bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nuclear structure and reaction studies near doubly magic 270Hs
Authors: Türler A. 
Published: July 2011

Abstract
Fast on-line gas chemical separations of Hs (hassium, element 108) in the form of HsO4 were applied to investigate the reactions 26Mg + 248Cm and 36S + 238U. In an experiment at the gas-filled separator DGFRS the reaction 48Ca + 226Ra was studied. In all cases the product of complete nuclear fusion is 274Hs*. For the first time, the new nuclide 270Hs was produced in the 4n evaporation channel and its decay properties investigated. The nuclide 270Hs was predicted by microscopic-macroscopic calculations to be a deformed doubly magic nucleus and its decay properties are therefore of special interest to theory. Also, much more detailed information was gained on the decay of 269Hs and its daughters, which led to a new assignment of decay properties of the daughter nuclides 265Sg and 261Rf. There is evidence fo r isomeric states in 265Sg and 261Rf, while 266Sg is not an alpha-particle emitter as believed previously, but decays by spontaneous fission (SF) with a rather short half-life. Also, interesting features of the used reaction 26Mg + 248Cm led to the discovery of the nucleus 271Hs in the same experiments. An investigation of the influence of the Q-value on the fusion reaction in relation to the location of the fusion barrier showed, that the high binding energy of 48Ca largely compensates for the lower fusion probability compared to more asymmetric reactions, while 36S is not as promising as a projectile.
Onset of effects of testosterone treatment and time span until maximum effects are achieved
Authors: Saad Farid , Aversa Antonio , Isidori Andrea M , Zafalon Livia , Zitzmann Michael , Gooren Louis 
Published: July 2011

ObjectiveTestosterone has a spectrum of effects on the male organism. This review attempts to determine, from published studies, the time-course of the effects induced by testosterone replacement therapy from their first manifestation until maximum effects are attained.DesignLiterature data on testosterone replacement.ResultsEffects on sexual interest appear after 3 weeks plateauing at 6 weeks, with no further increments expected beyond. Changes in erections/ejaculations may require up to 6 months. Effects on quality of life manifest within 3–4 weeks, but maximum benefits take longer. Effects on depressive mood become detectable after 3–6 weeks with a maximum after 18–30 weeks. Effects on erythropoiesis are evident at 3 months, peaking at 9–12 months. Prostate-specific antigen and volume rise, marginally, plateauing at 12 months; further increase should be related to aging rather than therapy. Effects on lipids appear after 4 weeks, maximal after 6–12 months. Insulin sensitivity may improve within few days, but effects on glycemic control become evident only after 3–12 months. Changes in fat mass, lean body mass, and muscle strength occur within 12–16 weeks, stabilize at 6–12 months, but can marginally continue over years. Effects on inflammation occur within 3–12 weeks. Effects on bone are detectable already after 6 months while continuing at least for 3 years.ConclusionThe time-course of the spectrum of effects of testosterone shows considerable variation, probably related to pharmacodynamics of the testosterone preparation. Genomic and non-genomic effects, androgen receptor polymorphism and intracellular steroid metabolism further contribute to such diversity.
Phenotype–genotype correlation and follow-up in adult patients with hypokalaemia of renal origin suggesting Gitelman syndrome
Authors: Balavoine A S , Bataille P , Vanhille P , Azar R , Noël C , Asseman P , Soudan B , Wémeau J L , Vantyghem M C 
Published: July 2011

IntroductionGitelman syndrome (GS) is a tubulopathy caused bySLC12A3gene mutations, which lead to hypokalaemic alkalosis, secondary hyperaldosteronism, hypomagnesaemia and hypocalciuria.AimThe aim of this study was to assess the prevalence ofSLC12A3gene mutations in adult hypokalaemic patients; to compare the phenotype of homozygous, heterozygous and non-mutated patients; and to determine the efficiency of treatment.MethodsClinical, biological and genetic data were recorded in 26 patients.ResultsScreening for theSLC12A3gene detected two mutations in 15 patients (six homozygous and nine compound heterozygous), one mutation in six patients and no mutation in five patients. There was no statistical difference in clinical symptoms at diagnosis between the three groups. Systolic blood pressure tended to be lower in patients with two mutations (P=0.16). Hypertension was unexpectedly detected in four patients. Five patients with two mutated alleles and two with heterozygosity had severe manifestations of GS. Significant differences were observed between the three groups in blood potassium, chloride, magnesium, supine aldosterone, 24 h urine chloride and magnesium levels and in modification of the diet in renal disease. Mean blood potassium levels increased from 2.8±0.3, 3.5±0.5 and 3.2±0.3 before treatment to 3.2±0.5, 3.7±0.6 and 3.7±0.3 mmol/l with treatment in groups with two (P=0.003), one and no mutated alleles respectively.ConclusionIn adult patients referred for renal hypokalaemia, we confirmed the presence of mutations of theSLC12A3gene in 80% of cases. GS was more severe in patients with two mutated alleles than in those with one or no mutated alleles. High blood pressure should not rule out the diagnosis, especially in older patients.
Pregnancy-associated plasma protein A in obese children: relationship to markers and risk factors of atherosclerosis and members of the IGF system
Authors: Woelfle Joachim , Roth Christian L , Wunsch Rainer , Reinehr Thomas 
Published: July 2011

BackgroundPregnancy-associated plasma protein A (PAPPA) is a large placenta-derived glycoprotein, which serves as a protease of several IGF-binding proteins (IGFBPs). In non-pregnant adults, measurable PAPPA levels were detected and have been implicated in the pathophysiology of atherosclerotic plaques. However, data in children is lacking.ObjectiveTo study the relationship between PAPPA, markers of atherosclerosis, and members of the IGF system in pediatric obesity.Patients and designEighty-two obese and 52 nonobese children and 1-year longitudinal follow-up study for obese cohort.InterventionOutpatient 1-year intervention program based on exercise, behavior, and nutrition therapy.Main outcome measuresChanges in PAPPA levels, carotid intima media thickness (IMT), weight, blood pressure, lipids, metabolic markers, and members of IGF system.ResultsBaseline PAPPA (PAPPABL) serum levels did not differ between obese and lean subjects. PAPPABLcorrelated significantly with IGF1, IGFBP1, and serum cholesterol. During the 1-year-program mean IMT decreased from 0.66±0.01 to 0.63±0.01 mm (P<0.05) and PAPPA from 1.83±0.12 to 1.58±0.11 μU/l (P<0.00). In linear regression analysis with IMT after intervention as dependent variable, PAPPA contributed significantly to the observed variance. The longitudinal change of PAPPA correlated significantly with the change of serum triglycerides.ConclusionIn this cohort of obese children, PAPPA serum levels correlated significantly with other cardiovascular risk factors. The lack of a direct correlation between PAPPA and IMT suggests that the described association of atherosclerotic plaques and increased PAPPA levels might reflect an indirect mechanism of PAPPA with cardiovascular risk factors such as serum lipids rather than a direct effect on the vasculature.
Evaluation of and Recommendations for Growth References for Very Low Birth Weight (≤1500 Grams) Infants in the United States
Authors: Sherry Bettylou , Mei Zuguo , Grummer-Strawn Laurence , Dietz William H. 
Published: July 2011

Objective. To determine the best available growth reference for evaluating the growth status of very low birth weight (VLBW; ≤1500 g) infants in the United States.Methods. We evaluated currently available growth references for VLBW infants in studies by Casey (Infant Health and Development Program [IHDP]), Brandt, Gairdner and Pearson, and Babson and Benda. We selected the 1 that best met a priori criteria and compared it with the new Centers for Disease Control and Prevention (CDC) growth charts. We evaluated the performance of both the selected VLBW reference and the CDC growth charts for use with VLBW infants by plotting data from 2 external data sets of VLBW infants (from Child Health and Development Studies [CHDS]) and linked the CDC’s Pregnancy Nutrition Surveillance System/Pediatric Nutrition Surveillance System Data (PNSS/PedNSS) on both references. Age was adjusted for gestational age in all of the VLBW data set comparisons.Results. The IHDP reference met the greatest number of our evaluation criteria. The IHDP charts are the most recent, are based on a relatively large sample of VLBW infants in the United States, and are adjusted for gestational age at birth (using the standard of birth at 40 weeks) to account for prematurity. The IHDP VLBW infants, based on corrected postnatal age, compared with the non-VLBW infants included in the new CDC growth charts showed more rapid growth in length-for-age from birth (40 weeks) to 24 months, were nearly equivalent in weight-for-age at birth (40 weeks), yet demonstrated less rapid growth in weight-for-age from 40 weeks to 24 months. The performance evaluation of the IHDP and CDC growth reference based on the 2 external VLBW data sets (CHDS and PNSS/PedNSS) showed that the IHDP charts more closely matched the external data sets in relative position on the graphs and growth patterns for length-for-age, but the CDC growth charts more closely matched the external data sets in the growth pattern for weight-for-length. In weight-for-age, because of the lack of stability in the pattern, we could not determine which reference the external data growth pattern more closely matched.Conclusions. Our evaluation of growth references for VLBW infants yielded no clear, simple recommendation. The inconsistencies in the discrepancies across anthropometric indices between the 2 external combined VLBW data sets (CHDS and PNSS/PedNSS) and the IHDP reference and the CDC growth charts make it difficult to recommend 1 reference. Therefore, we recommend using either the IHDP reference or the CDC growth charts to evaluate the growth of VLBW infants. The choice of which to use depends on its purpose. The IHDP reference is the best available reference for comparisons of the growth of a VLBW infant with those of other VLBW infants. The CDC growth charts allow comparison of the growth of a VLBW infant with that of non-VLBW infants.
Transcriptome Analysis of Human Diabetic Kidney Disease
Authors: Woroniecka Karolina I. , Park Ae Seo Deok , Mohtat Davoud , Thomas David B. , Pullman James M. , Susztak Katalin 
Published: July 2011

OBJECTIVE
Diabetic kidney disease (DKD) is the single leading cause of kidney failure in the U.S., for which a cure has not yet been found. The aim of our study was to provide an unbiased catalog of gene-expression changes in human diabetic kidney biopsy samples.

RESEARCH DESIGN AND METHODS
Affymetrix expression arrays were used to identify differentially regulated transcripts in 44 microdissected human kidney samples. DKD samples were significant for their racial diversity and decreased glomerular filtration rate (~25–35 mL/min). Stringent statistical analysis, using the Benjamini-Hochberg corrected two-tailed t test, was used to identify differentially expressed transcripts in control and diseased glomeruli and tubuli. Two different web-based algorithms were used to define differentially regulated pathways.

RESULTS
We identified 1,700 differentially expressed probesets in DKD glomeruli and 1,831 in diabetic tubuli, and 330 probesets were commonly differentially expressed in both compartments. Pathway analysis highlighted the regulation of Ras homolog gene family member A, Cdc42, integrin, integrin-linked kinase, and vascular endothelial growth factor signaling in DKD glomeruli. The tubulointerstitial compartment showed strong enrichment for inflammation-related pathways. The canonical complement signaling pathway was determined to be statistically differentially regulated in both DKD glomeruli and tubuli and was associated with increased glomerulosclerosis even in a different set of DKD samples.

CONCLUSIONS
Our studies have cataloged gene-expression regulation and identified multiple novel genes and pathways that may play a role in the pathogenesis of DKD or could serve as biomarkers.
Physical Activity Attenuates the Effect of Low Birth Weight on Insulin Resistance in Adolescents
Authors: Ortega Francisco B. , Ruiz Jonatan R. , Hurtig-Wennlöf Anita , Meirhaeghe Aline , González-Gross Marcela , Moreno Luis A. , Molnar Dénes , Kafatos Anthony , Gottrand Frederic , Widhalm Kurt , Labayen Idoia , Sjöström Michael 
Published: July 2011

OBJECTIVE
To examine whether physical activity influences the association between birth weight and insulin resistance in adolescents.

RESEARCH DESIGN AND METHODS
The study comprised adolescents who participated in two cross-sectional studies: the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) study (n = 520, mean age = 14.6 years) and the Swedish part of the European Youth Heart Study (EYHS) (n = 269, mean age = 15.6 years). Participants had valid data on birth weight (parental recall), BMI, sexual maturation, maternal education, breastfeeding, physical activity (accelerometry, counts/minute), fasting glucose, and insulin. Insulin resistance was assessed by homeostasis model assessment–insulin resistance (HOMA-IR). Maternal education level and breastfeeding duration were reported by the mothers.

RESULTS
There was a significant interaction of physical activity in the association between birth weight and HOMA-IR (logarithmically transformed) in both the HELENA study and the EYHS (P = 0.05 and P = 0.03, respectively), after adjusting for sex, age, sexual maturation, BMI, maternal education level, and breastfeeding duration. Stratified analyses by physical activity levels (below/above median) showed a borderline inverse association between birth weight and HOMA-IR in the low-active group (standardized β = −0.094, P = 0.09, and standardized β = −0.156, P = 0.06, for HELENA and EYHS, respectively), whereas no evidence of association was found in the high-active group (standardized β = −0.031, P = 0.62, and standardized β = 0.053, P = 0.55, for HELENA and EYHS, respectively).

CONCLUSIONS
Higher levels of physical activity may attenuate the adverse effects of low birth weight on insulin sensitivity in adolescents. More observational data, from larger and more powerful studies, are required to test these findings.
Immunosuppressive Effects of Streptozotocin-Induced Diabetes Result in Absolute Lymphopenia and a Relative Increase of T Regulatory Cells
Authors: Muller Yannick D. , Golshayan Déla , Ehirchiou Driss , Wyss Jean Christophe , Giovannoni Laurianne , Meier Raphael , Serre-Beinier Véronique , Puga Yung Gisella , Morel Philippe , Bühler Leo H. , Seebach Jörg D. 
Published: July 2011

OBJECTIVEStreptozotocin (STZ) is the most widely used diabetogenic agent in animal models of islet transplantation. However, the immunomodifying effects of STZ and the ensuing hyperglycemia on lymphocyte subsets, particularly on T regulatory cells (Tregs), remain poorly understood.RESEARCH DESIGN AND METHODSThis study evaluated how STZ-induced diabetes affects adaptive immunity and the consequences thereof on allograft rejection in murine models of islet and skin transplantation. The respective toxicity of STZ and hyperglycemia on lymphocyte subsets was tested in vitro. The effect of hyperglycemia was assessed independently of STZ in vivo by the removal of transplanted syngeneic islets, using an insulin pump, and with rat insulin promoter diphtheria toxin receptor transgenic mice.RESULTSEarly lymphopenia in both blood and spleen was demonstrated after STZ administration. Direct toxicity of STZ on lymphocytes, particularly on CD8+ cells and B cells, was shown in vitro. Hyperglycemia also correlated with blood and spleen lymphopenia in vivo but was not lymphotoxic in vitro. Independently of hyperglycemia, STZ led to a relative increase of Tregs in vivo, with the latter retaining their suppressive capacity in vitro. The higher frequency of Tregs was associated with Treg proliferation in the blood, but not in the spleen, and higher blood levels of transforming growth factor-β. Finally, STZ administration delayed islet and skin allograft rejection compared with naive mice.CONCLUSIONSThese data highlight the direct and indirect immunosuppressive effects of STZ and acute hyperglycemia, respectively. Thus, these results have important implications for the future development of tolerance-based protocols and their translation from the laboratory to the clinic.
Oxidative Phosphorylation Flexibility in the Liver of Mice Resistant to High-Fat Diet–Induced Hepatic Steatosis
Authors: Poussin Carinne , Ibberson Mark , Hall Diana , Ding Jun , Soto Jamie , Abel E. Dale , Thorens Bernard 
Published: July 2011

OBJECTIVE
To identify metabolic pathways that may underlie susceptibility or resistance to high-fat diet–induced hepatic steatosis.

RESEARCH DESIGN AND METHODS
We performed comparative transcriptomic analysis of the livers of A/J and C57Bl/6 mice, which are, respectively, resistant and susceptible to high-fat diet–induced hepatosteatosis and obesity. Mice from both strains were fed a normal chow or a high-fat diet for 2, 10, and 30 days, and transcriptomic data were analyzed by time-dependent gene set enrichment analysis. Biochemical analysis of mitochondrial respiration was performed to confirm the transcriptomic analysis.

RESULTS
Time-dependent gene set enrichment analysis revealed a rapid, transient, and coordinate upregulation of 13 oxidative phosphorylation genes after initiation of high-fat diet feeding in the A/J, but not in the C57Bl/6, mouse livers. Biochemical analysis using liver mitochondria from both strains of mice confirmed a rapid increase by high-fat diet feeding of the respiration rate in A/J but not C57Bl/6 mice. Importantly, ATP production was the same in both types of mitochondria, indicating increased uncoupling of the A/J mitochondria.

CONCLUSIONS
Together with previous data showing increased expression of mitochondrial β-oxidation genes in C57Bl/6 but not A/J mouse livers, our present study suggests that an important aspect of the adaptation of livers to high-fat diet feeding is to increase the activity of the oxidative phosphorylation chain and its uncoupling to dissipate the excess of incoming metabolic energy and to reduce the production of reactive oxygen species. The flexibility in oxidative phosphorylation activity may thus participate in the protection of A/J mouse livers against the initial damages induced by high-fat diet feeding that may lead to hepatosteatosis.
In vitro inhibition of feline leukaemia virus infection by synthetic peptides derived from the transmembrane domain
Authors: Boenzli Eva , Robert-Tissot Céline , Sabatino Giuseppina , Cattori Valentino , Meli Marina Luisa , Gutte Bernd , Rovero Paolo , Flynn Norman , Hofmann-Lehmann Regina , Lutz Hans 
Published: July 2011

Background The feline leukaemia virus (FeLV) is a gamma-retrovirus commonly affecting cats. Infection with this virus often leads to fatal outcomes and, so far, no cure is available for this disease. Synthetic peptides with structures mimicking the transmembrane protein of the viral surface proteins hold the potential to effectively interfere with viral entry by hampering the fusion of viral and host cell membranes and constitute a novel approach for the treatment of infections with retroviruses. We identified and synthetically produced 11 FeLV peptides and evaluated their potential to block FeLV infection in vitro. Methods Cell cultures were exposed to FeLV subgroup A prior to the addition of the peptides. The inhibitory effect of the peptides was assessed by measuring FeLV gag protein in the supernatant of peptide versus mock-treated cell cultures using an ELISA. Results A peptide (EPK364) of 37 amino acids in length, with sequence homology to the HIV fusion inhibitor T-20, significantly suppressed viral replication by 88%, whereas no effects were found for shorter peptides. Two structurally modified variants of EPK364 also inhibited viral replication by up to 58% (EPK397) and 27% (EPK398). Conclusions Our data support the identification of synthetic FeLV peptides that have the potential for a curative short-term therapy of viraemic cats. In addition, these peptides might become an important tool in xenotrans-plantation, where endogenous gammaretroviruses of the donor species might be able to infect the host.
Macrophage Differentiation and Polarization via Phosphatidylinositol 3-Kinase/Akt–ERK Signaling Pathway Conferred by Serum Amyloid P Component
Authors: Zhang Weijuan , Xu Wei , Xiong Sidong 
Published: July 2011

AbstractMacrophage differentiation and polarization is influenced by, and act on, many processes associated with autoimmunity. However, the molecular mechanisms underlying macrophage polarization in systemic lupus erythematosus (SLE) remain largely debated. We previously demonstrated that macrophage M2b polarization conferred by activated lymphocyte-derived (ALD)-DNA immunization could initiate and propagate murine lupus nephritis. Serum amyloid P component (SAP), a conserved acute-phase protein in mice, has been reported to bind to DNA and modulate immune responses. In this study, murine SAP was shown to promote macrophage-mediated ALD-DNA uptake through binding to ALD-DNA (SAP/ALD-DNA). Moreover, macrophage phenotypic switch from a proinflammatory M2b phenotype induced by ALD-DNA alone to an anti-inflammatory M2a phenotype stimulated with SAP/ALD-DNA were found because of PI3K/Akt–ERK signaling activation. Both in vivo SAP supplements and adoptive transfer of ex vivo programmed M2a macrophages induced by SAP/ALD-DNA into SLE mice could efficiently alleviate lupus nephritis. Importantly, increased IL-10 secretion, accompanied by anti-inflammatory effect exerted by M2a macrophages, was found to predominantly impede macrophage M2b polarization. Furthermore, neutralization of IL-10 notably reduced the suppressive effect of M2a macrophages. Our results demonstrate that binding of SAP to ALD-DNA could switch macrophage phenotypic polarization from proinflammatory M2b to anti-inflammatory M2a via PI3K/Akt–ERK signaling activation, thus exerting protective and therapeutic interventions on murine lupus nephritis. These data provide a possible molecular mechanism responsible for modulation of macrophage polarization in the context of lupus nephritis and open a new potential therapeutic avenue for SLE.