bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of SSR markers associated with saccharification yield using pool-based genome-wide association mapping in sorghum
Authors: Wang Yi-Hong , Poudel Durga D. , Hasenstein Karl H. 
Published: November 2011

Saccharification describes the conversion of plant biomass by cellulase into glucose. Because plants have never been selected for high saccharification yield, cellulosic ethanol production faces a significant bottleneck. To improve saccharification yield, it is critical to identify the genes that affect this process. In this study, we used pool-based genome-wide association mapping to identify simple sequence repeat (SSR) markers associated with saccharification yield. Screening of 703 SSR markers against the low and high saccharification pools identified two markers on the sorghum chromosomes 2 (23-1062) and 4 (74-508c) associated with saccharification yield. The association was significant at 1% using either general or mixed linear models. Localization of these markers based on the whole genome sequence indicates that 23-1062 is 223 kb from a β–glucanase (Bg) gene and 74-508c is 81 kb from a steroid-binding protein (Sbp) gene. Bg is critical for cell wall assembly and degradation, but Sbp can suppress the expression of Bg as demonstrated in Arabidopsis (Yang et al. 2005). These markers are found physically close to genes encoding plant cell wall synthesis enzymes such as xyloglucan fucosyltransferase (149 kb from 74-508c) and UDP-d-glucose 4-epimerase (46 kb from 23-1062). Genetic transformation of selected candidate genes is in progress to examine their effect on saccharification yield in plants.
Use of Multifunctional Sigma-2 Receptor Ligand Conjugates to Trigger Cancer-Selective Cell Death Signaling
Authors: Spitzer Dirk , Simon Peter O. , Kashiwagi Hiroyuki , Xu Jinbin , Zeng Chenbo , Vangveravong Suwanna , Zhou Dong , Chang Katherine , McDunn Jonathan E. , Hornick John R. , Goedegebuure Peter , Hotchkiss Richard S. , Mach Robert H. , Hawkins William G. 
Published: November 2011

Abstract
One major challenge in the development of cancer therapeutics is the selective delivery of the drugs to their cellular targets. In the case of pancreatic cancer, the σ-2 receptor is a unique target that triggers apoptosis upon activation. We have previously developed a series of chemical compounds with high affinity for the σ-2 receptor and showed rapid internalization of the ligands. One particular specific ligand of the σ-2 receptor, SV119, binds to pancreatic cancer cells and induces target cell death in vitro and in vivo. In this study, we characterized the ability of SV119 to selectively deliver other death-inducing cargos to augment the cytotoxic properties of SV119 itself. When conjugated to SV119, small molecules that are known to interfere with intracellular prosurvival pathways retained their ability to induce cell death, the efficiency of which was enhanced by the combinatorial effect of SV119 delivered with its small molecule cargo. Our findings define a simple platform technology to increase the tumor-selective delivery of small molecule therapeutics via σ-2 ligands, permitting chemotherapeutic synergy that can optimize efficacy and patient benefit. Cancer Res; 72(1); 201–9. ©2011 AACR.
Regulation of CXCL8/IL-8 Expression by Zonula Occludens-1 in Human Breast Cancer Cells
Authors: Brysse Anne , Mestdagt Mélanie , Polette Myriam , Luczka Emilie , Hunziker Walter , Noël Agnès , Birembaut Philippe , Foidart Jean-Michel , Gilles Christine 
Published: November 2011

Abstract
Accumulating data now suggest that ZO-1, once delocalized from tight junctions, could be implicated in the regulation of tumor-promoting genes. Because of their major implication in different steps of tumor progression, we investigated here the influence of ZO-1 on chemokines expression in breast cancer cells. Using GeneArray analysis to compare chemokine mRNA expression in breast tumor cells transfected with a siRNA against ZO-1, we identified CXCL-8IL-8 as a major potential target of ZO-1 signaling, being strongly downregulated following ZO-1 siRNA transfection. Examining further the relationship between ZO-1 and interleukin-8 (CXCL8/IL-8), we first showed that CXCL8/IL-8 expression correlates with a relocalization of ZO-1 in several breast cancer cell lines. Moreover, CXCL8/IL-8 is downregulated in invasive BT549 cells transfected with three different ZO-1 siRNA and overexpressed in noninvasive BT20 and SKBR3 cells transfected with vectors expressing ZO-1. We also provide evidence for an activation of the CXCL8/IL-8 promoter by ZO-1. Finally, we show that the regulation of CXCL8/IL-8 by ZO-1 is independent of the β-catenin pathway. Our results thus clearly show an implication of ZO-1 in CXCL8/IL-8 regulation. Because of the major implications of CXCL8/IL-8 in tumor invasion, such a regulation could play an important role in breast cancer progression. Mol Cancer Res; 10(1); 121–32. ©2011 AACR.
MiR-126 Acts as a Tumor Suppressor in Pancreatic Cancer Cells via the Regulation of ADAM9
Authors: Hamada Shin , Satoh Kennichi , Fujibuchi Wataru , Hirota Morihisa , Kanno Atsushi , Unno Jun , Masamune Atsushi , Kikuta Kazuhiro , Kume Kiyoshi , Shimosegawa Tooru 
Published: November 2011

Abstract
The epithelial-mesenchymal transition (EMT) is a critical step for pancreatic cancer cells as an entry of metastatic disease. Wide variety of cytokines and signaling pathways are involved in this complex process while the entire picture is still cryptic. Recently, miRNA was found to regulate cellular function including EMT by targeting multiple mRNAs. We conducted comprehensive analysis of miRNA expression profiles in invasive ductal adenocarcinoma (IDA), intraductal papillary mucinous adenoma, intraductal papillary mucinous carcinoma, and human pancreatic cancer cell line to elucidate essential miRNAs which regulate invasive growth of pancreatic cancer cells. Along with higher expression of miR-21 which has been shown to be highly expressed in IDA, reduced expression of miR-126 in IDA and pancreatic cancer cell line was detected. The miR-126 was found to target ADAM9 (disintegrin and metalloproteinase domain-containing protein 9) which is highly expressed in pancreatic cancer. The direct interaction between miR-126 and ADAM9 mRNA was confirmed by 3′ untranslated region assay. Reexpression of miR-126 and siRNA-based knockdown of ADAM9 in pancreatic cancer cells resulted in reduced cellular migration, invasion, and induction of epithelial marker E-cadherin. We showed for the first time that the miR-126/ADAM9 axis plays essential role in the inhibition of invasive growth of pancreatic cancer cells. Mol Cancer Res; 10(1); 3–10. ©2011 AACR.
Silencing of DLC1 Upregulates PAI-1 Expression and Reduces Migration in Normal Prostate Cells
Authors: Shih Yi-Ping , Takada Yoshikazu , Lo Su Hao 
Published: November 2011

Abstract
Deleted in liver cancer 1 (DLC1) is a GTPase-activating protein (GAP) domain containing tumor suppressor that localizes to focal adhesions. In cancer cells, loss of DLC1 is known to enhance cancer cell migration. However, the role of DLC1 in normal cell migration has not been well studied. Here, we show that silencing of DLC1 (shDLC1) in normal prostate epithelial cells reduces cell migration in both Transwell and wound-healing assays. This migration defect is mainly due to upregulation of plasminogen activator inhibitor 1 (PAI-1). Silencing of PAI-1 rescues the shDLC1-reduced migration phenotype. Reexpression of DLC1 suppresses PAI-1 and restores the migration defect as well. In contrast, DLC1-K714E (GAP inactive) mutant neither decreases the PAI-1 level nor rescues the shDLC1 migration defect. Interestingly, DLC1-Y442F (tensin-binding and focal adhesion–localizing defective) mutant is able to suppress PAI-1 expression but does not restore the migration defect. Furthermore, PAI-1 upregulation in shDLC1 cells is EGFR-MEK pathway dependent and is able to promote in vitro angiogenesis. Together, our results show that at least the following two new mechanisms are involved in DLC1-mediated normal cell migration: (i) DLC1 modulates the expression of PAI-1, which is a negative regulator for cell migration, in a GAP domain and EGFR-MEK–dependent manner and (ii) Independent of PAI-1, the interaction of DLC1 with tensin members positively regulates cell migration. Mol Cancer Res; 10(1); 34–9. ©2011 AACR.
Genetic and Epigenetic Inactivation of Extracellular Superoxide Dismutase Promotes an Invasive Phenotype in Human Lung Cancer by Disrupting ECM Homeostasis
Authors: Teoh-Fitzgerald Melissa L.T. , Fitzgerald Matthew P. , Jensen Taylor J. , Futscher Bernard W. , Domann Frederick E. 
Published: November 2011

Abstract
Extracellular superoxide dismutase (EcSOD) is an important superoxide scavenger in the lung in which its loss, sequence variation, or abnormal expression contributes to lung diseases; however, the role of EcSOD in lung cancer has yet to be studied. We hypothesized that EcSOD loss could affect malignant progression in lung, and could be either genetic or epigenetic in nature. To test this, we analyzed EcSOD expression, gene copy number, promoter methylation, and chromatin accessibility in normal lung and carcinoma cells. We found that normal airway epithelial cells expressed abundant EcSOD and had an unmethylated promoter, whereas EcSOD-negative lung cancer cells displayed aberrant promoter hypermethylation and decreased chromatin accessibility. 5-aza-dC induced EcSOD suggesting that cytosine methylation was causal, in part, to silencing. In 48/50 lung tumors, EcSOD mRNA was significantly lower as early as stage I, and the EcSOD promoter was hypermethylated in 8/10 (80%) adenocarcinomas compared with 0/5 normal lung samples. In addition, 20% of the tumors showed loss of heterozygosity (LOH) of EcSOD. Reexpression of EcSOD attenuated the malignant phenotype of lung carcinoma cells by significantly decreasing invasion and survival. Finally, EcSOD decreased heparanase and syndecan-1 mRNAs in part by reducing NF-κB. By contrast, MnSOD and CuZnSOD showed no significant changes in lung tumors and had no effect on heparanase expression. Taken together, the loss of EcSOD expression is unique among the superoxide dismutases in lung cancer and is the result of EcSOD promoter methylation and LOH, suggesting that its early loss may contribute to ECM remodeling and malignant progression. Mol Cancer Res; 10(1); 40–51. ©2011 AACR.
Prevalence and Significance of Alterations in Cardiac Structure and Function in Patients With Heart Failure and a Preserved Ejection Fraction
Authors: Zile Michael R. , Gottdiener John S. , Hetzel Scott J. , McMurray John J. , Komajda Michel , McKelvie Robert , Baicu Catalin F. , Massie Barry M. , Carson Peter E. 
Published: November 2011

Background—
The purpose of this study was to examine the prevalence of abnormalities in cardiac structure and function present in patients with heart failure and a preserved ejection fraction (HFPEF) and to determine whether these alterations in structure and function were associated with cardiovascular morbidity and mortality.

Methods and Results—

The Irbesartan in HFPEF trial (I-PRESERVE) enrolled 4128 patients; echocardiographic determination of left ventricular (LV) volume, mass, left atrial (LA) size, systolic function, and diastolic function were made at baseline in 745 patients. The primary end point was death or protocol-specific cardiovascular hospitalization. A secondary end point was the composite of heart failure death or heart failure hospitalization. Associations between baseline structure and function and patient outcomes were examined using univariate and multivariable Cox proportional hazard analyses. In this substudy, LV hypertrophy or concentric remodeling was present in 59%, LA enlargement was present in 66%, and diastolic dysfunction was present in 69% of the patients. Multivariable analyses controlling for 7 clinical variables (including log N-terminal pro-B–type natriuretic peptide) indicated that increased LV mass, mass/volume ratio, and LA size were independently associated with an increased risk of both primary and heart failure events (all
P
<0.05).

Conclusions—
Left ventricular hypertrophy or concentric remodeling, LA enlargement, and diastolic dysfunction were present in the majority of patients with HFPEF. Left ventricular mass and LA size were independently associated with an increased risk of morbidity and mortality. The presence of structural remodeling and diastolic dysfunction may be useful additions to diagnostic criteria and provide important prognostic insights in patients with HFPEF.

Clinical Trial Registration—

http://www.clinicaltrials.gov
. Unique identifier: NCT00095238.
Benefit of Transferring ST-Segment–Elevation Myocardial Infarction Patients for Percutaneous Coronary Intervention Compared With Administration of Onsite Fibrinolytic Declines as Delays Increase
Authors: Pinto Duane S. , Frederick Paul D. , Chakrabarti Anjan K. , Kirtane Ajay J. , Ullman Edward , Dejam Andre , Miller Dave P. , Henry Timothy D. , Gibson C. Michael 
Published: November 2011

Background—
Although randomized trials suggest that transfer for primary percutaneous coronary intervention (X-PCI) in ST-segment–elevation myocardial infarction is superior to onsite fibrinolytic therapy (O-FT), the generalizability of these findings to routine clinical practice is unclear because door-to-balloon (XDB) times are rapid in randomized trials but are frequently prolonged in practice. We hypothesized that delays resulting from transfer would reduce the survival advantage of X-PCI compared with O-FT.

Methods and Results—
ST-segment–elevation myocardial infarction patients enrolled in the National Registry of Myocardial Infarction (NRMI) within 12 hours of pain onset were identified. Propensity matching of patients treated with X-PCI and O-FT was performed, and the effect of PCI-related delay on in-hospital mortality was assessed. PCI-related delay was calculated by subtracting the XDB from the door-to-needle time in each matched pair. Conditional logistic regression adjusted for patient and hospital variables identified the XDB door-to-needle time at which no mortality advantage for X-PCI over O-FT was present. Eighty-one percent of X-PCI patients were matched (n=9506) to O-FT patients (n=9506). In the matched cohort, X-PCI was performed with delays >90 minutes in 68%. Multivariable analysis found no mortality advantage for X-PCI over O-FT when XDB door-to-needle time exceeded ≈120 minutes.

Conclusion—
PCI-related delays are extensive among patients transferred for X-PCI and are associated with poorer outcomes. No differential excess in mortality was seen with X-PCI compared with O-FT even with long PCI-related delays, but as XDB door-to-needle time times increase, the mortality advantage for X-PCI over O-FT declines.
Identification of a Danger-Associated Peptide From Apolipoprotein B100 (ApoBDS-1) That Triggers Innate Proatherogenic Responses
Authors: Ketelhuth Daniel F.J. , Rios Francisco J.O. , Wang Yajuan , Liu Huiqing , Johansson Maria E. , Fredrikson Gunilla N. , Hedin Ulf , Gidlund Magnus , Nilsson Jan , Hansson Göran K. , Yan Zhong-qun 
Published: November 2011

Background—
Subendothelial deposited low-density lipoprotein particles are a known inflammatory factor in atherosclerosis. However, the causal components derived from low-density lipoprotein are still poorly defined. Apolipoprotein B100 (ApoB100) is the unexchangeable protein component of low-density lipoprotein, and the progression of atherosclerosis is associated with immune responses to ApoB100-derived peptides. In this study, we analyzed the proinflammatory activity of ApoB100 peptides in atherosclerosis.

Methods and Results—

By screening a peptide library of ApoB100, we identified a distinct native peptide referred to as ApoB100 danger-associated signal 1 (ApoBDS-1), which shows sequence-specific bioactivity in stimulation of interleukin-8, CCL2, and interleukin-6. ApoBDS-1 activates mitogen-activated protein kinase and calcium signaling, thereby effecting the expression of interleukin-8 in innate immune cells. Ex vivo stimulation of carotid plaques with ApoBDS-1 enhances interleukin-8 and prostaglandin E
2
release. Furthermore, we demonstrated that ApoBDS-1–positive peptide fragments are present in atherosclerotic lesions using immunoassays and that low-molecular-weight fractions isolated from plaque show ApoBDS-1 activity inducing interleukin-8 production.

Conclusions—
Our data show that ApoBDS-1 is a previously unrecognized peptide with robust proinflammatory activity, contributing to the disease-promoting effects of low-density lipoprotein in the pathogenesis of atherosclerosis.
Effects of Δ9-Tetrahydrocannabinol Administration on Human Encoding and Recall Memory Function: A Pharmacological fMRI Study
Authors: Bossong Matthijs G. , Jager Gerry , van Hell Hendrika H. , Zuurman Lineke , Jansma J. Martijn , Mehta Mitul A. , van Gerven Joop M. A. , Kahn René S. , Ramsey Nick F. 
Published: November 2011

Abstract
Deficits in memory function are an incapacitating aspect of various psychiatric and neurological disorders. Animal studies have recently provided strong evidence for involvement of the endocannabinoid (eCB) system in memory function. Neuropsychological studies in humans have shown less convincing evidence but suggest that administration of cannabinoid substances affects encoding rather than recall of information. In this study, we examined the effects of perturbation of the eCB system on memory function during both encoding and recall. We performed a pharmacological MRI study with a placebo-controlled, crossover design, investigating the effects of Δ9-tetrahydrocannabinol (THC) inhalation on associative memory-related brain function in 13 healthy volunteers. Performance and brain activation during associative memory were assessed using a pictorial memory task, consisting of separate encoding and recall conditions. Administration of THC caused reductions in activity during encoding in the right insula, the right inferior frontal gyrus, and the left middle occipital gyrus and a network-wide increase in activity during recall, which was most prominent in bilateral cuneus and precuneus. THC administration did not affect task performance, but while during placebo recall activity significantly explained variance in performance, this effect disappeared after THC. These findings suggest eCB involvement in encoding of pictorial information. Increased precuneus activity could reflect impaired recall function, but the absence of THC effects on task performance suggests a compensatory mechanism. These results further emphasize the eCB system as a potential novel target for treatment of memory disorders and a promising target for development of new therapies to reduce memory deficits in humans.
Interaction between Visual- and Goal-related Neuronal Signals on the Trajectories of Saccadic Eye Movements
Authors: White Brian J. , Theeuwes Jan , Munoz Douglas P. 
Published: November 2011

Abstract
During natural viewing, the trajectories of saccadic eye movements often deviate dramatically from a straight-line path between objects. In human studies, saccades have been shown to deviate toward or away from salient visual distractors depending on visual- and goal-related parameters, but the neurophysiological basis for this is not well understood. Some studies suggest that deviation toward is associated with competition between simultaneously active sites within the intermediate layers of the superior colliculus (SC), a midbrain structure that integrates sensory and goal-related signals for the production of saccades. In contrast, deviation away is hypothesized to reflect a higher-level process, whereby the neural site associated with the distractor isactively suppressed via a form of endogenous, top–down inhibition. We tested this hypothesis by measuring presaccadic distractor-evoked activation of SC visuomotor neurons while monkeys performed a simple task configured specifically to induce a high degree of saccades that deviate away. In the SC, cognitive processes such as top–down expectation are represented as variation in the sustained, low-frequency presaccadic discharge. We reasoned that any inhibition at the distractor-related locus associated with saccade deviation should affect the excitability of the neuron, thereby affecting the discharge rate. We found that, although the task produced robust deviation away, there was no evidence of a relationship between saccade deviation and distractor-evoked activation outside a short perisaccadic window that began no earlier than 22 msec before saccade onset. This indicates that deviation away is not adequately explained by a form of sustained, top–down inhibition at the distractor-related locus in the SC. The results are discussed in relation to the primary sources of inhibition associated with saccadic control.
Contemporary Trends in Procedural Volume for Adult Facial Trauma, 1996‐2006
Authors: Lee Linda N. , Bhattacharyya Neil 
Published: November 2011

ObjectivesTo determine how rates of operative facial fractures may have changed between 1996 and 2006 and to determine the potential impact of such change on otolaryngology residency surgical key indicator cases.Study DesignHistorical cohort study.SettingAcademic medical center.Subjects and MethodsThe National Hospital Discharge Survey (NHDS) and National Survey of Ambulatory Surgery (NSAS) 1996 and 2006 cases were reviewed, extracting all cases of adult nasal, malar/zygomatic, maxillary, and mandibular fracture reductions in inpatient and outpatient settings, respectively. Procedure rates for each facial fracture were tabulated and compared between 1996 and 2006.ResultsOverall in 1996, there were an estimated 113,041 ± 3740 operative facial fracture repairs performed. Among the 3 key indicator fracture repairs most relevant to otolaryngologists, there were 15,810 ± 2143 open nasal fracture reductions, 9360 ± 1742 open zygomaticomaxillary (ZMC) fracture reductions, and 20,214 ± 2585 open mandibular fracture repairs. Overall in 2006, there were 120,463 ± 7554 total facial fracture procedures, with 11,613 ± 2846 open nasal fracture reductions, 10,216 ± 2881 open ZMC fracture reductions, and 17,965 ± 3171 open mandibular repairs. Comparing cohorts, there was no significant change in number of open nasal, ZMC, or mandibular fracture repairs (P =. 24, P =. 58, P =. 80, respectively).ConclusionFacial fracture procedure rates have remained largely stable over the past 10 years. These data have implications for otolaryngology training programs and could help guide resident education in facial trauma.
Treating Spousal Violence ‘Differently’
Authors: Laster Kathy , Douglas Roger 
Published: November 2011

Commentators maintain that the criminal justice system deals differently, and therefore unfairly, with victims of spousal assault. Quantitative and qualitative studies supporting this contention, however, generally fail to make appropriate comparisons with the processing of like crimes. Police arrest rates for spousal violence, for example, are inappropriately compared with those for crime in general. Extrapolating from police arrest practices to other criminal justice processes involves the unwarranted assumption that what is true of one aspect of the system applies throughout. This study compares the processing of cases of spousal assault with that of acquaintance and stranger assaults. An examination of 332 cases in two regional courts of summary jurisdiction in Australia reveals no evidence that spousal assault cases were treated differently to other assaults at the charging, plea, or sentencing stages. The study concludes that the goal of parity of treatment may not promote fairness, nor be appropriate to spousal assault cases.