bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neurochemical differences in two rat strains exposed to social isolation rearing
Authors: Trabace Luigia , Zotti Margherita , Colaianna Marilena , Morgese Maria G. , Schiavone Stefania , Tucci Paolo , Harvey Brian H. , Wegener Gregers , Cuomo Vincenzo 
Published: October 2011

Objective: Isolation rearing of rats provides a non-pharmacological method of inducing behavioural changes in rodents that resemble schizophrenia or depression. Nevertheless, results are variable within different strains. We focused on neurochemical changes in several in vivo and post-mortem brain regions of Wistar (W) and Lister Hooded (LH) rats following post-weaning social separation.Methods: Experiments were conducted after 6–8 weeks of isolation. For post-mortem studies, prefrontal cortex (PFC), nucleus accumbens (NAC), hippocampus (Hipp) and striatum (St) were collected by tissue dissection. In vivo experiments were conducted by microdialysis in the PFC. Analyses of dopamine (DA), serotonin (5-HT) levels and relative turnover were performed by using high-performance liquid chromatography.Results: We found significant strain-related differences in biogenic amine content. LH rats were characterised by markedly raised DA, along with its turnover reduction, in all the post-mortem brain regions examined as well as in microdialysis samples, while in W rats 5-HT tissue concentration was lower in PFC and St and higher in NAC and Hipp. Cortical extracellular 5-HT concentrations were increased in group housed and decreased in isolated W animals. Moreover, isolation increased DA concentrations in the PFC of LH rats, and decreased 5-HT in W rats in NAC and Hipp. Lately, 5-HT turnover was also affected by both strain and isolation conditions.Conclusions: This study suggests that W and LH rats have markedly different neurochemical profiles in response to isolation, resulting in altered monoamine levels that vary according to brain area and rat strain. These findings highlight the importance of selecting an appropriate rat strain when considering isolation rearing to model symptoms of schizophrenia and/or depression.
Treatment for trichiasis through a combination of eyelash trephination and electrocautery
Authors: Han Jae‐Hyung , Doh Sang‐Hee 
Published: October 2011

Abstract.Purpose:  This article introduces 3‐mm‐deep eyelash trephination combined with electrocautery as a way to increase the success rate for treatment for trichiasis.Method:  We have modified surgical instruments, ready‐made ophthalmic microtrephine and cautery tip for a 3‐mm‐deep eyelash trephination and electrocautery. After eyelash trephination with microtrephine, electrocautery was added with a bended cautery tip after embedding in the trephination site. The trephined eyelids were photographed biweekly and checked for recurrence until 8 weeks after operation.Result:  Eyelash trephination combined with electrocautery was carried out on 20 Korean patients. The number of removed cilia was 109. Of these, the number of successfully removed hair follicles was 89. During 8 weeks, the total recurring rate of eyelash trephination combined with electorcautery was 17%. In the case of hair follicle removal success with electrocautery, the recurring rate was as low as 11%, but in the case of hair follicle removal failure with electrocautery, recurring rate is 45%. We checked the depth of removed eyelash follicles, and the mean depth was 2.03 ± 0.085 mm in this study. No serious complication was found during the period of this study.Conclusion:  The eyelash trephination combined with electrocautery for trichiasis is a method with a low recurrence rate and few complications.
A phenotypic study of congenital stationary night blindness (CSNB) associated with mutations in the GRM6 gene
Authors: Sergouniotis Panagiotis I. , Robson Anthony G. , Li Zheng , Devery Sophie , Holder Graham E. , Moore Anthony T. , Webster Andrew R. 
Published: October 2011

Abstract.Purpose:  To describe the clinical phenotype and the molecular pathology in a group of patients with congenital stationary night blindness due to mutations in GRM6, a gene encoding the ON bipolar metabotropic glutamate receptor 6 (mGluR6).Methods:  Nine patients from seven families (age range, 7–75; median, 10 years) with a clinical diagnosis of autosomal recessive complete congenital stationary night blindness were ascertained. Clinical examination, imaging and electrophysiological assessment were performed. The coding region and intron–exon boundaries of GRM6 were sequenced.Results:  The median visual acuity for the cohort was 0.2 logMAR (range 0–3). Most patients had myopic astigmatism with the median spherical equivalent being −5.375 dioptres (−0.125 to −18.75). Fundoscopy was within normal limits in 15 eyes; there was severe myopic maculopathy in three eyes. Other secondary complications included face turn because of nystagmus and strabismic amblyopia. All patients had electronegative dark‐adapted bright white flash electroretinograms (ERGs) consistent with dysfunction occurring postphototransduction. In the two oldest subjects (aged 75 and 58 years), there was additional photoreceptor dysfunction in keeping with myopic degeneration. ON–OFF ERGs showed generalized cone ON bipolar system dysfunction in all five patients tested. Pattern ERG P50 was normal (Ν = 1), subnormal (N = 2) or undetectable (N = 2). Nine mutations in GRM6 were detected in all seven families; six of these changes were novel.Conclusions:  The phenotype associated with GRM6 mutation is variable in terms of presentation, refractive error, visual acuity and macular function. ERGs are electronegative and suggest ON‐pathway dysfunction.
Phase Separation in Chalcogenide Glasses: The System AgAsSSe
Authors: Stehlik S. , Kolar J. , Haneda H. , Sakaguchi I. , Frumar M. , Wagner T. 
Published: October 2011

We report on visualization of a phase separation in Agx(As0.33S0.67)100−x and Agx(As0.33S0.335Se0.335)100−x chalcogenide glasses by means of atomic force microscopy (AFM). Sufficient topographical contrast (~20 nm) was achieved by selective polishing of a phase‐separated sample (Ag‐poor, Ag‐rich regions) and phase separation occurred within 0.5–20 at.% Ag and 2–18 at.% Ag in Agx(As0.33S0.67)100−x and Agx(As0.33S0.335Se0.335)100−x systems, respectively. Homogenous regions were observed below and above the phase separation lower and upper limits. Direct comparison of scanning electron microscopy and atomic force microscopy sensitivity of phase separation detection is shown. In addition, concentration of silver in particular phases of AgAsS system was evaluated by NanoSIMS (secondary ion mass spectroscopy) and very similar concentration of silver was detected in the phases at boundaries of immiscibility region.
Important Role of Caspase-8 for Chemosensitivity of ALL Cells
Authors: Ehrhardt Harald , Wachter Franziska , Maurer Martina , Stahnke Karsten , Jeremias Irmela 
Published: October 2011

Abstract
Purpose: Sensitivity of tumor cells toward chemotherapy mainly determines the prognosis of patients suffering from acute lymphoblastic leukemia (ALL); nevertheless, underlying mechanisms regulating chemosensitivity remain poorly understood. Here, we aimed at characterizing the role of caspase-8 for chemosensitivity of B- and T-ALL cells.
Experimental Design: Primary tumor cells from children with ALL were evaluated for expression levels of the caspase-8 protein, were amplified in nonobese diabetic/severe combined immunodeficient mice, transfected with siRNA, and evaluated for their chemosensitivity in vitro.
Results: Effective cell death in B- and T-ALL cells depended on the presence of caspase-8 for the majority of cytotoxic drugs routinely used in antileukemia treatment. Caspase-8 was activated independently from extrinsic apoptosis signaling. Accordingly in primary ALL cells, the expression level of caspase-8 protein correlated with cell death sensitivity toward defined cytotoxic drugs in vitro. In the subgroup of primary ALL cells, with low expression of caspase-8, methotrexate (MTX) upregulated the expression of caspase-8 mediated by the transcription factor p53, suggesting epigenetic silencing of caspase-8. RNA interference in patient-derived B- and T-ALL cells revealed that effective cell death induction by most routine drug combinations involving MTX depended on the presence of caspase-8.
Conclusion: Our results indicate that caspase-8 is crucial for the high antileukemic efficiency of numerous routine cytotoxic drugs. Reexpression of epigenetically downregulated caspase-8 represents a promising approach to increase efficiency of antileukemic therapy. Clin Cancer Res; 17(24); 7605–13. ©2011 AACR.
Inhibition of DNA-Dependent Protein Kinase Induces Accelerated Senescence in Irradiated Human Cancer Cells
Authors: Azad Arun , Jackson Susan , Cullinane Carleen , Natoli Anthony , Neilsen Paul M. , Callen David F. , Maira Sauveur-Michel , Hackl Wolfgang , McArthur Grant A. , Solomon Benjamin 
Published: October 2011

AbstractDNA-dependent protein kinase (DNA-PK) plays a pivotal role in the repair of DNA double-strand breaks (DSB) and is centrally involved in regulating cellular radiosensitivity. Here, we identify DNA-PK as a key therapeutic target for augmenting accelerated senescence in irradiated human cancer cells. We find that BEZ235, a novel inhibitor of DNA-PK and phosphoinositide 3-kinase (PI3K)/mTOR, abrogates radiation-induced DSB repair resulting in cellular radiosensitization and growth delay of irradiated tumor xenografts. Importantly, radiation enhancement by BEZ235 coincides with a prominent p53-dependent accelerated senescence phenotype characterized by positive β-galactosidase staining, G2–M cell-cycle arrest, enlarged and flattened cellular morphology, and increased p21 expression and senescence-associated cytokine secretion. Because this senescence response to BEZ235 is accompanied by unrepaired DNA DSBs, we examined whether selective targeting of DNA-PK also induces accelerated senescence in irradiated cells. Significantly, we show that specific pharmacologic inhibition of DNA-PK, but not PI3K or mTORC1, delays DSB repair leading to accelerated senescence after radiation. We additionally show that PRKDC knockdown using siRNA promotes a striking accelerated senescence phenotype in irradiated cells comparable with that of BEZ235. Thus, in the context of radiation treatment, our data indicate that inhibition of DNA-PK is sufficient for the induction of accelerated senescence. These results validate DNA-PK as an important therapeutic target in irradiated cancer cells and establish accelerated senescence as a novel mechanism of radiosensitization induced by DNA-PK blockade. Mol Cancer Res; 9(12); 1696–707. ©2011 AACR.
Nuclear Receptor LXR as a Novel Therapeutic Antitumoral Target in Glioblastoma
Authors: Moschetta Antonio 
Published: October 2011

Abstract
Both primary and transformed cells need cholesterol for their growth. Guo and colleagues unraveled the connection between epidermal growth factor receptor mutations in glioblastoma and increased cholesterol influx via sterol regulatory element-binding protein 1 and low-density lipoprotein receptor (LDLR) increase. They propose the activation of the liver X receptor–inducible degrader of LDLR–LDLR axis as a therapeutic approach to reduce intracellular cholesterol, block tumor growth, and induce cell death. Cancer Discovery; 1(5): 381–2. ©2011 AACR.
Commentary on Guo et al., p. 442.
Selective MicroRNA Suppression in Human Thoracic Aneurysms
Authors: Jones Jeffrey A. , Stroud Robert E. , O'Quinn Elizabeth C. , Black Laurel E. , Barth Jeremy L. , Elefteriades John A. , Bavaria Joseph E. , Gorman Joseph H. , Gorman Robert C. , Spinale Francis G. , Ikonomidis John S. 
Published: October 2011

Background—
Increasing evidence points to a direct role for altered microRNA (miRNA or miR) expression levels in cardiovascular remodeling and disease progression. Although alterations in miR expression levels have been directly linked to cardiac hypertrophy, fibrosis, and remodeling, their role in regulating gene expression during thoracic aortic aneurysm (TAA) development has yet to be explored.

Methods and Results—
The present study examined miR expression levels in aortic tissue specimens collected from patients with ascending TAAs by quantitative real-time PCR, and observed decreased miR expression (miRs -1, -21, -29a, -133a, and -486) as compared with normal aortic specimens. A significant relationship between miR expression levels (miRs -1, -21, -29a, and -133a) and aortic diameter was identified; as aortic diameter increased, miR expression decreased. Through the use of a bioinformatics approach, members of the matrix metalloproteinase (MMP) family, proteins involved in TAA development, were examined for putative miR binding sites. MMP-2 and MMP-9 were identified as potential targets for miR-29a and miR-133a, respectively, and MMP-2 was subsequently verified as a miR-29a target in vitro. A significant inverse relationship between miR-29a and total MMP-2 was then identified in the clinical TAA specimens.

Conclusions—
These findings demonstrate altered miR expression patterns in clinical TAA specimens, suggesting that the loss of specific miR expression may allow for the elaboration of specific MMPs capable of driving aortic remodeling during TAA development. Importantly, these data suggest that these miRs have biological and clinical relevance to the behavior of TAAs and may provide significant targets for therapeutic and diagnostic applications.
Effect of Heparin Administration on Metabolomic Profiles in Samples Obtained During Cardiac Catheterization
Authors: Brunner Michael P. , Shah Svati H. , Craig Damian M. , Stevens Robert D. , Muehlbauer Michael J. , Bain James R. , Newgard Christopher B. , Kraus William E. , Granger Christopher B. , Sketch Michael H. , Newby L. Kristin 
Published: October 2011

Background—
Metabolic profiling holds promise for early detection of coronary artery disease and assessing risk for ischemic events. Heparin is frequently administered (1) to treat acute coronary syndromes; and (2) during routine cardiac catheterization procedures. Because it stimulates lipolysis, heparin is a potential confounder of metabolic profiling in these populations.

Methods and Results—

Using mass spectrometry and conventional immunoassays, we evaluated how unfractionated heparin administration affected 69 peripheral blood metabolites (acylcarnitines, amino acids, nonesterified fatty acids and their oxidation byproducts, conventional lipids, glucose, and C-reactive protein) in samples obtained pre- and postcardiac catheterization from 19 patients who received heparin and 10 patients who did not. Using unpaired
t
tests, we compared the changes in mean metabolite levels before and after the procedure between the nonheparin and heparin groups. Clinical characteristics of the nonheparin and heparin groups, indication for cardiac catheterization, procedure performed, and other periprocedural variables were similar. The mean change between pre- and postprocedure β-hydroxybutyrate (5.43 versus 66.84 μmol/L;
P
=0.009), ketones (21.17 versus 98.49 μmol/L;
P
=0.009), nonesterified fatty acids (0.37 versus 1.20 mmol/L;
P
=0.017), and triglycerides (−9.33 versus −36.50 mg/dL;
P
=0.007) was significantly different between the nonheparin and heparin groups, respectively. There were no significant differences between groups in the other metabolites measured.

Conclusions—
Heparin administration during cardiac catheterization induced changes in peripheral blood metabolites that were consistent with known lipolytic effects of heparin and define a metabolite signature associated with heparin administration. These findings are important for accurate interpretation of future metabolic profiling studies in populations exposed to heparin.
Marine Downscaling of a Future Climate Scenario for Australian Boundary Currents
Authors: Sun Chaojiao , Feng Ming , Matear Richard J. , Chamberlain Matthew A. , Craig Peter , Ridgway Ken R. , Schiller Andreas 
Published: October 2011

Abstract
Ocean boundary currents are poorly represented in existing coupled climate models, partly because of their insufficient resolution to resolve narrow jets. Therefore, there is limited confidence in the simulated response of boundary currents to climate change by climate models. To address this issue, the eddy-resolving Ocean Forecasting Australia Model (OFAM) was used, forced with bias-corrected output in the 2060s under the Special Report on Emissions Scenarios (SRES) A1B from the CSIRO Mark version 3.5 (Mk3.5) climate model, to provide downscaled regional ocean projections. CSIRO Mk3.5 captures a number of robust changes that are common to most climate models that are consistent with observed changes, including the weakening of the equatorial Pacific zonal wind stress and the strengthening of the wind stress curl in the Southern Pacific, important for driving the boundary currents around Australia.
The 1990s climate is downscaled using air–sea fluxes from the 40-yr European Centre for Medium-Range Weather Forecasts Re-Analysis (ERA-40). The current speed, seasonality, and volume transports of the Australian boundary currents show much greater fidelity to the observations in the downscaled model. Between the 1990s and the 2060s, the downscaling with the OFAM simulates a 15% reduction in the Leeuwin Current (LC) transport, a 20% decrease in the Indonesian Throughflow (ITF) transport, a 12% increase in the East Australian Current (EAC) core transport, and a 35% increase in the EAC extension. The projected changes by the downscaling model are consistent with observed trends over the past several decades and with changes in wind-driven circulation derived from Sverdrup dynamics. Although the direction of change projected from downscaling is usually in agreement with CSIRO Mk3.5, there are important regional details and differences that will impact the response of ecosystems to climate change.
The strategy for the diagnosis of invasive pulmonary aspergillosis should depend on both the underlying condition and the leukocyte count of patients with hematologic malignancies
Authors: Bergeron Anne , Porcher Raphaël , Sulahian Annie , de Bazelaire Cédric , Chagnon Karine , Raffoux Emmanuel , Vekhoff Anne , Cornet Muriel , Isnard Françoise , Brethon Benoit , Lacroix Claire , Poirot Jean Louis , Bouges Claire , Derouin Francis , Tazi Abdellatif , Ribaud Patricia 
Published: October 2011

Abstract
The identification of the causative organism in invasive pulmonary aspergillosis (IPA) is recommended. We investigated whether a mycologic diagnostic strategy could be optimized based on patient characteristics. Fifty-five patients were enrolled in a prospective study. The presence of Aspergillus in respiratory samples occurred more frequently in non-acute leukemia (AL) patients than in AL patients (P = .0003), and in patients with leukocyte counts more than 100/mm3 (P = .002). In a logistic regression model, these 2 factors appeared to be independent, with an adjusted odds ratio of 7.14 (95% confidence interval, 1.40-36.5) for non-AL patients and an adjusted odds ratio of 6.97 (95% confidence interval, 1.33-36.5) for patients with leukocyte counts more than 100/mm3. A positive mycologic result was also more frequent among patients with lung CT scan signs of airway-invasive disease than among other patients (P = .043). Airway-invasive signs were more frequent among non-AL patients (P = .049), whereas angioinvasive disease was more frequent among both AL patients (P = .01) and patients with leukocyte counts less than 100/mm3 (P = .001). A concomitant pulmonary infection was identified more frequently among non-AL patients (P = .005 vs allogeneic hematopoietic stem cell transplant and P = .048 vs others). Our results suggest that different strategies for diagnosing IPA should be considered based on the underlying condition.
Distinct Ldb1/NLI complexes orchestrate γ-globin repression and reactivation through ETO2 in human adult erythroid cells
Authors: Kiefer Christine M. , Lee Jongjoo , Hou Chunhui , Dale Ryan K. , Lee Y. Terry , Meier Emily R. , Miller Jeffrey L. , Dean Ann 
Published: October 2011

AbstractThe Ldb1/GATA-1/TAL1/LMO2 complex mediates long-range interaction between the β-globin locus control region (LCR) and gene in adult mouse erythroid cells, but whether this complex mediates chromatin interactions at other developmental stages or in human cells is unknown. We investigated NLI (Ldb1 homolog) complex occupancy and chromatin conformation of the β-globin locus in human erythroid cells. In addition to the LCR, we found robust NLI complex occupancy at a site downstream of the Aγ-globin gene within sequences of BGL3, an intergenic RNA transcript. In cells primarily transcribing β-globin, BGL3 is not transcribed and BGL3 sequences are occupied by NLI core complex members, together with corepressor ETO2 and by γ-globin repressor BCL11A. The LCR and β-globin gene establish proximity in these cells. In contrast, when γ-globin transcription is reactivated in these cells, ETO2 participation in the NLI complex at BGL3 is diminished, as is BCL11A occupancy, and both BGL3 and γ-globin are transcribed. In these cells, proximity between the BGL3/γ-globin region and the LCR is established. We conclude that alternative NLI complexes mediate γ-globin transcription or silencing through long-range LCR interactions involving an intergenic site of noncoding RNA transcription and that ETO2 is critical to this process.
Risk factors for acute GVHD and survival after hematopoietic cell transplantation
Authors: Jagasia Madan , Arora Mukta , Flowers Mary E. D. , Chao Nelson J. , McCarthy Philip L. , Cutler Corey S. , Urbano-Ispizua Alvaro , Pavletic Steven Z. , Haagenson Michael D. , Zhang Mei-Jie , Antin Joseph H. , Bolwell Brian J. , Bredeson Christopher , Cahn Jean-Yves , Cairo Mitchell , Gale Robert Peter , Gupta Vikas , Lee Stephanie J. , Litzow Mark , Weisdorf Daniel J. , Horowitz Mary M. , Hahn Theresa 
Published: October 2011

Abstract
Risk factors for acute GVHD (AGVHD), overall survival, and transplant-related mortality were evaluated in adults receiving allogeneic hematopoietic cell transplants (1999-2005) from HLA-identical sibling donors (SDs; n = 3191) or unrelated donors (URDs; n = 2370) and reported to the Center for International Blood and Marrow Transplant Research, Minneapolis, MN. To understand the impact of transplant regimen on AGVHD risk, 6 treatment categories were evaluated: (1) myeloablative conditioning (MA) with total body irradiation (TBI) + PBSCs, (2) MA + TBI + BM, (3) MA + nonTBI + PBSCs, (4) MA + nonTBI + BM, (5) reduced intensity conditioning (RIC) + PBSCs, and (6) RIC + BM. The cumulative incidences of grades B-D AGVHD were 39% (95% confidence interval [CI], 37%-41%) in the SD cohort and 59% (95% CI, 57%-61%) in the URD cohort. Patients receiving SD transplants with MA + nonTBI + BM and RIC + PBSCs had significantly lower risks of grades B-D AGVHD than patients in other treatment categories. Those receiving URD transplants with MA + TBI + BM, MA + nonTBI + BM, RIC + BM, or RIC + PBSCs had lower risks of grades B-D AGVHD than those in other treatment categories. The 5-year probabilities of survival were 46% (95% CI, 44%-49%) with SD transplants and 33% (95% CI, 31%-35%) with URD transplants. Conditioning intensity, TBI and graft source have a combined effect on risk of AGVHD that must be considered in deciding on a treatment strategy for individual patients.