bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide analysis of hepatic LRH-1 reveals a promoter binding preference and suggests a role in regulating genes of lipid metabolism in concert with FXR
Authors: Chong Hansook Kim , Biesinger Jacob , Seo Young-Kyo , Xie Xiaohui , Osborne Timothy F 
Published: February 2012

AbstractBackgroundIn a previous genome-wide analysis of FXR binding to hepatic chromatin, we noticed that an extra nuclear receptor (NR) half-site was co-enriched close to the FXR binding IR-1 elements and we provided limited support that the monomeric LRH-1 receptor that binds to NR half-sites might function together with FXR to activate gene expression.ResultsTo analyze the global pattern for LRH-1 binding and to determine whether it might associate with FXR on a whole genome-wide scale, we analyzed LRH-1 binding to the entire hepatic genome using a non-biased genome-wide ChIP-seq approach. We identified over 10,600 LRH-1 binding sites in hepatic chromatin and over 20% were located within 2 kb of the 5' end of a known mouse gene. Additionally, the results demonstrate that a significant fraction of the genome sites occupied by LRH-1 are located close to FXR binding sites revealed in our earlier study. A Gene ontology analysis revealed that genes preferentially enriched in the LRH-1/FXR overlapping gene set are related to lipid metabolism. These results demonstrate that LRH-1 recruits FXR to lipid metabolic genes. A significant fraction of FXR binding peaks also contain a nuclear receptor half-site that does not bind LRH-1 suggesting that additional monomeric nuclear receptors such as RORs and NR4As family members may also target FXR to other pathway selective genes related to other areas of metabolism such as glucose metabolism where FXR has also been shown to play an important role.ConclusionThese results document an important role for LRH-1 in hepatic metabolism through acting predominantly at proximal promoter sites and working in concert with additional nuclear receptors that bind to neighboring sites
Zonation related function and ubiquitination regulation in human hepatocellular carcinoma cells in dynamic vs. static culture conditions
Authors: Cheng Shu , Prot Jean-Matthieu , Leclerc Eric , Bois Frédéric Y 
Published: February 2012

AbstractBackgroundUnderstanding hepatic zonation is important both for liver physiology and pathology. There is currently no effective systemic chemotherapy for human hepatocellular carcinoma (HCC) and its pathogenesis is of special interest. Genomic and proteomic data of HCC cells in different culture models, coupled to pathway-based analysis, can help identify HCC-related gene and pathway dysfunctions.ResultsWe identified zonation-related expression profiles contributing to selective phenotypes of HCC, by integrating relevant experimental observations through gene set enrichment analysis (GSEA). Analysis was based on gene and protein expression data measured on a human HCC cell line (HepG2/C3A) in two culture conditions: dynamic microfluidic biochips and static Petri dishes. Metabolic activity (HCC-related cytochromes P450) and genetic information processing were dominant in the dynamic cultures, in contrast to kinase signaling and cancer-specific profiles in static cultures. That, together with analysis of the published literature, leads us to propose that biochips culture conditions induce a periportal-like hepatocyte phenotype while standard plates cultures are more representative of a perivenous-like phenotype. Both proteomic data and GSEA results further reveal distinct ubiquitin-mediated protein regulation in the two culture conditions.ConclusionsPathways analysis, using gene and protein expression data from two cell culture models, confirmed specific human HCC phenotypes with regard to CYPs and kinases, and revealed a zonation-related pattern of expression. Ubiquitin-mediated regulation mechanism gives plausible explanations of our findings. Altogether, our results suggest that strategies aimed at inhibiting activated kinases and signaling pathways may lead to enhanced metabolism-mediated drug resistance of treated tumors. If that were the case, mitigating inhibition or targeting inactive forms of kinases would be an alternative.
Evaluation of cellular uptake and intracellular trafficking as determining factors of gene expression for amino acid-substituted gemini surfactant-based DNA nanoparticles
Authors: Singh Jagbir , Michel Deborah , Chitanda Jackson M , Verrall Ronald E , Badea Ildiko 
Published: February 2012

Abstract

Background
Gene transfer using non-viral vectors offers a non-immunogenic and safe method of gene delivery. Cellular uptake and intracellular trafficking of the nanoparticles can impact on the transfection efficiency of these vectors. Therefore, understanding the physicochemical properties that may influence the cellular uptake and the intracellular trafficking can aid the design of more efficient non-viral gene delivery systems. Recently, we developed novel amino acid-substituted gemini surfactants that showed higher transfection efficiency than their parent compound. In this study, we evaluated the mechanism of cellular uptake of the plasmid/gemini surfactant/helper lipid nanoparticles and their effect on the transfection efficiency.

Results
Nanoparticles were incubated with Sf 1 Ep cells in the presence of different endocytic inhibitors and gene expression (interferon-γ) was measured using ELISA. Clathrin-mediated and caveolae-mediated uptake were found to be equally contributing to cellular internalization of both P/12-7NH-12/L (parent gemini surfactant) and P/12-7NGK-12/L (amino acid-substituted gemini surfactant) nanoparticles. The plasmid and the helper lipid were fluorescently tagged to track the nanoparticles inside the cells, using confocal laser scanning microscopy. Transmission electron microscopy images showed that the P/12-7NGK-12/L particles were cylindrical while the P/12-7NH-12/L particles were spherical which may influence the cellular uptake behaviour of these particles. Dye exclusion assay and pH-titration of the nanoparticles suggested that high buffering capacity, pH-dependent increase in particle size and balanced DNA binding properties may be contributing to a more efficient endosomal escape of P/12-7NGK-12/L compared to the P/12-7NH-12/L nanoparticles, leading to higher gene expression.

Conclusion
Amino-acid substitution in the spacer of gemini surfactant did not alter the cellular uptake pathway, showing similar pattern to the unsubstituted parent gemini surfactant. Glycyl-lysine substitution in the gemini spacer improved buffering capacity and imparted a pH-dependent increase of particle size. This property conferred to the P/12-7NGK-12/L nanoparticles the ability to escape efficiently from clathrin-mediated endosomes. Balanced binding properties (protection and release) of the 12-7NGK-12 in the presence of polyanions could contribute to the facile release of the nanoparticles internalized via caveolae-mediated uptake. A more efficient endosomal escape of the P/12-7NGK-12/L nanoparticles lead to higher gene expression compared to the parent gemini surfactant.
L Type Ca2+ Channel Blockers Prevent Oxaliplatin-Induced Cold Hyperalgesia and TRPM8 Overexpression in Rats
Authors: Kawashiri Takehiro , Egashira Nobuaki , Kurobe Kentaro , Tsutsumi Kuniaki , Yamashita Yuji , Ushio Soichiro , Yano Takahisa , Oishi Ryozo 
Published: February 2012

Background: Oxaliplatin is an important drug used in the treatment of colorectal cancer. However, it frequently causes severe acute and chronic peripheral neuropathies. We recently reported that repeated administration of oxaliplatin induced cold hyperalgesia in the early phase and mechanical allodynia in the late phase in rats, and that oxalate derived from oxaliplatin is involved in the cold hyperalgesia. In the present study, we examined the effects of Ca2+ channel blockers on oxaliplatin-induced cold hyperalgesia in rats. Methods: Cold hyperalgesia was assessed by the acetone test. Oxaliplatin (4 mg/kg), sodium oxalate (1.3 mg/kg) or vehicle was injected i.p. on days 1 and 2. Ca2+ (diltiazem, nifedipine and ethosuximide) and Na+ (mexiletine) channel blockers were administered p.o. simultaneously with oxaliplatin or oxalate on days 1 and 2. Results: Oxaliplatin (4 mg/kg) induced cold hyperalgesia and increased in the transient receptor potential melastatin 8 (TRPM8) mRNA levels in the dorsal root ganglia (DRG). Furthermore, oxalate (1.3 mg/kg) significantly induced the increase in TRPM8 protein in the DRG. Treatment with oxaliplatin and oxalate (500 μM for each) also increased the TRPM8 mRNA levels and induced Ca2+ influx and nuclear factor of activated T-cell (NFAT) nuclear translocation in cultured DRG cells. These changes induced by oxalate were inhibited by nifedipine, diltiazem and mexiletine. Interestingly, co-administration with nifedipine, diltiazem or mexiletine prevented the oxaliplatin-induced cold hyperalgesia and increase in the TRPM8 mRNA levels in the DRG. Conclusions: These data suggest that the L type Ca2+ channels/NFAT/TRPM8 pathway is a downstream mediator for oxaliplatin-induced cold hyperalgesia, and that Ca2+ channel blockers have prophylactic potential for acute neuropathy.
The yeast mitogen-activated protein kinase Slt2 is involved in the cellular response to genotoxic stress
Authors: Soriano-Carot María , Bañó M Carmen , Igual J Carlos 
Published: February 2012

AbstractBackgroundThe maintenance of genomic integrity is essential for cell viability. Complex signalling pathways (DNA integrity checkpoints) mediate the response to genotoxic stresses. Identifying new functions involved in the cellular response to DNA-damage is crucial. TheSaccharomyces cerevisiae SLT2gene encodes a member of the mitogen-activated protein kinase (MAPK) cascade whose main function is the maintenance of the cell wall integrity. However, different observations suggest thatSLT2may also have a role related to DNA metabolism.ResultsThis work consisted in a comprehensive study to connect the Slt2 protein to genome integrity maintenance in response to genotoxic stresses. Theslt2mutant strain was hypersensitive to a variety of genotoxic treatments, including incubation with hydroxyurea (HU), methylmetanosulfonate (MMS), phleomycin or UV irradiation. Furthermore, Slt2 was activated by all these treatments, which suggests that Slt2 plays a central role in the cellular response to genotoxic stresses. Activation of Slt2 was not dependent on the DNA integrity checkpoint. For MMS and UV, Slt2 activation required progression through the cell cycle. In contrast, HU also activated Slt2 in nocodazol-arrested cells, which suggests that Slt2 may respond to dNTP pools alterations. However, neither the protein level of the distinct ribonucleotide reductase subunits nor the dNTP pools were affected in aslt2mutant strain. An analysis of the checkpoint function revealed that Slt2 was not required for either cell cycle arrest or the activation of the Rad53 checkpoint kinase in response to DNA damage. However,slt2mutant cells showed an elongated bud and partially impaired Swe1 degradation after replicative stress, indicating that Slt2 could contribute, in parallel with Rad53, to bud morphogenesis control after genotoxic stresses.ConclusionsSlt2 is activated by several genotoxic treatments and is required to properly cope with DNA damage. Slt2 function is important for bud morphogenesis and optimal Swe1 degradation under replicative stress. The MAPK Slt2 appears as a new player in the cellular response to genotoxic stresses.
Caipirini: using gene sets to rank literature
Authors: Soldatos Theodoros G , O'Donoghue Seán I , Satagopam Venkata P , Barbosa-Silva Adriano , Pavlopoulos Georgios A , Wanderley-Nogueira Ana Carolina , Soares-Cavalcanti Nina Mota , Schneider Reinhard 
Published: February 2012

Abstract

Background
Keeping up-to-date with bioscience literature is becoming increasingly challenging. Several recent methods help meet this challenge by allowing literature search to be launched based on lists of abstracts that the user judges to be 'interesting'. Some methods go further by allowing the user to provide a second input set of 'uninteresting' abstracts; these two input sets are then used to search and rank literature by relevance. In this work we present the service 'Caipirini' (http://caipirini.org) that also allows two input sets, but takes the novel approach of allowing ranking of literature based on one or more sets of genes.

Results
To evaluate the usefulness of Caipirini, we used two test cases, one related to the human cell cycle, and a second related to disease defense mechanisms in Arabidopsis thaliana. In both cases, the new method achieved high precision in finding literature related to the biological mechanisms underlying the input data sets.

Conclusions
To our knowledge Caipirini is the first service enabling literature search directly based on biological relevance to gene sets; thus, Caipirini gives the research community a new way to unlock hidden knowledge from gene sets derived via high-throughput experiments.
Evaluation of antigen specific recognition and cell mediated cytotoxicity by a modified lysispot assay in a rat colon carcinoma model
Authors: Bordignon Valentina , Cordiali-Fei Paola , Rinaldi Monica , Signori Emanuela , Cottarelli Andrea , Zonfrillo Manuela , Ensoli Fabrizio , Rasi Guido , Fuggetta Maria Pia 
Published: February 2012

Abstract

Background
Antigen-specific CD8+ cytotoxic T lymphocytes represent potent effector cells of the adaptive immune response against viruses as well as tumours. Therefore assays capable at exploring the generation and function of cytotoxic T lymphocytes represent an important objective for both clinical and experimental settings.

Methods
Here we show a simple and reproducible assay for the evaluation of antigen-specific CD8+ cytotoxic T lymphocytes based on a LysiSpot technique for the simultaneous determination of antigen-specific IFN-γ production and assessment of tumor cytolysis. The assay was developed within an experimental model of colorectal carcinoma, induced by the colorectal tumor cell line DHD-K12 that induces tumors in BDIX rats and, in turn, elicits a tumor- specific immune response.

Results
Using DHD-K12 cells transfected to express Escherichia coli β-galactosidase as target cells, and by the fine setting of spot colours detection, we have developed an in vitro assay that allows the recognition of cytotoxic T lymphocytes induced in BDIX rats as well as the assessment of anti-tumour cytotoxicity. The method highlighted that in the present experimental model the tumour antigen-specific immune response was bound to killing target cells in the proportion of 55%, while 45% of activated cells were not cytotoxic but released IFN-γ. Moreover in this model by an ELISPOT assay we demonstrated the specific recognition of a nonapeptide epitope called CSH-275 constitutionally express in DHD-K12 cells.

Conclusions
The assay proved to be highly sensitive and specific, detecting even low frequencies of cytotoxic/activated cells and providing the evaluation of cytokine-expressing T cells as well as the extent of cytotoxicity against the target cells as independent functions. This assay may represent an important tool to be adopted in experimental settings including the development of vaccines or immune therapeutic strategies
Foundation for what? Commentary on … Current position of psychiatry in UK foundation schools
Authors: Bhugra Dinesh 
Published: February 2012

SummaryTwo years of foundation training were added to the medical students' transition from learning theory in medical school to trainee clinical practice, replacing one year of house jobs or internship. In the recent few years there has been a tremendous amount of debate about undergraduate medical training and changes in regulations which led to the Collins review in 2010. The review proposed that trainees need more exposure to community-based placements such as psychiatry, public health and community paediatrics and that they also need to learn to deal with chronic conditions. Bearing in mind that nearly a third of the general practitioner's patients will have psychiatric problems, it is essential that all doctors gain some exposure to psychiatric practice. It is crucial that this exposure is appropriate and adequate so that the next generation of doctors can provide accessible services that patients will be willing to use.
Reject analysis in direct digital radiography
Authors: Andersen Eivind Richter , Jorde Jannike , Taoussi Nadia , Yaqoob Sadia Halima , Konst Bente , Seierstad Therese 
Published: January 2012

Background Reject analysis can be used as a quality indicator, and is an important tool in localizing areas where optimization is required. Reducing number of rejects is important yielding reduced patient exposure and increased cost-effectiveness. Purpose To determine rejection rates and causes in direct digital radiography. Material and Methods Data were collected during a three-month period in spring 2010 at two direct digital laboratories in Norway. All X-ray examinations, types, numbers, and reasons for rejections were obtained using automatic reject analysis software. Thirteen causes for rejection could be selected. Results Out of the 27,284 acquired images, 3206 were rejected, yielding an overall rejection rate of 12%. Highest rejection rates were found for examination of knees, shoulders, and wrist. In all, 77% of the rejected images arose from positioning errors. Conclusion An overall rejection rate of 12% indicates a need for optimizing radiographic practice in the department.
Carcinoma ex pleomorphic adenoma of the parotid gland
Authors: Kashiwagi Nobuo , Murakami Takamichi , Chikugo Takaaki , Tomita Yasuhiko , Kawano Kiyoshi , Nakanishi Katsuyuki , Mori Kazunori , Tomiyama Noriyuki 
Published: January 2012

Background Carcinoma ex pleomorphic adenoma (CXPA) is a rare aggressive epithelial malignancy arising from a primary or recurrent benign mixed tumor. Only a few case reports describing the radiologic features of CXPA have been published. Purpose To describe and characterize the magnetic resonance (MR) imaging findings of CXPA in the parotid gland and correlate them with pathologic findings. Material and Methods The MR images of surgically proven CXPA in the parotid gland of five men and five women ranging in age from 28 to 75 years (mean 52 years) were retrospectively reviewed. All MR images were evaluated with emphasis on the size, margin characteristics, extraparotid infiltration, the presence of an encapsulated component, and signal intensity on T2-weighted or short-inversion-time inversion recovery (STIR) images. Results The average maximal diameter was 4.3 cm. All 10 tumors had ill-defined boundaries, and seven tumors showed extraparotid infiltration, reflecting invasive growth of the malignant component identified on histological examination. Eight tumors had a round encapsulated component and seven of those signal intensities were a mixture of hypo- and hyperintensity on T2-weighted or STIR images. Histological correlation of these components revealed fibrously encapsulated tumors containing hyalinization and myxoid tissue, suggesting degenerated pleomorphic adenoma. Invasive malignant components had non-specific and various signal intensities. Conclusion An invasive parotid mass co-existing with a round encapsulated component is suggestive of carcinoma ex pleomorphic adenoma.
Detection and size of pulmonary lesions: how accurate is MRI? A prospective comparison of CT and MRI
Authors: Heye Tobias , Ley Sebastian , Heussel Claus Peter , Dienemann Hendrik , Kauczor Hans-Ulrich , Hosch Waldemar , Libicher Martin 
Published: January 2012

Background Although CT is the modality of choice for morphological lung imaging, an increasing proportion of chest imaging is performed by MRI due to the utilization of whole-body MRI. Therefore, the diagnostic performance of MRI in reliably detecting pulmonary lesions should be established. Purpose To investigate the detection rate of pulmonary lesions by MRI that can be expected in a clinical setting and to assess the accuracy of lesion measurement by MRI compared to CT. Material and Methods Twenty-eight patients (median age 66 years) with indication for CT imaging due to suspected thoracic malignancy were prospectively included. Chest MRI performed on the same day as CT, comprised unenhanced TrueFisp, ecg-gated T2-weighted HASTE, T1-weighted VIBE, and contrast-enhanced T1-weighted, fat-saturated VIBE sequences. MR sequences were evaluated for lesion detection by two readers independently and measurement of lesion size was performed. MR findings were correlated with CT. Results One hundred and eight pulmonary lesions (20 thoracic malignancies, 88 lung nodules) were detected by CT in 26 patients. Lesions were ruled out in two patients. All thoracic malignancies were identified by MRI with strong correlation ( r = 0.97−0.99; P < 0.01) in lesion size measurement compared to CT. Unenhanced, T1-weighted VIBE correctly classified 94% of thoracic malignancies into T-stages. Contrast-enhanced, T1-weighted VIBE performed best in identifying 36% of lung nodules, 40% were detected combining unenhanced and contrast-enhanced T1-weighted VIBE. Detection rate increased to 65% for the combined sequences regarding lesions ≥5 mm. Lesion size measurement by all MR sequences strongly correlated with CT ( r = 0.96−0.97; P = 0.01). Conclusion MRI is as accurate as CT in detection and size measurement of primary thoracic malignancies >1 cm in diameter. If a lung lesion is detected by MRI, it is a reliable finding and its measurement is accurate. CT remains superior in detecting small lung nodules (<6 mm). Detection rate of MRI for small lesions is improved using a multi-sequence protocol including contrast administration.
Value of percutaneous embolotherapy for the management of traumatic vascular limb injury
Authors: Maleux Geert , Herten Pieter-Jan , Vaninbroukx Johan , Thijs Marleen , Nijs Stefaan , Fourneau Inge , Heye Sam 
Published: January 2012

Background Arterial injuries to the extremities may result in severe hemorrhagic complications. Open surgical repair has been the standard of care for these patients, but endovascular management may be a valuable, less invasive alternative. Purpose To evaluate the safety, efficacy and long-term durability of embolotherapy for the management of hemorrhagic, traumatic vascular injuries in upper and lower limbs. Material and Methods Patients with traumatic or iatrogenic hemorrhagic vascular injuries to the extremities and managed with endovascular embolotherapy in the authors' institution between 1998 and 2010 were included in this retrospective study. Embolization was performed with different embolic materials; technical and long-term clinical outcome was assessed by review of the medical records or by telephone interviews of the referring physicians. Results Embolization was performed in 31 patients. In six patients the vascular lesion was traumatic, in the remaining 25 patients the lesion was of iatrogenic origin. Angiographic vascular lesions identified were: contrast extravasation ( n = 19, 61%), pseudoaneurysm ( n = 8, 26%), and pseudoaneurysm with arteriovenous fistula ( n = 3, 10%). Primary and secondary clinical success was obtained in 84% and 97% of cases, respectively. Procedure-related complications occurred in five patients (16%). Most of them were mild. One patient expired 34 days after the procedure due to amputation-stump infection, septicaemia, and multiple organ failure. Long-term outcome showed no recurrent bleeding or other embolization-related complications. Conclusion Embolotherapy for the management of hemorrhagic, traumatic vascular injuries in upper and lower limbs is relatively safe, very effective without recurrence or other embolization-related symptoms.