bluuebunny/crossref_metadata_2025_split huggingface dataset:
A PBL Experience in the Teaching of Computer Graphics
Authors: Martí E. , Gil D. , Julià C. 
Published: March 2006

Abstract Project‐Based Learning (PBL) is an educational strategy to improve student's learning capability that, in recent years, has had a progressive acceptance in undergraduate studies. This methodology is based on solving a problem or project in a student working group. In this way, PBL focuses on learning the necessary tools to correctly find a solution to given problems. Since the learning initiative is transferred to the student, the PBL method promotes students own abilities. This allows a better assessment of the true workload that carries out the student in the subject. It follows that the methodology conforms to the guidelines of the Bologna document, which quantifies the student workload in a subject by means of the European credit transfer system (ECTS). PBL is currently applied in undergraduate studies needing strong practical training such as medicine, nursing or law sciences. Although this is also the case in engineering studies, amazingly, few experiences have been reported. In this paper we propose to use PBL in the educational organization of the Computer Graphics subjects in the Computer Science degree. Our PBL project focuses in the development of a C++ graphical environment based on the OpenGL libraries for visualization and handling of different graphical objects. The starting point is a basic skeleton that already includes lighting functions, perspective projection with mouse interaction to change the point of view and three predefined objects. Students have to complete this skeleton by adding their own functions to solve the project. A total number of 10 projects have been proposed and successfully solved. The exercises range from human face rendering to articulated objects, such as robot arms or puppets. In the present paper we extensively report the statement and educational objectives for two of the projects: solar system visualization and a chess game. We report our earlier educational experience based on the standard classroom theoretical, problem and practice sessions and the reasons that motivated searching for other learning methods. We have mainly chosen PBL because it improves the student learning initiative. We have applied the PBL educational model since the beginning of the second semester. The student's feedback increases in his interest for the subject. We present a comparative study of the teachers' and students' workload between PBL and the classic teaching approach, which suggests that the workload increase in PBL is not as high as it seems.
Elucidating the murine brain transcriptional network in a segregating mouse population to identify core functional modules for obesity and diabetes
Authors: Lum Pek Yee , Chen Yanqing , Zhu Jun , Lamb John , Melmed Shlomo , Wang Susanna , Drake Tom A. , Lusis Aldons J. , Schadt Eric E. 
Published: March 2006

AbstractComplex biological systems are best modeled as highly modular, fluid systems exhibiting a plasticity that allows them to adapt to a vast array of changing conditions. Here we highlight several novel network‐based approaches to elucidate genetic networks underlying complex traits. These integrative genomic approaches combine large‐scale genotypic and gene expression results in segregating mouse populations to reconstruct reliable genetic networks underlying complex traits such as disease or drug response. We apply these novel approaches to one of the most extensive surveys of gene expression studies ever undertaken in whole brain in a segregating mouse population. More than 23,000 genes were monitored in whole brain samples from more than 300 mice derived from an F2 intercross population and genotyped at over 1200 SNP markers uniformly spread over the entire genome. We explore the topological properties of the brain transcriptional network and highlight different approaches to inferring causal associations among genes by integrating genotypic and expression data. We demonstrate the utility of these approaches by identifying and experimentally validating brain gene expression traits predicted to respond to a strong expression quantitative trait locus (eQTL) for the pituitary tumor‐transforming 1 gene (Pttg1) that coincides with the physical location of this gene (a cis eQTL). We identify core functional modules making up the brain transcriptional network in mice that are coherent for core biological processes associated with metabolic disease traits including obesity and diabetes.
The norepinephrine transporter and its regulation
Authors: Mandela Prashant , Ordway Gregory A. 
Published: March 2006

AbstractFor many years, the norepinephrine transporter (NET) was considered a ‘static’ protein that contributed to the termination of the action of norepinephrine in the synapse of noradrenergic neurons. The concept that the NET is dynamically regulated, adjusting noradrenergic transmission by changing its function and/or expression, was considered initially in the mid 1980s. Since that time, a plethora of studies demonstrate that the NET is regulated by several intracellular and extracellular signaling molecules, and that phosphorylation of the NET is a major pathway regulating its cell surface expression and thereby its function. The NET is a target of action of a number of drugs that are used long‐term therapeutically or abused chronically. This has driven numerous investigations of how the NET and its function are regulated by long‐term exposure to drugs. While repeated exposure to many drugs has been shown to affect NET function and expression, the intracellular mechanisms for these effects remains elusive.
Role of phospholipase D2 in the agonist‐induced and constitutive endocytosis of G‐protein coupled receptors
Authors: Koch Thomas , Wu Dai‐Fei , Yang Li‐Quan , Brandenburg Lars‐Ove , Höllt Volker 
Published: March 2006

AbstractWe have recently shown that the μ‐opioid receptor [MOR1, also termed μ‐opioid peptide (MOP) receptor] is associated with the phospholipase D2 (PLD2), a phospholipid‐specific phosphodiesterase located in the plasma membrane. We further demonstrated that, in human embryonic kidney (HEK) 293 cells co‐expressing MOR1 and PLD2, treatment with (D‐Ala2, Me Phe4, Glyol5)enkephalin (DAMGO) led to an increase in PLD2 activity and an induction of receptor endocytosis, whereas morphine, which does not induce opioid receptor endocytosis, failed to activate PLD2. In contrast, a C‐terminal splice variant of the μ‐opioid receptor (MOR1D, also termed MOP1D) exhibited robust endocytosis in response to both DAMGO and morphine treatment. We report here that MOR1D also mediates an agonist‐independent (constitutive) PLD2‐activation facilitating agonist‐induced and constitutive receptor endocytosis. Inhibition of PLD2 activity by over‐expression of a dominant negative PLD2 (nPLD2) blocked the constitutive PLD2 activation and impaired the endocytosis of MOR1D receptors. Moreover, we provide evidence that the endocytotic trafficking of the δ‐opioid receptor [DOR, also termed δ‐opioid peptide (DOP) receptor] and cannabinoid receptor isoform 1 (CB1) is also mediated by a PLD2‐dependent pathway. These data indicate the generally important role for PLD2 in the regulation of agonist‐dependent and agonist‐independent G protein‐coupled receptor (GPCR) endocytosis.
Ethanol enhancement of cocaine‐ and amphetamine‐regulated transcript mRNA and peptide expression in the nucleus accumbens
Authors: Salinas Armando , Wilde Jennifer D. , Maldve Regina E. 
Published: March 2006

AbstractCocaine‐ and amphetamine‐regulated transcript (CART) is a peptide neurotransmitter that has been implicated in drug reward and reinforcement. CART mRNA and peptide expression are highly concentrated in several compartments of the mesolimbic reward pathway. Several lines of evidence suggest that CART peptides may contribute to rewarding behaviors and the addiction liability of psychostimulants; however, there are no reports of basic work concerning CART in relation to alcohol and mechanisms of alcohol dependence development. Therefore, in this study we investigated the response of CART transcript and peptide to acute ethanol administration in vivo. Rats were administered ethanol (1 g/kg or 3.5 g/kg, 1 h, ip) and CART expression was measured by RT‐PCR in the nucleus accumbens (NAcc). Ethanol (3.5 g/kg) increased CART transcription markedly. The interactions of dopamine on ethanol‐induced CART expression were further evaluated pharmacologically using D1 and D2/D3 receptor antagonists. Both SCH 23390 (0.25 mg/kg) or raclopride (0.2 mg/kg) pre‐treatment significantly suppressed ethanol‐enhancement of CART mRNA transcription. Confocal immunofluorescence microscopy revealed that CART peptide immunoreactivity was also enhanced in both the core and the shell of the NAcc by ethanol administration. These findings demonstrate that CART mRNA and peptide expression are responsive to acute ethanol administrated in vivo and suggests that CART peptides may be important in regulating the rewarding and reinforcing properties of ethanol.
Mu‐opioid receptors are involved in the tolerance to nicotine antinociception
Authors: Galeote Lola , Kieffer Brigitte L. , Maldonado Rafael , Berrendero Fernando 
Published: March 2006

AbstractSeveral studies have shown the participation of the endogenous opioid system on the antinociceptive effects and addictive properties of nicotine. The aim of the present study was to explore the involvement of the mu‐opioid receptors in the development of tolerance to nicotine antinociception. Chronic treatment of C57BL/6 mice with nicotine (5 mg/kg s.c., three times daily during 12 days) resulted in tolerance to its antinociceptive responses in the tail‐immersion test. We investigated the possible existence of adaptive changes in the expression and/or functional activity of mu‐opioid receptors in these tolerant mice by using autoradiography of [3H]d‐Ala2‐MePhe4‐Gly‐ol5 enkephalin ([3H]DAMGO) binding and DAMGO‐stimulated guanosine [35S]5′‐(γ‐thio)‐triphosphate ([35S]GTPγS) binding. The density of mu‐opioid receptors in the spinal cord was not modified in nicotine‐tolerant mice, whereas a decrease was found in the caudate‐putamen, as well as in the core and the shell of the nucleus accumbens. However, the functional activity of these receptors was significantly increased in the spinal cord as a consequence of nicotine treatment. To further investigate the role of mu‐opioid receptors in the tolerance to nicotine‐induced antinociception, we evaluated this response in C57BL/6 mu‐opioid receptor knockout mice. Chronic nicotine treatment produced tolerance in both wild‐type and knockout animals, but tolerance developed faster in mice lacking mu‐opioid receptors. These results indicate that mu‐opioid receptors play an important role in the development of tolerance to nicotine antinociceptive effects.
Functional expression of the organic cation/carnitine transporter 2 in rat astrocytes
Authors: Inazu Masato , Takeda Hiroshi , Maehara Katsuyuki , Miyashita Kyoji , Tomoda Akio , Matsumiya Teruhiko 
Published: March 2006

AbstractIn this study, we sought to identify the transporters that mediate the uptake ofl‐carnitine and acetyl‐l‐carnitine in cultured rat cortical astrocytes.l‐[3H]carnitine and acetyl‐l‐[3H]carnitine uptake were both saturable, and mediated by a single Na+‐dependent transport system. Uptake of both was inhibited byl‐carnitine,d‐carnitine, acetyl‐l‐carnitine and various organic cations. Acylcarnitines (acetyl‐, butyryl‐, hexanoyl‐, octanoyl‐ and palmitoyl‐l‐carnitine) also interacted withl‐[3H]carnitine and acetyl‐l‐[3H]carnitine transport. 2‐Amino‐2‐norbornane carboxylic acid, a known inhibitor of amino acid transporter B0,+(ATB0,+), did not cause any significant inhibition. A highly significant correlation was found between the potencies of acylcarnitines in the inhibition ofl‐[3H]carnitine and acetyl‐l‐[3H]carnitine uptake and the acyl chain length of acylcarnitines. The expression of mRNA for organic cation/carnitine transporters (OCTNs), carnitine transporter 2 (CT2) and ATB0,+in astrocytes was investigated by reverse transcription (RT)–PCR. OCTN2 mRNA was expressed in astrocytes, whereas the expression of OCTN1, OCTN3 and CT2 mRNA could not be detected. ATB0,+mRNA was expressed at very low levels in astrocytes. Western blotting analysis indicated that anti‐OCTN2 polyclonal antibody recognized a band of 70 kDa in both kidney and astrocyte preparations. OCTN2 immunoreactivity was detected in rat astrocytes by immunocytochemical staining. Inhibition of OCTN2 expression by RNA interference significantly inhibitedl‐[3H]carnitine and acetyl‐l‐[3H]carnitine uptake into astrocytes. These results suggest that OCTN2 is functionally expressed in rat astrocytes, and is responsible forl‐carnitine and acetyl‐l‐carnitine uptake in these cells.
Neuroprotection against focal ischemic brain injury by the peroxisome proliferator‐activated receptor‐γ agonist rosiglitazone
Authors: Luo Yumin , Yin Wei , Signore Armando P. , Zhang Feng , Hong Zhen , Wang Suping , Graham Steven H. , Chen Jun 
Published: March 2006

AbstractPeroxisome proliferator‐activated receptor gamma (PPAR‐γ) is a nuclear membrane‐associated transcription factor that governs the expression of various inflammatory genes. PPAR‐γ agonists protect peripheral organs from ischemic injury. In the present study, we investigated whether the PPAR‐γ agonist rosiglitazone is neuroprotective against focal ischemic brain injury. C57/B6 mice underwent 1.5‐h middle cerebral artery occlusion, and received either vehicle or rosiglitazone treatment of 0.75, 1.5, 3, 6 or 12 mg/kg (n = 9 per group). Cerebral infarct volume, neurological function, expression of pro‐inflammatory proteins and neutrophil accumulation were assessed after ischemia and reperfusion. At 48 h after ischemia, infarct volume was significantly decreased with 3–12 mg/kg of rosiglitazone, with a time window of efficacy of 2 h after ischemia at the optimal dose (6 mg/kg). Neutrophil accumulation was significantly decreased in the brain parenchyma of rosiglitazone‐treated mice. Ischemia‐induced expression of several inflammatory cytokines and chemokines was markedly reduced in rosiglitazone‐treated brains, as determined using proteomic‐array analysis. Rosiglitazone treatment improved neurological function at 7 days after ischemia. Moreover, in cultured cortical primary microglia, rosiglitazone attenuated inflammatory responses by decreasing lipopolysaccharide‐induced release of tumor necrosis factor‐α, interleukin (IL)‐1β and IL‐6. These results suggest that the PPAR‐γ agonist rosiglitazone has neuroprotective properties that are at least partially mediated via anti‐inflammatory actions, and is thus a potential novel therapeutic agent for stroke.
Pharmacologically induced calcium oscillations protect neurons from increases in cytosolic calcium after trauma
Authors: Geddes‐Klein Donna M. , Serbest Gul , Mesfin Mahlet N. , Cohen Akiva S. , Meaney David F. 
Published: March 2006

AbstractIncreases in cytosolic calcium ([Ca2+]i) following mechanical injury are often considered a major contributing factor to the cellular sequelae in traumatic brain injury (TBI). However, very little is known on how developmental changes may affect the calcium signaling in mechanically injured neurons. One key feature in the developing brain that may directly impact its sensitivity to stretch is the reduced inhibition which results in spontaneous [Ca2+]i oscillations. In this study, we examined the mechanism of stretch‐induced [Ca2+]i transients in 18‐days in vitro (DIV) neurons exhibiting bicuculline‐induced [Ca2+]i oscillations. We used an in vitro model of mechanical trauma to apply a defined uniaxial strain to cultured cortical neurons and used increases in [Ca2+]i as a measure of the neuronal response to the stretch insult. We found that stretch‐induced increases in [Ca2+]i in 18‐DIV neurons were inhibited by pretreatment with either the NMDA receptor antagonist, APV [D(‐)‐2‐Amino‐5‐phosphonopentanoic acid], or by depolymerizing the actin cytoskeleton prior to stretch. Blocking synaptic NMDA receptors prior to stretch significantly attenuated most of the [Ca2+]i transient. In comparison, cultures with pharmacologically induced [Ca2+]i oscillations showed a substantially reduced [Ca2+]i peak after stretch. We provide evidence showing that a contributing factor to this mechanical desensitization from induced [Ca2+]i oscillations is the PKC‐mediated uncoupling of NMDA receptors (NMDARs) from spectrin, an actin‐associated protein, thereby rendering neurons insensitive to stretch. These results provide novel insights into how the [Ca2+]i response to stretch is initiated, and how reduced inhibition – a feature of the developing brain – may affect the sensitivity of the immature brain to trauma.
A one‐carbon modification of protein lysine associated with elevated oxidative stress in human substantia nigra
Authors: Floor Erik , Maples Anne M. , Rankin Carolyn A. , Yaganti Vamsee M. , Shank Sylvan S. , Nichols Grant S. , O'Laughlin Michael , Galeva Nadezhda A. , Williams Todd D. 
Published: March 2006

AbstractWe describe for the first time a naturally occurring lysine modification that is converted to methyllysine by reduction with sodium borohydride. This modification is ∼1.7 times as abundant in soluble proteins from human substantia nigra pars compacta as in proteins from other brain regions, possibly as a result of elevated oxidative stress in the nigra. Proteins from cultured PC12 cells exposed to oxidative stress conditions also contain elevated levels of this lysine modification. The abundance of the naturally occurring modification is roughly 0.08 nmoles/mg protein in either unstressed brain or PC12 cells. Modification levels remain stable in isolated proteins incubated for 2 h at 37°C in pH 7 buffer. We propose that the endogenous modification is the lysine Schiff base, ε‐N‐methylenelysine, and that lysine modifications may result from a reaction with formaldehyde in vivo. Rat brain contains ∼60 nmoles/g wet weight of formaldehyde, which probably includes both free and reversibly bound forms. Adding ∼35 µm HCHO to PC12 cell growth medium introduces methylenelysine modifications in cell proteins and impairs cell viability. The existence of this post‐translational modification suggests new mechanisms of oxidative stress that may contribute to tissue degeneration, including loss of nigral dopamine neurons during normal aging and in Parkinson's disease.
Choline acetyltransferase activity at different ages in brain of Ts65Dn mice, an animal model for Down's syndrome and related neurodegenerative diseases
Authors: Contestabile Andrea , Fila Tatiana , Bartesaghi Renata , Contestabile Antonio , Ciani Elisabetta 
Published: March 2006

AbstractTs65Dn mice, trisomic for a portion of chromosome 16 segmentally homologous to human chromosome 21, are an animal model for Down's syndrome and related neurodegenerative diseases, such as dementia of the Alzheimer type. In these mice, cognitive deficits and alterations in number of basal forebrain cholinergic neurons have been described. We have measured in Ts65Dn mice the catalytic activity of the cholinergic marker, choline acetyltransferase (ChAT), as well as the activity of the acetylcholine‐degrading enzyme acetylcholinesterase (AChE), in the hippocampus and in cortical targets of basal forebrain cholinergic neurons. In mice aged 10 months, ChAT activity was significantly higher in Ts65Dn mice, compared to 2N animals, in the hippocampus, olfactory bulb, olfactory cortex, pre‐frontal cortex, but not in other neocortical regions. At 19 months of age, on the other hand, no differences in ChAT activity were found. Thus, alterations of ChAT activity in these forebrain areas seem to recapitulate those recently described in patients scored as cases of mild cognitive impairment or mild Alzheimer's disease. Other neurochemical markers putatively associated with the disease progression, such as those implicating astrocytic hyperactivity and overproduction of amyloid precursor protein family, were preferentially found altered in some brain regions at the oldest age examined (19 months).
Reduction of iron‐regulated amyloid precursor protein and β‐amyloid peptide by (–)‐epigallocatechin‐3‐gallate in cell cultures: implications for iron chelation in Alzheimer's disease
Authors: Reznichenko L. , Amit T. , Zheng H. , Avramovich‐Tirosh Y. , Youdim M. B. H. , O. Weinreb  , Mandel S. 
Published: March 2006

AbstractBrain iron dysregulation and its association with amyloid precursor protein (APP) plaque formation are implicated in Alzheimer's disease (AD) pathology and so iron chelation could be considered a rational therapeutic strategy for AD. Here we analyzed the effect of the main polyphenol constituent of green tea, (–)‐epigallocatechin‐3‐gallate (EGCG), which possesses metal‐chelating and radical‐scavenging properties, on the regulation of the iron metabolism‐related proteins APP and transferrin receptor (TfR). EGCG exhibited potent iron‐chelating activity comparable to that of the prototype iron chelator desferrioxamine, and dose dependently (1–10 µm) increased TfR protein and mRNA levels in human SH‐SY5Y neuroblastoma cells. Both the immature and full‐length cellular holo‐APP were significantly reduced by EGCG, as shown by two‐dimensional gel electrophoresis, without altering APP mRNA levels, suggesting a post‐transcriptional action. Indeed, EGCG suppressed the translation of a luciferase reporter gene fused to the APP mRNA 5′‐untranslated region, encompassing the APP iron‐responsive element. The finding that Fe2SO4 reversed the action of EGCG on APP and TfR proteins reinforces the likelihood that these effects are mediated through modulation of the intracellular iron pool. Furthermore, EGCG reduced toxic β‐amyloid peptide generation in Chinese hamster ovary cells overexpressing the APP ‘Swedish’ mutation. Thus, the natural non‐toxic brain‐permeable EGCG may provide a potential therapeutic approach for AD and other iron‐associated disorders.
XBP1 induces WFS1 through an endoplasmic reticulum stress response element‐like motif in SH‐SY5Y cells
Authors: Kakiuchi Chihiro , Ishiwata Mizuho , Hayashi Akiko , Kato Tadafumi 
Published: March 2006

AbstractXBP1 is a key transcription factor in the endoplasmic reticulum (ER) stress response pathway. In a previous study, we suggested a possible link between XBP1 and bipolar disorder, but its role in neuronal cells has not yet been clarified. Here we examined the target genes of XBP1, using DNA microarray analysis in SH‐SY5Y cells transfected with an XBP1‐expressing vector. Among the genes up‐regulated by XBP1, the most significant p‐value was observed for WFS1, which is an ER stress response‐related gene. Examining the promoter region of WFS1, we found a conserved sequence (CGAGGCGCACCGTGATTGG) that is highly similar to the ER stress response element (ERSE). A promoter assay showed that this ERSE‐like motif is critical for the regulation of WFS1 by XBP1. An electrophoretic mobility shift assay suggested that XBP1 does not directly bind to this sequence. Our results demonstrate that WFS1 is one of the target genes of XBP1 in SH‐SY5Y cells.