bluuebunny/crossref_metadata_2025_split huggingface dataset:
The phosphatidylinositol transfer protein RdgBβ binds 14-3-3 via its unstructured C-terminus, whereas its lipid-binding domain interacts with the integral membrane protein ATRAP (angiotensin II type I receptor-associated protein)
Authors: Garner Kathryn , Li Michelle , Ugwuanya Natalie , Cockcroft Shamshad 
Published: July 2011

PITPs [PI (phosphatidylinositol) transfer proteins] bind and transfer PI between intracellular membranes and participate in many cellular processes including signalling, lipid metabolism and membrane traffic. The largely uncharacterized PITP RdgBβ (PITPNC1; retinal degeneration type B β), contains a long C-terminal disordered region following its defining N-terminal PITP domain. In the present study we report that the C-terminus contains two tandem phosphorylated binding sites (Ser274 and Ser299) for 14-3-3. The C-terminus also contains PEST sequences which are shielded by 14-3-3 binding. Like many proteins containing PEST sequences, the levels of RdgBβ are regulated by proteolysis. RdgBβ is degraded with a half-life of 4 h following ubiquitination via the proteasome. A mutant RdgBβ which is unable to bind 14-3-3 is degraded even faster with a half-life of 2 h. In vitro, RdgBβ is 100-fold less active than PITPα for PI transfer, and RdgBβ proteins (wild-type and a mutant that cannot bind 14-3-3) expressed in COS-7 cells or endogenous proteins from heart cytosol do not exhibit transfer activity. When cells are treated with PMA, the PITP domain of RdgBβ interacts with the integral membrane protein ATRAP (angiotensin II type I receptor-associated protein; also known as AGTRAP) causing membrane recruitment. We suggest that RdgBβ executes its function following recruitment to membranes via its PITP domain and the C-terminal end of the protein could regulate entry to the hydrophobic cavity.
Crystal structure of the glutamate receptor GluA1 N-terminal domain
Authors: Yao Guorui , Zong Yinong , Gu Shenyan , Zhou Jie , Xu Huaxi , Mathews Irimpan I. , Jin Rongsheng 
Published: July 2011

The AMPA (α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) subfamily of iGluRs (ionotropic glutamate receptors) is essential for fast excitatory neurotransmission in the central nervous system. The malfunction of AMPARs (AMPA receptors) has been implicated in many neurological diseases, including Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis. The active channels of AMPARs and other iGluR subfamilies are tetramers formed exclusively by assembly of subunits within the same subfamily. It has been proposed that the assembly process is controlled mainly by the extracellular ATD (N-terminal domain) of iGluR. In addition, ATD has also been implicated in synaptogenesis, iGluR trafficking and trans-synaptic signalling, through unknown mechanisms. We report in the present study a 2.5 Å (1 Å=0.1 nm) resolution crystal structure of the ATD of GluA1. Comparative analyses of the structure of GluA1-ATD and other subunits sheds light on our understanding of how ATD drives subfamily-specific assembly of AMPARs. In addition, analysis of the crystal lattice of GluA1-ATD suggests a novel mechanism by which the ATD might participate in inter-tetramer AMPAR clustering, as well as in trans-synaptic protein–protein interactions.
Characterization of bone‐marrow‐derived rat mesenchymal stem cells depending on donor age
Authors: Gala Kamila , Burdzińska Anna , Idziak Marta , Makula Jolanta , Pa̧czek Leszek 
Published: July 2011

AbstractIt is generally accepted that autologous transfers, as non‐immunogenic, constitute the safest approach in cellular transplantations. However, this attitude is often associated with the need for isolation and extracorporeal propagation of cells derived from aged patients. Thus the knowledge about relationship between aging and the properties of MSCs (mesenchymal stem cells) is crucial in developing new clinical strategies. The aim of this study was to perform complex comparison of MSC derived from young and aged individuals, which included phenotype, proliferating rate, osteogenic and adipogenic potential and secretory activity. Evaluated populations were isolated from bone marrow of 3‐month‐old and 24‐month‐old rats. There was no significant difference in membrane antigen expression and PDT (population doubling time). Additionally, the adipogenic and osteogenic potential did not vary between studied populations. The reaction of MSCs to either mitogen [bFGF (basic fibroblast growth factor)] or oxidative stress (H2O2)in vitrodisplayed a very similar pattern in both analysed populations. There was no difference in TGFβ1 (transforming growth factor β1) and VEGF (vascular endothelial growth factor) secretion measured by ELISA test and gene expression evaluated by real‐time PCR. However, the expression of the gene for IL‐1α (interleukin‐1α) was 8‐fold lower in oMSC (MSC isolated from old rats). These results indicate that aging individuals can be considered as candidates for autologous transplantation of bone‐marrow‐derived MSCs.
Guanosine supplementation reduces the antiproliferative and apoptotic effects of the IMPDH inhibitor gnidilatimonoein in K562 cells
Authors: Nouri Kazem , Yazdanparast Razieh , Sarafnejad Abdolfattah 
Published: July 2011

AbstractIMPDH (inosine 5′‐monophosphate dehydrogenase) is the rate‐limiting enzyme in the de novo biosynthetic pathway of guanine nucleotides, which is usually up‐regulated in human leukaemia cell lines. Our previous studies have classified gnidilatimonoein, isolated from Daphne mucronata, as an IMPDH inhibitor and a strong antiproliferative agent among several types of leukaemia cells. In the present study, we investigated the effects of gnidilatimonoein on intracellular GTP pool size and its link to differentiation and apoptosis of K562 cells. It was found that gnidilatimonoein inhibited cell proliferation and induced G0/G1 cell cycle arrest in K562 cells after 24 h exposure to a single dose of gnidilatimonoein (1.5 μM), while no significant effects were observed on unstimulated and phytohaemagglutinin‐stimulated peripheral blood lymphocyte cells at the gnidilatimonoein dose (1.5 μM) used. Based on the morphological changes, Wright −Giemsa staining, benzidine assay and the expression of cell surface markers [GPIIb (glycoprotein IIb) and glycophorin A], as analysed by flow cytometry, we found that K562 cells had differentiated towards megakaryocytic lineage. In addition, gnidilatimonoein induced apoptosis among K562 cells based on Acridine Orange/ethidium bromide and annexin V/propidium iodide double‐staining observations. These changes, which were abrogated by the addition of guanosine, became evident when the intracellular GTP level decreased to approx. 20–35% of the untreated control level. Based on these findings, it can be concluded that gnidilatimonoein induces differentiation and apoptosis in K562 cells through perturbation of GTP metabolism, as one of its routes of action.
Identification of the VIL2 enhancer in human embryonic kidney cells
Authors: Gao Shu‐Ying , Dai Yan‐Peng , Long Xia , Zhang Fang‐Ting , Yu Jie 
Published: July 2011

AbstractWe previously demonstrated that the VIL2 −87/+134 region exhibited promoter activity in some human cells, and a region further upstream of this promoter might contain an enhancer. However, the properties and location of this VIL2 enhancer remain unclear. In this study, we cloned the VIL2 −1541/ −706 segment and investigated its transcriptional regulatory properties via luciferase assays in transiently transfected HEK‐293 cells (human embryonic kidney cells). The VIL2 −1541/ −706 was found to exhibit promoter activity. Furthermore, when this segment was located upstream of the VIL2 or SV40 (simian virus 40) promoters in the forward orientation, the expression levels of luciferase were dramatically enhanced. However, this transcriptional enhancement disappeared when this segment was located upstream of the promoter in the reverse orientation or downstream of the reporter gene in the forward or reverse orientation. In deletion experiments, we found several potential regulatory regions within the VIL2 −1541/ −706. When these regions were separately located upstream of the VIL2 or SV40 promoters, only the −1297/ −1186 considerably enhanced the activity of these promoters. Although the other regulatory regions exhibited significant transcriptional regulation in deletion experiments, they weakly enhanced VIL2 promoter activity and/or did not regulate SV40 promoter activity. These results suggest that the DNA sequence upstream of the VIL2 promoter functions as an enhancer in a position‐ and orientation‐dependent manner, and the VIL2 −1297/ −1186, which acts as a key enhancer, probably regulates VIL2 transcription in combination with other potential regulatory regions located upstream of the VIL2 promoter.
Doxorubicin-induced cardiac dysfunction is attenuated by ciclosporin treatment in mice through improvements in mitochondrial bioenergetics
Authors: Marechal Xavier , Montaigne David , Marciniak Camille , Marchetti Philippe , Hassoun Sidi Mohamed , Beauvillain Jean Claude , Lancel Steve , Neviere Remi 
Published: July 2011

We tested whether inhibition of mitochondrial membrane potential dissipation by CsA (ciclosporin A) would prevent doxorubicin-induced myocardial and mitochondrial dysfunction. Acute and subchronic models of doxorubicin exposition were performed in mice with either a single intraperitoneal bolus (10 mg/kg of body weight, intraperitoneal) or one injection of 4 mg·kg−1 of body weight·week−1 during 5 weeks. Follow-up was at 1.5 weeks and 16 weeks in acute and subchronic models respectively. Mice received either CsA (1 mg/kg of body weight, intraperitoneal on alternate days) or saline until follow-up. Heart function was evaluated by echocardiography. Mitochondrial measurements included oxygen consumption, membrane potential and externally added calcium-induced mitochondrial permeability transition. Mitochondrial mass was evaluated by transmission electronic microscopy and mtDNA (mitochondrial DNA) content. Mitochondrial dynamics were detected as the expression of GTPases involved in mitochondrial fusion and fission. In both the acute and chronic models, doxorubicin decreased left ventricular fractional shortening and survival. Heart function and survival were improved by CsA, but not by tacrolimus (FK506), a ciclosporin derivative with no inhibitory effect on the mitochondrial transition pore. In the acute model, doxorubicin exposure was associated with increased mtDNA content, mitochondrial fragmentation and changes in mitochondrial fusion- and fission-related transcripts [increases in Mfn2 (mitofusin 2), Opa1 (optic atrophy 1 homologue) and Fis1 (fission 1 homologue), and no changes in Drp1 (dynamin 1-like)]. CsA did not alter mitochondrial biogenesis, but prevented mitochondrial fragmentation and partially restored the mitochondrial energy-producing capacity. These findings suggest that in vivo CsA treatment may limit MPTP (mitochondrial permeability transition pore) opening, mitochondrial potential loss and contractile depression in acute and chronic models of cardiac toxicity induced by doxorubicin.
Maternal antioxidant blocks programmed cardiovascular and behavioural stress responses in adult mice
Authors: Roghair Robert D. , Wemmie John A. , Volk Kenneth A. , Scholz Thomas D. , Lamb Fred S. , Segar Jeffrey L. 
Published: July 2011

Intra-uterine growth restriction is an independent risk factor for adult psychiatric and cardiovascular diseases. In humans, intra-uterine growth restriction is associated with increased placental and fetal oxidative stress, as well as down-regulation of placental 11β-HSD (11β-hydroxysteroid dehydrogenase). Decreased placental 11β-HSD activity increases fetal exposure to maternal glucocorticoids, further increasing fetal oxidative stress. To explore the developmental origins of co-morbid hypertension and anxiety disorders, we increased fetal glucocorticoid exposure by administering the 11β-HSD inhibitor CBX (carbenoxolone; 12 mg·kg−1 of body weight·day−1) during the final week of murine gestation. We hypothesized that maternal antioxidant (tempol throughout pregnancy) would block glucocorticoid-programmed anxiety, vascular dysfunction and hypertension. Anxiety-related behaviour (conditioned fear) and the haemodynamic response to stress were measured in adult mice. Maternal CBX administration significantly increased conditioned fear responses of adult females. Among the offspring of CBX-injected dams, maternal tempol markedly attenuated the behavioural and cardiovascular responses to psychological stress. Compared with offspring of undisturbed dams, male offspring of dams that received daily third trimester saline injections had increased stress-evoked pressure responses that were blocked by maternal tempol. In contrast, tempol did not block CBX-induced aortic dysfunction in female mice (measured by myography and lucigenin-enhanced chemiluminescence). We conclude that maternal stress and exaggerated fetal glucocorticoid exposure enhance sex-specific stress responses, as well as alterations in aortic reactivity. Because concurrent tempol attenuated conditioned fear and stress reactivity even among the offspring of saline-injected dams, we speculate that antenatal stressors programme offspring stress reactivity in a cycle that may be broken by antenatal antioxidant therapy.
Cytochrome P450 metabolites of arachidonic acid are elevated in stroke patients compared with healthy controls
Authors: Ward Natalie C. , Croft Kevin D. , Blacker David , Hankey Graeme J. , Barden Anne , Mori Trevor A. , Puddey Ian B. , Beer Christopher D. 
Published: July 2011

CYP450AAM [arachidonic acid metabolites of the CYP450 (cytochrome P450) enzyme system] have a range of biological functions. CYP450AAM are involved in the pathogenesis of hypertension, renal function and vascular function, yet their role in stroke has not been clarified. We aimed at determining the levels of circulating CYP450 metabolites in patients with acute ischaemic stroke (&lt;96 h) compared with healthy age- and gender-matched controls. This was a retrospective case-controlled study of 44 acute ischaemic stroke patients and 44 matched controls. A subset of acute ischaemic stroke patients was available for follow-up. Acute ischaemic stroke patients had elevated plasma CYP450AAM, including 20-HETE (20-hydroxyeicosatetraenoic acid) (1921±170 compared with 1108±170 pmol/l, P&lt;0.001), EETs (epoxyeicosatrienoic acids) (77.88±3.34 compared with 35.35±3.34 nmol/l, P&lt;0.0001) and DiHETEs (dihydroxyeicosatetraenoic acids) (92.87±4.61 compared with 68.17±4.61 nmol/l, P&lt;0.0001), as well as increased plasma F2-isoprostane levels (3754±538 compared with 1947±538 pmol/l, P&lt;0.02), the latter a marker of oxidative stress, compared with controls. In a subset analysis of the stroke patients, plasma 20-HETE, EETs and F2-isoprostanes were attenuated 30 days after the stroke. Baseline 20-HETE levels were also associated with lesion size and functional indices within the stroke patients. The present study highlights the elevation in CYP450AAM and oxidative stress in acute ischaemic stroke patients. Further investigation of the effect this has on long-term clinical outcome or whether this can be modified by treatment is warranted.
Computational studies of a cut-wire pair and combined metamaterials
Authors: Nguyen Thanh Tung , Lievens Peter , Lee Young Pak , Vu Dinh Lam 
Published: July 2011

Abstract
The transfer-matrix method and finite-integration simulations show how the transmission properties of combined metamaterials, which consist of metallic cut-wire pairs and continuous wires, are affected by geometric parameters. The corresponding effective permittivity and permeability are retrieved from the complex scattering parameters using the standard retrieval procedure. The electromagnetic properties of the cut-wire pair as well as the left-handed behavior of the combined structure are understood by the effective medium theory. In addition, the dimensional dependence of transmission properties, the shapes of cut-wire pairs and continuous wire, and the impact of dielectric spacer are both examined. Finally, by expanding the results of previous research (Koschny et al 2003 Phys. Rev. Lett.
93 016608), we generalize the transmission picture of combined structures in terms of the correlation between electric and magnetic responses.
A negative feedback controlled hybrid mode locked Nd : YAG laser using a semiconductor quantum dot saturable absorber
Authors: Buganov Oleg V , Nguyen Dai Hung , Tikhomirov Sergei A , Onuschenko Alexei A 
Published: July 2011

Abstract
The parameters of a solid-state PbS quantum dot saturable absorber, optical elements, resonator and feedback circuit have been adjusted for stable and highly efficient hybrid mode-locking Nd : YAG laser operation. A highly stable microsecond pulse train (40–50 μs) containing about 5000 ps pulses and 3 mJ total train energy was generated with a repetition rate of 10 Hz. This all solid-state hybrid mode-locked Nd : YAG laser was used for synchronous pumping of a femtosecond Ti : sapphire laser.
MethylCoder: software pipeline for bisulfite-treated sequences
Authors: Pedersen Brent , Hsieh Tzung-Fu , Ibarra Christian , Fischer Robert L. 
Published: July 2011

Abstract
Motivation: MethylCoder is a software program that generates per-base methylation data given a set of bisulfite-treated reads. It provides the option to use either of two existing short-read aligners, each with different strengths. It accounts for soft-masked alignments and overlapping paired-end reads. MethylCoder outputs data in text and binary formats in addition to the final alignment in SAM format, so that common high-throughput sequencing tools can be used on the resulting output. It is more flexible than existing software and competitive in terms of speed and memory use.
Availability: MethylCoder requires only a python interpreter and a C compiler to run. Extensive documentation and the full source code are available under the MIT license at: https://github.com/brentp/methylcode.
Contact: bpederse@gmail.com
Computational reconstruction of primordial prototypes of elementary functional loops in modern proteins
Authors: Goncearenco Alexander , Berezovsky Igor N. 
Published: July 2011

Abstract
Motivation: Enzymes are complex catalytic machines, which perform sequences of elementary chemical transformations resulting in biochemical function. The building blocks of enzymes, elementary functional loops (EFLs), possess distinct functional signatures and provide catalytic and binding amino acids to the enzyme's active sites. The goal of this work is to obtain primordial prototypes of EFLs that existed before the formation of enzymatic domains and served as their building blocks.
Results: We developed a computational strategy for reconstructing ancient prototypes of EFLs based on the comparison of sequence segments on the proteomic scale, which goes beyond detection of conserved functional motifs in homologous proteins. We illustrate the procedure by a CxxC-containing prototype with a very basic and ancient elementary function of metal/metal-containing cofactor binding and redox activity. Acquiring the prototypes of EFLs is necessary for revealing how the original set of protein folds with enzymatic functions emerged in predomain evolution.
Supplementary Information: Supplementary data are available at Bioinformatics online.
Contact: igor.berezovsky@uni.no
A meta‐analysis of the association of adiponectin gene polymorphisms with coronary heart disease in Chinese Han population
Authors: Zhang Bu‐Chun , Li Wei‐Ming , Xu Ya‐Wei 
Published: July 2011

SummaryObjective  Variants of adiponectin gene have been reported to be associated with coronary heart disease (CHD), but the available data on this relationship are inconsistent. A meta‐analysis was performed to quantitatively analyse the association of adiponectin gene polymorphisms with coronary artery disease using previous case–control studies in Chinese Han populations.Methods  Several electronic databases were searched for relevant articles up to January 2011. After data collection and gene loci selection, a meta‐analysis was performed to assess heterogeneity, combine results and evaluate variations. Publication bias was examined by the Egger’s linear regression test. Hardy–Weinberg equilibrium (HWE) test and by omitting one study at a time was employed for the sensitivity analysis.Results  Eleven studies covering 4303 subjects focusing on two polymorphisms [+45T→G (rs2241766) and +276G→T (rs1501299)] in the adiponectin gene and risk of CHD were included in the meta‐analysis. Combined analyses of studies of the SNP+45 showed no significant overall association with CHD, yielding ORs of 1·03 (0·80, 1·34) and 1·32 (0·86, 2·03) under a dominant and recessive model, respectively, with strong evidence of heterogeneity. Similar results were also obtained in other genetic models. Concerning SNP+276, a significantly decreased CHD risk was observed under a dominant model, a codominant model and a allele contrast model, with an odds ratio of 0·67 (0·54, 0·83), 0·77 (0·62, 0·94) and 0·69 (0·55, 0·86), respectively. Sensitivity analysis confirmed the reliability and stability of this meta‐analysis.Conclusions  The accumulated evidence suggested that the adiponectin gene polymorphism, SNP+45, is not associated with CHD, but the SNP+276T allele might be associated with decreased risk of CHD in the Chinese Han population. More well‐designed large studies are required for the validation of this association.
Age‐related modification of antioxidant enzyme activities in relation to cardiovascular risk factors
Authors: Fabian Elisabeth , Bogner Michaela , Elmadfa Ibrahim 
Published: July 2011

Eur J Clin Invest 2012; 42 (1): 42–48AbstractBackground  Since oxidative stress might cause and promote cardiovascular risk factors such as oxidized low‐density lipoproteins (oxLDL), apolipoprotein(a) [apo(a)], asymmetric dimethylarginine (ADMA) and fetuin A, we investigated antioxidant enzyme activities in relation to the vascular redox balance and these risk factors in elderly people.Materials and methods  For this observational study, a total of 102 subjects were recruited and divided into three groups: A (70–74 years/n = 48), B (75–79 years/n = 35) and C (≥80 years/n = 19). Activities of the erythrocyte antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GSH‐Px) and catalase (CAT) were determined photometrically oxLDL, apo(a), ADMA and fetuin A by ELISA. Plasma concentrations of the lipid peroxidation products malondialdehyde (MDA) and conjugated dienes (CD) were analysed with HPLC.Results  There were no significant age‐associated alterations in apo(a) levels, but there was a significant age‐related decrease in activities of SOD (A>C, B>C: P < 0·01), CAT (A>C: P < 0·05) and GSH‐Px (A>C: P < 0·05), accompanied by a significant increase in oxLDL (A<C: P < 0·001; B<C: P < 0·05), ADMA (A<B: P < 0·05; A<C: P < 0·001), MDA (A<C, B<C: P < 0·01) and CD (A<C, B<C: P < 0·01), and a significant decrease in fetuin A (A>C: P < 0·01; B>C: P < 0·05). Consequently, all groups showed significant negative age‐associated correlations between CAT and MDA (A, B, C: P < 0·05), GSH‐Px and CD (A, C: P < 0·01; B: P < 0·05), SOD and oxLDL (A, B: P < 0·05; C: P < 0·01), and fetuin A and MDA (A: P < 0·01; B, C: P < 0·05), and a significant positive correlation between oxLDL and ADMA (A, B: P < 0·05; C: P < 0·01).Conclusions  This study indicates a significant age‐related decrease in antioxidant enzyme activities accompanied by significantly increased systemic oxidative stress, which promotes the cardiovascular risk factors oxLDL, ADMA and fetuin A in elderly people.