bluuebunny/crossref_metadata_2025_split huggingface dataset:
Insulin Reduces Cerebral Ischemia/Reperfusion Injury in the Hippocampus of Diabetic Rats
Authors: Collino Massimo , Aragno Manuela , Castiglia Sara , Tomasinelli Chiara , Thiemermann Christoph , Boccuzzi Giuseppe , Fantozzi Roberto 
Published: October 2008

OBJECTIVE—There is evidence that insulin reduces brain injury evoked by ischemia/reperfusion (I/R). However, the molecular mechanisms underlying the protective effects of insulin remain unknown. Insulin is a well-known inhibitor of glycogen synthase kinase-3β (GSK-3β). Here, we investigate the role of GSK-3β inhibition on I/R-induced cerebral injury in a rat model of insulinopenic diabetes.
RESEARCH DESIGN AND METHODS—Rats with streptozotocin-induced diabetes were subjected to 30-min occlusion of common carotid arteries followed by 1 or 24 h of reperfusion. Insulin (2–12 IU/kg i.v.) or the selective GSK-3β inhibitor TDZD-8 (0.2–3 mg/kg i.v.) was administered during reperfusion.
RESULTS—Insulin or TDZD-8 dramatically reduced infarct volume and levels of S100B protein, a marker of cerebral injury. Both drugs induced phosphorylation of the Ser9 residue, thereby inactivating GSK-3β in the rat hippocampus. Insulin, but not TDZD-8, lowered blood glucose. The hippocampi of the drug-treated animals displayed reduced oxidative stress at 1 h of reperfusion as shown by the decreased generation of reactive oxygen species and lipid peroxidation. I/R-induced activation of nuclear factor-κB was attenuated by both drug treatments. At 24 h of reperfusion, TDZD-8 and insulin significantly reduced plasma levels of tumor necrosis factor-α; neutrophil infiltration, measured as myeloperoxidase activity and intercellular-adhesion-molecule-1 expression; and cyclooxygenase-2 and inducible-NO-synthase expression.
CONCLUSIONS—Acute administration of insulin or TDZD-8 reduced cerebral I/R injury in diabetic rats. We propose that the inhibitory effect on the activity of GSK-3β contributes to the protective effect of insulin independently of any effects on blood glucose.
Genome-Wide Linkage and Admixture Mapping of Type 2 Diabetes in African American Families From the American Diabetes Association GENNID (Genetics of NIDDM) Study Cohort
Authors: Elbein Steven C. , Das Swapan K. , Hallman D. Michael , Hanis Craig L. , Hasstedt Sandra J. 
Published: October 2008

OBJECTIVE—We used a single nucleotide polymorphism (SNP) map in a large cohort of 580 African American families to identify regions linked to type 2 diabetes, age of type 2 diabetes diagnosis, and BMI.
RESEARCH DESIGN AND METHODS—After removing outliers and problematic samples, we conducted linkage analysis using 5,914 SNPs in 1,344 individuals from 530 families. Linkage analysis was conducted using variance components for type 2 diabetes, age of type 2 diabetes diagnosis, and BMI and nonparametric linkage analyses. Ordered subset analyses were conducted ranking on age of type 2 diabetes diagnosis, BMI, waist circumference, waist-to-hip ratio, and amount of European admixture. Admixture mapping was conducted using 4,486 markers not in linkage disequilibrium.
RESULTS—The strongest signal for type 2 diabetes (logarithm of odds [LOD] 4.53) was a broad peak on chromosome 2, with weaker linkage to age of type 2 diabetes diagnosis (LOD 1.82). Type 2 diabetes and age of type 2 diabetes diagnosis were linked to chromosome 13p (3–22 cM; LOD 2.42 and 2.46, respectively). Age of type 2 diabetes diagnosis was linked to 18p (66 cM; LOD 2.96). We replicated previous reports on chromosome 7p (79 cM; LOD 2.93). Ordered subset analysis did not overlap with linkage of unselected families. The best admixture score was on chromosome 12 (90 cM; P = 0.0003).
CONCLUSIONS—The linkage regions on chromosomes 7 (27–78 cM) and 18p overlap prior reports, whereas regions on 2p and 13p linkage are novel. Among potential candidate genes implicated are TCF7L1, VAMP5, VAMP8, CDK8, INSIG2, IPF1, PAX8, IL18R1, members of the IL1 and IL1 receptor families, and MAP4K4. These studies provide a complementary approach to genome-wide association scans to identify causative genes for African American diabetes.
Follow-Up Analysis of Genome-Wide Association Data Identifies Novel Loci for Type 1 Diabetes
Authors: Grant Struan F.A. , Qu Hui-Qi , Bradfield Jonathan P. , Marchand Luc , Kim Cecilia E. , Glessner Joseph T. , Grabs Rosemarie , Taback Shayne P. , Frackelton Edward C. , Eckert Andrew W. , Annaiah Kiran , Lawson Margaret L. , Otieno F. George , Santa Erin , Shaner Julie L. , Smith Ryan M. , Skraban Robert , Imielinski Marcin , Chiavacci Rosetta M. , Grundmeier Robert W. , Stanley Charles A. , Kirsch Susan E. , Waggott Daryl , Paterson Andrew D. , Monos Dimitri S. ,   the DCCT/EDIC Research Group, Polychronakos Constantin , Hakonarson Hakon 
Published: October 2008

OBJECTIVE—Two recent genome-wide association (GWA) studies have revealed novel loci for type 1 diabetes, a common multifactorial disease with a strong genetic component. To fully utilize the GWA data that we had obtained by genotyping 563 type 1 diabetes probands and 1,146 control subjects, as well as 483 case subject–parent trios, using the Illumina HumanHap550 BeadChip, we designed a full stage 2 study to capture other possible association signals.
RESEARCH DESIGN AND METHODS—From our existing datasets, we selected 982 markers with P &lt; 0.05 in both GWA cohorts. Genotyping these in an independent set of 636 nuclear families with 974 affected offspring revealed 75 markers that also had P &lt; 0.05 in this third cohort. Among these, six single nucleotide polymorphisms in five novel loci also had P &lt; 0.05 in the Wellcome Trust Case-Control Consortium dataset and were further tested in 1,303 type 1 diabetes probands from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) plus 1,673 control subjects.
RESULTS—Two markers (rs9976767 and rs3757247) remained significant after adjusting for the number of tests in this last cohort; they reside in UBASH3A (OR 1.16; combined P = 2.33 × 10−8) and BACH2 (1.13; combined P = 1.25 × 10−6).
CONCLUSIONS—Evaluation of a large number of statistical GWA candidates in several independent cohorts has revealed additional loci that are associated with type 1 diabetes. The two genes at these respective loci, UBASH3A and BACH2, are both biologically relevant to autoimmunity.
Effect of a Successful Intensive Lifestyle Program on Insulin Sensitivity and Glucose Tolerance in Obese Youth
Authors: Shaw Melissa , Savoye Mary , Cali Anna , Dziura James , Tamborlane William V. , Caprio Sonia 
Published: October 2008

OBJECTIVE—To evaluate the impact on glucose metabolism of a lifestyle program (the Yale Bright Bodies Program) for obese children.
RESEARCH DESIGN AND METHODS—Thirteen Bright Bodies and ten clinic-care control subjects who were part of a large randomized clinical trial had 75-g oral glucose tolerance tests at the beginning and end of the 12-month study.
RESULTS—Bright Bodies subjects had significantly greater decreases in weight, BMI, and body fat than clinic-care subjects, and the Bright Body subjects’ changes in body composition were accompanied by marked improvements in insulin sensitivity (P = 0.009) and glucose tolerance (P = 0.04).
CONCLUSIONS—An intensive lifestyle program that successfully reduces body weight and body fat can markedly improve insulin sensitivity and glucose metabolism in obese youth.
Serum Levels of the Adipokine FGF21 Depend on Renal Function
Authors: Stein Sebastian , Bachmann Anette , Lössner Ulrike , Kratzsch Jürgen , Blüher Matthias , Stumvoll Michael , Fasshauer Mathias 
Published: October 2008

OBJECTIVE—To investigate renal elimination of the adipokine fibroblast growth factor 21 (FGF21) by determining circulating FGF21 levels in patients on chronic hemodialysis (CD) as compared with control subjects with a glomerular filtration rate (GFR) &gt;50 ml/min.
RESEARCH DESIGN AND METHODS—FGF21 was determined by enzyme-linked immunosorbent assay in control (n = 60) and CD (n = 60) patients and correlated to clinical and biochemical measures of renal function, glucose and lipid metabolism, and inflammation in both groups.
RESULTS—Median serum FGF21 levels were &gt;15-fold higher in CD patients (3,710.6 ng/l) than in subjects with a GFR &gt;50 ml/min (201.9 ng/l) (P &lt; 0.001). Furthermore, serum creatinine positively and GFR negatively predicted FGF21 concentrations in multiple regression analyses in control subjects (P &lt; 0.05).
CONCLUSIONS—FGF21 serum levels increase in CD patients and are related to markers of renal function in control subjects.
Correlation between the levels of survivin and survivin promoter-driven gene expression in cancer and non-cancer cells
Authors: Konopka Krystyna , Spain Christopher , Yen Allison , Overlid Nathan , Gebremedhin Senait , Düzgüneş Nejat 
Published: October 2008

AbstractSurvivin, a member of the inhibitor of apoptosis (IAP) protein family, is associated with malignant transformation and is over-expressed in most human tumors. Using lipoplex-mediated transfection, we evaluated the activity of the reporter enzyme, luciferase, expressed from plasmids encoding the enzyme under the control of either the cytomegalovirus (CMV) or survivin promoters, in tumor- and non-tumor-derived human and murine cells. We also examined whether there is a correlation between the survivin promoter-driven expression of luciferase and the level of endogenous survivin. Human cancer cells (HeLa, KB, HSC-3, H357, H376, H413), oral keratinocytes, GMSM-K, and chemically immortalized human mammary cells, 184A-1, were transfected with Metafectene at 2 μl/1 μg DNA. Murine squamous cell carcinoma cells, SCCVII, mouse embryonic fibroblasts, NIH-3T3, and murine immortalized mammary cells, NMuMG, were transfected with Metafectene PRO at 2 μl/1 μg DNA. The expression of luciferase was driven by the CMV promoter (pCMV.Luc), the human survivin promoter (pSRVN.Luc-1430), or the murine survivin promoters (pSRVN.Luc-1342 and pSRVN.Luc-194). Luciferase activity was measured, using the Luciferase Assay System and expressed as relative light units (RLU) per ml of cell lysate or per mg of protein. The level of survivin in the lysates of human cells was determined by ELISA and expressed as ng survivin/mg protein. In all cell lines, significantly higher luciferase activity was driven by the CMV promoter than by survivin promoters. The expression of luciferase driven by the CMV and survivin promoters in murine cells was much higher than that in human cells. The cells displayed very different susceptibilities to transfection; nevertheless, high CMV-driven luciferase activity appeared to correlate with high survivin-promoter driven luciferase expression. The survivin concentration in lysates of cancer cells ranged from 5.8 ± 2.3 to 24.3 ± 2.9 ng/mg protein (mean, 13.7 ng/mg). Surprisingly, elevated survivin protein was determined in lysates of non-tumor-derived cells. Survivin levels for GMSM-K and 184A-1 cells, were 16.7 ± 8.7 and 13.5 ± 6.2 ng/mg protein, respectively. The expression of endogenous survivin did not correlate with the level of survivin promoter-driven transgene activity in the same cells. The expression of survivin by non-tumorigenic, transformed cell lines may be necessary for their proliferative activity. The level of survivin promoter-driven gene expression achieved via liposomal vectors in OSCC cells was too low to be useful in cancer-cell specific gene therapy.
Probable annual floods in a small lowland river estimated with the use of various sets of data
Authors: Banasik Kazimierz , Byczkowski Andrzej 
Published: October 2008

Probable annual floods in a small lowland river estimated with the use of various sets of data
The results of estimation of the probable annual flood flows with the use of various sets of data from a small agricultural lowland river are presented. The traditional statistical series are formed from the annual maximum (AM) flows of hydrological years. After examination of the homogeneity of the series, two sets of data were formed (AM1 of 34 elements and AM2 of 40 elements), which differed in the significance level of one of the stationary tests. The other series for flood frequency analysis has been formed by selecting peaks over threshold discharges (POT). A computer program, developed by IMGW (Institute of Hydrology and Water Management), and spreadsheet were applied for frequency analysis with the use of AM series and POT series, respectively. Results of computations with the use of AM1 and AM2 data indicate for nonsignificant differences in probable flood flows, and significant with the probable flood flow estimated with the POT data.
Possible effects of climate change on ecological functioning of shallow lakes, Lake Loenderveen as a case study
Authors: Schep Sebastiaan , Ter Heerdt Gerard , Janse Jan , Ouboter Maarten 
Published: October 2008

Possible effects of climate change on ecological functioning of shallow lakes, Lake Loenderveen as a case study
The European Water Framework Directive (WFD) requires all inland and coastal waters to reach "good ecological status" by 2015. The good ecological status of shallow lakes can be characterised by clear water dominated by submerged vegetation. The ecological response of shallow lakes on nutrients largely depends on morphological and hydrological features, such as water depth, retention time, water level fluctuations, bottom type, fetch etc. These features determine the "critical nutrient load" of a lake. When the actual nutrient load of a lake is higher than the critical nutrient load, the ecological quality of this lake will deteriorate, resulting in a turbid state dominated by algae. Climate change might lead to changes in both environmental factors and ecosystem response. This certainly will have an effect on the ecological status. As an illustration the results of a multidiscipline study of a shallow peaty lake (Loenderveen) are presented, including hydrology, geochemistry and ecology. Ground- and surface water flows, nutrient dynamics and ecosystem functioning have been studied culminating in an application of the ecological model of the lake (PCLake). Future scenarios were implemented through changing precipitation, evaporation and temperature. Climate change will lead to higher nutrient loads and lower critical nutrient loads. As a consequence lakes shift easier from clear water to a turbid state.
Hydrological background of the dune slack vegetation in the Kiskunság
Authors: Margóczi Katalin , Szanyi János , Aradi Eszter , Busa-Fekete Bertalan 
Published: October 2008

Hydrological background of the dune slack vegetation in the Kiskunság
In the southern Kiskunság the natural vegetation (sand steppe, fen meadow, fen or marsh and alkali vegetation) survived in the dune slack meadows (DSM). The vegetation of these meadows are species rich, and has high natural value. The main goal of this study is to reveal the hydrological backgrounds in order to help conservation of the natural values. Two DSM was investigated (MM and CS site): vegetation was sampled, observation wells were planted, and data of other wells in similar position were used to describe the hydrological background of the vegetation. The characteristic groundwater level of the same vegetation type in the relatively wet 2005 year was higher in MM site, than in the CS site. We suppose, that this is a consequence of the earlier vegetation change because of the strong decrease of groundwater level in the region of MM site. The model of hydraulic flow system showed that the DSMs are situated in hydraulic discharge zones. We suppose, that an upward flow plays an important role in development of alkali vegetation in the CS site. Cross-correlation coefficient between groundwater and previous precipitation indicated a quick infiltration of rainwater into the soil, and a pressure front of the groundwater stream reaching the area of well after 22-23 days after rainfall. The quick and strong regional hydrological changes, especially the decrease of groundwater level would endanger this valuable vegetation, but certain resistance and plasticity of it is rather possible.
Multispectral processing of high‐resolution radiometric data for soil mapping
Authors: Beckett Kirsty 
Published: October 2008

ABSTRACTSoil radioactivity is dominantly a product of the local geology and mineralization, physical and chemical weathering processes within the profile, and soil organic content. Recent studies have shown that local soil patterns can be confidently mapped at scales of 1:10 000 using new high spatial resolution airborne and ground radiometric data acquired with standard 256‐channel gamma‐ray spectrometry systems and sodium‐iodide (NaI) crystal packs. In this study, a new multispectral processing methodology was developed to assess the 256‐channel spectral soil response. The study identified seven distinct gamma‐ray energy peaks, all products of the potassium‐40, uranium‐238 or thorium‐232 decay series, whose spatial and spectral relationships could be used to interpret soil properties and/or soil conditions.In the case studies presented, interpretation of complementary thorium and uranium channels (isolated using the new multispectral processing methodology) reveal additional spatial patterns and spectral information that were unattainable using standard processing methods. In one example, soil conditions attributed to a local, developing clay‐soil unit were resolved by the increased 228Ac (actinium) to 208Tl (thorium) channel response. In a separate example, a change in ratio between 214Bi (uranium) energies 1120 keV and 1764 keV, produced during the same decay emission, was used to differentiate soil conditions in the top 40 cm of an expansive sandy loam on clay duplex soil unit. A decrease in the 1120 keV to 1764 keV ratio was interpreted as an increase in soil density as the lower gamma‐ray energy emissions are preferentially attenuated with increased density. Relative increases in the 1120 keV and 1764 keV channel responses were interpreted as an increase in uranium concentration in the soil profile. With the clay as the dominant uranium contributor, integrated interpretation of the 214Bi channels suggested that in these areas there was an increase in clay percentage within the surface sandy loam, which may result in local increased water‐logging susceptibility.This paper also theorizes that interpretation of the spatial displacement of thorium‐232 decay series 228Ac and 208Tl peaks, produced from decay events approximately 2 years (half‐life) apart, can be used to identify decay series disequilibrium conditions resulting from local soil–water processes or other recent soil activity. This information contributes to an understanding of the soil processes active in the area. In addition, identification of disequilibrium decay conditions may highlight locations where standard radiometric (radioelement) processing, which relies on equilibrium conditions, may be erroneous.
The
Nrf
H
Cytochrome

c

Quinol Dehydrogenase
Authors: Thackray Sarah J , Bruckmann Chiara , Mowat Christopher G , Forouhar Farhad , Chapman Stephen K , Tong Liang 
Published: October 2008

Abstract

Indoleamine 2,3‐dioxygenase (IDO) and tryptophan 2,3‐dioxygenase (TDO) are heme‐containing enzymes from a small family of homologous enzymes. Despite both catalyzing the dioxygenation of
L
‐tryptophan, the first step in the kynurenine pathway, the sequence similarity between TDO and IDO is low. Alignment of sequences across this family of enzymes is only possible on the basis of their structures. Human IDO shows activity toward a wider range of substrates than TDO, and is found throughout the body, while TDO is limited to the liver and epidermis in mammals. To date, no functional prokaryotic IDO has been identified, while TDO is found in many bacteria. TDO and IDO have been implicated in a number of human physiological conditions, including suppression of T‐cell proliferation and the immune escape of cancers, making them attractive targets for drug discovery.
Nickel Regulatory Transcription Factor,
Nik
R
Authors: Phillips Christine M , Drennan Catherine L 
Published: October 2008

Abstract
The variety of roles that transition metals fulfill within the cell is staggering, but the concentrations of these metals must be tightly regulated to maintain minimal requisite levels and simultaneously prevent metal‐induced oxidative stress or inappropriate metal‐binding events. A variety of bacteria control the concentration of the transition metal nickel using the transcriptional repressor NikR. To suppress the import of nickel, the NikR protein binds nickel ions, inducing NikR's affinity for a promoter region upstream of a gene encoding a nickel‐specific importer. This binding event blocks RNA polymerase from attaching to the DNA, preventing the expression of further nickel‐specific importers. A variety of biochemical, structural, and spectroscopic studies on NikR have provided interesting insight into the overall function and structure of this regulatory protein.
The
Mgt
E
Mg
2+
Transporter
Authors: Maguire Michael E 
Published: October 2008

Abstract

The MgtE class of Mg
2+
ion transporter is widespread in the bacteria, with over 50% of current genomic sequences and most marine metagenome sequences exhibiting a homolog. MgtE is the primary provider of cytosolic Mg
2+
in those organisms that carry it. MgtE homologs are widespread in the metazoa and fungi (SLC41 family) but apparently absent in the plants. In bacteria, MgtE functions as a Mg
2+
influx system, while in eukaryotes specific MgtE proteins may function as either influx or efflux systems. Despite their ubiquity, virtually nothing is known about the physiological role of MgtE. Bacterial MgtE proteins are homodimers, with the entire soluble domain at the N terminus and the entire membrane domain at the C terminus. A recent crystal structure of

Thermus thermophilus

MgtE putatively in the closed form shows that the membrane domain consists of 5 transmembrane helices, each at a substantial angle to the plane of the membrane, giving 10 transmembrane helices in the dimer. The pore is formed primarily by transmembrane segments 2 and 5. Each membrane domain is connected to the soluble domain by a single α‐helix orthogonal to the membrane. Attached to this ‘connecting helix’ is a soluble domain containing a superhelical bundle of 10 α‐helices (‘N domain’) followed by duplicated tandem cystathionine β‐synthase‐like motifs, which end in the ‘connecting helix.’ The N domain has structural homology to the FliG protein of the flagellar motor. It is not clear how Mg
2+
is recognized and selected. The crystal structure also contains several sites for bound Mg
2+
ions, one within the pore. Two Mg
2+
sites per monomer connect the ‘connecting helice’ and CBS domain to the membrane domain, while two additional sites per monomer connect the CBS‐ and N domains. The structure of the soluble domain with and without Mg
2+
has also been solved. The absence of Mg
2+
does not alter the structure of the N domain significantly, but the structure of the tandem cystathionine β‐synthase domains within each monomer does change to some extent. The largest change due to the absence of Mg
2+
is that the entire cystathionine β‐synthase domain rotates and slightly twists 120° from the N domain. It is not clear if this rotation is part of the mechanism by which the pore opens and closes. Presumably, the bound Mg
2+
ions in the soluble domain play a role in sensing Mg
2+
, and their dissociation could allow domain movement and lead to opening of the pore.