bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictors of offending among prisoners: the role of attention-deficit hyperactivity disorder and substance use
Authors: Young S , Wells J , Gudjonsson GH
Published: June 2010

The aim of the study was to investigate predictors of offending among prisoners from official records after controlling for age at first conviction and antisocial personality disorder. The participants were 198 Scottish prisoners, who had completed Diagnostic Statistical Manual IV screens for child and adult attention-deficit hyperactivity disorder (ADHD) symptoms and the Millon Clinical Multiaxial Inventory III for Axis I and Axis II disorders. The ADHD symptomatic group had significantly higher rates of total, acquisitive and violent offending than other prisoners, as well as greater regular heroin use. Hierarchical multiple regressions, using child and adult symptoms as dimensions, showed that frequent use of heroin in the year prior to imprisonment was the single most powerful predictor of the extent of total offending, with ADHD symptoms also adding independently to the variance in offending. In contrast, for violent offending, ADHD symptoms were the strongest predictor followed by alcohol dependence. The findings demonstrate the importance of heroin use and ADHD symptoms in the persistence of offending. There is an urgent need to treat drug addiction and ADHD symptoms in order to reduce offending among the most persistent offenders. Recently, treatment programmes have been developed for adults with ADHD, heroin and crack cocaine addiction which can be applied to this population.
The Family Is Worthy of Being Rebuilt: Perceptions of the Jewish Family in Mandate Palestine, 1918-1948
Authors: Razi Tammy
Published: June 2010

Although the Jewish community of Palestine was an extremely family-oriented society and the institute of the family played a major role in the establishment of the new Zionist nationhood, the historiography has henceforth paid little attention to its role, images, and functions. This article will examine the diverse and often contradictory perceptions and influences that have shaped the Zionist discourse regarding the family in the Jewish settlement of Palestine during the British mandate period. Traditional Jewish perceptions intertwined with modern, bourgeois, and revolutionary notions of the family, whether national or socialist. These contradictory perceptions were manifested in the contested professional and public discourse regarding the many dysfunctional urban families in Tel Aviv, who were treated by welfare authorities and mental health specialists during the 1930s and 1940s.
The Relation of Humor and Child Development: Social, Adaptive, and Emotional Aspects
Authors: Semrud-Clikeman Margaret , Glass Kimberly
Published: June 2010

A sense of humor has been linked to social competence, popularity, and adaptability. The purpose of this review was to investigate the extant research in humor in childhood. Emerging work on the neuroanatomy of humor was discussed with findings of right hemispheric involvement for the comprehension and appreciation of humor for the affective network and the left hemisphere for cognitive understanding. These findings are intriguing when examining humor functioning in children with various disabilities, particularly the right hemisphere for children with autistic spectrum disorders or nonverbal learning disabilities. Examination of research in humor in childhood disabilities found most articles on humor in children with autistic spectrum disorder or mental retardation, with few to none in learning disabilities or attention deficit hyperactivity disorder. It was concluded that further study is needed to understand humor in children with disabilities and that such understanding will assist with interventions.
Limit-cycle Oscillations of Functionally Graded Material Plates Subject to Aerodynamic and Thermal Loads
Authors: Hesham Hamed Ibrahim  , Tawfik Mohammad
Published: June 2010

The nonlinear flutter and thermal buckling of a functionally graded material (FGM) plate panel subjected to combined thermal and aerodynamic loads are investigated using a finite element model based on the thin plate theory and von Karman strain-displacement relations to account for moderately large deflection. The thermal load is assumed to be steady-state constant temperature distribution, and the aerodynamic pressure is modeled using the quasi-steady first-order piston theory. The governing nonlinear equations of motion are obtained using the principle of virtual work adopting an approach based on the thermal strain being a cumulative physical quantity to account for temperature dependent material properties. The static nonlinear equations are solved by Newton-Raphson numerical technique to get the thermal post-buckling deflection. The dynamic nonlinear equations of motion are transformed to modal coordinates to reduce the computational efforts. The Newmark implicit integration scheme is employed to solve the second order ordinary differential equations of motion. Finally, the buckling temperature, post-buckling deflection and the nonlinear limit-cycle oscillations of an FGM panel are presented, illustrating the effect of volume fraction exponent, dynamic pressure, temperature rise, and boundary conditions on the panel response.
The organization of delayed second language correction
Authors: Rolin-Ianziti Jeanne
Published: June 2010

The present study uses a conversation analytic framework to examine the organization of a type of classroom talk: the delayed correction sequence. Such talk occurs when teacher and students interactively correct errors after the students have completed a communicative activity. This study investigates naturally occurring instances of correction accomplished by four teachers of introductory French and their students and uncovers two main approaches to delayed correction: (1) teacher-initiated correction, and (2) teacher-initiated student-correction. The detailed examination of delayed correction examples may be fruitful to training purposes by showing teachers the options they may enact in the language classroom.
Influence of Environmental Factors on Performance of Sorptive Building Materials
Authors: Seo Janghoo , Kato Shinsuke , Ataka Yuji , Yang Jeong-Hoon
Published: June 2010

Recently, sorptive building materials have been used to improve indoor air quality in Japan. By making use of sorptive building materials, the concentration of volatile organic compounds (VOCs) within rooms can be reduced without the need to install any special equipment. In this paper, the effect of sorptive building materials with respect to reducing toluene concentrations in the air of small test chambers has been assessed using sorption flux. We have also examined how environmental parameters influence concentration reduction performance. The effectiveness of activated carbon at reducing toluene concentrations when used as a sorptive building material depend considerably on the air exchange rate of the chamber, the load factor of the sorptive materials and the mass transfer coefficient. In order to evaluate and compare the sorptive performance of various building materials, it is necessary to conduct tests under identical parameter conditions. The experimental results and computational fluid dynamics analysis show that sorptive building materials are a fairly effective agent for reducing indoor VOC concentrations, and that this effect can be expected to be replicated during practical use.
Cognitive Status Changes Based on Time of Day in Nursing Home Patients With and Without Dementia
Authors: Madhusoodanan Subramoniam , Madhusoodanan Neha , Serper Mark , Sullivan Stephen J. , D'Antonio Emily , Negi Rohini , Brenner Ronald
Published: June 2010

Background: Changes in behavior and cognition have been observed with disruption of the circadian rhythm. Methods: This study examined the effects of time of day (TOD) on administration of Mini-Mental State Examinations (MMSEs) in nursing home patients with dementia (patients) or functional psychiatric disorders (control), using repeated measures analyses of covariance (ANCOVAs). Results: Controls (n = 34) scored significantly higher than patients (n = 38) on total MMSE and all subscales. Within the patients, men and women performed equally in the morning, but women performed marginally worse in the afternoon on total MMSE scores, orientation, and immediate recall and men performed significantly better in the afternoon. Within the control, no gender or time effects were detected. Conclusion: Results indicate that TOD had no significant impact on cognitive status in patients with dementia or patients with other psychiatric illnesses. No changes in activity timings are recommended in nursing home patients with dementia.
Patient-Centered Communication During the Disclosure of a Dementia Diagnosis
Authors: Zaleta Alexandra K. , Carpenter Brian D.
Published: June 2010

This study examined physician use of patient-centered communication during disclosure of a dementia diagnosis. Fifty-four patients (mean age = 74.13) and companions (mean age = 65.67; n = 34 spouses/partners, 12 adult children, 8 other) were diagnosed with very mild (n = 36) or mild (n = 18) dementia at an Alzheimer’s Disease Research Center. Audio recordings of these triadic encounters were evaluated with the Roter Interaction Analysis System. Physicians utilized moderate but variable amounts of patient-centered behaviors including positive rapport building, facilitation, and patient activation (P < .001). Physicians far less frequently used emotional rapport building (P < 0.001). Physicians who demonstrated more patient-centered communication also exhibited greater positive affect (P < 0.05). The use of patient-centered behaviors and positive affect was more variable between physicians than within physicians and may be more dependent on individual physician characteristics than dementia severity or age and gender of patients and companions.
New mechanism for Notch signaling to endothelium at a distance by Delta-like 4 incorporation into exosomes
Authors: Sheldon Helen , Heikamp Emily , Turley Helen , Dragovic Rebecca , Thomas Peter , Oon Chern Ein , Leek Russell , Edelmann Mariola , Kessler Benedikt , Sainson Richard C. A. , Sargent Ian , Li Ji-Liang , Harris Adrian L.
Published: June 2010

Notch signaling is an evolutionary conserved pathway that is mediated by cell-cell contact. It is involved in a variety of developmental processes and has an essential role in vascular development and angiogenesis. Delta-like 4 (Dll4) is a Notch ligand that is up-regulated during angiogenesis. It is expressed in endothelial cells and regulates the differentiation between tip cells and stalk cells of neovasculature. Here, we present evidence that Dll4 is incorporated into endothelial exosomes. It can also be incorporated into the exosomes of tumor cells that overexpress Dll4. These exosomes can transfer the Dll4 protein to other endothelial cells and incorporate it into their cell membrane, which results in an inhibition of Notch signaling and a loss of Notch receptor. Transfer of Dll4 was also shown in vivo from tumor cells to host endothelium. Addition of Dll4 exosomes confers a tip cell phenotype on the endothelial cell, which results in a high Dll4/Notch-receptor ratio, low Notch signaling, and filopodia formation. This was further evidenced by increased branching in a tube-formation assay and in vivo. This reversal in phenotype appears to enhance vessel formation and is a new form of signaling for Notch ligands that expands their signaling potential beyond cell-cell contact.
High-resolution mapping of prostaglandin E2–dependent signaling networks identifies a constitutively active PKA signaling node in CD8+CD45RO+ T cells
Authors: Oberprieler Nikolaus G. , Lemeer Simone , Kalland Maria E. , Torgersen Knut M. , Heck Albert J. R. , Taskén Kjetil
Published: June 2010

To analyze prostaglandin E2 (PGE2) signaling in lymphoid cells, we introduce a multipronged strategy, combining temporal quantitative phosphoproteomics and phospho flow cytometry. We describe the PGE2-induced phosphoproteome by simultaneous monitoring of approximately 250 regulated phospho-epitopes, which, according to kinase prediction algorithms, originate from a limited number of kinase networks. Assessing these signaling pathways by phospho flow cytometry provided higher temporal resolution at various PGE2 concentrations in multiple lymphoid cell subsets. This showed elevated levels of protein kinase A (PKA) signaling in unstimulated CD8+CD45RO+ T cells, which correlated with suppressed proximal T-cell receptor signaling, indicating that PKA sets the threshold for activation. The combination of phosphoproteomics and high throughput phospho flow cytometry applied here provides a comprehensive generic framework for the analysis of signaling networks in mixed cell populations.
NUP98-MLL fusion in human acute myeloblastic leukemia
Authors: Kaltenbach Sophie , Soler Gwendoline , Barin Carole , Gervais Carine , Bernard Olivier A. , Penard-Lacronique Virginie , Romana Serge P.
Published: June 2010

Posttranscriptional modifications of histones play important roles in the control of chromatin structure and transcription. H3K4 (histone H3 lysine 4) methylation by the SET domain of the trithorax-group protein MLL (mixed-lineage leukemia) is important for the control of homeobox (HOX) gene expression during development. MLL is tethered to the HOXA locus through interaction of its amino-terminus with menin. MLL fusion proteins associated with human leukemia contain the menin interaction peptide and frequently recruit H3K79 (histone H3 lysine 79) methylation activity. This allows sustained expression of HOXA genes important for cellular transformation. We have characterized a novel recurrent chromosomal aberration, inv(11)(p15q23), as an isolated chromosomal abnormality in 2 patients with acute myeloid leukemia. This aberration is predicted to result in the expression of an NUP98 (nucleoporin 98 kDa)–MLL fusion protein that is unable to interact with menin. As expected, low levels of HOXA gene expression were observed in the patients' samples. This fusion protein is predicted to participate in cellular transformation by activating MLL targets other than HOXA genes.
An efficient biological pathway layout algorithm combining grid-layout and spring embedder for complicated cellular location information
Authors: Kojima Kaname , Nagasaki Masao , Miyano Satoru
Published: June 2010

Background

Graph drawing is one of the important techniques for understanding biological regulations in a cell or among cells at the pathway level. Among many available layout algorithms, the spring embedder algorithm is widely used not only for pathway drawing but also for circuit placement and www visualization and so on because of the harmonized appearance of its results. For pathway drawing, location information is essential for its comprehension. However, complex shapes need to be taken into account when torus-shaped location information such as nuclear inner membrane, nuclear outer membrane, and plasma membrane is considered. Unfortunately, the spring embedder algorithm cannot easily handle such information. In addition, crossings between edges and nodes are usually not considered explicitly.

Results

We proposed a new grid-layout algorithm based on the spring embedder algorithm that can handle location information and provide layouts with harmonized appearance. In grid-layout algorithms, the mapping of nodes to grid points that minimizes a cost function is searched. By imposing positional constraints on grid points, location information including complex shapes can be easily considered. Our layout algorithm includes the spring embedder cost as a component of the cost function. We further extend the layout algorithm to enable dynamic update of the positions and sizes of compartments at each step.

Conclusions

The new spring embedder-based grid-layout algorithm and a spring embedder algorithm are applied to three biological pathways; endothelial cell model, Fas-induced apoptosis model, and C. elegans cell fate simulation model. From the positional constraints, all the results of our algorithm satisfy location information, and hence, more comprehensible layouts are obtained as compared to the spring embedder algorithm. From the comparison of the number of crossings, the results of the grid-layout-based algorithm tend to contain more crossings than those of the spring embedder algorithm due to the positional constraints. For a fair comparison, we also apply our proposed method without positional constraints. This comparison shows that these results contain less crossings than those of the spring embedder algorithm. We also compared layouts of the proposed algorithm with and without compartment update and verified that latter can reach better local optima.
Rapid and sensitive detection of Citrus Bacterial Canker by loop-mediated isothermal amplification combined with simple visual evaluation methods
Authors: Rigano Luciano A , Marano María R , Castagnaro Atilio P , Do Amaral Alexandre Morais , Vojnov Adrian A
Published: June 2010

Background

Citrus Bacterial Canker (CBC) is a major, highly contagious disease of citrus plants present in many countries in Asia, Africa and America, but not in the Mediterranean area. There are three types of Citrus Bacterial Canker, named A, B, and C that have different genotypes and posses variation in host range within citrus species. The causative agent for type A CBC isXanthomonas citrisubsp.citri, whileXanthomonas fuscanssubsp.aurantifolii, strain B causes type B CBC andXanthomonas fuscanssubsp.aurantifoliistrain C causes CBC type C. The early and accurate identification of those bacteria is essential for the protection of the citrus industry. Detection methods based on bacterial isolation, antibodies or polymerase chain reaction (PCR) have been developed previously; however, these approaches may be time consuming, laborious and, in the case of PCR, it requires expensive laboratory equipment. Loop-mediated isothermal amplification (LAMP), which is a novel isothermal DNA amplification technique, is sensitive, specific, fast and requires no specialized laboratory equipment.

Results

A loop-mediated isothermal amplification assay for the diagnosis of Citrus Bacterial Canker (CBC-LAMP) was developed and evaluated. DNA samples were obtained from infected plants or cultured bacteria. A typical ladder-like pattern on gel electrophoresis was observed in all positive samples in contrast to the negative controls. In addition, amplification products were detected by visual inspection using SYBRGreen and using a lateral flow dipstick, eliminating the need for gel electrophoresis. The sensitivity and specificity of the assay were evaluated in different conditions and using several sample sources which included purified DNA, bacterium culture and infected plant tissue. The sensitivity of the CBC-LAMP was 10 fg of pureXccDNA, 5 CFU in culture samples and 18 CFU in samples of infected plant tissue. No cross reaction was observed with DNA of other phytopathogenic bacteria. The assay was capable of detecting CBC-causing strains from several geographical origins and pathotypes.

Conclusions

The CBC-LAMP technique is a simple, fast, sensitive and specific method for the diagnosis of Citrus Bacterial Canker. This method can be useful in the phytosanitary programs of the citrus industry worldwide.
Plant neighbor identity influences plant biochemistry and physiology related to defense
Authors: Broz Amanda K , Broeckling Corey D , De-la-Peña Clelia , Lewis Matthew R , Greene Erick , Callaway Ragan M , Sumner Lloyd W , Vivanco Jorge M
Published: June 2010

Background

Chemical and biological processes dictate an individual organism's ability to recognize and respond to other organisms. A small but growing body of evidence suggests that plants may be capable of recognizing and responding to neighboring plants in a species specific fashion. Here we tested whether or not individuals of the invasive exotic weed, Centaurea maculosa, would modulate their defensive strategy in response to different plant neighbors.

Results

In the greenhouse, C. maculosa individuals were paired with either conspecific (C. maculosa) or heterospecific (Festuca idahoensis) plant neighbors and elicited with the plant defense signaling molecule methyl jasmonate to mimic insect herbivory. We found that elicited C. maculosa plants grown with conspecific neighbors exhibited increased levels of total phenolics, whereas those grown with heterospecific neighbors allocated more resources towards growth. To further investigate these results in the field, we conducted a metabolomics analysis to explore chemical differences between individuals of C. maculosa growing in naturally occurring conspecific and heterospecific field stands. Similar to the greenhouse results, C. maculosa individuals accumulated higher levels of defense-related secondary metabolites and lower levels of primary metabolites when growing in conspecific versus heterospecific field stands. Leaf herbivory was similar in both stand types; however, a separate field study positively correlated specialist herbivore load with higher densities of C. maculosa conspecifics.

Conclusions

Our results suggest that an individual C. maculosa plant can change its defensive strategy based on the identity of its plant neighbors. This is likely to have important consequences for individual and community success.
The CaaX specificities of Arabidopsis protein prenyltransferases explain era1 and ggb phenotypes
Authors: Andrews Michelle , Huizinga David H , Crowell Dring N
Published: June 2010

Background

Protein prenylation is a common post-translational modification in metazoans, protozoans, fungi, and plants. This modification, which mediates protein-membrane and protein-protein interactions, is characterized by the covalent attachment of a fifteen-carbon farnesyl or twenty-carbon geranylgeranyl group to the cysteine residue of a carboxyl terminal CaaX motif. In Arabidopsis, era1 mutants lacking protein farnesyltransferase exhibit enlarged meristems, supernumerary floral organs, an enhanced response to abscisic acid (ABA), and drought tolerance. In contrast, ggb mutants lacking protein geranylgeranyltransferase type 1 exhibit subtle changes in ABA and auxin responsiveness, but develop normally.

Results

We have expressed recombinant Arabidopsis protein farnesyltransferase (PFT) and protein geranylgeranyltransferase type 1 (PGGT1) in E. coli and characterized purified enzymes with respect to kinetic constants and substrate specificities. Our results indicate that, whereas PFT exhibits little specificity for the terminal amino acid of the CaaX motif, PGGT1 exclusively prenylates CaaX proteins with a leucine in the terminal position. Moreover, we found that different substrates exhibit similar Km but different kcat values in the presence of PFT and PGGT1, indicating that substrate specificities are determined primarily by reactivity rather than binding affinity.

Conclusions

The data presented here potentially explain the relatively strong phenotype of era1 mutants and weak phenotype of ggb mutants. Specifically, the substrate specificities of PFT and PGGT1 suggest that PFT can compensate for loss of PGGT1 in ggb mutants more effectively than PGGT1 can compensate for loss of PFT in era1 mutants. Moreover, our results indicate that PFT and PGGT1 substrate specificities are primarily due to differences in catalysis, rather than differences in substrate binding.
Identification of a new 130 bp cis-acting element in the TsVP1 promoter involved in the salt stress response from Thellungiella halophila
Authors: Sun Qinghua , Gao Feng , Zhao Lei , Li Kunpeng , Zhang Juren
Published: June 2010

Background

Salt stress is one of the major abiotic stresses affecting plant growth and productivity. Vacuolar H+-pyrophosphatase (H+-PPase) genes play an important role in salt stress tolerance in multiple species.

Results

In this study, the promoter from the vacuolar H+-pyrophosphatase from Thellungiella halophila (TsVP1) was cloned and compared with the AVP1 promoter from Arabidopsis thaliana. Sequence analysis indicated that these two promoters had seven similar motifs at similar positions. To determine which tissues the two promoters are active in, transgenic plants were produced with expression of the GUS reporter gene under the control of one of the promoters. In transgenic Arabidopsis with the TsVP1 promoter, the GUS reporter gene had strong activity in almost all tissues except the seeds and the activity was induced in both shoots and roots, especially in the root tips, when treated with salt stress. Such induction was not found in transgenic Arabidopsis with the AVP1 promoter. By analyzing different 5' deletion mutants of the TsVP1 promoter, an 856 bp region (-2200 to -1344) was found to contain enhancer elements that increased gene expression levels. Two AAATGA motifs, which may be the key elements for the anther specific expression profile, in the deleted TsVP1 promoters (PT2 to PT6) were also identified. A 130 bp region (-667 to -538) was finally identified as the key sequence for the salt stress response by analyzing the different mutants both with and without salt stress. GUS transient assay in tobacco leaves suggested the 130 bp region was sufficient for the salt stress response. Bioinformatic analysis also revealed that there may be novel motifs in this region that are the key elements for the salt stress responsive activity of the TsVP1 promoter.

Conclusions

The TsVP1 promoter had strong activity in almost all tissues except the seeds. In addition, its activity was induced by salt stress in leaves and roots, especially in root tips. A 130 bp region (-667 to -538) was identified as the key region for responding to salt stress.
SNAI2/Slug promotes growth and invasion in human gliomas
Authors: Yang Hong Wei , Menon Lata G , Black Peter M , Carroll Rona S , Johnson Mark D
Published: June 2010

Background

Numerous factors that contribute to malignant glioma invasion have been identified, but the upstream genes coordinating this process are poorly known.

Methods

To identify genes controlling glioma invasion, we used genome-wide mRNA expression profiles of primary human glioblastomas to develop an expression-based rank ordering of 30 transcription factors that have previously been implicated in the regulation of invasion and metastasis in cancer.

Results

Using this approach, we identified the oncogenic transcriptional repressor,SNAI2/Slug, among the upper tenth percentile of invasion-related transcription factors overexpressed in glioblastomas.SNAI2mRNA expression correlated with histologic grade and invasive phenotype in primary human glioma specimens, and was induced by EGF receptor activation in human glioblastoma cells. Overexpression ofSNAI2/Slug increased glioblastoma cell proliferation and invasionin vitroand promoted angiogenesis and glioblastoma growthin vivo. Importantly, knockdown of endogenousSNAI2/Slug in glioblastoma cells decreased invasion and increased survival in a mouse intracranial human glioblastoma transplantation model.

Conclusion

This genome-scale approach has thus identifiedSNAI2/Slug as a regulator of growth and invasion in human gliomas.
α-Amylase inhibitor-1 gene from Phaseolus vulgaris expressed in Coffea arabicaplants inhibits α-amylases from the coffee berry borer pest
Authors: Barbosa Aulus EAD , Albuquerque Érika VS , Silva Maria CM , Souza Djair SL , Oliveira-Neto Osmundo B , Valencia Arnubio , Rocha Thales L , Grossi-de-Sa Maria F
Published: June 2010

Background

Coffee is an important crop and is crucial to the economy of many developing countries, generating around US$70 billion per year. There are 115 species in the Coffea genus, but only two, C. arabica and C. canephora, are commercially cultivated. Coffee plants are attacked by many pathogens and insect-pests, which affect not only the production of coffee but also its grain quality, reducing the commercial value of the product. The main insect-pest, the coffee berry borer (Hypotheneumus hampei), is responsible for worldwide annual losses of around US$500 million. The coffee berry borer exclusively damages the coffee berries, and it is mainly controlled by organochlorine insecticides that are both toxic and carcinogenic. Unfortunately, natural resistance in the genus Coffea to H. hampei has not been documented. To overcome these problems, biotechnological strategies can be used to introduce an α-amylase inhibitor gene (α-AI1), which confers resistance against the coffee berry borer insect-pest, into C. arabica plants.

Results

We transformed C. arabica with the α-amylase inhibitor-1 gene (α-AI1) from the common bean, Phaseolus vulgaris, under control of the seed-specific phytohemagglutinin promoter (PHA-L). The presence of the α-AI1 gene in six regenerated transgenic T1 coffee plants was identified by PCR and Southern blotting. Immunoblotting and ELISA experiments using antibodies against α-AI1 inhibitor showed a maximum α-AI1 concentration of 0.29% in crude seed extracts. Inhibitory in vitro assays of the α-AI1 protein against H. hampei α-amylases in transgenic seed extracts showed up to 88% inhibition of enzyme activity.

Conclusions

This is the first report showing the production of transgenic coffee plants with the biotechnological potential to control the coffee berry borer, the most important insect-pest of crop coffee.
Ezetimibe + simvastatin versus doubling the dose of simvastatin in high cardiovascular risk diabetics: a multicenter, randomized trial (the LEAD study)
Authors: Bardini Gianluca , Giorda Carlo B , Pontiroli Antonio E , Le Grazie Cristina , Rotella Carlo M
Published: June 2010

Background

The primary goal of therapy in patients with hypercholesterolemia and coronary heart disease (CHD) is reducing low-density lipoprotein cholesterol (LDL-C). This was a multicenter, randomized, double-blind, double-dummy study in patients with type 2 diabetes mellitus (T2DM).

Methods

Adult patients with T2DM and CHD (N = 93) on a stable dose of simvastatin 20 mg with LDL-C ≥ 2.6 mmol/L (100 mg/dL) and ≤ 4.1 mmol/L (160 mg/dL) were randomized to ezetimibe 10 mg plus simvastatin 20 mg (EZ + simva 10/20 mg) or simvastatin 40 mg for 6 weeks. Percent change in LDL-C, high-density lipoprotein cholesterol, and triglycerides was assessed.

Results

EZ + simva 10/20 mg produced a significantly greater change from treated baseline compared with simvastatin 40 mg in LDL-C (-32.2% vs -20.8%; p < 0.01) and total cholesterol (-20.6% vs -13.2%; p < 0.01). A greater proportion of patients achieved LDL-C < 2.6 mmol/L with EZ + simva 10/20 mg than with simvastatin 40 mg, but this was not statistically significant (78.4% vs 60%; odds ratio = 2.81; p = 0.052). Changes in high-density lipoprotein cholesterol and triglycerides were similar between treatments. Both treatments were generally well-tolerated.

Conclusions

These results demonstrate that EZ + simva 10/20 mg may provide a superior alternative for LDL-C lowering vs doubling the dose of simvastatin to 40 mg in hyperlipidemic patients with T2DM and CHD. In addition, the combination therapy may provide an alternative treatment for patients who require further LDL-C reduction than they can achieve with simvastatin 20 mg alone.
Interaction between circulating galectin-3 and cancer-associated MUC1 enhances tumour cell homotypic aggregation and prevents anoikis
Authors: Zhao Qicheng , Barclay Monica , Hilkens John , Guo Xiuli , Barrow Hannah , Rhodes Jonathan M , Yu Lu-Gang
Published: June 2010

Background

Formation of tumour cell aggregation/emboli prolongs the survival of circulating tumour cells in the circulation, enhances their physical trapping in the micro-vasculature and thus increases metastatic spread of the cancer cells to remote sites.

Results

It shows here that the presence of the galactoside-binding galectin-3, whose concentration is markedly increased in the blood circulation of cancer patients, increases cancer cell homotypic aggregation under anchorage-independent conditions by interaction with the oncofetal Thomsen-Friedenreich carbohydrate (Galβ1,3GalNAcα-, TF) antigen on the cancer-associated transmembrane mucin protein MUC1. The galectin-3-MUC1 interaction induces MUC1 cell surface polarization and exposure of the cell surface adhesion molecules including E-cadherin. The enhanced cancer cell homotypic aggregation by galectin-MUC1 interaction increases the survival of the tumour cells under anchorage-independent conditions by allowing them to avoid initiation of anoikis (suspension-induced apoptosis).

Conclusion

These results suggest that the interaction between free circulating galectin-3 and cancer-associated MUC1 promotes embolus formation and survival of disseminating tumour cells in the circulation. This provides new information into our understanding of the molecular mechanisms of cancer cell haematogenous dissemination and suggests that targeting the interaction of circulating galectin-3 with MUC1 in the circulation may represent an effective therapeutic approach for preventing metastasis.
Arterial elasticity imaging: comparison of finite-element analysis models with high-resolution ultrasound speckle tracking
Authors: Park Dae Woo , Richards Michael S , Rubin Jonathan M , Hamilton James , Kruger Grant H , Weitzel William F
Published: June 2010

Background

The nonlinear mechanical properties of internal organs and tissues may be measured with unparalleled precision using ultrasound imaging with phase-sensitive speckle tracking. The many potential applications of this important noninvasive diagnostic approach include measurement of arterial stiffness, which is associated with numerous major disease processes. The accuracy of previous ultrasound measurements of arterial stiffness and vascular elasticity has been limited by the relatively low strain of nonlinear structures under normal physiologic pressure and the measurement assumption that the effect of the surrounding tissue modulus might be ignored in both physiologic and pressure equalized conditions.

Methods

This study performed high-resolution ultrasound imaging of the brachial artery in a healthy adult subject under normal physiologic pressure and the use of external pressure (pressure equalization) to increase strain. These ultrasound results were compared to measurements of arterial strain as determined by finite-element analysis models with and without a surrounding tissue, which was represented by homogenous material with fixed elastic modulus.

Results

Use of the pressure equalization technique during imaging resulted in average strain values of 26% and 18% at the top and sides, respectively, compared to 5% and 2%, at the top and sides, respectively, under physiologic pressure. In the artery model that included surrounding tissue, strain was 19% and 16% under pressure equalization versus 9% and 13% at the top and sides, respectively, under physiologic pressure. The model without surrounding tissue had slightly higher levels of strain under physiologic pressure compared to the other model, but the resulting strain values under pressure equalization were > 60% and did not correspond to experimental values.

Conclusions

Since pressure equalization may increase the dynamic range of strain imaging, the effect of the surrounding tissue on strain should be incorporated into models of arterial strain, particularly when the pressure equalization technique is used.
P66shc and its downstream Eps8 and Rac1 proteins are upregulated in esophageal cancers
Authors: Bashir Muneesa , Kirmani Deeba , Bhat Hina F , Baba Rafia A , Hamza Rouf , Naqash Sameer , Wani Nisar A , Andrabi Khurshid I , Zargar Mohammad A , Khanday Firdous A
Published: June 2010

Members of Shc (src homology and collagen homology) family, p46shc, p52shc, p66shc have known to be related to cell proliferation and carcinogenesis. Whereas p46shc and p52shc drive the reaction forward, the role of p66shc in cancers remains to be understood clearly. Hence, their expression in cancers needs to be evaluated carefully so that Shc analysis may provide prognostic information in the development of carcinogenesis. In the present study, the expression of p66shc and its associate targets namely Eps8 (epidermal pathway substrate 8), Rac1 (ras-related C3 botulinum toxin substrate1) and Grb2 (growth factor receptor bound protein 2) were examined in fresh tissue specimens from patients with esophageal squamous cell carcinoma and esophageal adenocarcinoma using western blot analysis. A thorough analysis of both esophageal squamous cell carcinoma and adenocarcinoma showed p66shc expression to be significantly higher in both types of carcinomas as compared to the controls. The controls of adenocarcinoma show a higher basal expression level of p66shc as compared to the controls of squamous cell carcinoma. The expression level of downstream targets of p66shc i.e., eps8 and rac1 was also found to be consistently higher in human esophageal carcinomas, and hence correlated positively with p66shc expression. However the expression of grb2 was found to be equal in both esophageal squamous cell carcinoma and adenocarcinoma. The above results suggest that the pathway operated by p66shc in cancers does not involve the participation of Ras and Grb2 as downstream targets instead it operates the pathway involving Eps8 and Rac1 proteins. From the results it is also suggestive that p66shc may have a role in the regulation of esophageal carcinomas and represents a possible mechanism of signaling for the development of squamous cell carcinoma and adenocarcinoma of esophagus.
Downstream of tyrosine kinase/docking protein 6, as a novel substrate of tropomyosin-related kinase C receptor, is involved in neurotrophin 3-mediated neurite outgrowth in mouse cortex neurons
Authors: Li Wei qi , Shi Lei , You Yuan gang , Gong Yan hua , Yin Bin , Yuan Jian gang , Peng Xiao zhong
Published: June 2010

Background

The downstream of tyrosine kinase/docking protein (Dok) adaptor protein family has seven members, Dok1 to Dok7, that act as substrates of multiple receptor tyrosine kinase and non-receptor tyrosine kinase. The tropomyosin-related kinase (Trk) receptor family, which has three members (TrkA, TrkB and TrkC), are receptor tyrosine kinases that play pivotal roles in many stages of nervous system development, such as differentiation, migration, axon and dendrite projection and neuron patterning. Upon related neurotrophin growth factor stimulation, dimerisation and autophosphorylation of Trk receptors can occur, recruiting adaptor proteins to mediate signal transduction.

Results

In this report, by using yeast two-hybrid assays, glutathione S-transferase (GST) precipitation assays and coimmunoprecipitation (Co-IP) experiments, we demonstrate that Dok6 selectively binds to the NPQY motif of TrkC through its phosphotyrosine-binding (PTB) domain in a kinase activity-dependent manner. We further confirmed their interaction by coimmunoprecipitation and colocalisation in E18.5 mouse cortex neurons, which provided more in vivo evidence. Next, we demonstrated that Dok6 is involved in neurite outgrowth in mouse cortex neurons via the RNAi method. Knockdown of Dok6 decreased neurite outgrowth in cortical neurons upon neurotrophin 3 (NT-3) stimulation.

Conclusions

We conclude that Dok6 interacts with the NPQY motif of the TrkC receptor through its PTB domain in a kinase activity-dependent manner, and works as a novel substrate of the TrkC receptor involved in NT-3-mediated neurite outgrowth in mouse cortex neurons.
Immunohistochemical analysis of Metadherin in proliferative and cancerous breast tissue
Authors: Su Peng , Zhang Qinghui , Yang Qifeng
Published: June 2010

Background

Metadherin (MTDH) has been reported to be associated with cancer progression in various types of human cancers including breast cancer. Whether MTDH contributes to carcinogenesis of breast cancer is still unknown. In the present study, we investigated the expression of MTDH in normal, UDH (usual ductal hyperplasia), ADH (atypical ductal hyperplasia), DCIS (ductal carcinoma in situ) and invasive cancer to explore the possible role of MTDH for breast cancer carcinogenesis.

Methods

Immunohistochemistry was employed on paraffin sections of surgical removed breast samples.

Results

The immunohistochemical results showed almost no staining in normal tissue, moderate staining in ADH and UDH, intense MTDH stains in DCIS and cancer. Statistical analysis demonstrated significant different MTDH expression between proliferative and cancerous breast lesions (p < 0.001). MTDH was positively correlated with the histological differentiation of DCIS (p = 0.028). In breast cancer, statistical analysis revealed a significant correlation between MTDH expression with patients' age (p = 0.042), ER status (p = 0.018) and p53 status (p = 0.001). We also examined the effect of MTDH on cell proliferation in DCIS and cancer, and we found that MTDH overexpression was significantly correlated with high Ki67 index (p = 0.008 and p = 0.036, respectively).

Conclusions

MTDH overexpression could be identified in proliferative breast lesions and may contribute to breast cancer progression.
Rehabilitation of torture survivors in five countries: common themes and challenges
Authors: McColl Helen , Higson-Smith Craig , Gjerding Sarah , Omar Mostafa H , Rahman Basma Abdel , Hamed Mona , El Dawla Aida S , Fredericks Miriam , Paulsen Nicole , Shabalala Gugu , Low-Shang Carmen , Perez Fernando Valadez , Colin Liliana S , Hernandez Aurora D , Lavaire Eliomara , Zuñiga Arely PA , Calidonio Lucia , Martinez Carmen L , Jamei Yasser Abu , Awad Zeyad
Published: June 2010

Background

Torture continues to be a global problem and there is a need for prevention and rehabilitation efforts. There is little available data on torture survivors from studies designed and conducted by health professionals in low income countries. This study is a collaboration between five centres from Gaza, Egypt, Mexico, Honduras and South Africa who provide health, social and legal services to torture survivors, advocate for the prevention of torture and are part of the network of the International Rehabilitation Council for Torture Victims (IRCT).

Methods

Socio-demographic, clinical and torture exposure data was collected on the torture survivors attending the five centres at presentation and then at three and six month follow-up periods. This sample of torture survivors is presented using a range of descriptive statistics. Change over time is demonstrated with repeated measures analysis of variance.

Results

Of the 306 torture survivors, 23% were asylum seekers or refugees, 24% were socially isolated, 11% in prison. A high level of traumatic events was experienced. 64% had suffered head injury whilst tortured and 24% had ongoing torture injury problems. There was high prevalence of symptoms of anxiety, depression, post traumatic stress as well as medically unexplained somatic symptoms. The analysis demonstrates a modest drop in symptoms over the six months of the study.

Conclusions

Data showed that the torture survivors seen in these five centres had high levels of exposure to torture events and high rates of clinical symptoms. In order to provide effective services to torture survivors, health professionals at torture rehabilitation centres in low income countries need to be supported to collect relevant data to document the needs of torture survivors and to evaluate the centres' interventions.
pARIS-htt: an optimised expression platform to study huntingtin reveals functional domains required for vesicular trafficking
Authors: Pardo Raúl , Molina-Calavita Maria , Poizat Ghislaine , Keryer Guy , Humbert Sandrine , Saudou Frédéric
Published: June 2010

Background

Huntingtin (htt) is a multi-domain protein of 350 kDa that is mutated in Huntington's disease (HD) but whose function is yet to be fully understood. This absence of information is due in part to the difficulty of manipulating large DNA fragments by using conventional molecular cloning techniques. Consequently, few studies have addressed the cellular function(s) of full-length htt and its dysfunction(s) associated with the disease.

Results

We describe a flexible synthetic vector encoding full-length htt called pARIS-htt (A daptable, R NAi I nsensitive & S ynthetic). It includes synthetic cDNA coding for full-length human htt modified so that: 1) it is improved for codon usage, 2) it is insensitive to four different siRNAs allowing gene replacement studies, 3) it contains unique restriction sites (URSs) dispersed throughout the entire sequence without modifying the translated amino acid sequence, 4) it contains multiple cloning sites at the N and C-ter ends and 5) it is Gateway compatible. These modifications facilitate mutagenesis, tagging and cloning into diverse expression plasmids. Htt regulates dynein/dynactin-dependent trafficking of vesicles, such as brain-derived neurotrophic factor (BDNF)-containing vesicles, and of organelles, including reforming and maintenance of the Golgi near the cell centre. We used tests of these trafficking functions to validate various pARIS-htt constructs. We demonstrated, after silencing of endogenous htt, that full-length htt expressed from pARIS-htt rescues Golgi apparatus reformation following reversible microtubule disruption. A mutant form of htt that contains a 100Q expansion and a htt form devoid of either HAP1 or dynein interaction domains are both unable to rescue loss of endogenous htt. These mutants have also an impaired capacity to promote BDNF vesicular trafficking in neuronal cells.

Conclusion

We report the validation of a synthetic gene encoding full-length htt protein that will facilitate analyses of its structure/function. This may help provide relevant information about the cellular dysfunctions operating during the disease. As proof of principle, we show that either polyQ expansion or deletion of key interacting domains within full-length htt protein impairs its function in transport indicating that HD mutation induces defects on intrinsic properties of the protein and further demonstrating the importance of studying htt in its full-length context.
Jigs and Tools Foe Motor Car Work
Authors: Plant A. E.
Published: June 2010

Digest of Paper which gained the Prize of Five Guineas awarded by the Council to the Graduate writing the best Paper during the year ending with the Annual Meeting in March, 1910:—
Car Design and Car Usage
Authors: Duffield Edgar N.
Published: June 2010

A Plea for the fuller Appreciation by Car Designers of the limited mechanical Knowledge and engineering Sense of those who buy Cars, together with some Notes of a few Directions in which Design should Be modified with Advantage equally to Manufacturer and User
Some Problems Connected with High-Speed Compression-Ignition Engine Development
Authors: Dicksee C. B.
Published: June 2010

This paper was read by Mr. Dicksee on the occasion of the second Joint iMeeting of eleven Scientific Institutions, as follows:— The Chemical Engineering Group, the Diesel Engine Users' Association, the Institute of Fuel, the Institute of Marine Engineers, the Institution of Automobile Engineers, the Institution of Mechanical Engineers, the Institution of Petroleum Technologists, the Junior Institution of Engineers, the North-East Coast Institution of Engineers and Shipbuilders, the Royal Aeronautical Society, and the Society of Engineers.

Following last year's precedent, the Chair was taken by Mr. Tookey, President of the Institution of Automobile Engineers, who introduced Mr. A. E. L. Chorlton as Chairman for the meeting.

Mr. Chorlton gave it as his opinion that meetings of this nature must be exceedingly valuable as a means of expressing to the nation a combined technical opinion which must have far more weight than an expression of more individual character. He suggested that a continuation of the practice might lead to the formation of something in the nature of a Technical Parliament, and asked those present to consider the possibility of some such result. Mr. Chorlton went on to emphasize the importance of research for all classes of mechanical engineering, laying special stress on the need for co-ordination of research among all parties.