bluuebunny/crossref_metadata_2025 huggingface dataset:
Selection of long oligonucleotides for gene expression microarrays using weighted rank-sum strategy
Authors: Hu Guangan , Llinás Manuel , Li Jingguang , Preiser Peter Rainer , Bozdech Zbynek
Published: September 2007

Background

The design of long oligonucleotides for spotted DNA microarrays requires detailed attention to ensure their optimal performance in the hybridization process. The main challenge is to select an optimal oligonucleotide element that represents each genetic locus/gene in the genome and is unique, devoid of internal structures and repetitive sequences and its Tm is uniform with all other elements on the microarray. Currently, all of the publicly available programs for DNA long oligonucleotide microarray selection utilize various combinations of cutoffs in which each parameter (uniqueness, Tm, and secondary structure) is evaluated and filtered individually. The use of the cutoffs can, however, lead to information loss and to selection of suboptimal oligonucleotides, especially for genomes with extreme distribution of the GC content, a large proportion of repetitive sequences or the presence of large gene families with highly homologous members.

Results

Here we present the program OligoRankPick which is using a weighted rank-based strategy to select microarray oligonucleotide elements via an integer weighted linear function. This approach optimizes the selection criteria (weight score) for each gene individually, accommodating variable properties of the DNA sequence along the genome. The designed algorithm was tested using three microbial genomes Escherichia coli, Saccharomyces cerevisiae and the human malaria parasite species Plasmodium falciparum. In comparison to other published algorithms OligoRankPick provides significant improvements in oligonucleotide design for all three genomes with the most significant improvements observed in the microarray design for P. falciparum whose genome is characterized by large fluctuations of GC content, and abundant gene duplications.

Conclusion

OligoRankPick is an efficient tool for the design of long oligonucleotide DNA microarrays which does not rely on direct oligonucleotide exclusion by parameter cutoffs but instead optimizes all parameters in context of each other. The weighted rank-sum strategy utilized by this algorithm provides high flexibility of oligonucleotide selection which accommodates extreme variability of DNA sequence properties along genomes of many organisms.
A machine learning approach for the identification of odorant binding proteins from sequence-derived properties
Authors: Pugalenthi Ganesan , Tang Ke , Suganthan PN , Archunan G , Sowdhamini R
Published: September 2007

Background

Odorant binding proteins (OBPs) are believed to shuttle odorants from the environment to the underlying odorant receptors, for which they could potentially serve as odorant presenters. Although several sequence based search methods have been exploited for protein family prediction, less effort has been devoted to the prediction of OBPs from sequence data and this area is more challenging due to poor sequence identity between these proteins.

Results

In this paper, we propose a new algorithm that uses Regularized Least Squares Classifier (RLSC) in conjunction with multiple physicochemical properties of amino acids to predict odorant-binding proteins. The algorithm was applied to the dataset derived from Pfam and GenDiS database and we obtained overall prediction accuracy of 97.7% (94.5% and 98.4% for positive and negative classes respectively).

Conclusion

Our study suggests that RLSC is potentially useful for predicting the odorant binding proteins from sequence-derived properties irrespective of sequence similarity. Our method predicts 92.8% of 56 odorant binding proteins non-homologous to any protein in the swissprot database and 97.1% of the 414 independent dataset proteins, suggesting the usefulness of RLSC method for facilitating the prediction of odorant binding proteins from sequence information.
Apposition of iroquois expressing and non-expressing cells leads to cell sorting and fold formation in the Drosophilaimaginal wing disc
Authors: Villa-Cuesta Eugenia , González-Pérez Esther , Modolell Juan
Published: September 2007

Background

The organization of the different tissues of an animal requires mechanisms that regulate cell-cell adhesion to promote and maintain the physical separation of adjacent cell populations. In the Drosophila imaginal wing disc the iroquois homeobox genes are expressed in the notum anlage and contribute to the specification of notum identity. These genes are not expressed in the adjacent wing hinge territory. These territories are separated by an approximately straight boundary that in the mature disc is associated with an epithelial fold. The mechanism by which these two cell populations are kept separate is unclear.

Results

Here we show that the Iro-C genes participate in keeping the notum and wing cell populations separate. Indeed, within the notum anlage, cells not expressing Iro-C tend to join together and sort out from their Iro-C expressing neighbours. We also show that apposition of Iro-C expressing and non-expressing cells induces invagination and apico-basal shortening of the Iro-C- cells. This effect probably underlies formation of the fold that separates the notum and wing hinge territories. In addition, cells overexpressing a member of the Iro-C contact one another and become organized in a network of thin strings that surrounds and isolates large groups of non-overexpressing cells. The strings appear to exert a pulling force along their longitudinal axis.

Conclusion

Apposition of cells expressing and non-expressing the Iro-C, as it occurs in the notum-wing hinge border of the Drosophila wing disc, influences cell behaviour. It leads to cell sorting, and cellular invagination and apical-basal shortening. These effects probably account for keeping the prospective notum and wing hinge cell populations separate and underlie epithelial fold formation. Cells that overexpress a member of the Iro-C and that confront non-expressing cells establish contacts between themselves and become organized in a network of thin strings. This is a complex and unique phenotype that might be important for the generation of a straight notum-wing hinge border.
Genome-wide association and linkage analyses of hemostatic factors and hematological phenotypes in the Framingham Heart Study
Authors: Yang Qiong , Kathiresan Sekar , Lin Jing-Ping , Tofler Geoffrey H , O'Donnell Christopher J
Published: September 2007

Background

Increased circulating levels of hemostatic factors as well as anemia have been associated with increased risk of cardiovascular disease (CVD). Known associations between hemostatic factors and sequence variants at genes encoding these factors explain only a small proportion of total phenotypic variation. We sought to confirm known putative loci and identify novel loci that may influence either trait in genome-wide association and linkage analyses using the Affymetrix GeneChip 100K single nucleotide polymorphism (SNP) set.

Methods

Plasma levels of circulating hemostatic factors (fibrinogen, factor VII, plasminogen activator inhibitor-1, von Willebrand factor, tissue plasminogen activator, D-dimer) and hematological phenotypes (platelet aggregation, viscosity, hemoglobin, red blood cell count, mean corpuscular volume, mean corpuscular hemoglobin concentration) were obtained in approximately 1000 Framingham Heart Study (FHS) participants from 310 families. Population-based association analyses using the generalized estimating equations (GEE), family-based association test (FBAT), and multipoint variance components linkage analyses were performed on the multivariable adjusted residuals of hemostatic and hematological phenotypes.

Results

In association analysis, the lowest GEE p-value for hemostatic factors was p = 4.5*10-16 for factor VII at SNP rs561241, a variant located near the F7 gene and in complete linkage disequilibrium (LD) (r2 = 1) with the Arg353Gln F7 SNP previously shown to account for 9% of total phenotypic variance. The lowest GEE p-value for hematological phenotypes was 7*10-8 at SNP rs2412522 on chromosome 4 for mean corpuscular hemoglobin concentration. We presented top 25 most significant GEE results with p-values in the range of 10-6 to 10-5 for hemostatic or hematological phenotypes. In relating 100K SNPs to known candidate genes, we identified two SNPs (rs1582055, rs4897475) in erythrocyte membrane protein band 4.1-like 2 (EPB41L2) associated with hematological phenotypes (GEE p < 10-3). In linkage analyses, the highest linkage LOD score for hemostatic factors was 3.3 for factor VII on chromosome 10 around 15 Mb, and for hematological phenotypes, LOD 3.4 for hemoglobin on chromosome 4 around 55 Mb. All GEE and FBAT association and variance components linkage results can be found at http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?id=phs000007

Conclusion

Using genome-wide association methodology, we have successfully identified a SNP in complete LD with a sequence variant previously shown to be strongly associated with factor VII, providing proof of principle for this approach. Further study of additional strongly associated SNPs and linked regions may identify novel variants that influence the inter-individual variability in hemostatic factors and hematological phenotypes.
Genetic correlates of longevity and selected age-related phenotypes: a genome-wide association study in the Framingham Study
Authors: Lunetta Kathryn L , D'Agostino Ralph B , Karasik David , Benjamin Emelia J , Guo Chao-Yu , Govindaraju Raju , Kiel Douglas P , Kelly-Hayes Margaret , Massaro Joseph M , Pencina Michael J , Seshadri Sudha , Murabito Joanne M
Published: September 2007

Background

Family studies and heritability estimates provide evidence for a genetic contribution to variation in the human life span.

Methods

We conducted a genome wide association study (Affymetrix 100K SNP GeneChip) for longevity-related traits in a community-based sample. We report on 5 longevity and aging traits in up to 1345 Framingham Study participants from 330 families. Multivariable-adjusted residuals were computed using appropriate models (Cox proportional hazards, logistic, or linear regression) and the residuals from these models were used to test for association with qualifying SNPs (70, 987 autosomal SNPs with genotypic call rate ≥80%, minor allele frequency ≥10%, Hardy-Weinberg test p ≥ 0.001).

Results

In family-based association test (FBAT) models, 8 SNPs in two regions approximately 500 kb apart on chromosome 1 (physical positions 73,091,610 and 73, 527,652) were associated with age at death (p-value < 10-5). The two sets of SNPs were in high linkage disequilibrium (minimum r2 = 0.58). The top 30 SNPs for generalized estimating equation (GEE) tests of association with age at death included rs10507486 (p = 0.0001) and rs4943794 (p = 0.0002), SNPs intronic to FOXO1A, a gene implicated in lifespan extension in animal models. FBAT models identified 7 SNPs and GEE models identified 9 SNPs associated with both age at death and morbidity-free survival at age 65 including rs2374983 near PON1. In the analysis of selected candidate genes, SNP associations (FBAT or GEE p-value < 0.01) were identified for age at death in or near the following genes: FOXO1A, GAPDH, KL, LEPR, PON1, PSEN1, SOD2, and WRN. Top ranked SNP associations in the GEE model for age at natural menopause included rs6910534 (p = 0.00003) near FOXO3a and rs3751591 (p = 0.00006) in CYP19A1. Results of all longevity phenotype-genotype associations for all autosomal SNPs are web posted at http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?id=phs000007.

Conclusion

Longevity and aging traits are associated with SNPs on the Affymetrix 100K GeneChip. None of the associations achieved genome-wide significance. These data generate hypotheses and serve as a resource for replication as more genes and biologic pathways are proposed as contributing to longevity and healthy aging.
Potential drug-drug and drug-disease interactions in prescriptions for ambulatory patients over 50 years of age in family medicine clinics in Mexico City
Authors: Doubova Svetlana Vladislavovna , Reyes-Morales Hortensia , Torres-Arreola Laura del Pilar , Suárez-Ortega Magdalena
Published: September 2007

Background

In Mexico, inappropriate prescription of drugs with potential interactions causing serious risks to patient health has been little studied. Work in this area has focused mainly on hospitalized patients, with only specific drug combinations analyzed; moreover, the studies have not produced conclusive results. In the present study, we determined the frequency of potential drug-drug and drug-disease interactions in prescriptions for ambulatory patients over 50 years of age, who used Mexican Institute of Social Security (IMSS) family medicine clinics. In addition, we aimed to identify the associated factors for these interactions.

Methods

We collected information on general patient characteristics, medical histories, and medication (complete data). The study included 624 ambulatory patients over 50 years of age, with non-malignant pain syndrome, who made ambulatory visits to two IMSS family medicine clinics in Mexico City. The patients received 7-day prescriptions for non-opioid analgesics. The potential interactions were identified by using the Thompson Micromedex program. Data were analyzed using descriptive, bivariate and multiple logistic regression analyses.

Results

The average number of prescribed drugs was 5.9 ± 2.5. About 80.0% of patients had prescriptions implying one or more potential drug-drug interactions and 3.8% of patients were prescribed drug combinations with interactions that should be avoided. Also, 64.0% of patients had prescriptions implying one or more potential drug disease interactions. The factors significantly associated with having one or more potential interactions included: taking 5 or more medicines (adjusted Odds Ratio (OR): 4.34, 95%CI: 2.76–6.83), patient age 60 years or older (adjusted OR: 1.66, 95% CI: 1.01–2.74) and suffering from cardiovascular diseases (adjusted OR: 7.26, 95% CI: 4.61–11.44).

Conclusion

The high frequency of prescription of drugs with potential drug interactions showed in this study suggests that it is common practice in primary care level. To lower the frequency of potential interactions it could be necessary to make a careful selection of therapeutic alternatives, and in cases without other options, patients should be continuously monitored to identify adverse events.
Selective repression of retinoic acid target genes by RIP140 during induced tumor cell differentiation of pluripotent human embryonal carcinoma cells
Authors: Heim Kelly C , White Kristina A , Deng Dexin , Tomlinson Craig R , Moore Jason H , Freemantle Sarah J , Spinella Michael J
Published: September 2007

Background

The use of retinoids as anti-cancer agents has been limited due to resistance and low efficacy. The dynamics of nuclear receptor coregulation are incompletely understood. Cell-and context-specific activities of nuclear receptors may be in part due to distinct coregulator complexes recruited to distinct subsets of target genes. RIP140 (also called NRIP1) is a ligand-dependent corepressor that is inducible with retinoic acid (RA). We had previously shown that RIP140 limits RA induced tumor cell differentiation of embryonal carcinoma; the pluriopotent stem cells of testicular germ cell tumors. This implies that RIP140 represses key genes required for RA-mediated tumor cell differentiation. Identification of these genes would be of considerable interest.

Results

To begin to address this issue, microarray technology was employed to elucidate in a de novo fashion the global role of RIP140 in RA target gene regulation of embryonal carcinoma. Subclasses of genes were affected by RIP140 in distinct manners.

Interestingly, approximately half of the RA-dependent genes were unaffected by RIP140. Hence, RIP140 appears to discriminate between different classes of RA target genes. In general, RIP140-dependent gene expression was consistent with RIP140 functioning to limit RA signaling and tumor cell differentiation. Few if any genes were regulated in a manner to support a role for RIP140 in "active repression". We also demonstrated that RIP140 silencing sensitizes embryonal carcinoma cells to low doses of RA.

Conclusion

Together the data demonstrates that RIP140 has profound effects on RA-mediated gene expression in this cancer stem cell model. The RIP140-dependent RA target genes identified here may be particularly important in mediating RA-induced tumor cell differentiation and the findings suggest that RIP140 may be an attractive target to sensitize tumor cells to retinoid-based differentiation therapy. We discuss these data in the context of proposed models of RIP140-mediated repression.
Mediterranean diet and insulin sensitivity, lipid profile and blood pressure levels, in overweight and obese people; The Attica study
Authors: Tzima Natalia , Pitsavos Christos , Panagiotakos Demosthenes B. , Skoumas John , Zampelas Antonis , Chrysohoou Christina , Stefanadis Christodoulos
Published: September 2007

Background

We aimed to investigate if overweight and obese adults "close" to Mediterranean diet present better insulin, lipids profile and better pressure levels, compared to individuals close to a more Westernized diet.

Methods

The ATTICA study is a population-based cohort that has randomly enrolled 3042 adult men and women, stratified by age – gender, from the greater area of Athens, during 2001–2002. Of them, in this work were have studied 1762 participants with excess body weight, meaning overweight (BMI: 25–29.9 kg/m2) and obese (BMI>30 kg/m2). 1064 were men and 698 women (20–89 years old). Adherence to Mediterranean diet was assessed through a diet-score that was based on a validated food-frequency questionnaire. Blood pressure was measured and also fasting glucose, insulin and blood lipids. Insulin sensitivity was also assessed by the homeostasis model assessment (HOMA) approach (glucose × insulin/22.5).

Results

Individuals with excess bodyweight in the highest tertile of diet score, were more insulin sensitive than those in the lowest tertile (11.4% lower HOMA, p = 0.06), had 13% lower levels of total cholesterol (p = 0.001) and 3 mmHg decrease of systolic blood pressure levels (p < 0.001), when adjusted for age, sex and BMI. Multivariate analysis after taking into account several confounders demonstrated that insulin sensitivity, total cholesterol and systolic blood pressure were independently but only modestly correlated with Mediterranean diet in people with excess bodyweight.

Conclusion

Adherence to Mediterranean diet is modeslty associated with a better insulin sensitivity, lower levels of total cholesterol and lower levels of systolic blood pressure in overweight and obese subjects. This may suggest that compared to general population, the beneficial effect of this diet in cardiovascular system of excess body weight people is limited.
Spontaneous regression of metastatic renal cell carcinoma: case report
Authors: Lekanidi Katerina , Vlachou Paraskevi A. , Morgan Bruno , Vasanthan Subramaniam
Published: September 2007

Spontaneous regression of metastatic renal cell carcinoma is rarely observed. A case of suspected spontaneous regression of pulmonary metastases following nephrectomy for histologically proven renal cell carcinoma without systemic treatment is presented along with a brief review of the literature.
Whole body bone scintigraphy in osseous hydatosis: a case report
Authors: Ebrahimi Abdolali , Assadi Majid , Saghari Mohsen , Eftekhari Mohammad , Gholami Amir , Ghasemikhah Reza , Assadi Sakineh
Published: September 2007

Hydatid disease is common in many parts of the world, and causes considerable health and economic loss. This disease may develop in almost any part of the body.

Bone involvement is often asymptomatic, and its diagnosis is primarily based on radiographic findings. A whole body bone scan is able to show the extent and distribution of lesions.

We describe an unusual case of multifocal skeletal hydatosis and also explain the clinical and diagnostic points. We hope to stimulate a high index of suspicion among clinicians to facilitate early diagnosis and to consider this disease as a differential diagnosis in cases of multiple abnormal activity in bone scintigraphy especially among people in endemic areas.
A global analysis of genetic interactions in Caenorhabditis elegans
Authors: Byrne Alexandra B , Weirauch Matthew T , Wong Victoria , Koeva Martina , Dixon Scott J , Stuart Joshua M , Roy Peter J
Published: September 2007

Background

Understanding gene function and genetic relationships is fundamental to our efforts to better understand biological systems. Previous studies systematically describing genetic interactions on a global scale have either focused on core biological processes in protozoans or surveyed catastrophic interactions in metazoans. Here, we describe a reliable high-throughput approach capable of revealing both weak and strong genetic interactions in the nematode Caenorhabditis elegans.

Results

We investigated interactions between 11 'query' mutants in conserved signal transduction pathways and hundreds of 'target' genes compromised by RNA interference (RNAi). Mutant-RNAi combinations that grew more slowly than controls were identified, and genetic interactions inferred through an unbiased global analysis of the interaction matrix. A network of 1,246 interactions was uncovered, establishing the largest metazoan genetic-interaction network to date. We refer to this approach as systematic genetic interaction analysis (SGI). To investigate how genetic interactions connect genes on a global scale, we superimposed the SGI network on existing networks of physical, genetic, phenotypic and coexpression interactions. We identified 56 putative functional modules within the superimposed network, one of which regulates fat accumulation and is coordinated by interactions with bar-1(ga80), which encodes a homolog of β-catenin. We also discovered that SGI interactions link distinct subnetworks on a global scale. Finally, we showed that the properties of genetic networks are conserved between C. elegans and Saccharomyces cerevisiae, but that the connectivity of interactions within the current networks is not.

Conclusions

Synthetic genetic interactions may reveal redundancy among functional modules on a global scale, which is a previously unappreciated level of organization within metazoan systems. Although the buffering between functional modules may differ between species, studying these differences may provide insight into the evolution of divergent form and function.
Notch3 and IL-1β exert opposing effects on a vascular smooth muscle cell inflammatory pathway in which NF-κB drives crosstalk
Authors: Clément Nathalie , Gueguen Marie , Glorian Martine , Blaise Régis , Andréani Marise , Brou Christel , Bausero Pedro , Limon Isabelle
Published: September 2007

Atherogenesis begins with the transfer of monocytes from the lumen to the intimal layer of arteries. The paracrine activity acquired by these monocytes shifts vascular smooth muscle cells from a contractile-quiescent to a secretory-proliferative phenotype, allowing them to survive and migrate in the intima. Transformed and relocated, they also start to produce and/or secrete inflammatory enzymes, converting them into inflammatory cells. Activation of the Notch pathway, a crucial determinant of cell fate, regulates some of the new features acquired by these cells as it triggers vascular smooth muscle cells to grow and inhibits their death and migration. Here, we evaluate whether and how the Notch pathway regulates the cell transition towards an inflammatory or de-differentiated state. Activation of the Notch pathway by the notch ligand Delta1, as well as overexpression of the active form of Notch3, prevents this phenomenon [initiated by interleukin 1β (IL-1β)], whereas inhibiting the Notch pathway enhances the transition. IL-1β decreases the expression of Notch3 and Notch target genes. As shown by using an IκBα-mutated form, the decrease of Notch3 signaling elements occurs subsequent to dissociation of the NF-κB complex. These results demonstrate that the Notch3 pathway is attenuated through NF-κB activation, allowing vascular smooth muscle cells to switch into an inflammatory state.
Specificity of RGS10A as a key component in the RANKL signaling mechanism for osteoclast differentiation
Authors: Yang Shuying , Chen Wei , Stashenko Philip , Li Yi-Ping
Published: September 2007

Significant progress has been made in studies of the mechanisms by which RANKL induces terminal osteoclast differentiation. However, many crucial details in the RANKL-evoked signaling pathway for osteoclast differentiation remain to be defined. We characterized genes specifically expressed in osteoclasts by differential screening of a human osteoclastoma cDNA library, and found that the regulator of G-protein signaling 10A (RGS10A), but not the RGS10B isoform, was specifically expressed in human osteoclasts. The expression of RGS10A is also induced by RANKL in osteoclast precursors and is prominently expressed in mouse osteoclast-like cells. RGS10A silencing by RNA interference blocked intracellular [Ca2+]i oscillations, the expression of NFAT2, and osteoclast terminal differentiation in both bone marrow cells and osteoclast precursor cell lines. Reintroduction of RGS10A rescued the impaired osteoclast differentiation. RGS10A silencing also resulted in premature osteoclast apoptosis. RGS10A silencing affected the RANKL-[Ca2+]i oscillation-NFAT2 signaling pathway but not other RANKL-induced responses. Our data demonstrate that target components of RGS10A are distinct from those of RGS12 in the RANKL signaling mechanism. Our results thus show the specificity of RGS10A as a key component in the RANKL-evoked signaling pathway for osteoclast differentiation, which may present a promising target for therapeutic intervention.
Adenomatous polyposis coli (APC): a multi-functional tumor suppressor gene
Authors: Aoki Koji , Taketo Makoto M.
Published: September 2007

The adenomatous polyposis coli (APC) gene is a key tumor suppressor gene. Mutations in the gene have been found not only in most colon cancers but also in some other cancers, such as those of the liver. The APC gene product is a 312 kDa protein that has multiple domains, through which it binds to various proteins, including β-catenin, axin, CtBP, Asefs, IQGAP1, EB1 and microtubules. Studies using mutant mice and cultured cells have demonstrated that APC suppresses canonical Wnt signalling, which is essential for tumorigenesis, development and homeostasis of a variety of cell types, such as epithelial and lymphoid cells. Further studies have suggested that APC plays roles in several other fundamental cellular processes. These include cell adhesion and migration, organization of the actin and microtubule networks, spindle formation and chromosome segregation. Deregulation of these processes caused by mutations in APC is implicated in the initiation and expansion of colon cancer.
Oxidation of Alcohols with Hydrogen Peroxide Catalyzed by Molybdenum(VI)–Peroxo Complex under Solvent-free Conditions
Authors: Luan Yi , Wang Ge , Luck Rudy L , Yang Mu , Han Xiao
Published: September 2007

The oxidation of primary, secondary, allylic, and aromatic alcohols to the corresponding carbonyl compounds proceeds in high yield catalyzed by molybdenum(VI)–peroxo complex with H2O2 under solvent-free conditions. Secondary –OH group are selectively oxidized even in the presence of a primary –OH group. Products/catalyst separation can be easily carried out by simple extraction and the catalytic system can be reused without much loss of activity.
Capillary-assembled Microchip for the Electrochemical Determination of Glucose
Authors: Inadumi Shingo , Hisamoto Hideaki , Mizutani Fumio
Published: September 2007

An electrochemical glucose-sensing chip is developed based on a capillary-assembled microchip (CAs-CHIP) technique, which involves the simple assemblage of square capillaries possessing anti-interferential, glucose-sensing and electrochemical-detecting functions in poly(dimethylsiloxane) micro-channels.
Diastereoselective Cyanomethylation of Chiral N-(tert-Butylsulfinyl)imines Promoted by Lewis Bases
Authors: Mukaiyama Teruaki , Michida Makoto
Published: September 2007

Cyanomethylation of chiral N-(tert-butylsulfinyl)imines with 2-trimethylsilylacetonitrile (TMSCH2CN) in the presence of a Lewis base such as tetrabutylammonium phenoxide (PhONn-Bu4) proceeds smoothly to afford the corresponding β-amino nitriles in good to high yields with excellent diastereoselectivities.
Porphyrin/MgCl2/Silica Gel Composite as a Cobalt-free Humidity Indicator
Authors: Fueda Yoshiyuki , Matsumoto Jin , Shiragami Tsutomu , Nobuhara Kazunori , Yasuda Masahide
Published: September 2007

In order to develop cobalt-free humidity indicator, the composite consisted of porphyrin, MgCl2, and silica gel was prepared. The composite exhibited a reversible color change from green to purple under dry and humid conditions, respectively.
Large Scale Fabrication of NiS Hollow Spheres with Controllable Diameter Sizes
Authors: Yin Xing , Wu Changzheng , Wang Chengle , Xie Yi
Published: September 2007

NiS hollow spheres with controllable diameter sizes have been prepared in large scale by a simple method, where cyclohexylamine, as both solvent and reductant, successfully controlled the rate of releasing S2−. NiS nanoparticles were self-aggregated into hollow spheres around the in situ formed poly(N-vinyl-2-pyrrolidone) (PVP, Mw=30,000) spherical micelles in the cyclohexylamine media. The as-obtained high-quality NiS hollow spheres with loosely packed nanoparticles would show interesting applications in optical device and lithium-ion battery.
Chemical Cross-Linking and Mass Spectrometry as Structure Determination Tools
Authors: Novak Petr , Giannakopulos Anastassios E.
Published: September 2007

Chemical cross-linking is becoming a valuable tool for the high-order structure determination of proteins and protein complexes. Cross-linking methodology is able to provide low-resolution structures when at least something is known already about the proteins under investigation. The suitability of top-down and bottom-up methodologies is discussed and further potential applications of chemical cross-linking of proteins, as well as combinations with other techniques such as hydrogen/deuterium exchange and molecular modeling, are suggested.
Nucleotide synthetase ribozymes may have emerged first in the RNA world
Authors: Ma Wentao , Yu Chunwu , Zhang Wentao , Hu Jiming
Published: September 2007

Though the “RNA world” hypothesis has gained a central role in ideas concerning the origin of life, the scenario concerning its emergence remains uncertain. It has been speculated that the first scene may have been the emergence of a template-dependent RNA synthetase ribozyme, which catalyzed its own replication: thus, “RNA replicase.” However, the speculation remains uncertain, primarily because of the large sequence length requirement of such a replicase and the lack of a convincing mechanism to ensure its self-favoring features. Instead, we propose a nucleotide synthetase ribozyme as an alternative candidate, especially considering recent experimental evidence suggesting the possibility of effective nonenzymatic template-directed synthesis of RNA. A computer simulation was conducted to support our proposal. The conditions for the emergence of the nucleotide synthetase ribozyme are discussed, based on dynamic analysis on a computer. We suggest the template-dependent RNA synthetase ribozyme emerged later, perhaps after the emergence of protocells.
High-Resolution Neurometabolic Coupling in the Lateral Geniculate Nucleus
Authors: Li Baowang , Freeman Ralph D.
Published: September 2007

The relationships between neural and metabolic processes in activated brain regions are central to the interpretation of noninvasive imaging. To examine this relationship, we have used a specialized sensor to measure simultaneously tissue oxygen changes and neural activity in colocalized regions of the cat's lateral geniculate nucleus (LGN). Previous work with this sensor has shown that a decrease or increase in tissue oxygen can be elicited by selective control of the location and extent of neural activation in the LGN. In the current study, to evaluate the temporal integration and homogeneity of neurometabolic coupling, we have determined the relationship between multiunit extracellular neural activity and tissue oxygen responses to visual stimuli of various durations and contrasts. Our results show that the negative but not the positive oxygen response changes in an approximately linear manner with stimulus duration. The relationship between the negative oxygen response and neural activity is relatively constant with stimulus duration. Moreover, both negative and positive oxygen responses saturate at high stimulus contrast levels. Coupling between neural activity and negative oxygen responses is well described by a power law function. These results help elucidate differences between the initial negative and subsequent positive metabolic responses and may be directly relevant to questions concerning brain mapping with functional magnetic resonance imaging.
Excessive Activation of Poly(ADP-Ribose) Polymerase Contributes to Inherited Photoreceptor Degeneration in the Retinal Degeneration 1 Mouse
Authors: Paquet-Durand François , Silva José , Talukdar Tanuja , Johnson Leif E. , Azadi Seifollah , van Veen Theo , Ueffing Marius , Hauck Stefanie M. , Ekström Per A. R.
Published: September 2007

Retinitis pigmentosa (RP) is an inherited blinding disease for which there is no treatment available. It is characterized by a progressive and neurodegenerative loss of photoreceptors but the underlying mechanisms are poorly understood. Excessive activation of the enzyme poly(ADP-ribose) polymerase (PARP) has recently been shown to be involved in several neuropathologies. To investigate the possible role of PARP in retinal photoreceptor degeneration, we used the retinal degeneration 1 (rd1) mouse RP model to study PARP expression, PARP activity, and to test the effects of PARP inhibition on photoreceptor viability. PARP expression was found to be equal between rd1 and wild-type counterpart retinas. In contrast to this, a dramatic increase in both PARP activity per se and PARP product formation was detected byin situassays in rd1 photoreceptors actively undergoing cell death. Furthermore, PARP activity colabeled with oxidatively damaged DNA and nuclear translocation of AIF (apoptosis-inducing factor), suggesting activation of PARP as a bridge between these events in the degenerating photoreceptors. The PARP-specific inhibitor PJ34 [N-(6-oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide·HCl[ reduced the number of cells exhibiting death markers in a short-term retinal culture paradigm, a protective effect that was translated into an increased number of surviving photoreceptors when the inhibitor was used in a long-term culture setting. Our results thus demonstrate an involvement of PARP activity in rd1 photoreceptor cell death, which could have a bearing on the understanding of neurodegenerations as such. The findings also suggest that the therapeutical possibilities of PARP inhibition should include retinal diseases like RP.
Gray Matter Differences Correlate with Spontaneous Strategies in a Human Virtual Navigation Task
Authors: Bohbot Véronique D. , Lerch Jason , Thorndycraft Brook , Iaria Giuseppe , Zijdenbos Alex P.
Published: September 2007

Young healthy participants spontaneously use different strategies in a virtual radial maze, an adaptation of a task typically used with rodents. Functional magnetic resonance imaging confirmed previously that people who used spatial memory strategies showed increased activity in the hippocampus, whereas response strategies were associated with activity in the caudate nucleus. Here, voxel based morphometry was used to identify brain regions covarying with the navigational strategies used by individuals. Results showed that spatial learners had significantly more gray matter in the hippocampus and less gray matter in the caudate nucleus compared with response learners. Furthermore, the gray matter in the hippocampus was negatively correlated to the gray matter in the caudate nucleus, suggesting a competitive interaction between these two brain areas. In a second analysis, the gray matter of regions known to be anatomically connected to the hippocampus, such as the amygdala, parahippocampal, perirhinal, entorhinal and orbitofrontal cortices were shown to covary with gray matter in the hippocampus. Because low gray matter in the hippocampus is a risk factor for Alzheimer's disease, these results have important implications for intervention programs that aim at functional recovery in these brain areas. In addition, these data suggest that spatial strategies may provide protective effects against degeneration of the hippocampus that occurs with normal aging.
NMDA Receptor Surface Trafficking and Synaptic Subunit Composition Are Developmentally Regulated by the Extracellular Matrix Protein Reelin
Authors: Groc Laurent , Choquet Daniel , Stephenson F. Anne , Verrier Danièle , Manzoni Olivier J. , Chavis Pascale
Published: September 2007

During postnatal development, changes in the subunit composition of glutamate receptors of the NMDA subtype (NMDARs) are key to the refinement of excitatory synapses. Hypotheses for maturation of synaptic NMDARs include regulation of their expression levels, membrane targeting, and surface movements. In addition, several members of extracellular matrix (ECM) proteins such as Reelin are involved in synaptic plasticity. However, it is not known whether and how ECM proteins regulate synaptic NMDAR maturation. To probe the participation of NMDARs to synaptic currents and NMDARs surface dynamics, we used electrophysiological recordings and single-particle tracking in cultured hippocampal neurons. Our results show that, during maturation, Reelin orchestrates the regulation of subunit composition of synaptic NMDARs and controls the surface mobility of NR2B subunits. During postnatal maturation, we observed a marked decrease of NR1/NR2B receptor participation to NMDAR-mediated synaptic currents concomitant with the accumulation of Reelin at active synapses. Blockade of the function of Reelin prevented the maturation-dependent reduction in NR1/NR2B-mediated synaptic currents. The reduction of NR1/NR2B receptors was not inhibited by blocking synaptic activity but required β1-containing integrin receptors. Single-particle tracking showed that inhibition of Reelin decreased the surface mobility of native NR2B-containing NMDARs, whereas their synaptic dwell time increased. Conversely, recombinant Reelin dramatically reduced NR2B-mediated synaptic currents and the time spent by NR2B subunits within synapses. Our data reveal a new mode of control of synaptic NMDAR assembly at postnatal hippocampal synapses and an unprecedented role of ECM proteins in regulating glutamate receptor surface diffusion.
Parallel Evolution of Cortical Areas Involved in Skilled Hand Use
Authors: Padberg Jeffrey , Franca João G. , Cooke Dylan F. , Soares Juliana G. M. , Rosa Marcello G. P. , Fiorani Mario , Gattass Ricardo , Krubitzer Leah
Published: September 2007

Dexterous hands, used to manipulate food, tools, and other objects, are one of the hallmarks of primate evolution. However, the neural substrate of fine manual control necessary for these behaviors remains unclear. Here, we describe the functional organization of parietal cortical areas 2 and 5 in the cebus monkey. Whereas other New World monkeys can be quite dexterous, and possess a poorly developed area 5, cebus monkeys are the only New World primate known to use a precision grip, and thus have an extended repertoire of manual behaviors. Unlike other New World Monkeys, but much like the macaque monkey, cebus monkeys possess a proprioceptive cortical area 2 and a well developed area 5, which is associated with motor planning and the generation of internal body coordinates necessary for visually guided reaching, grasping, and manipulation. The similarity of these fields in cebus monkeys and distantly related macaque monkeys with similar manual abilities indicates that the range of cortical organizations that can emerge in primates is constrained, and those that emerge are the result of highly conserved developmental mechanisms that shape the boundaries and topographic organizations of cortical areas.
Monoamine Oxidase-B Mediates Ecstasy-Induced Neurotoxic Effects to Adolescent Rat Brain Mitochondria
Authors: Alves Ema , Summavielle Teresa , Alves Cecília Juliana , Gomes-da-Silva Joana , Barata José Custódio , Fernandes Eduarda , de Lourdes Bastos Maria , Tavares Maria Amélia , Carvalho Félix
Published: September 2007

3,4-Methylenedioxymethamphetamine (MDMA)-induced neurotoxicity and the protective role of monoamine oxidase-B (MAO-B) inhibition were evaluated at the mitochondrial level in various regions of the adolescent rat brain. Four groups of adolescent male Wistar rats were used: (1) saline control, (2) exposed to MDMA (4 × 10 mg/kg, i.p.; two hourly), (3) treated with selegiline (2 mg/kg, i.p.) 30 min before the same dosing of MDMA, and (4) treated with selegiline (2 mg/kg, i.p.). Body temperatures were monitored throughout the whole experiment. Animals were killed 2 weeks later, and mitochondria were isolated from several brain regions. Our results showed that “binge” MDMA administration causes, along with sustained hyperthermia, long-term alterations in brain mitochondria as evidenced by increased levels of lipid peroxides and protein carbonyls. Additionally, analysis of mitochondrial DNA (mtDNA) revealed that NDI nicotinamide adenine dinucleotide phosphate dehydrogenase subunit I and NDII (nicotinamide adenine dinucleotide phosphate dehydrogenase subunit II) subunits of mitochondrial complex I and cytochromecoxidase subunit I of complex IV suffered deletions in MDMA-exposed animals. Inhibition of MAO-B by selegiline did not reduce hyperthermia but reversed MDMA-induced effects in the oxidative stress markers, mtDNA, and related protein expression. These results indicate that monoamine oxidation by MAO-B with subsequent mitochondrial damage may be an important contributing factor for MDMA-induced neurotoxicity.
Caloric Restriction Increases Learning Consolidation and Facilitates Synaptic Plasticity through Mechanisms Dependent on NR2B Subunits of the NMDA Receptor
Authors: Fontán-Lozano Ángela , Sáez-Cassanelli José Luis , Inda Mari Carmen , de los Santos-Arteaga Mercedes , Sierra-Domínguez Sergio Antonio , López-Lluch Guillermo , Delgado-García José María , Carrión Ángel Manuel
Published: September 2007

One of the main focal points of aging research is the search for treatments that will prevent or ameliorate the learning and memory deficiencies associated with aging. Here we have examined the effects of maintaining mature mice on a long-term intermittent fasting diet (L-IFD). We found that L-IFD enhances learning and consolidation processes. We also assessed the long-term changes in synaptic efficiency in these animals. L-IFD mice showed an increase in low-theta-band oscillations, paired-pulse facilitation, and facilitation of long-term synaptic plasticity in the hippocampus with respect to mice fedad libitum. In addition, we found an increase in the expression of the NMDA receptor subunit NR2B in some brain areas of L-IFD mice. Specific antagonism of this subunit in the hippocampus reversed the beneficial effects of L-IFD. These data provide a molecular and cellular mechanism by which L-IFD may enhance cognition, ameliorating some aging-associated cognitive deficits.
Chemical Interactions between Fibrosarcoma Cancer Cells and Sensory Neurons Contribute to Cancer Pain
Authors: Khasabova Iryna A. , Stucky Cheryl L. , Harding-Rose Catherine , Eikmeier Laura , Beitz Alvin J. , Coicou Lia G. , Hanson Amy E. , Simone Donald A. , Seybold Virginia S.
Published: September 2007

In an experimental model of cancer pain, the hyperalgesia that occurs with osteolytic tumor growth is associated with the sensitization of nociceptors. We examined functional and molecular changes in small-diameter dorsal root ganglion (DRG) neurons to determine cellular mechanisms underlying this sensitization. The occurrence of a Ca2+transient in response to either KCl (25 mm) or capsaicin (500 nm) increased in small neurons isolated from murine L3–L6 DRGs ipsilateral to fibrosarcoma cell tumors. The increased responses were associated with increased mRNA levels for the Ca2+channel subunit α2δ1 and TRPV1 receptor. Pretreatment with gabapentin, an inhibitor of the α2δ1 subunit, blocked the increased response to KClin vitroand the mechanical hyperalgesia in tumor-bearing micein vivo. Similar increases in neuronal responsiveness occurred when DRG neurons from naive mice and fibrosarcoma cells were cocultured for 48 h. The CC chemokine ligand 2 (CCL2) may contribute to the tumor cell-induced sensitization because CCL2 immunoreactivity was present in tumors, high levels of CCL2 peptide were present in microperfusates from tumors, and treatment of DRG neuronsin vitrowith CCL2 increased the amount of mRNA for the α2δ1 subunit. Together, our data provide strong evidence that the chemical mediator CCL2 is released from tumor cells and evokes phenotypic changes in sensory neurons, including increases in voltage-gated Ca2+channels that likely underlie the mechanical hyperalgesia in the fibrosarcoma cancer model. More broadly, this study provides a novelin vitromodel to resolve the cellular and molecular mechanisms by which tumor cells drive functional changes in nociceptors.
Nicotine-Induced Dystonic Arousal Complex in a Mouse Line Harboring a Human Autosomal-Dominant Nocturnal Frontal Lobe Epilepsy Mutation
Authors: Teper Yaroslav , Whyte Douglas , Cahir Elizabeth , Lester Henry A. , Grady Sharon R. , Marks Michael J. , Cohen Bruce N. , Fonck Carlos , McClure-Begley Tristan , McIntosh J. Michael , Labarca Cesar , Lawrence Andrew , Chen Feng , Gantois Ilse , Davies Philip J. , Petrou Steven , Murphy Mark , Waddington John , Horne Malcolm K. , Berkovic Samuel F. , Drago John
Published: September 2007

We generated a mouse line harboring an autosomal-dominant nocturnal frontal lobe epilepsy (ADNFLE) mutation: the α4 nicotinic receptor S248F knock-in strain. In this mouse, modest nicotine doses (1–2 mg/kg) elicit a novel behavior termed the dystonic arousal complex (DAC). The DAC includes stereotypical head movements, body jerking, and forelimb dystonia; these behaviors resemble some core features of ADNFLE. A marked Straub tail is an additional component of the DAC. Similar to attacks in ADNFLE, the DAC can be partially suppressed by the sodium channel blocker carbamazepine or by pre-exposure to a very low dose of nicotine (0.1 mg/kg). The DAC is centrally mediated, genetically highly penetrant, and, surprisingly, not associated with overt ictal electrical activity as assessed by (1) epidural or frontal lobe depth-electrode electroencephalography or (2) hippocampal c-fos-regulated gene expression. Heterozygous knock-in mice are partially protected from nicotine-induced seizures. The noncompetitive antagonist mecamylamine does not suppress the DAC, although it suppresses high-dose nicotine-induced wild-type-like seizures. Experiments on agonist-induced86Rb+and neurotransmitter efflux from synaptosomes and on α4S248Fβ2 receptors expressed in oocytes confirm that the S248F mutation confers resistance to mecamylamine blockade. Genetic background, gender, and mutant gene expression levels modulate expression of the DAC phenotype in mice. The S248F mouse thus appears to provide a model for the paroxysmal dystonic element of ADNFLE semiology. Our model complements what is seen in other ADNFLE animal models. Together, these mice cover the spectrum of behavioral and electrographic events seen in the human condition.