bluuebunny/crossref_metadata_2025_split huggingface dataset:
Understanding the targeting of the RB family proteins by viral oncoproteins to defeat their oncogenic machinery
Authors: Bellacchio Emanuele , Paggi Marco G. 
Published: June 2012

AbstractThe retinoblastoma (RB) family consists of three genes, RB1, RBL1, and RBL2, that code for the pRb, p107, and pRb2/p130 proteins, respectively. All these factors have pivotal roles in controlling fundamental cellular mechanisms such as cell cycle, differentiation and apoptosis. The founder and the most investigated RB family protein is pRb, which is considered to be the paradigm of tumor suppressors. However, p107 and pRb2/p130 clearly display a high degree of structural and functional homology with pRb. Interestingly, these factors were first identified as physical targets of the Adenovirus E1A oncoprotein. Indeed, RB family proteins are the most important and widely investigated targets of small DNA virus oncoproteins, such as Adenovirus E1A, human papillomavirus E7 and Simian virus 40 large T antigen. By interacting with pRb and with other RB family members, these oncoproteins neutralize their growth suppressive properties, thus stimulating proliferation of the infected cells, de‐differentiation, and resistance to apoptosis. All these acquired features strongly favor the rise and selection of immortalized and mutation‐prone cells, leading to a higher propensity in undergoing transformation. Our present work aims to illustrate and delve into these protein–protein interactions. Considering that these viral oncoproteins are dispensable for normal cellular functions, they can create “oncogene addiction” in the infected/transformed cells. This makes the possibility to dismantle these interactions extremely attractive, thus promoting the development of highly specific smart molecules capable of targeting only the infected/transformed cells that express these viral factors. J. Cell. Physiol. 228: 285–291, 2013. © 2012 Wiley Periodicals, Inc.
Augmented LPS responsiveness in type 1 diabetes‐derived osteoclasts
Authors: Catalfamo Dana L. , Calderon Nadia L. , Harden Scott W. , Sorenson Heather L. , Neiva Kathleen G. , Wallet Shannon M. 
Published: June 2012

AbstractBone abnormalities are frequent co‐morbidities of type 1 diabetes (T1D) and are principally mediated by osteoblasts and osteoclasts which in turn are regulated by immunologic mediators. While decreased skeletal health in T1D involves alterations in osteoblast maturation and function, the effect of altered immune function on osteoclasts in T1D‐associated bone and joint pathologies is less understood. Here T1D‐associated osteoclast‐specific differentiation and function in the presence and absence of inflammatory mediators was characterized utilizing bone marrow‐derived osteoclasts (BM‐OCs) isolated from non‐obese diabetic (NOD) mice, a model for spontaneous autoimmune diabetes with pathology similar to individuals with T1D. Differentiation and osteoclast‐mediated bone resorption were evaluated along with cathepsin K, MMP‐9, and immune soluble mediator expression. The effect of lipopolysaccharide (LPS), a pro‐inflammatory cytokine cocktail, and NOD‐derived conditioned supernatants on BM‐OC function was also determined. Although NOD BM‐OCs cultures contained smaller osteoclasts, they resorbed more bone concomitant with increased cathepsin K, MMP‐9, and pro‐osteoclastogenic mediator expression. NOD BM‐OCs also displayed an inhibition of LPS‐induced deactivation that was not a result of soluble mediators produced by NOD BM‐OCs, although a pro‐inflammatory milieu did enhance NOD BM‐OCs bone resorption. Together these data indicate that osteoclasts from a T1D mouse model hyper‐respond to RANK‐L resulting in excessive bone degradation via enhanced cathepsin K and MMP‐9 secretion concomitant with an increased expression of pro‐osteoclastic soluble mediators. Our data also suggest that inhibition of LPS‐induced deactivation in NOD‐derived BM‐OC cultures is most likely due to NOD osteoclast responsiveness rather than LPS‐induced expression of soluble mediators. J. Cell. Physiol. 228: 349–361, 2013. © 2012 Wiley Periodicals, Inc.
On the role of retinoblastoma family proteins in the establishment and maintenance of the epigenetic landscape
Authors: Fiorentino Francesco Paolo , Marchesi Irene , Giordano Antonio 
Published: June 2012

AbstractRB family members are negative regulators of the cell cycle, involved in numerous biological processes such as cellular senescence, development and differentiation. Disruption of RB family pathways are linked to loss of cell cycle control, cellular immortalization and cancer. RB family, and in particular the most studied member RB/p105, has been considered a tumor suppressor gene by more than three decades, and numerous efforts have been done to understand his molecular activity. However, the epigenetic mechanisms behind Rb‐mediated tumor suppression have been uncovered only in recent years. In this review, the role of RB family members in cancer epigenetics will be discussed. We start with an introduction to epigenomes, chromatin modifications and cancer epigenetics. In order to provide a clear picture of the involvement of RB family in the epigenetic field, we describe the RB family role in the epigenetic landscape dynamics based on the heterochromatin variety involved, facultative or constitutive. We want to stress that, despite dissimilar modulations, RB family is involved in both mammalian varieties of heterochromatin establishment and maintenance and that disruption of RB family pathways drives to alterations of both heterochromatin structures, thus to the global epigenetic landscape. J. Cell. Physiol. 228: 276–284, 2013. © 2012 Wiley Periodicals, Inc.
Retinoic acid protects cardiomyocytes from high glucose‐induced apoptosis through inhibition of NF‐κB signaling Pathway
Authors: Nizamutdinova Irina T. , Guleria Rakeshwar S. , Singh Amar B. , Kendall Jonathan A. , Baker Kenneth M. , Pan Jing 
Published: June 2012

AbstractWe have previously shown that retinoic acid (RA) has protective effects on high glucose (HG)‐induced cardiomyocyte apoptosis. To further elucidate the molecular mechanisms of RA effects, we determined the interaction between nuclear factor (NF)‐κB and RA signaling. HG induced a sustained phosphorylation of IKK/IκBα and transcriptional activation of NF‐κB in cardiomyocytes. Activated NF‐κB signaling has an important role in HG‐induced cardiomyocyte apoptosis and gene expression of interleukin‐6 (IL‐6), tumor necrosis factor (TNF)‐α, and monocyte chemoattractant protein‐1 (MCP‐1). All‐trans RA (ATRA) and LGD1069, through activation of RAR/RXR‐mediated signaling, inhibited the HG‐mediated effects in cardiomyocytes. The inhibitory effect of RA on NF‐κB activation was mediated through inhibition of IKK/IκBα phosphorylation. ATRA and LGD1069 treatment promoted protein phosphatase 2A (PP2A) activity, which was significantly suppressed by HG stimulation. The RA effects on IKK and IκBα were blocked by okadaic acid or silencing the expression of PP2Ac‐subunit, indicating that the inhibitory effect of RA on NF‐κB is regulated through activation of PP2A and subsequent dephosphorylation of IKK/IκBα. Moreover, ATRA and LGD1069 reversed the decreased PP2A activity and inhibited the activation of IKK/IκBα and gene expression of MCP‐1, IL‐6, and TNF‐α in the hearts of Zucker diabetic fatty rats. In summary, our findings suggest that the suppressed activation of PP2A contributed to sustained activation of NF‐κB in HG‐stimulated cardiomyocytes; and that the protective effect of RA on hyperglycemia‐induced cardiomyocyte apoptosis and inflammatory responses is partially regulated through activation of PP2A and suppression of NF‐κB‐mediated signaling and downstream targets. J. Cell. Physiol. 228: 380–392, 2013. © 2012 Wiley Periodicals, Inc.
Decolorization of textile dyes by Bjerkandera sp. BOL 13 using waste biomass as carbon source
Authors: Jonstrup Maria , Kumar Naresh , Guieysse Benoit , Murto Marika , Mattiasson Bo 
Published: June 2012

AbstractBACKGROUND: Phanerochaete chrysosporium, Trametes versicolor and Bjerkandera sp BOL13 were compared for decolorization of azo dyes supplied individually or as a mixture. The dye decolorization was also evaluated during continuous treatment under non‐sterile conditions using a lignocellulosic growth substrate.RESULTS: Bjerkandera sp BOL13 showed the highest dye decolorization potential. This fungus was also found to support high decolorization of Remazol Red RR at an initial pH of 4‐6 and when using straw as co‐substrate. The fungus was evaluated for Remazol Red RR decolorization in a continuously fed packed‐bed bioreactor operated under non‐sterile conditions with 3 days of hydraulic retention time. When glucose was supplied as growth‐substrate, decolorization efficiencies of 65‐90% were maintained for 12 days in a bioreactor packed with wooden material. The decolorization efficiency was lower when glucose was not fed to the fungus or when a plastic material was used as packing. Higher manganese peroxidase and laccase activities were also recorded when the wood packing was used. Contamination caused a drop in decolorization efficiency after 17‐19 days operation.CONCLUSIONS: The potential of Bjerkandera sp BOL13 for decolorization of azo dyes under non‐sterile conditions using lignocellulosic growth substrates was demonstrated. Research is needed to reduce contamination under non‐sterile conditions. © 2012 Society of Chemical Industry
Methodology for advanced measurement accuracy of the overall volumetric oxygen transfer coefficient with application to hydrocarbon–aqueous dispersions
Authors: Clarke Kim G , Manyuchi Musaida M 
Published: June 2012

AbstractAccurate quantification of the overall volumetric oxygen transfer coefficient (KLa) is essential for the success of aerobic bioprocesses. In hydrocarbon‐based bioprocesses where KLa is depressed at higher viscosities, this is particularly critical. In this study an accessible methodology for KLa determination has been developed and validated for alkane‐based systems under a wide range of process conditions. Critical to measurement accuracy in around 90% of the KLa values was the incorporation of the response lag. Neglect of the response lag resulted in errors greater than 5% above KLa = 0.3Kp to KLa = 0.6Kp (where Kp is the inverse response lag or probe constant), at least 1.5‐fold to 3‐fold lower than the analogous KLa in water. Further, Kp varied significantly with both alkane concentration and chain length. A sensitivity analysis confirmed − 25% to 90% error in KLa with 30% over‐ and under‐estimation of Kp respectively. When incorporating Kp values specific to the process conditions, accurate KLa values were confirmed in 0 to 20% (v/v) C10–13 and C14–20 aqueous dispersions over 600 to 1200 rpm agitation. Copyright © 2012 Society of Chemical Industry
Novel two‐in‐one bioreactor greatly improves lactic acid production from xylose by Lactobacillus pentosus
Authors: Puah Sze Min , Huynh Han Vinh , Wu Jin Chuan 
Published: June 2012

AbstractBACKGROUND: Simultaneous xylose isomerization and fermentation was investigated to improve the lactic acid production from xylose by Lactobacillus pentosus in a novel two‐in‐one bioreactor constructed by packing the immobilized xylose isomerase (65 g) in a fixed bed reactor (diameter 56 mm × 66 mm, packing volume 154 mL) with a permeable wall, which was installed inside a conventional fermenter (2 L) and rotated along the axis together with the mechanical stirrer of the fermenter.RESULTS: Xylose (20 g L−1) was completely consumed within 24 h in the novel bioreactor, compared with 72 h needed for the control without packed enzyme. The maximum cell density (17.5 g L−1) in the novel bioreactor was twice that in the control and the lactic acid productivity (0.58 g L−1 h−1) was 3.8 times higher. Repeated use of the immobilized enzyme showed that the lactic acid productivity and yield obviously dropped after the first batch fermentation but maintained almost unchanged afterwards.CONCLUSION: Simultaneous xylose isomerization and fermentation significantly improved lactic acid production from xylose by Lactobacillus pentosus. The novel bioreactor made it easier to recycle and reuse the immobilized enzyme. © 2012 Society of Chemical Industry
A Cartesian non‐uniform grid interpolation method for fast field evaluation on elongated domains
Authors: Costa Nadav , Boag Amir 
Published: June 2012

SUMMARYAn algorithm for performing a fast evaluation on time harmonic fields radiated by two‐dimensional source constellations with elongated geometry is introduced. The suggested scheme attains a linear computational complexity. At the core of the algorithm is the idea of phase and amplitude compensation facilitating the conversion of fields radiated by spatially confined sources into bandlimited functions of the suitable coordinates. Thus, the fields or potentials are represented by their samples on sparse left‐side and right‐side non‐uniform Cartesian grids. These grids are employed both for the representation of outgoing fields and as targets for accumulating the incoming fields. Integrating this approach with the divide‐and‐conquer strategy, the algorithm relies on a binary hierarchical decomposition of the computational domain. The total field is computed via a two‐way multilevel process, which passes through all of the left‐side and right‐side grids, while systematically aggregating all subdomains' contributions, ending with the field interpolation back to the desired observation points. Copyright © 2012 John Wiley & Sons, Ltd.
Transcriptional profiling of microdissected areas of active multiple sclerosis lesions reveals activation of heat shock protein genes
Authors: Mycko Marcin P. , Brosnan Celia F. , Raine Cedric S. , Fendler Wojciech , Selmaj Krzysztof W. 
Published: June 2012

AbstractHeat shock proteins (HSPs) are stress‐responsive proteins that serve as important molecules contributing to cellular “protein triage.” We and others have reported an increase of selected HSPs in multiple sclerosis (MS) lesions. However, the exact expression pattern of HSP family genes in MS is not known. The aim of our research was to assess global transcriptional changes of all gene members of the HSP families within MS lesions and associated normal‐appearing white matter (NAWM). To this end, we used laser capture microdissection (LCM) to isolate defined regions of chronic–active MS lesions (n = 5), one of the most common types of MS lesions. To identify changes in HSP genes in relation to different areas of the plaque, we used genome‐wide microarray analysis. We detected a significant change in the transcriptional profile of the demyelinated region compared with NAWM. In particular, overall expression of different HSP genes was upregulated in different areas of chronic–active lesion. These changes were linked to an upregulation of heat shock factor 4 (HSF4). This is the first global analysis of transcriptional changes in HSPs in the central nervous system during MS. The results support a relationship between HSP activation and lesion activity. © 2012 Wiley Periodicals, Inc.
Dopaminergic modulation of low‐Mg2+‐induced epileptiform activity in the intact hippocampus of the newborn mouse in vitro
Authors: Sharopov Salim , Moser Jochen , Chen Rongqing , Kolbaev Sergey N. , Bernedo Viviane E. , Werhahn Konrad J. , Luhmann Heiko J. , Kilb Werner 
Published: June 2012

AbstractTo investigate whether epileptiform activity in the immature brain is modulated by dopamine, we examined the effects of dopaminergic agonists and antagonists in an intact in vitro preparation of the isolated corticohippocampal formation of immature (postnatal days 3 and 4) C57/Bl6 mice using field potential recordings from CA3. Epileptiform discharges were induced by a reduction of the extracellular Mg2+ concentration to 0.2 mM. These experiments revealed that low concentrations of dopamine (<0.3 μM) attenuated epileptiform activity, whereas >3 μM dopamine enhanced epileptiform activity. The D1‐agonist SKF38393 (10 μM) had a strong proconvulsive effect, and the D2‐like agonist quinpirole (10 μM) mediated a weak anticonvulsive effect. The proconvulsive effect of 10 μM dopamine was completely abolished by the D1‐like receptor antagonist SCH39166 (2 μM) or the D2‐like antagonist sulpiride (10 μM), whereas the D2 antagonist L‐741626 (50 nM) and the D3 antagonist SB‐277011‐A (0.1 μM) were without effect. The anticonvulsive effect of 0.1 μM dopamine could be suppressed by D1‐like, D2, or D3 receptor antagonists. A proconvulsive effect of 10 μM dopamine was also observed when AMPA, NMDA, or GABAA receptors were blocked. In summary, these results suggest that 1) dopamine influences epileptiform activity already at early developmental stages; 2) dopamine can bidirectionally influence the excitability; 3) D1‐like receptors mediate the proconvulsive effect of high dopamine concentrations, although the pharmacology of the anticonvulsive effect is less clear; and 4) dopamine‐induced alterations in GABAergic and glutamatergic systems may contribute to this effect. © 2012 Wiley Periodicals, Inc.
Transgenic mice expressing yellow fluorescent protein under control of the human tyrosine hydroxylase promoter
Authors: Choi Eun Yang , Yang Jae Won , Park Myung Sun , Sun Woong , Kim Hyun , Kim Seung U. , Lee Myung Ae 
Published: June 2012

AbstractPathogenesis of Parkinson's disease and related catecholaminergic neurological disorders is closely associated with changes in the levels of tyrosine hydroxylase (TH). Therefore, investigation of the regulation of the TH gene system should assist in understanding the pathomechanisms involved in these neurological disorders. To identify regulatory domains that direct human TH expression in the central nervous system (CNS), we generated two transgenic mouse lines in which enhanced yellow fluorescent protein (EYFP) is expressed under the control of either 3.2‐kb (hTHP‐EYFP construct) human TH promoter or 3.2‐kb promoter with 2‐kb 3′‐flanking regions (hTHP‐ex3‐EYFP construct) of the TH gene. In the adult transgenic mouse brain, the hTHP‐EYFP construct directs neuron‐specific EYFP expression in various CNS areas, such as olfactory bulb, striatum, interpeduncular nucleus, cerebral cortex, hippocampus, and particularly dentate gyrus. Although these EYFP‐positive cells were identified as mature neurons, few EYFP‐positive cells were TH‐positive neurons. On the other hand, we could detect the EYFP mRNA expression in a subset of neurons in the olfactory bulb, midbrain, and cerebellum, in which expression of endogenous TH is enriched, with hTHP‐ex3‐EYFP transgenic mice. These results indicate that the 3.2‐kb sequence upstream of the TH gene is not sufficient for proper expression and that the 2‐kb sequence from the translation start site to exon 3 is necessary for expression of EYFP in a subset of catecholaminergic neurons. © 2012 Wiley Periodicals, Inc.
S‐52, a novel nootropic compound, protects against β‐amyloid induced neuronal injury by attenuating mitochondrial dysfunction
Authors: Gao Xin , Zheng Chun Yan , Qin Guo Wei , Tang Xi Can , Zhang Hai Yan 
Published: June 2012

AbstractAccumulating evidence suggests that β‐amyloid (Aβ)‐induced oxidative DNA damage and mitochondrial dysfunction may initiate and contribute to the progression of Alzheimer's disease (AD). This study evaluated the neuroprotective effects of S‐52, a novel nootropic compound, on Aβ‐induced mitochondrial failure. In an established paradigm of moderate cellular injury induced by Aβ, S‐52 was observed to attenuate the toxicity of Aβ to energy metabolism, mitochondrial membrane structure, and key enzymes in the electron transport chain and tricarboxylic acid cycle. In addition, S‐52 also effectively inhibited reactive oxygen species accumulation dose dependently not only in Aβ‐harmed cells but also in unharmed, normal cells. The role of S‐52 as a scavenger of free radicals is involved in the antioxidative effect of this compound. The beneficial effects on mitochondria and oxidative stress extend the neuroprotective effects of S‐52. The present study provides crucial information for better understanding the beneficial profiles of this compound and discovering novel potential drug candidates for AD therapy. © 2012 Wiley Periodicals, Inc.
Effects of vascular endothelial growth factor in ischemic stroke
Authors: Ma Yihui , Zechariah Anil , Qu Yan , Hermann Dirk M. 
Published: June 2012

AbstractVascular endothelial growth factor (VEGF) is a pleiotropic growth factor that is crucially involved in neurovascular remodeling in the ischemic brain. VEGF promotes angiogenesis, protects ischemic neurons from injury, has potent anti‐inflammatory actions, and promotes brain plasticity, in addition to enhancing the recruitment and proliferation of neural precursor cells. These broad actions make VEGF interesting as a model molecule that allows understanding endogenous responses of the brain to injuries. However, several studies indicate that the route and timing of VEGF administration are crucial for the effects of VEGF on ischemic brain tissue. Hence, systemic VEGF delivery in the very acute stroke phase may exacerbate brain damage because of the promotion of blood–brain barrier breakdown that inevitably accompanies vascular growth. Future studies aimed at the promotion of neurovascular remodeling in ischemic stroke should carefully take into consideration pleiotropic actions of angiogenic growth factors beyond vascular growth. © 2012 Wiley Periodicals, Inc.
Magnesium sulfate treatment decreases the initial brain damage alterations produced after perinatal asphyxia in fetal lambs
Authors: Goñi‐de‐Cerio Felipe , Alvarez Antonia , Lara‐Celador Idoia , Alvarez Francisco J. , Alonso‐Alconada Daniel , Hilario Enrique 
Published: June 2012

AbstractThe aim of this work was to analyze the effect of MgSO4 treatment in the brain after hypoxic–ischemic (HI) injury in premature fetal lambs. Injury was induced by partial occlusion of umbilical cord for 60 min, and then the preterm lambs (80–90% of gestation) were randomly assigned to one of the following groups: control group, in which the animals were managed by conventional mechanical ventilation for 3 hr; 3 hr postpartial cord occlusion (3‐hr‐PCO) group, in which injured animals were managed by ventilation and then sacrificed 3 hr after HI; and MgSO4 group, in which animals received 400 mg/kg MgSO4 for 20 min soon after HI was induced and were managed by ventilation for 3 hr. Brains were analyzed for apoptosis by TUNEL assay. Cell viability and intracellular state studies were assessed by flow cytometry. The delayed death index was significantly increased in the 3‐hr‐PCO group in comparison with control. Administration of MgSO4 elicited a delay in cell death that was similar to that in the control group. The 3‐hr‐PCO group showed a significantly higher concentration of reactive oxygen species, mitochondrial damage, and intracellular calcium in comparison with control and MgSO4‐ treated groups. Our results suggest that MgSO4 treatment might have potential therapeutic benefits after the HI event. © 2012 Wiley Periodicals, Inc.