bluuebunny/crossref_metadata_2025 huggingface dataset:
Recent Advances in Research of HIV Infection: Implications of Viral and Host Genetics on Treatment and Prevention
Authors: Haaland R.E. , Johnson J.A. , Tang J.
Published: March 2013

The genetic diversity among human immunodeficiency virus (HIV) subtypes as well as the variability of viral sequences found in HIV-infected individuals presents a number of difficult obstacles for the development of universally effective HIV treatment and prevention methods. Here, we present a brief summary of recent developments in the analysis of viral genetics and human genomics to provide insight into future methods for HIV treatment and prevention. Recent studies have mined viral sequences found in newly infected individuals to identify common features of all transmitted viruses that could provide potential targets for HIV vaccine development. Analysis of human immunogenetics has identified specific alleles associated with reduced virus loads in HIV-infected individuals providing valuable information that may influence individual responses to treatment and prevention methods. Increased sensitivity of antiretroviral drug resistance testing has improved the detection of hidden drug resistant virus but also highlighted the potential for drug resistant viruses to reduce the effectiveness of clinical treatment regimens. The rapidly expanding amount of data generated by studies of viral genetics and human immunogenetics will provide valuable information to guide the design of new strategies to improve clinical treatment and enhance HIV vaccine development.
Phenotype and Secretory Responses to Oxidative Stress in Microglia
Authors: Pathipati Praneeti , Müller Sebastian , Jiang Xiangning , Ferriero Donna
Published: March 2013

The neonatal brain is particularly susceptible to oxidative stress. Our group has previously shown that following hypoxic-ischemic injury, hydrogen peroxide (H2O2) levels rise significantly particularly in the neonatal brain and are sustained for up to 7 days. This rapidly accumulated H2O2 is detrimental in the iron-rich immature brain as it can lead to the generation of dangerous free radicals that can cause extensive injury. To date, there is limited literature on the effects of increased H2O2 levels on microglial cells, which have been extensively implicated in the ensuing inflammatory injury. Microglial cultures were derived from the P1 mouse brain and exposed to either bolus concentrations of H2O2 (15 or 50 μM) or varying concentrations of continuous exposure for 4, 18 or 24 h. Continuous exposure of microglia to H2O2 was generated using the glucose oxidase-catalase system generating levels of H2O2 <10 μM. Reactive oxygen species and nitric oxide expression were measured. Conditioned medium was collected and analyzed for secreted cytokine levels. Treated cell extracts were processed for glutathione (oxidized and reduced) content and fixed cells were labeled for M1 and M2a phenotype markers. Overall, it is evident that microglial exposure to continuous H2O2 has pleiotropic and biphasic effects. Continuous exposure to very low levels of H2O2 is more damaging to cell survival than higher bolus doses at 18 h, and can produce considerably high levels of pro- and anti-inflammatory cytokines by 18 h. Significantly high levels of various chemokines/chemotactic molecules such as G-CSF, MIP-1b and MIP-2 are also produced in response to continuous low-dose H2O2 by 18 h. Interestingly, no prominent cytokine responses were seen with bolus treatment at any of the time points studied. H2O2 exposure promotes an M2a microglial phenotype in the absence of IL-4/IL-13 signaling, suggesting a wound-healing role for microglia and a delayed activation mechanism for H2O2 after such an insult. Together, these specific effects can be used to clarify the microglial cell responses following injury in the immature brain.
Genetic Variation in MAOA Modulates Prefrontal Cortical Regulation of Approach-Avoidance Reactions
Authors: Ernst Lena H. , Lutz Elisabeth , Ehlis Ann-Christine , Fallgatter Andreas J. , Reif Andreas , Plichta Michael M.
Published: March 2013

Background: Regulation of automatic approach and avoidance behavior requires affective and cognitive control, which are both influenced by a genetic variation in the gene encoding Monoamine Oxidase A (termed MAOA-uVNTR). Methods: The current study investigated MAOA genotype as a moderator of prefrontal cortical activation measured with functional near-infrared spectroscopy (fNIRS) in 37 healthy young adults during performance of the approach-avoidance task with positive and negative pictures. Results: Carriers of the low- compared to the high-expressing genetic variant (MAOA-L vs. MAOA-H) showed increasing regulatory activity in the right dorsolateral prefrontal cortex (DLPFC) during incompatible conditions (approach negative, avoid positive). This might have been a compensatory mechanism for stronger emotional reactions as shown in previous studies and might have prevented any influence of incompatibility on behavior. In contrast, fewer errors but also lower activity in the right DLPFC during processing of negative compared to positive stimuli indicated MAOA-H carriers to have used other regulatory areas. This resulted in slower reaction times in incompatible conditions, but - in line with the known better cognitive regulation efficiency - allowed them to perform incompatible reactions without activating the DLPFC as the highest control instance. Carriers of one low- and one high-expressing allele lay as an intermediate group between the reactions of the low- and high-expressing groups. Conclusions: The relatively small sample size and restriction to fNIRS for assessment of cortical activity limit our findings. Nevertheless, these first results suggest monoam-inergic mechanisms to contribute to interindividual differences in the two basic behavioral principles of approach and avoidance and their neuronal correlates.
Bitter Taste Perception and Dietary Intake Patterns in Irish Children
Authors: O'Brien Sinead A. , Feeney Emma L. , Scannell Amalia G.M. , Markey Anne , Gibney Eileen R.
Published: March 2013

Background/Aims: Variations in bitter receptor gene TAS2R38 affect the perception of bitter-tasting compound 6-n-propylthiouracil (PROP). The perception of PROP has been associated, in some reports, with the perception of fat and sweet tastes, and various food preferences and intakes. The aim was to investigate nutrient intakes and food patterns in a group of Irish children, using K-means cluster analysis, and compare these with TAS2R38 genotype and PROP taster status. Methods: Dietary intake was measured via a 3-day diet history in 483 children aged 7-13 years. Children were genotyped for TAS2R38 variation, and PROP taster status was assessed. Anthropometric and socioeconomic data were also obtained. Results: No differences were observed in macronutrient, micronutrient, or food group consumption between the TAS2R38 genotype and PROP taster groups. K-means cluster analysis identified two distinct dietary patterns, termed ‘more healthful' and ‘less healthful' clusters. The clusters did not differ in frequencies of TAS2R38 genotype nor PROP taster status groups, suggesting that dietary patterns are not influenced by bitter taste perception. Conclusion: Bitterness perception, as measured by either TAS2R38 genotype or PROP taster status, does not appear to exert a significant effect on patterns of dietary intakes.
Arterial Stiffness
Authors: Avolio Alberto
Published: March 2013

Stiffness of large arteries has been long recognized as a significant determinant of pulse pressure. However, it is only in recent decades, with the accumulation of longitudinal data from large and varied epidemiological studies of morbidity and mortality associated with cardiovascular disease, that it has emerged as an independent predictor of cardiovascular risk. This has generated substantial interest in investigations related to intrinsic causative and associated factors responsible for the alteration of mechanical properties of the arterial wall, with the aim to uncover specific pathways that could be interrogated to prevent or reverse arterial stiffening. Much has been written on the haemodynamic relevance of arterial stiffness in terms of the quantification of pulsatile relationships of blood pressure and flow in conduit arteries. Indeed, much of this early work regarded blood vessels as passive elastic conduits, with the endothelial layer considered as an inactive lining of the lumen and as an interface to flowing blood. However, recent advances in molecular biology and increased technological sophistication for the detection of low concentrations of biochemical compounds have elucidated the highly important regulatory role of the endothelial cell affecting vascular function. These techniques have enabled research into the interaction of the underlying passive mechanical properties of the arterial wall with the active cellular and molecular processes that regulate the local environment of the load-bearing components. This review addresses these emerging concepts.
Modulation of Shallow-Water Equatorial Waves due to a Varying Equivalent Height Background
Authors: Dias Juliana , Silva Dias Pedro L. , Kiladis George N. , Gehne Maria
Published: March 2013

The dynamics of convectively coupled equatorial waves (CCEWs) is analyzed in an idealized model of the large-scale atmospheric circulation. The model is composed of a linear rotating shallow-water system with a variable equivalent height, or equivalent gravity wave speed, which varies in space. This model is based on the hypothesis that moist convection acts to remove convective instability, therefore modulating the equivalent height of a shallow-water system. Asymptotic solutions are derived in the case of a small perturbation around a constant coefficient, which is assumed to be a mean moist equivalent height derived from satellite observations. The first-order solutions correspond to the free normal modes of the linear shallow-water system and the second-order flow is derived solving a perturbation eigenvalue problem. The asymptotic solutions are documented in the case of a zonally varying equivalent height and for wavenumbers and frequencies that are consistent with observations of CCEWs. This analysis shows that the dynamics of the secondary divergence and its impact on the full divergence varies mode by mode. For instance, for a negative equivalent height anomaly, which is interpreted as a moister background, the secondary divergence is nearly in phase with the primary divergence in the case of Kelvin waves—in contrast to mixed Rossby–gravity waves where the secondary divergence acts to attenuate the primary divergence. While highly idealized, the modeled waves share some features with observations, providing a mechanism for the relationship between CCEWs phase speed, amplitude, and horizontal structure.
The Ensemble Kalman Filter Analyses and Forecasts of the 8 May 2003 Oklahoma City Tornadic Supercell Storm Using Single- and Double-Moment Microphysics Schemes
Authors: Yussouf Nusrat , Mansell Edward R. , Wicker Louis J. , Wheatley Dustan M. , Stensrud David J.
Published: March 2013

A combined mesoscale and storm-scale ensemble data-assimilation and prediction system is developed using the Advanced Research core of the Weather Research and Forecasting Model (WRF-ARW) and the ensemble adjustment Kalman filter (EAKF) from the Data Assimilation Research Testbed (DART) software package for a short-range ensemble forecast of an 8 May 2003 Oklahoma City, Oklahoma, tornadic supercell storm. Traditional atmospheric observations are assimilated into a 45-member mesoscale ensemble over a continental U.S. domain starting 3 days prior to the event. A one-way-nested 45-member storm-scale ensemble is initialized centered on the tornadic event at 2100 UTC on the day of the event. Three radar observation assimilation and forecast experiments are conducted at storm scale using a single-moment, a semi-double-moment, and a full double-moment bulk microphysics scheme. Results indicate that the EAKF initializes the supercell storm into the model with good accuracy after a 1-h-long radar observation assimilation window. The ensemble forecasts capture the movement of the main supercell storm that matches reasonably well with radar observations. The reflectivity structure of the supercell storm using a double-moment microphysics scheme appears to compare better to the observations than that using a single-moment scheme. In addition, the ensemble system predicts the probability of a strong low-level vorticity track of the tornadic supercell that correlates well with the observed rotation track. The rapid 3-min update cycle of the storm-scale ensemble from the radar observations seems to enhance the skill of the ensemble and the confidence of an imminent tornado threat. The encouraging results obtained from this study show promise for a short-range probabilistic storm-scale forecast of supercell thunderstorms, which is the main goal of NOAA's Warn-on-Forecast initiative.
Quasi-Biweekly Mode and Its Modulation on the Diurnal Rainfall in Taiwan Forecasted by the CFS
Authors: Wang Shih-Yu , Chia Hsin-Hsing , Gillies Robert R. , Jiang Xianan
Published: March 2013

The occurrence of diurnal afternoon convection in Taiwan undergoes substantial modulation from tropical intraseasonal oscillations in the western North Pacific, including the quasi-biweekly (QBW) mode. By analyzing surface station observations and the Climate Forecast System (CFS) Reanalyses (CFSR), as well as the NCEP CFS version 2 (CFSv2) reforecast data over 18 summers from 1993 to 2010, it was found that the QBW mode plays a significant role in the formation of episodic diurnal convection. When the cyclonic circulation of the QBW mode is located west of Taiwan, followed by an anticyclonic circulation to the east, Taiwan's diurnal convection activity tends to intensify and persists for about 4–7 days. Synoptically, this situation reflects the enhanced subtropical anticyclone leading to fair weather conditions and increased monsoon southwesterly winds moistening the lower troposphere, all of which are conducive to thermally induced diurnal convection in Taiwan. The opposite situation tends to suppress the diurnal convection activity for a sustained period of time. Based upon this synoptic linkage, an empirical relationship between the precipitation diurnal amplitude and low-level circulation fields of the CFSv2 is derived. It was found that the CFSv2 forecast exhibits an effective lead time ranging from 16 to 24 days for the QBW mode and, subsequently, diurnal convection episodes in Taiwan.
Elusive Lamentations: What Are They About?
Authors: Gerstenberger Erhard S.
Published: March 2013

More than in other Hebrew writings, the enigmatic queries for origin, use, and theology of the small Book of Lamentations cannot easily be appeased. There are too many discrepancies in our literary, historical, and theological data of these five chapters of literature. Affinities with ancient Sumerian city laments as well as echoes of analogous experiences in modern experience open up new dimensions in the interpretation of Lamentations.
’êkāh: A Gasp of Desperation (Lamentations 1:1)
Authors: Bergant Dianne
Published: March 2013

The horror described in the Book of Lamentations engenders terror-fraught cries from those entrapped by them. The laments that comprise the book plumb the depths of human tragedy and desperation without rushing prematurely into consolation and relief.
The Silent God in Lamentations
Authors: Harris Beau , Mandolfo Carleen
Published: March 2013

Interpreting God’s silence may prove as fruitful to communities of faith as a firm understanding of God’s words. Against the backdrop of Lamentations’ boisterous lament, God’s silence speaks volumes.
Acoustic emission–based monitoring approach for friction stir welding of aluminum alloy AA6063-T6 with different tool pin profiles
Authors: Subramaniam Senthilkumar , S Narayanan , S Denis Ashok
Published: March 2013

Friction stir welding process is one of the solid-state welding processes, which is suitable to weld a range of similar and dissimilar material combinations by moving a shouldered, rotating tool along the joint line of weld materials. In this work, friction stir welding tools with square, circular, and triangular pin profiles are used to join the aluminum alloy AA6063-T6 flat plates. Acoustic emission technique is applied to monitor and analyze the effect of tool pin profile on tensile strength of the weld joints. A correlation study was made between the different acoustic emission signal parameters with the tensile strength of the weld joints. The proposed approach will be useful for in-process monitoring and control of the weld quality in friction stir welding process.
An investigation of cutting force and tool–work interface temperature in milling of Al–SiCp metal matrix composite
Authors: Jayakumar K , Mathew Jose , Joseph M A
Published: March 2013

Aluminium–SiC particulate metal matrix composites have attracted much interest in recent years among practitioners and researchers in the field of aerospace, automobile, nuclear, electronic packaging and other industries due to their low coefficient of thermal expansion, high strength and stiffness, hardness, wear and corrosion resistance properties. The present study focuses on aluminium A356 alloy with four different volume % of SiC particle–reinforced metal matrix composites synthesized by vacuum hot-pressing technique to achieve uniform dispersion of finer reinforcement over the matrix with higher densification. In order to study the machinability issues of the developed composites, computer numerical control end milling studies were conducted using central composite experimental design by varying cutting speed, feed and depth of cut, and the responses such as cutting forces and tool–work interface temperature were measured. The effect of machining parameters and reinforcement on the matrix during machining was analysed and optimized, which gives valuable guidelines to the manufacturing industries. The response surface models were developed and compared with experimental results. The results show that increase in volume % of SiCp reinforcement over the matrix results in higher tool–work interface temperature and needs higher cutting force during machining process.
Interrupted machining analysis for Ti6Al4V and Ti5553 titanium alloys using physical vapor deposition (PVD)–coated carbide inserts
Authors: Khanna Navneet , Sangwan Kuldip S
Published: March 2013

In this research, effect of physical vapor deposition–coated (TiAlN–TiN) carbide inserts with various edge preparations (cutting edge radius) and rake angles on cutting forces and temperature is studied at different cutting parameters for the interrupted machining of Ti6Al4V. It is noted that with the increase of edge radius, cutting and feed forces as well as temperature increase, and the effect on the feed force is more significant. Similarly, forces and temperature are measured for three different rake angles at two different feed rates keeping all other parameters constant. Forces and temperature show a decreasing trend with increasing rake angle. A comparison of the machining performance of Ti5553 and Ti6Al4V is also presented. Ti5553 alloy shows higher temperature as compared with Ti6Al4V at all cutting parameters because of its high hardness and strength attained due to the higher concentration of β stabilizers (Mo and V). Results of this research would be helpful for the tool manufacturers in designing novel geometries for coated cutting tools, used to machine wide range of α/β and β titanium alloys.
Numerical and experimental investigation of defect detection in polymer materials by means of digital shearography with thermal loading
Authors: Akbari Davood , Soltani Naser , Farahani Mohammadreza
Published: March 2013

Laser shearography is a relatively new and useful method for nondestructive testing of many kinds of material that need robust methods to be applicable in industrial environments. To get the best results of this inspection method, adjusting the loading parameters properly and precisely is of a great consideration. In this article, a new numerical–experimental procedure to study the effects of thermal loading parameters in the shearography test of defected materials is presented. In this regard, a numerical procedure was developed to simulate shearographic fringe patterns using finite element analysis and supplementary programming. The modeling method was evaluated using experimental tests in a Plexiglas circle subjected to the thermal and mechanical loadings. Flat-bottom holes indicating internal defects of the test part were simulated and experimented to study the parameters that should be adjusted and controlled to get desirable outcomes from shearography nondestructive testing. It has been showed that for each distinct case of nondestructive testing, a thermal loading diagram can be extracted to get credible results.
Deep sequencing and genome-wide analysis reveals the expansion of MicroRNA genes in the gall midge Mayetiola destructor
Authors: Khajuria Chitvan , Williams Christie E , El Bouhssini Mustapha , Whitworth R Jeff , Richards Stephen , Stuart Jeffrey J , Chen Ming-Shun
Published: March 2013

Background

MicroRNAs (miRNAs) are small non-coding RNAs that play critical roles in regulating post transcriptional gene expression. Gall midges encompass a large group of insects that are of economic importance and also possess fascinating biological traits. The gall midge Mayetiola destructor, commonly known as the Hessian fly, is a destructive pest of wheat and model organism for studying gall midge biology and insect – host plant interactions.

Results

In this study, we systematically analyzed miRNAs from the Hessian fly. Deep-sequencing a Hessian fly larval transcriptome led to the identification of 89 miRNA species that are either identical or very similar to known miRNAs from other insects, and 184 novel miRNAs that have not been reported from other species. A genome-wide search through a draft Hessian fly genome sequence identified a total of 611 putative miRNA-encoding genes based on sequence similarity and the existence of a stem-loop structure for miRNA precursors. Analysis of the 611 putative genes revealed a striking feature: the dramatic expansion of several miRNA gene families. The largest family contained 91 genes that encoded 20 different miRNAs. Microarray analyses revealed the expression of miRNA genes was strictly regulated during Hessian fly larval development and abundance of many miRNA genes were affected by host genotypes.

Conclusion

The identification of a large number of miRNAs for the first time from a gall midge provides a foundation for further studies of miRNA functions in gall midge biology and behavior. The dramatic expansion of identical or similar miRNAs provides a unique system to study functional relations among miRNA iso-genes as well as changes in sequence specificity due to small changes in miRNAs and in their mRNA targets. These results may also facilitate the identification of miRNA genes for potential pest control through transgenic approaches.
Epidemic of measles following the nationwide mass immunization campaign
Authors: Gao Jie , Chen Enfu , Wang Zhigang , Shen Jichuan , He Hanqing , Ma Huilai , Zeng Guang , Zhu Bao-Ping
Published: March 2013

Background

A prolonged measles epidemic occurred in Wenzhou City, China after a nationwide measles mass immunization campaign (MMIC) in 2010. We conducted an investigation to identify factors contributing to this epidemic and to provide evidence-based recommendations for measles elimination strategies in China.

Methods

Measles was diagnosed using the national standard case-definitions. We estimated the population vaccination coverage based on the proportion of measles patients that had been vaccinated. In a case–control investigation, all measles patients who received treatment in The Second Affiliated Hospital of Wenzhou Medical College (Hospital S) during November 1 to December 31, 2010 served as cases; controls were randomly selected among all other patients who received treatment in Hospital S during the same time period, frequency matched by month of hospital visit. We reviewed medical records of case- and control-patients to compare their exposure history at Hospital S and to its intravenous rehydration room (IV room) during the incubation period (7–21 days before their illness onset).

Results

The attack rate of measles in Wenzhou City was 3.3/100,000 during September 1, 2010 to January 11, 2011. Children aged 8-11 m had the highest attack rate (171/100,000) of all age groups. In children not age-eligible for the MMIC but should have been routinely vaccinated after the MMIC, the vaccination rate was only 52%. In the case–control investigation, 60% (25/42) of case-patients compared with 21% (35/168) of control-patients had visited Hospital S (adjusted ORM-H = 5.5, 95% CI = 2.7–11). Among unvaccinated children who had received treatment in Hospital S, 84% (21/25) of case-patients compared 38% (11/29) of control-patients had visited the IV room (adjusted ORM-H = 9.2, 95% CI = 1.5–59).

Conclusion

Relaxed routine measles vaccination among children after the MMIC was the main factor responsible for this epidemic. Exposure in the IV room at Hospital S facilitated the epidemic. To reach the goal of measles elimination, the Chinese public health authorities should make greater efforts to improve timely routine measles vaccination, and to reduce nosocomial transmission.
The CARD8 p.C10X mutation associates with a low anti-glycans antibody response in patients with Crohn’s disease
Authors: Vasseur Francis , Sendid Boualem , Broly Franck , Gower-Rousseau Corinne , Sarazin Aurore , Standaert-Vitse Annie , Colombel Jean-Frederic , Poulain Daniel , Jouault Thierry
Published: March 2013

Background

Crohn’s disease (CD) is associated with elevated anti-glycans antibody response in 60% of CD patients, and 25% of healthy first-degree relatives (HFDRs), suggesting a genetic influence for this humoral response. In mice, anti-glucan antibody response depends on the NLRP3 inflammasome. Here, we explored the effect of mutated CARD8, a component of the inflammasome, on anti-glycans antibody response in human.

Methods

The association between p.C10X mutation (rs2043211) of the CARD8 gene and the levels of anti-glycans antibody response was examined in 39 CD families. The family-based QTDT association test was used to test for the genetic association between CARD8 p.C10X mutation and anti-glycan antibodies in the pedigrees. The difference in antibody responses determined by ELISA was tested in a subgroup of CD probands (one per family) and in a subgroup of HFDRs using the Wilcoxon Kruskal Wallis non-parametric test.

Results

The QTDT familial transmission tests showed that the p.C10X mutation of CARD8 was significantly associated with lower levels of antibody to mannans and glucans but not chitin (p=0.024, p=0.0028 and p=0.577, for ASCA, ALCA and ACCA, respectively). These associations were independent of NOD2 and NOD1 genetic backgrounds. The p.C10X mutation significantly associated or displayed a trend toward lower ASCA and ALCA levels (p=0.038 and p=0.08, respectively) only in the subgroup of CD probands. Such associations were not significant for ACCA levels in both subgroups of CD probands and of HFDRs.

Conclusion

Our results show that ASCA and ALCA but not ACCA levels are under the influence of CARD8 genotype. Alteration of CARD8, a component of inflammasome, is associated with lower levels of antibodies directed to mannans and glucans at least in CD patients.
Diagnosis of partial complex regional pain syndrome type 1 of the hand: retrospective study of 16 cases and literature review
Authors: Konzelmann Michel , Deriaz Olivier , Luthi François
Published: March 2013

Background

The partial form of the complex regional pain syndrome of the hand type 1 (CRPS 1), involving only 1 to 3 fingers, is a rare condition first described in 1972. The aim of the study is to define more precisely the diagnosis workup and the prognosis of this clinical entity.

Methods

Retrospective study of CRPS1 partial form observed during five years in a rehabilitation ward. Application of The Budapest criteria, evaluation of radiological exams, therapeutic results and vocational outcomes. Comparison with cases from literature review.

Results

132 patients were hospitalized with the diagnosis of CRPS type 1 of the hand. 16 partial forms were isolated: 11 men, 5 women with a mean age of 43 years. Among these patients, 14 (88%) met The Budapest criteria and the two remaining cases were diagnosed by using the three phase bone scintigraphy. Only moderate improvement was obtained in the majority of the patients. At the maximal time of follow-up (4 to 9 years), 50% of the patients hadn’t returned to work. From the literature review, 19 cases were eligible for clinical comparisons. The main differences between our series and the literature were: more men involved, later diagnosis and worst prognosis in term of return to work.

Conclusions

This is the largest series of consecutive partial form of CRPS. The Budapest criteria are sufficient for the diagnosis in 88% of cases. As in complete form of CRPS1 of the hand, three phase bone scintigraphy should only be used in doubtful cases in the first six months of the illness. Partial form of CRPS1 of the hand is rare and its prevalence remains unknown. Long term prognosis (4 to 9 years) is poor in our series, 50% of patients didn’t returned to work.
Increased phosphorylation of histone H3 at serine 10 is involved in Epstein-Barr virus latent membrane protein-1-induced carcinogenesis of nasopharyngeal carcinoma
Authors: Li Binbin , Huang Guoliang , Zhang Xiangning , Li Rong , Wang Jian , Dong Ziming , He Zhiwei
Published: March 2013

Background

Increased histone H3 phosphorylation is an essential regulatory mechanism for neoplastic cell transformation. We aimed to explore the role of histone H3 phosphorylation at serine10 (p-H3Ser10) in Epstein-Barr virus (EBV) latent membrane protein-1 (LMP1)-induced carcinogenesis of nasopharyngeal carcinoma (NPC).

Methods

The expression of p-H3Ser10 was detected by the immunohistochemical analysis in NPC, chronic nasopharyngitis and normal nasopharynx tissues, and its correlation with LMP1 was analyzed in NPC tissues and cell lines. Using the small interfering RNA (siRNA)-H3 and histone H3 mutant (S10A), the effect of histone H3 Ser10 motif on LMP1-induced CNE1 cell proliferation, transformation and activator protein-1 (AP-1) activation were evaluated by CCK-8, focus-forming and reporter gene assay respectively. Mitogen- and stress-activated kinase 1 (MSK1) kinase activity and phosphorylation were detected by in vitro kinase assay and western blot. Using MSK1 inhibitor H89 or siRNA-MSK1, the regulatory role of MSK1 on histone H3 phosphorylation and AP-1 activation were analyzed.

Results

Immunohistochemical analysis revealed that the expression of p-H3Ser10 was significantly higher in the poorly differentiated NPC tissues than that in chronic nasopharyngitis (p <0.05) and normal nasopharynx tissues (p <0.001). Moreover, high level of p-H3Ser10 was positively correlated with the expression of LMP1 in NPC tissues (χ
2=6.700, p =0.01; C=0.350) and cell lines. The knockdown and mutant (S10A) of histone H3 suppressed LMP1-induced CNE1 cell proliferation, foci formation and AP-1 activation. In addition, LMP1 could increase MSK1 kinase activity and phosphorylation. MSK1 inhibitor H89 or knockdown of MSK1 by siRNA blocked LMP1-induced phosphorylation of histone H3 at Ser10 and AP-1 activation.

Conclusion

EBV-LMP1 can induce phosphorylation of histone H3 at Ser10 via MSK1. Increased phosphorylation of histone H3 at Ser10 is likely a crucial regulatory mechanism involved in LMP1-induced carcinogenesis of NPC.
The impact of KRAS mutations on VEGF-A production and tumour vascular network
Authors: Figueras Agnès , Arbos Maria Antonia , Quiles Maria Teresa , Viñals Francesc , Germà Josep Ramón , Capellà Gabriel
Published: March 2013

Background

The malignant potential of tumour cells may be influenced by the molecular nature of KRAS mutations being codon 13 mutations less aggressive than codon 12 ones. Their metabolic profile is also different, with an increased anaerobic glycolytic metabolism in cells harbouring codon 12 KRAS mutations compared with cells containing codon 13 mutations. We hypothesized that this distinct metabolic behaviour could be associated with different HIF-1α expression and a distinct angiogenic profile.

Methods

Codon13 KRAS mutation (ASP13) or codon12 KRAS mutation (CYS12) NIH3T3 transfectants were analyzed in vitro and in vivo. Expression of HIF-1α, and VEGF-A was studied at RNA and protein levels. Regulation of VEGF-A promoter activity was assessed by means of luciferase assays using different plasmid constructs. Vascular network was assessed in tumors growing after subcutaneous inoculation. Non parametric statistics were used for analysis of results.

Results

Our results show that in normoxic conditions ASP13 transfectants exhibited less HIF-1α protein levels and activity than CYS12. In contrast, codon 13 transfectants exhibited higher VEGF-A mRNA and protein levels and enhanced VEGF-A promoter activity. These differences were due to a differential activation of Sp1/AP2 transcription elements of the VEGF-A promoter associated with increased ERKs signalling in ASP13 transfectants. Subcutaneous CYS12 tumours expressed less VEGF-A and showed a higher microvessel density (MVD) than ASP13 tumours. In contrast, prominent vessels were only observed in the latter.

Conclusion

Subtle changes in the molecular nature of KRAS oncogene activating mutations occurring in tumour cells have a major impact on the vascular strategy devised providing with new insights on the role of KRAS mutations on angiogenesis.
A functional polymorphism T309G in MDM2 gene promoter, intensified by Helicobacter pylori lipopolysaccharide, is associated with both an increased susceptibility and poor prognosis of gastric carcinoma in Chinese patients
Authors: Pan Xiaolin , Li Yuqin , Feng Jin , Wang Xiaoyong , Hao Bo , Shi Ruihua , Zhang Guoxin
Published: March 2013

Background

Studies on the association between MDM2 SNP309 (T > G) and gastric cancer have reported conflicting results. Thus, the aim of this study was to investigate whether MDM2 SNP309 is associated with susceptibility and prognosis of gastric carcinoma in Chinese patients.

Methods

Total of 574 gastric carcinoma cases and 574 age- and sex-matched healthy controls were included. MDM2 polymorphism was detected by PCR- RFLP and infection of Helicobacter pylori (H. pylori) by a validated serology test. The functionality of MDM2 SNP309, with or without H. pylori lipopolysaccharide (LPS), was examined by dual-luciferase assay. Kaplan-Meier survival curves were used to evaluate survival. Additional, a meta-analysis was conducted to verity the findings.

Results

MDM2 SNP309G/G genotype was associated with an increased risk of gastric carcinoma when compared with T/T genotype or T carriers (both P < 0.01), and a joint effect between MDM2 SNP309G/G and H. pylori infection was observed to intensify gastric carcinoma risk. SNP309G/G was identified as an independent marker of poor overall survival of carcinoma. In vitro, the luciferase assay further showed an increased transcriptional activity of SNP309G allele compared with SNP309T allele, and the function of polymorphism T309G in MDM2 gene promoter was intensified by H. pylori LPS. Pooled results from the meta-analysis confirmed that SNP309G/G genotype had a significantly increased risk of gastric carcinoma compared with T/T genotype or T carriers, consistent with the case–control findings.

Conclusions

MDM2 SNP309G allele is associated with an increased risk and poor prognosis of gastric carcinoma in Chinese patients. Additional, there is a joint effect of MDM2 SNP309G/G allele and H. pylori infection on gastric carcinoma development, which may attribute to H. pylori LPS.
A comparative analysis of the properties of regulated promoter systems commonly used for recombinant gene expression in Escherichia coli
Authors: Balzer Simone , Kucharova Veronika , Megerle Judith , Lale Rahmi , Brautaset Trygve , Valla Svein
Published: March 2013

Background

Production of recombinant proteins in bacteria for academic and commercial purposes is a well established field; however the outcomes of process developments for specific proteins are still often unpredictable. One reason is the limited understanding of the performance of expression cassettes relative to each other due to different genetic contexts. Here we report the results of a systematic study aiming at exclusively comparing commonly used regulator/promoter systems by standardizing the designs of the replicon backbones.

Results

The vectors used in this study are based on either the RK2- or the pMB1- origin of replication and contain the regulator/promoter regions of XylS/Pm (wild-type), XylS/Pm ML1-17 (a Pm variant), LacI/P

T7lac

, LacI/P

trc
and AraC/P

BAD
to control expression of different proteins with various origins. Generally and not unexpected high expression levels correlate with high replicon copy number and the LacI/P

T7lac
system generates more transcript than all the four other cassettes. However, this transcriptional feature does not always lead to a correspondingly more efficient protein production, particularly if protein functionality is considered. In most cases the XylS/Pm ML1-17 and LacI/P

T7lac
systems gave rise to the highest amounts of functional protein production, and the XylS/Pm ML1-17 is the most flexible in the sense that it does not require any specific features of the host. The AraC/P

BAD
system is very good with respect to tightness, and a commonly used bioinformatics prediction tool (RBS calculator) suggested that it has the most translation-efficient UTR. Expression was also studied by flow cytometry in individual cells, and the results indicate that cell to cell heterogeneity is very relevant for understanding protein production at the population level.

Conclusions

The choice of expression system needs to be evaluated for each specific case, but we believe that the standardized vectors developed for this study can be used to more easily identify the nature of case-specific bottlenecks. By then taking into account the relevant characteristics of each expression cassette it will be easier to make the best choice with respect to the goal of achieving high levels of protein expression in functional or non-functional form.
Immunoproteomic analysis of Plasmodium falciparum antigens using sera from patients with clinical history of imported malaria
Authors: Costa Rita M , Nogueira Fátima , de Sousa Karina P , Vitorino Rui , Silva Marcelo S
Published: March 2013

Background

The malaria caused by Plasmodium falciparum remains a serious public health problem in the world, due largely to the absence of an effective vaccine. There is a lack of information on the structural properties and antigens capable of activating the immunological mechanisms for the induction of protective immunity. Therefore, the objective of this study is to evaluate the serological reactivity of sera from individuals with imported malaria and identify major immunogenic proteins.

Methods

The study was conducted in 227 individuals with imported malaria and 23 healthy individuals who had never been in areas endemic for malaria. The determination of anti-P. falciparum IgG antibodies was performed by an ELISA validated and optimized for this study. Sera showing higher reactivity to anti-P. falciparum by ELISA were analysed by immunoblotting and immunogenic proteins were identified by mass spectroscopy.

Results

The results of anti-P. falciparum antibodies research by ELISA indicates 78 positive, 137 negative and 12 indeterminate sera. Analysis of immunoblotting demonstrated a consistent pattern with respect to immunoreactivity of antigens with molecular weights in the range of 40 to 60 kDa. Between 40 and 60 kDa six immunogenic proteins were identified: elongation factor-1 alpha (EF-1α), protein disulphide isomerase (PDI); phosphoglycerate kinase (PGK); 78 kDa glucose-regulated protein homologue (GRP-78); rhoptry-associated protein 2 (RAP-2) and rhoptry-associated protein 3 (RAP-3).

Conclusions

It was identified immunogenic proteins essential for parasite survival in the host, two of which (RAP-2 and RAP-3) are already described in the literature as proteins that play an important role in the invasion of erythrocytes by extracellular merozoites.
Quality of life and the related factors in spouses of veterans with chronic spinal cord injury
Authors: Ebrahimzadeh Mohammad Hossein , Shojaei Bibi-Soheila , Golhasani-Keshtan Farideh , Soltani-Moghaddas Seyed Hossein , Fattahi Asieh Sadat , Mazloumi Seyed Mahdi
Published: March 2013

Background

The quality of life (QOL) of caregivers of individuals with chronic spinal cord injuries may be affected by several factors. Moreover, this issue is yet to be documented fully in the literature.

The purpose of this study was to evaluate the health related quality of life of spouses who act as primary caregivers of veterans with chronic spinal cord injuries in Iran.

Methods

The study consisted of 72 wives of 72 veterans who were categorized as spinal cord injured patients based on the American Spinal Injury Association (ASIA) classification. Health related quality of life was assessed by the Short Form (SF-36) Health Survey. Pearson's correlation was carried out to find any correlation between demographic variables with SF-36 dimensions. To find the effect of the factors like age, employment status, duration of care giving, education, presence or absence of knee osteoarthritis, and mechanical back pain on different domains of the SF-36 health survey, Multivariate analysis of variance (MANOVA) was used.

Results

The mean age of the participants was 44.7 years. According to the ASIA classification 88.9% and 11.1% of the veterans were paraplegic and tetraplegic respectively. Fifty percent of them had a complete injury (ASIA A) and 85% of the spouses were exclusive care givers. All of the SF-36 scores of the spouses were significantly lower than the normal population. Pearson's correlation demonstrated a negative significant correlation between both age and duration of caring with the PF domain. The number of children had a negative correlation with RE and VT.

Conclusion

The burden of caregiving can impact the QOL of caregivers and cause health problems. These problems can cause limitations for caregiver spouses and it can lead to a decrease in the quality of given care.
Boiling local heat transfer enhancement in minichannels using nanofluids
Authors: Chehade Ali Ahmad , Gualous Hasna Louahlia , Le Masson Stephane , Fardoun Farouk , Besq Anthony
Published: March 2013

This paper reports an experimental study on nanofluid convective boiling heat transfer in parallel rectangular minichannels of 800 μm hydraulic diameter. Experiments are conducted with pure water and silver nanoparticles suspended in water base fluid. Two small volume fractions of silver nanoparticles suspended in water are tested: 0.000237% and 0.000475%. The experimental results show that the local heat transfer coefficient, local heat flux, and local wall temperature are affected by silver nanoparticle concentration in water base fluid. In addition, different correlations established for boiling flow heat transfer in minichannels or macrochannels are evaluated. It is found that the correlation of Kandlikar and Balasubramanian is the closest to the water boiling heat transfer results. The boiling local heat transfer enhancement by adding silver nanoparticles in base fluid is not uniform along the channel flow. Better performances and highest effect of nanoparticle concentration on the heat transfer are obtained at the minichannels entrance.
A cytotoxic hydroperoxy sterol from the brown alga, Nizamuddinia zanardinii
Authors: Moghadam Maryam Hamzeloo , Firouzi Jamileh , Saeidnia Soodabeh , Hajimehdipoor Homa , Jamili Shahla , Rustaiyan Abdolhossein , Gohari Ahmad R
Published: March 2013

Background

The marine environment is a unique source of bioactive natural products, of which Nizamuddinia zanardinii is an important brown algae distributed in Oman Sea. Literature revealed that there is no report on phytochemistry and pharmacology of this valuable algae.

Methods

Bioguided fractionation of the methanolic extract of Nizamuddinia zanardinii, collected from Oman Sea, led to the isolation of a hydroperoxy sterol. Its structure was determined by analysis of the spectroscopic data as 24-hydroperoxy-24-vinyl cholesterol (HVC). In vitro cytotoxic activity of this compound was evaluated against HT29, MCF7, A549, HepG2 and MDBK cell lines.

Results

Although 24(R)-hydroproxy-24-vinylcholesterol has been previously reported from Sargassum and Padina species, it is the first report on the presence of this compound from N. zanardinii. This compound exhibited cytotoxicity in all cell lines (IC50, 3.62, 9.09, 17.96, 32.31 and 37.31 μg/mL respectively). HVC was also evaluated for apoptotic activity and demonstrated positive results in terminal deoxynucleotidyl transferase dUTP Nick End labeling (TUNEL) assay suggesting it a candidate for further apoptotic studies.

Conclusions

Nizamuddinia zanardinii, a remarkable brown algae of Oman Sea, is a good source of hydroproxy sterols with promising cytotoxic on various cell lines particularly human colon adenocarcinoma.
Overexpression of MACC1 and Its significance in human Breast Cancer Progression
Authors: Huang Yongbo , Zhang Huizhong , Cai Junchao , Fang Lishan , Wu Jueheng , Ye Caisheng , Zhu Xun , Li Mengfeng
Published: March 2013

Background

Metastasis-associated in colon cancer-1 (MACC1) was first identified as a transcriptional activator for proto-oncogene c-MET expression, and its overexpression is frequently associated with metastatic progression for multiply tumor types. In the present study, we analyzed for the first time the expression of MACC1 in breast cancer and its correlation with clinicopathologic features, including metastasis and patient survival.

Results

MACC1 protein expression was analyzed in two cohorts of clinicopathologically characterized breast cancer using immunohistochemistry. Statistical analysis showed a significant correlation of MACC1 expression with the primary tumor, lymph node metastasis, distant metastasis classifications as well as the clinical staging in breast cancer patients. Moreover, overexpression of MACC1 was associated with both a reduced recurrence-free survival (RFS) and poorer patients' overall survival (OS). Multivariate analysis with a Cox proportional-hazards model suggested that MACC1 expression was an independent prognostic indicator for RFS and OS. Stratification of breast cancer patients according to the estrogen receptor (ER) status revealed that MACC1 was prognostic for both ER-negative and ER-positive patients.

Conclusions

MACC1 may represent a potentially useful biomarker for the prognosis of breast cancer patients and might be involved in progression of breast cancer.