bluuebunny/crossref_metadata_2025_split huggingface dataset:
GATA3 is a master regulator of the transcriptional response to low-dose ionizing radiation in human keratinocytes
Authors: Bonin Florian , Molina Manuella , Malet Claude , Ginestet Chantal , Berthier-Vergnes Odile , Martin Michèle T , Lamartine Jérôme 
Published: September 2009

Abstract

Background
The general population is constantly exposed to low levels of radiation through natural, occupational or medical irradiation. Even if the biological effects of low-level radiation have been intensely debated and investigated, the molecular mechanisms underlying the cellular response to low doses remain largely unknown.

Results
The present study investigated the role of GATA3 protein in the control of the cellular and molecular response of human keratinocytes exposed to a 1 cGy dose of X-rays. Chromatin immunoprecipitation showed GATA3 to be able to bind the promoter of 4 genes responding to a 1 cGy exposure. To go further into the role of GATA3 after ionizing radiation exposure, we studied the cellular and molecular consequences of radiation in GATA3 knock-down cells. Knock-down was obtained by lentiviral-mediated expression of an shRNA targeting the GATA3 transcript in differentiated keratinocytes. First, radiosensitivity was assessed: the toxicity, in terms of immediate survival (with XTT test), associated with 1 cGy radiation was found to be increased in GATA3 knock-down cells. The impact of GATA3 knock-down on the transcriptome of X-ray irradiated cells was also investigated, using oligonucleotide microarrays to assess changes between 3 h and 72 h post-irradiation in normal vs GATA3 knock-down backgrounds; transcriptome response was found to be completely altered in GATA3 knock-down cells, with a strong induction/repression peak 48 h after irradiation. Functional annotation revealed enrichment in genes known to be involved in chaperone activity, TGFβ signalling and stress response.

Conclusion
Taken together, these data indicate that GATA3 is an important regulator of the cellular and molecular response of epidermal cells to very low doses of radiation.
Susceptibility of Pediococcus isolates to antimicrobial compounds in relation to hop-resistance and beer-spoilage
Authors: Haakensen Monique , Vickers David M , Ziola Barry 
Published: September 2009

Abstract

Background
Though important in the context of food microbiology and as potential pathogens in immuno-compromised humans, bacterial isolates belonging to the genus Pediococcus are best known for their association with contamination of ethanol fermentation processes (beer, wine, or fuel ethanol). Use of antimicrobial compounds (e.g., hop-compounds, Penicillin) by some industries to combat Pediococcus contaminants is long-standing, yet knowledge about the resistance of pediococci to antimicrobial agents is minimal. Here we examined Pediococcus isolates to determine whether antibiotic resistance is associated with resistance to hops, presence of genes known to correlate with beer spoilage, or with ability to grow in beer.

Results
Lactic acid bacteria susceptibility test broth medium (LSM) used in combination with commercially available GPN3F antimicrobial susceptibility plates was an effective method for assessing antimicrobial susceptibility of Pediococcus isolates. We report the finding of Vancomycin-susceptible Pediococcus isolates from four species. Interestingly, we found that hop-resistant, beer-spoilage, and beer-spoilage gene-harbouring isolates had a tendency to be more susceptible, rather than more resistant, to antimicrobial compounds.

Conclusion
Our findings indicate that the mechanisms involved in conferring hop-resistance or ability to spoil beer by Pediococcus isolates are not associated with resistance to antibiotics commonly used for treatment of human infections. Also, Vancomycin-resistance was found to be isolate-specific and not intrinsic to the genus as previously believed.
Ontogeny of ATP hydrolysis and isoform expression of the Plasma Membrane Ca2+-ATPase in mouse brain
Authors: Marcos Daniel , Sepulveda M Rosario , Berrocal María , Mata Ana M 
Published: September 2009

Abstract

Background
Plasma membrane Ca2+-ATPases (PMCAs) are high affinity Ca2+ transporters actively involved in intracellular Ca2+ homeostasis. Considering the critical role of Ca2+ signalling in neuronal development and plasticity, we have analyzed PMCA-mediated Ca2+-ATPase activity and PMCA-isoform content in membranes from mouse cortex, hippocampus and cerebellum during postnatal development.

Results
PMCA activity was detected from birth, with a faster evolution in cortex than in hippocampus and cerebellum. Western blots revealed the presence of the four isoforms in all regions, with similar increase in their expression patterns as those seen for the activity profile. Immunohistochemistry assays in cortex and hippocampus showed co-expression of all isoforms in the neuropil associated with synapses and in the plasma membrane of pyramidal cells soma, while cerebellum showed a more isoform-specific distribution pattern in Purkinje cells.

Conclusion
These results show an upregulation of PMCA activity and PMCA isoforms expression during brain development in mouse, with specific localizations mainly in cerebellum. Overall, our findings support a close relationship between the ontogeny of PMCA isoforms and specific requirements of Ca2+ during development of different brain areas.
Cripto-1 overexpression is involved in the tumorigenesis of nasopharyngeal carcinoma
Authors: Wu Zhengrong , Li Gang , Wu Lirong , Weng Desheng , Li Xiangping , Yao Kaitai 
Published: September 2009

Abstract

Background
Human Cripto-1, a member of the EGF-CFC family, is indispensable for early embryonic development. Cripto-1 plays an important oncogenic role during tumorigenesis and is overexpressed in a wide range of epithelial carcinomas, yet little is known about Cripto-1 in nasopharyngeal carcinoma (NPC). The aim of this study was to analyze the roles of Cripto-1 in the progression and clinical characteristics in NPC clinical samples and cell lines.

Methods
The expression of Cripto-1 at mRNA level was detected by the reverse transcription-polymerase chain reaction (RT-PCR) and real time RT-PCR, and western blot was used to examine the protein expression. Cripto-1 expression and its clinical characteristics were investigated by performing immunohistochemical analysis on a total of 37 NPC clinical tissue samples. Lentiviral vectors were constructed to get an efficient expression of anti-Cripto-1 siRNA in CNE-2 and C666-1 cells, with invalid RNAi sequence as control. After the inhibition of the endogenous Cripto-1, the growth, cell cycle and invasion of cells were detected by MTT, FACS and Boyden chamber assay respectively. Moreover, in vivo, the proliferation of the tumor cells was evaluated in xenotransplant nude mice model with whole-body visualizing instrument.

Results
The results of real-time RT-PCR and western blot showed that the expression level of Cripto-1 was markedly higher in NPC cell lines than that in the immortalized nasopharyngeal epithelial cell at both mRNA and protein levels. RT-PCR of 17 NPC tissues showed a high expression rate in 76.5% (13/17) cases. In an immunohistochemical study, Cripto-1 was found to express in 54.1% (20/37) cases of NPC. In addition, Cripto-1 overexpression was significantly associated with N classification (p = 0.034), distant metastasis (p = 0.036), and clinical stage (p = 0.007). Inhibition of endogenous Cripto-1 by lentivirus-mediated RNAi silencing technique suppressed NPC cell growth and invasion in vitro. In vivo, the average weight (p = 0.026) and volume (p = 0.044) of tumor in CNE-2/GFP+/Cripto-1- xenotransplant mice group were significantly lower than those in the control group. The Ki67 index was obviously lower in Cripto-1 RNAi treated tumors (p < 0.01).

Conclusion
Data of this study suggest that Cripto-1 overexpression is connected with the tumorigenesis and progression of NPC, lentivector-mediated RNAi might be feasible for the inhibition of the growth and invasion of NPC.
Par-3 partitioning defective 3 homolog (C. elegans) and androgen-induced prostate proliferative shutoff associated protein genes are mutationally inactivated in prostate cancer cells
Authors: Kunnev Dimiter , Ivanov Igor , Ionov Yurij 
Published: September 2009

Abstract

Background
Gene identification by nonsense-mediated mRNA decay inhibition (GINI) has proven its usefulness in identifying mutant genes in cancer cell lines. An increase in transcription in response to NMD inhibition of a subset of genes is a major cause of false positives when genes are selected for sequencing analysis. To distinguish between mRNA accumulations caused by stress response-induced transcription and nonsense-containing mRNA stabilizations is a challenge in identifying mutant genes using GINI.

Methods
To identify potential tumor-suppressor genes mutated in prostate cancer cell lines, we applied a version of GINI that involves inhibition of NMD in two steps. In the first step, NMD is inhibited in duplicate tissue-culture plates. During this step, both the substrate for NMD and stress-response mRNA transcripts are accumulated in cells. In the second step, transcription is inhibited in both plates and NMD is inhibited in one plate and released in the second plate. Microarray analysis of gene-expression profiles in both plates after the second step detects only the differences in mRNA degradation but not in mRNA accumulation.

Results
Analyzing gene expression profile alterations in 22RV1 and LNCaP prostate cancer cells following NMD inhibition we selected candidates for sequencing analysis in both cell lines. Sequencing identified inactivating mutations in both alleles of the PARD3 and AS3 genes in the LNCaP and 22RV1 cells, respectively. Introduction of a wild-type PARD3 cDNA into the LNCaP cells resulted in a higher proliferation rate in tissue culture, a higher adhesion of LNCaP cells to the components of extracellular matrix and impaired the growth of the LNCaP cells in soft agar and in a three-dimensional cell-culture.

Conclusion
The mutational inactivation in a prostate cancer cell line of the PARD3 gene involved in asymmetric cell division and maintenance of cell-polarity suggests that the loss of cell-polarity contributes to prostate carcinogenesis.
A systematic review of the international published literature relating to quality of institutional care for people with longer term mental health problems
Authors: Taylor Tatiana L , Killaspy Helen , Wright Christine , Turton Penny , White Sarah , Kallert Thomas W , Schuster Mirjam , Cervilla Jorge A , Brangier Paulette , Raboch Jiri , Kališová Lucie , Onchev Georgi , Dimitrov Hristo , Mezzina Roberto , Wolf Kinou , Wiersma Durk , Visser Ellen , Kiejna Andrzej , Piotrowski Patryk , Ploumpidis Dimitri , Gonidakis Fragiskos , Caldas-de-Almeida José , Cardoso Graça , King Michael B 
Published: September 2009

AbstractBackgroundA proportion of people with mental health problems require longer term care in a psychiatric or social care institution. However, there are no internationally agreed quality standards for institutional care and no method to assess common care standards across countries.We aimed to identify the key components of institutional care for people with longer term mental health problems and the effectiveness of these components.MethodsWe undertook a systematic review of the literature using comprehensive search terms in 11 electronic databases and identified 12,182 titles. We viewed 550 abstracts, reviewed 223 papers and included 110 of these. A "critical interpretative synthesis" of the evidence was used to identify domains of institutional care that are key to service users' recovery.ResultsWe identified eight domains of institutional care that were key to service users' recovery: living conditions; interventions for schizophrenia; physical health; restraint and seclusion; staff training and support; therapeutic relationship; autonomy and service user involvement; and clinical governance. Evidence was strongest for specific interventions for the treatment of schizophrenia (family psychoeducation, cognitive behavioural therapy (CBT) and vocational rehabilitation).ConclusionInstitutions should, ideally, be community based, operate a flexible regime, maintain a low density of residents and maximise residents' privacy. For service users with a diagnosis of schizophrenia, specific interventions (CBT, family interventions involving psychoeducation, and supported employment) should be provided through integrated programmes. Restraint and seclusion should be avoided wherever possible and staff should have adequate training in de-escalation techniques. Regular staff supervision should be provided and this should support service user involvement in decision making and positive therapeutic relationships between staff and service users. There should be clear lines of clinical governance that ensure adherence to evidence-based guidelines and attention should be paid to service users' physical health through regular screening.
Laparoscopic versus open left lateral segmentectomy
Authors: Carswell Kirstin A , Sagias Filippos G , Murgatroyd Beth , Rela Mohamed , Heaton Nigel , Patel Ameet G 
Published: September 2009

Abstract

Background
Laparoscopic liver surgery is becoming increasingly common. This cohort study was designed to directly compare perioperative outcomes of the left lateral segmentectomy via laparoscopic and open approach.

Methods
Between 2002 and 2006 43 left lateral segmentectomies were performed at King's College Hospital. Those excluded from analysis included previous liver resections, polycystic liver disease, liver cirrhosis and synchronous operations. Of 20 patients analysed, laparoscopic (n = 10) were compared with open left lateral segmentectomy (n = 10). Both groups had similar patient characteristics.

Results
Morbidity rates were similar with no wound or chest infection in either group. The conversion rate was 10% (1/10). There was no difference in operating time between the groups (median time 220 minutes versus 179 minutes, p = 0.315). Surgical margins for all lesions were clear. Less postoperative opiate analgesics were required in the laparoscopic group (median 2 days versus 5 days, p = 0.005). The median postoperative in-hospital stay was less in the laparoscopic group (6 days vs 9 days, p = 0.005). There was no mortality.

Conclusion
Laparoscopic left lateral segmentectomy is safe and feasible. Laparoscopic patients may benefit from requiring less postoperative opiate analgesia and a shorter post-operative in-hospital stay.
The proprotein convertase PC5/6 is protective against intestinal tumorigenesis: in vivo mouse model
Authors: Sun Xiaowei , Essalmani Rachid , Seidah Nabil G , Prat Annik 
Published: September 2009

Abstract

Background
The secretory basic amino acid-specific proprotein convertases (PCs) have often been associated with cancer/metastasis. By controlling the cleavage of cancer-associated proteins, PCs play key roles in multiple steps of cancer development. Most analyses of the implication of PCs in cancer/metastasis relied on the use of in vitro overexpression systems or inhibitors that can affect more than one PC. Aside from the role of furin in salivary gland tumorigenesis, no other in vivo genetic model of PC-knockout was reported in relation to cancer development.

Results
Since PC5/6 is highly expressed in the small intestine, the present study examined its in vivo role in intestinal tumorigenesis. Analysis of human intestinal tumors at various stages showed a systematic down-regulation of PC5/6 expression. Since gene inactivation of PC5/6 leads to lethality at birth, we generated mice lacking PC5/6 in enterocytes and analyzed the impact of the presence or absence of this PC in the mouse Apc

Min/+model that develops numerous adenocarcinomas along the intestinal tract. This resulted in viable mice with almost no expression of PC5/6 in small intestine, but with no overt phenotype. The data showed that by themselves Apc

Min/+tumors express lower levels of PC5/6 mRNA, and that the lack of PC5/6 in enterocytes results in a significantly higher tumor number in the duodenum, with a similar trend in other intestinal segments. Finally, the absence of PC5/6 is also associated with a premature mortality of Apc

Min/+mice.

Conclusion
Overall, these data suggest that intestinal PC5/6 is protective towards tumorigenesis, especially in mouse duodenum, and possibly in human colon.
Function, regulation and pathological roles of the Gab/DOS docking proteins
Authors: Wöhrle Franziska U , Daly Roger J , Brummer Tilman 
Published: September 2009

AbstractSince their discovery a little more than a decade ago, the docking proteins of the Gab/DOS family have emerged as important signalling elements in metazoans. Gab/DOS proteins integrate and amplify signals from a wide variety of sources including growth factor, cytokine and antigen receptors as well as cell adhesion molecules. They also contribute to signal diversification by channelling the information from activated receptors into signalling pathways with distinct biological functions. Recent approaches in protein biochemistry and systems biology have revealed that Gab proteins are subject to complex regulation by feed-forward and feedback phosphorylation events as well as protein-protein interactions. Thus, Gab/DOS docking proteins are at the centre of entire signalling subsystems and fulfil an important if not essential role in many physiological processes. Furthermore, aberrant signalling by Gab proteins has been increasingly linked to human diseases from various forms of neoplasia to Alzheimer's disease.In this review, we provide a detailed overview of the structure, effector functions, regulation and evolution of the Gab/DOS family. We also summarize recent findings implicating Gab proteins, in particular the Gab2 isoform, in leukaemia, solid tumours and other human diseases.
Sponge budding is a spatiotemporal morphological patterning process: Insights from synchrotron radiation-based x-ray microtomography into the asexual reproduction of Tethya wilhelma
Authors: Hammel Jörg U , Herzen Julia , Beckmann Felix , Nickel Michael 
Published: September 2009

Abstract

Background
Primary agametic-asexual reproduction mechanisms such as budding and fission are present in all non-bilaterian and many bilaterian animal taxa and are likely to be metazoan ground pattern characters. Cnidarians display highly organized and regulated budding processes. In contrast, budding in poriferans was thought to be less specific and related to the general ability of this group to reorganize their tissues. Here we test the hypothesis of morphological pattern formation during sponge budding.

Results
We investigated the budding process in Tethya wilhelma (Demospongiae) by applying 3D morphometrics to high resolution synchrotron radiation-based x-ray microtomography (SR-μCT) image data. We followed the morphogenesis of characteristic body structures and identified distinct morphological states which indeed reveal characteristic spatiotemporal morphological patterns in sponge bud development. We discovered the distribution of skeletal elements, canal system and sponge tissue to be based on a sequential series of distinct morphological states. Based on morphometric data we defined four typical bud stages. Once they have reached the final stage buds are released as fully functional juvenile sponges which are morphologically and functionally equivalent to adult specimens.

Conclusion
Our results demonstrate that budding in demosponges is considerably more highly organized and regulated than previously assumed. Morphological pattern formation in asexual reproduction with underlying genetic regulation seems to have evolved early in metazoans and was likely part of the developmental program of the last common ancestor of all Metazoa (LCAM).
Measles Resurgence Associated with Continued Circulation of Genotype H1 Viruses in China, 2005
Authors: Ji Yixin , Zhang Yan , Xu Songtao , Zhu Zhen , Zuo Shuyan , Jiang Xiaohong , Lu Peishan , Wang Changyin , Liang Yong , Zheng Huanying , Liu Yang , Mao Naiying , Liang Xiaofeng , Featherstone David Alexander , Rota Paul A , Bellini William J , Xu Wenbo 
Published: September 2009

Abstract
Measles morbidity and mortality decreased significantly after measles vaccine was introduced into China in 1965. From 1995 to 2004, average annual measles incidence decreased to 5.6 cases per 100,000 population following the establishment of a national two-dose regimen. Molecular characterization of wild-type measles viruses demonstrated that genotype H1 was endemic and widely distributed throughout the country in China during 1995-2004. A total of 124,865 cases and 55 deaths were reported from the National Notifiable Diseases Reporting System (NNDRS) in 2005, which represented a 69.05% increase compared with 2004. Over 16,000 serum samples obtained from 914 measles outbreaks and the measles IgM positive rate was 81%. 213 wild-type measles viruses were isolated from 18 of 31 provinces in China during 2005, and all of the isolates belonged to genotype H1. The ranges of the nucleotide sequence and predicted amino acid sequence homologies of the 213 genotype H1 strains were 93.4%-100% and 90.0%-100%, respectively. H1-associated cases and outbreaks caused the measles resurgence in China in 2005. H1 genotype has the most inner variation within genotype, it could be divided into 2 clusters, and cluster 1 viruses were predominant in China throughout 2005.
Recombinant Adeno-Associated Virus Serotype 6 (rAAV2/6)-Mediated Gene Transfer to Nociceptive Neurons through Different Routes of Delivery
Authors: Towne Chris , Pertin Marie , Beggah Ahmed T , Aebischer Patrick , Decosterd Isabelle 
Published: September 2009

Background Gene transfer to nociceptive neurons of the dorsal root ganglia (DRG) is a promising approach to dissect mechanisms of pain in rodents and is a potential therapeutic strategy for the treatment of persistent pain disorders such as neuropathic pain. A number of studies have demonstrated transduction of DRG neurons using herpes simplex virus, adenovirus and more recently, adeno-associated virus (AAV). Recombinant AAV are currently the gene transfer vehicles of choice for the nervous system and have several advantages over other vectors, including stable and safe gene expression. We have explored the capacity of recombinant AAV serotype 6 (rAAV2/6) to deliver genes to DRG neurons and characterized the transduction of nociceptors through five different routes of administration in mice. Results Direct injection of rAAV2/6 expressing green fluorescent protein (eGFP) into the sciatic nerve resulted in transduction of up to 30% eGFP-positive cells of L4 DRG neurons in a dose dependant manner. More than 90% of transduced cells were small and medium sized neurons (< 700 μm2), predominantly colocalized with markers of nociceptive neurons, and had eGFP-positive central terminal fibers in the superficial lamina of the spinal cord dorsal horn. The efficiency and profile of transduction was independent of mouse genetic background. Intrathecal administration of rAAV2/6 gave the highest level of transduction (≈ 60%) and had a similar size profile and colocalization with nociceptive neurons. Intrathecal administration also transduced DRG neurons at cervical and thoracic levels and resulted in comparable levels of transduction in a mouse model for neuropathic pain. Subcutaneous and intramuscular delivery resulted in low levels of transduction in the L4 DRG. Likewise, delivery via tail vein injection resulted in relatively few eGFP-positive cells within the DRG, however, this transduction was observed at all vertebral levels and corresponded to large non-nociceptive cell types. Conclusion We have found that rAAV2/6 is an efficient vector to deliver transgenes to nociceptive neurons in mice. Furthermore, the characterization of the transduction profile may facilitate gene transfer studies to dissect mechanisms behind neuropathic pain.