bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effects of Estrogen-Responsive Element- and Ligand-Induced Structural Changes on the Recruitment of Cofactors and Transcriptional Responses by ERα and ERβ
Authors: Yi Ping , Driscoll Mark D. , Huang Jing , Bhagat Sumedha , Hilf Russell , Bambara Robert A. , Muyan Mesut 
Published: January 2014

AbstractEstrogen signaling is mediated by ERα and -β. ERs are converted from an inactive form to a transcriptionally active state through conformational changes induced by ligand and estrogen-responsive element (ERE) sequences. We show here that ERα and ERβ bind to an ERE independently from ER ligands. We found that although the binding affinity of ERβ for an ERE is 2-fold lower than that of ERα, both ERs use the same nucleotides for DNA contacts. We show that both EREs and ligands are independent modulators of ER conformation. Specifically, the ERE primarily determines the receptor-DNA affinity, whereas the structure of the ER ligand dictates the affinity of ER for particular cofactors. We found that the ligand-dependent cofactor transcriptional intermediary factor-2, through a distinct surface, also interacts with ERα preferentially and independently of ligand. The extent of interaction, however, is dependent upon the ER-ERE affinity. In transfected cells, ERα is more transcriptionally active than ERβ. The ERE sequence, however, determines the potency of gene induction when either ER subtype binds to an agonist. Antagonists prevent ERs from inducing transcription independently from ERE sequences. Thus, ERE- and ligand-induced structural changes are independent determinants for the recruitment of cofactors and transcriptional responses. The ability of ERα to differentially recruit a cofactor could contribute to ER subtype-specific gene responses.
8-Cl-Adenosine Inhibits Proliferation and Causes Apoptosis in B-Lymphocytes via Protein Kinase A-Dependent and Independent Effects: Implications for Treatment of Carney Complex-Associated Tumors
Authors: Robinson-White Audrey , Bossis Ioannis , Hsiao Hui-Pin , Nesterova Maria , Leitner Wolfgang W. , Stratakis Constantine A. 
Published: January 2014

ABSTRACT

Context
Carney complex, a multiple neoplasia syndrome, characterized primarily by spotty skin pigmentation and a variety of endocrine and other tumors, is caused by mutations in PRKAR1A, the gene that codes for the RIα subunit of protein kinase (PKA). PKA controls cell proliferation in many cell types. The cAMP analogue 8-Cl-adenosine (8-Cl-ADO) is thought to inhibit cancer cell proliferation.

Objective
The objective of the study was to study the antiproliferative effects of 8-Cl-ADO on growth and proliferation in B-lymphocytes of Carney complex patients that have PKA defects and to determine whether 8-CL-ADO could be used as a therapeutic agent in the treatment of Carney complex-associated tumors.

Design
We used a multiparametric approach (i.e. growth and proliferation assays, PKA, and PKA subunit assays, cAMP and [3H] cAMP binding assays, and apoptosis assays) to understand the growth and proliferative effects of 8-Cl-ADO on human B-lymphocytes.

Results
8-Cl-ADO inhibited proliferation, mainly through its intracellular transport and metabolism, which induced apoptosis. PKA activity, cAMP levels, and 3H-cAMP binding were increased or decreased, respectively, by 8-Cl-ADO, whereas PKA subunit levels were differentially affected. 8-Cl-ADO also inhibited proliferation induced by G protein-coupled receptors for isoproterenol and adenosine and proliferation induced by other tyrosine kinase receptors.

Conclusions
8-Cl-ADO in addition to unambiguously inhibiting proliferation and inducing apoptosis in a PKA-independent manner also has PKA-dependent effects that are unmasked by a mutant PRKAR1A. Thus, 8-Cl-ADO could serve as a therapeutic agent in patients with Carney complex-related tumors.
Partial Primary Deficiency of Insulin-Like Growth Factor (IGF)-I Activity Associated with IGF1 Mutation Demonstrates Its Critical Role in Growth and Brain Development
Authors: Netchine Irène , Azzi Salah , Houang Muriel , Seurin Danielle , Perin Laurence , Ricort Jean-Marc , Daubas Claudine , Legay Christine , Mester Jan , Herich Robert , Godeau François , Le Bouc Yves 
Published: January 2014

ABSTRACT

Context
IGF-I is essential for fetal and postnatal development. Only three IGF1 defects leading to dramatic loss of binding to its type 1 receptor, IGF-1R, have been reported.

Patient
We describe a very lean boy who has intrauterine growth restriction and progressive postnatal growth failure associated with normal hearing, microcephaly, and mild intellectual impairment. He had markedly reduced concentrations of IGF-I, with IGFBP-3 and ALS serum levels in the upper normal range or above. IGF-I serum concentrations differed according to the immunoassay used. A higher than average GH dose was required for catch-up growth. Given the mismatch between IGF-I and IGFBP-3 levels, we sequenced his IGF1 gene.

Result
We identified a homozygous missense IGF1 mutation. This causes the replacement of a highly conserved amino acid (arginine 36) by a glutamine (R36Q) in the C domain of the predicted peptide. We showed that the abnormal IGF-I peptide has reduced mitogenic activity and partial loss of binding to its receptor IGF-1R. The patient’s IGF-I level was undetectable in a highly specific monoclonal assay but elevated in a polyclonal assay.

Conclusion
This first report of mild deficiency of IGF-I activity demonstrates that the integrity of IGF-I signaling is important for normal growth and brain development. Molecular defects leading to partial loss of IGF-I activity may not be uncommon in patients born small for gestational age. The characterization of this complex phenotype and identification of such molecular defects have therapeutic implications, particularly now that, in addition to GH, recombinant IGF-I is available for clinical use.
Neonatal Diabetes Caused by Mutations in Sulfonylurea Receptor 1: Interplay between Expression and Mg-Nucleotide Gating Defects of ATP-Sensitive Potassium Channels
Authors: Zhou Qing , Garin Intza , Castaño Luis , Argente Jesús , Muñoz-Calvo Ma. Teresa , Perez de Nanclares Guiomar , Shyng Show-Ling 
Published: January 2014

Abstract
Context: ATP-sensitive potassium (KATP) channels regulate insulin secretion by coupling glucose metabolism to β-cell membrane potential. Gain-of-function mutations in the sulfonylurea receptor 1 (SUR1) or Kir6.2 channel subunit underlie neonatal diabetes.
Objective: The objective of the study was to determine the mechanisms by which two SUR1 mutations, E208K and V324M, associated with transient neonatal diabetes affect KATP channel function.
Design: E208K or V324M mutant SUR1 was coexpressed with Kir6.2 in COS cells, and expression and gating properties of the resulting channels were assessed biochemically and electrophysiologically.
Results: Both E208K and V324M augment channel response to MgADP stimulation without altering sensitivity to ATP4− or sulfonylureas. Surprisingly, whereas E208K causes only a small increase in MgADP response consistent with the mild transient diabetes phenotype, V324M causes a severe activating gating defect. Unlike E208K, V324M also impairs channel expression at the cell surface, which is expected to dampen its functional impact on β-cells. When either mutation was combined with a mutation in the second nucleotide binding domain of SUR1 previously shown to abolish Mg-nucleotide response, the activating effect of E208K and V324M was also abolished. Moreover, combination of E208K and V324M results in channels with Mg-nucleotide sensitivity greater than that seen in individual mutations alone.
Conclusion: The results demonstrate that E208K and V324M, located in distinct domains of SUR1, enhance transduction of Mg-nucleotide stimulation from the SUR1 nucleotide binding folds to Kir6.2. Furthermore, they suggest that diabetes severity is determined by interplay between effects of a mutation on channel expression and channel gating.
Altered Autophagy in Human Adipose Tissues in Obesity
Authors: Kovsan Julia , Blüher Matthias , Tarnovscki Tanya , Klöting Nora , Kirshtein Boris , Madar Liron , Shai Iris , Golan Rachel , Harman-Boehm Ilana , Schön Michael R. , Greenberg Andrew S. , Elazar Zvulun , Bashan Nava , Rudich Assaf 
Published: January 2014

Abstract
Context: Autophagy is a housekeeping mechanism, involved in metabolic regulation and stress response, shown recently to regulate lipid droplets biogenesis/breakdown and adipose tissue phenotype.
Objective: We hypothesized that in human obesity autophagy may be altered in adipose tissue in a fat depot and distribution-dependent manner.
Setting and Patients: Paired omental (Om) and sc adipose tissue samples were used from obese and nonobese (n = 65, cohort 1); lean, sc-obese and intraabdominally obese (n = 196, cohort 2); severely obese persons without diabetes or obesity-associated morbidity, matched for being insulin sensitive or resistant (n = 60, cohort 3).
Results: Protein and mRNA levels of the autophagy genes Atg5, LC3A, and LC3B were increased in Om compared with sc, more pronounced among obese persons, particularly if with intraabdominal fat accumulation. Both adipocytes and stromal-vascular cells contribute to the expression of autophagy genes. The increased number of autophagosomes and elevated autophagic flux assessed in fat explants incubated with lysosomal inhibitors were observed in obesity, particularly in Om. The degree of visceral adiposity and adipocyte hypertrophy accounted for approximately 50% of the variance in Atg5 mRNA levels by multivariate regression analysis, whereas age, sex, measures of insulin sensitivity, inflammation, and adipose tissue stress were excluded from the model. Moreover, in cohort 3, the autophagy marker genes were increased in those who were insulin resistant compared with insulin sensitive, particularly in Om.
Conclusions: Autophagy is up-regulated in adipose tissue of obese persons, especially in Om, correlating with the degree of obesity, visceral fat distribution, and adipocyte hypertrophy. This may precede the occurrence of obesity-associated morbidity.
A Heterozygous Mutation of the Insulin-Like Growth Factor-I Receptor Causes Retention of the Nascent Protein in the Endoplasmic Reticulum and Results in Intrauterine and Postnatal Growth Retardation
Authors: Wallborn Tillmann , Wüller Stefan , Klammt Jürgen , Kruis Tassilo , Kratzsch Jürgen , Schmidt Gabriele , Schlicke Marina , Müller Eva , Schmitz van de Leur Hildegard , Kiess Wieland , Pfäffle Roland 
Published: January 2014

Abstract
Background: Mutations in the IGF-I receptor (IGF1R) gene can be responsible for intrauterine and postnatal growth disorders.
Objective: Here we report on a novel mutation in the IGF1R gene in a female patient. The aim of our study was to analyze the functional impact of this mutation.
Patient: At birth, the girl’s length was 47 cm [−1.82 sd score (SDS)], and her weight was 2250 g (−2.26 SDS). Clinical examination revealed microcephaly and retarded cognitive development. She showed no postnatal catch-up growth but had relatively high IGF-I levels (+1.83 to +2.17 SDS).
Results: Denaturing HPLC screening and direct DNA sequencing disclosed a heterozygous missense mutation resulting in an amino acid exchange from valine to glutamic acid at position 599 (V599E-IGF1R). Using various cell systems, we found that the V599E-IGF1R mutant was not tyrosine phosphorylated and had an impaired downstream signaling in the presence of IGF-I. Flow cytometry and live cell confocal laser scanning microscopy revealed a lack of cell surface expression due to an extensive retention of V599E-IGF1R proteins within the endoplasmic reticulum.
Conclusion: The V599E-IGF1R mutation interferes with the receptor’s trafficking path, thereby abrogating proreceptor processing and plasma membrane localization. Diminished cell surface receptor density solely expressed from the patient’s wild-type allele is supposed to lead to insufficient IGF-I signaling. We hypothesize that this mechanism results in intrauterine and postnatal growth retardation of the affected patient. The reported retention of the nascent IGF1R in the endoplasmic reticulum presents a novel mechanism of IGF-I resistance.
pH-Responsive Wettable Fabrics with Hierarchical Structures
Authors: Zhang Yabin , Guo Zhiguang 
Published: January 2014

Abstract
An acid–base-responsive fabric was fabricated by combining a facile chemical deposition of micro- and nanostructure CuO microspheres with the following assembly of mixed thiols (containing HS(CH2)17CH3 and HS(CH2)10COOH). It was found that the hierarchical CuO fabric modified with mixed thiols containing 0.8 molar ratio of HS(CH2)10COOH shows good pH responsivity, which can switch between high hydrophobicity for an acid and a superhydrophilicity for base.
Iodine fortification may influence the age-related change in thyroid volume: a longitudinal population-based study (DanThyr)
Authors: Krejbjerg Anne , Bjergved Lena , Pedersen Inge Bülow , Carlé Allan , Jørgensen Torben , Perrild Hans , Ovesen Lars , Rasmussen Lone Banke , Knudsen Nils , Laurberg Peter 
Published: January 2014

ObjectiveTo assess the individuals' thyroid volume changes after the mandatory nationwide iodine fortification (IF) program in two Danish areas with different iodine intake at baseline (Copenhagen, mild iodine deficiency (ID) and Aalborg, moderate ID).DesignA longitudinal population-based study (DanThyr).MethodsWe examined 2465 adults before (1997) and after (2008) the Danish IF of salt (2000). Ultrasonography was carried out by the same sonographers using the same equipment, after controlling performances. Participants treated for thyroid disease were excluded from analyses.ResultsOverall, median thyroid volume had increased in Copenhagen (11.8–12.2 ml, P=0.001) and decreased in Aalborg, although not significantly (13.3–13.1 ml, P=0.07) during the 11 years of follow-up.In both regions, there was an age-related trend in individual changes in thyroid volume from baseline to follow-up; thyroid volume increased in women <40 years of age and decreased in women >40 years of age.In a multivariate regression model, higher age at entry was a predictor (P<0.05) for thyroid volume decrease >20% during the follow-up period (women aged 40–45 years: odds ratio (OR) 4.3 (95% CI, 2.2–8.2); women aged 60–65 years: 5.8 (2.9–11.6)) and individuals of higher age were also less likely to have an increase in thyroid volume (women aged 40–45 years: OR 0.2 (0.1–0.3); women aged 60–65: OR 0.3 (0.2–0.4)).ConclusionsAge-dependent differences in thyroid volume and enlargement had leveled out after the Danish iodization program. Thus, the previously observed increase in thyroid volume with age may have been caused by ID.
Composites and Structures for Regenerative Engineering
Authors: Laurencin Cato T. , James Roshan 
Published: January 2014

ABSTRACTRegenerative engineering was conceptualized by bridging the lessons learned in developmental biology and stem cell science with biomaterial constructs and engineering principles to ultimately generate de novo tissue. We seek to incorporate our understanding of natural tissue development to design tissue-inducing biomaterials, structures and composites than can stimulate the regeneration of complex tissues, organs, and organ systems through location-specific topographies and physico-chemical cues incorporated into a continuous phase. This combination of classical top-down tissue engineering approach with bottom-up strategies used in regenerative biology represents a new multidisciplinary paradigm. Advanced surface topographies and material scales are used to control cell fate and the consequent regenerative capacity.Musculoskeletal tissues are critical to the normal functioning of an individual and following damage or degeneration they show extremely limited endogenous regenerative capacity. The increasing demand for biologically compatible donor tissue and organ transplants far outstrips the availability leading to an acute shortage. We have developed several biomimetic structures using various biomaterial platforms to combine optimal mechanical properties, porosity, bioactivity, and functionality to effect repair and regeneration of hard tissues such as bone, and soft tissues such as ligament and tendon. Starting with simple structures, we have developed composite and multi-scale systems that very closely mimic the native tissue architecture and material composition. Ultimately, we aim to modulate the regenerative potential, including proliferation, phenotype maturation, matrix production, and apoptosis through cell-scaffold and host –scaffold interactions developing complex tissues and organ systems.
Bodenschäden durch Freizeitaktivitäten im Wald: Regeneration durch Einzäunen
Authors: Rusterholz Hans-Peter , Baur Bruno 
Published: January 2014

Soil damage from recreational activities in forests: regeneration by fencing
Urban forests are popular recreation areas. Recreational activities, particularly the use of picnic places and playing areas, can cause damages to soil and above-ground vegetation, which in turn negatively affect other forest functions. Forest management plans propose management tools for resolving these conflicts. So far, little is known concerning the restoration success of temporary fencing of heavily impacted forest areas in order to prevent any further recreational use. Here, we report the results of a field experiment designed to examine the effects of fencing and soil scarification upon regeneration of soil and above-ground vegetation in a highly impacted forest in Allschwil, Switzerland. We assessed different soil and vegetation parameters in plots with and without soil scarification in the fenced area in the year before the regeneration experiment was initiated and over the following seven years. In parallel, the same variables were recorded in an undisturbed area and in an area with ongoing recreational use. Our study showed successful regeneration of the formerly degenerated soil and ground vegetation within seven years. In addition, the scarification of the upper soil layer accelerated regeneration of some soil parameters but had no effect on ground vegetation. We conclude that temporary fencing is a useful tool for the restoration of forest soil and vegetation in areas heavily impacted by recreational activities.
Assessment of Positional Variation of Maxillary Permanent First Molar with respect to the Infrazygomatic Crest (Key Ridge) in Skeletal Class I, II and III Cases
Authors: Kamble Ranjit , Hazarey Ananya , Hazarey Pushpa , Singh Jeet 
Published: January 2014

ABSTRACT

Introduction
To assess the positional variations of maxillary first permanent molar in horizontal and vertical plane with respect to infrazygomatic crest (key ridge) in skeletal class I, II and III cases.

Materials and methods
A total of 103 lateral cephalograms comprising of 40 skeletal class I (control group), 35 class II and 28 class III cases were selected and analyzed. Six parameters were chosen to compare the vertical and the horizontal variations of first permanent molars.

Results
The angulation of maxillary first molar with respect to key ridge in class II and III was 2.42° and 6.97° as compared to class I which was 5.35°. The mesiobuccal cusp tip of maxillary first molar from key ridge in class II and III was 2.11 and 5.46 mm respectively as compared to class I (1.62 mm). The mesiobuccal root tip of maxillary first molar from key ridge in class II and III was 2.14 and 2.82 mm as compared to class I (1.27 mm).

Conclusion
The maxillary first molar was not directly under the infrazygomatic crest and was ahead of the key ridge in all the groups. The maxillary first permanent molar was placed more mesially in class II and III cases as compared to the class I cases but, in class III, it was more upright as compared to class I and II.

How to cite this article
Kamble R, Hazarey A, Hazarey P, Singh J. Assessment of Positional Variation of Maxillary Permanent First Molar with respect to the Infrazygomatic Crest (Key Ridge) in Skeletal Class I, II and III Cases. World J Dent 2013;4(4):228-234.
A Prosthetic Alternative Treatment for Severe Anterior Ridge Defect using Fixed Removable Partial Denture Andrew's Bar System
Authors: Jain Ashish R 
Published: January 2014

ABSTRACTIt has been well documented that anterior ridge defects present in a patient are very difficult to treat properly. These defects have been treated with great amount of planning and complexities while using the conventional treatment approaches like removable or fixed prosthesis and options of implant. Though totally implant-supported restorations are very successful, dentists may resort to prescribe implant overdentures because of functional, anatomical economical or esthetic considerations. However, the loading conditions of the partially implant- supported overdenture may affect the long-term predictability of this type of restoration. The concept of the Andrew's bar system can be utilized. In some cases the Andrew's bar system is superior to the implant-supported fixed partial denture and other techniques for implant overdentures. The purpose of this article is to evaluate and describe the Andrew's bar system (a fixed removable partial denture), to treat a class III anterior ridge defect using natural teeth as abutments for its fixed component followed a removable component. The use of Andrew's bar system over implants offered the dentist another option in meeting patient's needs.How to cite this articleJain AR.A Prosthetic Alternative Treatment for Severe Anterior Ridge Defect using Fixed Removable Partial Denture Andrew's Bar System. World J Dent 2013;4(4):282-285.
Association of Polymyalgia Rheumatica With Socioeconomic Status in Primary Care: A Cross‐Sectional Observational Study
Authors: Hayward Richard A. , Rathod Trishna , Muller Sara , Hider Samantha L. , Roddy Edward , Mallen Christian D. 
Published: January 2014

ObjectivePolymyalgia rheumatica (PMR) is an inflammatory musculoskeletal condition predominantly diagnosed and managed in the community. Socioeconomic status (SES) is known to be associated with many inflammatory rheumatologic conditions, but has not been investigated in relation to PMR. This study aimed to investigate the association between PMR and SES at both the area and individual levels.MethodsPatients ages >50 years registered with 8 general practices in North Staffordshire were sent a questionnaire requesting details of their general health, SES, and lifestyle. Individual SES was measured using occupation, educational level, and perceived adequacy of income. Area‐level SES was measured using the Index of Multiple Deprivation, derived from respondents' postcodes. Electronic primary care medical records were searched for Read code diagnoses of PMR 2 years before and after the survey.ResultsOf the 13,831 respondents, 141 had a recorded PMR diagnosis in their electronic medical records, a prevalence of 10 per 1,000 patients. No association between PMR and SES was seen at either the individual or area level.ConclusionNo association was found between PMR and SES at either the area or individual level. Unlike several of the inflammatory arthritides that are more common in the more deprived areas, PMR shows no such association. In part this may be due to PMR affecting an older population. Although socioeconomic factors are important for clinicians and researchers to consider, in patients with PMR, further epidemiologic work is needed to fully characterize this disabling disorder.