bluuebunny/crossref_metadata_2025 huggingface dataset:
Mineralocorticoid receptor blockade ameliorates peritoneal fibrosis in new rat peritonitis model
Authors: Nishimura Hayato , Ito Yasuhiko , Mizuno Masashi , Tanaka Akio , Morita Yoshiki , Maruyama Shoichi , Yuzawa Yukio , Matsuo Seiichi
Published: March 2008

Peritoneal fibrosis (PF) is an important complication of long-term peritoneal dialysis. Although mineralocorticoid and mineralocorticoid receptor (MR) have attracted increasing attention in the field of vascular injury, including the heart, kidney, and vessels, little is known about the role of mineralocorticoid in PF. This work was designed to explore the effects of MR blockade on PF. We developed a new model of PF in rats based on mechanical scraping of the peritoneum. This model is characterized by acute-phase inflammation (neutrophil and macrophage infiltration on days 0–3) and late-phase PF (α-smooth muscle actin-positive fibroblast infiltration, type III collagen accumulation, and neoangiogenesis on days 7–14). Peritoneal thickening peaked on day 14. MR was expressed in rat peritoneum and a rat fibroblast cell line. Expression of its effector kinase [serum- and glucocorticoid-induced kinase-1 (Sgk1)], transforming growth factor-β (TGF-β), plasminogen activator inhibitor-1 (PAI-1), and CD31-positive vessels increased during the course of PF. Rats were treated with spironolactone, angiotensin receptor blockade (ARB), or angiotensin-converting enzyme inhibitor (ACEI)-ARB-spironolactone starting at 6 h after peritoneal scraping. All parameters, including peritoneal thickening, number of macrophages and CD31-positive vessels, and expression of monocyte chemoattractant protein-1, TGF-β, PAI-1, and Sgk1, were significantly suppressed by spironolactone (10 mg·kg−1·day−1). The effects of spironolactone (10 and 20 mg·kg−1·day−1) were very similar to those of triple blockade. ARB, but not ACEI, significantly reduced peritoneal thickening. Furthermore, peritoneal function assessed by peritoneal equilibration test was significantly improved by spironolactone. Our results suggest that MR is a potential target to prevent inflammation-induced PF in patients on peritoneal dialysis.
Determination of plasma and urinary angiotensinogen levels in rodents by newly developed ELISA
Authors: Kobori Hiroyuki , Katsurada Akemi , Miyata Kayoko , Ohashi Naro , Satou Ryousuke , Saito Toshie , Hagiwara Yoshiaki , Miyashita Kazuya , Navar L. Gabriel
Published: March 2008

We recently reported that urinary excretion rates of angiotensinogen provide a specific index of the intrarenal renin-angiotensin system status in angiotensin II-dependent hypertensive rats. Angiotensinogen concentrations in mouse plasma are thought to be much lower than those in rat plasma; however, detailed information is deficient due to lack of direct quantitative measurements of rodent angiotensinogen. To elucidate this issue, we have developed a quantitative method for measurement of rodent angiotensinogen using a sandwich-type ELISA. The standard curve for mouse and rat angiotensinogen exhibited a high linearity at 0.16–10 and 0.08–5 ng/ml, respectively, with correlation coefficients >0.99. While plasma angiotensinogen concentrations of male high serum IgA (HIGA) mice (IgA nephritis model animals, 1,308 ± 47 ng/ml; n = 10) were lower than those of control BALB/c mice (1,620 ± 384; n = 12), urinary angiotensinogen concentrations of HIGA mice (14.6 ± 1.5 ng/ml; n = 34) were higher than those of BALB/c mice (4.6 ± 0.1; n = 2). In a similar manner, while plasma angiotensinogen concentrations of Zucker diabetic fatty (ZDF) obese rats (type 2 diabetic model animals, 1,789 ± 50 ng/ml; n = 5) were lower than those of control ZDF lean rats (2,296 ± 47; n = 5), urinary angiotensinogen concentrations of ZDF obese rats (88.2 ± 11.4 ng/ml; n = 15) were higher than those of ZDF lean rats (31.3 ± 1.9; n = 15). These data indicate that plasma and urinary angiotensinogen concentrations are less in mice than rats. However, these data suggest that urinary angiotensinogen levels are different from plasma angiotensinogen levels in rodents. The development of rodent angiotensinogen ELISA allows quantitative comparisons in mouse and rat angiotensinogen levels in models of hypertension and cardiovascular and kidney diseases.
Susruta of India, an unrecognized contributor to the history of exercise physiology
Authors: Tipton Charles M.
Published: March 2008

When considering the history of exercise physiology, authors begin with Hippocrates and the “Golden Age” of Greece before mentioning Galen and the contributions from Rome. However, this approach has omitted the information from the ancient civilizations of India which flourished before and during the emergence of Mycenaen cultures. Specifically ignored have been 1) the tridosa doctrine (humoral theory), which as early as 1500 B.C., emphasized that disease occurred because of a displacement of one or more of the three humors, with health being achieved when the humors were in equilibrium and 2) the perspective of Susruta (Sushruta) who was a 600 B.C. physician who included exercise in his prescriptions to prevent and treat diseases. Susruta not only advocated exercise to maintain equilibrium among the humors, notably kapha, he promoted exercise to minimize the consequences of obesity and diabetes. To be effective, exercise had to be daily and moderate in intensity and never excessive or to exceed the half-maximum limit for exhaustion, because disease or even death could ensue. It is concluded that Susruta's concepts pertaining to chronic exercise and to the health benefits of exercise were “remarkably modern” and that future authors on the history of exercise physiology should include contributions from ancient India.
Spontaneous Recovery of Motor Memory During Saccade Adaptation
Authors: Ethier Vincent , Zee David S. , Shadmehr Reza
Published: March 2008

It is possible that motor adaptation in timescales of minutes is supported by two distinct processes: one process that learns slowly from error but has strong retention, and another that learns rapidly from error but has poor retention. This two-state model makes the prediction that if a period of adaptation is followed by a period of reverse-adaptation, then in the subsequent period in which errors are clamped to zero (error-clamp trials) there will be a spontaneous recovery, i.e., a rebound of behavior toward the initial level of adaptation. Here we tested and confirmed this prediction during double-step, on-axis, saccade adaptation. When people adapted their saccadic gain to a magnitude other than one (adaptation) and then the gain was rapidly reversed back to one (reverse-adaptation), in the subsequent error-clamp trials (visual target placed on the fovea after the saccade) the gain reverted toward the initially adapted value and then gradually reverted toward normal. We estimated that the fast system was about 20-fold more sensitive to error than the slow system, but had a time constant of 28 s, whereas the slow system had a time constant of nearly 8 min. Therefore short-term adaptive mechanisms that maintain accuracy of saccades rely on a memory system that has characteristics of a multistate process with a logarithmic distribution of timescales.
Discovery of subjective evaluations of product features in hotel reviews
Authors: Pekar Viktor , Shiyan Ou
Published: March 2008

Automated discovery and analysis of customer opinions on the web holds a lot of promise for present-day practices of market research and customer relationship management. Opinion mining attempts to come up with ways to automatically analyse subjectivity expressed in natural language text. Previous research on the topic has shown that the overall subjectivity expressed in a document, such as a customer review, can be assessed with accuracy that is feasible in real-world applications. In this paper, we address the challenge of identification of customer opinions expressed towards specific features of a product, such as service quality and location of a hotel. The paper proposes and investigates a method to recognize the relationships between subjective expressions and references to features of a product. While the method has been evaluated on customer hotel reviews, it can potentially find application also in many tasks where concrete statements need to be extracted from documents on heterogeneous topics such as posts in forums, comments on blogs, or utterances in a chat room.
Using a Cultural Framework to Assess the Nutrition Influences in Relation to Birth Outcomes Among African American Women of Childbearing Age: Application of the PEN-3 Theoretical Model
Authors: Kannan Srimathi , Webster DeWitt , Sparks Arlene , Acker Charlene M. , Greene-Moton Ella , Tropiano Elizabeth , Turner Tonya
Published: March 2008

The purpose is to present the process and results of focus groups conducted to access information for the design of a healthy eating curriculum to reduce maternal nutritional risks and enhance protective factors among African American women in relation to birth outcomes. Sixteen younger (19 to 25 years) and 20 older African American women (45 to 60 years), respectively, participated. The PEN-3 model, (Airhihenbuwa, 1995, 1999) guided the focus groups. Most women stated that culture and family relationships impacted their food choices. Younger women expressed creativity with recipes and presented a desire to be more involved with preparing foods. Older women expressed eagerness to teach family-centered culinary skill-building classes. Both groups of women acknowledged time and budget barriers, identified the prevalence of lactose intolerance, and recognized that large grocery stores that offered food variety were not located in their community. Health professionals are encouraged to consider these findings while designing interventions targeting young African American women's nutrition in relation to birth outcomes.
BH3-only proteins Noxa, Bmf, and Bim are necessary for arsenic trioxide–induced cell death in myeloma
Authors: Morales Alejo A. , Gutman Delia , Lee Kelvin P. , Boise Lawrence H.
Published: March 2008

The use of arsenic trioxide (ATO) to treat multiple myeloma (MM) is supported by preclinical studies as well as several phase 2 studies, but the precise mechanism(s) of action of ATO has not been completely elucidated. We used gene expression profiling to determine the regulation of apoptosis-related genes by ATO in 4 MM cell lines and then focused on Bcl-2 family genes. ATO induced up-regulation of 3 proapoptotic BH3-only proteins (Noxa, Bmf, and Puma) and down-regulation of 2 antiapoptotic proteins Mcl-1 and Bcl-XL. Coimmunoprecipitation demonstrated that Noxa and Puma bind Mcl-1 to release Bak and Bim within 6 hours of ATO addition. Bak and Bim are also released from Bcl-XL. Silencing of Bmf, Noxa, and Bim significantly protected cells from ATO-induced apoptosis, while Puma silencing had no effect. Consistent with a role for Noxa inhibition of Mcl-1, the Bad-mimetic ABT-737 synergized with ATO in the killing of 2 MM lines. Finally, Noxa expression was enhanced by GSH depletion and inhibited by increasing GSH levels in the cells. Understanding the pattern of BH3-only protein response should aid in the rational design of arsenic-containing regimens.
Methods for simultaneously identifying coherent local clusters with smooth global patterns in gene expression profiles
Authors: Tien Yin-Jing , Lee Yun-Shien , Wu Han-Ming , Chen Chun-Houh
Published: March 2008

Background

The hierarchical clustering tree (HCT) with a dendrogram [1] and the singular value decomposition (SVD) with a dimension-reduced representative map [2] are popular methods for two-way sorting the gene-by-array matrix map employed in gene expression profiling. While HCT dendrograms tend to optimize local coherent clustering patterns, SVD leading eigenvectors usually identify better global grouping and transitional structures.

Results

This study proposes a flipping mechanism for a conventional agglomerative HCT using a rank-two ellipse (R2E, an improved SVD algorithm for sorting purpose) seriation by Chen [3] as an external reference. While HCTs always produce permutations with good local behaviour, the rank-two ellipse seriation gives the best global grouping patterns and smooth transitional trends. The resulting algorithm automatically integrates the desirable properties of each method so that users have access to a clustering and visualization environment for gene expression profiles that preserves coherent local clusters and identifies global grouping trends.

Conclusion

We demonstrate, through four examples, that the proposed method not only possesses better numerical and statistical properties, it also provides more meaningful biomedical insights than other sorting algorithms. We suggest that sorted proximity matrices for genes and arrays, in addition to the gene-by-array expression matrix, can greatly aid in the search for comprehensive understanding of gene expression structures. Software for the proposed methods can be obtained at http://gap.stat.sinica.edu.tw/Software/GAP.
Systematic sequencing of mRNA from the Antarctic krill (Euphausia superba) and first tissue specific transcriptional signature
Authors: De Pittà Cristiano , Bertolucci Cristiano , Mazzotta Gabriella M , Bernante Filippo , Rizzo Giorgia , De Nardi Barbara , Pallavicini Alberto , Lanfranchi Gerolamo , Costa Rodolfo
Published: March 2008

Background

Little is known about the genome sequences of Euphausiacea (krill) although these crustaceans are abundant components of the pelagic ecosystems in all oceans and used for aquaculture and pharmaceutical industry. This study reports the results of an expressed sequence tag (EST) sequencing project from different tissues of Euphausia superba (the Antarctic krill).

Results

We have constructed and sequenced five cDNA libraries from different Antarctic krill tissues: head, abdomen, thoracopods and photophores. We have identified 1.770 high-quality ESTs which were assembled into 216 overlapping clusters and 801 singletons resulting in a total of 1.017 non-redundant sequences. Quantitative RT-PCR analysis was performed to quantify and validate the expression levels of ten genes presenting different EST countings in krill tissues. In addition, bioinformatic screening of the non-redundant E. superba sequences identified 69 microsatellite containing ESTs. Clusters, consensuses and related similarity and gene ontology searches were organized in a dedicated E. superba database http://krill.cribi.unipd.it.

Conclusion

We defined the first tissue transcriptional signatures of E. superba based on functional categorization among the examined tissues. The analyses of annotated transcripts showed a higher similarity with genes from insects with respect to Malacostraca possibly as an effect of the limited number of Malacostraca sequences in the public databases. Our catalogue provides for the first time a genomic tool to investigate the biology of the Antarctic krill.
Flexible nets: disorder and induced fit in the associations of p53 and 14-3-3 with their partners
Authors: Oldfield Christopher J , Meng Jingwei , Yang Jack Y , Yang Mary Qu , Uversky Vladimir N , Dunker A Keith
Published: March 2008

Background

Proteins are involved in many interactions with other proteins leading to networks that regulate and control a wide variety of physiological processes. Some of these proteins, called hub proteins or hubs, bind to many different protein partners. Protein intrinsic disorder, via diversity arising from structural plasticity or flexibility, provide a means for hubs to associate with many partners (Dunker AK, Cortese MS, Romero P, Iakoucheva LM, Uversky VN: Flexible Nets: The roles of intrinsic disorder in protein interaction networks. FEBS J 2005, 272:5129-5148).

Results

Here we present a detailed examination of two divergent examples: 1) p53, which uses different disordered regions to bind to different partners and which also has several individual disordered regions that each bind to multiple partners, and 2) 14-3-3, which is a structured protein that associates with many different intrinsically disordered partners. For both examples, three-dimensional structures of multiple complexes reveal that the flexibility and plasticity of intrinsically disordered protein regions as well as induced-fit changes in the structured regions are both important for binding diversity.

Conclusions

These data support the conjecture that hub proteins often utilize intrinsic disorder to bind to multiple partners and provide detailed information about induced fit in structured regions.
Supervised learning method for the prediction of subcellular localization of proteins using amino acid and amino acid pair composition
Authors: Habib Tanwir , Zhang Chaoyang , Yang Jack Y , Yang Mary Qu , Deng Youping
Published: March 2008

Background

Occurrence of protein in the cell is an important step in understanding its function. It is highly desirable to predict a protein's subcellular locations automatically from its sequence. Most studied methods for prediction of subcellular localization of proteins are signal peptides, the location by sequence homology, and the correlation between the total amino acid compositions of proteins. Taking amino-acid composition and amino acid pair composition into consideration helps improving the prediction accuracy.

Results

We constructed a dataset of protein sequences from SWISS-PROT database and segmented them into 12 classes based on their subcellular locations. SVM modules were trained to predict the subcellular location based on amino acid composition and amino acid pair composition. Results were calculated after 10-fold cross validation. Radial Basis Function (RBF) outperformed polynomial and linear kernel functions. Total prediction accuracy reached to 71.8% for amino acid composition and 77.0% for amino acid pair composition. In order to observe the impact of number of subcellular locations we constructed two more datasets of nine and five subcellular locations. Total accuracy was further improved to 79.9% and 85.66%.

Conclusions

A new SVM based approach is presented based on amino acid and amino acid pair composition. Result shows that data simulation and taking more protein features into consideration improves the accuracy to a great extent. It was also noticed that the data set needs to be crafted to take account of the distribution of data in all the classes.
Identification of transcription factor and microRNA binding sites in responsible to fetal alcohol syndrome
Authors: Wang Guohua , Wang Xin , Wang Yadong , Yang Jack Y , Li Lang , Nephew Kenneth P , Edenberg Howard J , Zhou Feng C , Liu Yunlong
Published: March 2008

This is a first report, using our MotifModeler informatics program, to simultaneously identify transcription factor (TF) and microRNA (miRNA) binding sites from gene expression microarray data. Based on the assumption that gene expression is controlled by combinatorial effects of transcription factors binding in the 5'-upstream regulatory region and miRNAs binding in the 3'-untranslated region (3'-UTR), we developed a model for (1) predicting the most influential cis-acting elements under a given biological condition, and (2) estimating the effects of those elements on gene expression levels. The regulatory regions, TF and miRNA, which mediate the differential genes expression in fetal alcohol syndrome were unknown; microarray data from alcohol exposure paradigm was used. The model predicted strong inhibitory effects of 5' cis-acting elements and stimulatory effects of 3'-UTR under alcohol treatment. Current predictive model derived a key hypothesis for the first time a novel role of miRNAs in gene expression changes associated with abnormal mouse embryo development after alcohol exposure. This suggests that disturbance of miRNA functions may contribute to the alcohol-induced developmental deficiencies.
xMAN: extreme MApping of OligoNucleotides
Authors: Li Wei , Carroll Jason S , Brown Myles , Liu X Shirley
Published: March 2008

Background

The ability to rapidly map millions of oligonucleotide fragments to a reference genome is crucial to many high throughput genomic technologies.

Results

We propose an intuitive and efficient algorithm, titled ex treme MA pping of OligoN ucleotide (xMAN), to rapidly map millions of oligonucleotide fragments to a genome of any length. By converting oligonucleotides to integers hashed in RAM, xMAN can scan through genomes using bit shifting operation and achieve at least one order of magnitude speed increase over existing tools. xMAN can map the 42 million 25-mer probes on the Affymetrix whole human genome tiling arrays to the entire genome in less than 6 CPU hours.

Conclusions

In addition to the speed advantage, we found the probe mapping of xMAN to substantially improve the final analysis results in both a spike-in experiment on ENCODE tiling arrays and an estrogen receptor ChIP-chip experiment on whole human genome tiling arrays. Those improvements were confirmed by direct ChIP and real-time PCR assay. xMAN can be further extended for application to other high-throughput genomic technologies for oligonucleotide mapping.
A hybrid machine learning-based method for classifying the Cushing's Syndrome with comorbid adrenocortical lesions
Authors: Yang Jack Y , Yang Mary Qu , Luo Zuojie , Ma Yan , Li Jianling , Deng Youping , Huang Xudong
Published: March 2008

Background

The prognosis for many cancers could be improved dramatically if they could be detected while still at the microscopic disease stage. It follows from a comprehensive statistical analysis that a number of antigens such as hTERT, PCNA and Ki-67 can be considered as cancer markers, while another set of antigens such as P27KIP1 and FHIT are possible markers for normal tissue. Because more than one marker must be considered to obtain a classification of cancer or no cancer, and if cancer, to classify it as malignant, borderline, or benign, we must develop an intelligent decision system that can fullfill such an unmet medical need.

Results

We have developed an intelligent decision system using machine learning techniques and markers to characterize tissue as cancerous, non-cancerous or borderline. The system incorporates learning techniques such as variants of support vector machines, neural networks, decision trees, self-organizing feature maps (SOFM) and recursive maximum contrast trees (RMCT). These variants and algorithms we have developed, tend to detect microscopic pathological changes based on features derived from gene expression levels and metabolic profiles. We have also used immunohistochemistry techniques to measure the gene expression profiles from a number of antigens such as cyclin E, P27KIP1, FHIT, Ki-67, PCNA, Bax, Bcl-2, P53, Fas, FasL and hTERT in several particular types of neuroendocrine tumors such as pheochromocytomas, paragangliomas, and the adrenocortical carcinomas (ACC), adenomas (ACA), and hyperplasia (ACH) involved with Cushing's syndrome. We provided statistical evidence that higher expression levels of hTERT, PCNA and Ki-67 etc. are associated with a higher risk that the tumors are malignant or borderline as opposed to benign. We also investigated whether higher expression levels of P27KIP1 and FHIT, etc., are associated with a decreased risk of adrenomedullary tumors. While no significant difference was found between cell-arrest antigens such as P27KIP1 for malignant, borderline, and benign tumors, there was a significant difference between expression levels of such antigens in normal adrenal medulla samples and in adrenomedullary tumors.

Conclusions

Our frame work focused on not only different classification schemes and feature selection algorithms, but also ensemble methods such as boosting and bagging in an effort to improve upon the accuracy of the individual classifiers. It is evident that when all sorts of machine learning and statistically learning techniques are combined appropriately into one integrated intelligent medical decision system, the prediction power can be enhanced significantly. This research has many potential applications; it might provide an alternative diagnostic tool and a better understanding of the mechanisms involved in malignant transformation as well as information that is useful for treatment planning and cancer prevention.
Gene rearrangement analysis and ancestral order inference from chloroplast genomes with inverted repeat
Authors: Yue Feng , Cui Liying , dePamphilis Claude W , Moret Bernard ME , Tang Jijun
Published: March 2008

Background

Genome evolution is shaped not only by nucleotide substitutions, but also by structural changes including gene and genome duplications, insertions, deletions and gene order rearrangements. The most popular methods for reconstructing phylogeny from genome rearrangements include GRAPPA and MGR. However these methods are limited to cases where equal gene content or few deletions can be assumed. Since conserved duplicated regions are present in many chloroplast genomes, the inference of inverted repeats is needed in chloroplast phylogeny analysis and ancestral genome reconstruction.

Results

We extend GRAPPA and develop a new method GRAPPA-IR to handle chloroplast genomes. A test of GRAPPA-IR using divergent chloroplast genomes from land plants and green algae recovers the phylogeny congruent with prior studies, while analysis that do not consider IR structure fail to obtain the accepted topology. Our extensive simulation study also confirms that GRAPPA has better accuracy then the existing methods.

Conclusions

Tests on a biological and simulated dataset show GRAPPA-IR can accurately recover the genome phylogeny as well as ancestral gene orders. Close analysis of the ancestral genome structure suggests that genome rearrangement in chloroplasts is probably limited by inverted repeats with a conserved core region. In addition, the boundaries of inverted repeats are hot spots for gene duplications or deletions. The new GRAPPA-IR is available from http://phylo.cse.sc.edu.
Improving prediction accuracy of tumor classification by reusing genes discarded during gene selection
Authors: Yang Jack Y , Li Guo-Zheng , Meng Hao-Hua , Yang Mary Qu , Deng Youping
Published: March 2008

Background

Since the high dimensionality of gene expression microarray data sets degrades the generalization performance of classifiers, feature selection, which selects relevant features and discards irrelevant and redundant features, has been widely used in the bioinformatics field. Multi-task learning is a novel technique to improve prediction accuracy of tumor classification by using information contained in such discarded redundant features, but which features should be discarded or used as input or output remains an open issue.

Results

We demonstrate a framework for automatically selecting features to be input, output, and discarded by using a genetic algorithm, and propose two algorithms: GA-MTL (Genetic algorithm based multi-task learning) and e-GA-MTL (an enhanced version of GA-MTL). Experimental results demonstrate that this framework is effective at selecting features for multi-task learning, and that GA-MTL and e-GA-MTL perform better than other heuristic methods.

Conclusions

Genetic algorithms are a powerful technique to select features for multi-task learning automatically; GA-MTL and e-GA-MTL are shown to to improve generalization performance of classifiers on microarray data sets.
Investigation of transmembrane proteins using a computational approach
Authors: Yang Jack Y , Yang Mary Qu , Dunker A Keith , Deng Youping , Huang Xudong
Published: March 2008

Background

An important subfamily of membrane proteins are the transmembrane α-helical proteins, in which the membrane-spanning regions are made up of α-helices. Given the obvious biological and medical significance of these proteins, it is of tremendous practical importance to identify the location of transmembrane segments. The difficulty of inferring the secondary or tertiary structure of transmembrane proteins using experimental techniques has led to a surge of interest in applying techniques from machine learning and bioinformatics to infer secondary structure from primary structure in these proteins. We are therefore interested in determining which physicochemical properties are most useful for discriminating transmembrane segments from non-transmembrane segments in transmembrane proteins, and for discriminating intrinsically unstructured segments from intrinsically structured segments in transmembrane proteins, and in using the results of these investigations to develop classifiers to identify transmembrane segments in transmembrane proteins.

Results

We determined that the most useful properties for discriminating transmembrane segments from non-transmembrane segments and for discriminating intrinsically unstructured segments from intrinsically structured segments in transmembrane proteins were hydropathy, polarity, and flexibility, and used the results of this analysis to construct classifiers to discriminate transmembrane segments from non-transmembrane segments using four classification techniques: two variants of the Self-Organizing Global Ranking algorithm, a decision tree algorithm, and a support vector machine algorithm. All four techniques exhibited good performance, with out-of-sample accuracies of approximately 75%.

Conclusions

Several interesting observations emerged from our study: intrinsically unstructured segments and transmembrane segments tend to have opposite properties; transmembrane proteins appear to be much richer in intrinsically unstructured segments than other proteins; and, in approximately 70% of transmembrane proteins that contain intrinsically unstructured segments, the intrinsically unstructured segments are close to transmembrane segments.
Protein disorder prediction at multiple levels of sensitivity and specificity
Authors: Hecker Joshua , Yang Jack Y , Cheng Jianlin
Published: March 2008

Background

Many protein regions and some entire proteins have no definite tertiary structure, existing instead as dynamic, disorder ensembles under different physiochemical circumstances. Identification of these protein disorder regions is important for protein production, protein structure prediction and determination, and protein function annotation. A number of different disorder prediction software and web services have been developed since the first predictor was designed by Dunker's lab in 1997. However, most of the software packages use a pre-defined threshold to select ordered or disordered residues. In many situations, users need to choose ordered or disordered residues at different sensitivity and specificity levels.

Results

Here we benchmark a state of the art disorder predictor, DISpro, on a large protein disorder dataset created from Protein Data Bank and systematically evaluate the relationship of sensitivity and specificity. Also, we extend its functionality to allow users to trade off specificity and sensitivity by setting different decision thresholds. Moreover, we compare DISpro with seven other automated disorder predictors on the 95 protein targets used in the seventh edition of Critical Assessment of Techniques for Protein Structure Prediction (CASP7). DISpro is ranked as one of the best predictors.

Conclusion

The evaluation and extension of DISpro make it a more valuable and useful tool for structural and functional genomics.
Antibody contributes to heterosubtypic protection against influenza A-induced tachypnea in cotton rats
Authors: Straight Timothy M , Ottolini Martin G , Prince Gregory A , Eichelberger Maryna C
Published: March 2008

Background

Influenza virus infection or vaccination evokes an antibody response to viral hemagglutinin (HA) and neuraminidase (NA) surface glycoproteins, which results in immunity against influenza A viruses of the same HA and NA subtype. A heterosubtypic immune response that offers some protection against different influenza A subtypes has been suggested from epidemiologic studies in human influenza outbreaks, and has been induced in experimental animal models. Original studies of such cross-protection showed that cytotoxic T lymphocytes (CTL) protect H3N2-immune mice from a lethal H1N1 infection. More recent studies in mice demonstrate that antibodies also contribute to heterosubtypic immunity (HSI). We previously demonstrated that HSI in cotton rats (Sigmodon hispidus) is characterized by protection of H3N2-immune animals from influenza H1N1-induced increase in respiratory rate (tachypnea). Alternatively, H1N1-immune animals are protected from H3N2-induced tachypnea. The experiments described in this report were designed to elucidate the immune mechanism that prevents this very early sign of disease.

Results

Our results show that cotton rats provided with H1N1-immune serum prior to challenge with an H3N2 virus were protected from influenza-associated tachypnea, with the degree of protection correlating with the antibody titer transferred. Immunization with an inactivated preparation of virus delivered intramuscularly also provided some protection suggesting that CTL and/or mucosal antibody responses are not required for protection. Antibodies specific for conserved epitopes present on the virus exterior are likely to facilitate this protection since prophylactic treatment of cotton rats with anti-M2e (the extracellular domain of M2) but not anti-nucleoprotein (NP) reduced virus-induced tachypnea.

Conclusion

In the cotton rat model of heterosubtypic immunity, humoral immunity plays a role in protecting animals from influenza-induced tachypea. Partial protection against respiratory disease caused by different influenza A subtypes can be attained with either live virus administered intranasally or inactivated virus delivered intramuscularly suggesting that either vaccine regimen may provide some protection against potential pandemic outbreaks in humans.
Dissecting the role of putative CD81 binding regions of E2 in mediating HCV entry: Putative CD81 binding region 1 is not involved in CD81 binding
Authors: Rothwangl Katharina B , Manicassamy Balaji , Uprichard Susan L , Rong Lijun
Published: March 2008

Background

Hepatitis C virus (HCV) encodes two transmembrane glycoproteins E1 and E2 which form a heterodimer. E1 is believed to mediate fusion while E2 has been shown to bind cellular receptors including CD81. In this study, alanine substitutions in E2 were generated within putative CD81 binding regions to define residues critical for viral entry. The effect of each mutation was tested by challenging susceptible cell lines with mutant HCV E1E2 pseudotyped viruses generated using a lentiviral system (HCVpp). In addition to assaying infectivity, producer cell expression and HCVpp incorporation of HCV E1 and E2 proteins, CD81 binding profiles, and E1E2 association of mutants were examined.

Results

Based on these characteristics, mutants either displayed wt characteristics (high infectivity [≥ 50% of wt HCVpp], CD81 binding, E1E2 expression, association, and incorporation into viral particles and proper conformation) or segregated into 4 distinct low infectivity (≤ 50% of wt HCVpp) mutant phenotypes: (I) CD81 binding deficient (despite wt E1E2 expression, incorporation and association and proper conformation); (II) CD81 binding competent, but lack of E1 detection on the viral particle, (despite adequate E1E2 expression in producer cell lysates and proper conformation); (III) CD81 binding competent, with adequate E1E2 expression, incorporation, association, and proper E2 conformation (i.e. no defect identified to explain the reduced infectivity observed); (IV) CD81 binding deficient due to disruption of E2 mutant protein conformation.

Conclusion

Although most alanine substitutions within the putative CD81 binding region 1 (amino acids 474–492) displayed greatly reduced HCVpp infectivity, they retained soluble CD81 binding, proper E2 conformation, E1E2 association and incorporation into HCVpp suggesting that region 1 of E2 does not mediate binding to CD81. In contrast, conformationally correct E2 mutants (Y527 and W529) within the second putative CD81 binding region (amino acids 522–551) disrupted binding of E2 to CD81-GST, suggesting that region 2 is critical to CD81 binding. Likewise, all conformationally intact mutants within the third putative CD81 binding region (amino acids 612–619), except L615A, were important for E2 binding to CD81-GST. This region is highly conserved across genotypes, underlining its importance in mediating viral entry.
Vascularization of the Dorsal Root Ganglia and Peripheral Nerve of the Mouse: Implications for Chemical-Induced Peripheral Sensory Neuropathies
Authors: Jimenez-Andrade Juan M , Herrera Monica B , Ghilardi Joseph R , Vardanyan Marina , Melemedjian Ohannes K , Mantyh Patrick W
Published: March 2008

Although a variety of industrial chemicals, as well as several chemotherapeutic agents used to treat cancer or HIV, preferentially induce a peripheral sensory neuropathy what remains unclear is why these agents induce a sensory vs. a motor or mixed neuropathy. Previous studies have shown that the endothelial cells that vascularize the dorsal root ganglion (DRG), which houses the primary afferent sensory neurons, are unique in that they have large fenestrations and are permeable to a variety of low and high molecular weight agents. In the present report we used whole-mount preparations, immunohistochemistry, and confocal laser scanning microscopy to show that the cell body-rich area of the L4 mouse DRG has a 7 fold higher density of CD31+ capillaries than cell fiber rich area of the DRG or the distal or proximal aspect of the sciatic nerve. This dense vascularization, coupled with the high permeability of these capillaries, may synergistically contribute, and in part explain, why many potentially neurotoxic agents preferentially accumulate and injure cells within the DRG. Currently, cancer survivors and HIV patients constitute the largest and most rapidly expanding groups that have chemically induced peripheral sensory neuropathy. Understanding the unique aspects of the vascularization of the DRG and closing the endothelial fenestrations of the rich vascular bed of capillaries that vascularize the DRG before intravenous administration of anti-neoplastic or anti-HIV therapies, may offer a mechanism based approach to attenuate these chemically induced peripheral neuropathies in these patients.
Postoperative gastric dilatation causing abdominal compartment syndrome
Authors: Mahajna Ahmad , Mitkal Sharon , Krausz Michael M
Published: March 2008

Objective

To study the effect of postoperative gastric dilatation on intra-abdominal pressure (IAP).

Design and setting

Single case report from a primary teaching hospital.

Patients and methods

A 72-year-old woman demonstrated a sudden respiratory and cardiovascular collapse following resection of a retroperitoneal sarcoma. This collapse was caused by abdominal compartment syndrome due to gastric dilatation.

Results

The patient was re-explored, an enormously distended stomach was found with the nasogastric tube situated in a small sliding hernia which prevented drainage of the distended stomach. Re-positioning of the nasogastric tube, allowed the decompression of the stomach and the patient's condition immediately improved.

Conclusion

Acute abdominal distention following major abdominal surgery may result from acute gastric dilatation, leading to oliguria and increased airway pressures. Untreated gastric dilatation can cause abdominal compartment syndrome.
Endotoxemia down-regulates bone marrow lymphopoiesis but stimulates myelopoiesis: the effect of G6PD deficiency
Authors: Chandra Rachna , Villanueva Erika , Feketova Eleonora , Machiedo George W , Haskó György , Deitch Edwin A , Spolarics Zoltán
Published: March 2008

Bone marrow (BM) dysfunction is an important component of immunomodulation. This study investigated alterations in cell content, apoptotic responses, and cell proliferation in BM, blood, and spleen in endotoxemic mice (LPS from Escherichia coli). As the decreased antioxidant status associated with glucose-6-phosphate dehydrogenase (G6PD) deficiency has been shown to modulate the innate immune response, we also tested whether a G6PD mutation (80% decrease in cellular enzyme activity) alters BM responses during endotoxemia. LPS decreased BM myeloid (CD45+CD11b+) and B lymphoid (CD45+CD19+CD11b–) cell content compared with controls. In contrast, LPS increased CD11b+ myeloid but decreased T and B cell counts in the circulation. Endotoxemia inhibited spontaneous, heat shock, and H2O2-induced apoptosis as well as proliferative activity in BM lymphoid cells. In contrast, BM myeloid cell apoptosis was not altered, and their proliferative activity was increased during endotoxemia. Following LPS, splenic myeloid cell content was increased, and T and B cell content was unchanged; furthermore, splenocytes showed increased apoptosis compared with controls. BM cell content, including lymphoid and myeloid cells, was greater in G6PD mutant than wild-type (WT) mice, and LPS decreased BM cell counts to a greater degree in mutant than WT mice. Endotoxemia caused widespread inhibition of BM cytokine and chemokine production; however, IL-6 production was increased compared with controls. LPS-induced IL-6 production was decreased in G6PD mutant animals compared with WT. This study indicates that endotoxin inversely affects BM myeloid and lymphoid cell production. LPS-induced down-regulation of B cell production contributes to the generalized lymphopenia and lymphocyte dysfunction observed following nonspecific immune challenges.
A Simulation Study of Alkanes in Linde Type A Zeolites
Authors: García-Sánchez Almudena , García-Pérez Elena , Dubbeldam David , Krishna Rajamani , Calero Sofía
Published: March 2008

Monte Carlo simulations were performed to study the adsorption and diffusion of small hydrocarbons in Linde Type A zeolites as a function of their calcium/sodium ratio. The diffusion studies were focused on methane whereas the adsorption simulations were performed from methane up to pentane. The results obtained showed that an increase in the number of cations in the structure (exchange of univalent sodium ions by divalent calcium ions) led to an increase in the adsorption of linear alkanes at low and medium pressure, but caused a decrease in adsorption at the highest pressures. An increase in the amount of cations favours molecular attraction and hence results in lower mobility. At higher cation loading the ions block the windows interconnecting the LTA cages, leading to a further decrease in diffusion. Methane self-diffusion coefficients obtained from our simulations were twice as high for the Linde Type 5A zeolite as for the Linde Type 4A zeolite. These results are consistent with previous experimental studies and provide a molecular picture of the influence of the zeolite type, the amount of cations contained and their location in the structure.
Catalytic Oxidation of Thiophenes with Air and PW/SBA-15
Authors: Dai Wei , Zhou Yaping , Wang Shengqiang , Long Lei , Zhou Li
Published: March 2008

Catalytic oxidation is considered a viable method for reducing the sulphur level of transportation fuels and H2O2 is usually used as the oxidant. For this reason, it is essential that any extraction operation must remove the oxidation product from the fuel. A new oxidation method is studied in the present work. Instead of H2O2, air was used as the oxidant and phosphotungstic acid (PW) was used as the catalyst; the latter was imbedded in the pore spaces of the mesoporous silica material SBA-15 to form a PW/SBA-15 composite. The oxidation reaction occurred in the pore spaces of the composite and the polar reaction products were immediately adsorbed there. As a consequence, there was no need for a subsequent exaction operation. Desulphurization experiments were carried out using a model fuel composed of n-octane and thiophene. The content of thiophene was reduced from 2000 ppmw to less than 1 ppmw at 50°C and ambient pressure. The saturated PW/SBA-15 composite was regenerated at 350°C by using a nitrogen flow for 4 h. Such conditions allowed the catalytic activity to be recovered.
Kinetic Coefficients for Mixed Adsorbate Fluids in Narrow Pores
Authors: Tovbin Yu.K. , Rabinovich A.B. , Yeremich D.V.
Published: March 2008

The kinetic coefficients (trace diffusion, mutual diffusion and shear viscosity) of molecules in slit-like and sphero-cylindrical mesoporous systems were studied in terms of the modified lattice-gas model (LGM). The LGM equations were derived for molecules of the mixture having a spherical shape and similar size. A new equation for the velocity of the thermal molecule was used. The theory takes the change in the mechanism of particle migration in different phases into account, viz. from pair collisions for the gas to the overcoming of the activation barrier by thermofluctuation for dense phases. At low mixture densities corresponding to an ideal gas phase, the LGM expression for the mutual diffusion coefficient agrees with the expression of the rigorous kinetic theory of gases. The theory allows the calculation of the kinetic coefficients for the components of binary mixtures in full gas-liquid density areas. The supramolecular structure of the sphero-cylindrical system was modelled by sections with a simple regular geometry (cylindrical and spherical) with the additional inclusion of junctions between different pore sections. The contributions of the near-wall regions caused by the molecule-wall potential to the general appearance of the phase diagrams and the effect of the pore size on the capillary condensation conditions were discussed.
Temperature Effects on Physical Properties and Mechanical Behavior of Granite: Experimental Investigation of Material Damage
Authors: Takarli Mokhfi , Prince-Agbodjan William
Published: March 2008

In this paper, the effect of thermal treatment on physical and mechanical properties of a granitic rock is experimentally investigated. The open porosity, gas permeability, P-wave velocity (and their attenuation), ultimate strength, and Young’s modulus are measured on samples heated at temperatures ranging from 105°C to 600°C. First, results show good correlations between the evolution of physical properties and the amount of the damage induced by the thermal treatment. Second, the mechanical parameters are shown to be dependent on the microcracks’ density in the samples. The effect of temperature on the failure process in granite is also investigated using strain gauge measurements and permeability evolution in a uniaxial compressive test. The results show that the extent of the crack closure stage depends on the initial crack density and that the crack thresholds, which characterize the failure process of the rock under compressive loading, decrease with the thermal treatment.
Farewell to the World: Suicide Notes from Turkey
Authors: Demirel Birol , Akar Taner , Sayin Aslihan , Candansayar Selçuk , Leenaars Antoon A.
Published: March 2008

There has been limited study of suicide in Islamic countries. This paper marks the first study of suicide notes in Turkey, an Islamic country. Using a classification scheme, 49 suicide notes (a rate of 34.5%) were studied. The results show that note writers do not differ greatly from other suicides. Further analysis of younger (<40) and older (>40) suicide note writers reveal few significant differences. Our results, together with the results of classification studies in different countries, suggest that caution is in order in transposing findings from one country to other countries. Future study of suicide notes should, in fact, focus on cross‐cultural investigation.