bluuebunny/crossref_metadata_2025_split huggingface dataset:
FE65 proteins regulate NMDA receptor activation‐induced amyloid precursor protein processing
Authors: Suh Jaehong , Lyckman Alvin , Wang Lirong , Eckman Elizabeth A. , Guénette Suzanne Y. 
Published: August 2011

J. Neurochem. (2011) 119, 377–388.AbstractAmyloid precursor protein (APP) family members and their proteolytic products are implicated in normal nervous system function and Alzheimer’s disease pathogenesis. APP processing and Aβ secretion are regulated by neuronal activity. Various data suggest that NMDA receptor (NMDAR) activity plays a role in both non‐amyloidogenic and amyloidogenic APP processing depending on whether synaptic or extrasynaptic NMDARs are activated, respectively. The APP‐interacting FE65 proteins modulate APP trafficking and processing in cell lines, but little is known about their contribution to APP trafficking and processing in neurons, either in vivo or in vitro. In this study, we examined the contribution of the FE65 protein family to APP trafficking and processing in WT and FE65/FE65L1 double knockout neurons under basal conditions and following NMDAR activation. We report that FE65 proteins facilitate neuronal Aβ secretion without affecting APP fast axonal transport to pre‐synaptic terminals. In addition, FE65 proteins facilitate an NMDAR‐dependent non‐amyloidogenic APP processing pathway. Generation of high‐molecular weight (HMW) species bearing an APP C‐terminal epitope was also observed following NMDAR activation. These HMW species require proteasomal and calpain activities for their accumulation. Recovery of APP polypeptide fragments from electroeluted HMW species having molecular weights consistent with calpain I cleavage of APP suggests that HMW species are complexes formed from APP metabolic products. Our results indicate that the FE65 proteins contribute to physiological APP processing and accumulation of APP metabolic products resulting from NMDAR activation.
Age‐related decline in osteoblastogenesis and 1α‐hydroxylase/CYP27B1 in human mesenchymal stem cells: stimulation by parathyroid hormone
Authors: Geng Shuo , Zhou Shuanhu , Glowacki Julie 
Published: August 2011

SummaryWith aging, there is a decline in bone mass and in osteoblast differentiation of human mesenchymal stem cells (hMSCs) in vitro. Osteoblastogenesis can be stimulated with 1,25‐dihydroxyvitamin D3 [1,25(OH)2D3] and, in some hMSCs, by the precursor 25‐hydroxyvitamin D3 (25OHD3). CYP27B1/1α‐hydroxylase activates 25OHD3 and, to a variable degree, hMSCs express CYP27B1. In this study, we tested the hypotheses (i) that age affects responsiveness to 25OHD3 and expression/activity of CYP27B1 in hMSCs and (ii) that parathyroid hormone (PTH) upregulates CYP27B1 in hMSCs, as it does in renal cells. There were age‐related declines in osteoblastogenesis (n = 8, P = 0.0286) and in CYP27B1 gene expression (n = 27, r = −0.498; P = 0.008) in hMSCs. Unlike hMSCs from young subjects (≤50 years), hMSCs from older subjects (≥55 years) were resistant to 25OHD3 stimulation of osteoblastogenesis. PTH1‐34 (100 nm) provided hMSCs with responsiveness to 25OHD3 (P = 0.0313, Wilcoxon matched pairs test) and with two episodes of increased 1,25(OH)2D3 synthesis, of cAMP response element binding protein (CREB) activation, and of CYP27B1 upregulation. Both increases in CYP27B1 expression by PTH were obliterated by CREB‐siRNA or KG‐501 (which specifically inhibits the downstream binding of activated CREB). Only the second period of CREB signaling was diminished by AG1024, an inhibitor of insulin‐like growth factor‐I receptor kinase. Thus, PTH stimulated hMSCs from elders with responsiveness to 25OHD3 by upregulating expression/activity of CYP27B1 and did so through CREB and IGF‐I pathways.
Oncogenes induce senescence with incomplete growth arrest and suppress the DNA damage response in immortalized cells
Authors: Sherman Michael Y. , Meng Le , Stampfer Martha , Gabai Vladimir L. , Yaglom Julia A. 
Published: August 2011

SummaryActivation of the Her2 (ErbB2) oncogene is implicated in the development of breast, ovary and other cancers. Here, we show that expression of NeuT, a mutant‐activated rodent isoform of Her2, in immortalized breast epithelial cells, while promoting senescence‐associated morphological changes, up‐regulation of senescence‐associated β‐galactosidase activity, and accumulation of the cyclin‐dependent kinase inhibitor p21, failed to trigger the major senescence end‐point, i.e. permanent growth arrest. Similar senescence‐associated phenotype with incomplete growth arrest, which we dubbed senescence with incomplete growth arrest (SWING), could also be triggered by the expression of the Ras oncogene. SWING phenotype was stable, and persisted in tumor xenografts established from NeuT‐transduced cells. Furthermore, a significant population of cells in SWING state was found in tumors in the MMTV/NeuT transgenic mouse model. SWING cells showed downregulation of histone H2AX, critical for repair of double‐stranded DNA breaks, and impaired activation of Chk1 kinase. Overall, SWING cells were characterized by increased DNA instability and hypersensitivity to genotoxic stresses. We propose that the SWING state could be a stage in the process of cancer development.
Genistein aglycone, a soy‐derived isoflavone, improves skin changes induced by ovariectomy in rats
Authors: Polito Francesca , Marini Herbert , Bitto Alessandra , Irrera Natasha , Vaccaro Mario , Adamo Elena Bianca , Micali Antonio , Squadrito Francesco , Minutoli Letteria , Altavilla Domenica 
Published: August 2011

BACKGROUND AND PURPOSE Ovariectomy accelerates age‐related skin changes as adequate oestrogen levels are required to control structural integrity and functional capacity of skin. Genistein, a soy‐derived isoflavone, has been tested in anti‐ageing cosmetic preparations with interesting results on skin elasticity, photoaging and skin cancer prevention. We investigated the effects of genistein aglycone and compared them with systemic raloxifene hydrochloride and 17‐α‐ethinyloestradiol on skin changes in aged, ovariectomized (OVX) rats.EXPERIMENTAL APPROACH Six months after ovariectomy, rats were randomly allocated to different groups and treated, daily, with genistein aglycone (1 and 10 mg·kg−1 s.c.), raloxifene hydrochloride (0.05 and 0.5 mg·kg−1 s.c.) or 17‐α‐ethinyloestradiol (0.003 and 0.03 mg·kg−1 s.c.) for 12 weeks. Controls were untreated OVX and sham OVX rats. At the end of the treatment period, a skin biopsy was carried out and skin samples were assessed for molecular, histological and functional changes.KEY RESULTS Skin samples of untreated OVX rats showed a decrease in TGF‐β1, VEGF, MMP‐2, MMP‐9, tissue inhibitor of metalloproteinase (TIMP)‐1 and TIMP‐2 compared with sham OVX rats. All the treatments significantly restored this depressed molecular profile revealed in OVX rats. Genistein aglycone, 1 mg·kg−1, also significantly increased the thickness of collagen and breaking strength of skin in the OVX rats.CONCLUSIONS AND IMPLICATIONS Relatively long‐term, systemic treatment with genistein aglycone shows comparable efficacy to oestrogen in reversing some molecular, histological and functional changes of the skin associated with ovariectomy in aged rats. This suggests that genistein aglycone might be an effective alternative therapy for the management of age‐related skin changes in postmenopausal women.
Application of implicit attitude measures to the blood donation context
Authors: Warfel Regina M. , France Christopher R. , France Janis L. 
Published: August 2011

BACKGROUND: Past blood donation research has relied on explicit (self‐report) measures to understand blood donation motivations, but has not yet considered the inherent implicit or automatic processing involved in decision‐making. This study addresses this limitation by introducing and validating two novel implicit measures of blood donation attitudes.STUDY DESIGN AND METHODS: Healthy young adults (n = 253) performed both image and word versions of a Single Target Implicit Association Test (ST‐IAT) and then completed self‐report measures of blood donation attitudes, blood and needle fears, social desirability, and donation intention.RESULTS: These results affirmed the validity of the blood donation ST‐IATs in at least three ways. First, as expected, nondonors demonstrated more negative implicit donation attitudes than donors. Second, the implicit measures were significantly related in expected directions with explicit measures of donation attitudes as well as blood and needle fears. Finally, implicit donation attitudes were significantly related to donation intention, and the Image ST‐IAT (but not the Word ST‐IAT) significantly enhanced prediction of donation intention over and above needle fears and marginally enhanced prediction over and above blood fears.CONCLUSION: Image and word versions of the blood donation ST‐IAT offer a valid method of assessing underlying automatic attitudes toward blood donation.
Riboflavin and ultraviolet light treatment potentiates vasodilator‐stimulated phosphoprotein Ser‐239 phosphorylation in platelet concentrates during storage
Authors: Schubert Peter , Culibrk Brankica , Coupland Danielle , Scammell Ken , Gyongyossy‐Issa Maria , Devine Dana V. 
Published: August 2011

BACKGROUND: Pathogen reduction technologies (PRTs) were developed to improve the safety of platelet concentrates (PCs) for transfusion purposes; however, several studies report a negative impact on the in vitro and in vivo platelet (PLT) quality. Therefore, analyses of the underlying molecular processes triggered by PRT treatments are necessary to understand their effects on PLT function.STUDY DESIGN AND METHODS: In two separate two‐arm studies PCs prepared in plasma for storage either by the leukoreduced buffy coat (BC‐PCs) or by the leukoreduced apheresis (AP‐PCs) method were treated with or without riboflavin and ultraviolet (UV) light (Mirasol; 6.24 J/mL; 265‐375 nm). Samples were drawn after treatment and after 1, 4, and 6 days of storage with subsequent analyses performed using in vitro measurements for PLT quality monitoring. Semiquantitative proteomic studies identified proteins that changed in band intensities in response to treatment or storage. Protein validation and subsequent biochemical studies were carried out by immunoblot analyses.RESULTS: The proteomic results identified changes mainly of proteins associated with the structure and regulation of the cytoskeleton. Focusing on the vasodilator‐stimulated phosphoprotein (VASP) in AP‐PCs revealed a storage‐dependent, but treatment‐independent, delocalization and a strong treatment‐dependent phosphorylation at Ser‐239 that was also present, but to a much lesser degree in BC‐PCs. This modification correlated exponentially with PLT activation as determined by P‐selectin expression.CONCLUSION: Treatment of PCs with Mirasol leads to the amplification of VASP Ser‐239 phosphorylation, which is linked to actin dynamics and regulation of integrin αIIbβ3 activation. This change offers one explanation for Mirasol's impact on PLT in vitro quality measures. The Ser‐239 phosphorylation level of VASP might be a useful protein marker for riboflavin and UV light–mediated PLT compromise.
Learning Foreign Sounds in an Alien World: Videogame Training Improves Non‐Native Speech Categorization
Authors: Lim Sung‐joo , Holt Lori L. 
Published: August 2011

AbstractAlthough speech categories are defined by multiple acoustic dimensions, some are perceptually weighted more than others and there are residual effects of native‐language weightings in non‐native speech perception. Recent research on nonlinguistic sound category learning suggests that the distribution characteristics of experienced sounds influence perceptual cue weights: Increasing variability across a dimension leads listeners to rely upon it less in subsequent category learning (Holt & Lotto, 2006). The present experiment investigated the implications of this among native Japanese learning English /r/‐/l/ categories. Training was accomplished using a videogame paradigm that emphasizes associations among sound categories, visual information, and players’ responses to videogame characters rather than overt categorization or explicit feedback. Subjects who played the game for 2.5 h across 5 days exhibited improvements in /r/‐/l/ perception on par with 2–4 weeks of explicit categorization training in previous research and exhibited a shift toward more native‐like perceptual cue weights.
Age Estimation by Measurements of Developing Teeth: Accuracy of Cameriere’s Method on a Brazilian Sample
Authors: Fernandes Mário Marques , Tinoco Rachel Lima Ribeiro , de Braganca Daniel Pereira Parreiras , de Lima Silas Henrique Rabelo , Junior Luiz Francesquini , Junior Eduardo Daruge 
Published: August 2011

Abstract:  Developing teeth are commonly the criteria used for age estimation in children and young adults. The method developed by Cameriere et al. (Int J Legal Med 2006;120:49‐52) is based on measures of teeth with open apex, and application of a formula, to estimate chronological age of children. The present study evaluated a sample of panoramic radiographs from Brazilian children from 5 to 15 years of age, to evaluate the accuracy of the method proposed by Cameriere et al. The results has proven the system reliable for age estimation, with a median residual error of −0.014 years between chronological and estimated ages (p = 0.603). There was a slight tendency to overestimate the ages of 5–10 years and underestimate the ages of 11–15 years.
Trauma, exile and mental health in young refugees
Authors: Montgomery E. 
Published: August 2011

Montgomery E. Trauma, exile and mental health in young refugees.Objective: To review evidence of trauma and exile‐related mental health in young refugees from the Middle East.Method: A review of four empirical studies: i) a qualitative study of 11 children from torture surviving families, ii) a cohort study of 311 3–15‐year‐old asylum‐seeking children, iii) a qualitative study of 14 members of torture surviving families and iv) a follow‐up study of 131 11–23‐year‐old refugees.Results: The reactions of the children were not necessarily post‐traumatic stress disorder specific. Seventy‐seven per cent suffered from anxiety, sleep disturbance and/or depressed mood at arrival. Sleep disturbance (prevalence 34%) was primarily predicted by a family history of violence. At follow‐up, 25.9% suffered from clinically relevant psychological symptoms. Traumatic experiences before arrival and stressful events in exile predicted internalizing behaviour, witnessing violence and frequent school changes in exile predicted externalizing behaviour. School participation, Danish friends, language proficiency and mother’s education predicted less long‐term psychological problems.Conclusion: Psychological problems are frequent in refugee children, but the extents are reduced over time in exile. Traumatic experience before arrival is most important for the short‐term reaction of the children while aspects of life in exile are important for the children’s ability to recover from early traumatization.
Unexpected mechanisms sustain the stress gradient hypothesis in a tropical alpine environment
Authors: Anthelme Fabien , Buendia Belen , Mazoyer Charlotte , Dangles Olivier 
Published: August 2011

AbstractQuestionsDoes facilitation among plants increase with elevation in a humid tropical alpine system in which climatic and ecological conditions differ from other alpine environments? What mechanisms are involved in the interactions?LocationVolcano Antisana, Eastern Cordillera of the Ecuadorian Andes (00°28′S, 78°09′W).MethodsWe selected the cushion‐forming Azorella aretioides as a potential nurse plant along an altitudinal gradient (4400, 4550 and 4700 m) in the high tropical Andes. We quantified its effects on other plants at species and community levels by comparing the product vegetation cover × number of individuals of every vascular species found inside and outside 265 cushions, using the relative interaction index. We inferred potential mechanisms behind the interactions through analysis of microclimate, soil moisture and soil nutrient measurements inside and outside cushions.ResultsPredictions of the stress gradient hypothesis (SGH) were corroborated at community level, with transition from competitive or neutral effects of A. aretioides at 4400 and 4550 m to facilitative effects at 4700 m. Strong species‐specific effects were observed along the altitudinal gradient, with a substantial effect of local habitat disturbance on the outcome of plant–plant interactions. Surprisingly, cushions lowered air and soil temperatures and air humidity, which reduced at higher elevations. Facilitation appeared to be caused by higher soil moisture and nutrient content beneath cushions.ConclusionsOur data extend the framework of the SGH by corroborating it for the first time in a tropical alpine system. However, the mechanisms underlying plant–plant interactions differed from those generally reported from alpine environments, with facilitation varying according to resource‐mediated stress (nutrients). It remains to be tested whether this is specific to tropical alpine systems.
Variation of the γ opacity by the He II Lyman continuum constrains the location of the γ-ray emission region in the blazar 3C 454.3
Authors: Stern Boris E. , Poutanen Juri 
Published: August 2011

Abstract
We study spectral properties of the brightest γ-ray blazar 3C 454.3 using 138 weeks of observations by the Fermi Gamma-ray Space Telescope (Fermi). We probe the behaviour of the source as a function of time at different brightness levels. The Fermi spectra in the GeV range can be well described by a wide underlying lognormal distribution with the photon—photon absorption breaks produced by the He ii and H i Lyman recombination continua (LyC). We find a power-law dependence of the peak energy on flux and discover anticorrelation between the column density of the He ii LyC and flux. This implies that the γ-ray emission zone lies close to the boundary of the high-ionization part of the broad-line region and moves away from the black hole when the flux increases. Identification of the γ-ray production with the relativistic jet implies that the jet is already accelerated at sub-parsec distances from the central black hole, which favours the Blandford—Znajek process as the jet launching mechanism.
Ancient giants: on the farthest galaxy at z = 8.6
Authors: Dayal Pratika , Ferrara Andrea 
Published: August 2011

Abstract
The observational frontiers for the detection of high-redshift galaxies have recently been pushed to unimaginable distances with the record-holding Lyman alpha emitter (LAE) UDFy-38135539 discovered at redshift z= 8.6. However, the physical nature and the implications of this discovery have yet to be assessed. By selecting galaxies with observed luminosities similar to UDFy-38135539 in state-of-the-art cosmological simulations tuned to reproduce the large-scale properties of LAEs, we bracket the physical nature of UDFy-38135539: it has a star formation rate ∼2.7–3.7 M⊙ yr−1, it contains 108.3-8.7 M⊙ of stars 50–80 Myr old, with stellar metallicity ∼0.03–0.12 Z⊙. For any of the simulated galaxies to be visible as a LAE in the observed range, the intergalactic neutral hydrogen fraction at z= 8.6 must be χH I≤ 0.2 and extra ionizing radiation from sources clustered around UDFy-38135539 is necessary. Finally, we predict that there is a 70 per cent (15 per cent) probability of detecting at least one such source from JWST (HST/WFC3) observations in a physical radius ∼0.4 Mpc around UDFy-38135539.
The regulation of blood perfusion in the renal cortex and medulla by reactive oxygen species and nitric oxide in the anaesthetised rat
Authors: Ahmeda A. F. , Johns E. J. 
Published: August 2011

Abstract
Aims:  The regulation of blood flow through the renal medulla is important in determining blood pressure, and its dysregulation in pathophysiological states, such as oxidative stress, may contribute to the development of hypertension. This investigation examined the hypothesis that reactive oxygen species has both direct and indirect actions, via scavenging NO, to determine the degree of blood perfusion through the renal medulla.
Methods:  Groups of male Wistar rats received a renal interstitial infusion of either tempol, a superoxide dismutase (SOD) mimetic, or tempol plus catalase (tem + cat), or diethyldithio‐carbamic acid (DETC) a SOD inhibitor, or L‐NAME alone or L‐NAME followed by DETC.
Results:  Medullary blood perfusion (MBP) increased by 16 ± 1% (P < 0.05) following the renal infusion of tempol and by 35 ± 4%% (P < 0.05) when tem + cat was infused. Cortical blood perfusion (CBP) was unchanged during the administration of tempol and tem + cat. The renal interstitial infusion of DETC reduced CBP by 13 ± 2%, (P < 0.05) and MBP by 22 ± 3% (P < 0.05). Infusion of L‐NAME to block NOS did not change CBP but decreased MBP by 12 ± 4%, which was (P < 0.05) less than the reduction obtained with DETC. Administration of DETC in the presence of L‐NAME reduced CBP and MBP by 17 and 14%, respectively, the latter response being approximately half that obtained when only DETC was infused.
Conclusions:  These findings demonstrated that both reactive oxygen species and NO determined the level of MBP. The findings support the hypothesis that reactive oxygen species can act both indirectly, via scavenging of NO, and directly via H2O2 to modulate blood perfusion in the medulla.
Interplay of endothelial and inducible nitric oxide synthases modulates the vascular response to ischaemia–reperfusion in the rabbit lung
Authors: Sedoris K. C. , Gozal E. , Ovechkin A. V. , Theile A. R. , Roberts A. M. 
Published: August 2011

Abstract
Aim:  Lung ischaemia–reperfusion induces nitric oxide synthesis and reactive nitrogen species, decreasing nitric oxide bioavailability. We hypothesized that in the ventilated lung, this process begins during ischaemia and intensifies with reperfusion, contributing to ischaemia–reperfusion‐induced pulmonary vasoconstriction. The aim was to determine whether ischaemia–reperfusion alters inducible and endothelial nitric oxide synthase expression/activity, reactive nitrogen species generation, and nitric oxide bioavailability, potentially affecting pulmonary perfusion.
Methods:  Ischaemia–reperfusion was induced for various times in anesthetized rabbits with ventilated lungs by reversibly occluding the right pulmonary artery and initiating reperfusion. Nitric oxide synthase activity/expression and phosphorylation, reactive nitrogen species generation and total nitrate/nitrite were determined in lung tissue.
Results:  Inducible nitric oxide synthase expression and activity, and reactive nitrogen species formation coincided with increased pulmonary vascular resistance during reperfusion and increased with ischaemia duration, further increasing after 2‐h reperfusion. Total nitrate/nitrite also increased with ischaemia but decreased after 2‐h reperfusion. Pre‐treatment with an inducible nitric oxide synthase inhibitor (1400W; Cayman Chemical Company, Ann Arbor, MI, USA) attenuated inducible nitric oxide synthase activity, reactive nitrogen species generation and pulmonary vascular resistance, but did not affect total nitrate/nitrite. Endothelial nitric oxide synthase expression was unchanged by ischaemia–reperfusion; however, its phosphorylation on serine 1177 and dephosphorylation on threonine 495 was uncoupled, suggesting decreased endothelial nitric oxide synthase activity. 1400W prevented uncoupling of endothelial nitric oxide synthase phosphorylation, maintaining its activity during reperfusion.
Conclusion:  Ischaemia–reperfusion up‐regulates inducible nitric oxide synthesis and/activity, which coincides with reduced endothelial nitric oxide synthase activity as suggested by its uncoupling and may contribute to ischaemia–reperfusion‐induced pulmonary vasoconstriction.