bluuebunny/crossref_metadata_2025 huggingface dataset:
Strength Variability of Inserts in Sandwich Panels
Authors: Raghu Nikhil , Battley Mark , Southward Temoana
Published: June 2009

Bonded inserts are commonly used to introduce localized loads into sandwich panels. This article investigates sources of variability in the pull-out strength of metallic inserts in aramid honeycomb sandwich panels. Finite element modeling is used to investigate the sensitivity of core stresses to potting depth in partially potted inserts, which is found to be significant. Experimental specimens showed large variations in potting radii and cell wall dimensions, both critical parameters since the failure mode is predominantly core shear, adjacent to the potting. Foam core specimens were also tested and showed significantly lower variability in pull-out strength compared with honeycomb specimens.
6-Sulfatoxymelatonin Collected From Infant Diapers: Feasibility and Implications for Urinary Biochemical Markers
Authors: Thomas Karen A.
Published: June 2009

The purpose of this study was to assess feasibility and acceptability of using a diaper pad for collection of in-home infant urinary samples and to test the accuracy of diaper pad extraction for 6-sulfatoxymelatonin and creatinine, which was used to correct assay results for urinary volume. To assess feasibility and acceptability, urine samples from 20 infants were collected over a 24-hr day using a cotton pad inserted in the diaper. The accuracy of diaper pad extraction was evaluated in the laboratory using urine samples collected from 11 adult volunteers and assayed using enzyme immunosorbent assay (EIA). Urine samples were divided, one aliquot was assayed without extraction, and one aliquot was instilled into a diaper pad, extracted, and assayed. Mothers found diaper pad collection acceptable and easy to perform. Of 144 infant urinary samples obtained in the home environment, 59% were usable for assay purposes, and the remaining either were contaminated with stool or were of insufficient volume. While creatinine values from diaper pad extracted and nonextracted samples were highly correlated (r2 = .947), those of creatinine-corrected 6-sulfatoxymelatonin were not (r2 = .216). Diaper pad collection procedures altered 6-sulfatoxymelatonin values. Implications for measurement of urinary biochemical substances and statistical analysis are discussed.
Selling terror: The symbolization and positioning of Jihad
Authors: O'Shaughnessy Nicholas J. , Baines Paul R.
Published: June 2009

Public speculation has turned to how terrorists are made. One increasingly attributed source is propaganda (see Powell, 1967), the `propaganda of the deed' — physical violence — but also the audio-visual. Terrorism is a language of symbolic action: in the choice of the victims, in the choice of terrorist act, the drama created and the various official responses sought. We are in a new era, when the terrorist act does not simply speak for itself via its symbolism, but is amplified through a vast constellation of modern media. We explore the symbolism inherent in the construction of selected Islamist audio-visual propaganda made available on the internet today and seek to access the `meaning' of terrorist visualities through semiotic analysis, particularly using the Positioning Triad (Baines et al., 2008) and the deconstruction technique (Derrida, 1967) to encourage a new thread of political marketing/propaganda research. We conclude that a common theme projected in our sample is that of the West as permanent aggressor, with Muslims depicted as piously aggrieved for the wrongs done unto them.
Exceptional Rule Learning in a Longitudinal Case Study of Williams Syndrome: Acquisition of Past Tense
Authors: Jacobson Peggy F. , Smith Cairns Helen
Published: June 2009

Conflicting reports of language ability in Williams syndrome (WS) are confusing and may hinder accurate clinical decisions with respect to therapeutic services and educational placements for children with WS.This longitudinal case study examined the acquisition of regular and irregular past tense verbs in a child with WS. The development of regular and irregular verbs was monitored using an elicited production task, supplemented with informal language samples and a grammaticality judgment task. The authors found an unusual profile of regular and irregular past tense use that both approximated and diverged from normal expectations at various stages. The unusual pattern of past tense acquisition is presented in its relation to other language problems known with regard to WS. Clinical implications for assessment and intervention are discussed.
Case Study: Parent-Implemented Prelinguistic Milieu Teaching With a High Risk Dyad
Authors: McCathren Rebecca B.
Published: June 2009

The purpose of this study was twofold. The first purpose was to determine if a mother with mild developmental disabilities living in poverty was able to implement Prelinguistic Milieu Teaching (PMT) strategies. The strategies included following the child’s lead, arranging the environment to increase opportunities for communication, imitating the child’s play and communication behaviors, modeling play and communication, and using words to map the child’s experience and actions. The second purpose was to see if using these strategies resulted in increased intentional communication in her daughter. Intentional communication is when the young child coordinates the use of eye gaze, vocalizations, and/or gestures to achieve a particular communication outcome. The child is demonstrating intentional communication when she persistently alternates gaze between the adult and the object or event of interest or includes attention to both the adult and object in an interaction. For example, a child might reach toward an out-of-reach toy and look back and forth between the toy and the parent, communicating that she wants her parent to get the toy for her. The results indicated that the mother was able to implement the PMT strategies, and the use of these strategies increased her daughter’s intentional communication.
Preliminary Results on Efficacy in Closure of Transsphincteric and Rectovaginal Fistulas Associated With Crohn's Disease Using New Biomaterials
Authors: Schwandner Oliver , Fuerst Alois
Published: June 2009

Background and aims: it was the aim of this prospective study to analyze the efficacy of the Surgisis® AFP™ anal fistula plug and the Surgisis® mesh for the closure of complex fistulas in Crohn`s disease. Methods: All patients with perianal Crohn's disease suffering from transsphincteric and rectovaginal fistulas who underwent surgery using the Surgisis® anal fistula plug or the Surgisis® mesh were prospectively enrolled in this study. Inclusion criteria included transsphincteric single-tract fistulas and rectovaginal fistulas. Surgery was performed using a standardized technique, including irrigation of the fistula tract, placement and internal fixation of the Surgisis® anal fistula plug, and combined transanal/transvaginal excision of rectovaginal fistula with transvaginal placement of the mesh. Success was defined as closure of both internal and external (perianal or vaginal) openings, absence of drainage without further intervention, and absence of abscess formation. Follow-up information was obtained from clinical examination 3, 6, 9, and 12 months postoperatively. Results: Within the observation period, a total of 16 procedures were performed. After a mean follow-up of 9 months and 1 patient lost to follow-up, the overall success rate was 75%. For transsphincteric fistulas, the success rate was 77%, whereas it was 66% in rectovaginal fistulas associated with Crohn's disease. All 4 patients with failure had reoperation. Rate of stoma reversal in those patients who had fecal diversion was 66%. No deterioration of continence was documented. Conclusion: The short-term success rates are promising. Further analysis is needed to explain the definite role of this technique in comparison with traditional surgical techniques.
Pairing and recombination features during meiosis in Cebus paraguayanus (Primates: Platyrrhini)
Authors: Garcia-Cruz Raquel , Robles Pedro , Steinberg Eliana R , Camats Nuria , Brieño Miguel A , Garcia-Caldés Montserrat , Mudry Marta D
Published: June 2009

Background

Among neotropical Primates, the Cai monkeyCebus paraguayanus(CPA) presents long, conserved chromosome syntenies with the human karyotype (HSA) as well as numerous C+ blocks in different chromosome pairs.

In this study, immunofluorescence (IF) against two proteins of the Synaptonemal Complex (SC), namely REC8 and SYCP1, two recombination protein markers (RPA and MLH1), and one protein involved in the pachytene checkpoint machinery (BRCA1) was performed in CPA spermatocytes in order to analyze chromosome meiotic behavior in detail.

Results

Although in the vast majority of pachytene cells all autosomes were paired and synapsed, in a small number of nuclei the heterochromatic C-positive terminal region of bivalent 11 remained unpaired. The analysis of 75 CPA cells at pachytene revealed a mean of 43.22 MLH1 foci per nucleus and 1.07 MLH1 foci in each CPA bivalent 11, always positioned in the region homologous to HSA chromosome 21.

Conclusion

Our results suggest that C blocks undergo delayed pairing and synapsis, although they do not interfere with the general progress of pairing and synapsis.
LD2SNPing: linkage disequilibrium plotter and RFLP enzyme mining for tag SNPs
Authors: Chang Hsueh-Wei , Chuang Li-Yeh , Chang Yan-Jhu , Cheng Yu-Huei , Hung Yu-Chen , Chen Hsiang-Chi , Yang Cheng-Hong
Published: June 2009

Background

Linkage disequilibrium (LD) mapping is commonly used to evaluate markers for genome-wide association studies. Most types of LD software focus strictly on LD analysis and visualization, but lack supporting services for genotyping.

Results

We developed a freeware called LD2SNPing, which provides a complete package of mining tools for genotyping and LD analysis environments. The software provides SNP ID- and gene-centric online retrievals for SNP information and tag SNP selection from dbSNP/NCBI and HapMap, respectively. Restriction fragment length polymorphism (RFLP) enzyme information for SNP genotype is available to all SNP IDs and tag SNPs. Single and multiple SNP inputs are possible in order to perform LD analysis by online retrieval from HapMap and NCBI. An LD statistics section provides D, D', r
2, δ

Q
, ρ, and the P values of the Hardy-Weinberg Equilibrium for each SNP marker, and Chi-square and likelihood-ratio tests for the pair-wise association of two SNPs in LD calculation. Finally, 2D and 3D plots, as well as plain-text output of the results, can be selected.

Conclusion

LD2SNPing thus provides a novel visualization environment for multiple SNP input, which facilitates SNP association studies. The software, user manual, and tutorial are freely available at http://bio.kuas.edu.tw/LD2NPing.
The highly conserved serine threonine kinase StkP of Streptococcus pneumoniae contributes to penicillin susceptibility independently from genes encoding penicillin-binding proteins
Authors: Dias Ricardo , Félix David , Caniça Manuela , Trombe Marie-Claude
Published: June 2009

Background

The serine/threonine kinase StkP ofStreptococcus pneumoniaeis a major virulence factor in the mouse model of infection. StkP is a modular protein with a N-terminal kinase domain a C-terminal PASTA domain carrying the signature of penicillin-binding protein (PBP) and prokaryotic serine threonine kinase. In laboratory cultures, one target of StkP is the phosphoglucosamine mutase GlmM involved in the first steps of peptidoglycan biosynthesis. In order to further elucidate the importance of StkP inS. pneumoniae, its role in resistance to β-lactams has been assessed by mutational analysis in laboratory cultures and its genetic conservation has been investigated in isolates from infected sites (virulent), asymptomatic carriers, susceptible and non-susceptible to β-lactams.

Results

Deletion replacement mutation instkPconferred hypersensitivity to penicillin G and was epistatic on mutations in PBP2X, PBP2B and PBP1A from the resistant 9V clinical isolate URA1258. Genetic analysis of 55 clinical isolates identified 11 StkP alleles differing from the reference R6 allele. None relevant mutation in the kinase or the PASTA domains were found to account for susceptibility of the isolates. Rather the minimal inhibitory concentration (MIC) values of the strains appeared to be determined by their PBP alleles.

Conclusion

The results of genetic dissection analysis in lab strain Cp1015 reveal that StkP is involved in the bacterial response to penicillin and is epistatic on mutations PBP 2B, 2X and 1A. However analysis of the clinical isolates did not allow us to find the StkP alleles putatively involved in determining the virulence or the resistance level of a given strain, suggesting a strong conservation of StkP in clinical isolates.
RNF168, a new RING finger, MIU-containing protein that modifies chromatin by ubiquitination of histones H2A and H2AX
Authors: Pinato Sabrina , Scandiuzzi Cristina , Arnaudo Nadia , Citterio Elisabetta , Gaudino Giovanni , Penengo Lorenza
Published: June 2009

Background

Modulation of chromatin structure has emerged as a critical molecular device to control gene expression. Histones undergo different post-translational modifications that increase chromatin accessibility to a number of regulatory factors. Among them, histone ubiquitination appears relevant in nuclear processes that govern gene silencing, either by inhibiting or activating transcription, and maintain genome stability, acting as scaffold to properly organize the DNA damage response. Thus, it is of paramount importance the identification and the characterization of new ubiquitin ligases that address histones.

Results

We identified and characterized RNF168, a new chromatin-associated RING finger protein. We demonstrated that RNF168 is endowed with ubiquitin ligase activity both in vitro and in vivo, which targets histones H2A and H2AX, but not H2B, forming K63 polyubiquitin chains. We previously described the presence within RNF168 sequence of two MIU domains, responsible for the binding to ubiquitinated proteins. Here we showed that inactivation of the MIUs impairs ubiquitin binding ability in vitro and reduces chromatin association of RNF168 in vivo. Moreover, upon formation of DNA double strand breaks induced by chemical and physical agents, RNF168 is recruited to the DNA damage foci, where it co-localizes with γH2AX and 53BP1. The localization of RNF168 at the site of damage highly increases the local concentration of ubiquitinated proteins and determines the prolonged ubiquitination signal.

Conclusion

The RING finger protein RNF168 is a new ubiquitin ligase that functions as chromatin modifier, through histone ubiquitination. We hypothesize a dual function for RNF168. In normal condition RNF168 modifies chromatin structure by modulating ubiquitination of histone H2A. Upon DNA lesions, RNF168 is recruited to DNA damage response foci where it contributes to increase the amount of ubiquitinated proteins, thereby facilitating the downstream signalling cascade.
Mild forms of hypophosphatasia mostly result from dominant negative effect of severe alleles or from compound heterozygosity for severe and moderate alleles
Authors: Fauvert Delphine , Brun-Heath Isabelle , Lia-Baldini Anne-Sophie , Bellazi Linda , Taillandier Agnès , Serre Jean-Louis , de Mazancourt Philippe , Mornet Etienne
Published: June 2009

Background

Mild hypophosphatasia (HPP) phenotype may result from ALPL gene mutations exhibiting residual alkaline phosphatase activity or from severe heterozygous mutations exhibiting a dominant negative effect. In order to determine the cause of our failure to detect a second mutation by sequencing in patients with mild HPP and carrying on a single heterozygous mutation, we tested the possible dominant effect of 35 mutations carried by these patients.

Methods

We tested the mutations by site-directed mutagenesis. We also genotyped 8 exonic and intronic ALPL gene polymorphisms in the patients and in a control group in order to detect the possible existence of a recurrent intronic mild mutation.

Results

We found that most of the tested mutations exhibit a dominant negative effect that may account for the mild HPP phenotype, and that for at least some of the patients, a second mutation in linkage disequilibrium with a particular haplotype could not be ruled out.

Conclusion

Mild HPP results in part from compound heterozygosity for severe and moderate mutations, but also in a large part from heterozygous mutations with a dominant negative effect.
Polymorphisms in NF-κB Inhibitors and Risk of Epithelial Ovarian Cancer
Authors: White Kristin L , Vierkant Robert A , Phelan Catherine M , Fridley Brooke L , Anderson Stephanie , Knutson Keith L , Schildkraut Joellen M , Cunningham Julie M , Kelemen Linda E , Pankratz V Shane , Rider David N , Liebow Mark , Hartmann Lynn C , Sellers Thomas A , Goode Ellen L
Published: June 2009

Background

The nuclear factor-κB (NF-κB) family is a set of transcription factors with key roles in the induction of the inflammatory response and may be the link between inflammation and cancer development. This pathway has been shown to influence ovarian epithelial tissue repair. Inhibitors of κB (IκB) prevent NF-κB activation by sequestering NF-κB proteins in the cytoplasm until IκB proteins are phosphorylated and degraded.

Methods

We used a case-control study to evaluate the association between single nucleotide polymorphisms (SNPs) in NFKBIA and NFKBIB (the genes encoding IκBα and IκBβ, respectively) and risk of epithelial ovarian cancer. We queried 19 tagSNPs and putative-functional SNPs among 930 epithelial ovarian cancer cases and 1,037 controls from two studies.

Results

The minor allele for one synonymous SNP in NFKBIA, rs1957106, was associated with decreased risk (p = 0.03).

Conclusion

Considering the number of single-SNP tests performed and null gene-level results, we conclude that NFKBIA and NFKBIB are not likely to harbor ovarian cancer risk alleles. Due to its biological significance in ovarian cancer, additional genes encoding NF-κB subunits, activating and inhibiting molecules, and signaling molecules warrant interrogation.
Characteristics of suicide attempters with family history of suicide attempt: a retrospective chart review
Authors: Nakagawa Makiko , Kawanishi Chiaki , Yamada Tomoki , Iwamoto Yoko , Sato Ryoko , Hasegawa Hana , Morita Satoshi , Odawara Toshinari , Hirayasu Yoshio
Published: June 2009

Background

Family history of suicide attempt is one of the risks of suicide. We aimed at exploring the characteristics of Japanese suicide attempters with and without a family history of suicide attempt.

Methods

Suicide attempters admitted to an urban emergency department from 2003 to 2008 were interviewed by two attending psychiatrists on items concerning family history of suicide attempt and other sociodemographic and clinical information. Subjects were divided into two groups based on the presence or absence of a family history of suicide attempt, and differences between the two groups were subsequently analyzed.

Results

Out of the 469 suicide attempters, 70 (14.9%) had a family history of suicide attempt. A significantly higher rate of suicide motive connected with family relations (odds ratio 2.21, confidence interval 1.18–4.17,p< .05) as well as a significantly higher rate of deliberate self-harm (odds ratio 2.51, confidence interval 1.38–4.57,p< .05) were observed in patients with a family history of suicide compared to those without such history. No significant differences were observed in other items investigated.

Conclusion

The present study has revealed the characteristics of suicide attempters with a family history of suicide attempt. Further understanding of the situation of such individuals is expected to lead to better treatment provision and outcomes, and family function might be a suitable focus in their treatment.
Pregnant women's attitudes towards alcohol consumption
Authors: Raymond Neil , Beer Charlotte , Glazebrook Cristine , Sayal Kapil
Published: June 2009

Background

There is uncertainty as to whether there is a safe threshold for drinking alcohol during pregnancy. We explored pregnant women's attitudes towards drinking alcohol in pregnancy and their attitudes towards sources of information about drinking in pregnancy following recent changes in UK government guidance.

Methods

A qualitative study involving individual, semi-structured interviews with 20 pregnant women recruited from community organisations in the UK. Interview transcripts were analysed qualitatively using thematic analysis.

Results

Most women found information and advice about safe levels of drinking in pregnancy confusing and lacking in evidence and detail. Although most women considered that there were risks involved with drinking in pregnancy and these perceptions influenced their behaviour, only six women reported abstinence. Women reported being influenced by advice from family and friends and their experiences of previous pregnancies. Many had received no individual advice from general practitioners or midwives relating to drinking during pregnancy.

Conclusion

Pregnant women wished to take responsibility for their own health and make choices based on informed advice. In order to do so, they require clear and consistent advice about safe levels of drinking from policy makers and health professionals. This is an important issue as women might drink socially during their pregnancy.
Radical Prostatectomy: Hospital volumes and surgical volumes – does practice make perfect?
Authors: Urbanek Cydney , Turpen Ryan , Rosser Charles J
Published: June 2009

Background

Between the years 1993 and 2003, more than 140,000 men underwent radical prostatectomy (RP), thus making RP one of the most common treatment options for localized prostate cancer in the United States.

Discussion

Localized prostate cancer treated by RP is one of the more challenging procedures performed by urologic surgeons. Studies suggest a definite learning curve in performing this procedure with optimal results noted after performing >500 RPs. But is surgical volume everything? How do hospital volumes of RP weigh in? Could fellowship training in RP reduce the critical volume needed to reach an 'experienced' level?

As we continue to glean data as to how to optimize outcomes after RP, we must not only consider surgeon and hospital volumes of RP, but also consider training of the individual surgeon.
Components of the E. coli envelope are affected by and can react to protein over-production in the cytoplasm
Authors: Villa Riccardo , Lotti Marina , Gatti-Lafranconi Pietro
Published: June 2009

Background

Protein over-expression in bacteria is still the easiest, cheapest and therefore preferred way to obtain large amounts of proteins for industrial and laboratory scale preparations. Several studies emphasized the importance of understanding cellular and molecular mechanisms triggered by protein over-production in order to obtain higher yield and better quality of the recombinant product. Almost every step leading to a fully functional polypeptide has been investigated, from mRNA stability to the role of molecular chaperones, from aggregation to bottlenecks in the secretory pathway. In this context, we focused on the still poorly addressed relationship between protein production in the cytoplasm and the bacterial envelope, an active and reactive cell compartment that controls interactions with the environment and several major cellular processes. Results available to date show that the accumulation of foreign proteins in the cytoplasm induces changes in the membrane lipids and in the levels of mRNAs for some membrane proteins. However, a direct connection between membrane protein expression levels and soluble/aggregated protein accumulation in the cytoplasm has never been reported.

Results

By the use of a combined physiological and proteomic approach, we investigated the effects on the cell membrane of E. coli of the overexpression of two recombinant proteins, the B. cepacia lipase (BCL) and the green fluorescent protein (GFP). Both polypeptides are expressed in the cytoplasm at similar levels but GFP is fully soluble whereas inactive BCL accumulates in inclusion bodies.

Growth and viability of the transformed cells were tested in the presence of different drugs. We found that chloramphenycol preferentially inhibited the strain over-producing GFP while SDS was more effective when BCL inclusion bodies accumulated in the cytoplasm. In contrast, both proteins induced a similar response in the membrane proteome, i.e. increased levels of LamB, OmpF, OmpA and TolC. Under all tested conditions, the lipopolysaccharide was not affected, suggesting that a specific rather than a generalized rearrangement of the envelope was induced.

Conclusion

Taking together physiological and biochemical evidence, our work indicates that the E. coli envelope can sense protein over-expression in the cytoplasm and react by modulating the abundance of some membrane proteins, with possible consequences on the membrane traffic of small solutes, i.e. nutrients, drugs and metabolites. Such a response seems to be independent on the nature of the protein being over-expressed. On the other hand both our data reported herein and previous results indicate that membrane lipids may act as a second stress sensor responsive to the aggregation state of the recombinant protein and further contribute to changes in cellular exchanges with the environment.
Anti-Anopheles darlingi saliva antibodies as marker of Plasmodium vivax infection and clinical immunity in the Brazilian Amazon
Authors: Andrade Bruno Bezerril , Rocha Bruno Coelho , Reis-Filho Antonio , Camargo Luís Marcelo Aranha , Tadei Wanderli Pedro , Moreira Luciano Andrade , Barral Aldina , Barral-Netto Manoel
Published: June 2009

Background

Despite governmental and private efforts on providing malaria control, this disease continues to be a major health threat. Thus, innovative strategies are needed to reduce disease burden. The malaria vectors, through the injection of saliva into the host skin, play important role on disease transmission and may influence malaria morbidity. This study describes the humoral immune response against Anopheles (An.) darlingi saliva in volunteers from the Brazilian Amazon and addresses the association between levels of specific antibodies and clinical presentation of Plasmodium (P.) vivax infection.

Methods

Adult volunteers from communities in the Rondônia State, Brazil, were screened in order to assess the presence of P. vivax infection by light microscopy and nested PCR. Non-infected volunteers and individuals with symptomatic or symptomless infection were randomly selected and plasma collected. An. darlingi salivary gland sonicates (SGS) were prepared and used to measure anti-saliva antibody levels. Plasma interleukin (IL)-10 and interferon (IFN)-γ levels were also estimated and correlated to anti-SGS levels.

Results

Individuals infected with P. vivax presented higher levels of anti-SGS than non-infected individuals and antibody levels could discriminate infection. Furthermore, anti-saliva antibody measurement was also useful to distinguish asymptomatic infection from non-infection, with a high likelihood ratio. Interestingly, individuals with asymptomatic parasitaemia presented higher titers of anti-SGS and lower IFN-γ/IL-10 ratio than symptomatic ones. In P. vivax-infected asymptomatic individuals, the IFN-γ/IL-10 ratio was inversely correlated to anti-SGS titers, although not for while in symptomatic volunteers.

Conclusion

The estimation of anti-An. darlingi antibody levels can indicate the probable P. vivax infection status and also could serve as a marker of disease severity in this region of Brazilian Amazon.
Effect of dioxins on regulation of tyrosine hydroxylase gene expression by aryl hydrocarbon receptor: a neurotoxicology study
Authors: Akahoshi Eiichi , Yoshimura Seiko , Uruno Saeko , Ishihara-Sugano Mitsuko
Published: June 2009

Background

Dioxins and related compounds are suspected of causing neurological disruption. Epidemiological studies indicated that exposure to these compounds caused neurodevelopmental disturbances such as learning disability and attention deficit hyperactivity disorder, which are thought to be closely related to dopaminergic dysfunction. Although the molecular mechanism of their actions has not been fully investigated, a major participant in the process is aryl hydrocarbon receptor (AhR). This study focused on the effect of 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) exposure on the regulation of TH, a rate-limiting enzyme of dopamine synthesis, gene expression by AhR.

Methods

N2a-Rβ cells were established by transfecting murine neuroblastoma Neuro2a with the rat AhR cDNA. TH expression induced by TCDD was assessed by RT-PCR and Western blotting. Participation of AhR in TCDD-induced TH gene expression was confirmed by suppressing AhR expression using the siRNA method. Catecholamines including dopamine were measured by high-performance liquid chromatography. A reporter gene assay was used to identify regulatory motifs in the promoter region of TH gene. Binding of AhR with the regulatory motif was confirmed by an electrophoretic mobility shift assay (EMSA).

Results

Induction of TH by TCDD through AhR activation was detected at mRNA and protein levels. Induced TH protein was functional and its expression increased dopamine synthesis. The reporter gene assay and EMSA indicated that AhR directly regulated TH gene expression. Regulatory sequence called aryl hydrocarbon receptor responsive element III (AHRE-III) was identified upstream of the TH gene from -285 bp to -167 bp. Under TCDD exposure, an AhR complex was bound to AHRE-III as well as the xenobiotic response element (XRE), though AHRE-III was not identical to XRE, the conventional AhR-binding motif.

Conclusion

Our results suggest TCDD directly regulate the dopamine system by TH gene transactivation via an AhR-AHRE-III-mediated pathway. The AhR- mediated pathway could have a particular AhR-mediated genomic control pathway transmitting the effects of TCDD action to target cells in the development of dopaminergic disabilities.
Lipoprotein-associated phospholipase A2 (Lp-PLA2) activity, platelet-activating factor acetylhydrolase (PAF-AH) in leukocytes and body composition in healthy adults
Authors: Detopoulou Paraskevi , Nomikos Tzortzis , Fragopoulou Elizabeth , Panagiotakos Demosthenis B , Pitsavos Christos , Stefanadis Christodoulos , Antonopoulou Smaragdi
Published: June 2009

Background

Lipoprotein-associated phospholipase A2 (Lp-PLA2) also known as serum platelet activating factor acetylhydrolase (PAF-AH) activity constitutes a novel risk marker for cardiovascular disease. Leukocytes constitute one main cellular source of circulating Lp-PLA2. The aim of the present study was to evaluate the association of both serum and leukocyte PAF-AH activities with fat distribution and lean tissue. One hundred healthy volunteers without cardiovascular disease history participated in this study (n = 52 men, 44 ± 13 years and n = 48 women, 43 ± 13 years). Body composition was assessed with dual-energy X-ray absorptiometry, while anthropometrical indices were also measured. The activity of Lp-PLA2 and levels of lipid and glycemic parameters were determined in fasting samples.

Results

Mean Lp-PLA2 activity was 24.8 ± 4.5 and 19.6 ± 5.0 nmol/min/mL in men and women, respectively (P < 0.001). Mean activity of PAF-AH in leukocyte homogenates was 386 ± 127 pmol/min/mg and 292 ± 92 pmol/min/mg in men and women, correspondingly (P < 0.001). In multiple regression models upper and total adiposity measures were positively associated with Lp-PLA2 activity in men after adjusting for LDL-cholesterol, age, smoking, hs-CRP and physical activity, whereas no associations were found with PAF-AH leukocyte homogenates activity. Hierarchical analysis revealed that the variables with the highest explanatory ability of Lp-PLA2 activity in men, were DXA deriving L1–L4 region of interest and arms fat (increase in R2 = 0.136, P = 0.005 and increase in R2 = 0.118, P = 0.009, respectively), followed by trunk fat and total fat. In women, no association of body composition variables with Lp-PLA2 nor PAF-AH leukocyte homogenates activity was found.

Conclusion

Lp-PLA2 activity is differentiated across levels of adiposity and topology of adipose tissue, whereas no association was found regarding PAF-AH leukocyte homogenates activity. Our findings suggest that Lp-PLA2 may compensate for the adiposity-associated increases in inflammatory and oxidative burden, in men.
Cellular immune response to intrastriatally implanted allogeneic bone marrow stromal cells in a rat model of Parkinson's disease
Authors: Camp Dianne M , Loeffler David A , Farrah Diane M , Borneman Jade N , LeWitt Peter A
Published: June 2009

Background

Marrow stromal cells (MSC), the non-hematopoietic precursor cells in bone marrow, are being investigated for therapeutic potential in CNS disorders. Although in vitro studies have suggested that MSC may be immunologically inert, their immunogenicity following transplantation into allogeneic recipients is unclear. The primary objective of this study was to investigate the cellular immune response to MSC injected into the striatum of allogeneic recipients (6-hydroxydopamine [6-OHDA]-hemilesioned rats, an animal model of Parkinson's disease [PD]), and the secondary objective was to determine the ability of these cells to prevent nigrostriatal dopamine depletion and associated motor deficits in these animals.

Methods

5-Bromo-2-deoxyuridine (BrdU) – labeled MSC from two allogeneic sources (Wistar and ACI rats) were implanted into the striatum of adult Wistar rats at the same time as 6-OHDA was administered into the substantia nigra. Behavioral tests were administered one to two weeks before and 16–20 days after 6-OHDA lesioning and MSC transplantation. Immunocytochemical staining for T helper and T cytotoxic lymphocytes, microglia/macrophages, and major histocompatibility class I and II antigens was performed on post-transplantation days 22–24. MSC were detected with an anti-BrdU antibody.

Results

Tissue injury due to the transplantation procedure produced a localized cellular immune response. Unexpectedly, both sources of allogeneic MSC generated robust cellular immune responses in the host striatum; the extent of this response was similar in the two allograft systems. Despite these immune responses, BrdU+ cells (presumptive MSC) remained in the striatum of all animals that received MSC. The numbers of remaining MSC tended to be increased (p = 0.055) in rats receiving Wistar MSC versus those receiving ACI MSC. MSC administration did not prevent behavioral deficits or dopamine depletion in the 6-OHDA-lesioned animals.

Conclusion

MSC, when implanted into the striatum of allogeneic animals, provoke a marked immune response which is not sufficient to clear these cells by 22–24 days post-transplantation. In the experimental paradigm in this study, MSC did not prevent nigrostriatal dopamine depletion and its associated behavioral deficits. Additional studies are indicated to clarify the effects of this immune response on MSC survival and function before initiating trials with these cells in patients with PD or other neurodegenerative disorders.
Reproductive age mortality survey (RAMOS) in Accra, Ghana
Authors: Zakariah Afisah Yakubu , Alexander Sophie , van Roosmalen Jos , Buekens Pierre , Kwawukume Enyonam Yao , Frimpong Patrick
Published: June 2009

Background

Maternal mortality remains a severe problem in many parts of the world, despite efforts to reach MDG 5. In addition, underreporting is an issue especially in low income countries. Our objective has been to identify the magnitude of maternal deaths and the degree of underreporting of these deaths in Accra Metropolis in Ghana during a one year period.

Methods

A Reproductive Age Mortality survey (RAMOS) was carried out in the Accra Metropolis for the period 1st January 2002-31st December 2002. We reviewed records of female deaths aged 10–50 years in the Metropolis for the whole year 2002 using multiple sources. Maternal deaths identified through the review were compared with the officially reported maternal deaths for the same period.

Results

At the end of the study, a total of 179 maternal deaths out of 9,248 female deaths between the ages of 10–50 years were identified. One hundred and one (N = 101) of these were reported, giving an underreporting rate of 44%. The 179 cases consisted of 146 (81.6%) direct maternal deaths and 32 (17.9%) indirect maternal deaths and 1 (0.6%) non maternal death. The most frequent causes of direct maternal deaths were obstetric haemorrhage (57; 32%), pregnancies with abortive outcome (37; 20.8%), (pre) eclampsia (26; 14.6%) and puerperal sepsis (13; 7.3%). The most frequent indirect cause was sickle cell crisis in pregnancy (13; 7.3%).

Conclusion

A Reproductive Age Mortality Survey is an effective method that could be used to update data on maternal mortality in Ghana while efforts are made to improve on maternal death audits in the health facilities. Strengthening the existing community based volunteers to report deaths that take place at home and the civil registration systems of births and deaths is also highly recommended.
Using an electrohydraulic ankle foot orthosis to study modifications in feedforward control during locomotor adaptation to force fields applied in stance
Authors: Noel Martin , Fortin Karine , Bouyer Laurent J
Published: June 2009

Background

Adapting to external forces during walking has been proposed as a tool to improve locomotion after central nervous system injury. However, sensorimotor integration during walking varies according to the timing in the gait cycle, suggesting that adaptation may also depend on gait phases. In this study, an ElectroHydraulic AFO (EHO) was used to apply forces specifically during mid-stance and push-off to evaluate if feedforward movement control can be adapted in these 2 gait phases.

Methods

Eleven healthy subjects walked on a treadmill before (3 min), during (5 min) and after (5 min) exposure to 2 force fields applied by the EHO (mid-stance/push-off; ~10 Nm, towards dorsiflexion). To evaluate modifications in feedforward control, strides with no force field ('catch strides') were unexpectedly inserted during the force field walking period.

Results

When initially exposed to a mid-stance force field (FF20%), subjects showed a significant increase in ankle dorsiflexion velocity. Catches applied early into the FF20% were similar to baseline (P > 0.99). Subjects gradually adapted by returning ankle velocity to baseline over ~50 strides. Catches applied thereafter showed decreased ankle velocity where the force field was normally applied, indicating the presence of feedforward adaptation. When initially exposed to a push-off force field (FF50%), plantarflexion velocity was reduced in the zone of force field application. No adaptation occurred over the 5 min exposure. Catch strides kinematics remained similar to control at all times, suggesting no feedforward adaptation. As a control, force fields assisting plantarflexion (-3.5 to -9.5 Nm) were applied and increased ankle plantarflexion during push-off, confirming that the lack of kinematic changes during FF50% catch strides were not simply due to a large ankle impedance.

Conclusion

Together these results show that ankle exoskeletons such as the EHO can be used to study phase-specific adaptive control of the ankle during locomotion. Our data suggest that, for short duration exposure, a feedforward modification in torque output occurs during mid-stance but not during push-off. These findings are important for the design of novel rehabilitation methods, as they suggest that the ability to use resistive force fields for training may depend on targeted gait phases.
A system biology approach highlights a hormonal enhancer effect on regulation of genes in a nitrate responsive "biomodule"
Authors: Nero Damion , Krouk Gabriel , Tranchina Daniel , Coruzzi Gloria M
Published: June 2009

Background

Nitrate-induced reprogramming of the transcriptome has recently been shown to be highly context dependent. Herein, a systems biology approach was developed to identify the components and role of cross-talk between nitrate and hormone signals, likely to be involved in the conditional response of NO3
- signaling.

Results

Biclustering was used to identify a set of genes that are N-responsive across a range of Nitrogen (N)-treatment backgrounds (i.e. nitrogen treatments under different growth conditions) using a meta-dataset of 76 Affymetrix ATH1 chips from 5 different laboratories. Twenty-one biclusters were found to be N-responsive across subsets of this meta-dataset. N-bicluster 9 (126 genes) was selected for further analysis, as it was shown to be reproducibly responsive to NO3
- as a signal, across a wide-variety of background conditions and datasets. N-bicluster 9 genes were then used as "seed" to identify putative cross-talk mechanisms between nitrate and hormone signaling. For this, the 126 nitrate-regulated genes in N-bicluster 9 were biclustered over a meta-dataset of 278 ATH1 chips spanning a variety of hormone treatments. This analysis divided the bicluster 9 genes into two classes: i) genes controlled by NO3
- only vs. ii) genes controlled by both NO3
- and hormones. The genes in the latter group showed a NO3
- response that is significantly enhanced, compared to the former. In silico analysis identified two Cis-Regulatory Elements candidates (CRE) (E2F, HSE) potentially involved the interplay between NO3
- and hormonal signals.

Conclusion

This systems analysis enabled us to derive a hypothesis in which hormone signals are proposed to enhance the nitrate response, providing a potential mechanistic explanation for the link between nitrate signaling and the control of plant development.
New sequence-based data on the relative DNA contents of chromosomes in the normal male and female human diploid genomes for radiation molecular cytogenetics
Authors: Repin Mikhail V , Golubev Pavel I , Repina Ludmila A
Published: June 2009

Background

The objective of this work is to obtain the correct relative DNA contents of chromosomes in the normal male and female human diploid genomes for the use at FISH analysis of radiation-induced chromosome aberrations.

Results

The relative DNA contents of chromosomes in the male and female human diploid genomes have been calculated from the publicly available international Human Genome Project data. New sequence-based data on the relative DNA contents of human chromosomes were compared with the data recommended by the International Atomic Energy Agency in 2001. The differences in the values of the relative DNA contents of chromosomes obtained by using different approaches for 15 human chromosomes, mainly for large chromosomes, were below 2%. For the chromosomes 13, 17, 20 and 22 the differences were above 5%.

Conclusion

New sequence-based data on the relative DNA contents of chromosomes in the normal male and female human diploid genomes were obtained. This approach, based on the genome sequence, can be recommended for the use in radiation molecular cytogenetics.
Metabolic-network-driven analysis of bacterial ecological strategies
Authors: Freilich Shiri , Kreimer Anat , Borenstein Elhanan , Yosef Nir , Sharan Roded , Gophna Uri , Ruppin Eytan
Published: June 2009

Background

The growth-rate of an organism is an important phenotypic trait, directly affecting its ability to survive in a given environment. Here we present the first large scale computational study of the association between ecological strategies and growth rate across 113 bacterial species, occupying a variety of metabolic habitats. Genomic data are used to reconstruct the species' metabolic networks and habitable metabolic environments. These reconstructions are then used to investigate the typical ecological strategies taken by organisms in terms of two basic species-specific measures: metabolic variability - the ability of a species to survive in a variety of different environments; and co-habitation score vector - the distribution of other species that co-inhabit each environment.

Results

We find that growth rate is significantly correlated with metabolic variability and the level of co-habitation (that is, competition) encountered by an organism. Most bacterial organisms adopt one of two main ecological strategies: a specialized niche with little co-habitation, associated with a typically slow rate of growth; or ecological diversity with intense co-habitation, associated with a typically fast rate of growth.

Conclusions

The pattern observed suggests a universal principle where metabolic flexibility is associated with a need to grow fast, possibly in the face of competition. This new ability to produce a quantitative description of the growth rate-metabolism-community relationship lays a computational foundation for the study of a variety of aspects of the communal metabolic life.
Cell-surface expression of Hsp70 on hematopoietic cancer cells after inhibition of HDAC activity
Authors: Jensen Helle , Andresen Lars , Hansen Karen Aagaard , Skov Søren
Published: June 2009

Chemotherapeutic stress sensitizes cancer cells for immunorecognition by facilitating Hsp70 cell surface expression.

We show that inhibition of HDAC activity leads to surface expression of Hsp70 on various hematopoietic cancer cells, an occurance that was not observed on naïve or activated peripheral blood cells. HDAC inhibitor-mediated Hsp70 surface expression was confined to the apoptotic Annexin V-positive cells and blocked by inhibition of apoptosis. Other chemotherapeutic inducers of apoptosis such as etoposide and camptothecin also led to a robust induction of Hsp70 surface expression. Hsp70 expression was, however, not caused by induction of apoptosis per se, as activated CD4 T cells remained Hsp70 surface-negative despite effective induction of apoptosis. Interestingly, inhibition of endolysosomes or normal ER/Golgi transport did not affect Hsp70 surface expression. Intracellular calcium and the transcription factor Sp1, which has been shown previously to be important for the intracellular stress mediated by HDAC inhibitors, were not involved in Hsp70 surface expression. We also found that HDAC inhibitors decreased cellular PMET activity and that a selective inhibition of PMET activity with extracellular NADH induced a robust Hsp70 surface expression. Our data suggest that inhibition of HDAC activity selectively induces surface expression of Hsp70 on hematopoietic cancer cells and that this may increase immunorecognition of these cells.
Free-surface multiple attenuation using inverse data processing in the coupled plane-wave domain
Authors: Ma Jitao , Sen Mrinal K. , Chen Xiaohong
Published: June 2009

Free-surface multiples contain a large amount of energy in the seismic data because of large reflectivity of the free surface. We propose a method for free-surface multiple attenuation by a simple muting in the inverse coupled plane-wave domain. Our method is based on inverse data processing and the well-known 2D invariant embedding technique. If the lateral variation in subsurface structure is smooth, the data are well compressed in the 2D coupled plane-wave domain, reducing computation costs and stabilizing the inversion procedure. Surface multiples and primaries are well separated in the inverse coupled plane-wave domain, and multiples can be eliminated by simple muting, which does not damage the primary energy. To reduce artifacts, wraparound, and noise introduced by the frequency-domain data matrix inversion, horizontal and vertical tapers are applied. A least-squares matrix inversion method is chosen to stabilize the inversion. Synthetic data examples show that plane-wave inverse data processing is stable and successful in attenuating free-surface multiples.