bluuebunny/crossref_metadata_2025_split huggingface dataset:
Growth Hormone, Acting in Part through the Insulin-Like Growth Factor Axis, Rescues Developmental, But Not Metabolic, Activity in the Mammary Gland of Mice Expressing a Single Allele of the Prolactin Receptor
Authors: Allan Gordon J. , Tonner Elizabeth , Barber Michael C. , Travers Maureen T. , Shand John H. , Vernon Richard G. , Kelly Paul A. , Binart Nadine , Flint David J. 
Published: October 2002

AbstractThe heterozygous prolactin (PRL) receptor (PRLR+/−) mouse fails to develop a fully functional mammary gland at the end of the first pregnancy and shows markedly impaired lobuloalveolar development and milk secretion in young females. PRL and GH, acting through the IGF system, have interactive effects to enhance epithelial cell survival. Thus, we propose that a reduction in the expression of the PRLR may lead to increased IGFBP-5 expression (proapoptotic) and that GH may rescue mammary development by increasing IGF-I, an important mitogen and survival factor for the mammary epithelium. Mammary IGF-binding protein-5 (IGFBP-5) concentrations and plasmin activity in PRLR+/− mice were increased on d 2 postpartum, indicative of increased cell death and extracellular matrix remodeling. After GH treatment, a restoration of mammary alveolar development and a reduction in the activities of IGFBP-5 and plasmin were observed. Despite the severely impaired mammary development in PRLR+/− mice, both mRNA and protein expression for caseins and acetyl-coenzyme A (acetyl-CoA) carboxylase and acetyl-CoA caboxylase-α mRNA increased at parturition, although not to the extent in wild-type animals. Surprisingly, GH treatment actually led to a further decrease in milk protein and acetyl-CoA carboxylase-αexpression when expressed per cell. This was confirmed by the smaller alveolar size, the relative paucity of milk in the mammary glands of GH-treated animals, and the inability of their pups to gain weight. In a subsequent study IGFBP-5 was administered to wild-type mice and produced a 45% decrease in mammary DNA content, a 30% decrease in parenchymal tissue, and impaired lactation. These results suggest that GH can improve mammary development in PRLR+/− mice, but that it fails to enhance metabolic activity. This may be due to the maintenance by GH/IGF-I of a proliferative, rather than a differentiative, phenotype.
Effects of Chronic Undernutrition on Glucose Uptake and Glucose Transporter Proteins in Rat Heart
Authors: Gavete M. Lucia , Agote Maria , Martin M. Angeles , Alvarez Carmen , Escriva Fernando 
Published: October 2002

Abstract
The high energy demands of myocardium are met through the metabolism of lipids and glucose. Importantly, enhanced glucose utilization rates are crucial adaptations of the cardiac cell to some pathological conditions, such as hypertrophy and ischemia, but the effects of undernutrition on heart glucose metabolism are unknown. Our previous studies have shown that undernutrition increases insulin-induced glucose uptake by skeletal muscle. Consequently, we considered the possibility of a similar adaptation in the heart. With this aim, undernourished rats both in the basal state and after euglycemic hyperinsulinemic clamps were used to determine the following parameters in myocardium: glucose uptake, glucose transporter (GLUT) content, and some key components of the insulin signaling cascade. Heart membranes were prepared by subcellular fractionation in sucrose gradients. Although GLUT-4, GLUT-1, and GLUT-3 proteins and GLUT-4/1 mRNAs were reduced by undernutrition, basal and insulin-stimulated 2-deoxyglucose uptake were significantly enhanced. Phosphoinositol 3-kinase activity remained greater than control values in both conditions. The abundance of p85α and p85β regulatory subunits of phosphoinositol 3-kinase was increased as was phospho-Akt during hyperinsulinemia. These changes seem to improve the insulin stimulus of GLUT-1 translocation, as its content was increased at the surface membrane. Such adaptations associated with undernutrition must be crucial to improvement of cardiac glucose uptake.
Glucagon-Like Peptide-1 Promotes Islet Cell Growth and Inhibits Apoptosis in Zucker Diabetic Rats
Authors: Farilla Loredana , Hui Hongxiang , Bertolotto Cristina , Kang Elizabeth , Bulotta Angela , Di Mario Umberto , Perfetti Riccardo 
Published: October 2002

AbstractA constant remodeling of islet cell mass mediated by proliferative and apoptotic stimuli ensures a dynamic response to a changing demand for insulin. In this study, we investigated the effect of glucagon-like peptide-1 (GLP-1) in Zucker diabetic rats, an animal model in which the onset of diabetes occurs when the proliferative potential and the rate of β-cell apoptosis no longer compensate for the increased demand for insulin. We subjected diabetic rats to a 2-d infusion of GLP-1 and tested their response to an ip glucose tolerance test. GLP-1 produced a significant increase of insulin secretion, which was paralleled by a decrease in plasma glucose levels (P &lt; 0.001 and P &lt; 0.01, respectively). Four days after the removal of the infusion pumps, rats were killed and the pancreas harvested to study the mechanism by which GLP-1 ameliorated glucose tolerance. Ex vivo immunostaining with the marker of cell proliferation, Ki-67, showed that the metabolic changes observed in rats treated with GLP-1 were associated with an increase in cell proliferation of the endocrine and exocrine component of the pancreas. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling staining, a marker of cellular apoptosis, indicated a reduction of apoptotic cells within the islet as well in the exocrine pancreas in GLP-1-treated rats. Double immunostaining for the apoptotic marker caspase-3 and for insulin showed a significant reduction of caspase-3 expression and an increase in insulin content in GLP-1-treated animals. Finally, staining of pancreatic sections with the nuclear dye 4,6-Diaminidino-2-phenyl-dihydrochloride demonstrated a marked reduction of fragmented nuclei in the islet cells of rats treated with GLP-1. Our findings provide evidence that the beneficial effects of GLP-1 in Zucker diabetic rats is mediated by an increase in islet cell proliferation and a decrease of cellular apoptosis.
The Increased Bone Mass in ΔFosB Transgenic Mice Is Independent of Circulating Leptin Levels
Authors: Kveiborg M. , Chiusaroli R. , Sims N. A. , Wu M. , Sabatakos G. , Horne W. C. , Baron R. 
Published: October 2002

AbstractTransgenic mice overexpressing ΔFosB, a naturally occurring splice variant of FosB, develop an osteosclerotic phenotype. The increased bone formation has been shown to be due, at least in part, to autonomous effects of ΔFosB isoforms on cells of the osteoblast lineage. However, abdominal fat and marrow adipocytes are also markedly decreased in ΔFosB mice, leading to low serum leptin levels. Increased bone mass has been linked to the absence of leptin and leptin receptor signaling in ob/ob and db/db mice. Thus, in addition to affecting directly osteoblastogenesis and bone formation, ΔFosB isoforms might increase bone mass indirectly via a decrease in leptin. To test this hypothesis, we restored normal circulating levels of leptin in ΔFosB mice via sc implanted osmotic pumps. Complete histomorphometric analysis demonstrated that trabecular bone volume as well as dynamic parameters of bone formation was unchanged by this treatment in both ΔFosB transgenic mice and control littermates. This demonstration that restoring circulating levels of leptin in ΔFosB transgenic mice failed to rescue the bone phenotype further indicates that the marked increase in bone formation is autonomous to the osteoblast lineage.
3′,5′-Cyclic Adenosine Monophosphate Augments Intracellular Ca2+ Concentration and Gonadotropin-Releasing Hormone (GnRH) Release in Immortalized GnRH Neurons in an Na+-Dependent Manner
Authors: Kaneishi Keisuke , Sakuma Yasuo , Kobayashi Hisae , Kato Masakatsu 
Published: October 2002

AbstractIn GT1-7 cells, cAMP increases the intracellular Ca2+ concentration ([Ca2+]i) through activation of the voltage-gated Ca2+ channels, thereby facilitating GnRH release. To activate these channels, the membrane potential must be depolarized. In the present study we hypothesize that cAMP depolarizes the cells by increasing the membrane Na+ permeability, as in the case of somatotrophs and pancreatic β-cells. To examine this, we analyzed [Ca2+]i and [Na+]i in GT1-7 cells by an intracellular ion-imaging technique along with cAMP assay by RIA.Forskolin, a direct activator of adenylyl cyclase, increased [Ca2+]i and [Na+]i via cAMP formation. The forskolin-induced increase in [Ca2+]i depended on the presence of Ca2+ and Na+ in the extracellular solution. This response was blocked by the voltage-gated Ca2+ channel blocker, nifedipine; the nonselective cation channel blocker, gadolinium (Gd3+); and the cyclic nucleotide-gated channel blocker, l-cis-diltiazem. In contrast, the forskolin-induced increase in [Na+]i depended only on extracellular Na+, not on Ca2+. Gd3+ and l-cis-diltiazem also blocked the increase in [Na+]i. Furthermore, the forskolin-induced increase in GnRH release was blunted in both low Ca2+ and low Na+ media. The results indicate that cAMP increases the membrane Na+ permeability, probably through nonselective cation channels on GT1-7 cells, thereby promoting GnRH release.
Surface and Catalytic Properties of NiO and Co3O4 Solids Doped with Cobalt and Nickel Ions
Authors: El-Shobaky G.A. , Turky A.M. , Ghozza A.M. 
Published: October 2002

The effects of doping NiO and Co3O4 solids with cobalt and nickel species on their surface and catalytic properties were investigated. The amounts of dopant, in the form of the corresponding nitrate, were varied between 0.5–6.0 mol% cobalt ions and 2.0–6.0 mol% nickel ions. Pure and variously doped solids were subjected to thermal treatment at 300–700°C. The techniques employed were XRD, nitrogen adsorption at −196°C, decomposition of H2O2 at 30–50°C and estimation of the amount of surface excess oxygen on the variously prepared solids as determined by the hydrazine method. The results obtained revealed that the pure and variously doped NiO samples precalcined at 300°C consisted of a finely divided NiO phase having an average particle size of ca. 40 Å. Pure and variously doped Co3O4 specimens preheated at 500°C and 700°C were composed of a Co3O4 phase with a much bigger particle size (230 Å and 350 Å, respectively, for the solids precalcined at 500°C and 700°C). Doping of NiO followed by thermal treatment at 300°C and 500°C resulted in a measurable decrease in its BET surface area (19–23%), while doping of Co3O4 with nickel species followed by heating at 500°C and 700°C brought about a significant increase in its specific surface area (56–60%). Doping each of the NiO and Co3O4 solids with cobalt and nickel species greatly increased the amount of surface excess oxygen and effected a considerable increase in their catalytic activities. This increase was, however, much more pronounced in the case of NiO which attained a value of ca. 100-fold. Doping of NiO with cobalt species followed by thermal treatment at 300°C and 500°C decreased the activation energy (DE) of the catalyzed reaction to an extent proportional to the amount of dopant added. On the other hand, doping of Co3O4 with nickel species followed by thermal treatment at 500°C and 700°C did not change the value of DE. These results suggest that doping of Co3O4 with nickel species did not modify the mechanism of the catalyzed reaction but increased the concentration of catalytically active sites without changing their energetic nature.
Adsorption of Polyelectrolytes at the Manganese Oxide(IV)–Polymer Solution Interface: Structure of Adsorbed Layers
Authors: Chibowski S. , Wiśniewska M. , Paszkiewicz M. 
Published: October 2002

The influence of the molecular weight of polyelectrolytes on their adsorption and on the structure of the adsorbed layers at the manganese oxide(IV)–polymer solution interface was determined. Polyacrylic acid (PAA) and polyacrylamide (PAM) were applied as ionic polymers. An explanation was proposed for the observed changes in surface charge and zeta potential of the solid in the presence of these polymers. The thickness of the adsorption layer of PAA and PAM was determined and the free energies of adsorption of these polymers on the MnO2 surface were calculated from the zeta potential measurements.
Childhood Trauma, Emotional Awareness, and Neural Correlates of Long-Term Nicotine Smoking
Authors: Quam Annika , Biernacki Kathryn , Ross Thomas J. , Salmeron Betty Jo , Janes Amy C. 
Published: January 2024

ImportanceTemporal dynamic measures provide insight into the neurobiological properties of nicotine use. It is critical to determine whether brain-based measures are associated with substance use risk factors, such as childhood trauma–related emotion dysregulation.ObjectiveTo assess temporal dynamic differences based on smoking status and examine the associations between childhood trauma, alexithymia, nicotine smoking, and default mode network (DMN) states.Design, Setting, and ParticipantsThis cross-sectional study was conducted in the Baltimore, Maryland, area at the National Institute on Drug Abuse. Participants included individuals aged 18 to 65 years who smoked nicotine long term and matched controls with no co-occurring substance use or psychiatric disorders. Participants were enrolled from August 8, 2013, to August 9, 2022. Analysis was conducted from August 2022 to July 2023.ExposureLong-term nicotine smoking.Main Outcomes and MeasuresThe main outcome was temporal dynamic differences based on smoking status. Coactivation pattern analysis was conducted based on 16-minute resting-state functional magnetic resonance imaging; total time in, persistence of, and frequency of transitions into states were evaluated. The associations between childhood trauma (Childhood Trauma Questionnaire), alexithymia (20-item Toronto Alexithymia Scale), and DMN temporal dynamics were assessed.ResultsThe sample included 204 participants (102 individuals who smoked nicotine and 102 control individuals) with a mean (SD) age of 37.53 (10.64) years (109 [53.4%] male). Compared with controls, individuals who smoked nicotine spent more time in the frontoinsular DMN (FI-DMN) state (mean difference, 25.63 seconds; 95% CI, 8.05-43.20 seconds; η2p = 0.04; P = .004 after Bonferroni correction). In those who smoked nicotine, greater alexithymia was associated with less time spent in the FI-DMN state (r, −0.26; 95% CI, −0.44 to −0.07; P = .007). In a moderated mediation analysis, alexithymia mediated the association between childhood trauma and time spent in the FI-DMN state only in individuals who smoked nicotine (c′ = −0.24; 95% CI, −0.58 to −0.03; P = .02).Conclusions and RelevanceCompared with controls, individuals who smoked nicotine spent more time in the FI-DMN state. Among those who smoked nicotine, childhood trauma–related alexithymia was associated with less time spent in the FI-DMN state, indicating that considering trauma-related factors may reveal alternative neurobiological underpinnings of substance use. These data may aid in reconciling contradictory findings in prior literature regarding the role of FI-DMN regions in substance use.
Mediating Factors in the Association of Maternal Educational Level With Pregnancy Outcomes
Authors: Rogne Tormod , Gill Dipender , Liew Zeyan , Shi Xiaoting , Stensrud Vilde Hatlevoll , Nilsen Tom Ivar Lund , Burgess Stephen 
Published: January 2024

ImportanceLower educational attainment is associated with increased risk of adverse pregnancy outcomes, but it is unclear which pathways mediate this association.ObjectiveTo investigate the association between educational attainment and pregnancy outcomes and the proportion of this association that is mediated through modifiable cardiometabolic risk factors.Design, Setting, and ParticipantsIn this 2-sample mendelian randomization (MR) cohort study, uncorrelated (R2 &amp;lt; 0.01) single-nucleotide variants (formerly single-nucleotide polymorphisms) associated with the exposure (P &amp;lt; 5 × 10−8) and mediators and genetic associations with the pregnancy outcomes from genome-wide association studies were extracted. All participants were of European ancestry and were largely from Finland, Iceland, the United Kingdom, or the US. The inverse variance–weighted method was used in the main analysis, and the weighted median, weighted mode, and MR Egger regression were used in sensitivity analyses. In mediation analyses, the direct effect of educational attainment estimated in multivariable MR was compared with the total effect estimated in the main univariable MR analysis. Data were extracted between December 1, 2022, and April 30, 2023.ExposureGenetically estimated educational attainment. The mediators considered were genetically estimated type 2 diabetes, body mass index, smoking, high-density lipoprotein cholesterol level, and systolic blood pressure.Main Outcomes and MeasuresEctopic pregnancy, hyperemesis gravidarum, gestational diabetes, preeclampsia, preterm birth, and offspring birth weight.ResultsThe analyses included 3 037 499 individuals with data on educational attainment, and those included in studies on pregnancy outcomes ranged from 141 014 for ectopic pregnancy to 270 002 with data on offspring birth weight. Each SD increase in genetically estimated educational attainment (ie, 3.4 years) was associated with an increased birth weight of 42 (95% CI, 28-56) g and an odds ratio ranging from 0.53 (95% CI, 0.46-0.60) for ectopic pregnancy to 0.81 (95% CI, 0.71-0.93) for preeclampsia. The combined proportion of the association that was mediated by the 5 cardiometabolic risk factors ranged from −17% (95% CI, −46% to 26%) for hyperemesis gravidarum to 78% (95% CI, 10%-208%) for preeclampsia. Sensitivity analyses accounting for pleiotropy were consistent with the main analyses.Conclusions and RelevanceIn this MR cohort study, intervening for type 2 diabetes, body mass index, smoking, high-density lipoprotein cholesterol level, and systolic blood pressure may lead to reductions in several adverse pregnancy outcomes associated with lower levels of education. Such public health interventions would serve to reduce health disparities attributable to social inequalities.
National and Provincial-Level Prevalence and Risk Factors of Carotid Atherosclerosis in Chinese Adults
Authors: Fu Jingzhu , Deng Yuhan , Ma Yuan , Man Sailimai , Yang Xiaochen , Yu Canqing , Lv Jun , Wang Bo , Li Liming 
Published: January 2024

ImportanceEpidemiologic studies on carotid atherosclerosis (CAS) based on nationwide ultrasonography measurements can contribute to understanding the future risk of cardiovascular diseases and identifying high-risk populations, thereby proposing more targeted prevention and treatment measures.ObjectivesTo estimate the prevalence of CAS within the general population of China and to investigate its distribution among populations with potential risk factors and variation across diverse geographic regions.Design, Setting, and ParticipantsThis multicenter, population-based cross-sectional study used China’s largest health check-up chain database to study 10 733 975 individuals aged 20 years or older from all 31 provinces in China who underwent check-ups from January 1, 2017, to June 30, 2022.Main Outcomes and MeasuresCarotid atherosclerosis was assessed and graded using ultrasonography as increased carotid intima-media thickness (cIMT), carotid plaque (CP), and carotid stenosis (CS). The overall and stratified prevalences were estimated among the general population and various subpopulations based on demographic characteristics, geographic regions, and cardiovascular disease risk factors. Mixed-effects regression models were used to analyze the risk factors for CAS.ResultsAmong 10 733 975 Chinese participants (mean [SD] age, 47.7 [13.4] years; 5 861 566 [54.6%] male), the estimated prevalences were 26.2% (95% CI, 25.0%-27.4%) for increased cIMT, 21.0% (95% CI, 19.8%-22.2%) for CP, and 0.56% (95% CI, 0.36%-0.76%) for CS. The prevalence of all CAS grades was higher among older adults (eg, increased cIMT: aged ≥80 years, 92.7%; 95% CI, 92.2%-93.3%), male participants (29.6%; 95% CI, 28.4%-30.7%), those residing in northern China (31.0%; 95% CI, 29.1%-32.9%), and those who had comorbid conditions, such as hypertension (50.8%; 95% CI, 49.7%-51.9%), diabetes (59.0%; 95% CI, 57.8%-60.1%), dyslipidemia (32.1%; 95% CI, 30.8%-33.3%), and metabolic syndrome (31.0%; 95% CI, 29.1%-32.9%). Most cardiovascular disease risk factors were independent risk factors for all CAS stages (eg, hypertension: 1.60 [95% CI, 1.60-1.61] for increased cIMT, 1.62 [95% CI, 1.62-1.63] for CP, and 1.48 [95% CI, 1.45-1.51] for CS). Moreover, the magnitude of the association between several cardiovascular disease risk factors and increased cIMT and CP differed between the sexes and geographic regions.Conclusions and RelevanceThese findings suggest that nearly one-quarter of Chinese adults have increased cIMT or CP. The burden of this disease is unevenly distributed across geographic regions and subpopulations and may require different levels of local planning, support, and management. Addressing these disparities is crucial for effectively preventing and managing cardiovascular and cerebrovascular diseases in China.