bluuebunny/crossref_metadata_2025_split huggingface dataset:
Age-dependent decrease in glutamine synthetase expression in the hippocampal astroglia of the triple transgenic Alzheimer's disease mouse model: mechanism for deficient glutamatergic transmission?
Authors: Olabarria Markel , Noristani Harun N , Verkhratsky Alexei , Rodríguez José J 
Published: July 2011

AbstractAstrocytes are fundamental for brain homeostasis and the progression and outcome of many neuropathologies including Alzheimer's disease (AD). In the triple transgenic mouse model of AD (3xTg-AD) generalised hippocampal astroglia atrophy precedes a restricted and specific β-amyloid (Aβ) plaque-related astrogliosis. Astrocytes are critical for CNS glutamatergic transmission being the principal elements of glutamate homeostasis through maintaining its synthesis, uptake and turnover via glutamate-glutamine shuttle. Glutamine synthetase (GS), which is specifically expressed in astrocytes, forms glutamine by an ATP-dependent amination of glutamate. Here, we report changes in GS astrocytic expression in two major cognitive areas of the hippocampus (the dentate gyrus, DG and the CA1) in 3xTg-AD animals aged between 9 and 18 months. We found a significant reduction in Nv(number of cell/mm3) of GS immunoreactive (GS-IR) astrocytes starting from 12 months (28.59%) of age in the DG, and sustained at 18 months (31.65%). CA1 decrease of GS-positive astrocytes Nv(33.26%) occurs at 18 months. This Nvreduction of GS-IR astrocytes is paralleled by a decrease in overall GS expression (determined by its optical density) that becomes significant at 18 months (21.61% and 19.68% in DG and CA1, respectively). GS-IR Nvchanges are directly associated with the presence of Aβ deposits showing a decrease of 47.92% as opposed to 23.47% in areas free of Aβ. These changes in GS containing astrocytes and GS-immunoreactivity indicate AD-related impairments of glutamate homeostatic system, at the advanced and late stages of the disease, which may affect the efficacy of glutamatergic transmission in the diseased brain that may contribute to the cognitive deficiency.
Mutant Prpf31 causes pre-mRNA splicing defects and rod photoreceptor cell degeneration in a zebrafish model for Retinitis pigmentosa
Authors: Yin Jun , Brocher Jan , Fischer Utz , Winkler Christoph 
Published: July 2011

Abstract

Background
Retinitis pigmentosa (RP) is an inherited eye disease characterized by the progressive degeneration of rod photoreceptor cells. Mutations in pre-mRNA splicing factors including PRPF31 have been identified as cause for RP, raising the question how mutations in general factors lead to tissue specific defects.

Results
We have recently shown that the zebrafish serves as an excellent model allowing the recapitulation of key events of RP. Here we use this model to investigate two pathogenic mutations in PRPF31, SP117 and AD5, causing the autosomal dominant form of RP. We show that SP117 leads to an unstable protein that is mislocalized to the rod cytoplasm. Importantly, its overexpression does not result in photoreceptor degeneration suggesting haploinsufficiency as the underlying cause in human RP patients carrying SP117. In contrast, overexpression of AD5 results in embryonic lethality, which can be rescued by wild-type Prpf31. Transgenic retina-specific expression of AD5 reveals that stable AD5 protein is initially localized in the nucleus but later found in the cytoplasm concurrent with progressing rod outer segment degeneration and apoptosis. Importantly, we show for the first time in vivo that retinal transcripts are wrongly spliced in adult transgenic retinas expressing AD5 and exhibiting increased apoptosis in rod photoreceptors.

Conclusion
Our data suggest that distinct mutations in Prpf31 can lead to photoreceptor degeneration through different mechanisms, by haploinsufficiency or dominant-negative effects. Analyzing the AD5 effects in our animal model in vivo, our data imply that aberrant splicing of distinct retinal transcripts contributes to the observed retina defects.
Combined logical and data-driven models for linking signalling pathways to cellular response
Authors: Melas Ioannis N , Mitsos Alexander , Messinis Dimitris E , Weiss Thomas S , Alexopoulos Leonidas G 
Published: July 2011

Abstract

Background
Signalling pathways are the cornerstone on understanding cell function and predicting cell behavior. Recently, logical models of canonical pathways have been optimised with high-throughput phosphoproteomic data to construct cell-type specific pathways. However, less is known on how signalling pathways can be linked to a cellular response such as cell growth, death, cytokine secretion, or transcriptional activity.

Results
In this work, we measure the signalling activity (phosphorylation levels) and phenotypic behavior (cytokine secretion) of normal and cancer hepatocytes treated with a combination of cytokines and inhibitors. Using the two datasets, we construct "extended" pathways that integrate intracellular activity with cellular responses using a hybrid logical/data-driven computational approach. Boolean logic is used whenever a priori knowledge is accessible (i.e., construction of canonical pathways), whereas a data-driven approach is used for linking cellular behavior to signalling activity via non-canonical edges. The extended pathway is subsequently optimised to fit signalling and behavioural data using an Integer Linear Programming formulation. As a result, we are able to construct maps of primary and transformed hepatocytes downstream of 7 receptors that are capable of explaining the secretion of 22 cytokines.

Conclusions
We developed a method for constructing extended pathways that start at the receptor level and via a complex intracellular signalling pathway identify those mechanisms that drive cellular behaviour. Our results constitute a proof-of-principle for construction of "extended pathways" that are capable of linking pathway activity to diverse responses such as growth, death, differentiation, gene expression, or cytokine secretion.
Genome-wide analysis of the transcription factor binding preference of human bi-directional promoters and functional annotation of related gene pairs
Authors: Liu Bingchuan , Chen Jiajia , Shen Bairong 
Published: July 2011

Abstract

Background
Bi-directional gene pairs have received considerable attention for their prevalence in vertebrate genomes. However, their biological relevance and exact regulatory mechanism remain less understood. To study the inner properties of this gene organization and the difference between bi- and uni-directional genes, we conducted a genome-wide investigation in terms of their sequence composition, functional association and regulatory motif discovery.

Results
We identified 1210 bi-directional gene pairs based on the GRCh37 assembly data, accounting for 11.6% of all the human genes owning RNAs. CpG islands were detected in 98.42% of bi-directional promoters and 61.07% of unidirectional promoters. Functional enrichment analysis in GO and GeneGO both revealed that bi-directional genes tend to be associated with housekeeping functions in metabolism pathways and nuclear processes, and 46.84% of the pair members are involved in the same biological function. By fold-enrichment analysis, we characterized 73 and 43 putative transcription factor binding sites(TFBS) that preferentially occur in bi-directional promoters from TRANSFAC and JASPAR database respectively. By text mining, some of them were verified by individual experiments and several novel binding motifs were also identified.

Conclusions
Bi-directional promoters feature a significant enrichment of CpG-islands as well as a high GC content. We provided insight into the function constraints of bi-directional genes and found that paired genes are biased toward functional similarities. We hypothesized that the functional association underlies the co-expression of bi-directional genes. Furthermore, we proposed a set of putative regulatory motifs in the bi-directional promoters for further experimental studies to investigate transcriptional regulation of bi-directional genes.
MetaDBSite: a meta approach to improve protein DNA-binding sites prediction
Authors: Si Jingna , Zhang Zengming , Lin Biaoyang , Schroeder Michael , Huang Bingding 
Published: July 2011

Abstract

Background
Protein-DNA interactions play an important role in many fundamental biological activities such as DNA replication, transcription and repair. Identification of amino acid residues involved in DNA binding site is critical for understanding of the mechanism of gene regulations. In the last decade, there have been a number of computational approaches developed to predict protein-DNA binding sites based on protein sequence and/or structural information.

Results
In this article, we present metaDBSite, a meta web server to predict DNA-binding residues for DNA-binding proteins. MetaDBSite integrates the prediction results from six available online web servers: DISIS, DNABindR, BindN, BindN-rf, DP-Bind and DBS-PRED and it solely uses sequence information of proteins. A large dataset of DNA-binding proteins is constructed from the Protein Data Bank and it serves as a gold-standard benchmark to evaluate the metaDBSite approach and the other six predictors.

Conclusions
The comparison results show that metaDBSite outperforms single individual approach. We believe that metaDBSite will become a useful and integrative tool for protein DNA-binding residues prediction. The MetaDBSite web-server is freely available at http://projects.biotec.tu-dresden.de/metadbsite/ and http://sysbio.zju.edu.cn/metadbsite.
Atlantoaxial subluxation as an early manifestation in an adolescent with undifferentiated spondyloarthritis: a case report and review of the literature
Authors: Muscal Eyal , Satyan Krishna B , Jea Andrew 
Published: July 2011

Abstract

Introduction
Atlantoaxial instability has been described as a manifestation of ankylosing spondylitis (juvenile and adult onset), reactive arthritis, juvenile idiopathic arthritis, and rheumatoid arthritis; however, it has rarely been reported as an early manifestation of these disorders. We present this case report to increase awareness of the condition in the hope that earlier recognition of this disease may prevent further serious injury.

Case presentation
We report the case of a 17-year-old Hispanic adolescent woman who was initially diagnosed with undifferentiated spondyloarthritis due to peripheral arthritis, enthesitis, a positive human leukocyte antigen B27 result, and inflammatory spinal pain lasting two months. Our patient experienced persistent and worsening occipitocervical pain and signs of myelopathy three months after diagnosis; consequently, we found atlantoaxial instability along with cervical spine bone erosion and pannus formation. She was treated surgically with a C1-2 posterior instrumented fusion and at six weeks post-operatively was started on tumor necrosis factor α blockade. Her occipitocervical symptoms subsided following surgery and initiation of immunomodulation.

Conclusions
Our report serves to emphasize to pediatric and adult general practitioners, pediatricians, internists, family physicians, pediatric and adult rheumatologists and spine surgeons that atlantoaxial subluxation may be an early manifestation of spondyloarthritis, and that the condition is treatable by surgical intervention and immunomodulation.
Mycoplasma hominis brain abscess following uterus curettage: a case report
Authors: Al Masalma Mouhamad , Drancourt Michel , Dufour Henry , Raoult Didier , Fournier Pierre-Edouard 
Published: July 2011

Abstract

Introduction

Mycoplasma hominis is mostly known for causing urogenital infections. However, it has rarely been described as an agent of brain abscess.

Case presentation
We describe a case of M. hominis brain abscess in a 41-year-old Caucasian woman following uterus curettage. The diagnosis was obtained by 16S rDNA amplification, cloning and sequencing from the abscess pus, and confirmed by a specifically designed real-time polymerase chain reaction assay.

Conclusions
Findings from our patient's case suggest that M. hominis should be considered as a potential agent of brain abscess, especially following uterine manipulation.
Fulminant hemophagocytic lymphohistiocytosis induced by pandemic A (H1N1) influenza: a case report
Authors: Willekens Christophe , Cornelius Aurélie , Guerry Mary-Jane , Wacrenier Agnès , Fourrier François 
Published: July 2011

Abstract

Introduction
Hemophagocytic lymphohistiocytosis induced by viral diseases is a well recognized entity. Severe forms of H5N1 influenza are known to be associated with symptoms very similar to a reactive hemophagocytic syndrome. We report a case of fulminant lymphohistiocytosis associated with the pandemic A (H1N1) variant.

Case presentation
A 42-year-old Caucasian woman developed a syndrome of fatal hemophagocytic lymphohistiocytosis shortly after H1N1 influenza. Initial symptoms of the viral disease were unusual, with acute abdominal involvement. Our patient's course was complicated by diffuse skin rash and ileal ischemia. Our patient died of refractory shock and multi-organ failure. Skin, ileum and colon histology was consistent with an acute apoptosis combined with an increased cellular regeneration.

Conclusions
Influenza may be complicated by severe forms of hemophagocytic lymphohistiocytosis. To ensure early recognition and treatment, physicians should be aware of the possible induction of the syndrome by the novel H1N1 variant. The rapid occurrence of a multi-organ involvement with evocative biological features of macrophage activation should alert clinicians.
Surgical and anesthetic considerations of laryngeal saccular cyst: a case report
Authors: Aidonis Ioannis , Skalimis Anargyros , Kirodimos Efthimios 
Published: July 2011

Abstract

Introduction
Supraglottic laryngeal cysts are benign, uncommon lesions that have the potential to cause airway compromise.

Case Presentation
We present a case of a 46-year-old Caucasian woman who was scheduled for excision of a large neck growth (saccular cyst) and was managed successfully. There was thorough consideration regarding anesthetic and surgical management. Steps taken led to a successful excision with no recurrence during follow up.

Conclusion
This case was an opportunity to consider the challenges in the airway management associated with such cysts and provided reassurance that excision of these cysts is associated with a good post-operative outcome.
Acute heroin intoxication in a baby chronically exposed to cocaine and heroin: a case report
Authors: Joya Xavier , Fríguls Bibiana , Simó Marta , Civit Ester , de la Torre Rafael , Palomeque Antonio , Vall Oriol , Pichini Simona , Garcia-Algar Oscar 
Published: July 2011

Abstract

Introduction
Acute intoxication with drugs of abuse in children is often only the tip of the iceberg, actually hiding chronic exposure. Analysis using non-conventional matrices such as hair can provide long-term information about exposure to recreational drugs.

Case presentation
We report the case of a one-month-old Caucasian boy admitted to our pediatric emergency unit with respiratory distress and neurological abnormalities. A routine urine test was positive for opiates, suggesting an acute opiate ingestion. No other drugs of misuse, such as cocaine, cannabis, amphetamines or derivatives, were detected in the baby's urine. Subsequently, hair samples from the baby and the parents were collected to evaluate the possibility of chronic exposure to drug misuse by segmental analysis. Opiates and cocaine metabolites were detected in hair samples from the baby boy and his parents.

Conclusions
In light of these and previous results, we recommend hair analysis in babies and children from risky environments to detect exposure to heroin and other drug misuse, which could provide the basis for specific social and health interventions.
Case report: BRCA in the Ashkenazi population: are current testing guidelines too exclusive?
Authors: Saunders Katherine H , Nazareth Shivani , Pressman Peter I 
Published: July 2011

Abstract
The BRCA1/2 genes account for a significant portion of hereditary breast and ovarian cancers and they are especially prevalent in the Ashkenazi Jewish population. Women who have a mutation can prevent breast and ovarian cancer with surgical intervention. We describe an Ashkenazi Jewish patient who illustrates that current testing criteria are too restrictive, particularly for this population of patients. The patient's sister was diagnosed with breast cancer at age 33; however, she was not a mutation carrier. Based on practice guidelines, the patient was not recommended genetic testing. She subsequently underwent direct-to-consumer (DTC) testing and discovered that she was a mutation carrier. This case demonstrates the need for clinicians to be aware of the higher prevalence of BRCA mutations in the Ashkenazi population. It also exemplifies the need to involve medical professionals, including genetic counselors, in the dissemination of DNA test results.
A shortest-path graph kernel for estimating gene product semantic similarity
Authors: Alvarez Marco A , Qi Xiaojun , Yan Changhui 
Published: July 2011

Abstract

Background
Existing methods for calculating semantic similarity between gene products using the Gene Ontology (GO) often rely on external resources, which are not part of the ontology. Consequently, changes in these external resources like biased term distribution caused by shifting of hot research topics, will affect the calculation of semantic similarity. One way to avoid this problem is to use semantic methods that are "intrinsic" to the ontology, i.e. independent of external knowledge.

Results
We present a shortest-path graph kernel (spgk) method that relies exclusively on the GO and its structure. In spgk, a gene product is represented by an induced subgraph of the GO, which consists of all the GO terms annotating it. Then a shortest-path graph kernel is used to compute the similarity between two graphs. In a comprehensive evaluation using a benchmark dataset, spgk compares favorably with other methods that depend on external resources. Compared with simUI, a method that is also intrinsic to GO, spgk achieves slightly better results on the benchmark dataset. Statistical tests show that the improvement is significant when the resolution and EC similarity correlation coefficient are used to measure the performance, but is insignificant when the Pfam similarity correlation coefficient is used.

Conclusions
Spgk uses a graph kernel method in polynomial time to exploit the structure of the GO to calculate semantic similarity between gene products. It provides an alternative to both methods that use external resources and "intrinsic" methods with comparable performance.
Sex differences in the inflammatory response of primary astrocytes to lipopolysaccharide
Authors: Santos-Galindo María , Acaz-Fonseca Estefanía , Bellini María J , Garcia-Segura Luis M 
Published: July 2011

AbstractBackgroundNumerous neurological and psychiatric disorders show sex differences in incidence, age of onset, symptomatology or outcome. Astrocytes, one of the glial cell types of the brain, show sex differences in number, differentiation and function. Since astrocytes are involved in the response of neural tissue to injury and inflammation, these cells may participate in the generation of sex differences in the response of the brain to pathological insults. To explore this hypothesis, we have examined whether male and female astrocytes show a different response to an inflammatory challenge and whether perinatal testosterone influences this response.MethodsCortical astrocyte cultures were prepared from postnatal day 1 (one day after birth) male or female CD1 mice pups. In addition, cortical astrocyte cultures were also prepared from female pups that were injected at birth with 100 μg of testosterone propionate or vehicle. Cultures were treated for 5 hours with medium containing lipopolysaccharide (LPS) or with control medium. The mRNA levels of IL6, interferon-inducible protein 10 (IP10), TNFα, IL1β, Toll-like receptor 4 (TLR4), steroidogenic acute regulatory protein and translocator protein were assessed by quantitative real-time polymerase chain reaction. Statistical significance was assessed by unpairedt-test or by one-way analysis of variance followed by the Tukeypost hoctest.ResultsThe mRNA levels of IL6, TNFα and IL1β after LPS treatment were significantly higher in astrocytes derived from male or androgenized females compared to astrocytes derived from control or vehicle-injected females. In contrast, IP10 mRNA levels after LPS treatment were higher in astrocytes derived from control or vehicle-injected females than in those obtained from males or androgenized females. The different response of male and female astrocytes to LPS was due neither to differences in the basal expression of the inflammatory molecules nor to differences in the expression of the LPS receptor TLR4. In contrast, the different inflammatory response was associated with increased mRNA levels of translocator protein, a key steroidogenic regulator, in female astrocytes that were treated with LPS.ConclusionsMale and female cortical astrocytes respond differentially to an inflammatory challenge and this may be predetermined by perinatal testosterone exposure.
Bicarbonate in diabetic ketoacidosis - a systematic review
Authors: Chua Horng Ruey , Schneider Antoine , Bellomo Rinaldo 
Published: July 2011

Abstract

Objective
This study was designed to examine the efficacy and risk of bicarbonate administration in the emergent treatment of severe acidemia in diabetic ketoacidosis (DKA).

Methods
PUBMED database was used to identify potentially relevant articles in the pediatric and adult DKA populations. DKA intervention studies on bicarbonate administration versus no bicarbonate in the emergent therapy, acid-base studies, studies on risk association with cerebral edema, and related case reports, were selected for review. Two reviewers independently conducted data extraction and assessed the citation relevance for inclusion.

Results
From 508 potentially relevant articles, 44 were included in the systematic review, including three adult randomized controlled trials (RCT) on bicarbonate administration versus no bicarbonate in DKA. We observed a marked heterogeneity in pH threshold, concentration, amount, and timing for bicarbonate administration in various studies. Two RCTs demonstrated transient improvement in metabolic acidosis with bicarbonate treatment within the initial 2 hours. There was no evidence of improved glycemic control or clinical efficacy. There was retrospective evidence of increased risk for cerebral edema and prolonged hospitalization in children who received bicarbonate, and weak evidence of transient paradoxical worsening of ketosis, and increased need for potassium supplementation. No studies involved patients with an initial pH < 6.85.

Conclusions
The evidence to date does not justify the administration of bicarbonate for the emergent treatment of DKA, especially in the pediatric population, in view of possible clinical harm and lack of sustained benefits.