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 .     

Reduced BMP Signaling Results in Hindlimb Fusion with Lethal Pelvic/Urogenital Organ Aplasia: A New Mouse Model of Sirenomelia

Sirenomelia, also known as mermaid syndrome, is a developmental malformation of the caudal body characterized by leg fusion and associated anomalies of pelvic/urogenital organs including bladder, kidney, rectum and external genitalia. Most affected infants are stillborn, and the few born alive rarely survive beyond the neonatal period. Despite the many clinical studies of sirenomelia in humans, little is known about the pathogenic developmental mechanisms that cause the complex array of phenotypes observed. Here, we provide new evidences that reduced BMP (Bone Morphogenetic Protein) signaling disrupts caudal body formation in mice and phenocopies sirenomelia. Bmp4 is strongly expressed in the developing caudal body structures including the peri-cloacal region and hindlimb field. In order to address the function of Bmp4 in caudal body formation, we utilized a conditional Bmp4 mouse allele (Bmp4^flox/flox) and the Isl1 (Islet1)-Cre mouse line. Isl1-Cre is expressed in the peri-cloacal region and the developing hindimb field. Isl1Cre;Bmp4^flox/flox conditional mutant mice displayed sirenomelia phenotypes including hindlimb fusion and pelvic/urogenital organ dysgenesis. Genetic lineage analyses indicate that Isl1-expressing cells contribute to both the aPCM (anterior Peri-Cloacal Mesenchyme) and the hindlimb bud. We show Bmp4 is essential for the aPCM formation independently with Shh signaling. Furthermore, we show Bmp4 is a major BMP ligand for caudal body formation as shown by compound genetic analyses of Bmp4 and Bmp7. Taken together, this study reveals coordinated development of caudal body structures including pelvic/urogenital organs and hindlimb orchestrated by BMP signaling in Isl1-expressing cells. Our study offers new insights into the pathogenesis of sirenomelia.     

A nationwide attempt to standardize growth hormone assays

The Growth Hormone (GH) and Its Related Factors Study Committee of the Foundation for Growth Science, Japan, has been conducting a quality control study for 15 years to improve the equality of diagnosis of GH deficiency. It found that the greatest differences in measured GH values were due to the different potencies of the kit standards, which were primarily adjusted to WHO standards for human GH of pituitary origin. With the collaboration of kit makers and the Study Group of Hypothalamo-Pituitary Disorders of the Ministry of Health, Labor and Welfare, all GH kits in Japan have begun using the same recombinant human GH standard since April 2005. As a result the diagnostic cut-off peak GH has changed from 10 to 6 ng/ml.     

Molecular characterization of ENU mouse mutagenesis and archives

The large-scale mouse mutagenesis with ENU has provided forward-genetic resources for functional genomics. The frozen sperm archive of ENU-mutagenized generation-1 (G1) mice could also provide a "mutant mouse library" that allows us to conduct reverse genetics in any particular target genes. We have archived frozen sperm as well as genomic DNA from 9224 G1 mice. By genome-wide screening of 63 target loci covering a sum of 197 Mbp of the mouse genome, a total of 148 ENU-induced mutations have been directly identified. The sites of mutations were primarily identified by temperature gradient capillary electrophoresis method followed by direct sequencing. The molecular characterization revealed that all the identified mutations were point mutations and mostly independent events except a few cases of redundant mutations. The base-substitution spectra in this study were different from those of the phenotype-based mutagenesis. The ENU-based gene-driven mutagenesis in the mouse now becomes feasible and practical.     

Variations in the C3, C3a receptor, and C5 genes affect susceptibility to bronchial asthma

Bronchial asthma (BA) is a common chronic inflammatory disease characterized by hyperresponsive airways, excess mucus production, eosinophil activation, and the production of IgE. The complement system plays an immunoregulatory role at the interface of innate and acquired immunities. Recent studies have provided evidence that C3, C3a receptor, and C5 are linked to airway hyperresponsiveness. To determine whether genetic variations in the genes of the complement system affect susceptibility to BA, we screened single nucleotide polymorphisms (SNPs) in C3, C5, the C3a receptor gene (C3AR1), and the C5a receptor gene (C5R1) and performed association studies in the Japanese population. The results of this SNP case-control study suggested an association between 4896C/T in the C3 gene and atopic childhood BA (P=0.0078) as well as adult BA (P=0.010). When patient data were stratified according to elevated total IgE levels, 4896C/T was more closely associated with adult BA (P=0.0016). A patient-only association study suggested that severity of childhood BA was associated with 1526G/A of the C3AR1 gene (P=0.0057). We identified a high-risk haplotype of the C3 gene for childhood (P=0.0021) and adult BA (P=0.0058) and a low-risk haplotype for adult BA (P=0.00011). We also identified a haplotype of the C5 gene that was protective against childhood BA (P=1.4×10^–6) and adult BA (P=0.00063). These results suggest that the C3 and C5 pathways of the complement system play important roles in the pathogenesis of BA and that polymorphisms of these genes affect susceptibility to BA.     

Glucagon and epinephrine-stimulated phospholipid methylation in hepatic microsomes

Phospholipid methylation by hepatic microsomes was measured following glucagon or epinephrine administration either to intact rats or to the isolated perfused liver. Both hormones stimulated the methylation measured as the incorporation of S-adenosyl-L-[methyl-³H]methionine into phospholipids. The labeled products were identified by thin layer chromatography and most of the counts were found to be incorporated into phosphatidylcholine. The stimulatory effects of the hormones were evident already 5 minutes following hormone administration both in $\text{in vivo}$ and in $\text{in vitro}$. The observed stimulation of the methylation process by glucagon and epinephrine might be related to the previously reported stimulatory effect of these hormones on the microsomal Ca²⁺-ATPase, and indicate that methylation process(es) might mediate some of the effects of these hormones.