bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrated Synthetic, Pharmacological, and Computational Investigation ofcis‐2‐(3,5‐Dichlorophenylcarbamoyl)cyclohexanecarboxylic Acid Enantiomers As Positive Allosteric Modulators of Metabotropic Glutamate Receptor Subtype 4
Authors: Christov Christo , González‐Bulnes Patricia , Malhaire Fanny , Karabencheva Tatyana , Goudet Cyril , Pin Jean‐Philippe , Llebaria Amadeu , Giraldo Jesús 
Published: December 2010

Abstract2‐(3,5‐Dichlorophenylcarbamoyl)cyclohexanecarboxylic acid (1) is a potent and selective positive allosteric modulator of metabotropic glutamate receptor subtype 4 (mGluR4). The activity of1was reported to reside in thecisdiastereomer with equal potency between its enantiomeric forms (Niswender et al.,Mol. Pharmacol.2008,74, 1345–1358). In the present study, the asymmetric synthesis of each of thecisenantiomers was performed, and their activities were compared with that of the racemictrans. In our assays, thecisenantiomers differ in potency, with one of them (1R,2S) higher and the other (1S,2R) lower than the racemictrans. High‐level quantum chemical calculations were carried out to characterize the structures of minimum energy in all‐isomer conformational space as well as particular intermediates between conformational transitions. Computational analysis identified structural features of1that can play a role in mGluR4 functionality and establish the basis for subsequent work, in which molecular chirality constructed on conformations derived from those found for the active (1R,2S) enantiomer can provide new ideas for drug discovery. Comparison between experimental and theoretical circular dichroism spectra confirmed both the absolute configuration of the (1R,2S) compound and its calculated most stable conformation, thereby supporting experimental and theoretical work.
Bioavailability of EPA and DHA delivered by gelled emulsions and soft gel capsules
Authors: Haug Ingvild J. , Sagmo Lise B. , Zeiss Daniel , Olsen Inge C. , Draget Kurt I. , Seternes Tore 
Published: December 2010

AbstractThis study presents data comparing the bioavailability of DHA and EPA delivered by two different formulations: One group received TAG fish oil in traditional soft gel capsules, whereas the other group received the TAG oil as droplets trapped inside a gelatin matrix (gelled emulsions). The incremental area under the curve (AUC0–26 h) of EPA and EPA + DHA in blood plasma from the gelled emulsions was significantly increased by 44.9 and 43.3%, respectively, compared to soft gel capsules. The maximum incremental concentration of EPA and EPA + DHA was significantly increased by 100.4 and 105.6%, respectively, compared to soft gel capsules. These results suggest that improved bioavailability of EPA and DHA may be achieved by incorporating emulsified TAG fish oil in a gel matrix prior to oral ingestion.Practical applications: This study presents a new type of vehicle for the delivery of PUFAs. The vehicles are soft and chewable with the possibility of adding flavours, sweeteners and colour, and this makes the vehicles ideal for delivery of PUFAs to consumers having problems swallowing large capsules or cod liver oil. The vehicles are already applied in products in several countries, including Norway.
Radical Intramolecular Arylation of Pyridinium Salts: A Straightforward Entry to 7‐Hydroxypyrido[2,1‐a]isoquinolinylium Salts
Authors: Castillo Rafael R. , Burgos Carolina , Vaquero Juan J. , Alvarez‐Builla Julio 
Published: December 2010

AbstractThe synthesis of 7‐hydroxypyrido[2,1‐a]isoquinolinylium salts can be achieved in moderate yields by intramolecular radical arylation of pyridinium salts obtained from substituted pyridines and o‐bromophenacyl bromides.
Kalman filtering and smoothing for model‐based signal extraction that depend on time‐varying spectra
Authors: Koopman Siem Jan , Wong Soon Yip 
Published: December 2010

AbstractWe develop a flexible semi‐parametric method for the introduction of time‐varying parameters in a model‐based signal extraction procedure. Dynamic model specifications for the parameters in the model are not required. We show that signal extraction based on Kalman filtering and smoothing can be made dependent on time‐varying sample spectra. Our new procedure starts with specifying the time‐varying spectrum as a semi‐parametric flexible spline function that can be formulated in state space form and can be treated by multivariate Kalman filter and smoothing methods. Next we show how a time series decomposition model can be made dependent on a time‐varying sample spectrum in a frequency domain analysis. The key insight is that the spectral likelihood function depends on the sample spectrum. The estimates of the model parameters are obtained by maximizing the spectral likelihood function. A time‐varying sample spectrum leads to a time‐varying spectral likelihood and hence we obtain time‐varying parameter estimates. The time series decomposition model with the resulting time‐varying parameters reflect the time‐varying spectrum accurately. This approach to model‐based signal extraction includes a bootstrap procedure to compute confidence intervals for the time‐varying parameter estimates. We illustrate the methodology by presenting a business cycle analysis for three quarterly US macroeconomic time series between 1947 and 2010. The empirical study provides strong evidence that the cyclical properties of macroeconomic time series have been changing over time. Copyright © 2010 John Wiley & Sons, Ltd.
Transoral robotic surgery and human papillomavirus status: Oncologic results
Authors: Cohen Marc A. , Weinstein Gregory S. , O'Malley Bert W. , Feldman Michael , Quon Harry 
Published: December 2010

AbstractBackgroundPatients with oropharyngeal squamous cell carcinoma (OPSCC) have been shown to have distinct outcome profiles based on their human papillomavirus (HPV) status. The purpose of this study was to assess HPV‐related outcomes after transoral robotic surgery (TORS) with adjuvant therapy as indicated.MethodsThis study consisted of a retrospective review of 50 patients with OPSCC within a prospective single‐arm cohort study. Outcome measures included HPV status, margin status, relapse pattern, and survival.ResultsThirty‐seven patients were HPV‐positive (74.0%) with 34 patients (91.9%) being serotype‐16. Negative margins were achieved in 92.3% (HPV‐negative) and 94.6% (HPV‐positive). In the HPV‐negative group, there were no local recurrences and 1 patient had both regional and distant recurrence (7.7%). In the HPV‐positive group, there were no local or regional recurrences and 2 patients (5.4%) had distant recurrences. There were no statistically significant differences in survival between the 2 cohorts (overall survival, disease‐specific survival, disease‐free survival).ConclusionTORS as a primary surgical modality, followed by adjuvant therapy as indicated, offers disease control in both HPV‐negative and HPV‐positive groups. We believe that multi‐institutional studies are warranted to further evaluate this novel approach for patients who are HPV negative and HPV positive. © 2010 Wiley Periodicals, Inc. Head Neck, 2011
Oral maxillary squamous carcinoma: An indication for neck dissection in the clinically negative neck
Authors: Montes David M. , Carlson Eric R. , Fernandes Rui , Ghali G. E. , Lubek Joshua , Ord Robert , Bell Bryan , Dierks Eric , Schmidt Brian L. 
Published: December 2010

AbstractBackgroundThis multicenter study was undertaken to characterize the metastatic behavior of oral maxillary squamous carcinoma and to determine the role of selective neck dissection.MethodsA retrospective, multicenter study of patients surgically treated for oral maxillary squamous carcinoma was completed. Data collected included primary tumor location, cervical lymph node status, and neck failure rate.ResultsThe study included 146 patients. The adjusted regional metastatic rate was 31.4%. Of those N0 (clinically negative) necks treated with or without neck dissection, 14.4% developed cervical metastasis. Within the cohort, 7.5% of patients died with distant disease. The regional salvage rate was 52.9%. None of the patients with locoregional failures were salvaged.ConclusionsMaxillary palatal, alveolar, and gingival squamous carcinomas exhibit aggressive regional metastatic behavior. Surgical salvage rates for neck failure are low; therefore, selective neck dissection (levels I–III) is recommended at the time of resection of T2, T3, and T4 maxillary squamous carcinomas. © 2010 Wiley Periodicals, Inc. Head Neck, 2011
Grid cell hexagonal patterns formed by fast self‐organized learning within entorhinal cortex
Authors: Mhatre Himanshu , Gorchetchnikov Anatoli , Grossberg Stephen 
Published: December 2010

AbstractGrid cells in the dorsal segment of the medial entorhinal cortex (dMEC) show remarkable hexagonal activity patterns, at multiple spatial scales, during spatial navigation. It has previously been shown how a self‐organizing map can convert firing patterns across entorhinal grid cells into hippocampal place cells that are capable of representing much larger spatial scales. Can grid cell firing fields also arise during navigation through learning within a self‐organizing map? This article describes a simple and general mathematical property of the trigonometry of spatial navigation which favors hexagonal patterns. The article also develops a neural model that can learn to exploit this trigonometric relationship. This GRIDSmap self‐organizing map model converts path integration signals into hexagonal grid cell patterns of multiple scales. GRIDSmap creates only grid cell firing patterns with the observed hexagonal structure, predicts how these hexagonal patterns can be learned from experience, and can process biologically plausible neural input and output signals during navigation. These results support an emerging unified computational framework based on a hierarchy of self‐organizing maps for explaining how entorhinal‐hippocampal interactions support spatial navigation. © 2010 Wiley Periodicals, Inc.
7,8‐dihydroxyflavone, a TrkB receptor agonist, blocks long‐term spatial memory impairment caused by immobilization stress in rats
Authors: Andero Raül , Daviu Núria , Escorihuela Rosa Maria , Nadal Roser , Armario Antonio 
Published: December 2010

AbstractPost‐traumatic stress disorder (PTSD) patients show cognitive deficits, but it is unclear whether these are a consequence of the pathology or a pre‐existing factor of vulnerability to PTSD. Animal models may help to demonstrate whether or not exposure to certain stressors can actually induce long‐lasting (LL; days) impairment of hippocampus‐dependent memory tasks and to characterize neurobiological mechanisms. Adult male rats were exposed to 2‐h immobilization on boards (IMO), a severe stressor, and spatial learning in the Morris water maze (MWM) was studied days later. Exposure to IMO did not modify learning or short‐term memory in the MWM when learning started 3 or 9 days after IMO, but stressed rats did show impaired long‐term memory at both times, in accordance with the severity of the stressor. New treatments to prevent PTSD symptoms are needed. Thus, considering the potential protective role of brain‐derived neurotrophic factor (BDNF) on hippocampal function, 7,8‐dihydroxyflavone (7,8‐DHF), a recently characterized agonist of the BDNF receptor TrkB, was given before or after IMO in additional experiments. Again, exposure to IMO resulted in LL deficit in long‐term memory, and such impairment was prevented by the administration of 7,8‐DHF either 2 h prior IMO or 8 h after the termination of IMO. The finding that IMO‐induced impairment of spatial memory was prevented by pharmacological potentiation of TrkB pathway with 7,8‐DHF even when the drug was given 8 h after IMO suggests that IMO‐induced impairment is likely to be a LL process that is strongly dependent on the integrity of the BDNF‐TrkB system and is susceptible to poststress therapeutic interventions. 7,8‐DHF may represent a new therapeutic approach for early treatment of subjects who have suffered traumatic experiences. © 2010 Wiley Periodicals, Inc.
Update on extracorporeal photopheresis in heart and lung transplantation
Authors: Marques Marisa B. , Schwartz Joseph 
Published: December 2010

AbstractTransplant rejection of solid organs remains a threat to thousands of patients despite modern immunosuppressive regimens. The currently available drugs are associated with severe complications such as hypertension, diabetes mellitus, renal failure, risk of infections, and malignancies among many others and, often enough, still allow episodes of rejection. New and less‐toxic immunologic measures are desperately needed to accomplish the desired tolerance to the transplant without the undesirable side effects. Extracorporeal photopheresis (ECP) has been shown to benefit especially patients with cardiac transplants, but also those who received lung allografts. ECP likely modulates the recipient's antigen‐specific immune responses and inflammation in transplantation by in vivo generation of apoptotic leukocytes. This review will highlight the need for ECP, how it is thought to act, and the published evidence for its role in cardiac and pulmonary transplantation. J. Clin. Apheresis, 2011. © 2010 Wiley‐Liss, Inc.
Oncogenic role of RUNX3 in head and neck cancer
Authors: Kudo Yasusei , Tsunematsu Takaaki , Takata Takashi 
Published: December 2010

AbstractCumulative evidences show that Runt‐related transcription factor 3 (RUNX3) has a tumor suppressive role in various cancers. In particular, RUNX3 appears to be an important component of the transforming growth factor‐β (TGF‐β)‐induced tumor suppression pathway. Contrary to reports on this tumor suppressive role of RUNX3, RUNX3 can also function as an oncogene when overexpressed. Recently, we found that RUNX3 overexpression was frequently observed and was well correlated with malignant behaviors in head and neck cancer, which is one of the most common types of human cancer. Moreover, it has been revealed that RUNX3 overexpression promoted cell growth and inhibited apoptosis in head and neck cancer cells. This review introduces the oncogenic role of RUNX3 in certain types of cancer including head and neck cancer. J. Cell. Biochem. 112: 387–393, 2011. © 2010 Wiley‐Liss, Inc.
Inducible expression of Runx2 results in multiorgan abnormalities in mice
Authors: He Nan , Xiao Zhousheng , Yin Tong , Stubbs Jason , Li Linheng , Quarles L. Darryl 
Published: December 2010

AbstractRunx2 is a transcription factor controlling skeletal development, and is also expressed in extraskeletal tissues where its function is not well understood. Existing Runx2 mutant and transgenic mouse models do not allow the necessary control of Runx2 expression to understand its functions in different tissues. We generated conditional, doxycyline‐inducible, triple transgenic mice (CMV‐Cre;ROSA26‐neoflox/+‐rtTA;Tet‐O‐Runx2) to investigate the effects of wide spread overexpression of Runx2. Osteoblasts isolated from CMV‐Cre;ROSA26‐neoflox/+‐rtTA; Tet‐O‐Runx2 mice demonstrated a dose‐dependent effect of doxycycline to stimulate Runx2 transgene expression. Doxycycline administration to CMV‐Cre;ROSA26‐neoflox/+‐rtTA;Tet‐O‐Runx2 mice induced Runx2 transgene expression in all tissues tested, with the highest levels observed in kidney, ovary, and bone. Runx2 overexpression resulted in deceased body size and reduced viability. With regard to bone, Runx2 overexpressing mice paradoxically displayed profound osteopenia and diminished osteogenesis. Induced expression of Runx2 in extraskeletal tissues resulted in ectopic calcification and induction of the osteogenic program in a limited number of tissues, including lung and muscle. In addition, the triple transgenic mice showed evidence of a myeloproliferative disorder and an apparent inhibition of lymphocyte development. Thus, overexpression of Runx2 both within and outside of the skeleton can have diverse biological effects. Use of tissue specific Cre mice will allow this model to be used to conditionally and inducibly overexpress Runx2 in different tissues and provide a means to study the post‐natal tissue‐ and cell context‐dependent functions of Runx2. J. Cell. Biochem. 112: 653–665, 2011. © 2010 Wiley‐Liss, Inc.
Loss of runt‐related transcription factor 3 causes development and progression of hepatocellular carcinoma
Authors: Shiraha Hidenori , Nishina Shin‐ichi , Yamamoto Kazuhide 
Published: December 2010

AbstractRunt‐related transcription factor 3 (RUNX3) is reported as a tumor suppressor gene for gastric cancer, and may be important in the development of hepatocellular carcinoma (HCC). RUNX3 expression is frequently lost or decreased by hemizygous deletion or hypermethylation of its promoter lesion in HCC. The significance of decreased expression of RUNX3 in HCC has not been fully elucidated, but is likely related to dysfunction of cell cycle regulation, decrement of apoptosis, enhancement of angiogenesis, and development of epithelial–mesenchymal transition. RUNX3 is a promising candidate as a tumor suppressor gene for HCC. J. Cell. Biochem. 112: 745–749, 2011. © 2010 Wiley‐Liss, Inc.
Molecular mechanisms that produce secondary MDS/AML by RUNX1/AML1 point mutations
Authors: Harada Yuka , Harada Hironori 
Published: December 2010

AbstractRUNX1/AML1 point mutations have been identified in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) patients. A heterozygous germline mutation of the RUNX1 gene causes a familial platelet disorder with a predisposition to AML. RUNX1 mutations have also been detected with high frequency in minimally differentiated AML M0 subtypes and myelodysplastic/myeloproliferative neoplasms. Here we propose a new disease category of myelodysplastic neoplasms (MDN) consisting of MDS refractory anemia with excess blasts and AML with myelodysplasia‐related changes, including therapy‐related cases. RUNX1 mutations have been detected in about 20% of patients with “MDN”. Among the MDN cases, histories of radiation exposure, therapy‐related myeloid neoplasms after successful treatment for acute promyelocytic leukemia, and leukemic transformation of myeloproliferative neoplasms have been reported to have a strong association with RUNX1 mutations. The mutations occur in a normal, a receptive, or a disease‐committed hematopoietic stem cell. It is suspected that the “MDN” phenotypes are defined by the RUNX1 mutations in addition to some other abnormalities. J. Cell. Biochem. 112: 425–432, 2011. © 2010 Wiley‐Liss, Inc.
An autonomous BMP2 regulatory element in mesenchymal cells
Authors: Kruithof Boudewijn P.T. , Fritz David T. , Liu Yijun , Garsetti Diane E. , Frank David B. , Pregizer Steven K. , Gaussin Vinciane , Mortlock Douglas P. , Rogers Melissa B. 
Published: December 2010

AbstractBMP2 is a morphogen that controls mesenchymal cell differentiation and behavior. For example, BMP2 concentration controls the differentiation of mesenchymal precursors into myocytes, adipocytes, chondrocytes, and osteoblasts. Sequences within the 3′untranslated region (UTR) of the Bmp2 mRNA mediate a post‐transcriptional block of protein synthesis. Interaction of cell and developmental stage‐specific trans‐regulatory factors with the 3′UTR is a nimble and versatile mechanism for modulating this potent morphogen in different cell types. We show here, that an ultra‐conserved sequence in the 3′UTR functions independently of promoter, coding region, and 3′UTR context in primary and immortalized tissue culture cells and in transgenic mice. Our findings indicate that the ultra‐conserved sequence is an autonomously functioning post‐transcriptional element that may be used to modulate the level of BMP2 and other proteins while retaining tissue specific regulatory elements. J. Cell. Biochem. 112: 666–674, 2011. © 2010 Wiley‐Liss, Inc.
Inhibition of HSP90‐dependent telomerase activity in amyloid β‐induced apoptosis of cerebral endothelial cells
Authors: Chiu Wen‐Ta , Shen Shing‐Chuan , Yang Liang‐Yo , Chow Jyh‐Ming , Wu Chin‐Yen , Chen Yen‐Chou 
Published: December 2010

AbstractAlthough apoptosis induced by amyloid β (Aβ) has been identified, the effect of Aβ on telomerase activity in relation to apoptosis induction remains unclear. In the present study, Aβ1–40 and Aβ25–35, but not Aβ1–16 and Aβ35–25, reduce the viability of primary cerebral endothelial cells (CECs) in accordance with apoptosis induction. Increases in caspase 3 and PARP protein cleavage with reductions of the Bcl‐2/Bax protein ratio accompanied by a loss in the mitochondria membrane potential were identified in Aβ1–40 and Aβ25–35‐treated CECs. A significant decrease in intracellular telomerase activity by Aβ1–40 and Aβ25–35 was detected; meanwhile, reduced telomerase activity by telomerase reverse transcriptase (TERT) siRNA enhanced the cytotoxic effect of Aβ. The addition of serum might block the Aβ25–35‐induced cytotoxic effect via elevated telomerase activity in according with stimulating phospho‐AKT protein expression, which was blocked by adding AKT inhibitor LY294002. Decreases in heat shock protein 90 (HSP90) and its client proteins including TERT, AKT, p53, CDK4 were observed in Aβ1–40 and Aβ25–35, but not Aβ1–16 and Aβ35–25, ‐treated CECs. The knockdown of HSP90 gene expression by HSP90 siRNA significantly inhibits telomerase activity with decreasing TERT protein expression. The application of HSP90 activity inhibitor geldanamycin (GA) and radicicol (RD) potentiates the telomerase inhibition and apoptosis induction of Aβ in CECs. An increase in protein ubiquitination by Aβ25–35, but not Aβ35–25, treatment was examined, and Aβ‐inhibited HSP90 and TERT protein expression and telomerase activity was reversed by adding proteasome inhibitor, MG132. Additionally, increased TERT protein ubiquitination by Aβ25–35 was detected in CECs via immunoprecipitation/Western blotting analysis. The data of the present study firstly demonstrates that telomerase inhibition contributes to the apoptosis induction of Aβ in CECs. J. Cell. Physiol. 226: 2041–2051, 2011. © 2010 Wiley‐Liss, Inc.
Role of bone marrow‐derived progenitor cells in the maintenance and regeneration of dental mesenchymal tissues
Authors: Zhou Jing , Shi Songtao , Shi Yuanyuan , Xie Han , Chen Lei , He Yong , Guo Weihua , Wen Lingying , Jin Yan 
Published: December 2010

AbstractWhile dental mesenchymal stem cells are well‐studied, the origin of these cells is still unclear. Bone marrow‐derived cells (BMDCs) have the potential to engraft into several tissues after injury, but whether they can become dental tissue‐specific progenitor cells under normal conditions and the relationship of these cells to the tissue‐resident cells are unknown. Thus, we transplanted green fluorescent protein (GFP)‐labeled BMDCs into irradiated wild‐type mice. We found that the engraftment of BMDCs participated in the regeneration and differentiated into periodontal specific cells after injury. Under normal conditions, there were more BMDCs engrafting into the dental mesenchymal tissue than other organs, in which the expression of stromal cell‐derived factor‐1 (SDF‐1) was significantly higher than in other organs, and the engraftment of cells increased with time. A small fraction of GFP+ cells maintained the mesenchymal stem cell phenotype positive for CD105, CD106, and CD90, which were significantly less than the tissue‐resident stem cells; meanwhile, GFP+/CD45+ cells were rare. Isolation and characterization of the dental pulp cells showed that the number of GFP+/Ki67+ cells were greater than the GFP−/Ki67+ cells. In addition, some GFP+ cells differentiated into the dental‐specific cells and expressed dental‐specific proteins, and can be found in the odontoblast layer after implantation of the apical bud. In conclusion, these data suggest that bone marrow progenitor cells communicate with dental tissues and become tissue‐specific mesenchymal progenitor cells to maintain tissue homeostasis. J. Cell. Physiol. 226: 2081–2090, 2011. © 2010 Wiley‐Liss, Inc.