bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular analysis and intestinal expression of SAR1 genes and proteins in Anderson's disease (Chylomicron retention disease)
Authors: Georges Amandine , Bonneau Jessica , Bonnefont-Rousselot Dominique , Champigneulle Jacqueline , Rabès Jean P , Abifadel Marianne , Aparicio Thomas , Guenedet Jean C , Bruckert Eric , Boileau Catherine , Morali Alain , Varret Mathilde , Aggerbeck Lawrence P , Samson-Bouma Marie E 
Published: January 2011

Abstract

Background
Anderson's disease (AD) or chylomicron retention disease (CMRD) is a very rare hereditary lipid malabsorption syndrome. In order to discover novel mutations in the SAR1B gene and to evaluate the expression, as compared to healthy subjects, of the Sar1 gene and protein paralogues in the intestine, we investigated three previously undescribed individuals with the disease.

Methods
The SAR1B, SAR1A and PCSK9 genes were sequenced. The expression of the SAR1B and SAR1A genes in intestinal biopsies of both normal individuals and patients was measured by RTqPCR. Immunohistochemistry using antibodies to recombinant Sar1 protein was used to evaluate the expression and localization of the Sar1 paralogues in the duodenal biopsies.

Results
Two patients had a novel SAR1B mutation (p.Asp48ThrfsX17). The third patient, who had a previously described SAR1B mutation (p.Leu28ArgfsX7), also had a p.Leu21dup variant of the PCSK9 gene. The expression of the SAR1B gene in duodenal biopsies from an AD/CMRD patient was significantly decreased whereas the expression of the SAR1A gene was significantly increased, as compared to healthy individuals. The Sar1 proteins were present in decreased amounts in enterocytes in duodenal biopsies from the patients as compared to those from healthy subjects.

Conclusions
Although the proteins encoded by the SAR1A and SAR1B genes are 90% identical, the increased expression of the SAR1A gene in AD/CMRD does not appear to compensate for the lack of the SAR1B protein. The PCSK9 variant, although reported to be associated with low levels of cholesterol, does not appear to exert any additional effect in this patient. The results provide further insight into the tissue-specific nature of AD/CMRD.
Genome-wide analysis of Ollier disease: Is it all in the genes?
Authors: Pansuriya Twinkal C , Oosting Jan , Krenács Tibor , Taminiau Antonie HM , Verdegaal Suzan HM , Sangiorgi Luca , Sciot Raf , Hogendoorn Pancras CW , Szuhai Karoly , Bovée Judith VMG 
Published: January 2011

Abstract

Background
Ollier disease is a rare, non-hereditary disorder which is characterized by the presence of multiple enchondromas (ECs), benign cartilaginous neoplasms arising within the medulla of the bone, with an asymmetric distribution. The risk of malignant transformation towards central chondrosarcoma (CS) is increased up to 35%. The aetiology of Ollier disease is unknown.

Methods
We undertook genome-wide copy number and loss of heterozygosity (LOH) analysis using Affymetrix SNP 6.0 array on 37 tumours of 28 Ollier patients in combination with expression array using Illumina BeadArray v3.0 for 7 ECs of 6 patients.

Results
Non-recurrent EC specific copy number alterations were found at FAM86D, PRKG1 and ANKS1B. LOH with copy number loss of chromosome 6 was found in two ECs from two unrelated Ollier patients. One of these patients also had LOH at chromosome 3. However, no common genomic alterations were found for all ECs. Using an integration approach of SNP and expression array we identified loss as well as down regulation of POU5F1 and gain as well as up regulation of NIPBL. None of these candidate regions were affected in more than two Ollier patients suggesting these changes to be random secondary events in EC development. An increased number of genetic alterations and LOH were found in Ollier CS which mainly involves chromosomes 9p, 6q, 5q and 3p.

Conclusions
We present the first genome-wide analysis of the largest international series of Ollier ECs and CS reported so far and demonstrate that copy number alterations and LOH are rare and non-recurrent in Ollier ECs while secondary CS are genetically unstable. One could predict that instead small deletions, point mutations or epigenetic mechanisms play a role in the origin of ECs of Ollier disease.
Conformation dependent monoclonal antibodies distinguish different replicating strains or conformers of prefibrillar Aβ oligomers
Authors: Kayed Rakez , Canto Isabel , Breydo Leonid , Rasool Suhail , Lukacsovich Tamas , Wu Jessica , Albay Ricardo , Pensalfini Anna , Yeung Stephen , Head Elizabeth , Marsh J Lawrence , Glabe Charles 
Published: January 2011

Abstract

Background
Age-related neurodegenerative diseases share a number of important pathological features, such as accumulation of misfolded proteins as amyloid oligomers and fibrils. Recent evidence suggests that soluble amyloid oligomers and not the insoluble amyloid fibrils may represent the primary pathological species of protein aggregates.

Results
We have produced several monoclonal antibodies that specifically recognize prefibrillar oligomers and do not recognize amyloid fibrils, monomer or natively folded proteins. Like the polyclonal antisera, the individual monoclonals recognize generic epitopes that do not depend on a specific linear amino acid sequence, but they display distinct preferences for different subsets of prefibrillar oligomers. Immunological analysis of a number of different prefibrillar Aβ oligomer preparations show that structural polymorphisms exist in Aβ prefibrillar oligomers that can be distinguished on the basis of their reactivity with monoclonal antibodies. Western blot analysis demonstrates that the conformers defined by the monoclonal antibodies have distinct size distributions, indicating that oligomer structure varies with size. The different conformational types of Aβ prefibrillar oligomers can serve as they serve as templates for monomer addition, indicating that they seed the conversion of Aβ monomer into more prefibrillar oligomers of the same type.

Conclusions
These results indicate that distinct structural variants or conformers of prefibrillar Aβ oligomers exist that are capable of seeding their own replication. These conformers may be analogous to different strains of prions.
MyD88-adaptor protein acts as a preventive mechanism for memory deficits in a mouse model of Alzheimer's disease
Authors: Michaud Jean-Philippe , Richard Karine L , Rivest Serge 
Published: January 2011

Abstract

Background
Alzheimer's disease (AD) is an age-related neurodegenerative disorder associated with brain innate immune activation mainly mediated by microglia. These cells are known to be activated in the brain of AD patients and to produce inflammatory cytokines and neurotoxic molecules in response to Amyloid beta (Aβ). Activation of microglia can also promote Aβ clearance via Toll-like receptors (TLRs). Myeloid differentiation factor 88 (MyD88) is the adaptor molecule for most of these innate immune receptors, transducing the intracellular signal from TLRs to nucleus.

Results
Here, we report that more than 50% reduction in MyD88 expression in a mouse model of AD accelerated spatial learning and memory deficits. Brain of APPswe/PS1-MyD88+/- mice was characterized by a delay in accumulation of Aβ plaques and increased soluble levels of Aβ oligomers. Furthermore, inflammatory monocyte subset and brain IL-1β gene expression were significantly reduced in APPswe/PS1 mice with impaired MyD88 signaling.

Conclusions
These data indicate that activation of MyD88 intracellular signaling pathway, likely by TLRs, acts as a natural innate immune mechanism to restrict disease progression of APPswe/PS1 mice.
Preclinical study of dimebon on β-amyloid-mediated neuropathology in Alzheimer's disease
Authors: Wang Jun , Ferruzzi Mario G , Varghese Merina , Qian Xianjuan , Cheng Alice , Xie Mathew , Zhao Wei , Ho Lap , Pasinetti Giulio M 
Published: January 2011

Abstract

Background
Dimebon is a retired non-selective antihistamine drug currently being investigated as a therapeutic agent for the treatment of Alzheimer's disease (AD). Results from several completed clinical trials are mixed and contradictory. Proper interpretations of these clinical observations, as well as future development of dimebon in AD treatment are complicated by the lack of concrete information on the mechanisms by which dimebon might benefit AD.

Results
The present studies are designed specifically to assess whether dimebon might modulate β-amyloid (Aβ)-mediated responses which are central to the development and progression of AD dementia. We found that dimebon is bioavailable in the brains of mice following oral administration. AD mice chronically treated with dimebon exhibited a trend of improvement in spatial memory function without affecting the levels of total Aβ as well as soluble oligomeric Aβ in the brain. The same trend of behavior improvement is also seen in wild type animals chronically treated with dimebon.

Conclusion
Collectively, our preclinical studies using the TgCRND8 AD mouse model demonstrated that dimebon might have some beneficial effect in improving cognitive function independent of Alzheimer's disease-type Aβ-related mechanisms or global energy metabolism in the brain. Observations from our study and others suggesting dimebon might improve cognition in wild type mice and rats raises the possibility that dimebon might be able to benefit cognitive function in patients with other neurodegenerative disorders, such as Huntington's disease, or in the aging population. Additional studies will be necessary to clarify the mechanisms by which dimebon might directly or indirectly benefit cognitive function.
SAMMate: a GUI tool for processing short read alignments in SAM/BAM format
Authors: Xu Guorong , Deng Nan , Zhao Zhiyu , Judeh Thair , Flemington Erik , Zhu Dongxiao 
Published: January 2011

Abstract

Background
Next Generation Sequencing (NGS) technology generates tens of millions of short reads for each DNA/RNA sample. A key step in NGS data analysis is the short read alignment of the generated sequences to a reference genome. Although storing alignment information in the Sequence Alignment/Map (SAM) or Binary SAM (BAM) format is now standard, biomedical researchers still have difficulty accessing this information.

Results
We have developed a Graphical User Interface (GUI) software tool named SAMMate. SAMMate allows biomedical researchers to quickly process SAM/BAM files and is compatible with both single-end and paired-end sequencing technologies. SAMMate also automates some standard procedures in DNA-seq and RNA-seq data analysis. Using either standard or customized annotation files, SAMMate allows users to accurately calculate the short read coverage of genomic intervals. In particular, for RNA-seq data SAMMate can accurately calculate the gene expression abundance scores for customized genomic intervals using short reads originating from both exons and exon-exon junctions. Furthermore, SAMMate can quickly calculate a whole-genome signal map at base-wise resolution allowing researchers to solve an array of bioinformatics problems. Finally, SAMMate can export both a wiggle file for alignment visualization in the UCSC genome browser and an alignment statistics report. The biological impact of these features is demonstrated via several case studies that predict miRNA targets using short read alignment information files.

Conclusions
With just a few mouse clicks, SAMMate will provide biomedical researchers easy access to important alignment information stored in SAM/BAM files. Our software is constantly updated and will greatly facilitate the downstream analysis of NGS data. Both the source code and the GUI executable are freely available under the GNU General Public License at http://sammate.sourceforge.net.
WebGimm: An integrated web-based platform for cluster analysis, functional analysis, and interactive visualization of results
Authors: Joshi Vineet K , Freudenberg Johannes M , Hu Zhen , Medvedovic Mario 
Published: January 2011

Abstract
Cluster analysis methods have been extensively researched, but the adoption of new methods is often hindered by technical barriers in their implementation and use. WebGimm is a free cluster analysis web-service, and an open source general purpose clustering web-server infrastructure designed to facilitate easy deployment of integrated cluster analysis servers based on clustering and functional annotation algorithms implemented in R. Integrated functional analyses and interactive browsing of both, clustering structure and functional annotations provides a complete analytical environment for cluster analysis and interpretation of results. The Java Web Start client-based interface is modeled after the familiar cluster/treeview packages making its use intuitive to a wide array of biomedical researchers. For biomedical researchers, WebGimm provides an avenue to access state of the art clustering procedures. For Bioinformatics methods developers, WebGimm offers a convenient avenue to deploy their newly developed clustering methods. WebGimm server, software and manuals can be freely accessed at http://ClusterAnalysis.org/.
Stochastic simulations of the tetracycline operon
Authors: Biliouris Konstantinos , Daoutidis Prodromos , Kaznessis Yiannis N 
Published: January 2011

Abstract

Background
The tetracycline operon is a self-regulated system. It is found naturally in bacteria where it confers resistance to antibiotic tetracycline. Because of the performance of the molecular elements of the tetracycline operon, these elements are widely used as parts of synthetic gene networks where the protein production can be efficiently turned on and off in response to the presence or the absence of tetracycline. In this paper, we investigate the dynamics of the tetracycline operon. To this end, we develop a mathematical model guided by experimental findings. Our model consists of biochemical reactions that capture the biomolecular interactions of this intriguing system. Having in mind that small biological systems are subjects to stochasticity, we use a stochastic algorithm to simulate the tetracycline operon behavior. A sensitivity analysis of two critical parameters embodied this system is also performed providing a useful understanding of the function of this system.

Results
Simulations generate a timeline of biomolecular events that confer resistance to bacteria against tetracycline. We monitor the amounts of intracellular TetR2 and TetA proteins, the two important regulatory and resistance molecules, as a function of intrecellular tetracycline. We find that lack of one of the promoters of the tetracycline operon has no influence on the total behavior of this system inferring that this promoter is not essential for Escherichia coli. Sensitivity analysis with respect to the binding strength of tetracycline to repressor and of repressor to operators suggests that these two parameters play a predominant role in the behavior of the system. The results of the simulations agree well with experimental observations such as tight repression, fast gene expression, induction with tetracycline, and small intracellular TetR2 amounts.

Conclusions
Computer simulations of the tetracycline operon afford augmented insight into the interplay between its molecular components. They provide useful explanations of how the components and their interactions have evolved to best serve bacteria carrying this operon. Therefore, simulations may assist in designing novel gene network architectures consisting of tetracycline operon components.
An 82-year-old Caucasian man with a ductal prostate adenocarcinoma with unusual cystoscopic appearance: a case report
Authors: Sfoungaristos Stavros , Katafigiotis Ioannis S , Tyritzis Stavros I , Kavouras Adamantios , Kanatas Panagiotis , Petas Anastasios 
Published: January 2011

Abstract

Introduction
Ductal adenocarcinoma is a rare variety of the common acinar adenocarcinoma. It usually presents with refractory symptoms, and during cystoscopy, it is seen as an exophytic lesion at the area of the verumontanum.

Case presentation
An 82-year-old Caucasian man was diagnosed with ductal adenocarcinoma of the prostate after undergoing transurethral resection of the prostate for urinary retention. Immunohistochemistry confirmed the nature of the tumor. The patient was treated with triptorelin, 3.75 mg once/month, and bicalutamide, 50 mg 1 × 1. The serum prostate-specific antigen at three, six and 12 months after transurethral resection of the prostate was 0.1 ng/ml. The patient remains asymptomatic, and he entered a six-month follow-up protocol.

Conclusion
Ductal adenocarcinoma often involves the central ducts of the gland and may present as an exophytic papillary lesion in the prostatic urethra. This is why it usually presents with refractory symptoms. The outcome for men with prostatic ductal adenocarcinoma is, in most studies, worse than the outcome for men with prostatic acinar adenocarcinoma. Aggressive management is indicated, even with low-volume metastatic disease.
Congenital spinal tumor in a patient with encephalocele and hydrocephalus: a case report
Authors: Radmanesh Farid , Nejat Farideh , Mahjoub Fatemeh , El Khashab Mostafa 
Published: January 2011

Abstract

Introduction
Encephalocele is a rare congenital abnormality of the central nervous system, where brain tissue protrudes from a defect in the skull. Some anomalies are associated with encephalocele. However, the association of spinal teratoma and encephalocele has not been reported in the English literature.

Case presentation
We report the case of an Iranian girl with a history of encephalocele surgery, who, at the age of four years, developed an intramedullary spinal teratoma, and discuss the pathogenesis of this association.

Conclusion
To the best of our knowledge, this is the first report of an association between encephalocele and spinal teratoma.
Hyaluronidase recruits mesenchymal-like cells to the lung and ameliorates fibrosis
Authors: Bitencourt Claudia S , Pereira Priscilla AT , Ramos Simone G , Sampaio Suely V , Arantes Eliane C , Aronoff David M , Faccioli Lúcia H 
Published: January 2011

AbstractHyaluronidases (HYALs) comprise a group of enzymes that degrade hyaluronic acid (HA). In this report, we reveal that a single intranasal inoculation of HYAL induces an increase in mononuclear cells within the bronchoalveolar space demonstrating a mesenchymal-like phenotype, expressing stem cell antigen-1 (SCA-1), CD44 and CD73 but not CD34, CD45, CD3, CD4, CD8 or CD19. This influx of mesenchymal stem cell (MSC)-like cells was dependent on leukotriene production within the lung parenchyma. These findings prompted experiments demonstrating that HYAL treatment potently blocked bleomycin-induced lung injury and fibrosis while decreasing transforming growth factor (TGF)-β production and collagen deposition. These data suggest that HYAL is a novel and promising tool to use autologous MSC-like cells in the treatment of pulmonary fibrosis.
DNA methylation-mediated control of learning and memory
Authors: Yu Nam-Kyung , Baek Sung Hee , Kaang Bong-Kiun 
Published: January 2011

Abstract
Animals constantly receive and respond to external or internal stimuli, and these experiences are learned and memorized in their brains. In animals, this is a crucial feature for survival, by making it possible for them to adapt their behavioral patterns to the ever-changing environment. For this learning and memory process, nerve cells in the brain undergo enormous molecular and cellular changes, not only in the input-output-related local subcellular compartments but also in the central nucleus. Interestingly, the DNA methylation pattern, which is normally stable in a terminally differentiated cell and defines the cell type identity, is emerging as an important regulatory mechanism of behavioral plasticity. The elucidation of how this covalent modification of DNA, which is known to be the most stable epigenetic mark, contributes to the complex orchestration of animal behavior is a fascinating new research area. We will overview the current understanding of the mechanism of modifying the methyl code on DNA and its impact on learning and memory.
6-Nitro-2-(3-hydroxypropyl)-1H-benz[de]isoquinoline-1,3-dione, a potent antitumor agent, induces cell cycle arrest and apoptosis
Authors: Mukherjee Asama , Dutta Sushanta , Shanmugavel Muthiah , Mondhe Dilip M , Sharma Parduman R , Singh Shashank K , Saxena Ajit K , Sanyal Utpal 
Published: January 2011

AbstractBackgroundAnticancer activities of several substituted naphthalimides (1H-benz[de]isoquinoline-1,3-diones) are well documented. Some of them have undergone Phase I-II clinical trials. Presently a series of ten N-(hydroxyalkyl) naphthalimides (compounds1a-j)were evaluated as antitumor agents.MethodsCompounds1a-jwere initially screened in MOLT-4, HL-60 and U-937 human tumor cell lines and results were compared with established clinical drugs. Cytotoxicities of compounds1dand1iwere further evaluated in a battery of human tumor cell lines and in normal human peripheral blood mononuclear cells. Cell cycle analysis of compound1itreated MOLT-4 cells was studied by flow cytometry. Its apoptosis inducing effect was carried out in MOLT-4 and HL-60 cells by flow cytometry using annexin V-FITC/PI double staining method. The activities of caspase-3 and caspase-6 in MOLT-4 cells following incubation with compound1iwere measured at different time intervals. Morphology of the MOLT-4 cells after treatment with1iwas examined under light microscope and transmission electron microscope.3H-Thymidine and3H-uridine incorporation in S-180 cells in vitro following treatment with 8 μM concentration of compounds1dand1iwere studied.Results6-Nitro-2-(3-hydroxypropyl)-1H-benz[de]isoquinoline-1,3-dione (compound1i), has exhibited maximum activity as it induced significant cytotoxicity in 8 out of 13 cell lines employed. Interestingly it did not show any cytotoxicity against human PBMC (IC50value 273 μM). Cell cycle analysis of compound1itreated MOLT-4 cells demonstrated rise in sub-G1fraction and concomitant accumulation of cells in S and G2/M phases, indicating up-regulation of apoptosis along with mitotic arrest and/or delay in exit of daughter cells from mitotic cycle respectively. Its apoptosis inducing effect was confirmed in flow cytometric study in MOLT-4 and the action was mediated by activation of both caspase 3 and 6. Light and transmission electron microscopic studies corroborated its apoptosis inducing efficacy at a concentration of 10 μM in MOLT-4 cells. Its apoptosis induction was also observed in HL-60 cells to an extent much greater than well known apoptosis inducing agents as camptothecin and cis-platin at 10 μM concentration each. It significantly inhibited DNA and RNA synthesis in S-180.ConclusionsIn essence, compound1ishowed potential as an antitumor agent.