bluuebunny/crossref_metadata_2025 huggingface dataset:
Myeloid malignancies: mutations, models and management
Authors: Murati Anne , Brecqueville Mandy , Devillier Raynier , Mozziconacci Marie-Joelle , Gelsi-Boyer Véronique , Birnbaum Daniel
Published: July 2012

Myeloid malignant diseases comprise chronic (including myelodysplastic syndromes, myeloproliferative neoplasms and chronic myelomonocytic leukemia) and acute (acute myeloid leukemia) stages. They are clonal diseases arising in hematopoietic stem or progenitor cells. Mutations responsible for these diseases occur in several genes whose encoded proteins belong principally to five classes: signaling pathways proteins (e.g. CBL, FLT3, JAK2, RAS), transcription factors (e.g. CEBPA, ETV6, RUNX1), epigenetic regulators (e.g. ASXL1, DNMT3A, EZH2, IDH1, IDH2, SUZ12, TET2, UTX), tumor suppressors (e.g. TP53), and components of the spliceosome (e.g. SF3B1, SRSF2). Large-scale sequencing efforts will soon lead to the establishment of a comprehensive repertoire of these mutations, allowing for a better definition and classification of myeloid malignancies, the identification of new prognostic markers and therapeutic targets, and the development of novel therapies. Given the importance of epigenetic deregulation in myeloid diseases, the use of drugs targeting epigenetic regulators appears as a most promising therapeutic approach.
Antitumor activity of zoledronic acid in primary breast cancer cells determined by the ATP tumor chemosensitivity assay
Authors: Fehm Tanja , Zwirner Manfred , Wallwiener Diethelm , Seeger Harald , Neubauer Hans
Published: July 2012

Background

The NeoAzure study has demonstrated that the use of the bisphosphonate zoledronic acid (Zol) in the neoadjuvant setting increases the rate of complete response in primary breast cancer and therefore indicates direct antitumor activity. The purpose of this study was to compare the antitumor effect of Zol with standard chemotherapy in primary breast cancer cells using ATP-tumor chemosensitivity assay (ATP-TCA).

Methods

Breast cancer specimens were obtained from patients with breast cancer who underwent primary breast cancer surgery at the Department of Obstetrics and Gynecology, Tübingen, Germany, between 2006 through 2009. Antitumor effects of Zol, TAC (Docetaxel, Adriamycin, Cyclophosphamide) and FEC (5-Fluorouracil, Epirubicin, Cyclophosphamide) were tested in 116 fresh human primary breast cancer specimens using ATP-TCA. ATP-TCA results were analyzed with different cut-off levels for the half maximal inhibitory concentration (IC50), for IC90 and for the sensitivity index (IndexSUM). Each single agent or combination was tested at six doubling dilutions from 6.25, 12.5, 25, 50, 100, and 200% of test drug concentrations (TDC) derived from the plasma peak concentrations determined by pharmacokinetic data. The assay was carried out in duplicate wells with positive and negative controls.

Results

The median IndexSUM value was lower for Zol than for the combined regimen FEC (36.8%) and TAC (12.9%), respectively, indicating increased antitumor activity of Zol in primary breast cancer cells. The difference regarding Zol and FEC was significant (p < 0.05). The median IC50 value for Zol (8.03% TDC) was significantly lower than the IC50 values for FEC (33.5% TDC) and TAC (19.3% TDC) treatment (p < 0.05). However, the median IC90 value for Zol (152.5% TDC) was significantly higher than the IC90 value obtained with TAC (49.5% TDC; p < 0.05), but similar to the IC90 value for FEC (180.9% TDC). In addition a significant positive correlation was observed for the IndexSum of Zol and the ER status (p < 0.01).

Conclusion

Zoledronic acid has a strong antitumor effect on primary breast cancer cells in vitro which is equal or superior to commonly used chemotherapeutic regimens for treating breast cancer.
Ephrin-A1 inhibits NSCLC tumor growth via induction of Cdx-2 a tumor suppressor gene
Authors: Sukka-Ganesh Bhagyalaxmi , Mohammed Kamal A , Kaye Frederic , Goldberg Eugene P , Nasreen Najmunnisa
Published: July 2012

Background

Tumor formation is a complex process which involves constitutive activation of oncogenes and suppression of tumor suppressor genes. Receptor EphA2 and its ligand ephrin-A1 form an important cell communication system with its functional role in cell-cell interaction and tumor growth. Loss of cell-cell adhesion is central to the cellular transformation and acquisition of metastatic potential. Claudins, the integrated tight junction (TJ) cell-cell adhesion proteins located on the apico-lateral portion of epithelial cells, functions in maintaining cell polarity. There is extensive evidence implicating Eph receptors and ephrins in malignancy, but the mechanisms how these molecular players affect TJ proteins and regulate tumor growth are not clear. In the present study we hypothesized that EphA2 signaling modulates claudin-2 gene expression via induction of cdx-2, a tumor suppressor gene in NSCLC cells.

Methods

The expression of EphA2, claudin-2 was determined in various NSCLC cell lines by using real-time quantitative polymerase chain reaction and Western blot analysis. The claudin-2 expression was also analyzed by immunofluorescence analysis. EphA2 and erk1/erk2 phosphorylation in ephrin-A1 activated cells was evaluated by Western blot analysis. The cell proliferation and tumor colony formation were determined by WST-1 and 3-D matrigel assays respectively.

Results

NSCLC cells over expressed receptor EphA2 and claudin-2. Ephrin-A1 treatment significantly down regulated the claudin-2 and EphA2 expression in NSCLC cells. The transient transfection of cells with vector containing ephrin-A1 construct (pcDNA-EFNA1) decreased the expression of claudin-2, EphA2 when compared to empty vector. In addition ephrin-A1 activation increased cdx-2 expression in A549 cells. In contrast over-expression of EphA2 with plasmid pcDNA-EphA2 up regulated claudin-2 mRNA expression and decreased cdx-2 expression. The transient transfection of cells with vector containing cdx-2 construct (pcMV-cdx-2) decreased the expression of claudin-2 in A549 cells. Moreover, silencing the expression of receptor EphA2 by siRNA significantly reduced claudin-2 expression and decreased cell proliferation and tumor formation. Furthermore, silencing cdx-2 gene expression before ephrin-A1 treatment increased claudin-2 expression along with increased cell proliferation and tumor growth in A549 cells.

Conclusions

Our study suggests that EphA2 signaling up-regulates the expression of the TJ-protein claudin-2 that plays an important role in promoting cell proliferation and tumor growth in NSCLC cells. We conclude that receptor EphA2 activation by ephrin-A1 induces tumor suppressor gene cdx-2 expression which attenuates cell proliferation, tumor growth and thus may be a promising therapeutic target against NSCLC.
The relationship between attention deficit hyperactivity disorder and premature infants in Taiwanese: a case control study
Authors: Chu Shih-Ming , Tsai Ming-Horng , Hwang Fan-Ming , Hsu Jen-Fu , Huang Hsuan Rong , Huang Yu-Shu
Published: July 2012

Background

Preterm survivors from the neonatal intensive care unit (NICU) are considered to be at risk for some neurobehavioral disorders such as attention-deficit/hyperactivity disorder (ADHD). The current study aimed to explore the relationship between ADHD and premature infants in Taiwan.

Methods

A total of 195 children (157 males and 38 females) diagnosed with ADHD based on DSM-IV and aged between 6 to 12 years and a control group of 212 (164 males, 48 females) age- and sex-matched healthy children were enrolled. The ADHD-Rating scale and CGI severity were performed by child psychiatrists. Demographic data of the children, including birth history, perinatal neurological and respiratory problems were collected to facilitate the investigation of whether a correlation exists between ADHD and prematurity.

Results

The ADHD group had a significantly higher rate of prematurity and significantly higher rate of low birth body weight (defined as <2500 g) than the control group (both P = 0.003). Pearson correlation showed a significantly negative correlation between gestational age and ADHD-RS score, inattentive score, hyperactivity and CGI-S score (P = 0.004, 0.013, 0.015 and 0.002, respectively). However, only a CGI-S score (P = 0.018) showed a significantly correlation between low birth weight and ADHD.

Conclusions

Premature infants have significantly more severe symptoms of ADHD at school age and they were highly correlated. Further study is necessary to determine the main effect and pathogenesis of moderate as well as extreme preterm birth on the development of ADHD.
Spatial clusters of suicide in Australia
Authors: Qi Xin , Hu Wenbiao , Page Andrew , Tong Shilu
Published: July 2012

Background

Understanding the spatial distribution of suicide can inform the planning, implementation and evaluation of suicide prevention activity. This study explored spatial clusters of suicide in Australia, and investigated likely socio-demographic determinants of these clusters.

Methods

National suicide and population data at a statistical local area (SLA) level were obtained from the Australian Bureau of Statistics for the period of 1999 to 2003. Standardised mortality ratios (SMR) were calculated at the SLA level, and Geographic Information System (GIS) techniques were applied to investigate the geographical distribution of suicides and detect clusters of high risk in Australia.

Results

Male suicide incidence was relatively high in the northeast of Australia, and parts of the east coast, central and southeast inland, compared with the national average. Among the total male population and males aged 15 to 34, Mornington Shire had the whole or a part of primary high risk cluster for suicide, followed by the Bathurst-Melville area, one of the secondary clusters in the north coastal area of the Northern Territory. Other secondary clusters changed with the selection of cluster radius and age group. For males aged 35 to 54 years, only one cluster in the east of the country was identified. There was only one significant female suicide cluster near Melbourne while other SLAs had very few female suicide cases and were not identified as clusters. Male suicide clusters had a higher proportion of Indigenous population and lower median socio-economic index for area (SEIFA) than the national average, but their shapes changed with selection of maximum cluster radii setting.

Conclusion

This study found high suicide risk clusters at the SLA level in Australia, which appeared to be associated with lower median socio-economic status and higher proportion of Indigenous population. Future suicide prevention programs should focus on these high risk areas.
Spatial-temporal analysis of malaria and the effect of environmental factors on its incidence in Yongcheng, China, 2006–2010
Authors: Zhang Yan , Liu Qi-Yong , Luan Rong-Sheng , Liu Xiao-Bo , Zhou Guang-Chao , Jiang Jing-Yi , Li Hong-Sheng , Li Zhi-Fang
Published: July 2012

Background

In 2003, Plasmodium vivax malaria has re-emerged in central eastern China including Yongcheng prefecture, Henan Province, where no case has been reported for eleven years. Our goals were to detect the space-time distribution pattern of malaria and to determine significant environmental variables contributing to malaria incidence in Yongcheng from 2006 to 2010, thus providing scientific basis for further optimizing current malaria surveillance and control programs.

Methods

This study examined the spatial and temporal heterogeneities in the risk of malaria and the influencing factors on malaria incidence using geographical information system (GIS) and time series analysis. Univariate analysis was conducted to estimate the crude correlations between malaria incidence and environmental variables, such as mosquito abundance and climatic factors. Multivariate analysis was implemented to construct predictive models to explore the principal environmental determinants on malaria epidemic using a Generalized Estimating Equation (GEE) approach.

Results

Annual malaria incidence at town-level decreased from the north to south, and monthly incidence at prefecture-level demonstrated a strong seasonal pattern with a peak from July to November. Yearly malaria incidence had a visual spatial association with yearly average temperature. Moreover, the best-fit temporal model (model 2) (QIC = 16.934, P<0.001, R2 = 0.818) indicated that significant factors contributing to malaria incidence were maximum temperature at one month lag, average humidity at one month lag, and malaria incidence of the previous month.

Conclusions

Findings supported the effects of environment factors on malaria incidence and indicated that malaria control targets should vary with intensity of malaria incidence, with more public resource allocated to control the source of infections instead of large scale An. sinensis control when malaria incidence was at a low level, which would benefit for optimizing the malaria surveillance project in China and some other countries with unstable or low malaria transmission.
Oxidative stress mediated arterial dysfunction in patients with obstructive sleep apnoea and the effect of continuous positive airway pressure treatment
Authors: Del Ben Maria , Fabiani Mario , Loffredo Lorenzo , Polimeni Licia , Carnevale Roberto , Baratta Francesco , Brunori Marco , Albanese Fabiana , Augelletti Teresa , Violi Francesco , Angelico Francesco
Published: July 2012

Background

Several studies suggest an increase of oxidative stress and a reduction of endothelial function in obstructive sleep apnoea syndrome (OSAS). We assessed the association between OSAS, endothelial dysfunction and oxidative stress. Further aim was to evaluate the effect of nasal continuous positive airway pressure (nCPAP) on oxidative stress and arterial dysfunction.

Methods

We studied 138 consecutive patients with heavy snoring and possible OSAS. Patients underwent unattended overnight home polysomnography. Ten patients with severe OSAS were revaluated after 6 months of nCPAP therapy. To assess oxidative stress in vivo, we measured urinary 8-iso-PGF2α and serum levels of soluble NOX2-derived peptide (sNOX2-dp). Serum levels of nitrite/nitrate (NOx) were also determined. Flow-mediated brachial artery dilation (FMD) was measured to asses endothelial function.

Results

Patients with severe OSAS had higher urinary 8-iso-PGF2α (p<0.001) and serum NOX2 and lower NOx. A negative association was observed between FMD and OSA severity. Apnea/hypopnea index was significantly correlated with the indices of central obesity and with urinary 8-isoprostanes (r=0.298, p<0.001). The metabolic syndrome (t=-4.63, p<0.001) and urinary 8-isoprostanes (t=-2.02, p<0.05) were the only independent predictors of FMD. After 6-months nCPAP treatment, a significant decrease of serum NOX2, (p<0.005) and urinary 8-iso-PGF2α (p<0.01) was observed, while serum NOx showed only a minor increase. A statistically significant increase of FMD was observed (from 3.6% to 7.0%).

Conclusions

The results of our study indicate that patients with OSAS and cardiometabolic comorbidities have increased oxidative stress and arterial dysfunction that are partially reversed by nCPAP treatment.
Whole plant based treatment of hypercholesterolemia with Crataegus laevigata in a zebrafish model
Authors: Littleton Robert M , Miller Matthew , Hove Jay R
Published: July 2012

Background

Consumers are increasingly turning to plant-based complementary and alternative medicines to treat hypercholesterolemia. Many of these treatments are untested and their efficacy is unknown. This multitude of potential remedies necessitates a model system amenable to testing large numbers of organisms that maintains similarity to humans in both mode of drug administration and overall physiology. Here we develop the larval zebrafish (4–30 days post fertilization) as a vertebrate model of dietary plant-based treatment of hypercholesterolemia and test the effects of Crataegus laevigata in this model.

Methods

Larval zebrafish were fed high cholesterol diets infused with fluorescent sterols and phytomedicines. Plants were ground with mortar and pestle into a fine powder before addition to food. Fluorescent sterols were utilized to optically quantify relative difference in intravascular cholesterol levels between groups of fish. We utilized the Zeiss 7-Live Duo high-speed confocal platform in order to both quantify intravascular sterol fluorescence and to capture video of the heart beat for determination of cardiac output.

Results

In this investigation we developed and utilized a larval zebrafish model to investigate dietary plant-based intervention of the pathophysiology of hypercholesterolemia. We found BODIPY-cholesterol effectively labels diet-introduced intravascular cholesterol levels (P < 0.05, Student’s t-test). We also established that zebrafish cardiac output declines as cholesterol dose increases (difference between 0.1% and 8% (w/w) high cholesterol diet-treated cardiac output significant at P < 0.05, 1-way ANOVA). Using this model, we found hawthorn leaves and flowers significantly reduce intravascular cholesterol levels (P < 0.05, 1-way ANOVA) and interact with cholesterol to impact cardiac output in hypercholesterolemic fish (2-way ANOVA, P < 0.05 for interaction effect).

Conclusions

The results of this study demonstrate that the larval zebrafish has the potential to become a powerful model to test plant based dietary intervention of hypercholesterolemia. Using this model we have shown that hawthorn leaves and flowers have the potential to affect cardiac output as well as intravascular cholesterol levels. Further, our observation that hawthorn leaves and flowers interact with cholesterol to impact cardiac output indicates that the physiological effects of hawthorn may depend on diet.
Community based study to compare the incidence and health services utilization pyramid for gastrointestinal, respiratory and dermal symptoms
Authors: Najnin Nusrat , Sinclair Martha , Forbes Andrew , Leder Karin
Published: July 2012

Background

Gastrointestinal (GI), respiratory and dermal symptoms are common and cause substantial morbidity, although the information on their exact incidence and comparative burden is limited. The aim of this study was to describe the epidemiology and rate these three major symptom complexes in order to improve our understanding of the health burden imposed by these symptoms.

Methods

We used data from a community based randomised control trial conducted from June 2007 to August 2008 among 277 South Australian families consuming rainwater. Using weekly health diaries, we prospectively collected information on GI (diarrhoea or vomiting), respiratory (sore throat, runny nose or cough) and dermal (rash, generalised itch or dermal infection) symptoms, as well as on relevant GP visits, time off work and/or hospitalisation due to these symptoms. Data were analysed using generalized estimating equations approach taking into account the variable number of weeks of follow-up of each individual and within-family clustering of responses.

Results

Over one year, at least one episode of GI symptoms was reported by 54% of participants (95% CI 50%-58%), at least one respiratory episode by 91% (95% CI 88%-93%) and at least one episode of dermal symptoms by 27% (95% CI 24%-30%). The average number of weeks per year during which respiratory symptoms occurred was four times greater than for GI or dermal symptoms (4.9, 1.2 and 1.2 weeks, respectively, p<0.001), with an average number of GP visits per person per year being twice as frequent (0.48, 0.26, 0.19 respectively, p<0.001). However, on a per episode basis, a higher proportion of people saw a GP or were hospitalised for GI symptoms.

Conclusions

This first comparative study of three different symptom complexes showed that although respiratory symptoms are most common, GI symptoms cause a greater per episode burden on healthcare resources. Measuring and comparing the community based burden of these symptom complexes will assist evidence-based allocation of resources.
Impact of 5-HT3 receptor antagonists on chemotherapy-induced nausea and vomiting: a retrospective cohort study
Authors: Lin Swu-Jane , Hatoum Hind T , Buchner Deborah , Cox David , Balu Sanjeev
Published: July 2012

Background

1st generation 5-hydroxytryptamine receptor antagonists (5-HT3 RAs), and palonosetron, a 2nd generation 5-HT3 RA, are indicated for the prevention of chemotherapy (CT)-induced nausea and vomiting (CINV) associated with moderately (MEC) and highly emetogenic CT agents (HEC). This study explores the impact of step therapy policies requiring use of an older 5-HT3 RA before palonosetron on risk of CINV associated with hospital or emergency department (ED) admissions.

Methods

Patients who received cyclophosphamide post breast cancer (BC) surgery or who were diagnosed with lung cancer on carboplatin (LC-carboplatin) or cisplatin (LC-cisplatin) were selected from PharMetrics’ (IMS LifeLink) claims dataset (2005-2008). Patients were followed for 6 months from initial CT administration for CINV events identified through ICD-9-CM codes. Patients were grouped into those initiated with older, generic 5-HT3 RAs (ondansetron, granisetron, and dolasetron) and those initiated and maintained on palonosetron throughout study follow-up. CINV events and CINV days were analyzed using multivariate regressions controlling for demographic and clinical variables.

Results

Eligible patients numbered 3,606 in BC, 4,497 in LC-carboplatin and 1,154 in LC-cisplatin cohorts, with 52%, 40%, and 34% in the palonosetron group, respectively. There was no significant difference between the two 5-HT3 RA groups in age or Charlson Comorbidity Index among the two MEC cohorts (BC and LC-carboplatin). Among the LC-cisplatin cohort, palonosetron users were older with more males than the older 5-HT3 RA group (age: 60.1 vs. 61.3; males, 66.9% vs. 56.9%). Compared to the older 5-HT3 RAs, the palonosetron groups incurred 22%-51% fewer 5-HT3 RA pharmacy claims, had fewer patients with CINV events (3.5% vs. 5.5% in BC, 9.5% vs. 12.8% in LC-carboplatin, 16.4% vs. 21.7% in LC-cisplatin), and had lower risk for CINV events (odds ratios 0.62, 0.71, or 0.71, respectively; p < 0.05). The BC and LC-carboplatin palonosetron groups experienced 50% and 30% fewer CINV days than the generic 5-HT3 RA group (p < 0.05).

Conclusions

Patients with breast or lung cancer initiated and maintained on palonosetron were at significantly lower risk for potentially costly CINV versus those on older 5-HT3 RAs. Further studies on impact of step therapy policy are warranted in order to minimize the clinical and economic burden of CINV.
Open-label trial with artemether-lumefantrine against uncomplicated Plasmodium falciparum malaria three years after its broad introduction in Jimma Zone, Ethiopia
Authors: Eshetu Teferi , Abdo Nasir , Bedru Kunuz H , Fekadu Sintayehu , Wieser Andreas , Pritsch Michael , Löscher Thomas , Berens-Riha Nicole
Published: July 2012

Background

In Jimma Zone, Ethiopia, the first-line treatment of uncomplicated falciparum malaria has been changed from sulphadoxine-pyrimethamine (SP) to artemether-lumefantrine (AL) in 2006. The objective of this study was to assess the effectiveness of AL in Jimma Zone two to three years after its broad introduction.

Methods

An open-label, single-arm, 42-day study of AL against falciparum malaria was conducted in four areas with moderate transmission in Jimma Zone between November 2008 and January 2009 and between August and December 2009. Patients (one-81 years) with uncomplicated Plasmodium falciparum mono-infection were consecutively enrolled. Follow-up visits were at day 2, 3, 7, 28 and 42 or any other day if symptoms reoccurred. Primary and secondary endpoints were PCR-corrected and uncorrected cure rates (molecular differentiation between recrudescence and re-infection) on days 28 and 42. Other secondary endpoints were gametocytaemia at day 7 and day 28, parasitaemia at day 2 and 3, and re-infection rates at day 28 and day 42.

Results

Of 348 enrolled patients, 313 and 301 completed follow-up at day 28 and at day 42, respectively. No early treatment failure occurred. For per protocol analysis, PCR-uncorrected cure rates at day 28 and 42 were 99.1% (95% CI 98.0-100.0) and 91.1% (95% CI 87.9-94.3), respectively. PCR-corrected cure rates at day 28 and 42 were 99.4% (95% CI 98.5-100.0) and 94.7% (95% CI 92.2-97.2), respectively. PCR-corrected cure rate at day 42 for children ≤5 years was 90.6% (95% CI 82.4-98.7) only. Adverse events were in general mild to moderate. Incidence of new infections was 3.4% during 42 days, no new infections with Plasmodium vivax were observed. Microscopically detected gametocytaemia was reduced by 80% between day 0 and day 7.

Conclusion

In general, AL was effective and well tolerated in Jimma Zone, Ethiopia. However, the PCR-corrected recrudescence rate per-protocol at day 42 for children ≤5 years was 9.4%. Therefore, further development should be monitored on a regular basis as recommended by WHO.
Sex differences in the response of the alveolar macrophage proteome to treatment with exogenous surfactant protein-A
Authors: Phelps David S , Umstead Todd M , Floros Joanna
Published: July 2012

Background

Male wild type (WT) C57BL/6 mice are less capable of clearing bacteria and surviving from bacterial pneumonia than females. However, if an oxidative stress (acute ozone exposure) occurs before infection, the advantage shifts to males who then survive at higher rates than females. We have previously demonstrated that survival in surfactant protein-A (SP-A) knockout (KO) mice compared to WT was significantly reduced. Because the alveolar macrophage (AM) is pivotal in host defense we hypothesized that SP-A and circulating sex hormones are responsible for these sex differences. We used 2D-DIGE to examine the relationship of sex and SP-A on the AM proteome. The role of SP-A was investigated by treating SP-A KO mice with exogenous SP-A for 6 and 18 hr and studying its effects on the AM proteome.

Results

We found: 1) less variance between KO males and females than between the WT counterparts by principal component analysis, indicating that SP-A plays a role in sex differences; 2) fewer changes in females when the total numbers of significantly changing protein spots or identified whole proteins in WT or 18 hr SP-A-treated males or females were compared to their respective KO groups; 3) more proteins with functions related to chaperones or protease balance and Nrf2-regulated proteins changed in response to SP-A in females than in males; and 4) the overall pattern of SP-A induced changes in actin-related proteins were similar in both sexes, although males had more significant changes.

Conclusions

Although there seems to be an interaction between sex and the effect of SP-A, it is unclear what the responsible mechanisms are. However, we found that several of the proteins that were expressed at significantly higher levels in females than in males in WT and/or in KO mice are known to interact with the estrogen receptor and may thus play a role in the SP-A/sex interaction. These include major vault protein, chaperonin subunit 2 (beta) (CCT2), and Rho GDP alpha dissociation inhibitor. We conclude that sex differences exist in the proteome of AM derived from male and female mice and that SP-A contributes to these sex differences.
Demonstration of photon Bloch oscillations and Wannier-Stark ladders in dual-periodical multilayer structures based on porous silicon
Authors: Estevez J Octavio , Arriaga Jesús , Mendez-Blas Antonio , Reyes-Ayona Edgar , Escorcia José , Agarwal Vivechana
Published: July 2012

Theoretical demonstration and experimental evidence of photon Bloch oscillations and Wannier-Stark ladders (WSLs) in dual-periodical (DP) multilayers, based on porous silicon, are presented. An introduction of the linear gradient in refractive indices in DP structure, which is composed by stacking two different periodic substructures N times, resulted in the appearance of WSLs. Theoretical time-resolved reflection spectrum shows the photon Bloch oscillations with a period of 130 fs. Depending on the values of the structural parameters, one can observe the WSLs in the near infrared or visible region which may allow the generation of terahertz radiation with a potential applications in several fields like imaging.
Strong convergence theorems for a common point of solution of variational inequality, solutions of equilibrium and fixed point problems
Authors: Zegeye Habtu , Shahzad Naseer , Alghamdi Mohammad Ali
Published: July 2012

We introduce an iterative process which converges strongly to a common point of solution of variational inequality problem for continuous monotone mapping, solution of equilibrium problem and a common fixed point of finite family of asymptotically regular uniformly continuous relatively asymptotically nonexpansive mappings in Banach spaces. Our scheme does not involve computation of C

n+1from C

n
for each n ≥ 1. Our theorems improve and unify most of the results that have been proved for this important class of nonlinear operators.

Mathematics Subject Classification (2000): 47H05, 47H09, 47H10, 47J05, 47J25
Force sensor in simulated skin and neural model mimic tactile SAI afferent spiking response to ramp and hold stimuli
Authors: Kim Elmer K , Wellnitz Scott A , Bourdon Sarah M , Lumpkin Ellen A , Gerling Gregory J
Published: July 2012

Background

The next generation of prosthetic limbs will restore sensory feedback to the nervous system by mimicking how skin mechanoreceptors, innervated by afferents, produce trains of action potentials in response to compressive stimuli. Prior work has addressed building sensors within skin substitutes for robotics, modeling skin mechanics and neural dynamics of mechanotransduction, and predicting response timing of action potentials for vibration. The effort here is unique because it accounts for skin elasticity by measuring force within simulated skin, utilizes few free model parameters for parsimony, and separates parameter fitting and model validation. Additionally, the ramp-and-hold, sustained stimuli used in this work capture the essential features of the everyday task of contacting and holding an object.

Methods

This systems integration effort computationally replicates the neural firing behavior for a slowly adapting type I (SAI) afferent in its temporally varying response to both intensity and rate of indentation force by combining a physical force sensor, housed in a skin-like substrate, with a mathematical model of neuronal spiking, the leaky integrate-and-fire. Comparison experiments were then conducted using ramp-and-hold stimuli on both the spiking-sensor model and mouse SAI afferents. The model parameters were iteratively fit against recorded SAI interspike intervals (ISI) before validating the model to assess its performance.

Results

Model-predicted spike firing compares favorably with that observed for single SAI afferents. As indentation magnitude increases (1.2, 1.3, to 1.4 mm), mean ISI decreases from 98.81 ± 24.73, 54.52 ± 6.94, to 41.11 ± 6.11 ms. Moreover, as rate of ramp-up increases, ISI during ramp-up decreases from 21.85 ± 5.33, 19.98 ± 3.10, to 15.42 ± 2.41 ms. Considering first spikes, the predicted latencies exhibited a decreasing trend as stimulus rate increased, as is observed in afferent recordings. Finally, the SAI afferent’s characteristic response of producing irregular ISIs is shown to be controllable via manipulating the output filtering from the sensor or adding stochastic noise.

Conclusions

This integrated engineering approach extends prior works focused upon neural dynamics and vibration. Future efforts will perfect measures of performance, such as first spike latency and irregular ISIs, and link the generation of characteristic features within trains of action potentials with current pulse waveforms that stimulate single action potentials at the peripheral afferent.
Isolation of a reassortant H13N2 virus from a mallard fecal sample in South Korea
Authors: Kang Hyun-Mi , Choi Jun-Gu , Kim Min-Chul , Kim Hye-Ryoung , Oem Jae-Ku , Bae You-Chan , Paek Mi-Ra , Kwon Jun-Hun , Lee Youn-Jeong
Published: July 2012

Background

Virus subtype H13N2, A/mallard/Kr/SH38-45/2010 (H13N2), was first isolated from a mallard fecal sample in South Korea.

Results

Phylogenetic analysis of all eight viral genes revealed that this virus emerged by genetic mixing between Eurasian and North American gene pools, and possibly between wild ducks and gulls. The H13 and N2 surface genes clustered together in a group with Eurasian isolates from gulls and wild birds, respectively. The PB2, PA, NP, M and NS segments belonged to the Eurasian lineage, whereas the PB1 gene clustered in the North American lineage. Furthermore, they showed a bird-dependent pattern in phylogenetic analysis: the M gene was similar to subtype H13 viruses within gulls, whereas other segments were similar to avian influenza viruses of other subtypes from wild ducks.

Conclusions

The data suggests that the novel reassortant H13N2 virus isolated in South Korea might have emerged by genetic reassortment between intercontinental and interspecies transmission in wild birds.
Comparison of serological assays for detecting antibodies in ducks exposed to H5 subtype avian influenza virus
Authors: Wibawa Hendra , Henning Joerg , Waluyati Dessie Eri , Usman Tri Bhakti , Lowther Sue , Bingham John , Junaidi Akhmad , Meers Joanne
Published: July 2012

Background

Chicken red blood cells (RBCs) are commonly used in hemagglutination inhibition (HI) tests to measure hemagglutinating antibodies against influenza viruses. The use of horse RBCs in the HI test can reportedly increase its sensitivity when testing human sera for avian influenza antibodies. This study aims to compare the proportion of positives detected and the agreement between two HI tests using either chicken or horse red blood cells for antibody detection in sera of ducks experimentally infected or naturally exposed to Indonesian H5 subtype avian influenza virus. In addition, comparison with a virus neutralisation (VN) test was conducted with the experimental sera.

Results

In the experimental study, the proportion of HI antibody-positive ducks increased slightly, from 0.57 when using chicken RBCs to 0.60 when using horse RBCs. The HI tests indicated almost perfect agreement (kappa = 0.86) when results were dichotomised (titre ≥ 4 log2), and substantial agreement (weighted kappa = 0.80) for log titres. Overall agreements between the two HI tests were greater than between either of the HI tests and the VN test. The use of horse RBCs also identified a higher proportion of antibody positives in field duck sera (0.08, compared to chicken RBCs 0.02), with also almost perfect agreements for dichotomized results (Prevalence and bias adjusted Kappa (PABAK) = 0.88) and for log titres (weighted PABAK = 0.93), respectively. Factors that might explain observed differences in the proportion of antibody-positive ducks and in the agreements between HI tests are discussed.

Conclusion

In conclusion, we identified a good agreement between HI tests. However, when horse RBCs were used, a higher proportion of sera was positive (titre ≥ 4 log2) than using chicken RBCs, especially during the early response against H5N1 virus. The HRBC-HI might be more responsive in identifying early H5N1 HPAI serological response and could be a recommended assay for avian influenza sero-surveillance in both wild and domestic birds.
The chemokine receptor cxcr5 regulates the regenerative neurogenesis response in the adult zebrafish brain
Authors: Kizil Caghan , Dudczig Stefanie , Kyritsis Nikos , Machate Anja , Blaesche Juliane , Kroehne Volker , Brand Michael
Published: July 2012

Background

Unlike mammals, zebrafish exhibits extensive neural regeneration after injury in adult stages of its lifetime due to the neurogenic activity of the radial glial cells. However, the genes involved in the regenerative neurogenesis response of the zebrafish brain are largely unknown. Thus, understanding the underlying principles of this regeneration capacity of the zebrafish brain is an interesting research realm that may offer vast clinical ramifications.

Results

In this paper, we characterized the expression pattern of cxcr5 and analyzed the function of this gene during adult neurogenesis and regeneration of the zebrafish telencephalon. We found that cxcr5 was upregulated transiently in the RGCs and neurons, and the expression in the immune cells such as leukocytes was negligible during both adult neurogenesis and regeneration. We observed that the transgenic misexpression of cxcr5 in the ventricular cells using dominant negative and full-length variants of the gene resulted in altered proliferation and neurogenesis response of the RGCs. When we knocked down cxcr5 using antisense morpholinos and cerebroventricular microinjection, we observed outcomes similar to the overexpression of the dominant negative cxcr5 variant.

Conclusions

Thus, based on our results, we propose that cxcr5 imposes a proliferative permissiveness to the radial glial cells and is required for differentiation of the RGCs to neurons, highlighting novel roles of cxcr5 in the nervous system of vertebrates. We therefore suggest that cxcr5 is an important cue for ventricular cell proliferation and regenerative neurogenesis in the adult zebrafish telencephalon. Further studies on the role of cxcr5 in mediating neuronal replenishment have the potential to produce clinical ramifications in efforts for regenerative therapeutic applications for human neurological disorders or acute injuries.
Synergistic influence of phosphorylation and metal ions on tau oligomer formation and coaggregation with α-synuclein at the single molecule level
Authors: Nübling Georg , Bader Benedikt , Levin Johannes , Hildebrandt Jenna , Kretzschmar Hans , Giese Armin
Published: July 2012

Background

Fibrillar amyloid-like deposits and co-deposits of tau and α-synuclein are found in several common neurodegenerative diseases. Recent evidence indicates that small oligomers are the most relevant toxic aggregate species. While tau fibril formation is well-characterized, factors influencing tau oligomerization and molecular interactions of tau and α-synuclein are not well understood.

Results

We used a novel approach applying confocal single-particle fluorescence to investigate the influence of tau phosphorylation and metal ions on tau oligomer formation and its coaggregation with α-synuclein at the level of individual oligomers. We show that Al3+ at physiologically relevant concentrations and tau phosphorylation by GSK-3β exert synergistic effects on the formation of a distinct SDS-resistant tau oligomer species even at nanomolar protein concentration. Moreover, tau phosphorylation and Al3+ as well as Fe3+ enhanced both formation of mixed oligomers and recruitment of α-synuclein in pre-formed tau oligomers.

Conclusions

Our findings provide a new perspective on interactions of tau phosphorylation, metal ions, and the formation of potentially toxic oligomer species, and elucidate molecular crosstalks between different aggregation pathways involved in neurodegeneration.
Multiple independent analyses reveal only transcription factors as an enriched functional class associated with microRNAs
Authors: Croft Larry , Szklarczyk Damian , Jensen Lars Juhl , Gorodkin Jan
Published: July 2012

Background

Transcription factors (TFs) have long been known to be principally activators of transcription in eukaryotes and prokaryotes. The growing awareness of the ubiquity of microRNAs (miRNAs) as suppressive regulators in eukaryotes, suggests the possibility of a mutual, preferential, self-regulatory connectivity between miRNAs and TFs. Here we investigate the connectivity from TFs and miRNAs to other genes and each other using text mining, TF promoter binding site and 6 different miRNA binding site prediction methods.

Results

In the first approach text mining of PubMed abstracts reveal statistically significant associations between miRNAs and both TFs and signal transduction gene classes. Secondly, prediction of miRNA targets in human and mouse 3’UTRs show enrichment only for TFs but not consistently across prediction methods for signal transduction or other gene classes. Furthermore, a random sample of 986 TarBase entries was scored for experimental evidence by manual inspection of the original papers, and enrichment for TFs was observed to increase with score. Low-scoring TarBase entries, where experimental evidence is anticorrelated miRNA:mRNA expression with predicted miRNA targets, appear not to select for real miRNA targets to any degree. Our manually validated text-mining results also suggests that miRNAs may be activated by more TFs than other classes of genes, as 7% of miRNA:TF co-occurrences in the literature were TFs activating miRNAs. This was confirmed when thirdly, we found enrichment for predicted, conserved TF binding sites in miRNA and TF genes compared to other gene classes.

Conclusions

We see enrichment of connections between miRNAs and TFs using several independent methods, suggestive of a network of mutual activating and suppressive regulation. We have also built regulatory networks (containing 2- and 3-loop motifs) for mouse and human using predicted miRNA and TF binding sites and we have developed a web server to search and display these loops, available for the community at http://rth.dk/resources/tfmirloop.
Breast systemic follicular lymphoma in a man: a case report
Authors: La Mantia Elvira , Cantile Monica , Liguori Giuseppina , Di Bonito Maurizio , De Chiara Annarosaria , D'Aiuto Massimiliano , Pannone Giuseppe , Franco Renato , Botti Gerardo
Published: July 2012

Introduction

Breast involvement by non-Hodgkin lymphoma is particularly rare in men. We describe the case of a patient with a rapidly growing, painless gynecomastia-like nodule in the left breast. On ultrasonography, the nodule was suspicious for breast carcinoma.

Case presentation

A breast biopsy from a 54-year-old Caucasian man showed the morphoimmunophenotypical features of grade 3 follicular lymphoma. Moreover, fluorescence in situ hybridization analysis showed a t(14,18) translocation suggesting breast involvement by a systemic lymphoma rather than a primary breast lymphoma. The histological diagnosis was subsequently confirmed after nodule excision. Mediastinal and abdominal node involvement was then identified on computed tomography and positron emission tomography scans during staging examinations. Our patient was treated with chemotherapy. After three years our patient experienced a right retro-areolar relapse. He then received two further cycles of chemotherapy but developed a myeloid acute leukemia and, as a result of this, he subsequently died.

Conclusions

The rarity of breast lymphomas, especially in men, and the problems related to the therapeutic choices with these tumors require molecular techniques in association with classical histological diagnosis.
A comparison and evaluation of five biclustering algorithms by quantifying goodness of biclusters for gene expression data
Authors: Li Li , Guo Yang , Wu Wenwu , Shi Youyi , Cheng Jian , Tao Shiheng
Published: July 2012

Background

Several biclustering algorithms have been proposed to identify biclusters, in which genes share similar expression patterns across a number of conditions. However, different algorithms would yield different biclusters and further lead to distinct conclusions. Therefore, some testing and comparisons between these algorithms are strongly required.

Methods

In this study, five biclustering algorithms (i.e. BIMAX, FABIA, ISA, QUBIC and SAMBA) were compared with each other in the cases where they were used to handle two expression datasets (GDS1620 and pathway) with different dimensions in Arabidopsis thaliana (A. thaliana)

GO (gene ontology) annotation and PPI (protein-protein interaction) network were used to verify the corresponding biological significance of biclusters from the five algorithms. To compare the algorithms’ performance and evaluate quality of identified biclusters, two scoring methods, namely weighted enrichment (WE) scoring and PPI scoring, were proposed in our study. For each dataset, after combining the scores of all biclusters into one unified ranking, we could evaluate the performance and behavior of the five biclustering algorithms in a better way.

Results

Both WE and PPI scoring methods has been proved effective to validate biological significance of the biclusters, and a significantly positive correlation between the two sets of scores has been tested to demonstrate the consistence of these two methods.

A comparative study of the above five algorithms has revealed that: (1) ISA is the most effective one among the five algorithms on the dataset of GDS1620 and BIMAX outperforms the other algorithms on the dataset of pathway. (2) Both ISA and BIMAX are data-dependent. The former one does not work well on the datasets with few genes, while the latter one holds well for the datasets with more conditions. (3) FABIA and QUBIC perform poorly in this study and they may be suitable to large datasets with more genes and more conditions. (4) SAMBA is also data-independent as it performs well on two given datasets. The comparison results provide useful information for researchers to choose a suitable algorithm for each given dataset.
Identity and diversity of blood meal hosts of biting midges (Diptera: Ceratopogonidae: Culicoides Latreille) in Denmark
Authors: Lassen Sandra B , Nielsen Søren Achim , Kristensen Michael
Published: July 2012

Background

Host preference studies in haematophagous insects e.g. Culicoides biting midges are pivotal to assess transmission routes of vector-borne diseases and critical for the development of veterinary contingency plans to identify which species should be included due to their risk potential. Species of Culicoides have been found in almost all parts of the world and known to live in a variety of habitats. Several parasites and viruses are transmitted by Culicoides biting midges including Bluetongue virus and Schmallenberg virus. The aim of the present study was to determine the identity and diversity of blood meals taken from vertebrate hosts in wild-caught Culicoides biting midges near livestock farms.

Methods

Biting midges were collected at weekly intervals for 20 weeks from May to October 2009 using light traps at four collection sites on the island Sealand, Denmark. Blood-fed female biting midges were sorted and head and wings were removed for morphological species identification. The thoraxes and abdomens including the blood meals of the individual females were subsequently subjected to DNA isolation. The molecular marker cytochrome oxidase I (COI barcode) was applied to identify the species of the collected biting midges (GenBank accessions JQ683259-JQ683374). The blood meals were first screened with a species-specific cytochrome b primer pair for cow and if negative with a universal cytochrome b primer pair followed by sequencing to identify mammal or avian blood meal hosts.

Results

Twenty-four species of biting midges were identified from the four study sites. A total of 111,356 Culicoides biting midges were collected, of which 2,164 were blood-fed. Specimens of twenty species were identified with blood in their abdomens. Blood meal sources were successfully identified by DNA sequencing from 242 (76%) out of 320 Culicoides specimens. Eight species of mammals and seven species of birds were identified as blood meal hosts. The most common host species was the cow, which constituted 77% of the identified blood meals. The second most numerous host species was the common wood pigeon, which constituted 6% of the identified blood meals.

Conclusions

Our results suggest that some Culicoides species are opportunistic and readily feed on a variety of mammals and birds, while others seems to be strictly mammalophilic or ornithophilic. Based on their number, dispersal potential and blood feeding behaviour, we conclude that Culicoides biting midges are potential vectors for many pathogens not yet introduced to Denmark.