Founder effect in a Belgian-Dutch fragile X population

For many years, the high prevalence of the fragile X syndrome was thought to be caused by a high mutation frequency. The recent isolation of the FMR1 gene and identification of the most prevalent mutation enable a more precise study of the fragile X mutation. As the vast majority of fragile X patients show amplification of an unstable trinucleotide repeat, DNA studies can now trace back the origin of the fragile X mutation. To date, de novo mutations leading to amplification of the CGG repeat have not yet been detected. Recently, linkage disequilibrium was found in the Australian and US populations between the fragile X mutation and adjacent polymorphic markers, suggesting a founder effect of the fragile X mutation. We present here a molecular study of Belgian and Dutch fragile X families. No de novo mutations could be found in 54 of these families. Moreover, we found significant (P < 0.0001) linkage disequilibrium in 68 unrelated fragile X patients between the fragile X mutation and an adjacent polymorphic microsatellite at DXS548. This suggests that a founder effect of the fragile X mutation also exists in the Belgian and Dutch populations. Both the absence of new mutations and the presence of linkage disequilibrium suggest that a few ancestral mutations are responsible for most of the patients with fragile X syndrome.     

Urban development and sustainability challenges chronicled by a century of construction material flows and stocks in Tiexi,China

Construction materials are considerable forces of global environmental impacts, but their dynamics vis‐à‐vis urban development are poorly documented, in part because their long lifespans require elusive and sometimes nonexistent decade‐long high‐resolution data. This study analyzes the construction material flow and stock trends that shaped and were shaped by the development, decline, and renewal of the Tiexi district of Shenyang, a microcosm of China's urban transformations since the early 20th century. Chronicling building‐by‐building the material flows and stock accumulations involved in the buildup of this area, we shed light on the physical resource context of its socioeconomic history. We find that 42 million tonnes of construction materials were needed to develop the Tiexi district from 1910 to 2018, and 18 million tonnes of material outflows were generated by end‐of‐life building demolition. However, over 55% of inflows and 93% of outflows occurred since 2002 during a complete redevelopment of the district. Only small portions of end‐of‐life materials could have been reused or recycled because of temporal and typological mismatches of supply and demand and technical limitations. Our analysis reveals a dramatic decrease in median building lifetimes to as low as 6 years in the early 21st century. These findings contribute to the discussion of long‐term environmental efficiency and sustainability of societal development through construction and reflect on the challenges of urban renewal processes not only in China but also in other developing and developed countries that lost (or may lose) their traditional economic base and restructure their urban forms. This article met the requirements for a Silver/Silver JIE data openness badge described at http://jie.click/badges .     

Biochemical and biological characterization of neutrophil chemotactic protein, a novel rabbit CXC chemokine from alveolar macrophages

The role of interleukin-8 (IL-8) and related CXC chemokines has been demonstrated in many human diseases. However, more profound studies, e.g., by blocking the effect of these inflammatory mediators, request animal models and hence the identification of all human counterparts for commonly used laboratory animals. In this study, we describe the identification of a novel neutrophil chemotactic protein (NCP) of the rabbit. Intact and NH(2)-terminally truncated NCP forms and IL-8 were isolated from LPS-stimulated rabbit alveolar macrophages and purified to homogeneity by a four-step purification procedure. Determination of the complete primary structure of NCP by mass spectrometry and NH(2)-terminal sequencing of natural protein revealed high structural homology with human epithelial cell-derived neutrophil attractant-78 (ENA-78) and granulocyte chemotactic protein-2 (GCP-2), two related ELR(+)CXC chemokines. Intact NCP(1-76) was found to be 10-fold less potent than truncated NCP(7, 8-76) at inducing neutrophil chemotaxis. NCP(7,8-76) was equally potent as intact rabbit IL-8 at chemoattracting human neutrophils and at inducing calcium fluxes in rabbit neutrophils, 1 ng/mL being the minimal effective concentration. However, like IL-8, NCP failed to induce monocyte or eosinophil migration at 300-fold higher concentrations. IL-8 desensitized the calcium increase induced by NCP and vice versa. Finally, intradermal injection of NCP induced a dose-dependent and significant infiltration of neutrophils in mice skin. It can be concluded that NCP is a novel rabbit CXC chemokine that is, like IL-8, implicated in animal models used to study various human disorders in which neutrophils play an important role.     

The effect of forest type on throughfall deposition and seepage flux: a review

Converting deciduous forests to coniferous plantations and vice versa causes environmental changes, but till now insight into the overall effect is lacking. This review, based on 38 case studies, aims to find out how coniferous and deciduous forests differ in terms of throughfall (+stemflow) deposition and seepage flux to groundwater. From the comparison of coniferous and deciduous stands at comparable sites, it can be inferred that deciduous forests receive less N and S via throughfall (+stemflow) deposition on the forest floor. In regions with relatively low open field deposition of atmospheric N (<10 kg N ha⁻¹ year⁻¹), lower NH₄⁺ mean throughfall (+stemflow) deposition was, however, reported under conifers compared to deciduous forest, while in regions with high atmospheric N pollution (>10 kg N ha⁻¹ year⁻¹), the opposite could be concluded. The higher the open field deposition of NH₄⁺, the bigger the difference between the coniferous and deciduous throughfall (+stemflow) deposition. Furthermore, it can be concluded that canopy exchange of K⁺, Ca²⁺ and Mg²⁺ is on average higher in deciduous stands. The significantly higher stand deposition flux of N and S in coniferous forests is reflected in a higher soil seepage flux of NO₃⁻, SO₄²⁻, K⁺, Ca²⁺, Mg²⁺ and Al(III). Considering a subset of papers for which all necessary data were available, a close relationship between throughfall (+stemflow) deposition and seepage was found for N, irrespective of the forest type, while this was not the case for S. This review shows that the higher input flux of N and S in coniferous forests clearly involves a higher seepage of NO₃⁻ and SO₄²⁻ and accompanying cations K⁺, Ca²⁺, Mg²⁺ and Al(III) into the groundwater, making this forest type more vulnerable to acidification and eutrophication compared to the deciduous forest type.     

Recurrent mutation in the first zinc finger of the orphan nuclear receptor NR2E3 causes autosomal dominant retinitis pigmentosa

"Autosomal dominant retinitis pigmentosa" (adRP) refers to a genetically heterogeneous group of retinal dystrophies, in which 54% of all cases can be attributed to 17 disease loci. Here, we describe the localization and identification of the photoreceptor cell-specific nuclear receptor gene NR2E3 as a novel disease locus and gene for adRP. A heterozygous mutation c.166G-->A (p.Gly56Arg) was identified in the first zinc finger of NR2E3 in a large Belgian family affected with adRP. Overall, this missense mutation was found in 3 families affected with adRP among 87 unrelated families with potentially dominant retinal dystrophies (3.4%), of which 47 were affected with RP (6.4%). Interestingly, affected members of these families display a novel recognizable NR2E3-related clinical subtype of adRP. Other mutations of NR2E3 have previously been shown to cause autosomal recessive enhanced S-cone syndrome, a specific retinal phenotype. We propose a different pathogenetic mechanism for these distinct dominant and recessive phenotypes, which may be attributed to the dual key role of NR2E3 in the regulation of photoreceptor-specific genes during rod development and maintenance.     

Former land use affects the nitrogen and phosphorus concentrations and biomass of forest herbs

The colonization rates of understorey plants into forests growing on former agricultural land differ remarkably among species. Different dispersal and recruitment largely account for the contrasting colonization rates, but different effects of the soil legacies of former agricultural land use on plant performance may also play a role. Seven herbaceous forest species were sampled in paired post-agricultural and ancient forest stands to study whether land-use history has an effect on the aboveground nutrient concentrations (N, P and N:P ratios) and biomass of forest herbs and, if so, whether slow and fast colonizing species respond differently. Results showed that P concentrations were significantly affected by former land use with higher concentrations in the post-agricultural stands. N concentrations were unaffected and N:P ratios were significantly higher in the ancient stands. Nutrient concentrations varied considerably among species, but the variation was unrelated to their colonization capacity. Six out of the seven species had higher biomass in the post-agricultural stands relative to the ancient stands, and the degree to which the species increased biomass was positively related to their colonization capacity, i.e., the fast colonizing species showed the strongest increase. Such differential responses to past land use may contribute to the contrasting colonization capacity of forest plants. Land-use history thus affected both the nutrient concentrations and biomass of forest herbs, and only the biomass response was related to colonization capacity.     

GCP-2/CXCL6 synergizes with other endothelial cell-derived chemokines in neutrophil mobilization and is associated with angiogenesis in gastrointestinal tumors

The precise role of chemokines in neovascularization during inflammation or tumor growth is not yet fully understood. We show here that the chemokines granulocyte chemotactic protein-2 (GCP-2/CXCL6), interleukin-8 (IL-8/CXCL8), and monocyte chemotactic protein-1 (MCP-1/CCL2) are co-induced in microvascular endothelial cells after stimulation with pro-inflammatory stimuli. In contrast with its weak proliferative effect on endothelial cells, GCP-2 synergized with MCP-1 in neutrophil chemotaxis. This synergy may represent a mechanism for tumor development and metastasis by providing efficient leukocyte infiltration in the absence of exogenous immune modulators. To mimic endothelial cell-derived GCP-2 in vivo, GCP-2 was intravenously injected and shown to provoke a dose-dependent systemic response, composed of an immediate granulopenia, followed by a profound granulocytosis. By immunohistochemistry, GCP-2 was further shown to be expressed by endothelial cells from human patients with gastrointestinal (GI) malignancies. GCP-2 staining correlated with leukocyte infiltration into the tumor and with the expression of the matrix metalloproteinase-9 (MMP-9/gelatinase B). Together with previous findings, these data suggest that the production of GCP-2 by endothelial cells within the tumor can contribute to tumor development through neovascularization due to endothelial cell chemotaxis and to tumor cell invasion and metastasis by attracting and activating neutrophils loaded with proteases that promote matrix degradation.