A genome-wide association study of northwestern Europeans involves the C-type natriuretic peptide signaling pathway in the etiology of human height variation

Northwestern Europeans are among the tallest of human populations. The increase in body height in these people appears to have reached a plateau, suggesting the ubiquitous presence of an optimal environment in which genetic factors may have exerted a particularly strong influence on human growth. Therefore, we performed a genome-wide association study (GWAS) of body height using 2.2 million markers in 10 074 individuals from three Dutch and one German population-based cohorts. Upon genotyping, the 12 most significantly height-associated single nucleotide polymorphisms (SNPs) from this GWAS in 6912 additional individuals of Dutch and Swedish origin, a genetic variant (rs6717918) on chromosome 2q37.1 was found to be associated with height at a genome-wide significance level (Pcombined= 3.4 × 10-9). Notably, a second SNP (rs6718438) located ∼450 bp away and in strong LD (r2= 0.77) with rs6717918 was previously found to be suggestive of a height association in 29 820 individuals of mainly northwestern European ancestry, and the over-expression of a nearby natriuretic peptide precursor type C (NPPC) gene, has been associated with overgrowth and skeletal anomalies. We also found a SNP (rs10472828) located on 5p14 near the natriuretic peptide receptor 3 (NPR3) gene, encoding a receptor of the NPPC ligand, to be associated with body height (Pcombined= 2.1 × 10-7). Taken together, these results suggest that variation in the C-type natriuretic peptide signaling pathway, involving the NPPC and NPR3 genes, plays an important role in determining human body height

C/EBPβ Promotes Transition from Proliferation to Hypertrophic Differentiation of Chondrocytes through Transactivation of p57Kip2

BACKGROUND: Although transition from proliferation to hypertrophic differentiation of chondrocytes is a crucial step for endochondral ossification in physiological skeletal growth and pathological disorders like osteoarthritis, the underlying mechanism remains an enigma. This study investigated the role of the transcription factor CCAAT/enhancer-binding protein beta (C/EBPbeta) in chondrocytes during endochondral ossification. METHODOLOGY/PRINCIPAL FINDINGS: Mouse embryos with homozygous deficiency in C/EBPbeta (C/EBPbeta-/-) exhibited dwarfism with elongated proliferative zone and delayed chondrocyte hypertrophy in the growth plate cartilage. In the cultures of primary C/EBPbeta-/- chondrocytes, cell proliferation was enhanced while hypertrophic differentiation was suppressed. Contrarily, retroviral overexpression of C/EBPbeta in chondrocytes suppressed the proliferation and enhanced the hypertrophy, suggesting the cell cycle arrest by C/EBPbeta. In fact, a DNA cell cycle histogram revealed that the C/EBPbeta overexpression caused accumulation of cells in the G0/G1 fraction. Among cell cycle factors, microarray and real-time RT-PCR analyses have identified the cyclin-dependent kinase inhibitor p57(Kip2) as the transcriptional target of C/EBPbeta. p57(Kip2) was co-localized with C/EBPbeta in late proliferative and pre-hypertrophic chondrocytes of the mouse growth plate, which was decreased by the C/EBPbeta deficiency. Luciferase-reporter and electrophoretic mobility shift assays identified the core responsive element of C/EBPbeta in the p57(Kip2) promoter between -150 and -130 bp region containing a putative C/EBP motif. The knockdown of p57(Kip2) by the siRNA inhibited the C/EBPbeta-induced chondrocyte hypertrophy. Finally, when we created the experimental osteoarthritis model by inducing instability in the knee joints of adult mice of wild-type and C/EBPbeta+/- littermates, the C/EBPbeta insufficiency caused resistance to joint cartilage destruction. CONCLUSIONS/SIGNIFICANCE: C/EBPbeta transactivates p57(Kip2) to promote transition from proliferation to hypertrophic differentiation of chondrocytes during endochondral ossification, suggesting that the C/EBPbeta-p57(Kip2) signal would be a therapeutic target of skeletal disorders like growth retardation and osteoarthritis

Pseudoacromegaly

© 2018 Elsevier Inc. Individuals with acromegaloid physical appearance or tall stature may be referred to endocrinologists to exclude growth hormone (GH) excess. While some of these subjects could be healthy individuals with normal variants of growth or physical traits, others will have acromegaly or pituitary gigantism, which are, in general, straightforward diagnoses upon assessment of the GH/IGF-1 axis. However, some patients with physical features resembling acromegaly – usually affecting the face and extremities –, or gigantism – accelerated growth/tall stature – will have no abnormalities in the GH axis. This scenario is termed pseudoacromegaly, and its correct diagnosis can be challenging due to the rarity and variability of these conditions, as well as due to significant overlap in their characteristics. In this review we aim to provide a comprehensive overview of pseudoacromegaly conditions, highlighting their similarities and differences with acromegaly and pituitary gigantism, to aid physicians with the diagnosis of patients with pseudoacromegaly.PM is supported by a clinical fellowship by Barts and the London Charity. Our studies on pituitary adenomas and related conditions received support from the Medical Research Council, Rosetrees Trust and the Wellcome Trust

Isolation, cultivation and identification of Borrelia burgdorferi genospecies from Ixodes ricinus from the city of Brno, Czech Republic

A total of 305 ticks (21 larvae, 243 nymphs, 19 females and 22 males) were collected by fl agging of vegetation in suburban woods of Pisárky Park (city of Brno) from July to October 2002. The midgut of each tick was dissected out and transferred individually into BSK-H medium. After cultivation, all specimens were examined by dark-fi eld microscopy (DFM) for the presence of borreliae. Out of 305 tick samples, 45 were (14.8%) DFM positive. The following polymerase chain reaction (PCR) then revealed 37 (12.1%) samples positive for the presence of Borrelia burgdorferi sensu lato DNA. All 37 samples were further analysed by restriction fragment length polymorphism (RFLP) method. PCR-RFLP analysis revealed 14 strains of B. afzelii (37.8%), 15 strains of B. garinii (40.5%) and 2 strains of B. burgdorferi sensu stricto (5.4%). Four samples (10.8%) showed a mixed population of these genospecies. Two samples produced atypical RFLP pattern which were detected by sequence analysis as B. valaisiana (5.4%). Isolation attempts resulted in 21 spirochaetal strains (including two stains of B. valaisiana). The results show the diversity of B. burgdorferi s.l. in tick population and refer the risk of infection by pathogenic borreliae in Brno

Vyuziti novych metod pri stanoveni Listerii v potravinach.

Available from STL, Prague, CZ / NTK - National Technical LibrarySIGLECZCzech Republi

Persistence of Arcobacter butzleri CCUG 30484 on plastic, stainless steel and glass surfaces Persistência de Arcobacter butzleri CCUG 30404 em superfícies de plástico, aço inox e vidro

The persistence of A. butzleri CCUG 30484 on various surfaces under 32% and 64% relative humidity suspended in physiological saline or nutrient broth to simulate relatively clean or soiled conditions was studied using various isolation techniques. Our study revealed that A. butzleri CCUG 30484 cells were able to survive for a considerable period of time, even after the droplet of suspending medium has been visibly dried. An extended survival on polypropylene coupons at both humidity levels was observed, particularly at soiled conditions.<br>Estudou-se a persistência de Arcobacter butzleri CCUG 30404 em várias superfícies de contato com alimentos a 32% e 64% de umidade relativa, suspenso em salina fisiológica e caldo nutriente para simular condições limpas e sujas. Nosso estudo indicou que A. butzleri CCUG 30404 foi capaz de sobreviver por longo tempo, mesmo após a secagem da gota. Observou-se que a sobrevivência for mais prolongada nos cupons de polipropileno, especialmente em condições sujas

The antiapoptotic protein Api5 and its partner, high molecular weight FGF2, are up-regulated in B cell chronic lymphoid leukemia.

International audienc