bluuebunny/crossref_metadata_2025_split huggingface dataset:
Converging on the function of intrinsically disordered nucleoporins in the nuclear pore complex
Authors: Peleg Orit , Lim Roderick Y.H. 
Published: May 2010

Abstract
Several biological mechanisms involve proteins or proteinaceous components that are intrinsically disordered. A case in point pertains to the nuclear pore complex (NPC), which regulates molecular transport between the nucleus and the cytoplasm. NPC functionality is dependent on unfolded domains rich in Phe-Gly (FG) repeats (i.e., FG-domains) that collectively act to promote or hinder cargo translocation. To a large extent, our understanding of FG-domain behavior is limited to in vitro investigations given the difficulty to resolve them directly in the NPC. Nevertheless, recent findings indicate a collective convergence towards rationalizing FG-domain function. This review aims to glean further insight into this fascinating problem by taking an objective look at the boundary conditions and contextual details underpinning FG-domain behavior in the NPC. Here, we treat the FG-domains as being commensurate with polymeric chains to address ambiguities such as for instance, how FG-domains tethered to the central channel of the NPC would behave differently as compared with their free-floating counterparts in solution. By bringing such fundamental questions to the fore, this review seeks to illuminate the importance of how such parameters can hold influence over the structure-function relation of intrinsically disordered proteins in the NPC and beyond.
Towards molecular systems biology of gene transcription and regulation
Authors: Cramer Patrick 
Published: May 2010

Abstract
Ten years after the determination of the RNA polymerase II structure, the basic mechanism of mRNA synthesis during gene transcription is known. In the future, the initiation and regulation of transcription must be studied with a combination of structural biology, biochemistry, functional genomics, and computational methods. In this article, the efforts of our laboratory to move from an integrated structural biology of gene transcription towards molecular systems biology of gene regulation are reviewed.
Assessment of the Nova StatSensor whole blood point-of-care creatinine analyzer for the measurement of kidney function in screening for chronic kidney disease
Authors: Shephard Mark , Peake Michael , Corso Olivia , Shephard Anne , Mazzachi Beryl , Spaeth Brooke , Barbara Jeffrey , Mathew Timothy 
Published: May 2010

Abstract

Background: Point-of-care testing for creatinine using a fingerprick sample and resultant estimated glomerular filtration rate has potential for screening for chronic kidney disease in community settings. This study assessed the applicability of the Nova StatSensor creatinine analyzer for this purpose.

Methods: Fingerprick samples from 100 patients (63 renal, 37 healthy volunteers; range 46–962 μmol/L) were assayed using two StatSensor analyzers. Lithium heparin venous plasma samples collected simultaneously were assayed in duplicate using the isotope dilution mass spectrometry-aligned Roche Creatinine Plus enzymatic assay on a Hitachi Modular P unit. Method comparison statistics and the ability of the StatSensor to correctly categorise estimated glomerular filtration rate above or below 60 mL/min were calculated pre- and post-alignment with the laboratory method.

Results: StatSensor 1 creatinine results (y) were much lower than the laboratory (y=0.75x+10.2, average bias –47.3, 95% limits of agreement –208 to +113 μmol/L). For estimated glomerular filtration rates above or below 60 mL/min, 100% and 87% of results respectively agreed with the laboratory estimated glomerular filtration rate (79% and 96% post-alignment). StatSensor 2 statistics were similar. The 95% limits of agreement between StatSensor creatinine results were –35 to +34 μmol/L.

Conclusions: Isotope dilution mass spectrometry alignment of the StatSensor will identify most patients with estimated glomerular filtration rate <60 mL/min, but there will be many falsely low estimated glomerular filtration rate results that require laboratory validation. Creatinine results need improvement.
Clin Chem Lab Med 2010;48:1113–9.
Theta-Band Phase Locking of Orbitofrontal Neurons during Reward Expectancy
Authors: van Wingerden Marijn , Vinck Martin , Lankelma Jan , Pennartz Cyriel M. A. 
Published: May 2010

The expectancy of a rewarding outcome following actions and cues is coded by a network of brain structures including the orbitofrontal cortex. Thus far, predicted reward was considered to be coded by time-averaged spike rates of neurons. However, besides firing rate, the precise timing of action potentials in relation to ongoing oscillations in local field potentials is thought to be of importance for effective communication between brain areas.We performed multineuron and field potential recordings in orbitofrontal cortex of rats performing olfactory discrimination learning to study the temporal structure of coding predictive of outcome. After associative learning, field potentials were marked by theta oscillations, both in advance and during delivery of reward. Orbitofrontal neurons, especially those coding information about upcoming reward with their firing rate, phase locked to these oscillations in anticipation of reward. When established associations were reversed, phase locking collapsed in the anticipatory task phase, but returned when reward became predictable again after relearning. Behaviorally, the outcome anticipation phase was marked by licking responses, but the frequency of lick responses was dissociated from the strength of theta-band phase locking. The strength of theta-band phase locking by orbitofrontal neurons robustly follows the dynamics of associative learning as measured by behavior and correlates with the rat's current outcome expectancy. Theta-band phase locking may facilitate communication of outcome-related information between reward-related brain areas and offers a novel mechanism for coding value signals during reinforcement learning.
Deficiency in B7-H1 (PD-L1)/PD-1 Coinhibition Triggers Pancreatic β-Cell Destruction by Insulin-Specific, Murine CD8 T-Cells
Authors: Rajasalu Tarvo , Brosi Helen , Schuster Cornelia , Spyrantis Andreas , Boehm Bernhard Otto , Chen Lieping , Reimann Jörg , Schirmbeck Reinhold 
Published: May 2010

OBJECTIVE
RIP-B7.1 mice expressing the costimulator molecule B7.1 (CD80) on pancreatic β-cells are a well established model to characterize preproinsulin-specific CD8 T-cell responses and experimental autoimmune diabetes (EAD). Different immunization strategies could prime preproinsulin-specific CD8 T-cells in wild-type C57BL/6 (B6) mice, but did not induce diabetes. We tested whether altering the B7-H1 (PD-L1) coinhibition on pancreatic β-cells can reveal a diabetogenic potential of preproinsulin-specific CD8 T-cells.

RESEARCH DESIGN AND METHODS
DNA-based immunization and adoptive T-cell transfers were used to characterize the induction of preproinsulin-specific CD8 T-cell responses and EAD in RIP-B7.1, B6, B7-H1−/−, PD-1−/− or bone marrow chimeric mice.

RESULTS
Preproinsulin-specific CD8 T-cells primed in B6 mice revealed their diabetogenic potential after adoptive transfer into congenic RIP-B7.1 hosts. Furthermore, preproinsulin-specific CD8 T-cells primed in anti-B7-H1 antibody-treated B6 mice, or primed in B7-H1−/− or PD-1−/− mice induced EAD. Immunization of bone marrow chimeric mice showed that deficiency of either B7-H.1 in pancreatic β-cells or of PD-1 in autoreactive CD8 T-cells induced EAD.

CONCLUSIONS
An imbalance between costimulator (B7.1) and coinhibitor (B7-H1) signals on pancreatic β-cells can trigger pancreatic β-cell-destruction by preproinsulin-specific CD8 T-cells. Hence, regulation of the susceptibility of the β-cells for a preproinsulin-specific CD8 T-cell attack can allow or suppress EAD.
T-Cell Protein Tyrosine Phosphatase Attenuates STAT3 and Insulin Signaling in the Liver to Regulate Gluconeogenesis
Authors: Fukushima Atsushi , Loh Kim , Galic Sandra , Fam Barbara , Shields Ben , Wiede Florian , Tremblay Michel L. , Watt Matthew J. , Andrikopoulos Sofianos , Tiganis Tony 
Published: May 2010

OBJECTIVE
Insulin-induced phosphatidylinositol 3-kinase (PI3K)/Akt signaling and interleukin-6 (IL-6)-instigated JAK/STAT3-signaling pathways in the liver inhibit the expression of gluconeogenic genes to decrease hepatic glucose output. The insulin receptor (IR) and JAK1 tyrosine kinases and STAT3 can serve as direct substrates for the T-cell protein tyrosine phosphatase (TCPTP). Homozygous TCPTP-deficiency results in perinatal lethality prohibiting any informative assessment of TCPTP's role in glucose homeostasis. Here we have used Ptpn2+/− mice to investigate TCPTP's function in glucose homeostasis.

RESEARCH DESIGN AND METHODS
We analyzed insulin sensitivity and gluconeogenesis in chow versus high-fat–fed (HFF) Ptpn2+/− and Ptpn2+/+ mice and insulin and IL-6 signaling and gluconeogenic gene expression in Ptpn2+/− and Ptpn2+/+ hepatocytes.

RESULTS
HFF Ptpn2+/− mice exhibited lower fasted blood glucose and decreased hepatic glucose output as determined in hyperinsulinemic euglycemic clamps and by the decreased blood glucose levels in pyruvate tolerance tests. The reduced hepatic glucose output coincided with decreased expression of the gluconeogenic genes G6pc and Pck1 and enhanced hepatic STAT3 phosphorylation and PI3K/Akt signaling in the fasted state. Insulin-induced IR-β–subunit Y1162/Y1163 phosphorylation and PI3K/Akt signaling and IL-6–induced STAT3 phosphorylation were also enhanced in isolated Ptpn2+/− hepatocytes. The increased insulin and IL-6 signaling resulted in enhanced suppression of G6pc and Pck1 mRNA.

CONCLUSIONS
Liver TCPTP antagonises both insulin and STAT3 signaling pathways to regulate gluconeogenic gene expression and hepatic glucose output.
Nitric Oxide Synthesis Is Reduced in Subjects With Type 2 Diabetes and Nephropathy
Authors: Tessari Paolo , Cecchet Diego , Cosma Alessandra , Vettore Monica , Coracina Anna , Millioni Renato , Iori Elisabetta , Puricelli Lucia , Avogaro Angelo , Vedovato Monica 
Published: May 2010

OBJECTIVE
Nitric oxide (NO) is a key metabolic and vascular regulator. Its production is stimulated by insulin. A reduced urinary excretion of NO products (NOx) is frequently found in type 2 diabetes, particularly in association with nephropathy. However, whether the decreased NOx excretion in type 2 diabetes is caused by a defective NOx production from arginine in response to hyperinsulinemia has never been studied.

RESEARCH DESIGN AND METHODS
We measured NOx fractional (FSR) and absolute (ASR) synthesis rates in type 2 diabetic patients with diabetic nephropathy and in control subjects, after l-[15N2-guanidino]-arginine infusion, and use of precursor–product relationships. The study was conducted both before and after an euglycemic hyperinsulinemic (∼1,000–1,200 pmol/l) clamp.

RESULTS
In type 2 diabetes, NOx FSR was reduced both under basal (19.3 ± 3.9% per day, vs. 22.9 ± 4.5% per day in control subjects) and hyperinsulinemic states (24.0 ± 5.6% per day, vs. 37.9 ± 6.4% per day in control subjects; P &lt; 0.03 by ANOVA). Similarly, in type 2 diabetes, NOx ASR was lower than in control subjects under both conditions (basal, 0.32 ± 0.06 vs. 0.89 ± 0.34 mol per day; hyperinsulinemia, 0.35 ± 0.07 vs. 1.15 ± 0.38 mol per day; P = 0.01 by ANOVA). In type 2 diabetes, the ability of insulin to stimulate both the FSR (4.7 ± 3.2% per day) and the ASR (0.03 ± 0.04 mol per day) of NOx was several-fold lower than that in control subjects (15.0 ± 2.9% per day and 0.25 ± 0.07 mol per day, P &lt; 0.03 and P &lt; 0.02, respectively). Also the fraction of arginine flux converted to NOx (basal, 0.22 ± 0.05% vs. 0.65 ± 0.25%; hyperinsulinemia, 0.32 ± 0.06% vs. 1.03 ± 0.33%) was sharply reduced in the patients (P &lt; 0.01 by ANOVA).

CONCLUSIONS
In type 2 diabetic patients with nephropathy, intravascular NOx synthesis from arginine is decreased under both basal and hyperinsulinemic states. This defect extends the concept of insulin resistance to NO metabolism.
The Effect of Oral Antidiabetic Agents on A1C Levels
Authors: Sherifali Diana , Nerenberg Kara , Pullenayegum Eleanor , Cheng Ji Emmy , Gerstein Hertzel C. 
Published: May 2010

OBJECTIVE
Previous reviews of the effect of oral antidiabetic (OAD) agents on A1C levels summarized studies with varying designs and methodological approaches. Using predetermined methodological criteria, we evaluated the effect of OAD agents on A1C levels.

RESEARCH DESIGN AND METHODS
The Excerpta Medica (EMBASE), the Medical Literature Analysis and Retrieval System Online (MEDLINE), and the Cochrane Central Register of Controlled Trials databases were searched from 1980 through May 2008. Reference lists from systematic reviews, meta-analyses, and clinical practice guidelines were also reviewed. Two evaluators independently selected and reviewed eligible studies.

RESULTS
A total of 61 trials reporting 103 comparisons met the selection criteria, which included 26,367 study participants, 15,760 randomized to an intervention drug(s), and 10,607 randomized to placebo. Most OAD agents lowered A1C levels by 0.5−1.25%, whereas thiazolidinediones and sulfonylureas lowered A1C levels by ∼1.0–1.25%. By meta-regression, a 1% higher baseline A1C level predicted a 0.5 (95% CI 0.1–0.9) greater reduction in A1C levels after 6 months of OAD agent therapy. No clear effect of diabetes duration on the change in A1C with therapy was noted.

CONCLUSIONS
The benefit of initiating an OAD agent is most apparent within the first 4 to 6 months, with A1C levels unlikely to fall more than 1.5% on average. Pretreated A1C levels have a modest effect on the fall of A1C levels in response to treatment.
TeleHealth Improves Diabetes Self-Management in an Underserved Community
Authors: Davis Richard M. , Hitch Angela D. , Salaam Muhammad M. , Herman William H. , Zimmer-Galler Ingrid E. , Mayer-Davis Elizabeth J. 
Published: May 2010

OBJECTIVE
To conduct a 1-year randomized clinical trial to evaluate a remote comprehensive diabetes self-management education (DSME) intervention, Diabetes TeleCare, administered by a dietitian and nurse/certified diabetes educator (CDE) in the setting of a federally qualified health center (FQHC) in rural South Carolina.

RESEARCH DESIGN AND METHODS
Participants were recruited from three member health centers of an FQHC and were randomized to either Diabetes TeleCare, a 12-month, 13-session curriculum delivered using telehealth strategies, or usual care.

RESULTS
Mixed linear regression model results for repeated measures showed a significant reduction in glycated hemoglobin (GHb) in the Diabetes TeleCare group from baseline to 6 and 12 months (9.4 ± 0.3, 8.3 ± 0.3, and 8.2 ± 0.4, respectively) compared with usual care (8.8 ± 0.3, 8.6 ± 0.3, and 8.6 ± 0.3, respectively). LDL cholesterol was reduced at 12 months in the Diabetes TeleCare group compared with usual care. Although not part of the original study design, GHb was reduced from baseline to 12 and 24 months in the Diabetes TeleCare group (9.2 ± 0.4, 7.4 ± 0.5, and 7.6 ± 0.5, respectively) compared with usual care (8.7 ± 0.4, 8.1 ± 0.4, and 8.1 ± 0.5, respectively) in a post hoc analysis of a subset of the randomized sample who completed a 24-month follow-up visit.

CONCLUSIONS
Telehealth effectively created access to successfully conduct a 1-year remote DSME by a nurse CDE and dietitian that improved metabolic control and reduced cardiovascular risk in an ethnically diverse and rural population.
A Randomized Controlled Trial Comparing Motivational Interviewing in Education to Structured Diabetes Education in Teens With Type 1 Diabetes
Authors: Wang Yu-Chi , Stewart Sunita M. , Mackenzie Marsha , Nakonezny Paul A. , Edwards Deidre , White Perrin C. 
Published: May 2010

OBJECTIVE
To compare motivational interviewing–based education (MI) and structured diabetes education (SDE) for improving A1C and psychosocial measures in adolescents with type 1 diabetes.

RESEARCH DESIGN AND METHODS
This study was a 9-month randomized controlled trial comparing MI (n = 21) to SDE (n = 23). Interventions were at baseline (T0) and 3 months (T1), with A1C and psychosocial measures obtained at 6 months (T2) and 9 months (T3).

RESULTS
Over the 6 months of follow-up, the SDE group had lower adjusted mean A1C value (least squares mean 10.31, SE 0.32) than the MI group (least squares mean 11.35, SE 0.34) (P = 0.03, d = −0.66). There were no differences on any of the psychosocial measures.

CONCLUSIONS
SDE is effective at improving metabolic control in adolescents with type 1 diabetes. Diabetes educators were proficient in learning MI.
Risk of Diabetes in U.S. Military Service Members in Relation to Combat Deployment and Mental Health
Authors: Boyko Edward J. , Jacobson Isabel G. , Smith Besa , Ryan Margaret A.K. , Hooper Tomoko I. , Amoroso Paul J. , Gackstetter Gary D. , Barrett-Connor Elizabeth , Smith Tyler C. ,   for the Millennium Cohort Study Team
Published: May 2010

OBJECTIVE
Few prospective data exist on the risk of diabetes in individuals serving in the U.S. military. The objectives of this study were to determine whether military deployment, combat exposures, and mental health conditions were related to the risk of newly reported diabetes over 3 years.

RESEARCH DESIGN AND METHODS
Data were from Millennium Cohort Study participants who completed baseline (July 2001–June 2003) and follow-up (June 2004–February 2006) questionnaires (follow-up response rate = 71.4%). After exclusion criteria were applied, adjusted analyses included 44,754 participants (median age 36 years, range 18–68 years). Survey instruments collected demographics, height, weight, lifestyle, military service, clinician-diagnosed diabetes, and other physical and mental health conditions. Deployment was defined by U.S. Department of Defense databases, and combat exposure was assessed by self-report at follow-up. Odds of newly reported diabetes were estimated using logistic regression analysis.

RESULTS
Occurrence of diabetes during follow-up was 3 per 1,000 person-years. Individuals reporting diabetes at follow-up were significantly older, had greater baseline BMI, and were less likely to be Caucasian. After adjustment for age, sex, BMI, education, race/ethnicity, military service characteristics, and mental health conditions, only baseline posttraumatic stress disorder (PTSD) was significantly associated with risk of diabetes (odds ratio 2.07 [95% CI 1.31–3.29]). Deployments since September 2001 were not significantly related to higher diabetes risk, with or without combat exposure.

CONCLUSIONS
In this military cohort, PTSD symptoms at baseline but not other mental health symptoms or military deployment experience were significantly associated with future risk of self-reported diabetes.
β-Cell Function Declines Within the First Year Postpartum in Women With Recent Glucose Intolerance in Pregnancy
Authors: Retnakaran Ravi , Qi Ying , Sermer Mathew , Connelly Philip W. , Hanley Anthony J.G. , Zinman Bernard 
Published: May 2010

OBJECTIVEBoth gestational diabetes mellitus (GDM) and mild glucose intolerance in pregnancy identify women at increased risk of future type 2 diabetes. In this context, we queried whether metabolic changes that occur in the 1st year postpartum vary in relation to gestational glucose tolerance status.RESEARCH DESIGN AND METHODSThree-hundred-and-ninety-two women underwent glucose challenge test (GCT) and oral glucose tolerance test (OGTT) in pregnancy followed by repeat OGTT at both 3 months' postpartum and 12 months' postpartum. The antepartum testing defined four gestational glucose tolerance groups: GDM (n = 107); gestational impaired glucose tolerance (GIGT) (n = 75); abnormal GCT with normal glucose tolerance (NGT) on OGTT (abnormal GCT NGT) (n = 137); and normal GCT with NGT on OGTT (normal GCT NGT) (n = 73).RESULTSThe prevalence of dysglycemia progressively increased across the groups from normal GCT NGT to abnormal GCT NGT to GIGT to GDM at both 3 months' postpartum (2.7% to 10.2% to 18.7% to 34.6%, P &lt; 0.0001) and 12 months' postpartum (2.7% to 11.7% to 17.3% to 32.7%, P &lt; 0.0001). Between 3 and 12 months' postpartum, the groups did not differ with respect to changes in waist circumference, weight, or insulin sensitivity. Importantly, however, they exhibited markedly different changes in β-cell function (Insulin Secretion-Sensitivity Index-2 [ISSI-2]) (P = 0.0036), with ISSI-2 declining in both the GDM and GIGT groups. Furthermore, on multiple linear regression analysis, both GDM (t = −3.06, P = 0.0024) and GIGT (t = −2.18, P = 0.03) emerged as independent negative predictors of the change in ISSI-2 between 3 and 12 months' postpartum.CONCLUSIONSWomen with GDM and GIGT exhibit declining β-cell function in the 1st year postpartum that likely contributes to their future diabetic risk.
An epidemiologic study of anhidrosis in horses in Florida
Authors: Johnson Eric B. , MacKay Robert J. , Hernandez Jorge A. 
Published: May 2010

Abstract
Objective—To estimate prevalence of and identify factors associated with anhidrosis in horses in Florida.
Design—Cross-sectional study and case-control study.
Animals—4,620 horses on 500 farms.
Procedures—A questionnaire was structured and mailed to farm owners or managers to obtain information related to diagnosis of anhidrosis in horses and exposure factors associated with this condition. The frequency of investigated farm- and animal-level factors was compared between farms and horses affected and not affected with anhidrosis, respectively.
Results—The prevalence of anhidrosis was 11% at the farm level and 2% at the animal level. The odds of anhidrosis were 2.13 and 4.40 times as high in farms located in central and southern Florida, respectively, compared with odds for farms in northern Florida. The odds of anhidrosis were 5.26 and 15.40 times as high in show and riding instruction operations, respectively, compared with odds for ranch operations. At the animal level, breed (Thoroughbreds and warmblood horses), foaling place (western or midwestern region of the United States), and family history of anhidrosis were significantly associated with anhidrosis.
Conclusions and Clinical Relevance—This study provides new information on the prevalence of and factors for anhidrosis in horses in Florida. Horses with a family history of anhidrosis should be examined by a veterinarian for diagnosis of this condition before they are exposed to exercise in a hot and humid climate.