bluuebunny/crossref_metadata_2025 huggingface dataset:
Gene bi-targeting by viral and human miRNAs
Authors: Veksler-Lublinsky Isana , Shemer-Avni Yonat , Kedem Klara , Ziv-Ukelson Michal
Published: May 2010

Background

MicroRNAs (miRNAs) are an abundant class of small noncoding RNAs (20-24 nts) that can affect gene expression by post-transcriptional regulation of mRNAs. They play important roles in several biological processes (e.g., development and cell cycle regulation). Numerous bioinformatics methods have been developed to identify the function of miRNAs by predicting their target mRNAs. Some viral organisms also encode miRNAs, a fact that contributes to the complex interactions between viruses and their hosts. A need arises to understand the functional relationship between viral and host miRNAs and their effect on viral and host genes. Our approach to meet this challenge is to identify modules where viral and host miRNAs cooperatively regulate host gene expression.

Results

We present a method to identify groups of viral and host miRNAs that cooperate in post-transcriptional gene regulation, and their target genes that are involved in similar biological processes. We call these groups (genes and miRNAs of human and viral origin) - modules. The modules are found in a new two-stage procedure, which we call bi-targeting, and is presented in this paper. The stages are (i) a new and efficient target prediction, and (ii) a new method for clustering objects of three different data types. In this work we integrate multiple information sources, including miRNA-target binding information, miRNA expression profiles, and GO annotations. Our hypotheses and the methods have been tested on human and Epstein Barr virus (EBV) miRNAs and human genes, for which we found 34 modules. We provide supporting evidence from biological and medical literature for two of our modules. Our code and data are available at http://www.cs.bgu.ac.il/~vaksler/BiTargeting.htm

Conclusions

The presented algorithm, which makes use of diverse biological data, is demonstrated to be an efficient approach for finding bi-targeting modules of viral and human miRNAs. These modules can contribute to a better understanding of viral-host interactions and the role that miRNAs play in them.
The gene transformer-2 of Anastrephafruit flies (Diptera, Tephritidae) and its evolution in insects
Authors: Sarno Francesca , Ruiz María F , Eirín-López José M , Perondini André LP , Selivon Denise , Sánchez Lucas
Published: May 2010

Background

In the tephritidsCeratitis,BactroceraandAnastrepha, the genetransformerprovides the memory device for sex determination via its auto-regulation; only in females is functional Tra protein produced. To date, the isolation and characterisation of the genetransformer-2in the tephritids has only been undertaken inCeratitis, and it has been shown that its function is required for the female-specific splicing ofdoublesexandtransformerpre-mRNA. It therefore participates intransformerauto-regulatory function. In this work, the characterisation of this gene in eleven tephritid species belonging to the less extensively analysed genusAnastrephawas undertaken in order to throw light on the evolution oftransformer-2.

Results

The genetransformer-2produces a protein of 249 amino acids in both sexes, which shows the features of the SR protein family. No significant partially spliced mRNA isoform specific to the male germ line was detected, unlike inDrosophila. It is transcribed in both sexes during development and in adult life, in both the soma and germ line. The injection ofAnastrepha transformer-2dsRNA intoAnastrephaembryos caused a change in the splicing pattern of the endogenoustransformeranddoublesexpre-mRNA of XX females from the female to the male mode. Consequently, these XX females were transformed into pseudomales. The comparison of the elevenAnastrephaTransformer-2 proteins among themselves, and with the Transformer-2 proteins of other insects, suggests the existence of negative selection acting at the protein level to maintain Transformer-2 structural features.

Conclusions

These results indicate thattransformer-2is required for sex determination inAnastrephathrough its participation in the female-specific splicing oftransformeranddoublesexpre-mRNAs. It is therefore needed for the auto-regulation of the genetransformer. Thus, thetransformer/transfomer-2 > doublesexelements at the bottom of the cascade, and their relationships, probably represent the ancestral state (which still exists in the Tephritidae, Calliphoridae and Muscidae lineages) of the extant cascade found in the Drosophilidae lineage (in whichtrais just another component of the sex determination gene cascade regulated bySex-lethal). In the phylogenetic lineage that gave rise to the drosophilids, evolution co-opted forSex-lethal, modified it, and converted it into the key gene controlling sex determination.
Duplication, concerted evolution and purifying selection drive the evolution of mosquito vitellogenin genes
Authors: Chen Song , Armistead Jennifer S , Provost-Javier Katie N , Sakamoto Joyce M , Rasgon Jason L
Published: May 2010

Background

Mosquito vitellogenin (Vtg) genes belong to a small multiple gene family that encodes the major yolk protein precursors required for egg production. Multiple Vtg genes have been cloned and characterized from several mosquito species, but their origin and molecular evolution are poorly understood.

Results

Here we used in silico and molecular cloning techniques to identify and characterize the evolution of the Vtg gene family from the genera Culex, Aedes/Ochlerotatus, and Anopheles. We identified the probable ancestral Vtg gene among different mosquito species by its conserved association with a novel gene approximately one kilobase upstream of the start codon. Phylogenetic analysis indicated that the Vtg gene family arose by duplication events, but that the pattern of duplication was different in each mosquito genera. Signatures of purifying selection were detected in Culex, Aedes and Anopheles. Gene conversion is a major driver of concerted evolution in Culex, while unequal crossover is likely the major driver of concerted evolution in Anopheles. In Aedes, smaller fragments have undergone gene conversion events.

Conclusions

The study shows concerted evolution and purifying selection shaped the evolution of mosquito Vtg genes following gene duplication. Additionally, similar evolutionary patterns were observed in the Vtg genes from other invertebrate and vertebrate organisms, suggesting that duplication, concerted evolution and purifying selection may be the major evolutionary forces driving Vtg gene evolution across highly divergent taxa.
Massively parallel pyrosequencing-based transcriptome analyses of small brown planthopper (Laodelphax striatellus), a vector insect transmitting rice stripe virus (RSV)
Authors: Zhang Fujie , Guo Hongyan , Zheng Huajun , Zhou Tong , Zhou Yijun , Wang Shengyue , Fang Rongxiang , Qian Wei , Chen Xiaoying
Published: May 2010

Background

The small brown planthopper (Laodelphax striatellus) is an important agricultural pest that not only damages rice plants by sap-sucking, but also acts as a vector that transmits rice stripe virus (RSV), which can cause even more serious yield loss. Despite being a model organism for studying entomology, population biology, plant protection, molecular interactions among plants, viruses and insects, only a few genomic sequences are available for this species. To investigate its transcriptome and determine the differences between viruliferous and naïve L. striatellus, we employed 454-FLX high-throughput pyrosequencing to generate EST databases of this insect.

Results

We obtained 201,281 and 218,681 high-quality reads from viruliferous and naïve L. striatellus, respectively, with an average read length as 230 bp. These reads were assembled into contigs and two EST databases were generated. When all reads were combined, 16,885 contigs and 24,607 singletons (a total of 41,492 unigenes) were obtained, which represents a transcriptome of the insect. BlastX search against the NCBI-NR database revealed that only 6,873 (16.6%) of these unigenes have significant matches. Comparison of the distribution of GO classification among viruliferous, naïve, and combined EST databases indicated that these libraries are broadly representative of the L. striatellus transcriptomes. Functionally diverse transcripts from RSV, endosymbiotic bacteria Wolbachia and yeast-like symbiotes were identified, which reflects the possible lifestyles of these microbial symbionts that live in the cells of the host insect. Comparative genomic analysis revealed that L. striatellus encodes similar innate immunity regulatory systems as other insects, such as RNA interference, JAK/STAT and partial Imd cascades, which might be involved in defense against viral infection. In addition, we determined the differences in gene expression between vector and naïve samples, which generated a list of candidate genes that are potentially involved in the symbiosis of L. striatellus and RSV.

Conclusions

To our knowledge, the present study is the first description of a genomic project for L. striatellus. The identification of transcripts from RSV, Wolbachia, yeast-like symbiotes and genes abundantly expressed in viruliferous insect, provided a starting-point for investigating the molecular basis of symbiosis among these organisms.
Primary gamma-herpesviral infection in Zambian children
Authors: Minhas Veenu , Brayfield Brad P , Crabtree Kay L , Kankasa Chipepo , Mitchell Charles D , Wood Charles
Published: May 2010

Background

HHV-8 is closely related to Epstein-Barr virus (EBV), but the clinical presentations of these two infections in early childhood are not well understood. Also, it is not known whether infection by one virus correlates with another. Here, we compare the natural history of infection by these two viruses along with the clinical manifestations and risk factors that are associated with early childhood infection in Zambia, which is an endemic area for HHV-8.

Methods

This study was conducted in a cohort of 12 month old Zambian children (N = 677). Data on socio-economic status and a wide range of clinical manifestations were collected. Logistic regression was used to test for significant associations between the collected variables and HHV-8 or EBV serostatus at 12 months of age.

Results

We observed a significantly higher seroprevalence for EBV (58.9%) as compared to HHV-8 (13.4%). HIV-1 infected children had at a significantly higher risk of being infected with HHV-8 (Odds ratio [OR] 3.69, 95% confidence interval [CI] 1.64 - 8.32). HIV-1 infection of the mothers was a significant risk factor for increased acquisition of EBV but not HHV-8 by children (OR 1.86, 05% CI 1.20 - 2.87). Self reported rash was marginally associated with primary infection for HHV-8 and EBV.

Conclusions

These results suggest that there is no correlation between EBV and HHV-8 infections. Infection by one does not increase the susceptibility for the second virus. Primary HHV-8 and EBV infection in early childhood may clinically present as rash but remains largely asymptomatic and may remain undetected in this population. HIV infection in the mother or child are important risk factors that contribute to EBV or HHV-8 infection.
A long-term follow-up of the imatinib mesylate treatment for the patients with recurrent gastrointestinal stromal tumor (GIST): the liver metastasis and the outcome
Authors: Zhu Jiang , Yang Yu , Zhou Lin , Jiang Ming , Hou Mei
Published: May 2010

Background

About 80% of patients with GIST would experience tumor recurrence or metastasis after radical resection. The most common site of the metastasis is the liver. Imatinib mesylate has been proved effective for advanced GIST. The present study was designed to further observe the effectiveness of the imatinib mesylate treatment on the recurrent GIST and the correlation between the liver metastasis and the outcome.

Methods

Forty-two patients who had recurrent GIST after the first radical resection were enrolled. According to the recurrent sites, the patients were divided into 3 groups: group LG (recurrent liver GISTs), group AG (recurrent abdominal GISTs) and group ALG (recurrent abdominal and liver GISTs). All the patients were given imatinib mesylate at an initial dose of 400 mg per day. Their clinical data was prospectively collected. A follow-up over 3 years was conducted. Tumor response, time to progression and survival were evaluated.

Results

The long-term Imatinib mesylate treatment was safe and well tolerated. At a median follow-up time for 39.5 months, the 3-year survival rate was 66.7%. Median TTP and OS were 37 months (95% CI: 28.2~45.8 months) and 48 months (95% CI: 37.0~58.9 months), respectively. There was no statistical difference in tumor response among the 3 groups. The similar TTP (P = 0.291) and OS (P = 0.160) were observed in the 3 groups.

Conclusions

The imatinib mesylate treatment could prolong the survival of the patients who have recurrent GIST after the radical surgery in spite of an existence of the liver metastasis. Survival was not significantly affected by liver metastasis when imatinib mesylate was warranted.
Seladin-1 expression is regulated by promoter methylation in adrenal cancer
Authors: Simi Lisa , Malentacchi Francesca , Luciani Paola , Gelmini Stefania , Deledda Cristiana , Arvia Rosaria , Mannelli Massimo , Peri Alessandro , Orlando Claudio
Published: May 2010

Background

Seladin-1 overexpression exerts a protective mechanism against apoptosis. Seladin-1 mRNA is variably expressed in normal human tissues. Adrenal glands show the highest levels of seladin-1 expression, which are significantly reduced in adrenal carcinomas (ACC). Since up to now seladin-1 mutations were not described, we investigated whether promoter methylation could account for the down-regulation of seladin-1 expression in ACC.

Methods

A methylation sensitive site was identified in the seladin-1 gene. We treated DNA extracted from two ACC cell lines (H295R and SW13) with the demethylating agent 5-Aza-2-deoxycytidine (5-Aza). Furthermore, to evaluate the presence of an epigenetic regulation also 'in vivo', seladin-1 methylation and its mRNA expression were measured in 9 ACC and in 5 normal adrenal glands.

Results

The treatment of cell lines with 5-Aza induced a significant increase of seladin-1 mRNA expression in H295R (fold increase, F.I. = 1.8; p = 0.02) and SW13 (F.I. = 2.9; p = 0.03). In ACC, methylation density of seladin-1 promoter was higher (2682 ± 686) than in normal adrenal glands (362 ± 97; p = 0.02). Seladin-1 mRNA expression in ACC (1452 ± 196) was significantly lower than in normal adrenal glands (3614 ± 949; p = 0.01).

Conclusion

On this basis, methylation could be involved in the altered pattern of seladin-1 gene expression in ACC.
From design to implementation - The Joint Asia Diabetes Evaluation (JADE) program: A descriptive report of an electronic web-based diabetes management program
Authors: Ko Gary T , So Wing-Yee , Tong Peter C , Le Coguiec Francois , Kerr Debborah , Lyubomirsky Greg , Tamesis Beaver , Wolthers Troels , Nan Jennifer , Chan Juliana
Published: May 2010

Background

The Joint Asia Diabetes Evaluation (JADE) Program is a web-based program incorporating a comprehensive risk engine, care protocols, and clinical decision support to improve ambulatory diabetes care.

Methods

The JADE Program uses information technology to facilitate healthcare professionals to create a diabetes registry and to deliver an evidence-based care and education protocol tailored to patients' risk profiles. With written informed consent from participating patients and care providers, all data are anonymized and stored in a databank to establish an Asian Diabetes Database for research and publication purpose.

Results

The JADE electronic portal (e-portal: http://www.jade-adf.org) is implemented as a Java application using the Apache web server, the mySQL database and the Cocoon framework. The JADE e-portal comprises a risk engine which predicts 5-year probability of major clinical events based on parameters collected during an annual comprehensive assessment. Based on this risk stratification, the JADE e-portal recommends a care protocol tailored to these risk levels with decision support triggered by various risk factors. Apart from establishing a registry for quality assurance and data tracking, the JADE e-portal also displays trends of risk factor control at each visit to promote doctor-patient dialogues and to empower both parties to make informed decisions.

Conclusions

The JADE Program is a prototype using information technology to facilitate implementation of a comprehensive care model, as recommended by the International Diabetes Federation. It also enables health care teams to record, manage, track and analyze the clinical course and outcomes of people with diabetes.
A nuclear targeting system in Plasmodium falciparum
Authors: Wittayacom Kanjana , Uthaipibull Chairat , Kumpornsin Krittikorn , Tinikul Ruchanok , Kochakarn Theerarat , Songprakhon Pucharee , Chookajorn Thanat
Published: May 2010

Background

The distinct differences in gene control mechanisms acting in the nucleus betweenPlasmodium falciparumand the human host could lead to new potential drug targets for anti-malarial development. New molecular toolkits are required for dissecting molecular machineries in theP. falciparumnucleus. One valuable tool commonly used in model organisms is protein targeting to specific sub-cellular locations. Targeting proteins to specified locations allows labeling of organelles for microscopy, or testing of how the protein of interest modulates organelle function. In recent years, this approach has been developed for various malaria organelles, such as the mitochondrion and the apicoplast. A tool for targeting a protein of choice to theP. falciparumnucleus using an exogenous nuclear localization sequence is reported here.

Methods

To develop a nuclear targeting system, a putative nuclear localization sequence was fused with green fluorescent protein (GFP). The nuclear localization sequence from the yeast transcription factor Gal4 was chosen because of its well-defined nuclear localization signal. A series of truncated Gal4 constructs was also created to narrow down the nuclear localization sequence necessary forP. falciparumnuclear import. Transfected parasites were analysed by fluorescent and laser-scanning confocal microscopy.

Results

The nuclear localization sequence of Gal4 is functional inP. falciparum. It effectively transported GFP into the nucleus, and the first 74 amino acid residues were sufficient for nuclear localization.

Conclusions

The Gal4 fusion technique enables specific transport of a protein of choice into theP. falciparumnucleus, and thus provides a tool for labeling nuclei without using DNA-staining dyes. The finding also indicates similarities between the nuclear transport mechanisms of yeast andP. falciparum. Since the nuclear transport system has been thoroughly studied in yeast, this could give clues to research on the same mechanism inP. falciparum.
Overdose experiences among injection drug users in Bangkok, Thailand
Authors: Milloy M-J , Fairbairn Nadia , Hayashi Kanna , Suwannawong Paisan , Kaplan Karyn , Wood Evan , Kerr Thomas
Published: May 2010

Background

Although previous studies have identified high levels of drug-related harm in Thailand, little is known about illicit drug overdose experiences among Thai drug users. We sought to investigate non-fatal overdose experiences and responses to overdose among a community-recruited sample of injection drug users (IDU) in Bangkok, Thailand.

Methods

Data for these analyses came from IDU participating in the Mit Sampan Community Research Project. The primary outcome of interest was a self-reported history of non-fatal overdose. We calculated the prevalence of past overdose and estimated its relationship with individual, drug-using, social, and structural factors using multivariate logistic regression. We also assessed the prevalence of ever witnessing an overdose and patterns of response to overdose.

Results

These analyses included 252 individuals; their median age was 36.5 years (IQR: 29.0 - 44.0) and 66 (26.2%) were female. A history of non-fatal overdose was reported by 75 (29.8%) participants. In a multivariate model, reporting a history of overdose was independently associated with a history of incarceration (Adjusted Odds Ratio [AOR] = 3.83, 95% Confidence Interval [CI]: 1.52 - 9.65, p = 0.004) and reporting use of drugs in combination (AOR = 2.48, 95% CI: 1.16 - 5.33, p = 0.019). A majority (67.9%) reported a history of witnessing an overdose; most reported responding to the most recent overdose using first aid (79.5%).

Conclusions

Experiencing and witnessing an overdose were common in this sample of Thai IDU. These findings support the need for increased provision of evidence-based responses to overdose including peer-based overdose interventions.
Selective and rapid monitoring of dual platelet inhibition by aspirin and P2Y12 antagonists by using multiple electrode aggregometry
Authors: Penz Sandra M , Bernlochner Isabell , Tóth Orsolya , Lorenz Reinhard , Calatzis Andreas , Siess Wolfgang
Published: May 2010

Background

Poor platelet inhibition by aspirin or clopidogrel has been associated with adverse outcomes in patients with cardiovascular diseases. A reliable and facile assay to measure platelet inhibition after treatment with aspirin and a P2Y12 antagonist is lacking. Multiple electrode aggregometry (MEA), which is being increasingly used in clinical studies, is sensitive to platelet inhibition by aspirin and clopidogrel, but a critical evaluation of MEA monitoring of dual anti-platelet therapy with aspirin and P2Y12 antagonists is missing.

Design and Methods

By performing in vitro and ex vivo experiments, we evaluated in healthy subjects the feasibility of using MEA to monitor platelet inhibition of P2Y12 antagonists (clopidogrel in vivo, cangrelor in vitro) and aspirin (100 mg per day in vivo, and 1 mM or 5.4 mM in vitro) alone, and in combination. Statistical analyses were performed by the Mann-Whitney rank sum test, student' t-test, analysis of variance followed by the Holm-Sidak test, where appropriate.

Results

ADP-induced platelet aggregation in hirudin-anticoagulated blood was inhibited by 99.3 ± 1.4% by in vitro addition of cangrelor (100 nM; p < 0.001) and by 64 ± 35% by oral clopidogrel (600 mg) intake (p < 0.05; values are means ± SD). Pre-incubation of blood with aspirin (1 mM) or oral aspirin intake (100 mg/day for 1 week) inhibited arachidonic acid (AA)-stimulated aggregation >95% and 100 ± 3.2%, respectively (p < 0.01). Aspirin did not influence ADP-induced platelet aggregation, either in vitro or ex vivo. Oral intake of clopidogrel did not significantly reduce AA-induced aggregation, but P2Y12 blockade by cangrelor (100 nM) in vitro diminished AA-stimulated aggregation by 53 ± 26% (p < 0.01). A feasibility study in healthy volunteers showed that dual anti-platelet drug intake (aspirin and clopidogrel) could be selectively monitored by MEA.

Conclusions

Selective platelet inhibition by aspirin and P2Y12 antagonists alone and in combination can be rapidly measured by MEA. We suggest that dual anti-platelet therapy with these two types of anti-platelet drugs can be optimized individually by measuring platelet responsiveness to ADP and AA with MEA before and after drug intake.
Enhancing versus Suppressive Effects of Stress on Immune Function: Implications for Immunoprotection versus Immunopathology
Authors: Dhabhar Firdaus S
Published: May 2010

It is widely believed that stress suppresses immune function and increases susceptibility to infections and cancer. Paradoxically, stress is also known to exacerbate allergic, autoimmune, and inflammatory diseases. These observations suggest that stress may have bidirectional effects on immune function, being immunosuppressive in some instances and immunoenhancing in others. It has recently been shown that in contrast to chronic stress that suppresses or dysregulates immune function, acute stress can be immunoenhancing. Acute stress enhances dendritic cell, neutrophil, macrophage, and lymphocyte trafficking, maturation, and function and has been shown to augment innate and adaptive immune responses. Acute stress experienced prior to novel antigen exposure enhances innate immunity and memory T-cell formation and results in a significant and long-lasting immunoenhancement. Acute stress experienced during antigen reexposure enhances secondary/adaptive immune responses. Therefore, depending on the conditions of immune activation and the immunizing antigen, acute stress may enhance the acquisition and expression of immunoprotection or immunopathology. In contrast, chronic stress dysregulates innate and adaptive immune responses by changing the type 1-type 2 cytokine balance and suppresses immunity by decreasing leukocyte numbers, trafficking, and function. Chronic stress also increases susceptibility to skin cancer by suppressing type 1 cytokines and protective T cells while increasing suppressor T-cell function. We have suggested that the adaptive purpose of a physiologic stress response may be to promote survival, with stress hormones and neurotransmitters serving as beacons that prepare the immune system for potential challenges (eg, wounding or infection) perceived by the brain (eg, detection of an attacker). However, this system may exacerbate immunopathology if the enhanced immune response is directed against innocuous or self-antigens or dysregulated following prolonged activation, as seen during chronic stress. In view of the ubiquitous nature of stress and its significant effects on immunoprotection and immunopathology, it is important to further elucidate the mechanisms mediating stress-immune interactions and to meaningfully translate findings from bench to bedside.
Stress and Childhood Asthma Risk: Overlapping Evidence from Animal Studies and Epidemiologic Research
Authors: Wright Rosalind J
Published: May 2010

Rapidly expanding evidence increasingly strengthens the evidence linking psychological factors to asthma and allergy expression. Parallel studies in animals and humans demonstrating the influence of prenatal maternal stress and early caregiving experiences on the disrupted regulation of defensive biological systems [eg, sympathetic and adrenomedullary (SAM) system and the hypothalamicpituitary-adrenocortical (HPA) axis] provide strong proof of concept for this line of research. The consequent altered neuroimmune responses may influence the expression of immune-mediated disorders such as asthma as well as enhance an individual's susceptibility to other environmental factors that may also contribute to asthma risk.
Expression of Nef from unintegrated HIV-1 DNA downregulates cell surface CXCR4 and CCR5 on T-lymphocytes
Authors: Sloan Richard D , Donahue Daniel A , Kuhl Björn D , Bar-Magen Tamara , Wainberg Mark A
Published: May 2010

Background

Transcription of HIV-1 cDNA prior to, or in the absence of, integration leads to synthesis of all classes of viral RNA transcripts. Yet only a limited range of viral proteins, including Nef, are translated in this context. Nef expression from unintegrated HIV-1 DNA has been shown to reduce cell surface CD4 levels in T-cells. We wished to determine whether Nef expressed from unintegrated DNA was also able to downregulate the chemokine coreceptors CXCR4 and CCR5.

Viral integration was blocked through use of an inactive integrase or by using the integrase inhibitor raltegravir. Infected cells bearing unintegrated DNA were assayed by flow cytometry in the GFP reporter cell line, Rev-CEM, for cell surface levels of CD4, CXCR4 and CCR5.

Results

In cells bearing only unintegrated HIV-1 DNA, we found that surface levels of CXCR4 were significantly reduced, while levels of CCR5 were also diminished, but not to the extent of CXCR4. We also confirmed the downregulation of CD4. Similar patterns of results were obtained with both integrase-deficient virus or with wild-type infections of cells treated with raltegravir. The Alu-HIV qPCR assay that we used for detection of proviral DNA did not detect any integrated viral DNA.

Conclusions

Our results demonstrate that Nef can be expressed from unintegrated DNA at functionally relevant levels and suggest a role for Nef in downregulation of CXCR4 and CCR5. These findings may help to explain how downregulation of CXCR4, CCR5 and CD4 might restrict superinfection and/or prevent signal transduction involving HIV-1 infected cells.
Rift Valley fever among febrile patients at New Halfa hospital, eastern Sudan
Authors: Hassanain Ahmed M , Noureldien Waleed , Karsany Mubarak S , Saeed Elnajeeb S , Aradaib Imadeldin E , Adam Ishag
Published: May 2010

Background

Since the first isolation of the Rift Valley Fever virus (RVFV) in 1930s, there have been several epizootics outbreaks in the tropic mainly in Africa including Sudan. Recognition of cases and diagnosis of RVF are critical for management and control of the disease.

Aims

To investigate the seroprevalence and risk factors for seropostive to RVFV IgG among febrile patients.

Methods

All febrile patients presented to New Halfa hospital in eastern Sudan during September through November 2007 were investigated to identify the cause of their fever including malaria and RFV.

Results

Out of 290 feverish patients presented to the hospital, malaria was diagnosis in 94 individuals. Fevers of unknown origin were diagnosed in 149 patients. Seropostive to RVFV IgG was detected by enzyme-linked immunosorbent assay in 122 (81.8%) of the sera from these 149 patients with fever of unknown origin. While socio-demographic characteristics (age, Job, education and residency) were not associated with seropostive to RVFV IgG, male (OR = 2.8, 95% CI = 1.0-7.6; P = 0.04) were at three times higher risk for seropostive to RVFV IgG.

Conclusion

There was a high seropostive to RVFV IgG in this setting, more research is needed perhaps using other methods like PCR and IGM.
Fruit and vegetable consumption and proinflammatory gene expression from peripheral blood mononuclear cells in young adults: a translational study
Authors: Hermsdorff Helen Hermana M , Zulet María Ángeles , Puchau Blanca , Martínez José Alfredo
Published: May 2010

Background

Fruits and vegetables are important sources of fiber and nutrients with a recognized antioxidant capacity, which could have beneficial effects on the proinflammatory status as well as some metabolic syndrome and cardiovascular disease features. The current study assessed the potential relationships of fruit and vegetable consumption with the plasma concentrations and mRNA expression values of some proinflammatory markers in young adults.

Methods

One-hundred and twenty healthy subjects (50 men/70 women; 20.8 ± 2.6 y; 22.3 ± 2.8 kg/m2) were enrolled. Experimental determinations included anthropometry, blood pressure and lifestyle features as well as blood biochemical and inflammatory measurements. The mRNA was isolated from peripheral blood mononuclear cells (PBMC) and the gene expression concerning selected inflammatory markers was assessed by quantitative real-time PCR. Nutritional intakes were estimated by a validated semi-quantitative food-frequency questionnaire.

Results

The highest tertile of energy-adjusted fruit and vegetable consumption (>660 g/d) was associated with lower plasma concentrations of C-reactive protein (CRP) and homocysteine and with lower ICAM1, IL1R1, IL6, TNFα and NFκB1 gene expression in PBMC (P for trend < 0.05), independently of gender, age, energy intake, physical activity, smoking, body mass index, systolic blood pressure and circulating non-esterified fatty acids. In addition, plasma CRP, homocysteine and TNFα concentrations and ICAM1, TNFα and NFκB1 gene expression in PBMC showed a descending trend as increased fiber intake (>19.5 g/d) from fruits and vegetables (P for trend < 0.05). Furthermore, the participants within the higher tertile (>11.8 mmol/d) of dietary total antioxidant capacity showed lower plasma CRP and mRNA values of ICAM1, IL1R1, IL6, TNFα and NFκB1 genes (P for trend < 0.05). The inverse association between fruit and vegetable consumption and study proinflammatory markers followed the same trend and remained statistically significant, after the inclusion of other foods/nutrients in the linear regression models.

Conclusion

A higher fruit and vegetable consumption was independently associated not only with reduced CRP and homocysteine concentrations but also with a lower mRNA expression in PBMC of some relevant proinflammatory markers in healthy young adults.
Minimal Important Difference (MID) of two commonly used outcome measures for foot problems
Authors: Landorf Karl B , Radford Joel A , Hudson Susie
Published: May 2010

Background

The Visual Analogue Scale (VAS) and the Foot Health Status Questionnaire (FHSQ) are two commonly used outcome measures for evaluating foot health. This study aimed to calculate the Minimal Important Difference (MID) of the VAS and the FHSQ.

Methods

184 participants with plantar heel pain were recruited from the general public to take part in two randomised trials (92 participants in each trial) that studied the effectiveness of two conservative interventions for plantar heel pain. Data from these participants were used to calculate the MIDs of the VAS and the FHSQ. An anchor‐based method was used to calculate the MIDs. Two distinct types of pain were investigated for the VAS: average pain and first‐step pain. All four domains of the FHSQ were investigated: foot pain, foot function, footwear and general foot health.

Results

The MID for the VAS using the anchor‐based approach was ‐8 mm (95% CI: ‐12 to ‐4) for average pain and ‐19 mm (95% CI: ‐25 to ‐13) for first‐step pain on the 100 mm VAS. The MID for the FHSQ was 13 points (95% CI: 6 to 19) for pain and 7 points (95% CI: 1 to 13) for function. The MID for the footwear domain of the FHSQ was ‐2 points (95% CI: ‐8 to 4) and 0 points (95% CI: ‐7 to 6) for the general foot health domain of the FHSQ.

Conclusion

The results of this study provide additional evidence for MID values of the VAS and the FHSQ for plantar heel pain. This is important for clinicians and researchers as it provides a greater understanding of how much improvement is required by a patient before a minimal, worthwhile change is experienced. The calculated MIDs will also assist researchers with prospective sample size calculations.
Management of bleeding following major trauma: an updated European guideline
Authors: Rossaint Rolf , Bouillon Bertil , Cerny Vladimir , Coats Timothy J , Duranteau Jacques , Fernández-Mondéjar Enrique , Hunt Beverley J , Komadina Radko , Nardi Giuseppe , Neugebauer Edmund , Ozier Yves , Riddez Louis , Schultz Arthur , Stahel Philip F , Vincent Jean-Louis , Spahn Donat R
Published: May 2010

Introduction

Evidence-based recommendations are needed to guide the acute management of the bleeding trauma patient, which when implemented may improve patient outcomes.

Methods

The multidisciplinary Task Force for Advanced Bleeding Care in Trauma was formed in 2005 with the aim of developing a guideline for the management of bleeding following severe injury. This document presents an updated version of the guideline published by the group in 2007. Recommendations were formulated using a nominal group process, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) hierarchy of evidence and based on a systematic review of published literature.

Results

Key changes encompassed in this version of the guideline include new recommendations on coagulation support and monitoring and the appropriate use of local haemostatic measures, tourniquets, calcium and desmopressin in the bleeding trauma patient. The remaining recommendations have been reevaluated and graded based on literature published since the last edition of the guideline. Consideration was also given to changes in clinical practice that have taken place during this time period as a result of both new evidence and changes in the general availability of relevant agents and technologies.

Conclusions

This guideline provides an evidence-based multidisciplinary approach to the management of critically injured bleeding trauma patients.
Seislet transform and seislet frame
Authors: Fomel Sergey , Liu Yang
Published: May 2010

We introduce a digital waveletlike transform, which is tailored specifically for representing seismic data. The transform provides a multiscale orthogonal basis with basis functions aligned along seismic events in the input data. It is defined with the help of the wavelet-lifting scheme combined with local plane-wave destruction. In the 1D case, the seislet transform is designed to follow locally sinusoidal components. In the 2D case, it is designed to follow local plane-wave components with smoothly variable slopes. If more than one component is present, the transform turns into an overcomplete representation or a tight frame. In these terms, the classic digital wavelet transform is simply a seislet transform for a zero frequency (in one dimension) or zero slope (in two dimensions). The main objective of the new transform is an effective seismic-data compression for designing efficient data-analysis algorithms. Traditional signal-processing tasks such as noise attenuation and trace interpolation become simply defined in the seislet domain. When applied in the offset direction on common-midpoint or common-image-point gathers, the seislet transform finds an additional application in optimal stacking of seismic records.
Protection of Pancreatic β-Cells by Group VIA Phospholipase A2-Mediated Repair of Mitochondrial Membrane Peroxidation
Authors: Zhao Zhengshan , Zhang Xu , Zhao Chunying , Choi Jinwoo , Shi Jieyi , Song Keying , Turk John , Ma Zhongmin Alex
Published: May 2010

Mitochondrial production of reactive oxygen species and oxidation of cardiolipin are key events in initiating apoptosis. We reported that group VIA Ca2+-independent phospholipase A2 (iPLA2β) localizes in and protects β-cell mitochondria from oxidative damage during staurosporine-induced apoptosis. Here, we used iPLA2β-null (iPLA2β−/−) mice to investigate the role of iPLA2β in the repair of mitochondrial membranes. We show that islets isolated from iPLA2β−/− mice are more sensitive to staurosporine-induced apoptosis than those from wild-type littermates and that 2 wk of daily ip administration of staurosporine to iPLA2β−/− mice impairs both the animals’ glucose tolerance and glucose-stimulated insulin secretion by their pancreatic islets. Moreover, the iPLA2β inhibitor bromoenol lactone caused mitochondrial membrane peroxidation and cytochrome c release, and these effects were reversed by N-acetyl cysteine. The mitochondrial antioxidant N-t-butyl hydroxylamine blocked staurosporine-induced cytochrome c release and caspase-3 activation in iPLA2β−/− islets. Furthermore, the collapse of mitochondrial membrane potential in INS-1 insulinoma cells caused by high glucose and fatty acid levels was attenuated by overexpressing iPLA2β. Interestingly, iPLA2β was expressed only at low levels in islet β-cells from obesity- and diabetes-prone db/db mice. These findings support the hypothesis that iPLA2β is important in repairing oxidized mitochondrial membrane components (e.g. cardiolipin) and that this prevents cytochrome c release in response to stimuli that otherwise induce apoptosis. The low iPLA2β expression level in db/db mouse β-cells may render them vulnerable to injury by reactive oxygen species.
Evidence for a Role of Prolactin in Calcium Homeostasis: Regulation of Intestinal Transient Receptor Potential Vanilloid Type 6, Intestinal Calcium Absorption, and the 25-Hydroxyvitamin D3 1α Hydroxylase Gene by Prolactin
Authors: Ajibade Dare V. , Dhawan Puneet , Fechner Adam J. , Meyer Mark B. , Pike J. Wesley , Christakos Sylvia
Published: May 2010

Increased calcium transport has been observed in vitamin D-deficient pregnant and lactating rats, indicating that another factor besides 1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) is involved in intestinal calcium transport. To investigate prolactin as a hormone involved in calcium homeostasis, vitamin D-deficient male mice were injected with 1,25(OH)2D3, prolactin, or prolactin + 1,25(OH)2D3. Prolactin alone (1 μg/g body weight 48, 24, and 4 h before termination) significantly induced duodenal transient receptor potential vanilloid type 6 (TRPV6) mRNA (4-fold) but caused no change in calbindin-D9k. Combined treatment with 1,25(OH)2D3 and prolactin resulted in an enhancement of the 1,25(OH)2D3 induction of duodenal TRPV6 mRNA, calbindin-D9k mRNA, and an induction of duodenal calcium transport [P < 0.05 compared with 1,25(OH)2D3 alone]. Because lactation is associated with an increase in circulating 1,25(OH)2D3, experiments were done to determine whether prolactin also has a direct effect on induction of 25-hydroxyvitamin D3 1α hydroxylase [1α(OH)ase]. Using AOK B-50 cells cotransfected with the prolactin receptor and the mouse 1α(OH)ase promoter −1651/+22 cooperative effects between prolactin and signal transducer and activator of transcription 5 were observed in the regulation of 1α(OH)ase. In addition, in prolactin receptor transfected AOK B-50 cells, prolactin treatment (400 ng/ml) and signal transducer and activator of transcription 5 significantly induced 1α(OH)ase protein as determined by Western blot analysis. Thus, prolactin, by multiple mechanisms, including regulation of vitamin D metabolism, induction of TRPV6 mRNA, and cooperation with 1,25(OH)2D3 in induction of intestinal calcium transport genes and intestinal calcium transport, can act as an important modulator of vitamin D-regulated calcium homeostasis.
Recipient cell nuclear factors are required for reprogramming by nuclear transfer
Authors: Egli Dieter , Eggan Kevin
Published: May 2010

Nuclear transfer allows the reprogramming of somatic cells to totipotency. The cell cycle state of the donor and recipient cells, as well as their extent of differentiation, have each been cited as important determinants of reprogramming success. Here, we have used donor and recipient cells at various cell cycle and developmental stages to investigate the importance of these parameters. We found that many stages of the cell cycle were compatible with reprogramming as long as a sufficient supply of essential nuclear factors, such as Brg1, were retained in the recipient cell following enucleation. Consistent with this conclusion, the increased efficiency of reprogramming when using donor nuclei from embryonic cells could be explained, at least in part, by reintroduction of embryonic nuclear factors along with the donor nucleus. By contrast, cell cycle synchrony between the donor nucleus and the recipient cell was not required at the time of transfer, as long as synchrony was reached by the first mitosis. Our findings demonstrate the remarkable flexibility of the reprogramming process and support the importance of nuclear transcriptional regulators in mediating reprogramming.
Dual mechanism controls asymmetric spindle position in ascidian germ cell precursors
Authors: Prodon François , Chenevert Janet , Hébras Céline , Dumollard Rémi , Faure Emmanuel , Gonzalez-Garcia Jose , Nishida Hiroki , Sardet Christian , McDougall Alex
Published: May 2010

Mitotic spindle orientation with respect to cortical polarity cues generates molecularly distinct daughter cells during asymmetric cell division (ACD). However, during ACD it remains unknown how the orientation of the mitotic spindle is regulated by cortical polarity cues until furrowing begins. In ascidians, the cortical centrosome-attracting body (CAB) generates three successive unequal cleavages and the asymmetric segregation of 40 localized postplasmic/PEM RNAs in germ cell precursors from the 8-64 cell stage. By combining fast 4D confocal fluorescence imaging with gene-silencing and classical blastomere isolation experiments, we show that spindle repositioning mechanisms are active from prometaphase until anaphase, when furrowing is initiated in B5.2 cells. We show that the vegetal-most spindle pole/centrosome is attracted towards the CAB during prometaphase, causing the spindle to position asymmetrically near the cortex. Next, during anaphase, the opposite spindle pole/centrosome is attracted towards the border with neighbouring B5.1 blastomeres, causing the spindle to rotate (10°/minute) and migrate (3 μm/minute). Dynamic 4D fluorescence imaging of filamentous actin and plasma membrane shows that precise orientation of the cleavage furrow is determined by this second phase of rotational spindle displacement. Furthermore, in pairs of isolated B5.2 blastomeres, the second phase of rotational spindle displacement was lost. Finally, knockdown of PEM1, a protein localized in the CAB and required for unequal cleavage in B5.2 cells, completely randomizes spindle orientation. Together these data show that two separate mechanisms active during mitosis are responsible for spindle positioning, leading to precise orientation of the cleavage furrow during ACD in the cells that give rise to the germ lineage in ascidians.
Drosophila adult muscle precursors form a network of interconnected cells and are specified by the rhomboid-triggered EGF pathway
Authors: Figeac Nicolas , Jagla Teresa , Aradhya Rajaguru , Da Ponte Jean Philippe , Jagla Krzysztof
Published: May 2010

In Drosophila, a population of muscle-committed stem-like cells called adult muscle precursors (AMPs) keeps an undifferentiated and quiescent state during embryonic life. The embryonic AMPs are at the origin of all adult fly muscles and, as we demonstrate here, they express repressors of myogenic differentiation and targets of the Notch pathway known to be involved in muscle cell stemness. By targeting GFP to the AMP cell membranes, we show that AMPs are tightly associated with the peripheral nervous system and with a subset of differentiated muscles. They send long cellular processes running along the peripheral nerves and, by the end of embryogenesis, form a network of interconnected cells. Based on evidence from laser ablation experiments, the main role of these cellular extensions is to maintain correct spatial positioning of AMPs. To gain insights into mechanisms that lead to AMP cell specification, we performed a gain-of-function screen with a special focus on lateral AMPs expressing the homeobox gene ladybird. Our data show that the rhomboid-triggered EGF signalling pathway controls both the specification and the subsequent maintenance of AMP cells. This finding is supported by the identification of EGF-secreting cells in the lateral domain and the EGF-dependent regulatory modules that drive expression of the ladybird gene in lateral AMPs. Taken together, our results reveal an unsuspected capacity of embryonic AMPs to form a cell network, and shed light on the mechanisms governing their specification and maintenance.
Quantity discrimination in salamanders
Authors: Krusche Paul , Uller Claudia , Dicke Ursula
Published: May 2010

We investigated discrimination of large quantities in salamanders of the genus Plethodon. Animals were challenged with two different quantities (8 vs 12 or 8 vs 16) in a two-alternative choice task. Stimuli were live crickets, videos of live crickets or images animated by a computer program. Salamanders reliably chose the larger of two quantities when the ratio between the sets was 1:2 and stimuli were live crickets or videos thereof. Magnitude discrimination was not successful when the ratio was 2:3, or when the ratio was 1:2 when stimuli were computer animated. Analysis of the salamanders' success and failure as well as analysis of stimulus features points towards movement as a dominant feature for quantity discrimination. The results are generally consistent with large quantity discrimination investigated in many other animals (e.g. primates, fish), current models of quantity representation (analogue magnitudes) and data on sensory aspects of amphibian prey-catching behaviour (neuronal motion processing).