bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Calcemic Response to Continuous Parathyroid Hormone (PTH)(1-34) Infusion in End-Stage Kidney Disease Varies According to Bone Turnover: A Potential Role for PTH(7-84)
Authors: Wesseling-Perry Katherine , Harkins G. Chris , Wang He-jing , Elashoff Robert , Gales Barbara , Horwitz Mara J. , Stewart Andrew F. , Jüppner Harald , Salusky Isidro B. 
Published: April 2010

Abstract
Context: Factors contributing to PTH resistance in dialysis patients remain elusive.
Objectives: The study assessed the skeletal and biochemical response to 46 h of PTH(1-34) infusion in dialysis patients.
Design: The study was a prospective, controlled assessment of response to PTH(1-34).
Setting: The study was performed at the University of California, Los Angeles, General Clinical Research Center.
Participants: Nineteen dialysis patients and 17 healthy volunteers were studied.
Intervention: PTH(1-34) was infused at a rate of 8 pmol/kg · h for 46 h. Bone biopsy was performed in all dialysis patients.
Main Outcome Measures: Serum calcium, phosphorus, 1,25-dihydroxyvitamin D, PTH (four separate assays), and FGF-23 were determined at baseline and h 7, 23, 35, and 46 of the infusion.
Results: Serum calcium levels rose in healthy volunteers (9.2 ± 0.1 to 11.9 ± 0.3 mg/dl; P &lt; 0.01) and in dialysis patients with adynamic/normal bone turnover (9.0 ± 0.3 to 10.7 ± 0.7 mg/dl; P &lt; 0.05) but did not change in dialysis patients with high bone turnover. Serum phosphorus levels declined in healthy volunteers (3.9 ± 0.1 to 3.5 ± 0.1 mg/dl; P &lt; 0.05) but increased in all dialysis patients (6.7 ± 0.4 to 8.0 ± 0.3 mg/dl; P &lt; 0.05). Full-length PTH(1-84) declined in all subjects; however, PTH(7-84) fragments declined only in healthy subjects and in dialysis patients with normal/adynamic bone but remained unchanged in dialysis patients with high bone turnover.
Conclusions: The skeleton of dialysis patients with high bone turnover is resistant to the calcemic actions of PTH. PTH(7-84) may contribute to this phenomenon.
Assessment of Serum Apelin Levels in Girls with Anorexia Nervosa
Authors: Ziora Katarzyna , Oświęcimska Joanna , Świętochowska Elżbieta , Ziora Dariusz , Ostrowska Zofia , Stojewska Małgorzata , Klimacka-Nawrot Ewa , Dyduch Antoni , Błońska-Fajfrowska Barbara 
Published: April 2010

AbstractContext: Pilot studies in rats have suggested that apelin (APE) is involved in the control of appetite and food intake. APE is secreted in the organs involved in the control of hunger and satiety: the stomach, hypothalamus, and fat tissue. Anorexia nervosa (AN) is an eating disorder that represents a good biological model of chronic fat tissue atrophy in humans. To date, there are no reports of APE expression in the fat tissue and its circulating concentrations in patients with AN.Objective: Our objective was to assess serum APE concentrations in girls with AN.Design, Participants, and Setting: APE-36 and APE-12 serum concentrations were evaluated in 87 Polish girls with restrictive AN, in 61 healthy (H) controls, 17 girls with no otherwise specified eating disorders (NOS), and 30 girls with simple obesity (OB).Results: Mean serum APE-36 and APE-12 concentrations in patients with AN and NOS were significantly lower than in the H and OB groups. However, no differences between AN, H, and NOS groups were observed when APE concentrations were calculated per body mass index (BMI). In participants with normal BMI, serum APE-36 (r = 0.35) and APE-12 (r = 0.37) concentrations correlated positively with BMI.Conclusions: We conclude that compared with H controls, serum APE-36 and APE-12 concentrations decreased as a result of fat tissue depletion in patients with AN. Conversely, obese adolescents had elevated APE-36 and APE-12 due to excessive fat mass as well as increased APE production in adipose tissue.
A New Missense Mutation in the Leptin Gene Causes Mild Obesity and Hypogonadism without Affecting T Cell Responsiveness
Authors: Fischer-Posovszky Pamela , von Schnurbein Julia , Moepps Barbara , Lahr Georgia , Strauss Gudrun , Barth Thomas F. , Kassubek Jan , Mühleder Hannes , Möller Peter , Debatin Klaus-Michael , Gierschik Peter , Wabitsch Martin 
Published: April 2010

Abstract
Objective: Leptin, a protein product of adipocytes, plays a critical role in the regulation of body weight, immune function, pubertal development, and fertility. So far, only three homozygous mutations in the leptin gene in a total of 13 individuals have been found leading to a phenotype of extreme obesity with marked hyperphagia and impaired immune function.
Design: Serum leptin was measured by ELISA. The leptin gene (OB) was sequenced in patient DNA. The effect of the identified novel mutation was assessed using HEK293 cells.
Results: We describe a 14-yr-old child of nonobese Austrian parents without known consanguinity. She had a body mass index of 31.5 kg/m2 (+2.46 sd score) and undetectable leptin serum levels. Sequencing of the leptin gene revealed a hitherto unknown homozygous transition (TTA to TCA) in exon 3 of the LEP gene resulting in a L72S replacement in the leptin protein. RT-PCR, Western blot, and immunohistochemical analysis indicated that the mutant leptin was expressed in the patient’s adipose tissue but retained within the cell. Using a heterologous cell system, we confirmed this finding and demonstrated that the side chain of Leu72 is crucial for intracellular leptin trafficking. Our patient showed signs of a hypogonadotropic hypogonadism. However, in contrast to the literature, she showed only mild obesity and a normal T cell responsiveness.
Conclusions: These findings shed a new light on the clinical consequences of leptin deficiency. Congenital leptin deficiency should be considered possible in pediatric patients with mild obesity even if parents are lean and unrelated.
Congenital Idiopathic Hypogonadotropic Hypogonadism: Evidence of Defects in the Hypothalamus, Pituitary, and Testes
Authors: Sykiotis Gerasimos P. , Hoang Xuan-Huong , Avbelj Magdalena , Hayes Frances J. , Thambundit Apisadaporn , Dwyer Andrew , Au Margaret , Plummer Lacey , Crowley William F. , Pitteloud Nelly 
Published: April 2010

AbstractContext: Idiopathic hypogonadotropic hypogonadism (IHH) with normal smell (normosmic IHH) or anosmia (Kallmann syndrome) is associated with defects in the production or action of GnRH. Accordingly, most IHH patients respond to physiological pulsatile GnRH replacement by normalizing serum LH, FSH, and testosterone (T) levels and achieving gametogenesis; some patients, however, show atypical responses. Interestingly, several IHH-associated genes are expressed in multiple compartments of the hypothalamic-pituitary-gonadal axis.Objective: The aim of the study was to investigate whether the clinical, biochemical, or genetic characteristics of IHH men with atypical responses to GnRH indicate alternative or additional defects in the hypothalamic-pituitary-gonadal axis.Subjects: We studied 90 IHH men undergoing long-term pulsatile GnRH treatment over 30 yr.Design and Setting: We conducted a retrospective study of response to GnRH at a Clinical Research Center.Interventions: Physiological regimens of pulsatile sc GnRH were administered for at least 12 months. Dose-response studies using iv GnRH pulses assessed the pituitary LH response.Main Outcome Measures: We measured serum T, LH, FSH, and inhibin B levels, sperm in ejaculate, and determined the sequence of IHH-associated genes.Results: Twenty-six percent of subjects displayed atypical responses to GnRH: 1) 10 remained hypogonadotropic and hypogonadal, demonstrating pituitary and testicular defects; 2) eight achieved spermatogenesis and normal T but only with hypergonadotropism, indicating impaired testicular responsiveness to gonadotropins; and 3) five remained azoospermic despite achieving adult testicular volumes and normal hormonal profiles, suggesting primary defects in spermatogenesis. Mutations were identified only in KAL1 across groups.Conclusion: In addition to hypothalamic GnRH deficiency, IHH men can have primary pituitary and/or testicular defects, which are unmasked by GnRH replacement.
Circulating Adiponectin Is Associated with Obesity and Serum Lipids in West Africans
Authors: Meilleur Katherine G. , Doumatey Ayo , Huang Hanxia , Charles Bashira , Chen Guanjie , Zhou Jie , Shriner Daniel , Adeyemo Adebowale , Rotimi Charles 
Published: April 2010

Context: Adiponectin, a hormone secreted by adipose tissue, has both metabolic and antiinflammatory properties. Although multiple studies have described the relationship between adiponectin and obesity in several human populations, no large studies have evaluated this relationship in Africans.
Objective: We investigated the relationship between adiponectin and measures of obesity, serum lipids, and insulin resistance in a large African cohort.
Design: Participants are from the Africa America Diabetes Mellitus (AADM) Study, a case-control study of genetic and other risk factors associated with development of type 2 diabetes in Africans.
Setting: Patients were recruited from five academic medical centers in Nigeria and Ghana (Accra and Kumasi in Ghana and Enugu, Ibadan, and Lagos in Nigeria) over 10 yr.
Main Outcome Measures: Circulating adiponectin levels were measured in 690 nondiabetic controls using an ELISA. The correlation between log-transformed circulating adiponectin levels and age, gender, measures of obesity (body mass index, waist circumference, and percent fat mass), and serum lipid levels was assessed. Linear regression was used to explore the association between adiponectin levels and measures of obesity, lipids, and insulin resistance as measured by homeostasis model assessment.
Results: Significant negative associations were observed between log-adiponectin levels and measures of obesity after adjusting for age and gender. Similarly, log-adiponectin levels were significantly negatively associated with serum triglycerides and insulin resistance but positively associated with high-density lipoprotein-cholesterol and total cholesterol after adjusting for age, gender, and body mass index.
Conclusions: Circulating adiponectin is significantly associated with measures of obesity, serum lipids, and insulin resistance in this study of West African populations.
c-Myc Is Required for the ChREBP-Dependent Activation of Glucose-Responsive Genes
Authors: Zhang Pili , Metukuri Mallikarjurna R. , Bindom Sharell M. , Prochownik Edward V. , O'Doherty Robert M. , Scott Donald K. 
Published: April 2010

AbstractGlucose regulates programs of gene expression that orchestrate changes in cellular phenotype in several metabolically active tissues. Carbohydrate response element-binding protein (ChREBP) and its binding partner, Mlx, mediate glucose-regulated gene expression by binding to carbohydrate response elements on target genes, such as the prototypical glucose-responsive gene, liver-type pyruvate kinase (Pklr). c-Myc is also required for the glucose response of the Pklr gene, although the relationship between c-Myc and ChREBP has not been defined. Here we describe the molecular events of the glucose-mediated activation of Pklr and determine the effects of decreasing the activity or abundance of c-Myc on this process. Time-course chromatin immunoprecipitation revealed a set of transcription factors [hepatocyte nuclear factor (HNF)1α, HNF4α, and RNA polymerase II (Pol II)] constitutively resident on the Pklr promoter, with a relative enrichment of acetylated histones 3 and 4 in the same region of the gene. Glucose did not affect HNF1α binding or the acetylation of histones H3 or H4. By contrast, glucose promoted the recruitment of ChREBP and c-Myc and increased the occupancy of HNF4α and RNA Pol II, which were coincident with the glucose-mediated increase in transcription as determined by a nuclear run-on assay. Depletion of c-Myc activity using a small molecule inhibitor (10058-F4/1RH) abolished the glucose-mediated recruitment of HNF4α, ChREBP, and RNA Pol II, without affecting basal gene expression, histone acetylation, and HNF1α or basal HNF4α occupancy. The activation and recruitment of ChREBP to several glucose-responsive genes were blocked by 1RH, indicating a general necessity for c-Myc in this process.
Mouse Oocytes Enable LH-Induced Maturation of the Cumulus-Oocyte Complex via Promoting EGF Receptor-Dependent Signaling
Authors: Su You-Qiang , Sugiura Koji , Li Qinglei , Wigglesworth Karen , Matzuk Martin M. , Eppig John J. 
Published: April 2010

Abstract
LH triggers the maturation of the cumulus-oocyte complex (COC), which is followed by ovulation. These ovarian follicular responses to LH are mediated by epidermal growth factor (EGF)-like growth factors produced by granulosa cells and require the participation of oocyte-derived paracrine factors. However, it is not clear how oocytes coordinate with the EGF receptor (EGFR) signaling to achieve COC maturation. The aim of the present study was to test the hypothesis that oocytes promote the expression of EGFR by cumulus cells, thus enabling them to respond to the LH-induced EGF-like peptides. Egfr mRNA and protein expression were dramatically reduced in cumulus cells of mutant mice deficient in the production of the oocyte-derived paracrine factors growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15). Moreover, microsurgical removal of oocytes from wild-type COCs dramatically reduced expression of Egfr mRNA and protein, and these levels were restored by either coculture with oocytes or treatment with recombinant GDF9 or GDF9 plus recombinant BMP15. Blocking Sma- and Mad-related protein (SMAD)2/3 phosphorylation in vitro inhibited Egfr expression in wild-type COCs and in GDF9-treated wild-type cumulus cells, and conditional deletion of Smad2 and Smad3 genes in granulosa cells in vivo resulted in the reduction of Egfr mRNA in cumulus cells. These results indicate that oocytes promote expression of Egfr in cumulus cells, and a SMAD2/3-dependent pathway is involved in this process. At least two oocyte-derived growth factors, GDF9 and BMP15, are required for EGFR expression by cumulus cells.
Small mammal survey in the upper Seli River valley, Sierra Leone
Authors: Decher Jan , Norris Ryan W. , Fahr Jakob 
Published: April 2010

Abstract
In 2006, an inventory of small mammals was conducted on the upper Seli River in central Sierra Leone on the southwestern fringe of the Loma-Man portion of the Guinea Highlands as part of the baseline surveys conducted for the Bumbuna Hydroelectric Project (BHP). We recorded a total of 35 mammal species, including three shrews (Soricomorpha), 19 bats (Chiroptera), 11 rodents (Rodentia), one primate, and one carnivore. New or first well-documented species for Sierra Leone are the shrew Crocidura nigeriae, the bats Myonycteris torquata, Rhinolophus denti knorri, and the rare horseshoe bat Rhinolophus ziama endemic to Upper Guinea. Also reported are two bat specimens apparently representing an undescribed species of Neoromicia related to N. nana. We support the creation of a protected area as an offset for areas lost to the inundation of the BHP reservoir.
A New Numerical Analysis for Edge Defects in Rectangular Sheet
Authors: Yan Xiangqiao , Liu Baoliang , Hu Zhaohui 
Published: April 2010

Abstract
This note deals with the rectangular tensile sheet with the single edge defect (crack, half-circular-hole crack and half-square-hole crack) by using the hybrid displacement discontinuity method (a boundary element method) proposed recently by Yan. Detailed solutions of the SIFs of the three plane elastic crack problems are given, which can reveal clearly the effect of geometric parameters of the cracked bodies on the SIFs. By comparing the calculated SIFs of the single edge half-circular-hole crack and the single edge half-square-hole crack with those of the single edge crack, in addition, a shielding effect of the half-circular-hole and the half-square-hole on the SIFs of the single edge crack is discussed. It is illustrated that the boundary element method is simple yet accurate for calculating the SIFs of complex crack problems in finite plate.
The Effect of Recent Admixture on Inference of Ancient Human Population History
Authors: Lohmueller Kirk E , Bustamante Carlos D , Clark Andrew G 
Published: April 2010

AbstractDespite the widespread study of genetic variation in admixed human populations, such as African-Americans, there has not been an evaluation of the effects of recent admixture on patterns of polymorphism or inferences about population demography. These issues are particularly relevant because estimates of the timing and magnitude of population growth in Africa have differed among previous studies, some of which examined African-American individuals. Here we use simulations and single-nucleotide polymorphism (SNP) data collected through direct resequencing and genotyping to investigate these issues. We find that when estimating the current population size and magnitude of recent growth in an ancestral population using the site frequency spectrum (SFS), it is possible to obtain reasonably accurate estimates of the parameters when using samples drawn from the admixed population under certain conditions. We also show that methods for demographic inference that use haplotype patterns are more sensitive to recent admixture than are methods based on the SFS. The analysis of human genetic variation data from the Yoruba people of Ibadan, Nigeria and African-Americans supports the predictions from the simulations. Our results have important implications for the evaluation of previous population genetic studies that have considered African-American individuals as a proxy for individuals from West Africa as well as for future population genetic studies of additional admixed populations.
Distribution of Fitness Effects Caused by Single-Nucleotide Substitutions in Bacteriophage f1
Authors: Peris Joan B , Davis Paulina , Cuevas José M , Nebot Miguel R , Sanjuán Rafael 
Published: April 2010

AbstractEmpirical knowledge of the fitness effects of mutations is important for understanding many evolutionary processes, yet this knowledge is often hampered by several sources of measurement error and bias. Most of these problems can be solved using site-directed mutagenesis to engineer single mutations, an approach particularly suited for viruses due to their small genomes. Here, we used this technique to measure the fitness effect of 100 single-nucleotide substitutions in the bacteriophage f1, a filamentous single-strand DNA virus. We found that approximately one-fifth of all mutations are lethal. Viable ones reduced fitness by 11% on average and were accurately described by a log-normal distribution. More than 90% of synonymous substitutions were selectively neutral, while those affecting intergenic regions reduced fitness by 14% on average. Mutations leading to amino acid substitutions had an overall mean deleterious effect of 37%, which increased to 45% for those changing the amino acid polarity. Interestingly, mutations affecting early steps of the infection cycle tended to be more deleterious than those affecting late steps. Finally, we observed at least two beneficial mutations. Our results confirm that high mutational sensitivity is a general property of viruses with small genomes, including RNA and single-strand DNA viruses infecting animals, plants, and bacteria.
The Evolutionary Dynamics of Operon Distributions in Eukaryote Genomes
Authors: Cutter Asher D , Agrawal Aneil F 
Published: April 2010

Abstract
Genes in nematode and ascidian genomes frequently occur in operons—multiple genes sharing a common promoter to generate a polycistronic primary transcript—and such genes comprise 15–20% of the coding genome for Caenorhabditis elegans and Ciona intestinalis. Recent work in nematodes has demonstrated that the identity of genes within operons is highly conserved among species and that the unifying feature of genes within operons is that they are expressed in germline tissue. However, it is generally unknown what processes are responsible for generating the distribution of operon sizes across the genome, which are composed of up to eight genes per operon. Here we investigate several models for operon evolution to better understand their abundance, distribution of sizes, and evolutionary dynamics over time. We find that birth–death models of operon evolution reasonably describe the relative abundance of operons of different sizes in the C. elegans and Ciona genomes and generate predictions about the number of monocistronic, nonoperon genes that likely participate in the birth–death process. This theory, and applications to C. elegans and Ciona, motivates several new and testable hypotheses about eukaryote operon evolution.
A Two-Stage Approximation for Analysis of Mixture Genetic Models in Large Pedigrees
Authors: Habier D , Totir L R , Fernando R L 
Published: April 2010

Abstract
Information from cosegregation of marker and QTL alleles, in addition to linkage disequilibrium (LD), can improve genomic selection. Variance components linear models have been proposed for this purpose, but accommodating dominance and epistasis is not straightforward with them. A full-Bayesian analysis of a mixture genetic model is favorable in this respect, but is computationally infeasible for whole-genome analyses. Thus, we propose an approximate two-step approach that neglects information from trait phenotypes in inferring ordered genotypes and segregation indicators of markers. Quantitative trait loci (QTL) fine-mapping scenarios, using high-density markers and pedigrees of five generations without genotyped females, were simulated to test this strategy against an exact full-Bayesian approach. The latter performed better in estimating QTL genotypes, but precision of QTL location and accuracy of genomic breeding values (GEBVs) did not differ for the two methods at realistically low LD. If, however, LD was higher, the exact approach resulted in a slightly higher accuracy of GEBVs. In conclusion, the two-step approach makes mixture genetic models computationally feasible for high-density markers and large pedigrees. Furthermore, markers need to be sampled only once and results can be used for the analysis of all traits. Further research is needed to evaluate the two-step approach for complex pedigrees and to analyze alternative strategies for modeling LD between QTL and markers.
Genes Required for Cellular UNC-6/Netrin Localization in Caenorhabditis elegans
Authors: Asakura Taro , Waga Naoko , Ogura Ken-ichi , Goshima Yoshio 
Published: April 2010

Abstract
UNC-6/Netrin is an evolutionarily conserved, secretory axon guidance molecule. In Caenorhabditis elegans, UNC-6 provides positional information to the axons of developing neurons, probably by establishing a concentration gradient from the ventral to the dorsal side of the animal. Although the proper localization of UNC-6 is important for accurate neuronal network formation, little is known about how its localization is regulated. Here, to examine the localization mechanism for UNC-6, we generated C. elegans expressing UNC-6 tagged with the fluorescent protein Venus and identified 13 genes, which are involved in the cellular localization of Venus∷UNC-6. For example, in unc-51, unc-14, and unc-104 mutants, the neurons showed an abnormal accumulation of Venus∷UNC-6 in the cell body and less than normal level of Venus∷UNC-6 in the axon. An aberrant accumulation of Venus∷UNC-6 in muscle cells was seen in unc-18 and unc-68 mutants. unc-51, unc-14, and unc-104 mutants also showed defects in the guidance of dorso-ventral axons, suggesting that the abnormal localization of UNC-6 disturbed the positional information it provides. We propose that these genes regulate the process of UNC-6 secretion: expression, maturation, sorting, transport, or exocytosis. Our findings provide novel insight into the localization mechanism of the axon guidance molecule UNC-6/Netrin.