bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intricate gene regulatory networks of helix‐loop‐helix (HLH) proteins support regulation of bone‐tissue related genes during osteoblast differentiation
Authors: Zhang Ying , Hassan Mohammad Q. , Li Zhao‐Yong , Stein Janet L. , Lian Jane B. , van Wijnen Andre J. , Stein Gary S. 
Published: July 2008

AbstractHelix‐loop‐helix (HLH) transcription factors are key regulators of neurogenesis, myogenesis and osteogenesis. Here the relative contributions of multiple classes of HLH factors to the expression of bone related genes during osteoblast maturation were compared. We examined the expression of a panel of HLH proteins (e.g., Twist1/2, USF1/2, c‐Myc, Id1 ∼ 4, E12/47, Stra13) and one Zn finger protein (Snail which recognizes a subset of E‐boxes), during osteoblast differentiation and their functional contributions to bone phenotypic gene regulation. While expression of Twist1, Stra13, E12/47 and Snail transcripts remains relatively constant, expression of Twist2 as well as the inhibitory factors Id1, Id2, Id3, and Id4 decreases and USF1 is up‐regulated during osteoblastic differentiation of MC3T3 cells. Forced expression of selected HLH transcription factors shows that Myc, Snail and USF factors increase expression of the bone markers osteocalcin (OC) and/or alkaline phosphatase (AP), while E12/47, Twist and Id factors decrease their expression. None of these factors affect Runx2 gene expression. Interestingly, Snail enhances expression of osteoblast markers, while Twist1 and Twist2 factors are cross‐regulated and inhibit bone specific gene expression and other HLH proteins (e.g., Id) indirectly. Thus, our data suggest that the integrated activities of negative and positive E‐box related regulatory factors control osteoblast differentiation. J. Cell. Biochem. 105: 487–496, 2008. © 2008 Wiley‐Liss, Inc.
Quercetin suppresses hypoxia‐induced accumulation of hypoxia‐inducible factor‐1α (HIF‐1α) through inhibiting protein synthesis
Authors: Lee Dae‐Hee , Lee Yong J. 
Published: July 2008

AbstractQuercetin, a ubiquitous bioactive plant flavonoid, has been shown to inhibit the proliferation of cancer cells and induce the accumulation of hypoxia‐inducible factor‐1α (HIF‐1α) in normoxia. In this study, under hypoxic conditions (1% O2), we examined the effect of quercetin on the intracellular level of HIF‐1α and extracellular level of vascular endothelial growth factor (VEGF) in a variety of human cancer cell lines. Surprisingly, we observed that quercetin suppressed the HIF‐1α accumulation during hypoxia in human prostate cancer LNCaP, colon cancer CX‐1, and breast cancer SkBr3 cells. Quercetin treatment also significantly reduced hypoxia‐induced secretion of VEGF. Suppression of HIF‐1α accumulation during treatment with quercetin in hypoxia was not prevented by treatment with 26S proteasome inhibitor MG132 or PI3K inhibitor LY294002. Interestingly, hypoxia (1% O2) in the presence of 100 µM quercetin inhibited protein synthesis by 94% during incubation for 8 h. Significant quercetin concentration‐dependent inhibition of protein synthesis and suppression of HIF‐1α accumulation were observed under hypoxic conditions. Treatment with 100 µM cycloheximide, a protein synthesis inhibitor, replicated the effect of quercetin by inhibiting HIF‐1α accumulation during hypoxia. These results suggest that suppression of HIF‐1α accumulation during treatment with quercetin under hypoxic conditions is due to inhibition of protein synthesis. J. Cell. Biochem. 105: 546–553, 2008. © 2008 Wiley‐Liss, Inc.
EVI1 recruits the histone methyltransferase SUV39H1 for transcription repression
Authors: Cattaneo Francesca , Nucifora Giuseppina 
Published: July 2008

AbstractEVI1 is an oncoprotein inappropriately expressed in acute myeloid leukemia and myelodysplastic syndrome cells. In vitro studies indicate that diverse biological properties can be attributed to this protein. Its role in leukemogenesis is still unclear but it is thought that overall EVI1 can act mostly as a transcription repressor through its interaction with a subset of histone deacetylases. Studies with histone deacetylase inhibitors have however indicated that EVI1‐mediated repression can be only partially rescued by deacetylase inhibitor drugs, suggesting that additional chromosomal modifications might occur to induce gene repression by EVI1. To investigate whether histone methylation contributes to the repressive potential of EVI1, we examined a potential association between EVI1, the histone methyltransferase (HMT) SUV39H1, and methyltransferase activity in vitro. We find that EVI1 directly interacts with SUV39H1 and that the proteins form an active complex with methyltransferase activity in vitro. Our data indicate that SUV39H1 enhances the transcription repressive potential of EVI1 in vivo. We suggest that EVI1 affects promoters' activity in two different pathways, by association with histone deacetylases and by recruiting chromatin‐modifying enzymes to impose a heterochromatin‐like structure establishing a lasting transcription repression. J. Cell. Biochem. 105: 344–352, 2008. © 2008 Wiley‐Liss, Inc.
Does clofazimine (B663) reach Mycobacterium leprae persisting in Schwann cells and endothelial cells of endoneurial blood vessels in peripheral nerves?
Authors: Kumar V. 
Published: July 2008

AbstractPeripheral nerve biopsies from 10 Lepromatous leprosy (LL) patients who were on multidrug treatment (MDT) were investigated by light and electron microscopy. Clofazimine (CLF) has been included as an essential component of MDT, which is the standard WHO regimen for treatment of leprosy. The patients receiving continuous MDT for a long period had viable bacilli in Schwann cells (SCs) of peripheral nerves whereas they had disappeared from the skin. Our ultrastructural observations clearly indicated the presence of CLF crystals in SCs. The crystals were in the form of osmiophilic rods of various shapes and sizes. On the other hand, the blood nerve barrier was clearly noticed in endoneurial blood vessels (EBV), and the barrier seems to play an important role for penetration of antileprosy drugs especially CLF. Microsc. Res. Tech., 2008 © 2008 Wiley‐Liss, Inc.
David Shakow and schizophrenia research at Worcester State Hospital: The roots of the scientist‐practitioner model
Authors: Cautin Robin L. 
Published: July 2008

AbstractAs Chief Psychologist and Director of Psychological Research at Worcester State Hospital (WSH), David Shakow (1901–1981) made substantial contributions to the scientific study of schizophrenia and by extension to the study of psychopathology in general. His methodological innovations—particularly on issues of diagnosis and conditions of testing—set a new standard for experimental rigor in the field. Shakow helped to establish many of what are considered basic facts about schizophrenia. His empirical work at WSH—specifically on the crossover effect—provided the scientific foundation for his theory of schizophrenic cognition, known as segmental set. Moreover, Shakow's schizophrenia work informed his developing ideas on the synergy between clinical practice and research. © 2008 Wiley Periodicals, Inc.
Science and culture around the Montessori's first “Children's Houses” in Rome (1907–1915)
Authors: Foschi Renato 
Published: July 2008

AbstractBetween 1907 and 1908, Maria Montessori's (1870–1952) educational method was elaborated at the Children's Houses of the San Lorenzo district in Rome. This pioneering experience was the basis for the international fame that came to Montessori after the publication of her 1909 volume dedicated to her “Method.” The “Montessori Method” was considered by some to be scientific, liberal, and revolutionary. The present article focuses upon the complex contexts of the method's elaboration. It shows how the Children's Houses developed in relation to a particular scientific and cultural eclecticism. It describes the factors that both favored and hindered the method's elaboration, by paying attention to the complex network of social, institutional, and scientific relationships revolving around the figure of Maria Montessori. A number of “contradictory” dimensions of Montessori's experience are also examined with a view to helping to revise her myth and offering the image of a scholar who was a real early‐twentieth‐century prototype of a “multiple” behavioral scientist. © 2008 Wiley Periodicals, Inc.
Body mass estimation in xenarthra: A predictive equation suitable for all quadrupedal terrestrial placentals?
Authors: De Esteban‐Trivigno Soledad , Mendoza Manuel , De Renzi Miquel 
Published: July 2008

AbstractThe Magnorder Xenarthra includes strange extinct groups, like glyptodonts, similar to large armadillos, and ground sloths, terrestrial relatives of the extant tree sloths. They have created considerable paleobiological interest in the last decades; however, the ecology of most of these species is still controversial or unknown. The body mass estimation of extinct species has great importance for paleobiological reconstructions. The commonest way to estimate body mass from fossils is through linear regression. However, if the studied species does not have similar extant relatives, the allometric pattern described by the regression could differ from those shown by the extinct group. That is the case for glyptodonts and ground sloths. Thus, stepwise multiple regression were developed including extant xenarthrans (their taxonomic relatives) and ungulates (their size and ecological relatives). Cases were weighted to maximize the taxonomic evenness. Twenty‐eight equations were obtained. The distribution of the percent of prediction error (%PE) was analyzed between taxonomic groups (Perissodactyla, Artiodactyla, and Xenarthra) and size groups (0–20 kg, 20–300 kg, and more than 300 kg). To assess the predictive power of the functions, equations were applied to species not included in the regression development [test set cross validation, (TSCV)]. Only five equations had a homogeneous %PE between the aforementioned groups. These were applied to five extinct species. A mean body mass of 80 kg was estimated for Propalaehoplophorus australis (Cingulata: Glyptodontidae), 594 kg for Scelidotherium leptocephalum (Phyllophaga: Mylodontidae), and 3,550.7 kg for Lestodon armatus (Phyllophaga: Mylodontidae). The high scatter of the body mass estimations obtained for Catonyx tarijensis (Phyllophaga: Mylodontidae) and Thalassocnus natans (Phyllophaga: Megatheriidae), probably due to different specializations, prevented us from predicting its body mass. Surprisingly, although obtained from ungulates and xenarthrans, these five selected equations were also able to predict the body mass of species from groups as different as rodents, carnivores, hyracoideans, or tubulidentates. This result suggests the presence of a complex common allometric pattern for all quadrupedal placentals. J. Morphol., 2008. © 2008 Wiley‐Liss, Inc.
Phage display screening in low dielectric media
Authors: Olofsson Linus , Söderberg Pernilla , Ankarloo Jonas , Nicholls Ian A. 
Published: July 2008

AbstractHere we report the first application of phage display screening in low dielectric media. Two series of phage clones with affinity for α‐chymotrypsin (CT) were selected from a Ph.D.TM‐C7C library, using either a buffer or acetonitrile in buffer (50%, v/v). The affinity of lysates, individual clones or selected cyclic peptides for the enzyme was studied by examining their influence on CT activity. Peptides displayed on phage selected in buffer provided significant protection from enzyme autolysis resulting in marked increase in CT activity (>100%). Phage selected in ACN provided some, albeit weak, protection from the detrimental influence on CT from ACN. In conclusion, the results demonstrate the potential for the application of phage display screening protocols to targets in media of low dielectricity. Copyright © 2008 John Wiley & Sons, Ltd.
Structural and dynamic roles of permanent water molecules in ligand molecular recognition by chicken liver bile acid binding protein
Authors: Ricchiuto Piero , Rocco Alessandro Guerini , Gianazza Elisabetta , Corrada Dario , Beringhelli Tiziana , Eberini Ivano 
Published: July 2008

AbstractChicken liver bile acid binding protein (cL‐BABP) crystallizes with water molecules in its binding site. To obtain insights on the role of internal water, we performed two 100 ns molecular dynamics (MD) simulations in explicit solvent for cL‐BABP, as apo form and as a complex with two molecules of cholic acid, and analyzed in detail the dynamics properties of all water molecules. The diffusion coefficients of the more persistent internal water molecules are significantly different from the bulk, but similar between the two protein forms. A different number of molecules and a different organization are observed for apo‐ and holo‐cL‐BABP. Most water molecules identified in the binding site of the apo‐crystal diffuse to the bulk during the simulation. In contrast, almost all the internal waters of the holo‐crystal maintain the same interactions with internal sidechains and ligands, which suggests they have a relevant role in protein‐ligand molecular recognition. Only in the presence of these water molecules we were able to reproduce, by a classical molecular docking approach, the structure of the complex cL‐BABP::cholic acid with a low ligand root mean square deviation (RMSD) with respect to its reference positioning. Literature data reported a conserved pattern of hydrogen bonds between a single water molecule and three amino acid residues of the binding site in a series of crystallized FABP. In cL‐BABP, the interactions between this conserved water molecule and the three residues are present in the crystal of both apo‐ and holo‐cL‐BABP but are lost immediately after the start of molecular dynamics. Copyright © 2008 John Wiley & Sons, Ltd.
Pain relief by gabapentin and pregabalin via supraspinal mechanisms after peripheral nerve injury
Authors: Tanabe Mitsuo , Takasu Keiko , Takeuchi Yuichi , Ono Hideki 
Published: July 2008

AbstractThe antihypersensitivity actions of gabapentin and pregabalin have been well characterized in a large number of studies, although the underlying mechanisms have yet to be defined. We have been focusing on the supraspinal structure as a possible site for their action and have demonstrated that intracerebroventricular (i.c.v.) administration of gabapentin and pregabalin indeed decreases thermal and mechanical hypersensitivity in a murine chronic pain model involving partial ligation of the sciatic nerve. This novel supraspinally mediated analgesic effect was markedly suppressed by either depletion of central noradrenaline (NA) or blockade of spinal α2‐adrenergic receptors. Moreover, i.c.v. injection of gabapentin and pregabalin increased spinal NA turnover in mice only after peripheral nerve injury. In locus coeruleus (LC) neurons in brainstem slices prepared from mice after peripheral nerve injury, gabapentin reduced the γ‐aminobutyric acid (GABA) type A receptor‐mediated inhibitory postsynaptic currents (IPSCs). Glutamate‐mediated excitatory synaptic transmission was hardly affected. Moreover, gabapentin did not reduce IPSCs in slices taken from mice given a sham operation. Although gabapentin altered neither the amplitude nor the frequency of miniature IPSCs, it reduced IPSCs together with an increase in the paired‐pulse ratio, suggesting that gabapentin acts on the presynaptic GABAergic nerve terminals in the LC. Together, the data suggest that gabapentin presynaptically reduces GABAergic synaptic transmission, thereby removing the inhibitory influence on LC neurons only in neuropathic pain states, leading to activation of the descending noradrenergic system. © 2008 Wiley‐Liss, Inc.
In vivo effects of phosphodiesterase inhibition on basal cyclic guanosine monophosphate levels in the prefrontal cortex, hippocampus and cerebellum of freely moving rats
Authors: Marte Antonella , Pepicelli Olimpia , Cavallero Anna , Raiteri Maurizio , Fedele Ernesto 
Published: July 2008

AbstractWe have characterized the various phosphodiesterases (PDE) that degrade cyclic GMP in the prefrontal cortex, hippocampus, and cerebellum using the microdialysis technique to measure in vivo extracellular cyclic GMP in awake rats. The following PDE blockers were used (100 and 1,000 μM): 8‐methoxymethyl‐IBMX (8‐MM‐IBMX), erythro‐9‐(2‐hydroxy‐3‐nonyl)adenine (EHNA), milrinone, rolipram, and zaprinast. For solubility reasons, sildenafil was tested only at 100 μM. All drugs were administered locally in the brain regions through the dialysis probe. At 100 μM, 8‐MM‐IBMX enhanced the cyclic nucleotide extracellular levels in the prefrontal cortex and hippocampus but not in the cerebellum; EHNA and milrinone were active only in the hippocampus; rolipram was devoid of any effect; zaprinast and sildenafil were effective in all three brain areas. At 1 mM, 8‐MM‐IBMX, milrinone, and zaprinast increased extracellular cyclic GMP in all the brain regions examined, EHNA became active also in the prefrontal cortex and rolipram showed a significant effect only in the cerebellum. This is the first in vivo functional study showing that, in cortex, PDE1, ‐2, and ‐5/9 degrade cGMP, with PDE9 probably playing a major role; in hippocampus, PDE5/9 and PDE1 are mainly involved and seem almost equally active, but PDE2 and ‐3 also contribute; in cerebellum, PDE5/9 are the main cGMP hydrolyzing enzymes, but also PDE1 and ‐4 significantly operate. © 2008 Wiley‐Liss, Inc.
Up‐regulation of brain‐derived neurotrophic factor by application of fibroblast growth factor‐2 to the cut optic nerve is important for long‐term survival of retinal ganglion cells
Authors: Blanco Rosa E. , Soto Ileana , Duprey‐Díaz Mildred , Blagburn Jonathan M. 
Published: July 2008

AbstractApplication of basic fibroblast growth factor (FGF‐2) to the optic nerve after axotomy promotes the survival of retinal ganglion cells (RGCs) in the frog Rana pipiens and results in a rapid up‐regulation of brain‐derived neurotrophic factor (BDNF) and TrkB synthesis by the RGCs. Here we investigate whether this up‐regulation is maintained over the long term and whether it is required for FGF‐2's survival effect. At 6 weeks after axotomy and FGF‐2 treatment, we found more RGCs immunopositive for BDNF protein and higher intensity of BDNF and TrkB immunostaining, accompanied by increases in BDNF and TrkB mRNA in RGCs. Application of fluorescently labeled siRNA targeted against BDNF to the cut RGC axons showed that it was transported to the cell bodies. Axonal siRNA treatment eliminated the increases in BDNF immunostaining and mRNA that were induced by FGF‐2 and had no effect on TrkB mRNA. This reduction in BDNF synthesis by siRNA greatly reduced the long‐term survival effect of FGF‐2 on RGCs. This, taken together with previous results, suggests that, although FGF‐2 may initially activate survival pathways via ERK signaling, its main long‐term survival effects are mediated via its up‐regulation of BDNF synthesis by the RGCs. © 2008 Wiley‐Liss, Inc.
Mechanism of neuroprotection by donepezil pretreatment in rat cortical neurons chronically treated with donepezil
Authors: Takada‐Takatori Yuki , Kume Toshiaki , Ohgi Yuta , Izumi Yasuhiko , Niidome Tetsuhiro , Fujii Takeshi , Sugimoto Hachiro , Akaike Akinori 
Published: July 2008

AbstractPreviously, we showed that in rat cortical neurons, chronic donepezil treatment (10 μM, 4 days) up‐regulates nicotinic receptors (nAChR) and makes neurons more sensitive to the neuroprotective effect of donepezil. Here we examined the mechanism of donepezil‐induced neuroprotection in neurons chronically treated with donepezil. The mechanism of neuroprotection was examined under different conditions of exposure to glutamate, acute and moderate, that induce cell death associated with necrotic and apoptotic cell death, respectively. Concomitant treatment with antagonists of nAChRs but not muscarinic receptors inhibited donepezil pretreatment‐induced neuroprotection against acute glutamate treatment‐induced death. Donepezil pretreatment prevented acute glutamate‐ and ionomycin‐induced neurotoxicity, but notS‐nitrosocysteine‐induced neurotoxicity, suggesting that donepezil protects neurons via nAChR at levels before nitric oxide synthase activation against acute glutamate neurotoxicity. Concomitant treatment with antagonists of nAChR or phosphatidylinositol 3‐kinase (PI3K) signaling inhibitors significantly inhibited neuroprotection against moderate glutamate neurotoxicity and decreased the phosphorylation level of Akt. Neuroprotection was also inhibited by treatment with inhibitor of mitogen‐activated protein kinase (MAPK) kinase. These results suggest that donepezil protects neurons against moderate glutamate neurotoxicity via nAChR‐PI3K‐Akt and MAPK signaling pathways. This study provides novel insight into the mechanism of donepezil‐induced neuroprotection that involves nAChR up‐regulation. © 2008 Wiley‐Liss, Inc.
Induction of the kynurenine pathway by neurotropic influenza a virus infection
Authors: Holtze Maria , Asp Linnéa , Schwieler Lilly , Engberg Göran , Karlsson Håkan 
Published: July 2008

AbstractGlutamatergic NMDA (N‐methylD‐aspartate) receptors play a critical role in brain development and neurotransmission. Kynurenic acid, an end product of tryptophan degradation along the kynurenine pathway, is an endogenous NMDA receptor antagonist. In the present study, the effects of neurotropic influenza A virus infection on the kynurenine pathway were investigated in mouse brain primary cell cultures and in mouse brain after infection on day 3 of postnatal life. Altered levels of transcripts encoding several key enzymes of the kynurenine pathway were observed in infected neuron and glial cell cultures. In vivo, changes in the levels of such transcripts in brain were observed on postnatal days 7 and 13 but not on day 24. On postnatal day 13, infiltrating T lymphocytes and increased levels of kynurenic acid were observed in the brains of the infected animals. Taken together, the present results indicate that central nervous system infections during early life can activate the entire kynurenine pathway. Such activation is likely to result in the generation of several bioactive metabolites, as supported by our finding of a transient increase of kynurenic acid. In light of its antagonistic actions on the NMDA receptor, kynurenic acid can potentially link infections with glutamatergic signaling in the developing brain. © 2008 Wiley‐Liss, Inc.