bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased severity of acute graft versus host disease as a result of differential expression following a homozygous gene deletion
Authors: Jervis S. , Collins P. , Tate D. , Foster L. , Bowman V. , Adhern C. , Bloor A. , Yin J. , Wynn R. , Poulton K. 
Published: June 2012

SummaryAcute graft versus host disease (aGvHD) is a major cause of early morbidity post‐haematopoietic stem cell transplantation with minor histocompatibility antigens being a contributing factor. One mHA encoded by the UDP glycosyltransferase 2 family polypeptide B17 (UGT2B17) gene has been shown to be immunogenic because of differential expression in the donor and recipient. We investigated the effects of a homozygous gene deletion of UGT2B17 on the severity of acute aGvHD post‐HSCT in HLA‐matched related donors. 115 donor and recipient HLA and UGT2B17 genotypes were determined using PCR‐SSO and PCR‐SSP, respectively. aGvHD grading was determined using routine criteria and dichotomized into either nonclinically significant (0–I) or clinically significant (II–IV). For all analyses, P‐values of ≤ 0.05 were considered significant. The frequency of the gene deletion within the total cohort tested was 29.1%. A significant increase in aGvHD severity (grades II‐IV) was seen in UGT2B17 recipients expressing the protein when transplanted with a UGT2B17 disparate donor (P = 0.011). We observed a significant association between UGT2B17 expressing recipients and UGT2B17 deficient donors with the severity of aGvHD. This study provides additional evidence that genomic variations may predispose to more severe aGvHD, but are not a mechanism for GvHD.
Evaluating TCE Abiotic and Biotic Degradation Pathways in a Permeable Reactive Barrier Using Compound Specific Isotope Analysis
Authors: Lojkasek‐Lima Paulo , Aravena Ramon , Shouakar‐Stash Orfan , Frape Shaun K. , Marchesi Massimo , Fiorenza Stephanie , Vogan John 
Published: June 2012

AbstractA pilot‐scale zero valent iron (ZVI) Permeable Reactive Barrier (PRB) was installed using an azimuth‐controlled ‐vertical hydrofracturing at an industrial facility to treat a chlorinated Volatile Organic Compound (VOC) plume. Following ZVI injection, no significant reduction in concentration was observed to occur with the exception of some multilevel monitoring wells, which also showed high levels of total organic carbon (TOC). These patterns suggested that the zero valent iron was not well distributed in the PRB creating leaky conditions. The geochemical data indicated reducing conditions in these areas where VOC reduction was observed, suggesting that biotic processes, associated to the guar used in the injection of the iron, could be a major mechanism of VOC degradation. Compound‐Specific Isotope Analysis (CSIA) using both carbon and chlorine stable isotopes were used as a complementary tool for evaluating the contribution of abiotic and biotic processes to VOC trends in the vicinity of the PRB. The isotopic data showed enriched isotope values around the PRB compared to the isotope composition of the VOC source confirming that VOC degradation is occurring along the PRB. A batch experiment using site groundwater collected near the VOC source and the ZVI used in the PRB was performed to evaluate the site‐specific abiotic isotopic fractionation patterns. Field isotopic trends, typical of biodegradations were observed at the site and were different from those obtained during the batch abiotic experiment. These differences in isotopic trends combined with changes in VOC concentrations and redox parameters suggested that biotic processes are the predominant pathways involved in the degradation of VOCs in the vicinity of the PRB.
Identification of a Novel, Recurrent SLC44A1‐PRKCA Fusion in Papillary Glioneuronal Tumor
Authors: Bridge Julia A. , Liu Xiao‐qiong , Sumegi Janos , Nelson Marilu , Reyes Christine , Bruch Leslie A. , Rosenblum Marc , Puccioni Mark J. , Bowdino Bradley S. , McComb Rodney D. 
Published: June 2012

AbstractMixed neuronal‐glial tumors are rare and challenging to subclassify. One recently recognized variant, papillary glioneuronal tumor (PGNT), is characterized by prominent pseudopapillary structures and glioneuronal elements. We identified a novel translocation, t(9;17)(q31;q24), as the sole karyotypic anomaly in two PGNTs. A fluorescence in situ hybridization (FISH)‐based positional cloning strategy revealed SLC44A1, a member of the choline transporter‐like protein family, and PRKCA, a protein kinase C family member of serine/threonine‐specific protein kinases, as the 9q31 and 17q24 breakpoint candidate genes, respectively. Reverse transcription‐polymerase chain reaction (RT‐PCR) analysis using a forward primer from SLC44A1 exon 5 and a reverse primer from PRKCA exon 10 confirmed the presence of a SLC44A1‐PRKCA fusion product in both tumors. Sequencing of each chimeric transcript uncovered an identical fusion cDNA junction occurring between SLC44A1 exon 15 and PRKCA exon 9. A dual‐color breakpoint‐spanning probe set custom‐designed for interphase cell recognition of the translocation event identified the fusion in a third PGNT. These results suggest that the t(9;17)(q31;q24) with the resultant novel fusion oncogene SLC44A1‐PRKCA is the defining molecular feature of PGNT that may be responsible for its pathogenesis. The FISH and RT‐PCR assays developed in this study can serve as valuable diagnostic adjuncts for this rare disease entity.
An unusually placed ectopic mandibular third molar: case report and discussion of management
Authors: Payne K. , Dickenson A. , Patel M. 
Published: June 2012

AbstractWe present the case of an ectopic mandibular third molar at the lower border of the ramus of the mandible associated with a dentigerous cyst. An extraoral surgical approach using a submandibular incision was used to extract the tooth. We discuss other reports of a similar nature and detail our management of this condition and the rationale for an extraoral surgical approach.
Role of prostaglandin D2 and the autonomic nervous system in niacin‐induced flushing (前列腺素D2与自主神经系统在烟酸引起的脸红中的作用)
Authors: PARSON Henri K. , HARATI Hadi , COOPER Deona , VINIK Aaron I. 
Published: June 2012

AbstractBackground:  Although niacin often has beneficial effects on the lipoprotein profile, flushing is an untoward effect associated with its use. Aspirin can only reduce the flushing response by 30–40%. Thus, the aim of the present study was to investigate the mechanisms of niacin‐induced flushing, with and without aspirin, in normal, healthy individuals.Methods:  Niacin‐induced flushing was evaluated in 30 healthy individuals after oral administration of 1000 mg niacin alone or with 325 mg aspirin. Neurological, autonomic nervous system, and skin blood flow measurements (using laser Doppler on the glabrous and hairy skin of each participant) were made at various times after drug administration. In addition, the systemic release of 9α,11β‐prostaglandin (PG) F2 was determined. Flushing symptoms of redness, warmth, tingling, itching, and intensity were recorded using the modified Flushing ASsessment Tool (FAST).Results:  After aspirin, the mean flushing scores for all symptoms decreased significantly; however, 36–53% of participants still had some degree of symptoms, even though aspirin completely blocked 11β‐PGF2 synthesis. Maximum skin blood flow (MaxSkBF) in both the glabrous and hairy forearm increased significantly after niacin, but decreased significantly after aspirin only in hairy skin. Regression analysis showed that, in glabrous skin, both PGF2 and parasympathetic activity were significant predictors of MaxSkBF after niacin, contributing 26% and 14%, respectively (total R2 = 40%).Conclusions:  The present study indicates, for the first time, that the parasympathetic nervous system, in addition to PGD2, may play an important role in niacin‐induced flushing. Changing the sympathetic/parasympathetic balance in favor of parasympathetic activation may be a good therapeutic target to reduce niacin‐induced flushing.
A major shift to the retention approach for forestry can help resolve some global forest sustainability issues
Authors: Lindenmayer D.B. , Franklin J.F. , Lõhmus A. , Baker S.C. , Bauhus J. , Beese W. , Brodie A. , Kiehl B. , Kouki J. , Pastur G. Martínez , Messier C. , Neyland M. , Palik B. , Sverdrup‐Thygeson A. , Volney J. , Wayne A. , Gustafsson L. 
Published: June 2012

AbstractApproximately 85% of the global forest estate is neither formally protected nor in areas dedicated to intensive wood production (e.g., plantations). Given the spatial extent of unprotected forests, finding management approaches that will sustain their multiple environmental, economic, and cultural values and prevent their conversion to other uses is imperative. The major global challenge of native forest management is further demonstrated by ongoing steep declines in forest biodiversity and carbon stocks. Here, we suggest that an essential part of such management—supplementing the protection of large reserves and sensitive areas within forest landscapes (e.g., aquatic features)—is the adoption of the retention approach in forests where logging occurs. This ecological approach to harvesting provides for permanent retention of important selected structures (e.g., trees and decayed logs) to provide for continuity of ecosystem structure, function, and species composition in the postharvest forest. The retention approach supports the integration of environmental, economic, and cultural values and is broadly applicable to tropical, temperate, and boreal forests, adaptable to different management objectives, and appropriate in different societal settings. The widespread adoption of the retention approach would be one of the most significant changes in management practice since the onset of modern high‐yield forestry.
Pathological changes in nephritis cases of non‐human primates in Assam
Authors: Nath Bichitra Gopal , Chakraborty Apurba , Rahman Taibur 
Published: June 2012

ABSTRACTBackground and aim: Occurrence of nephritis in non‐human primates is not common. The present study examined 27 carcasses of non‐human primates of Assam State Zoo and Department of Forest and Environment, Government of Assam, during the period from December 2007 to November 2009. Methods: Tissue samples were collected in 10% formol saline solution to be processed, sectioned and stained by routine histopathological procedures. Whenever warranted, special staining such as Brown and Brenn, Zeihl‐Neelsen's and modified Periodic Acid‐Schiff stains were used as per standard techniques. Results: Out of 27 non‐human primates, two rhesus macaque (Macaca mulatta) and one slow loris (Nycticebus coucang) died due to nephritis. At postmortem examination, grossly the kidneys were enlarged and pale in colour and the microscopic picture revealed acute glomerulonephritis characterized by increased cellularity of glomeruli. The swollen glomerular tufts with leucocytic infiltration completely occupied the Bowman's capsular space. Conclusions: Death due to nephritis was 11.11% in non‐human primates of Assam State Zoo and Department of Forest and Environment, Government of Assam.
First-in-Human Trial of a STAT3 Decoy Oligonucleotide in Head and Neck Tumors: Implications for Cancer Therapy
Authors: Sen Malabika , Thomas Sufi M. , Kim Seungwon , Yeh Joanne I. , Ferris Robert L. , Johnson Jonas T. , Duvvuri Umamaheswar , Lee Jessica , Sahu Nivedita , Joyce Sonali , Freilino Maria L. , Shi Haibin , Li Changyou , Ly Danith , Rapireddy Srinivas , Etter Jonathan P. , Li Pui-Kai , Wang Lin , Chiosea Simion , Seethala Raja R. , Gooding William E. , Chen Xiaomin , Kaminski Naftali , Pandit Kusum , Johnson Daniel E. , Grandis Jennifer R. 
Published: June 2012

Abstract
Despite evidence implicating transcription factors, including STAT3, in oncogenesis, these proteins have been regarded as “undruggable.” We developed a decoy targeting STAT3 and conducted a phase 0 trial. Expression levels of STAT3 target genes were decreased in head and neck cancers following injection with the STAT3 decoy compared with tumors receiving saline control. Decoys have not been amenable to systemic administration due to instability. To overcome this barrier, we linked the oligonucleotide strands using hexaethylene glycol spacers. This cyclic STAT3 decoy bound with high affinity to STAT3 protein, reduced cellular viability, and suppressed STAT3 target gene expression in cancer cells. Intravenous injection of the cyclic STAT3 decoy inhibited xenograft growth and downregulated STAT3 target genes in the tumors. These results provide the first demonstration of a successful strategy to inhibit tumor STAT3 signaling via systemic administration of a selective STAT3 inhibitor, thereby paving the way for broad clinical development.
Significance: This is the first study of a STAT3-selective inhibitor in humans and the first evidence that a transcription factor decoy can be modified to enable systemic delivery. These findings have therapeutic implications beyond STAT3 to other “undruggable” targets in human cancers. Cancer Discov; 2(8); 694–705. ©2012 AACR.
Read the Commentary on this article by Koppikar et al., p. 670.
This article is highlighted in the In This Issue feature, p. 653.
Induction of Angiotensin-Converting Enzyme and Activation of the Renin–Angiotensin System Contribute to 20-Hydroxyeicosatetraenoic Acid–Mediated Endothelial Dysfunction
Authors: Cheng Jennifer , Garcia Victor , Ding Yan , Wu Cheng-Chia , Thakar Krutanjali , Falck John R. , Ramu Errabelli , Schwartzman Michal Laniado 
Published: June 2012

Objective—

20-hydroxyeicosatetraenoic acid (20-HETE) promotes endothelial dysfunction by uncoupling endothelial NO synthase, stimulating O
2
−
production, and reducing NO bioavailability. Moreover, 20-HETE–dependent vascular dysfunction and hypertension are associated with upregulation of the renin–angiotensin system This study was undertaken to examine the contribution of renin–angiotensin system to 20-HETE actions in the vascular endothelium.

Methods and Results—

In endothelial cells, 20-HETE induced angiotensin-converting enzyme (ACE) mRNA levels and increased ACE protein and activity by 2- to 3-fold; these effects were negated with addition of the 20-HETE antagonist, 20-hydroxyeicosa-6(Z),15(Z)-dienoic acid (20 HEDE). 20-HETE induced ACE expression was protein kinase C independent and epidermal growth factor receptor tyrosine kinase and IκB kinase β dependent. ACE short interfering RNA abolished 20-HETE–mediated inhibition of NO production and stimulation of O
2
−
generation, whereas angiotensin II type 1 receptor short interfering RNA attenuated these effects by 40%. 20-HETE–stimulated O
2
−
production was negated by 20-HEDE and was attenuated by lisinopril and losartan. Importantly, 20-HETE–mediated impairment of acetylcholine-induced relaxation in rat renal interlobar arteries was also attenuated by lisinopril and losartan.

Conclusion—
These results indicate that ACE and angiotensin II type 1 receptor activation contribute to 20-HETE–mediated endothelial cell and vascular dysfunction and further enforce the notion that excessive production of 20-HETE within the vasculature leads to hypertension via mechanisms that include the induction of endothelial ACE, thus, perpetuating an increase in vascular angiotensin which, together with 20-HETE, promotes vascular dysfunction.
Soluble Epoxide Hydrolase
Authors: Gupta Nandita C. , Davis Catherine M. , Nelson Jonathan W. , Young Jennifer M. , Alkayed Nabil J. 
Published: June 2012

Objective—
Sex differences in cerebral ischemic injury are, in part, arrtibutable to the differences in cerebrovascular perfusion. We determined whether the brain microvascular endothelial cells (ECs) isolated from the female brain are more resistant to ischemic injury compared with male ECs, and whether the difference is attributable to lower expression of soluble epoxide hydrolase and higher levels of vasoprotective epoxyeicosatrienoic acids (EETs). We also determined whether protection by EETs is linked to the inhibition of rho-kinase (ROCK).

Methods and Results—
EC ischemic damage was measured after oxygen–glucose deprivation (OGD) using propidium iodide (PI) and cleaved caspase-3 labeling. Expression of soluble epoxide hydrolase was determined by quantitative polymerase chain reaction and immunocytochemistry, EETs levels by liquid chromatography-tandem mass spectrometry, and ROCK activity by ELISA. EC damage was higher in males compared with females, which correlated with higher soluble epoxide hydrolase mRNA, stronger immunoreactivity, and lower EETs compared with female ECs. Inhibition of soluble epoxide hydrolase abolished the sex difference in EC damage. ROCK activity was higher in male versus female ECs after OGD, and sex differences in EC damage and ROCK activity were abolished by 14,15-EET and ROCK inhibition.

Conclusion—
Sex differences in ischemic brain injury are, in part, attributable to differences in EET-mediated inhibition of EC ROCK activation after ischemia.
Combination Therapy With VELCADE and Tissue Plasminogen Activator Is Neuroprotective in Aged Rats After Stroke and Targets MicroRNA-146a and the Toll-Like Receptor Signaling Pathway
Authors: Zhang Li , Chopp Michael , Liu Xianshuang , Teng Hua , Tang Tao , Kassis Haifa , Zhang Zheng Gang 
Published: June 2012

Objective—
Activation of the toll-like receptor (TLR) signaling pathway exacerbates ischemic brain damage. The present study tested the hypothesis that combination treatment with VELCADE and tissue plasminogen activator (tPA) modulates the TLR signaling pathway on cerebral vasculature, which leads to neuroprotection in aged rats after stroke.

Methods and Results—
Focal cerebral ischemia acutely increased TLR2, TLR4, and interleukin-1 receptor–activated kinases 1 immunoreactivity on fibrin/fibrinogen-positive vessels in aged rats. Monotherapy of tPA further amplified these signals. However, VELCADE in combination with tPA-blocked stroke- and tPA-potentiated vascular TLR signals, leading to robust reduction of infarct volume compared with respective monotherapies. Quantitative reverse transcription polymerase chain reaction analysis of cerebral endothelial cells isolated by laser capture microdissection revealed that the combination treatment increased miR-l46a levels, which was inversely associated with the reduction of vascular interleukin-1 receptor–activated kinases 1 immunoreactivity. In vitro, fibrin upregulated interleukin-1 receptor–activated kinases 1 and TLR4 expression and downregulated miR-146a on primary human cerebral endothelial cells. VELCADE elevated miR-146 levels and abolished fibrin-increased interleukin-1 receptor activated kinases 1 proteins.

Conclusion—
Stroke acutely activates the TLR signaling pathway on cerebral vasculature. Upregulation of miR-146a and inactivation of ischemia and tPA-potentiated TLR signaling pathway by VELCADE may play an important role in the neuroprotective effect of the combination therapy of VELCADE and tPA for acute stroke.
High-Resolution Association Mapping of Atherosclerosis Loci in Mice
Authors: Bennett Brian J. , Orozco Luz , Kostem Emrah , Erbilgin Ayca , Dallinga Marchien , Neuhaus Isaac , Guan Bo , Wang Xuping , Eskin Eleazar , Lusis Aldons J. 
Published: June 2012

Objective—
The purpose of this study was to fine map previously identified quantitative trait loci affecting atherosclerosis in mice using association analysis.

Methods and Results—

We recently showed that high-resolution association analysis using common inbred strains of mice is feasible if corrected for population structure. To use this approach for atherosclerosis, which requires a sensitizing mutation, we bred human apolipoprotein B-100 transgenic mice with 22 different inbred strains to produce F1 heterozygotes. Mice carrying the dominant transgene were tested for association with high-density single nucleotide polymorphism maps. Here, we focus on high-resolution mapping of the previously described
atherosclerosis 30
locus on chromosome 1. Compared with the previous linkage analysis, association improved the resolution of the
atherosclerosis 30
locus by more than an order of magnitude. Using expression quantitative trait locus analysis, we identified one of the genes in the region, desmin, as a strong candidate.

Conclusion—
Our high-resolution mapping approach accurately identifies and fine maps known atherosclerosis quantitative trait loci. These results suggest that high-resolution genome-wide association analysis for atherosclerosis is feasible in mice.
Effect of Skeletal Muscle Na
+
Channel Delivered Via a Cell Platform on Cardiac Conduction and Arrhythmia Induction
Authors: Boink Gerard J.J. , Lu Jia , Driessen Helen E. , Duan Lian , Sosunov Eugene A. , Anyukhovsky Evgeny P. , Shlapakova Iryna N. , Lau David H. , Rosen Tove S. , Danilo Peter , Jia Zhiheng , Ozgen Nazira , Bobkov Yevgeniy , Guo Yuanjian , Brink Peter R. , Kryukova Yelena , Robinson Richard B. , Entcheva Emilia , Cohen Ira S. , Rosen Michael R. 
Published: June 2012

Background—

In depolarized myocardial infarct epicardial border zones, the cardiac sodium channel is largely inactivated, contributing to slow conduction and reentry. We have demonstrated that adenoviral delivery of the skeletal muscle Na
+
channel (SkM1) to epicardial border zones normalizes conduction and reduces induction of ventricular tachycardia/ventricular fibrillation. We now studied the impact of canine mesenchymal stem cells (cMSCs) in delivering SkM1.

Methods and Results—

cMSCs were isolated and transfected with SkM1. Coculture experiments showed cMSC/SkM1 but not cMSC alone and maintained fast conduction at depolarized potentials. We studied 3 groups in the canine 7d infarct: sham, cMSC, and cMSC/SkM1. In vivo epicardial border zones electrograms were broad and fragmented in sham, narrower in cMSCs, and narrow and unfragmented in cMSC/SkM1 (
P
<0.05). During programmed electrical stimulation of epicardial border zones, QRS duration in cMSC/SkM1 was shorter than in cMSC and sham (
P
<0.05). Programmed electrical stimulation–induced ventricular tachycardia/ventricular fibrillation was equivalent in all groups (
P
>0.05).

Conclusion—
cMSCs provide efficient delivery of SkM1 current. The interventions performed (cMSCs or cMSC/SkM1) were neither antiarrhythmic nor proarrhythmic. Comparing outcomes with cMSC/SkM1 and viral gene delivery highlights the criticality of the delivery platform to SkM1 antiarrhythmic efficacy.
Vulnerability beyond Stereotypes: Context and Agency in Hurricane Risk Communication
Authors: Lazrus Heather , Morrow Betty H. , Morss Rebecca E. , Lazo Jeffrey K. 
Published: June 2012

AbstractRisk communication may accentuate or alleviate the vulnerability of people who have particular difficulties responding to the threat of hazards such as hurricanes. The process of risk communication involves how hazard information is received, understood, and responded to by individuals and groups. Thus, risk communication and vulnerability interact through peoples' knowledge, attitudes, and practices. This study explores risk communication with several groups that may be at particular risk of hurricane impacts: older adults, newer residents, and persons with disabilities. Focus groups conducted in Miami, Florida, examined how members of these groups express their own vulnerability or agency in terms of receiving, interpreting, and responding to hurricane risk information. Findings indicate that people's interactions with risk information are deeply contextual and are facilitated by their individual agency to cope with their vulnerabilities.