone (control group), or in combination with a genetic or a phenotypic risk estimate for T2D (intervention groups). The primary outcome is objectively measured physical activity. Secondary outcomes include self-reported diet, self-reported weight, intention to be physically active and to engage in a healthy diet, anxiety, diabetes-related worry, self-rated health, and other cognitive and emotional outcomes. Follow-up occurs eight weeks post-intervention. Values at follow-up, adjusted for baseline, will be compared between randomised groups.

Discussion

This study will provide much needed evidence on the effects of providing information about the genetic and phenotypic risk of T2D. Importantly, it will be among the first to examine the impact of genetic risk information using a randomised controlled trial design, a population-based sample, and an objectively measured behavioural outcome. Results of this trial, along with recent evidence syntheses of similar studies, should inform policy concerning the availability and use of genetic risk information.

Trial registration

Current Controlled Trials ISRCTN09650496
An intervention program with the aim to improve and maintain work productivity for workers with rheumatoid arthritis: design of a randomized controlled trial and cost-effectiveness study
Authors: Vilsteren Myrthe van , Boot Cécile RL , Steenbeek Romy , Schaardenburg Dirkjan van , Voskuyl Alexandre E , Anema Johannes R
Published: July 2012

Background

Workers with rheumatoid arthritis (RA) often experience restrictions in functioning at work and participation in employment. Strategies to maintain work productivity exist, but these interventions do not involve the actual workplace. Therefore the aim of this study is to investigate the (cost)effectiveness of an intervention program at the workplace on work productivity for workers with RA.

Methods/design

This study is a randomized controlled trial (RCT) in specialized rheumatology treatment centers in or near Amsterdam, the Netherlands. Randomisation to either the control or the intervention group is performed at patient level. Both groups will receive care as usual by the rheumatologist, and patients in the intervention group will also take part in the intervention program. The intervention program consists of two components; integrated care, including a participatory workplace intervention. Integrated care involves a clinical occupational physician, who will act as care manager, to coordinate the care. The care manager has an intermediate role between clinical and occupational care. The participatory workplace intervention will be guided by an occupational therapist, and involves problem solving by the patient and the patients’ supervisor. The aim of the workplace intervention is to achieve consensus between patient and supervisor concerning feasible solutions for the obstacles for functioning at work. Data collection will take place at baseline and after 6 and 12 months by means of a questionnaire. The primary outcome measure is work productivity, measured by hours lost from work due to presenteeism. Secondary outcome measures include sick leave, quality of life, pain and fatigue. Cost-effectiveness of the intervention program will be evaluated from the societal perspective.

Discussion

Usual care of primary and outpatient health services is not aimed at improving work productivity. Therefore it is desirable to develop interventions aimed at improving functioning at work. If the intervention program will be (cost)effective, substantial improvements in work productivity might be obtained among workers with RA at lower costs. Results are expected in 2015.

Trial registration number

NTR2886
Decolorization of a recalcitrant organic compound (Melanoidin) by a novel thermotolerant yeast, Candida tropicalis RG-9
Authors: Tiwari Soni , Gaur Rajeeva , Singh Ranjan
Published: June 2012

Background

Sugarcane distilleries use molasses for ethanol production and generate large volume of effluent containing high biological oxygen demand (BOD) and chemical oxygen demand (COD) along with melanoidin pigment. Melanoidin is a recalcitrant compound that causes several toxic effects on living system, therefore, may be treated before disposal. The aim of this study was to isolate a potential thermotolerant melanoidin decolorizing yeast from natural resources, and optimized different physico-chemical and nutritional parameters.

Results

Total 24 yeasts were isolated from the soil samples of near by distillery site, in which isolate Y-9 showed maximum decolorization and identified as Candida tropicalis by Microbial Type Culture Collection (MTCC) Chandigarh, India. The decolorization yield was expressed as the decrease in the absorbance at 475 nm against initial absorbance at the same wavelength. Uninoculated medium served as control. Yeast showed maximum decolorization (75%) at 45°C using 0.2%, glucose; 0.2%, peptone; 0.05%, MgSO4; 0.01%, KH2PO4; pH-5.5 within 24 h of incubation under static condition. Decolorizing ability of yeast was also confirmed by high performance liquid chromatography (HPLC) analysis.

Conclusion

The yeast strain efficiently decolorized melanoidin pigment of distillery effluent at higher temperature than the other earlier reported strains of yeast, therefore, this strain could also be used at industrial level for melanoidin decolorization as it tolerated a wide range of temperature and pH with very small amount of carbon and nitrogen sources.
The inclusion of a partial meal replacement with or without inulin to a calorie restricted diet contributes to reach recommended intakes of micronutrients and decrease plasma triglycerides: A randomized clinical trial in obese Mexican women.
Authors: Tovar Alma Rosa , Caamaño María del Carmen , Garcia-Padilla Sandra , García Olga Patricia , Duarte Miguel Angel , Rosado Jorge L
Published: June 2012

Background

Obesity is a major public health problem in many poor countries where micronutrient deficiencies are prevalent. A partial meal replacement may be an effective strategy to decrease obesity and increase micronutrient intake in such populations. The objective was to evaluate the efficacy of a partial meal replacement with and without inulin on weight reduction, blood lipids and micronutrients intake in obese Mexican women.

Methods

In a randomized controlled clinical trial 144 women (18–50 y) with BMI ≥ 25 kg/m2, were allocated into one of the following treatments during 3 months: 1) Two doses/d of a partial meal replacement (PMR), 2) Two doses/d of PMR with inulin (PMR + I) , 3) Two doses/d of 5 g of inulin (INU) and 4) Control group (CON). All groups received a low calorie diet (LCD). Weight, height, hip and waist circumference were measured every 2 weeks and body composition, lipids and glucose concentration and nutrient intake were assessed at baseline and after 3 months.

Results

All groups significantly reduced weight, BMI, waist and hip circumference. Differences between groups were only observed in BMI and weight adjusted changes: At 45 days PMR group lost more weight than INU and CON groups by 0.9 and 1.2Kg, respectively. At 60 days, PMR + I and PMR groups lost more weight than in INU by 0.7 and 1Kg, respectively. Subjects in PMR, PMR + I and INU significantly decreased triglycerides. Energy intake was reduced in all groups. Fiber intake increased in PMR + I and INU groups. Some minerals and vitamins intakes were higher in PMR and PMR + I compared with INU and CON groups.

Conclusion

Inclusion of PMR with and without inulin to a LCD had no additional effect on weight reduction than a LCD alone but reduced triglycerides and improved intake of micronutrients during caloric restriction. PMR could be a good alternative for obese populations with micronutrient deficiencies.

ClinicalTrials.Gov ID

NCT01505023
Biomechanical evaluation of three surgical scenarios of posterior lumbar interbody fusion by finite element analysis
Authors: Xiao Zhitao , Wang Liya , Gong He , Zhu Dong
Published: June 2012

Background

For the treatment of low back pain, the following three scenarios of posterior lumbar interbody fusion (PLIF) were usually used, i.e., PLIF procedure with autogenous iliac bone (PAIB model), PLIF with cages made of PEEK (PCP model) or titanium (Ti) (PCT model) materiel. But the benefits or adverse effects among the three surgical scenarios were still not fully understood.

Method

Finite element analysis (FEA), as an efficient tool for the analysis of lumbar diseases, was used to establish a three-dimensional nonlinear L1-S1 FE model (intact model) with the ligaments of solid elements. Then it was modified to simulate the three scenarios of PLIF. 10 Nm moments with 400 N preload were applied to the upper L1 vertebral body under the loading conditions of extension, flexion, lateral bending and torsion, respectively.

Results

Different mechanical parameters were calculated to evaluate the differences among the three surgical models. The lowest stresses on the bone grafts and the greatest stresses on endplate were found in the PCT model. The PCP model obtained considerable stresses on the bone grafts and less stresses on ligaments. But the changes of stresses on the adjacent discs and endplate were minimal in the PAIB model.

Conclusions

The PCT model was inferior to the other two models. Both the PCP and PAIB models had their own relative merits. The findings provide theoretical basis for the choice of a suitable surgical scenario for different patients.
Different cellular response mechanisms contribute to the length-dependent cytotoxicity of multi-walled carbon nanotubes
Authors: Liu Dun , Wang Lijun , Wang Zhigang , Cuschieri Alfred
Published: July 2012

To date, there has not been an agreement on the best methods for the characterisation of multi-walled carbon nanotube (MWCNT) toxicity. The length of MWCNTs has been identified as a factor in in vitro and in vivo studies, in addition to their purity and biocompatible coating. Another unresolved issue relates to the variable toxicity of MWCNTs on different cell types. The present study addressed the effects of MWCNTs' length on mammalian immune and epithelial cancer cells RAW264.7 and MCF-7, respectively. Our data confirm that MWCNTs induce cytotoxicity in a length- and cell type-dependent manner. Whereas, longer (3 to 14 μm) MWCNTs exert high toxicity, especially to RAW264.7 cells, shorter (1.5 μm) MWCNTs are significantly less cytotoxic. These findings confirm that the degree of biocompatibility of MWCNTs is closely related to their length and that immune cells appear to be more susceptible to damage by MWCNTs. Our study also indicates that MWCNT nanotoxicity should be analysed for various components of cellular response, and cytotoxicity data should be validated by the use of more than one assay system. Results from chromogenic-based assays should be confirmed by trypan blue exclusion.
Co-infection of broilers with Ornithobacterium rhinotracheale and H9N2 avian influenza virus
Authors: Pan Qing , Liu Aijing , Zhang Faming , Ling Yong , Ou Changbo , Hou Na , He Cheng
Published: July 2012

Background

Since 2008, a progressive pneumonia has become prevalent in broilers and laying hens. This disease occurrs the first day after hatching and lasts more than 30 days, resulting in approximately 70% morbidity and 30% mortality in broilers. The objective of this study was to isolate and identify the pathogens that are responsible for the progressive pneumonia and establish an animal model for drug screening.

Results

193 serum samples were collected from 8 intensive farms from 5 provinces in China and analysed in the current research. Our clinical survey showed that 65.2% to 100% of breeding broilers, breeding layers, broilers and laying hens were seropositive for ORT antibodies. From 8 intensive farms, six ORT isolates were identified by PCR and biochemical assays, and two H9N2 viruses were isolated. Newcastle Disease Virus (NDV) and Infectious BronchitisVirus (IBV) were excluded. Typical pneumonia and airsacculitis were observed both in broilers inoculated intraperitoneally with an ORT isolate alone and in those co-infected with ORT and H9N2 virus isolates. Specifically, the survival rate was 30%, 20%, 70%, 50% and 90% in birds inoculated with ORT+H9N2 virus, ORT followed by H9N2 virus, H9N2 virus followed by ORT, and ORT or H9N2 virus alone, respectively.

Conclusions

The results of this study suggest that ORT infections of domestic poultry have been occurring frequently in China. ORT infection can induce higher economic losses and mortality if H9N2 AIV is also present. Although the isolation of ORT and H9N2 virus has been reported previously, there have been no reported co-infections of poultry with these two pathogens. This is the first report of co-infection of broilers with ORT and H9N2 virus, and this co-infection is probably associated with the outbreak of broiler airsacculitis in China, which has caused extensive economic losses.
Oxidative stress inhibits axonal transport: implications for neurodegenerative diseases
Authors: Fang Cheng , Bourdette Dennis , Banker Gary
Published: June 2012

Background

Reactive oxygen species (ROS) released by microglia and other inflammatory cells can cause axonal degeneration. A reduction in axonal transport has also been implicated as a cause of axonal dystrophies and neurodegeneration, but there is a paucity of experimental data concerning the effects of ROS on axonal transport. We used live cell imaging to examine the effects of hydrogen peroxide on the axonal transport of mitochondria and Golgi-derived vesicles in cultured rat hippocampal neurons.

Results

Hydrogen peroxide rapidly inhibited axonal transport, hours before any detectable changes in mitochondrial morphology or signs of axonal degeneration. Mitochondrial transport was affected earlier and was more severely inhibited than the transport of Golgi-derived vesicles. Anterograde vesicle transport was more susceptible to peroxide inhibition than retrograde transport. Axonal transport partially recovered following removal of hydrogen peroxide and local application of hydrogen peroxide inhibited transport, suggesting that the effects were not simply a result of nerve cell death. Sodium azide, an ATP synthesis blocker, had similar effects on axonal transport, suggesting that ATP depletion may contribute to the transport inhibition due to hydrogen peroxide.

Conclusions

These results indicate that inhibition of axonal transport is an early consequence of exposure to ROS and may contribute to subsequent axonal degeneration.
Sorting nexin 12 interacts with BACE1 and regulates BACE1-mediated APP processing
Authors: Zhao Yonghao , Wang Yunshu , Yang Jiaye , Wang Xin , Zhao Yingjun , Zhang Xian , Zhang Yun-wu
Published: June 2012

Background

β-site APP cleaving enzyme 1 (BACE1) cleaves β-amyloid precursor protein (APP) to initiate the production of β-amyloid (Aβ), the prime culprit in Alzheimer’s disease (AD). Dysregulation of the intracellular trafficking of BACE1 may affect Aβ generation, contributing to AD pathology. In this study, we investigated whether BACE1 trafficking and BACE1-mediated APP processing/Aβ generation are affected by sorting nexin 12 (SNX12), a member of the sorting nexin (SNX) family that is involved in protein trafficking regulation.

Results

Herein, we find that SNX12 is widely expressed in brain tissues and is mainly localized in the early endosomes. Overexpression of SNX12 does not affect the steady-state levels of APP, BACE1 or γ-secretase components, but dramatically reduces the levels of Aβ, soluble APPβ and APP β-carboxyl terminal fragments. Downregulation of SNX12 has the opposite effects. Modulation of SNX12 levels does not affect γ-secretase activity or in vitro β-secretase activity. Further studies reveal that SNX12 interacts with BACE1 and downregulation of SNX12 accelerates BACE1 endocytosis and decreases steady-state level of cell surface BACE1. Finally, we find that the SNX12 protein level is dramatically decreased in the brain of AD patients as compared to that of controls.

Conclusion

This study demonstrates that SNX12 can regulate the endocytosis of BACE1 through their interaction, thereby affecting β-processing of APP for Aβ production. The reduced level of SNX12 in AD brains suggests that an alteration of SNX12 may contribute to AD pathology. Therefore, inhibition of BACE1-mediated β-processing of APP by regulating SNX12 might serve as an alternative strategy in developing an AD intervention.
Does diagnostic delay of colorectal cancer result in malpractice claims? A retrospective analysis of the Swedish board of malpractice from 1995–2008
Authors: Hafström Larsolof , Johansson Henry , Ahlberg Jon
Published: June 2012

Aim

Delay in the diagnosis of colorectal cancer (CRC) may have important clinical and medico-legal implications. This study identifies the claims made on the basis of delay in the diagnosis of CRC to the Swedish insurance agency (whose English name is The County Council´s Mutual Insurance Company) and the impact and consequences of the delay on prognosis, treatment and survival for patients who reported the claims. The Company handles claims of medical malpractice where claimants seek compensation for alleged suffering and/or negative clinical impacts of diagnostic delays.

Material and methods

Between January 1, 1995 and December 31, 2008, a total of 80 patients filed claims for negative effects resulting from delays in the diagnosis of CRC. Review of the claims led to identification of delay for 62 patients. The clinical symptoms that were overlooked and other causes of delay that had any relation to therapy, prognosis and economic compensation were evaluated.

Results

The median delay in the diagnosis of CRC was six months. This delay was considered to have had an impact on the therapy in 20 % of the cases. The prognosis was postulated to have been adversely affected for 15 % of the patients. The delay was mainly caused by incomplete consideration of the symptoms hematoschisis or anaemia, changed bowel routine, or incomplete clinical or radiological examination and by misinterpretations of the results. No impact of duration of delay on survival was identified. The importance of identifying concomitant metastatic disease at diagnosis was overwhelming. Economic compensation was given in 79 % of the cases.

Conclusion

This study found that claims for compensation for delay in diagnosis of CRC are rare. The delay in the diagnosis of the primary tumour was considered to have had an impact on the magnitude of therapeutic measures for a fifth of the patients who filed claims. Economic compensation for the patients´ injuries was given in almost 80 % of the cases.
Effects of group metacognitive training (MCT) on mental capacity and functioning in patients with psychosis in a secure forensic psychiatric hospital: a prospective-cohort waiting list controlled study
Authors: Naughton Marie , Nulty Andrea , Abidin Zareena , Davoren Mary , O’Dwyer Sarah , Kennedy Harry G
Published: June 2012

Background

Metacognitive Training (MCT) is a manualised cognitive intervention for psychosis aimed at transferring knowledge of cognitive biases and providing corrective experiences. The aim of MCT is to facilitate symptom reduction and protect against relapse. In a naturalistic audit of clinical effectiveness we examined what effect group MCT has on mental capacity, symptoms of psychosis and global function in patients with a psychotic illness, when compared with a waiting list comparison group.

Methods

Of 93 patients detained in a forensic mental health hospital under both forensic and civil mental health legislation, 19 were assessed as suitable for MCT and 11 commenced. These were compared with 8 waiting list patients also deemed suitable for group MCT who did not receive it in the study timeframe. The PANSS, GAF, MacArthur Competence Assessment Tool- Treatment (MacCAT-T) and MacArthur Competence Assessment Tool-Fitness to Plead (MacCAT-FP) were recorded at baseline and repeated after group MCT or following treatment as usual in the waiting list group.

Results

When baseline functioning was accounted for, patients that attended MCT improved in capacity to consent to treatment as assessed by the MacCAT-T (p = 0.019). The more sessions attended, the greater the improvements in capacity to consent to treatment, mainly due to improvement in MacCAT-T understanding (p = 0.014) and reasoning . The GAF score improved in patients who attended the MCT group when compared to the waiting list group (p = 0.038) but there were no changes in PANSS scores.

Conclusion

Measures of functional mental capacity and global function can be used as outcome measures for MCT. MCT can be used successfully even in psychotic patients detained in a forensic setting. The restoration of elements of decision making capacity such as understanding and reasoning may be a hither-to unrecognised advantage of such treatment. Because pharmacotherapy can be optimised and there is likely to be enough time to complete the course, there are clear opportunities to benefit from such treatment programmes in forensic settings.
Biomechanical comparison between single-bundle and double-bundle anterior cruciate ligament reconstruction with hamstring tendon under cyclic loading condition
Authors: Nohmi Shuya , Ishibashi Yasuyuki , Tsuda Eiichi , Yamamoto Yuji , Tsukada Harehiko , Toh Satoshi
Published: July 2012

Purpose

The purpose of this study was to compare the anterior tibial translation (ATT) of the anterior cruciate ligament (ACL) reconstructed-knee between single-bundle and double-bundle ACL reconstruction under cyclic loading.

Methods

Single-bundle and double-bundle reconstructions of the knee were performed sequentially in randomized order on the same side using eight human amputated knees. After each reconstruction, the reconstructed-knee was subjected to 500-cycles of 0 to 100-N anterior tibial loads using a material testing machine. The ATT before and after cyclic loading and “laxity increase”, which indicated a permanent elongation of the graft construct, was also determined.

Results

The ATT after cyclic loading increased in both single-bundle and double-bundle reconstruction techniques compared to that without cyclic loading. Changes in ATT before and after cyclic loading were 3.9 ± 0.9 mm and 2.9 ± 0.6 mm respectively, and were significantly different. Laxity increase was also significantly different (4.3 ± 0.9 mm and 3.2 ± 0.8 mm respectively). Although no graft rupture or graft fixation failure was found during cyclic loading, the graft deviated into an eccentric position within the tunnel.

Conclusions

Although ATT was significantly increased in both single-bundle and double-bundle reconstruction with hamstring tendon after cyclic loading test, there was significant difference. Double-bundle reconstruction might be superior to prevent increasing ATT under cyclic loading. Deformation of hamstring tendon after cyclic loading might result in deterioration of knee stability after ACL reconstruction, and is one of disadvantages of soft tissue graft.
Current management and prognostic features for gastrointestinal stromal tumor (GIST)
Authors: Lamba Gurpreet , Gupta Ridhi , Lee Byung , Ambrale Samir , Liu Delong
Published: June 2012

Stromal or mesenchymal neoplasms affecting the gastrointestinal (GI) tract have undergone a remarkable evolution in how they are perceived, classified, approached, diagnosed and managed over the last 30 years. Gastrointestinal stromal tumors (GIST) account for approximately 1% to 3% of all malignant GI tumors. The clinical features can vary depending on the anatomic location, size and aggressiveness of the tumor. Metastatic GIST represents a successful example of molecular targeted therapy. In this comprehensive review, we discuss the epidemiology, clinical features and diagnostic modalities for GIST. We also describe treatment options for early stage, locally advanced and metastatic GIST. Indications for neoadjuvant and adjuvant therapy along with duration of therapy are also explained. A brief discussion of latest biomarkers and updates from recent meetings is also provided.
On the discrete dipole approximation investigation of the extinction spectra of Ag/glass nano-flower thin film with threefold symmetry
Authors: Abdi Fatemeh , Siabi-Gerjan Araz , Savaloni Hadi
Published: July 2012

The use of glancing angle deposition technique provides opportunities for the deposition of sculptured nanostructures of different shape. The optical properties of such nanostructures that are a function of the shape of these nanostructures may be investigated, using the discrete dipole approximation theory which is an appropriate method for solving the light scattering problem from objects of different shape and geometry. In this paper, the extinction spectra of Ag/glass-sculptured nano-flowers with threefold symmetry are modeled and calculated, while the results are compared with similar experimental observations. In modeling the nano-flower-shaped sculptured thin films, it is proposed that the nano-flower is formed as a combination of two chiral thin films with different dimensions. This structure was replaced with 1,405 electrical dipoles, and its extinction spectrum was calculated as a function of incident light angle and azimuthal angle. The extinction spectrum consists of both transverse and longitudinal modes of oscillations. The results showed that by increasing the incident angle, due to increase of amplitude of electrical oscillations, transverse oscillations shift towards longer wavelengths. It was also observed that at azimuthal angles close to nano-flower petals, where sharp points or recesses may exist, the intensity of extinction spectrum for longitudinal mode (long wavelengths in the extinction spectrum) increases.
E2F mediates enhanced alternative polyadenylation in proliferation
Authors: Elkon Ran , Drost Jarno , van Haaften Gijs , Jenal Mathias , Schrier Mariette , Oude Vrielink Joachim AF , Agami Reuven
Published: July 2012

Background

The majority of mammalian genes contain multiple poly(A) sites in their 3' UTRs. Alternative cleavage and polyadenylation are emerging as an important layer of gene regulation as they generate transcript isoforms that differ in their 3' UTRs, thereby modulating genes' response to 3' UTR-mediated regulation. Enhanced cleavage at 3' UTR proximal poly(A) sites resulting in global 3' UTR shortening was recently linked to proliferation and cancer. However, mechanisms that regulate this enhanced alternative polyadenylation are unknown.

Results

Here, we explored, on a transcriptome-wide scale, alternative polyadenylation events associated with cellular proliferation and neoplastic transformation. We applied a deep-sequencing technique for identification and quantification of poly(A) sites to two human cellular models, each examined under proliferative, arrested and transformed states. In both cell systems we observed global 3' UTR shortening associated with proliferation, a link that was markedly stronger than the association with transformation. Furthermore, we found that proliferation is also associated with enhanced cleavage at intronic poly(A) sites. Last, we found that the expression level of the set of genes that encode for 3'-end processing proteins is globally elevated in proliferation, and that E2F transcription factors contribute to this regulation.

Conclusions

Our results comprehensively identify alternative polyadenylation events associated with cellular proliferation and transformation, and demonstrate that the enhanced alternative polyadenylation in proliferative conditions results not only in global 3' UTR shortening but also in enhanced premature cleavage in introns. Our results also indicate that E2F-mediated co-transcriptional regulation of 3'-end processing genes is one of the mechanisms that links enhanced alternative polyadenylation to proliferation.
Effects of fluid changes on seismic reflections: Predicting amplitudes at gas reservoir directly from amplitudes at wet reservoir
Authors: Li Jingye , Dvorkin Jack
Published: June 2012

The equations for fluid substitution in a sample with known porosity and the mineral’s and pore-fluid’s elastic moduli are well-documented. Discussions continue on how to conduct fluid substitution in practical situations where more than one fluid phase is present and the porosity and mineralogy are not precisely defined. We pose a different question: If we agree on a fluid substitution method, and also agree that at partial saturation the bulk modulus of the “effective” pore fluid is the harmonic average of those of the components, can we conduct fluid substitution directly on the seismic reflection amplitude? To address this question, we conducted forward modeling synthetic exercises: We systematically varied the porosity, clay content, and thickness of the reservoir and assumed that the properties of the bounding shale are fixed. Next, we used a velocity-porosity model to compute the elastic properties of the dry-rock frame and applied Gassmann’s equation to compute these properties in wet rock as well as at partial gas saturation. After that, we generated prestack synthetic seismic reflections at the top of the reservoir at full saturation and at partial saturation, and related one to the other. We found that within our assumption framework, there is an almost linear relation between the intercepts of the P-to-P reflectivity for the wet and gas reservoir. The same is true for the gradients. We have provided best-linear-fit equations that summarize these results. We applied this technique to field data and found that we can approximately predict the seismic amplitude at a gas reservoir from that measured at a wet reservoir, given that all other properties of the rock remain fixed. The solution given here should be treated as a method, meaning it should be tested and modified for various rock types and textures.