bluuebunny/crossref_metadata_2025_split huggingface dataset:
Poliovirus 3C proteinase inhibition by organotelluranes
Authors: Gouvea Iuri E. , Santos Jorge A.N. , Burlandy Fernanda M. , Tersariol Ivarne L.S. , da Silva Edson E. , Juliano Maria A. , Juliano Luiz , Cunha Rodrigo L.O.R. 
Published: April 2011

Abstract
The 3C proteinase, essential for human poliovirus (PV) replication, has unique characteristics as its three-dimensional structure resembles chymotrypsin, but its catalytic nucleophile is a cysteine SH group rather than the OH group of serine. Here, we describe the use of tellurium compounds as inhibitors of PV3C proteinase. A rapid, stoichiometric and covalent inactivation of PV3C was observed with both a chloro-telluroxetane and a bis-vinylic organotellurane. These compounds also inhibit human cathepsins B, L, S, and K with second order rate constants higher than those obtained for PV3C. Chloro-telluroxetane inhibits replication of PV in human embryonic rhabdomyosarcoma cells in the low micromolar range and below the toxic level for the host cells. Bis-vinylic organotellurane is more effective as antiviral agent but reduces the cell viability by 20% at 10 μm, a concentration almost completely inhibiting virus growth. This is the first description of inhibition of viral 3C proteinase with antiviral property by this class of compounds.
The role of cathepsin E in terminal differentiation of keratinocytes
Authors: Kawakubo Tomoyo , Yasukochi Atsushi , Okamoto Kuniaki , Okamoto Yoshiko , Nakamura Seiji , Yamamoto Kenji 
Published: April 2011

AbstractCathepsin E (CatE) is predominantly expressed in the rapidly regenerating gastric mucosal cells and epidermal keratinocytes, in addition to the immune system cells. However, the role of CatE in these cells remains unclear. Here we report a crucial role of CatE in keratinocyte terminal differentiation. CatE deficiency in mice induces abnormal keratinocyte differentiation in the epidermis and hair follicle, characterized by the significant expansion of corium and the reduction of subcutaneous tissue and hair follicle. In a model of skin papillomas formed in three different genotypes of syngeneic mice, CatE deficiency results in significantly reduced expression and altered localization of the keratinocyte differentiation induced proteins, keratin 1 and loricrin. Involvement of CatE in the regulation of the expression of epidermal differentiation specific proteins was corroborated byin vitrostudies with primary cultures of keratinocytes from the three different genotypes of mice. In wild-type keratinocytes after differentiation inducing stimuli, the CatE expression profile was compatible to those of the terminal differentiation marker genes tested. Overexpression of CatE in mice enhances the keratinocyte terminal differentiation process, whereas CatE deficiency results in delayed differentiation accompanying the reduced expression or the ectopic localization of the differentiation markers. Our findings suggest that in keratinocytes CatE is functionally linked to the expression of terminal differentiation markers, thereby regulating epidermis formation and homeostasis.
In Vivo Conditional Pax4 Overexpression in Mature Islet β-Cells Prevents Stress-Induced Hyperglycemia in Mice
Authors: He Kai Hui Hu , Lorenzo Petra I. , Brun Thierry , Jimenez Moreno Carmen M. , Aeberhard Deborah , Ortega Jorge Vallejo , Cornu Marion , Thorel Fabrizio , Gjinovci Asllan , Thorens Bernard , Herrera Pedro L. , Meda Paolo , Wollheim Claes B. , Gauthier Benoit R. 
Published: April 2011

OBJECTIVE
To establish the role of the transcription factor Pax4 in pancreatic islet expansion and survival in response to physiological stress and its impact on glucose metabolism, we generated transgenic mice conditionally and selectively overexpressing Pax4 or a diabetes-linked mutant variant (Pax4R129W) in β-cells.

RESEARCH DESIGN AND METHODS
Glucose homeostasis and β-cell death and proliferation were assessed in Pax4- or Pax4R129W-overexpressing transgenic animals challenged with or without streptozotocin. Isolated transgenic islets were also exposed to cytokines, and apoptosis was evaluated by DNA fragmentation or cytochrome C release. The expression profiles of proliferation and apoptotic genes and β-cell markers were studied by immunohistochemistry and quantitative RT-PCR.

RESULTS
Pax4 but not Pax4R129W protected animals against streptozotocin-induced hyperglycemia and isolated islets from cytokine-mediated β-cell apoptosis. Cytochrome C release was abrogated in Pax4 islets treated with cytokines. Interleukin-1β transcript levels were suppressed in Pax4 islets, whereas they were increased along with NOS2 in Pax4R129W islets. Bcl-2, Cdk4, and c-myc expression levels were increased in Pax4 islets while MafA, insulin, and GLUT2 transcript levels were suppressed in both animal models. Long-term Pax4 expression promoted proliferation of a Pdx1-positive cell subpopulation while impeding insulin secretion. Suppression of Pax4 rescued this defect with a concomitant increase in pancreatic insulin content.

CONCLUSIONS
Pax4 protects adult islets from stress-induced apoptosis by suppressing selective nuclear factor-κB target genes while increasing Bcl-2 levels. Furthermore, it promotes dedifferentiation and proliferation of β-cells through MafA repression, with a concomitant increase in Cdk4 and c-myc expression.
Liver Enzymes Are Associated With Hepatic Insulin Resistance, Insulin Secretion, and Glucagon Concentration in Healthy Men and Women
Authors: Bonnet Fabrice , Ducluzeau Pierre-Henri , Gastaldelli Amalia , Laville Martine , Anderwald Christian H. , Konrad Thomas , Mari Andrea , Balkau Beverley ,   for the RISC Study Group
Published: April 2011

OBJECTIVE
The pathophysiological mechanisms to explain the association between risk of type 2 diabetes and elevated concentrations of γ-glutamyltransferase (GGT) and alanineaminotransferase (ALT) remain poorly characterized. We explored the association of liver enzymes with peripheral and hepatic insulin resistance, insulin secretion, insulin clearance, and glucagon concentration.

RESEARCH DESIGN AND METHODS
We studied 1,309 nondiabetic individuals from the Relationship between Insulin Sensitivity and Cardiovascular disease (RISC) study; all had a euglycemic-hyperinsulinemic clamp and an oral glucose tolerance test (OGTT) with assessment of insulin secretion and hepatic insulin extraction. The hepatic insulin resistance index was calculated in 393 individuals.

RESULTS
In both men and women, plasma concentrations of GGT and ALT were inversely related with insulin sensitivity (M/I) (all P &lt; 0.01). Likewise, the hepatic insulin resistance index was positively correlated with both GGT (r = 0.37, P &lt; 0.0001, men; r = 0.36, P &lt; 0.0001, women) and ALT (r = 0.25, P = 0.0005, men; r = 0.18, P = 0.01, women). These associations persisted in multivariable models. Increased GGT and ALT were significantly associated with higher insulin secretion rates and with both reduced endogenous clearance of insulin and hepatic insulin extraction during the OGTT (P = 0.0005 in men; P = 0.003 in women). Plasma fasting glucagon levels increased over ALT quartiles (men, quartile 4 vs. quartile 1 11.2 ± 5.1 vs. 9.3 ± 3.8 pmol/L, respectively, P = 0.0002; women, 9.0 ± 4.3 vs. 7.6 ± 3.1, P = 0.001).

CONCLUSIONS
In healthy individuals, increased GGT and ALT were biomarkers of both systemic and hepatic insulin resistance with concomitant increased insulin secretion and decreased hepatic insulin clearance. The novel finding of a positive correlation between ALT and fasting glucagon level concentrations warrants confirmation in type 2 diabetes.
Vitamin D Levels, Microvascular Complications, and Mortality in Type 1 Diabetes
Authors: Joergensen Christel , Hovind Peter , Schmedes Anne , Parving Hans-Henrik , Rossing Peter 
Published: April 2011

OBJECTIVE
To evaluate vitamin D as a predictor of all-cause mortality, progression from normoalbuminuria to micro- or macroalbuminuria, and the development of background or proliferative retinopathy in patients with type 1 diabetes.

RESEARCH DESIGN AND METHODS
A prospective observational follow-up study in which an inception cohort of type 1 diabetic patients was followed from onset of diabetes diagnosed between 1979 and 1984. Plasma vitamin D [25(OH)D3] levels were determined by high performance liquid chromatography/tandem mass spectrometry in 227 patients before the patients developed microalbuminuria. Values equal to or below the 10% percentile (15.5 nmol/L) were considered severe vitamin D deficiency.

RESULTS
Median (range) vitamin D was 44.6 (1.7–161.7) nmol/L. Vitamin D level was not associated with age, sex, urinary albumin excretion rate (UAER), or blood pressure. During follow-up, 44 (18%) patients died. In a Cox proportional hazards model, the hazard ratio for mortality in subjects with severe vitamin D deficiency was 2.7 (1.1–6.7), P = 0.03, after adjustment for UAER, HbA1c, and conventional cardiovascular risk factors (age, sex, blood pressure, cholesterol, smoking). Of the 220 patients, 81 (37%) developed microalbuminuria and 27 (12%) of these progressed to macroalbuminuria. Furthermore, 192 (87%) patients developed background retinopathy, whereas 34 (15%) progressed to proliferative retinopathy. Severe vitamin D deficiency at baseline did not predict the development of these microvascular complications.

CONCLUSIONS
In patients with type 1 diabetes, severe vitamin D deficiency independently predicts all-cause mortality but not development of microvascular complications in the eye and kidney. Whether vitamin D substitution in type 1 diabetic patients can improve the prognosis remains to be investigated.
Diabetic Retinopathy Predicts All-Cause Mortality and Cardiovascular Events in Both Type 1 and 2 Diabetes
Authors: Kramer Caroline K. , Rodrigues Ticiana C. , Canani Luis H. , Gross Jorge L. , Azevedo Mirela J. 
Published: April 2011

OBJECTIVE
The prognostic significance of diabetic retinopathy (DR) for death and cardiovascular (CV) outcomes is debated. We investigated the association of DR with all-cause mortality and CV events in patients with diabetes by a systematic review and meta-analysis.

RESEARCH DESIGN AND METHODS
The electronic databases Medline and Embase were searched for cohort studies that evaluated DR in type 2 or type 1 diabetic patients and reported total mortality and/or fatal and nonfatal CV events, including myocardial infarction, angina pectoris, coronary artery bypass graft, ischemic changes on a conventional 12-lead electrocardiogram, transient ischemic attack, nonfatal stroke, or lower leg amputation. Data extraction was performed by two reviewers independently. Pooled effect estimates were obtained by using random-effects meta-analysis.

RESULTS
The analysis included 20 studies that fulfilled the inclusion criteria, providing data from 19,234 patients. In patients with type 2 diabetes (n = 14,896), the presence of any degree of DR increased the chance for all-cause mortality and/or CV events by 2.34 (95% CI 1.96–2.80) compared with patients without DR. In patients with type 1 diabetes (n = 4,438), the corresponding odds ratio was 4.10 (1.50–11.18). These associations remained after adjusting for traditional CV risk factors. DR was also predictive of all-cause mortality in type 2 diabetes (odds ratio 2.41 [1.87–3.10]) and type 1 diabetes (3.65 [1.05–12.66]).

CONCLUSIONS
The presence of DR was associated with an increased risk of all-cause mortality and CV events in both type 2 and type 1 diabetic patients.
Subnormal, permutable, and embedded subgroups in finite groups
Authors: Beidleman James , Ragland Mathew 
Published: April 2011

Abstract
The purpose of this paper is to study the subgroup embedding properties of S-semipermutability, semipermutability, and seminormality. Here we say H is S-semipermutable (resp. semipermutable) in a group Gif H permutes which each Sylow subgroup (resp. subgroup) of G whose order is relatively prime to that of H. We say H is seminormal in a group G if H is normalized by subgroups of G whose order is relatively prime to that of H. In particular, we establish that a seminormal p-subgroup is subnormal. We also establish that the solvable groups in which S-permutability is a transitive relation are precisely the groups in which the subnormal subgroups are all S-semipermutable. Local characterizations of this result are also established.
Ethephon and Aventrol as tools to enhance spring rape productivity
Authors: Darginavičienė Jūratė , Novickienė Leonida , Gavelienė Virgilija , Jurkonienė Sigita , Kazlauskienė Danguolė 
Published: April 2011

Abstract
Ethephon and Aventrol were used as tools to provoke the processes taking part in the formation of rape seed yield and quality. Investigations on spring rape (Brassica napus L.) cultivars ‘Terra’ and ‘Landmark’ were carried out from 2008–2010. Ethephon (10 mM) and Aventrol (1 l/ha — pinolene 960 g/l) were used on different plant growth stages: BBCH-62–64 and BBCH-72–74, BBCH-80–82, respectively. Impact of ethephon manifested itself as activation of ethylene evocation by siliqua and a slight activation of growth of siliqua dehiscence zone. Siliqua cell plasmalemma and tonoplast H+-ATPases activation under the influence of ethephon occurred but did not lead to the destruction of transmembrane electrochemical potential. Extra seed yield and crude fat yield increased; tendency towards a lowering of the saturated/unsaturated fatty acid ratio was observed. Under the influence of Aventrol the dehiscence zone of siliqua was more closed when compared to the control and the ethephon treated variants, seed loss was significantly lowered and transmembrane cation transport was not damaged. The seed yield increased, and this was due to the accumulation of extra crude fat. Aventrol did not change the fatty acid content in rape seed oil. The positive impacts of ethephon and Aventrol for spring rape seed yield formation and possible mechanisms are discussed.
Genetic differences within natural and planted stands of Quercus petraea
Authors: Dostálek Jiří , Frantík Tomáš , Lukášová Miroslava 
Published: April 2011

Abstract
Five sessile oak [Quercus petraea (Matt.) Liebl.] stands from the Czech Republic were studied to learn about the impact of different types of forest management regimes on the genetic differences among tree populations and on population structures. One population had not been markedly affected by human activity, two populations represented unplanted stands that were extensively managed for a long period of time using the coppice system, and two populations were planted stands. Approximately 100 trees from each stand were mapped and subsequently genotyped using 10 nuclear microsatellite loci. We determined the spatial genetic structure of each population and the genetic differentiation among the populations. We found that: (i) the populations were genetically differentiated, but the differences between the unplanted and planted stands were not markedly significant; (ii) the genetic differentiation among the populations depended on the geographical distribution of the populations; (iii) within unplanted stands, a strong spatial genetic structure was seen; and (iv) within planted stands, no spatial genetic structure was observed. Our findings implies that the analysis of spatial genetic structure of the sessile oak forest stand can help reveal and determine its origin.
Polymorphisms of interleukin-4, -10 and 12B genes and diabetic retinopathy
Authors: Cilenšek Ines , Hercegovac Amela , Starčević Jovana , Vukojević Katarina , Babić Mirna , Živin Aleksandra 
Published: April 2011

Abstract
In diabetic retinopathy (DR) and other angiogenesis-associated diseases, increased levels of cytokines, inflammatory cells, and angiogenic factors are present. We investigated the hypothesis that rs2243250 polymorphism of the interleukin 4 (IL-4) gene or rs1800896 polymorphism of the interleukin 10 (IL-10) gene, and rs3212227 polymorphism of the 3’ untranslated region (3’ UTR) of the interleukin-12 p40 gene (IL12B) may be associated with the development of proliferative diabetic retinopathy (PDR) in Caucasians with type 2 diabetes (DM2). This cross sectional case — control study included 189 patients with PDR and 187 patients with type 2 diabetes without PDR. Polymorphisms rs1800896 of the IL-10 gene, rs2243250 of the IL-4 gene, and rs3212227 of IL12B gene were analyzed by ARMS -PCR and RFLP -PCR methods. Multivariate analysis demonstrated the GG genotype of the rs1800896 polymorphism of the IL-10 gene to be associated with increased risk for PDR (OR=1.99; 95% CI=1.11–3.57; P=0.02), whereas the TT genotype of the rs2243250 polymorphism of the IL-4 gene and the AA genotype of the rs3212227 polymorphism of the IL-12 gene were not independent risk factors for PDR. Our findings suggest that the genetic variations at the IL-10 promoter gene might be a genetic risk factor for PDR in Caucasians with type 2 diabetes.
A New Monitoring Protocol for Clozapine-Induced Myocarditis Based on an Analysis of 75 Cases and 94 Controls
Authors: Ronaldson Kathlyn J. , Fitzgerald Paul B. , Taylor Andrew J. , Topliss Duncan J. , McNeil John J. 
Published: April 2011

Objective: To develop an evidence-based monitoring protocol for clozapine-induced myocarditis. Methods: Potential cases of clozapine-related myocarditis occurring between January 1994 and January 2009 and a comparative group of patients taking clozapine for at least 45 days without cardiac disease were documented from the patients’ medical records. Results: A total of 75 cases and 94 controls were included. Nine cases died. The time to onset was 10–33 days with 83% of cases developing between days 14 and 21 inclusive. At least twice the upper limit of normal troponin was found in 90% of cases, but 5 cases had C-reactive protein more than 100 mg/L and left ventricular impairment by echocardiography without a clinically significant rise in troponin. The proposed monitoring protocol recommends obtaining baseline troponin I/T, C-reactive protein and echocardiography, and monitoring troponin and C-reactive protein on days 7, 14, 21 and 28. Mild elevation in troponin or C-reactive protein, persistent abnormally high heart rate or signs or symptoms consistent with infective illness should be followed by daily troponin and C-reactive protein investigation until features resolve. Cessation of clozapine is advised if troponin is more than twice the upper limit of normal or C-reactive protein is over 100 mg/L. Combining these two parameters has an estimated sensitivity for symptomatic clozapine-induced myocarditis of 100%. The sensitivity for asymptomatic disease is unknown. Conclusion: This protocol recommends active monitoring for 4 weeks, relying predominantly on troponin and C-reactive protein results. It encourages continuation of clozapine in the presence of mild illness, but defines a threshold for cessation.
Wavefront-optimized Surface Ablation With the Allegretto Wave Eye-Q Excimer Laser Platform: 12-month Visual and Refractive Results
Authors: Gambato Catia , Catania Anton Giulio , Vujosevic Stela , Midena Edoardo 
Published: April 2011

Purpose:
To evaluate the wavefront-optimized algorithm of the Allegretto Wave Eye-Q (Wavelight AG) 400-Hz excimer laser platform.

Methods:
Three hundred three eyes of 303 patients treated with advanced surface ablation were evaluated prospectively. Topical mitomycin C (MMC) was used when ablation was ≥80 μm. Efficacy, safety, and predictability at 12 months were quantified with subjective refraction, visual acuity (logMAR), and slit-lamp examination.

Results:
Mean postoperative uncorrected distance visual acuity (UDVA) was 20/20.5 (0.01±0.05 logMAR). Postoperative UDVA was equal or better than preoperative corrected distance visual acuity (CDVA) in 94.7% of eyes. Efficacy index was 1.05. Corrected distance visual acuity was maintained (93.7%) or improved (5.9%) in 99.6% of treated eyes. No patient lost ≥2 lines. Safety index was 1.05. Haze at 12 months was grade ≤0.5 in 98% of treated eyes and grade ≤1 in 100% of treated eyes. Mean postoperative manifest refraction spherical equivalent (MRSE) was −0.03±0.15 diopters (D). Postoperative MRSE was within ±0.50 D in 99% of eyes. Overcorrection was documented in 0.66% and undercorrection in 0.33% of eyes.

CONCLUSIONS:
The wavefront-optimized algorithm of the Allegretto Wave Eye-Q excimer laser platform showed good efficacy, safety, and predictability in advanced surface ablation, with or without MMC intraoperative use.
Irreducible Representations of Inner Quasidiagonal C*-Algebras
Authors: Blackadar Bruce , Kirchberg Eberhard 
Published: April 2011

AbstractIt is shown that a separable C*-algebra is inner quasidiagonal if and only if it has a separating family of quasidiagonal irreducible representations. As a consequence, a separable C*-algebra is a strong NF algebra if and only if it is nuclear and has a separating family of quasidiagonal irreducible representations. We also obtain some permanence properties of the class of inner quasidiagonal C*-algebras.
The Group Aut (μ) is Roelcke Precompact
Authors: Glasner Eli 
Published: April 2011

AbstractFollowing a similar result of Uspenskij on the unitary group of a separable Hilbert space, we show that, with respect to the lower (or Roelcke) uniform structure, the Polish group G = Aut(μ) of automorphisms of an atomless standard Borel probability space (X, μ) is precompact. We identify the corresponding compactification as the space of Markov operators on L2(μ) and deduce that the algebra of right and left uniformly continuous functions, the algebra of weakly almost periodic functions, and the algebra of Hilbert functions on G, i.e., functions on G arising from unitary representations, all coincide. Again following Uspenskij, we also conclude that G is totally minimal.