bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glycosylated Neurotensin Analogues Exhibit Sub‐picomolar Anticonvulsant Potency in a Pharmacoresistant Model of Epilepsy
Authors: Lee Hee‐Kyoung , Zhang Liuyin , Smith Misty D. , White H. Steve , Bulaj Grzegorz 
Published: January 2009

AbstractThe glycosylation of neuroactive peptidesis a promising strategy to treat neurological and psychiatric disorders. Herein we investigated the effects of site‐specific glycosylation of neurotensin (NT). The glycosylated analogues have low‐nanomolar affinities and agonist activities toward NTS1, and suppress seizures with sub‐picomolar potency. Our work points to a new research direction of exploring BBB‐permeable NT analogues as potential first‐in‐class antiepileptic drugs.magnified imageNeurotensin (NT) is an endogenous neuropeptide involved in a variety of central and peripheral neuromodulatory effects. Herein we show the effects of site‐specific glycosylation on the in vitro and in vivo pharmacological properties of this neuropeptide. NT analogues containing O‐linked disaccharides (β‐melibiose and α‐TF antigen) or β‐lactose units linked by a PEG3spacer were designed and chemically synthesized using Fmoc chemistry. For the latter analogue, Fmoc‐Glu‐(β‐Lac‐PEG3‐amide) was prepared. Our results indicate that the addition of the disaccharides does not negatively affect the sub‐nanomolar affinity or the low‐nanomolar agonist potency for the neurotensin receptor subtype 1 (NTS1). Interestingly, three glycosylated analogues exhibited sub‐picomolar potency in the 6 Hz limbic seizure mouse model of pharmacoresistant epilepsy following intracerebroventricular administration. Our results suggest for the first time that chemically modified NT analogues may lead to novel antiepileptic therapies.
Postmastectomy radiotherapy for breast cancer
Authors: Jagsi Reshma , Abrahamse Paul , Morrow Monica , Griggs Jennifer J. , Schwartz Kendra , Katz Steven J. 
Published: January 2009

AbstractBACKGROUND:Given accumulating evidence supporting postmastectomy radiotherapy (PMRT) in selected patients, it is important to evaluate patterns and correlates of PMRT utilization, including communication and attitudinal factors.METHODS:The authors surveyed 2382 patients diagnosed with breast cancer in 2002 and reported to the Los Angeles and Detroit Surveillance, Epidemiology, and End Results registries (n=1844, 77.4% response rate). Analyses were restricted to patients with nonmetastatic invasive breast cancer treated by mastectomy who had decided whether or not to undergo PMRT (n=396). The authors assessed rates of explanation, recommendation, and receipt of radiation by indication grouping, defined primarily by the 2001 American Society of Clinical Oncology guidelines. They evaluated correlates of PMRT receipt, including tumor and sociodemographic characteristics. They also explored patients' self‐reported reasons for nonreceipt of PMRT.RESULTS:The adjusted proportion in each indication group reporting that a provider had explained radiation was high (77% of those in whom PMRT was indicated, 76% of those in whom medical opinion was divided, and 73% of those in whom PMRT was not indicated; P = .10). The adjusted proportions reporting recommendations for radiation (86%, 35%, and 17%, respectively) and receipt (81%, 34%, and 10%, respectively) varied significantly by indication grouping (P < .001). On multivariate analysis, tumor size (P < .001), lymph node status (P < .001), comorbidity (P = .02), and chemotherapy receipt (P = .003) were found to be independent significant correlates of PMRT receipt. The most common reasons cited for not pursuing PMRT were lack of physician recommendation and perceived lack of need.CONCLUSIONS:PMRT receipt is strongly correlated with clinical indication. The authors found no sociodemographic disparities in utilization. However, approximately one‒fifth of patients with strong indications did not receive treatment. Cancer 2009. © 2009 American Cancer Society.
Loss of heterozygosities in Barrett esophagus, dysplasia, and adenocarcinoma detected by esophageal brushing cytology and gastroesophageal biopsy
Authors: Lin Xiaoqi , Finkelstein Sydney D. , Zhu Bing , Ujevich Beth J. , Silverman Jan. F. 
Published: January 2009

AbstractBACKGROUND:Esophageal brushing cytology (EBC) and gastroesophageal biopsy (GEB) are complementary procedures for the evaluation of gastroesophageal lesions that help guide surveillance and treatment.METHODS:The authors investigated loss of heterozygosity (LOH) of 17 microsatellite repeat markers near tumor suppressor genes in gastroesophageal lesions on 34 concomitant EBCs and GEBs.RESULTS:The results indicated that there was progressive accumulation of LOHs toward malignant transformation. EBC samples a greater area than GEB, and more LOHs are detected by EBC than GEB. The combination of cytomorphology and detection of LOHs can improve diagnostic accuracy and is a more useful methodology with which to evaluate gastroesophageal lesions than either EBC or GEB alone. The authors also found that LOHs at 1p36, 9p21, and 17p13 may play an important role in Barrett esophagus (BE), LOHs at 10q23, 17p13, and 17q12 in low‐grade dysplasia (LGD), LOHs at 5q23 and 17q21 in high‐grade dysplasia (HGD), and LOHs at 5q23 and 21q22 in adenocarcinoma.CONCLUSIONS:Detection of LOHs targeting tumor suppressor genes can be useful in evaluating gastroesophageal lesions, studying oncogenesis of gastroesophageal adenocarcinoma, and, in combination with EBC and GEB, determining surveillance for BE and LGD and/or treatment for HGD and adenocarcinoma. Cancer (Cancer Cytopathol) 2009. © 2009 American Cancer Society.
Mid‐IR Spectroscopy and Structural Features of Protonated Carbonic Acid in the Gas Phase
Authors: Chiavarino Barbara , Crestoni Maria Elisa , Fornarini Simonetta , Lanucara Francesco , Lemaire Joel , Maitre Philippe 
Published: January 2009

AbstractAn anti trihydroxycarbenium ion is revealed to be the gas‐phase structure of protonated carbonic acid by IR multiple‐photon dissociation spectroscopy (see picture for calculated structure and comparison of experimental and computed spectra). Deprotonation yields anti‐H2CO3 with a nominal gas‐phase basicity of 724 kJ mol−1.magnified image
Accuracy of Thinprep Imaging System in detecting atypical glandular cells
Authors: Jayamohan Yasodah , Karabakhtsian Rouzan G. , Banks Helen W. , Davey Diane D. 
Published: January 2009

AbstractThe aim of this study was to evaluate the accuracy of the ThinPrep Imaging System (Imager) in detecting atypical glandular cells (AGC) or adenocarcinoma in the 22 selected fields.All cases reported as AGC or adenocarcinoma from January 2005 to December 2006 that had been initially screened by the Imager were retrospectively reviewed to determine whether the most diagnostically relevant groups/cells were within the 22 selected fields. A total of 39 cases were reviewed. The cases were divided into two groups: the group with diagnostic cells detected within the 22 selected fields (accurately detected group) and the group with upgraded diagnosis following rescreening process (underdetected group).The Imager accurately detected 32 (82%) of cases with abnormal glandular cells, including six cases reported as adenocarcinoma, one case as adenocarcinoma in situ (AIS), and 25 cases as AGC. In seven (18%) cases, the Imager failed to detect the most abnormal cells within the 22 selected fields. Among these, one case was adenocarcinoma, while the rest were reported as AGC. Overall, four cases were assessed as atypical during quality control (QC) rescreening even though the Imager detected abnormal groups in most. Fourteen of 32 cases had abnormalities proven by histologic follow‐up.Overall, the Imager was effective in detecting most AGC, AIS and invasive adenocarcinomas. In a minority (18%) of cases, the Imager failed to detect the cells of interest within the 22 selected fields. However, full manual review of cases with potential atypical/reactive groups or endometrial groups in women ≥ 40 and QC rescreening of selected cases may help to minimize the underdetected cases. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.
Weathering the escarpment: chemical and physical rates and processes, south‐eastern Australia
Authors: Burke Benjamin C. , Heimsath Arjun M. , Dixon Jean L. , Chappell John , Yoo Kyungsoo 
Published: January 2009

AbstractDifferences in chemical weathering extent and character are expected to exist across topographic escarpments due to spatial gradients of climatic and/or tectonic forcing. The passive margin escarpment of south‐eastern Australia has a debated but generally accepted model of propagation in which it retreated (within 40 Ma) to near its current position following rifting between Australia and New Zealand 85–100 Ma before present. We focus on this escarpment to quantify chemical weathering rates and processes and how they may provide insight into scarp evolution and retreat. We compare chemical weathering extents and rates above and below the escarpment using a mass balance approach coupling major and trace element analyses with previous measurements of denudation rates using cosmogenic nuclides (10Be and 26Al). We find a slight gradient in saprolite chemical weathering rate as a percentage of total weathering rate across the escarpment. The lowlands area, encompassing the region extending from the base of the escarpment to the coast, experiences a greater extent of chemical weathering than the highland region above the escarpment. Percents of denudation attributable to saprolite weathering average 57 ± 6% and 47 ± 7% at low and high sites respectively. Furthermore, the chemical index of alteration (CIA), a ratio of immobile to mobile oxides in granitic material that increases with weathering extent, have corresponding average values of 73·7 ± 3·9 and 65·5 ± 3·4, indicating lower extents of weathering above the escarpment. Finally, we quantify variations in the rates and extent of chemical weathering at the hillslope scale across the escarpment to suggest new insight into how climate differences and hillslope topography help drive landscape evolution, potentially overprinting longer term tectonic forcing. Copyright © 2009 John Wiley & Sons, Ltd.
Strength of prefrontal activation predicts intensity of suggestion‐induced pain
Authors: Raij Tuukka T. , Numminen Jussi , Närvänen Sakari , Hiltunen Jaana , Hari Riitta 
Published: January 2009

AbstractSuggestion, a powerful factor in everyday social interaction, is most effective during hypnosis. Subjective evaluations and brain‐imaging findings converge to propose that hypnotic suggestion strongly modulates sensory processing. To reveal the brain regions that mediate such a modulation, we analyzed data from a functional‐magnetic‐resonance‐imaging study on hypnotic‐suggestion‐induced pain on 14 suggestible subjects. Activation strengths in the right dorsolateral prefrontal cortex (DLPFC) during initiation of suggestion for pain correlated positively with the subjective intensity of the subsequent suggestion‐induced pain, as well as with the strengths of the maximum pain‐related activation in the in the secondary somatosensory (SII) cortex. Furthermore, activation of the insula and the anterior cingulate cortex predicted the pain‐related SII activation. The right DLPFC, as an area important for executive functions, likely contributes to functional modulation in the modality‐specific target areas of given suggestions. Hum Brain Mapp 2009. © 2009 Wiley‐Liss, Inc.
Activation of the caudal anterior cingulate cortex due to task‐related interference in an auditory Stroop paradigm
Authors: Haupt Sven , Axmacher Nikolai , Cohen Michael X. , Elger Christian E. , Fell Juergen 
Published: January 2009

AbstractSuccessful information processing requires the focusing of attention on a certain stimulus property and the simultaneous suppression of irrelevant information. The Stroop task is a useful paradigm to study such attentional top‐down control in the presence of interference. Here, we investigated the neural correlates of an auditory Stroop task using fMRI. Subjects focused either on tone pitch (relatively high or low; phonetic task) or on the meaning of a spoken word (high/low/good; semantic task), while ignoring the other stimulus feature. We differentiated between task‐related (phonetic incongruent vs. semantic incongruent) and sensory‐level interference (phonetic incongruent vs. phonetic congruent). Task‐related interference activated similar regions as in visual Stroop tasks, including the anterior cingulate cortex (ACC) and the presupplementary motor‐area (pre‐SMA). More specifically, we observed that the very caudal/posterior part of the ACC was activated and not the dorsal/anterior region. Because identical stimuli but different task demands are compared in this contrast, it reflects conflict at a relatively high processing level. A more conventional contrast between incongruent and congruent phonetic trials was associated with a different cluster in the pre‐SMA/ACC which was observed in a large number of previous studies. Finally, functional connectivity analysis revealed that activity within the regions activated in the phonetic incongruent vs. semantic incongruent contrast was more strongly interrelated during semantically vs. phonetically incongruent trials. Taken together, we found (besides activation of regions well‐known from visual Stroop tasks) activation of the very caudal and posterior part of the ACC due to task‐related interference in an auditory Stroop task. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.
Vasoactive intestinal peptide acts via multiple signal pathways to regulate hippocampal NMDA receptors and synaptic transmission
Authors: Yang Kai , Trepanier Catherine H. , Li Hongbin , Beazely Michael A. , Lerner Ethan A. , Jackson Michael F. , MacDonald John F. 
Published: January 2009

AbstractVasoactive intestinal peptide (VIP) is a 28‐amino acid peptide, which belongs to a superfamily of structurally related peptide hormones including pituitary adenylate cyclase‐activating polypeptide (PACAP). Although several studies have identified the involvement of PACAP in learning and memory, little work has been done to investigate such a role for VIP. At least three receptors for VIP have been identified including the PACAP receptor (PAC1‐R) and the two VIP receptors (VPAC receptors). VIP can activate the PAC1‐R only if it is used at relatively high concentrations (e.g., 100 nM); however, at lower concentrations (e.g., 1 nM) it is selective for the VPAC receptors. Our lab has showed that PAC1‐R activation signals through PKC/CAKβ/Src pathway to regulate NMDA receptors; however, there is little known about the potential regulation of NMDA receptors by VPAC receptors. Our studies demonstrated that application of 1 nM VIP enhanced NMDA currents by stimulating the VPAC receptors as the effect was blocked by VPAC receptor antagonist [Ac‐Tyr1, D‐Phe2]GRF (1–29). This enhancement of NMDA currents was blocked by both Rp‐cAMPS and PKI14–22(they are highly specific PKA inhibitors), but not by the specific PKC inhibitor, bisindolylmaleimide I. In addition, the VIP‐induced enhancement of NMDA currents was accentuated by inhibition of phosphodiesterase 4, which inhibits the degradation of cAMP. This regulation of NMDA receptors also required the scaffolding protein AKAP. In contrast, the potentiation induced by high concentration of VIP (e.g., 100 nM) was mediated by PAC1‐R as well as by Src kinase. Overall, these results show that VIP can regulate NMDA receptors through different receptors and signaling pathways. © 2009 Wiley‐Liss, Inc.
Matrilysin (MMP‐7) cleaves C‐type lectin domain family 3 member A (CLEC3A) on tumor cell surface and modulates its cell adhesion activity
Authors: Tsunezumi Jun , Higashi Shouichi , Miyazaki Kaoru 
Published: January 2009

AbstractMatrilysin (MMP‐7) plays important roles in tumor progression. Previous studies have suggested that MMP‐7 binds to tumor cell surface and promotes their metastatic potential. In this study, we identified C‐type lectin domain family 3 member A (CLEC3A) as a membrane‐bound substrate of MMP‐7. Although this protein is known to be expressed specifically in cartilage, its message was found in normal breast and breast cancer tissues as well as breast and colon cancer cell lines. Because few studies have been done on CLEC3A, we overexpressed its recombinant protein in human cancer cells. CLEC3A was found in the cell membrane, extracellular matrix (ECM), and culture medium of the CLEC3A‐expressing cells. CLEC3A has a basic sequence in the NH2‐terminal domain and showed a strong heparin‐binding activity. MMP‐7 cleaved the 20‐kDa CLEC3A protein, dividing it to a 15‐kDa COOH‐terminal fragment and an NH2‐terminal fragment with the basic sequence. The 15‐kDa fragment no longer had heparin‐binding activity. Treatment of the CLEC3A‐expressing cells with MMP‐7 released the 15‐kDa CLEC3A into the culture supernatant. Furthermore, the 20‐kDa CLEC3A promoted cell adhesion to laminin‐332 and fibronectin substrates, but this activity was abrogated by the cleavage by MMP‐7. These results suggest that CLEC3A binds to heparan sulfate proteoglycans on cell surface, leading to the enhancement of cell adhesion to integrin ligands on ECM. It can be speculated that the cleavage of CLEC3A by MMP‐7 weakens the stable adhesion of tumor cells to the matrix and promotes their migration in tumor microenvironments. J. Cell. Biochem. 106: 693–702, 2009. © 2009 Wiley‐Liss, Inc.
Loss of cell–cell contacts induces NF‐κB via RhoA‐mediated activation of protein kinase D1
Authors: Cowell Catherine F. , Yan Irene K. , Eiseler Tim , Leightner Amanda C. , Döppler Heike , Storz Peter 
Published: January 2009

AbstractCell–cell contacts mediated by cadherins are known to inhibit the small Rho‐GTPase RhoA. We here show that in epithelial cells the disruption of these cell–cell contacts as mediated by a calcium switch leads to actin re‐organization and the activation of RhoA. We identified the serine/threonine kinase protein kinase D1 (PKD1) as a downstream target for RhoA in this pathway. After disruption of cell–cell contacts, PKD1 relayed RhoA activation to the induction of the transcription factor NF‐κB. We found that a signaling complex composed of the kinases ROCK, novel protein kinase C (nPKC), and Src family kinases (SFKs) is upstream of PKD1 and crucial for RhoA‐mediated NF‐κB activation. In conclusion, our data suggest a previously undescribed signaling pathway of how RhoA is activated by loss of cell–cell adhesions and by which it mediates the activation of NF‐κB. We propose that this pathway is of relevance for epithelial tumor cell biology, where loss of cell–cell contacts has been implicated in regulating cell survival and motility. J. Cell. Biochem. 106: 714–728, 2009. © 2009 Wiley‐Liss, Inc.
Secretory products from human adipocytes stimulate proinflammatory cytokine secretion from human endothelial cells
Authors: Sommer Grit , Kralisch Susan , Stangl Verena , Vietzke Angelika , Köhler Uwe , Stepan Holger , Faber Renaldo , Schubert Andreas , Lössner Ulrike , Bluher Matthias , Stumvoll Michael , Fasshauer Mathias 
Published: January 2009

AbstractHyperplasia and hypertrophy of fat cells can be found in obesity and increased adiposity is associated with endothelial dysfunction as an early event of atherosclerosis. However, it is unclear whether human adipocytes directly influence endothelial protein secretion. To study the crosstalk between fat and endothelial cells, human umbilical venous endothelial cells (HUVECs) were cultured in infranatants (Adipo) of primary differentiated human adipocytes. Interestingly, significantly increased secretion of 23 cytokines and chemokines from HUVECs was detected in four independent experiments after Adipo stimulation by protein array analysis detecting a total of 174 different proteins. Among those, time‐dependent Adipo‐induced upregulation of cytokine secretion in HUVECs was confirmed by ELISA for interleukin (IL)‐8, monokine induced by gamma interferon, macrophage inflammatory protein (MIP)‐1β, MIP‐3α, monocyte chemoattractant protein‐1, and IL‐6. Factors besides adiponectin, leptin, resistin, and tumor necrosis factor α appear to mediate these stimulatory effects. Our findings suggest that endothelial cell secretion is significantly influenced towards a proinflammatory pattern by adipocyte‐secreted factors. J. Cell. Biochem. 106: 729–737, 2009. © 2009 Wiley‐Liss, Inc.
Genomic location analysis by ChIP‐Seq
Authors: Barski Artem , Zhao Keji 
Published: January 2009

AbstractThe interaction of a multitude of transcription factors and other chromatin proteins with the genome can influence gene expression and subsequently cell differentiation and function. Thus systematic identification of binding targets of transcription factors is key to unraveling gene regulation networks. The recent development of ChIP‐Seq has revolutionized mapping of DNA–protein interactions. Now protein binding can be mapped in a truly genome‐wide manner with extremely high resolution. This review discusses ChIP‐Seq technology, its possible pitfalls, data analysis and several early applications. J. Cell. Biochem. 107: 11–18, 2009. © 2009 Wiley‐Liss, Inc.
Researching community‐based support networks: what policymakers should know
Authors: Dadich Ann 
Published: January 2009

AbstractSelf‐help support groups (SHSGs) have a valuable role in civic society. However, it is difficult to measure their value through sole use of the positivist approaches that interest policymakers. This is because SHSGs are consumer‐driven and voluntary. Thus, they cannot be regulated by research agendas or prescribed like treatment. Although social policy has an important role in the use and availability of SHSGs, the author argues that social policy research in this field needs to demonstrate paradigmatic plurality, finding balance between positivism and participatory practices. This involves engaging with group participants to identify indicators that measure group activities and impacts; appropriate research methods; and suitable timeframes. Only through paradigmatic plurality will social policy fulfill its role in enhancing community well‐being. © 2009 Wiley Periodicals, Inc.
Trend patterns in global sea surface temperature
Authors: Barbosa Susana M. , Andersen Ole B. 
Published: January 2009

AbstractIsolating long‐term trend in sea surface temperature (SST) from El Niño southern oscillation (ENSO) variability is fundamental for climate studies. In the present study, trend‐empirical orthogonal function (EOF) analysis, a robust space‐time method for extracting trend patterns, is applied to isolate low‐frequency variability from time series of SST anomalies for the 1982–2006 period. The first derived trend pattern reflects a systematic decrease in SST during the 25‐year period in the equatorial Pacific and an increase in most of the global ocean. The second trend pattern reflects mainly ENSO variability in the Pacific Ocean. The examination of the contribution of these low‐frequency modes to the globally averaged SST fluctuations indicates that they are able to account for most (>90%) of the variability observed in global mean SST. Trend‐EOFs perform better than conventional EOFs when the interest is on low‐frequency rather than on maximum variance patterns, particularly for short time series such as the ones resulting from satellite retrievals. Copyright © 2009 Royal Meteorological Society