bluuebunny/crossref_metadata_2025_split huggingface dataset:
TGF-β receptor II in epitheliaversusmesenchyme plays distinct roles in the developing lung
Authors: Chen H. , Zhuang F. , Liu Y-H. , Xu B. , del Moral P. , Deng W. , Chai Y. , Kolb M. , Gauldie J. , Warburton D. , Moses H. L. , Shi W. 
Published: March 2008

Transforming growth factor (TGF)-β signalling plays important roles in regulating lung development. However, the specific regulatory functions of TGF-β signalling in developing lung epithelialversusmesenchymal cells are still unknown.By immunostaining, the expression pattern of the TGF-β type II receptor (TβRII) was first determined in the developing mouse lung. The functions of TβRII in developing lung were then determined by conditionally knocking out TβRII in the lung epithelium of floxed-TβRII/surfactant protein C-reverse tetracycline transactivator/TetO-Cre miceversusmesenchyme of floxed-TβRII/Dermo1-Cre mice.TβRII was expressed only in distal airway epithelium at early gestation (embryonic day (E)11.5), but in both airway epithelium and mesenchyme from mid-gestation (E14.5) to post-natal day 14. Abrogation of TβRII in mouse lung epithelium resulted in retardation of post-natal lung alveolarisation, with markedly decreased type I alveolar epithelial cells, while no abnormality in prenatal lung development was observed. In contrast, blockade of TβRII in mesoderm-derived tissues, including lung mesenchyme, resulted in mildly abnormal lung branching and reduced cell proliferation after mid-gestation, accompanied by multiple defects in other organs, including diaphragmatic hernia. The primary lung branching defect was verified in embryonic lung explant culture.The novel findings of the present study suggest that transforming growth factor-β type II receptor-mediated transforming growth factor-β signalling plays distinct roles in lung epitheliumversusmesenchyme to differentially control specific stages of lung development.
Identification of transcripts overexpressed during airway epithelium differentiation
Authors: Chhin B. , Pham J. T. , El Zein L. , Kaiser K. , Merrot O. , Bouvagnet P. 
Published: March 2008

Human airway epithelium, the defence at the forefront of protecting the respiratory tract, evacuates inhaled particles by a permanent beating of epithelial cell cilia. When deficient, this organelle causes primary ciliary dyskinesia, and, despite numerous studies, data regarding ciliated cell gene expression remain incomplete. The aim of the present study was to identify genes specifically expressed in human ciliated respiratory cellsviatranscriptional analysis.The transcriptome of dedifferentiated epithelial cells was subtracted from that of fully redifferentiated cells using complementary DNA representational difference analysis. In order to validate the results, gene overexpression in ciliated cells was confirmed by real-time PCR, and by comparing the present list of genes overexpressed in ciliated cells to lists obtained in previous studies.A total of 53 known and 12 unknown genes overexpressed in ciliated cells were identified. The majority (66%) of known genes had never previously been reported as being involved in ciliogenesis, and the unknown genes represent hypothetical novel transcript isoforms or new genes not yet reported in databases. Finally, several genes identified here were located in genomic regions involved in primary ciliary dyskinesia by linkage analysis.In conclusion, the present study revealed sequences of new cilia-related genes, new transcript isoforms and novel genes which should be further characterised to aid understanding of their function(s) and their probable disorder-related involvement.
Neutrophil degranulation mediates severe lung damage triggered by streptococcal M1 protein
Authors: Soehnlein O. , Oehmcke S. , X  , Rothfuchs A. G. , Frithiof R. , van Rooijen N. , Mörgelin M. , Herwald H. , Lindbom L. 
Published: March 2008

Streptococcus pyogenesof the M1 serotype can cause streptococcal toxic shock syndrome commonly associated with acute lung injury. The aim of the present study was to investigate the role of neutrophils and their secretion products in M1 protein-induced lung damage.The degranulation of neutrophils by M1 protein was studied in whole blood using marker analysis for individual granule subsets. In mice, M1 protein was injected intravenously and the lung damage was assessed by histology, electron microscopy, cell count in bronchoalveolar lavage fluid and analysis of lung vascular permeability. Comparisons were made in mice with intact white blood count, neutropenic mice and neutropenic mice injected with the secretion of activated neutrophils.In whole blood, M1 protein forms complexes with fibrinogen that bind to β2-integrins on the neutrophil surface, resulting in degranulation of all four subsets of neutrophil granules. Intravenous injection of M1 protein into mice induced neutrophil accumulation in the lung, increase in vascular permeability and acute lung damage. Depletion of neutrophils from the circulation completely abrogated lung injury and vascular leakage. Interestingly, the lung damage was restored by injecting neutrophil secretion.The present data suggest that neutrophil granule proteins are directly responsible for lung damage induced by the streptococcal M1 protein.
Association of SAP130/SF3b-3 with Cullin-RING ubiquitin ligase complexes and its regulation by the COP9 signalosome
Authors: Menon Suchithra , Tsuge Tomohiko , Dohmae Naoshi , Takio Koji , Wei Ning 
Published: March 2008

Abstract

Background
Cullin-RING ubiquitin E3 ligases (CRLs) are regulated by modification of an ubiquitin-like protein, Nedd8 (also known as Rub1) on the cullin subunit. Neddylation is shown to facilitate E3 complex assembly; while un-neddylated cullins are bound by CAND1 that prevents recruitment of the substrates. The level of Nedd8 modification is critically dependent on the COP9 signalosome (CSN), an eight-subunit protein complex containing Nedd8 isopeptidase activity.

Results
We report isolation of SAP130 (SF3b-3) as a CSN1 interacting protein. SAP130 is homologous to DDB1, and is a component of SF3b RNA splicing complex and STAGA/TFTC transcription complexes, but its specific function within these complexes is unknown. We show that SAP130 can interact with a variety of cullin proteins. It forms tertiary complexes with fully assembled CRL E3 complexes such as SCFSkp2, Elongin B/C -Cul2- VHL and Cul4-DDB complex by binding to both N-terminal and C-terminal domain of cullins. SAP130 preferentially associates with neddylated cullins in vivo. However knock-down of CAND1 abolished this preference and increased association of SAP130 with Cul2. Furthermore, we provide evidence that CSN regulates SAP130-Cul2 interaction and SAP130-associated polyubiquitinating activity.

Conclusion
SAP130 is a cullin binding protein that is likely involved in the Nedd8 pathway. The association of SAP130 with various cullin member proteins such as Cul1, Cul2 and Cul4A is modulated by CAND1 and CSN. As an established component of transcription and RNA processing complexes, we hypothesis that SAP130 may link CRL mediated ubiquitination to gene expression.
Analysis of four achaete-scute homologs in Bombyx mori reveals new viewpoints of the evolution and functions of this gene family
Authors: Zhou Qingxiang , Zhang Tianyi , Xu Weihua , Yu Linlin , Yi Yongzhu , Zhang Zhifang 
Published: March 2008

AbstractBackgroundachaete-scutecomplexe (AS-C) has been widely studied at genetic, developmental and evolutional levels. Genes of this family encode proteins containing a highly conserved bHLH domain, which take part in the regulation of the development of central nervous system and peripheral nervous system. ManyAS-Chomologs have been isolated from various vertebrates and invertebrates. Also,AS-Cgenes are duplicated during the evolution of Diptera. Functions besides neural development controlling have also been found inDrosophila AS-Cgenes.ResultsWe cloned fourachaete-scutehomologs (ASH) from the lepidopteran model organismBombyx mori, including three proneural genes and one neural precursor gene. Proteins encoded by them contained the characteristic bHLH domain and the three proneural ones were also found to have the C-terminal conserved motif. These genes regulated promoter activity through the Class A E-boxesin vitro. Though bothBm-ASHandDrosophila AS-Chave four members, they are not in one by one corresponding relationships. Results of RT-PCR and real-time PCR showed thatBm-ASHgenes were expressed in different larval tissues, and had well-regulated expressional profiles during the development of embryo and wing/wing disc.ConclusionThere are fourachaete-scutehomologs inBombyx mori, the second insect having fourAS-Cgenes so far, and these genes have multiple functions in silkworm life cycle.AS-Cgene duplication in insects occurs after or parallel to, but not before the taxonomic order formation during evolution.
Transcriptome analysis of grain development in hexaploid wheat
Authors: Wan Yongfang , Poole Rebecca L , Huttly Alison K , Toscano-Underwood Claudia , Feeney Kevin , Welham Sue , Gooding Mike J , Mills Clare , Edwards Keith J , Shewry Peter R , Mitchell Rowan AC 
Published: March 2008

Abstract

Background
Hexaploid wheat is one of the most important cereal crops for human nutrition. Molecular understanding of the biology of the developing grain will assist the improvement of yield and quality traits for different environments. High quality transcriptomics is a powerful method to increase this understanding.

Results
The transcriptome of developing caryopses from hexaploid wheat (Triticum aestivum, cv. Hereward) was determined using Affymetrix wheat GeneChip® oligonucleotide arrays which have probes for 55,052 transcripts. Of these, 14,550 showed significant differential regulation in the period between 6 and 42 days after anthesis (daa). Large changes in transcript abundance were observed which were categorised into distinct phases of differentiation (6–10 daa), grain fill (12–21 daa) and desiccation/maturation (28–42 daa) and were associated with specific tissues and processes. A similar experiment on developing caryopses grown with dry and/or hot environmental treatments was also analysed, using the profiles established in the first experiment to show that most environmental treatment effects on transcription were due to acceleration of development, but that a few transcripts were specifically affected. Transcript abundance profiles in both experiments for nine selected known and putative wheat transcription factors were independently confirmed by real time RT-PCR. These expression profiles confirm or extend our knowledge of the roles of the known transcription factors and suggest roles for the unknown ones.

Conclusion
This transcriptome data will provide a valuable resource for molecular studies on wheat grain. It has been demonstrated how it can be used to distinguish general developmental shifts from specific effects of treatments on gene expression and to diagnose the probable tissue specificity and role of transcription factors.
The Innate Immune Database (IIDB)
Authors: Korb Martin , Rust Alistair G , Thorsson Vesteinn , Battail Christophe , Li Bin , Hwang Daehee , Kennedy Kathleen A , Roach Jared C , Rosenberger Carrie M , Gilchrist Mark , Zak Daniel , Johnson Carrie , Marzolf Bruz , Aderem Alan , Shmulevich Ilya , Bolouri Hamid 
Published: March 2008

Abstract

Background
As part of a National Institute of Allergy and Infectious Diseases funded collaborative project, we have performed over 150 microarray experiments measuring the response of C57/BL6 mouse bone marrow macrophages to toll-like receptor stimuli. These microarray expression profiles are available freely from our project web site http://www.innateImmunity-systemsbiology.org. Here, we report the development of a database of computationally predicted transcription factor binding sites and related genomic features for a set of over 2000 murine immune genes of interest. Our database, which includes microarray co-expression clusters and a host of web-based query, analysis and visualization facilities, is available freely via the internet. It provides a broad resource to the research community, and a stepping stone towards the delineation of the network of transcriptional regulatory interactions underlying the integrated response of macrophages to pathogens.

Description
We constructed a database indexed on genes and annotations of the immediate surrounding genomic regions. To facilitate both gene-specific and systems biology oriented research, our database provides the means to analyze individual genes or an entire genomic locus. Although our focus to-date has been on mammalian toll-like receptor signaling pathways, our database structure is not limited to this subject, and is intended to be broadly applicable to immunology. By focusing on selected immune-active genes, we were able to perform computationally intensive expression and sequence analyses that would currently be prohibitive if applied to the entire genome. Using six complementary computational algorithms and methodologies, we identified transcription factor binding sites based on the Position Weight Matrices available in TRANSFAC. For one example transcription factor (ATF3) for which experimental data is available, over 50% of our predicted binding sites coincide with genome-wide chromatin immnuopreciptation (ChIP-chip) results. Our database can be interrogated via a web interface. Genomic annotations and binding site predictions can be automatically viewed with a customized version of the Argo genome browser.

Conclusion
We present the Innate Immune Database (IIDB) as a community resource for immunologists interested in gene regulatory systems underlying innate responses to pathogens. The database website can be freely accessed at http://db.systemsbiology.net/IIDB.
C4B null alleles are not associated with genetic polymorphisms in the adjacent gene CYP21A2in autism
Authors: Sweeten Thayne L , Odell Daniel W , Odell J Dennis , Torres Anthony R 
Published: March 2008

Abstract

Background
Research indicates that the etiology of autism has a strong genetic component, yet so far the search for genes that contribute to the disorder, including several whole genome scans, has led to few consistent findings. However, three studies indicate that the complement C4B gene null allele (i.e. the missing or nonfunctional C4B gene) is significantly more frequent in individuals with autism. Due to the close proximity of the CYP21A2 gene to the C4B locus (3 kb) it was decided to examine samples from autistic subjects, including many with known C4B null alleles for common CYP21A2 mutations.

Methods
Samples from subjects diagnosed with autism and non-autistic controls (controls) previously typed for C4B null alleles were studied. Allele specific polymerase chain reaction (PCR) methods were used to determine 8 of the most common CYP21A2 genetic mutations, known to completely or partially inhibit 21-hydroxylase, the enzyme encoded by the CYP21A2 gene.

Results
Although the combined autism and control study subjects had 50 C4B null alleles only 15 CYP21A2 mutations were detected in over 2250 genotypes. Eight mutations were detected in the autistic samples and 7 in the controls. The frequency of CYP21A2 mutations was similar between the autism and control samples. Only one individual (autistic) carried a chromosome containing both C4B null allele and CYP21A2 mutations.
Comparison of different real-time PCR chemistries and their suitability for detection and quantification of genetically modified organisms
Authors: Buh Gašparič Meti , Cankar Katarina , Žel Jana , Gruden Kristina 
Published: March 2008

Abstract

Background
The real-time polymerase chain reaction is currently the method of choice for quantifying nucleic acids in different DNA based quantification applications. It is widely used also for detecting and quantifying genetically modified components in food and feed, predominantly employing TaqMan® and SYBR® Green real-time PCR chemistries. In our study four alternative chemistries: Lux™, Plexor™, Cycling Probe Technology and LNA® were extensively evaluated and compared using TaqMan® chemistry as a reference system.

Results
Amplicons were designed on the maize invertase gene and the 5'-junction of inserted transgene and plant genomic DNA in MON 810 event. Real-time assays were subsequently compared for their efficiency in PCR amplification, limits of detection and quantification, repeatability and accuracy to test the performance of the assays. Additionally, the specificity of established assays was checked on various transgenic and non-transgenic plant species. The overall applicability of the designed assays was evaluated, adding practicability and costs issues to the performance characteristics.

Conclusion
Although none of the chemistries significantly outperformed the others, there are certain characteristics that suggest that LNA® technology is an alternative to TaqMan® when designing assays for quantitative analysis. Because LNA® probes are much shorter they might be especially appropriate when high specificity is required and where the design of a common TaqMan® probe is difficult or even impossible due to sequence characteristics. Plexor™ on the other hand might be a method of choice for qualitative analysis when sensitivity, low cost and simplicity of use prevail.
Lymphangiogenesis and lymph node metastasis in breast cancer
Authors: Cunnick Giles H , Jiang Wen G , Douglas-Jones Tony , Watkins Gareth , Gomez Kelvin F , Morgan Mike J , Subramanian Ashok , Mokbel Kefah , Mansel Robert E 
Published: March 2008

Abstract

Introduction
There have been few studies on lymphangiogenesis in the past due to the lack of specific lymphatic endothelial markers, and lymphatic-specific growth factors. Recently, these limitations have been relieved by the discovery of a small number of potential lymphatic-specific markers. The relationship between lymphangiogenesis and regional or distant metastasis has not previously been investigated in humans. Using these lymphatic markers, it is possible to explore the relationship between lymphangiogenesis and tumour metastasis. This study indirectly quantified lymphangiogenesis by measuring mRNA expression of all seven lymphatic markers described above in breast cancers and correlated these markers with lymphatic involvement and survival.
The cDNA from 153 frozen archived breast samples were analysed with Q-PCR for all seven lymphangiogenic markers. This was correlated with various prognostic factors as well as patient survival.

Results
There was significantly greater expression of all 7 markers in malignant compared to benign breast tissue. In addition, there was greater expression in lymph node positive/grade 3 tumours when compared to lymph node negative/grade 1 tumours. In 5 of the markers, there was a greater expression in poor NPI prognostic tumours when compared to favourable prognostic tumours which was not statistically significant. There was no association between recurrence risk and lymphangiogenic marker expression.

Conclusion
In summary, the findings from this study show that lymphangiogenesis, measured by specific lymphatic marker expression, is higher in breast cancers than in normal breast tissue. Secondly, breast cancers which have metastasised to the regional lymphatics show higher expression compared to those which have not, although the individual differences for all five markers were not statistically significant.
Hospital Anxiety and Depression Scale (HADS): validation in a Greek general hospital sample
Authors: Michopoulos Ioannis , Douzenis Athanasios , Kalkavoura Christina , Christodoulou Christos , Michalopoulou Panayiota , Kalemi Georgia , Fineti Katerina , Patapis Paulos , Protopapas Konstantinos , Lykouras Lefteris 
Published: March 2008

Abstract

Background
The Hospital Anxiety and Depression Scale (HADS) has been used in several languages to assess anxiety and depression in general hospital patients with good results.

Methods
The HADS was administered to 521 participants (275 controls and 246 inpatients and outpatients of the Internal Medicine and Surgical Departments in 'Attikon' General Hospital in Athens). The Beck Depression Inventory (BDI) and the State-Trait Anxiety Inventory (STAI) were used as 'gold standards' for depression and anxiety respectively.

Results
The HADS presented high internal consistency; Cronbach's α cofficient was 0.884 (0.829 for anxiety and 0.840 for depression) and stability (test-retest intraclass correlation coefficient 0.944). Factor analysis showed a two-factor structure. The HADS showed high concurrent validity; the correlations of the scale and its subscales with the BDI and the STAI were high (0.722 – 0.749).

Conclusion
The Greek version of HADS showed good psychometric properties and could serve as a useful tool for clinicians to assess anxiety and depression in general hospital patients.
Non-Hodgkin's lymphoma in a woman with adult-onset Still's disease: a case report
Authors: Otrock Zaher K , Hatoum Hassan A , Uthman Imad W , Taher Ali T , Saab Shahrazad , Shamseddine Ali I 
Published: March 2008

Abstract

Introduction
Adult onset Still's disease is a chronic multisystemic inflammatory disorder characterized by high spiking fever, polyarthralgia and rash. Lymphadenopathy is a prominent feature of adult onset Still's disease and is seen in about 65% of patients. Searching the medical literature using the MEDLINE database from January 1966 through November 2007 we could only find two reported cases of adult onset Still's disease that had progressed to lymphoma.

Case presentation
We describe a woman who was diagnosed with adult onset Still's disease and developed lymphoma 10 months after the onset of her symptoms. She initially presented with fever and arthritis of the knees, ankles and shoulders, along with a nonpruritic skin rash, myalgia and weight loss. On physical examination she was found to have several enlarged anterior cervical lymph nodes and left posterior auricular lymph nodes all of which were non-tender, immobile and rubbery. Excisional biopsy of the cervical lymph nodes was negative for malignancy. Bone marrow biopsy was also negative for malignancy. She was treated with prednisone. She remained in good health until she presented 10 months later with low back pain, dyspnea and weight loss. Work up revealed malignant lymphoma. She was treated with chemotherapy and was doing well until she presented with abdominal pain. Work up revealed a cirrhotic liver and ascites. She then passed away from hepatorenal syndrome 13 years after the diagnosis of lymphoma. To our knowledge, this is the third reported case of such an occurrence.

Conclusion
Although the association between adult onset Still's disease and lymphoma has been rarely reported, careful screening for this malignancy in patients suspected to have adult onset Still's disease is warranted.