bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abcg2 deficiency augments oxidative stress and cognitive deficits in Tg‐SwDI transgenic mice
Authors: Zeng Yu , Callaghan Debbie , Xiong Huaqi , Yang Ze , Huang Peilin , Zhang Wandong 
Published: May 2012

J. Neurochem. (2012) 122, 456–469.AbstractOxidative stress and neuroinflammation play important roles in Alzheimer’s disease (AD). ABCG2 is a transporter protein expressed in the brain and involved in GSH transport. To study the roles of Abcg2 in oxidative stress and AD, we cross‐bred Tg‐SwDI and Abcg2‐KO mice and generated Tg‐SwDI/Abcg2‐KO (double‐tg) mice. Brain tissues from double‐tg, Tg‐SwDI, wild‐type, and Abcg2‐KO mice at various ages were analyzed. Aβ40 and Aβ42 were detected in Tg‐SwDI and double‐tg mice. Total brain GSH was decreased and levels of lipid/DNA oxidation were increased in 3‐month double‐tg compared to Tg‐SwDI mice. Low brain GSH was still detected in 9‐month double‐tg mice. Increased HMOX‐1 and MCP‐5 expression was observed in 9‐month double‐tg mice but not in Tg‐SwDI mice compared to WT and Abcg2‐KO mice. Increased HMOX‐1 and decreased ICAM‐1 expression were observed in 12‐month double‐tg mice compared to Tg‐SwDI mice. The levels of Nrf‐2 expression and activity were decreased in 6‐month double‐tg mice. Behavioral tests show impaired cognitive/memory performance of 9‐month double‐tg compared to Tg‐SwDI mice as well as WT and Abcg2‐KO mice. These results suggest that Abcg2 deficiency increases oxidative stress and alters inflammatory response in the brain and exacerbates cognitive/memory deficit in double‐tg mice at different developmental stages.
An allosteric modulator of metabotropic glutamate receptors (mGluR2), (+)‐TFMPIP, inhibits restraint stress‐induced phasic glutamate release in rat prefrontal cortex
Authors: Hascup Erin R. , Hascup Kevin N. , Pomerleau Francois , Huettl Peter , Hajos‐Korcsok Eva , Kehr Jan , Gerhardt Greg A. 
Published: May 2012

J. Neurochem. (2012) 122, 619–627.AbstractThe potential anxiolytic effects of a novel positive allosteric modulator (PAM) of the metabotropic glutamate receptor subgroup 2 (mGluR2) were investigated using a self‐referencing recording technique with enzyme‐based microelectrode arrays (MEAs) that reliably measures tonic and phasic changes in extracellular glutamate levels in awake rats. Studies involved glutamate measures in the rat prefrontal cortex during subcutaneous injections of the following: vehicle, a mGluR2/3 agonist, LY354740 (10 mg/kg), or a mGluR2 PAM, 1‐Methyl‐2‐((cis‐(R,R)‐3‐methyl‐4‐(4‐trifluoromethoxy‐2‐fluoro)phenyl)piperidin‐1‐yl)methyl)‐1H‐imidazo[4,5‐b]pyridine ((+)‐TFMPIP; 1.0 or 17.8 mg/kg). Studies assessed changes in tonic glutamate levels and the glutamatergic responses to a 5‐min restraint stress. Subcutaneous injection of (+)‐TFMPIP at a dose of 1.0 mg/kg (day 3: ‐7.1 ± 15.1 net AUC; day 5: ‐24.8 ± 24.9 net AUC) and 17.8 mg/kg (day 3: ‐46.5 ± 33.0 net AUC; day 5: 34.6 ± 36.8 net AUC) significantly attenuated the stress‐evoked glutamate release compared to vehicle controls (day 3: 134.7 ± 50.6 net AUC; day 5: 286.6 ± 104.5 net AUC), whereas the mGluR2/3 agonist LY354740 had no effect. None of the compounds significantly affected resting glutamate levels, which we have recently shown to be extensively derived from neurons. Taken together, these data support that systemic administration of (+)‐TFMPIP produces phasic rather than tonic release of glutamate that may play a major role in the effects of stress on glutamate neuronal systems in the prefrontal cortex.
Nicotine modulates multiple regions in the limbic stress network regulating activation of hypophysiotrophic neurons in hypothalamic paraventricular nucleus
Authors: Yu Guoliang , Sharp Burt M. 
Published: May 2012

J. Neurochem. (2012) 122, 628–640.AbstractNicotine intake affects CNS responses to stressors. We reported that nicotine self‐administration (SA) augmented the hypothalamo‐pituitary‐adrenal (HPA) stress response, in part because of the altered neurotransmission and neuropeptide expression within hypothalamic paraventricular nucleus (PVN). Limbic‐PVN interactions involving medial prefrontal cortex, amygdala, and bed nucleus of the stria terminalis (BST) greatly impact the HPA stress response. Therefore, we investigated the effects of nicotine SA on stress‐induced neuronal activation in limbic‐PVN network, using c‐Fos protein immunohistochemistry and retrograde tracing. Nicotine decreased stress‐induced c‐Fos in prelimbic cortex (PrL), anteroventral BST (avBST), and peri‐PVN, but increased c‐Fos induction in medial amygdala (MeA), locus coeruleus, and PVN. Fluoro‐gold (FG) was injected into avBST or PVN, as GABAergic neurons in avBST projecting to PVN corticotrophin‐releasing factor neurons relay information from both PrL glutamatergic and MeA GABAergic neurons. The stress‐induced c‐Fos expression in retrograde‐labeled FG+ neurons was decreased in PrL by nicotine, but increased in MeA, and also reduced in avBST. Therefore, within limbic‐PVN network, nicotine SA exerts selective regional effects on neuronal activation by stress. These findings expand the mechanistic framework by demonstrating altered limbic‐BST‐PVN interactions underlying the disinhibition of PVN corticotrophin‐releasing factor neurons, an essential component of the amplified HPA response to stress by nicotine.
Molecular mechanism of Jmjd3‐mediated interleukin‐6 gene regulation in endothelial cells underlying spinal cord injury
Authors: Lee Kwanghyun , Na Wonho , Lee Jee Youn , Na Jungtae , Cho Heejung , Wu Hongjin , Yune Tae Young , Kim Won‐Sun , Ju Bong‐Gun 
Published: May 2012

J. Neurochem. (2012) 122, 272–282.AbstractThe inflammatory response contributes substantially to secondary injury cascades after spinal cord injury, with both neurotoxic and protective effects. However, epigenetic regulations of inflammatory genes following spinal cord injury have yet to be characterized thoroughly. In this study, we found that histone H3K27me3 demethylase Jmjd3 expression is acutely up‐regulated in blood vessels of the injured spinal cord. We also observed up‐regulation of Jmjd3 gene expression in bEnd.3 endothelial cells that were subjected to oxygen‐glucose deprivation/reperfusion injury. When Jmjd3 was depleted by siRNA, oxygen‐glucose deprivation/reperfusion injury‐induced up‐regulation of IL‐6 was significantly inhibited. In addition, Jmjd3 associated with NF‐κB (p65/p50) and CCAAT‐enhancer‐binding protein β at the IL‐6 gene promoter. The recruitment of Jmjd3 coincided with decreased levels of tri‐methylated H3K27 as well as increased levels of mono‐methylated H3K27 at the IL‐6 gene promoter. Furthermore, Jmjd3 depletion did not result in significant changes of methylation level of H3K27 at the IL‐6 gene promoter. Collectively, our findings imply that Jmjd3‐mediated H3K27me3 demethylation is crucial for IL‐6 gene activation in endothelial cells, and this molecular event may regulate acute inflammatory response and integrity of the blood‐spinal cord barrier following spinal cord injury.
Data uncertainty and the selectivity of extinction risk in freshwater invertebrates
Authors: Bland Lucie M. , Collen Ben , Orme C. David L. , Bielby Jon 
Published: May 2012

AbstractAimTo investigate the impact of different treatments of the IUCN Data Deficient (DD) category on taxonomic and geographical patterns of extinction risk in crayfish, freshwater crabs and dragonflies.LocationGlobal.MethodsWe used contingency tables to evaluate taxonomic and geographical selectivity of data deficiency and extinction risk for three invertebrate taxonomic groups (crayfish, dragonflies and damselflies, and freshwater crabs) based on their IUCN Red List status. We investigated differences in patterns of data deficiency and extinction risk among taxonomic families, geographical realms and taxonomic families within geographical realms for each of the three groups. At each level, we evaluated the impact of uncertainty conferred by the conservation status of DD species on extinction risk patterns exhibited by that group. We evaluated three scenarios: excluding DD species, treating all DD species as non‐threatened and treating all DD species as threatened.ResultsAt the global scale, DD species were taxonomically non‐randomly distributed in freshwater crabs and dragonflies, and geographically non‐randomly distributed in all three taxonomic groups. Although the presence of under‐ or over‐threatened families and biogeographical realms was generally unchanging across scenarios, the strength of taxonomic and geographical selectivity of extinction risk varied. There was little consistent evidence for taxonomic selectivity of extinction risk at sub‐global scales in freshwater crabs and dragonflies, either among biogeographical realms or among scenarios.Main conclusionsGlobal patterns of taxonomic selectivity and geographical selectivity were generally consistent with one another and robust to different treatments of DD species. However, sub‐global scale conservation prioritization from these types of data sets will require increased investment to make accurate decisions. Given the current levels of data uncertainty, the relative importance of biological characteristics and threatening processes in driving extinctions in freshwater invertebrates cannot be easily determined. We recommend that DD species should be given high research priority to determine their true status.
Individual migratory patterns of two threatened seabirds revealed using stable isotope and geolocation analyses
Authors: Militão Teresa , Bourgeois Karen , Roscales Jose L. , González‐Solís Jacob 
Published: May 2012

AbstractAimIntraspecific variability in the migratory movements of seabirds is being revealed far more complex than hitherto recognized, and our lack of understanding undermines their effective protection. Our aim is to test whether the isotopic values of a single feather of two threatened seabirds, the Mediterranean (Puffinus yelkouan) and the Balearic (Puffinus mauretanicus) shearwaters allow the geographic assignment of birds to their non‐breeding areas.LocationThese two species are known to use three main non‐breeding areas: the NE Atlantic Ocean, the W Mediterranean and the Aegean‐Black seas.MethodsWe clustered in three groups the δ13C and δ15N values of the first primary feather (P1), inferred to be grown during the non‐breeding period, of 34 Mediterranean and 56 Balearic shearwaters accidentally caught by longliners. To link the isotopic values of P1 to its corresponding non‐breeding area, we performed a discriminant function analysis (DFA) based on the three clusters and applied this function to feathers of known origin: P1 from seven Mediterranean shearwaters from Hyères Archipelago (France) tracked with geolocators and body feathers from six chicks from Balearic shearwaters. To link the moulting patterns to the areas where the feathers were grown, we applied the DFA to a sequence of primary feathers of eight Balearic and five Mediterranean shearwaters (caught by longliners).ResultsIsotopic and tracking data indicate that none of the Mediterranean shearwaters migrated to the Atlantic. The cluster and discriminant function analyses revealed that 8% of Balearic and 54% of Mediterranean shearwater moulted P1 in the Mediterranean Sea. Migratory movements were reflected in the changing isotopic values of the primary sequences.Main conclusionsStable isotope analyses (SIA) are a powerful approach to reveal the intraspecific variability in the migratory patterns of seabirds that use distinct isotopic areas over their annual cycle. The assignment of birds to their non‐breeding areas by means of SIA is a simple and effective tool that can help to evaluate the impact of human activities in remote areas not only at population but also at individual level, which is an essential knowledge for the management and conservation of threatened species.
Fibroblasts from long‐lived mutant mice exhibit increased autophagy and lower TOR activity after nutrient deprivation or oxidative stress
Authors: Wang Min , Miller Richard A. 
Published: May 2012

SummaryPrevious work has shown that primary skin‐derived fibroblasts from long‐lived pituitary dwarf mutants resist the lethal effects of many forms of oxidative and nonoxidative stress. We hypothesized that increased autophagy may protect fibroblasts of Pit‐1dw/dw (Snell dwarf) mice from multiple forms of stress. We found that dwarf‐derived fibroblasts had higher levels of autophagy, using LC3 and p62 as markers, in response to amino acid deprivation, hydrogen peroxide, and paraquat. Fibroblasts from dwarf mice also showed diminished phosphorylation of mTOR, S6K, and 4EBP1, consistent with the higher levels of autophagy in these cells after stress. Similar results were also observed in fibroblasts from mutant mice lacking growth hormone receptor (GHRKO mice) after amino acid withdrawal. Our results suggested that increased autophagy, regulated by TOR‐dependent processes, may contribute to stress resistance in fibroblasts from long‐lived mutant mice.
Distinct effects of inflammation on gliosis, osmohomeostasis, and vascular integrity during amyloid beta‐induced retinal degeneration
Authors: Dinet Virginie , Bruban Julien , Chalour Naima , Maoui Agathe , An Na , Jonet Laurent , Buret Alain , Behar‐Cohen Francine , Klein Christophe , Tréton Jacques , Mascarelli Frédéric 
Published: May 2012

SummaryIn normal retinas, amyloid‐β (Aβ) accumulates in the subretinal space, at the interface of the retinal pigment epithelium, and the photoreceptor outer segments. However, the molecular and cellular effects of subretinal Aβ remain inadequately elucidated. We previously showed that subretinal injection of Aβ(1–42) induces retinal inflammation, followed by photoreceptor cell death. The retinal Müller glial (RMG) cells, which are the principal retinal glial cells, are metabolically coupled to photoreceptors. Their role in the maintenance of retinal water/potassium and glutamate homeostasis makes them important players in photoreceptor survival. This study investigated the effects of subretinal Aβ(1–42) on RMG cells and of Aβ(1–42)‐induced inflammation on retinal homeostasis. RMG cell gliosis (upregulation of GFAP, vimentin, and nestin) on day 1 postinjection and a proinflammatory phenotype were the first signs of retinal alteration induced by Aβ(1–42). On day 3, we detected modifications in the protein expression patterns of cyclooxygenase 2 (COX‐2), glutamine synthetase (GS), Kir4.1 [the inwardly rectifying potassium (Kir) channel], and aquaporin (AQP)‐4 water channels in RMG cells and of the photoreceptor‐associated AQP‐1. The integrity of the blood‐retina barrier was compromised and retinal edema developed. Aβ(1–42) induced endoplasmic reticulum stress associated with sustained upregulation of the proapoptotic factors of the unfolded protein response and persistent photoreceptor apoptosis. Indomethacin treatment decreased inflammation and reversed the Aβ(1–42)‐induced gliosis and modifications in the expression patterns of COX‐2, Kir4.1, and AQP‐1, but not of AQP‐4 or GS. Nor did it improve edema. Our study pinpoints the adaptive response to Aβ of specific RMG cell functions.
Peripheral refraction in myopia corrected with spectacles versus contact lenses
Authors: Backhouse Simon , Fox Stephanie , Ibrahim Basma , Phillips John R 
Published: May 2012

Citation information: Backhouse S, Fox S, Ibrahim B & Phillips JR. Peripheral refraction in myopia corrected with spectacles versus contact lenses. Ophthalmic Physiol Opt 2012, 32, 294–303. doi: 10.1111/j.1475‐1313.2012.00912.xAbstractPurpose:  Previous studies suggest that the refractive status of the peripheral retina can influence the development and progression of myopia. Our aim was to compare peripheral refractions in the same cohort of human eyes corrected with spectacle lenses vs soft contact lenses.Methods:  Ten young adults with moderate to high myopia (−5.00 D to −8.00 D) were investigated. Open‐field autorefraction was used to measure on‐ and off‐axis refractions with the eyes in primary gaze, when uncorrected, and when corrected with spectacles and contact lenses. Measures were made every 5° out to 30° horizontally in nasal and temporal retina and analysed as power vectors (M, J0, and J45). Partial coherence interferometry measures of eye size were also made on‐axis and off‐axis at 10º and 20º in nasal and temporal retina.Results:  Subjects (mean age 24; range 19–29 years) had an average on‐axis mean‐sphere refraction of −6.33 ± 0.31 D (mean ± 1 S.E.) and an average axial eye length of 25.99 ± 0.20 mm. The average relative peripheral refraction (RPR) for all subjects across all eccentricities was hyperopic when uncorrected (+0.90 ± 0.14 D) and also when corrected with spectacles (+1.01 ± 0.13 D) but changed to a myopic RPR when corrected with contact lenses (−1.84 ± 0.61 D). There was a highly significant effect of correction on peripheral refraction (p < 0.0001). Peripheral J0 astigmatism also became significantly more negative (less with‐the‐rule) on correction with contact lenses (p = 0.015), whereas J45 astigmatism remained unchanged. On‐ and off‐ axis eye length measures indicated a relatively prolate eye shape.Conclusions:  Correcting the on‐axis refractive error in moderate to high myopia with conventional spherical spectacle lenses results in hyperopic defocus in the peripheral retina. Correcting the same eyes with conventional spherical soft contact lenses results in significant myopic defocus in the peripheral retina. These results corroborate the general findings of earlier studies and the predictions of optical modelling by others. If the refractive status of the peripheral retina does influence myopia progression, then these results suggest that myopia progression should be slower with conventional contact lens wear than with conventional spectacle wear. However, previous studies comparing myopia progression with conventional spectacles and conventional contact lenses have reported no such difference.
Modulation of Pre‐Capillary Arteriolar Pressure with Drag‐Reducing Polymers: A Novel Method for Enhancing Microvascular Perfusion
Authors: PACELLA JOHN J. , KAMENEVA MARINA V. , BRANDS JUDITH , LIPOWSKY HERBERT H. , VINK HANS , LAVERY LINDA L. , VILLANUEVA FLORDELIZA S. 
Published: May 2012

Please cite this paper as: Pacella JJ, Kameneva MV, Brands J, Lipowsky HH, Vink H, Lavery LL, Villanueva FS. Modulation of pre‐capillary arteriolar pressure with drag‐reducing polymers: a novel method for enhancing microvascular perfusion. Microcirculation 19: 580–585, 2012.AbstractObjective:  We have shown that drag‐reducing polymers (DRP) enhance capillary perfusion during severe coronary stenosis and increase red blood cell velocity in capillaries, through uncertain mechanisms. We hypothesize that DRP decreases pressure loss from the aorta to the arteriolar compartment.Methods:  Intravital microscopy of the rat cremaster muscle and measurement of pressure in arterioles (diameters 20–132 μm) was performed in 24 rats. DRP (polyethylene oxide, 1 ppm) was infused i.v. and measurements were made at baseline and 20 minutes after completion of DRP infusion. In a 10‐rat subset, additional measurements were made three minutes after the start, and one to five and 10 minutes after completion of DRP.Results:  Twenty minutes after the completion of DRP, mean arteriolar pressure was 22% higher than baseline (from 42 ± 3 to 49 ± 3 mmHg, p < 0.005, n = 24). DRP decreased the pressure loss from the aorta to the arterioles by 24% (from 35 ± 6 to 27 ± 5 mmHg, p = 0.001, n = 10). In addition, there was a strong trend toward an increase in pressure at 10 minutes after the completion of DRP (n = 10).Conclusions:  Drag‐reducing polymers diminish pressure loss between the aorta and the arterioles. This results in a higher pre‐capillary pressure and probably explains the observed DRP enhancement in capillary perfusion.
Pharmacological Profiling of Store‐Operated Ca2+ Entry in Retinal Arteriolar Smooth Muscle
Authors: MCGAHON MARY K. , MCKEE JONATHAN , DASH DURGA P. , BROWN EOIN , SIMPSON DAVID A. , CURTIS TIMOTHY M. , McGEOWN JAMES G. , SCHOLFIELD CHARLES N. 
Published: May 2012

Please cite this paper as: McGahon MK, McKee J, Dash DP, Brown E, Simpson DA, Curtis TM, McGeown JG, Scholfield CN. Pharmacological profiling of store‐operated Ca2+ entry in retinal arteriolar smooth muscle. Microcirculation 19: 586–597, 2012.AbstractObjective:  Pharmacological profiling of SOCE and molecular profiling of ORAI and TRPC expression in arterioles.Methods:  Fura‐2‐based microfluorimetry was used to assess CPA‐induced SOCE in rat retinal arteriolar myocytes. Arteriolar ORAI and TRP transcript expression was screened using RT‐PCR.Results:  The SKF96365 and LOE908 blocked SOCE (IC50s of 1.2 and 1.4 μm, respectively). Gd3+ and La3+ potently inhibited SOCE (IC50s of 21 and 42 nm, respectively), but Ni2+ showed lower potency (IC50 = 11.6 μm). 2APB inhibited SOCE (IC50 = 3.7 μm) but enhanced basal influx (>100 μm). Verapamil and nifedipine had no effect at concentrations that inhibit L‐type Ca2+ channels, but diltiazem inhibited SOCE by approximately 40% (≥0.1 μm). The RT‐PCR demonstrated transcript expression for ORAI 1, 2, and 3, and TRPC1, 3, 4, and 7. Transcripts for TRPV1 and 2, which are activated by 2APB, were also expressed.Conclusions:  The pharmacological profile of SOCE in retinal arteriolar smooth muscle appears unique when compared with other vascular tissues. This suggests that the molecular mechanisms underlying SOCE can differ, even in closely related tissues. Taken together, the pharmacological and molecular data are most consistent with involvement of TRPC1 in SOCE, although involvement of ORAI or other TRPC channels cannot be excluded.
Concurrent sensitization to metals and occupation
Authors: Rui Francesca , Bovenzi Massimo , Prodi Andrea , Fortina Anna Belloni , Romano Ilaria , Corradin Maria Teresa , Filon Francesca Larese 
Published: May 2012

Background. Cosensitization to nickel, cobalt and chromium occurs in the general population and in some occupational groups.Objectives. To estimate the isolated and concurrent occurrence of nickel, cobalt and chromium contact sensitization and their association with individual and occupational risk factors.Patients/methods. Twelve thousand four hundred and ninety‐two patients were patch tested with the European baseline series between 1997 and 2004 in north‐eastern Italy. The associations between patch test results and patient characteristics and occupations were investigated by means of multinomial logistic regression analysis.Results. Of the patients, 34.7% (4334 patients) had one or more positive patch test reactions to metals. As compared with those with negative reactions to all three metals, nickel sensitization was significantly higher in females than in males, not only as monosensitization, but also as cosensitization with cobalt, with chromium, or with both metals. Building and related trades workers showed positive reactions to chromium + nickel [odds ratio (OR) 1.99; 95% confidence interval (CI) 1.05–3.76) and chromium + cobalt (OR 2.61; 95% CI 1.46–4.67]. Cleaning workers showed a high prevalence of nickel, chromium, nickel + chromium and nickel + cobalt + chromium cosensitization (ORs 1.29, 1.66, 2.11, and 1.79, respectively). An excess risk for cosensitization to all three metals was found in textile and leather workers (OR 2.19; 95% CI 1.10–4.33), and in bartenders (OR 2.10; 95% CI 1.03–4.26).Conclusions. Some occupational groups are more likely to develop nickel, cobalt and chromium cosensitization.