‘Hitting the target and missing the point’: Analysis of air permeability data for new UK dwellings and what it reveals about the testing procedure

Airtightness testing is widely undertaken to assess the as-built performance of dwellings, in support of achieving energy and ventilation strategies. Mandatory schemes operate in some countries, such as the UK, to ensure that dwellings are built in accordance with their design air permeability. However, testing is only useful if the results give a true picture of the airtightness of the building. Previous literature has investigated factors which could influence airtightness test results but has not questioned data quality, despite the pressure on builders to achieve design targets. This paper presents air permeability results from the largest UK dataset, comprising 144,024 dwellings tested under the Air Tightness Testing and Measurement Association (ATTMA) scheme. The data show an unexpected distribution of test results with narrow peaks just within test targets. Such results were not expected theoretically but do reflect findings in other fields where performance-based targets are in place. Such a close match between design and tested airtightness may be achieved by remedial works taking place during the test rather than afterwards. Recommendations are made with respect to quality assurance systems, design guidance and on-site sealing practices to increase the likelihood of long-term airtight buildings being constructed first time

Bark beetle population dynamics in the Anthropocene: Challenges and solutions

Tree-killing bark beetles are the most economically important insects in conifer forests worldwide. However, despite N200 years of research, the drivers of population eruptions and crashes are still not fully understood and the existing knowledge is thus insufficient to face the challenges posed by the Anthropocene. We critically analyze potential biotic and abiotic drivers of population dynamics of an exemplary species, the European spruce bark beetle (ESBB) (Ips typographus) and present a multivariate approach that integrates the many drivers governing this bark beetle system. We call for hypothesis-driven, large-scale collaborative research efforts to improve our understanding of the population dynamics of this and other bark beetle pests. Our approach can serve as a blueprint for tackling other eruptive forest insects

Contacts of underserved tuberculosis patients have higher odds of TB disease in North West England: a cohort study

OBJECTIVE: To investigate the association between patients' social risk factors and the risk of tuberculous infection and TB disease among their contacts in England. DESIGN: This was a cohort study of all TB cases from North West England diagnosed between 27 March 2012 and 28 June 2016. The social risk factors of TB cases were evaluated to estimate their need for enhanced case management (ECM), from 0 (standard of care) to 3 (intensive social support). RESULTS: A total of 2139 cases and their 10 019 contacts met the eligibility criteria. Being a contact of a patient with smear-positive TB with high ECM or being of Black Caribbean ethnicity was independently associated with greater odds of active TB disease (smear-positive vs. smear-negative, OR 5.3, 95%CI 3.2–8.7; ECM-3 vs. ECM-0, OR 2.2, 95%CI 1.01–5.0; Black Caribbean vs. White, OR 7.4, 95%CI 2.1–25). Being a contact of a patient with smear-positive TB or of Black Caribbean ethnicity was also independently associated with greater odds of tuberculous infection (smear-positive vs. smear-negative, OR 5.3, 95%CI 3.8–7.3; and Black Caribbean vs. White, OR 6.7, 95%CI 2.0–25). CONCLUSIONS: The social complexity and ethnicity of patients were associated with tuberculous infection and TB disease in their contacts

The solution structure of the N-terminal domain of hepatocyte growth factor reveals a potential heparin-binding site

AbstractBackground: Hepatocyte growth factor (HGF) is a multipotent growth factor that transduces a wide range of biological signals, including mitogenesis, motogenesis, and morphogenesis. The N-terminal (N) domain of HGF, containing a hairpin-loop region, is important for receptor binding and the potent biological activities of HGF. The N domain is also the primary binding site for heparin or heparan sulfate, which enhances receptor/ligand oligomerization and modulates receptor-dependent mitogenesis. The rational design of artificial modulators of HGF signaling requires a detailed understanding of the structures of HGF and its receptor, as well as the role of heparin proteoglycan; this study represents the first step towards that goal.Results: We report here a high-resolution solution structure of the N domain of HGF. This first structure of HGF reveals a novel folding topology with a distinct pattern of charge distribution and indicates a possible heparin-binding site.Conclusions: The hairpin-loop region of the N domain plays a major role in stabilizing the structure and contributes to a putative heparin-binding site, which explains why it is required for biological functions. These results suggest several basic and/or polar residues that may be important for use in further mutational studies of heparin binding

Tissue inhibitor of metalloproteinase-1 (TIMP-1) regulates mesenchymal stem cells through let-7f microRNA and Wnt/β-catenin signaling

Tissue inhibitor of metalloproteinases 1 (TIMP-1) is a matrix metalloproteinase (MMP)-independent regulator of growth and apoptosis in various cell types. The receptors and signaling pathways that are involved in the growth factor activities of TIMP-1, however, remain controversial. RNA interference of TIMP-1 has revealed that endogenous TIMP-1 suppresses the proliferation, metabolic activity, and osteogenic differentiation capacity of human mesenchymal stem cells (hMSCs). The knockdown of TIMP-1 in hMSCs activated the Wnt/β-catenin signaling pathway as indicated by the increased stability and nuclear localization of β-catenin in TIMP-1–deficient hMSCs. Moreover, TIMP-1 knockdown cells exhibited enhanced β-catenin transcriptional activity, determined by Wnt/β-catenin target gene expression analysis and a luciferase-based β-catenin– activated reporter assay. An analysis of a mutant form of TIMP-1 that cannot inhibit MMP indicated that the effect of TIMP-1 on β-catenin signaling is MMP independent. Furthermore, the binding of CD63 to TIMP-1 on the surface of hMSCs is essential for the TIMP-1–mediated effects on Wnt/β-catenin signaling. An array analysis of microRNAs (miRNAs) and transfection studies with specific miRNA inhibitors and mimics showed that let-7f miRNA is crucial for the regulation of β-catenin activity and osteogenic differentiation by TIMP-1. Let-7f was up-regulated in TIMP-1–depleted hMSCs and demonstrably reduced axin 2, an antagonist of β-catenin stability. Our results demonstrate that TIMP-1 is a direct regulator of hMSC functions and reveal a regulatory network in which let-7f modulates Wnt/β-catenin activity

Eavesdropping on the Arctic: Automated bioacoustics reveal dynamics in songbird breeding phenology

Bioacoustic networks could vastly expand the coverage of wildlife monitoring to complement satellite observations of climate and vegetation. This approach would enable global-scale understanding of how climate change influences phenomena such as migratory timing of avian species. The enormous data sets that autonomous recorders typically generate demand automated analyses that remain largely undeveloped. We devised automated signal processing and machine learning approaches to estimate dates on which songbird communities arrived at arctic breeding grounds. Acoustically estimated dates agreed well with those determined via traditional surveys and were strongly related to the landscape’s snow-free dates. We found that environmental conditions heavily influenced daily variation in songbird vocal activity, especially before egg laying. Our novel approaches demonstrate that variation in avian migratory arrival can be detected autonomously. Large-scale deployment of this innovation in wildlife monitoring would enable the coverage necessary to assess and forecast changes in bird migration in the face of climate change

Identification and Dynamics of a Heparin-Binding Site in Hepatocyte Growth Factor †

Hepatocyte growth factor (HGF) is a heparin-binding, multipotent growth factor that transduces a wide range of biological signals, including mitogenesis, motogenesis, and morphogenesis. Heparin or closely related heparan sulfate has profound effects on HGF signaling. A heparin-binding site in the N-terminal (N) domain of HGF was proposed on the basis of the clustering of surface positive charges [Zhou, H., Mazzulla, M. J., Kaufman, J. D., Stahl, S. J., Wingfield, P. T., Rubin, J. S., Bottaro, D. P., and Byrd, R. A. (1998) Structure 6, 109-116]. In the present study, we confirmed this binding site in a heparin titration experiment monitored by nuclear magnetic resonance spectroscopy, and we estimated the apparent dissociation constant (K(d)) of the heparin-protein complex by NMR and fluorescence techniques. The primary heparin-binding site is composed of Lys60, Lys62, and Arg73, with additional contributions from the adjacent Arg76, Lys78, and N-terminal basic residues. The K(d) of binding is in the micromolar range. A heparin disaccharide analogue, sucrose octasulfate, binds with similar affinity to the N domain and to a naturally occurring HGF isoform, NK1, at nearly the same region as in heparin binding. (15)N relaxation data indicate structural flexibility on a microsecond-to-millisecond time scale around the primary binding site in the N domain. This flexibility appears to be dramatically reduced by ligand binding. On the basis of the NK1 crystal structure, we propose a model in which heparin binds to the two primary binding sites and the N-terminal regions of the N domains and stabilizes an NK1 dimer

Food availability, energetic constraints and reproductive development in a wild seasonally breeding songbird

1. In many organisms, food availability is a proximate cue that synchronizes seasonal development of the reproductive system with optimal environmental conditions. Growth of the gonads and secondary sexual characteristics is orchestrated by the hypothalamic–pituitary–gonadal (HPG) axis. However, our understanding of the physiological mechanisms by which food availability modulates activity of the HPG axis is limited. 2. It is thought that many factors, including energetic status, modulate seasonal reproductive activation. We tested the hypothesis that food availability modulates the activity of the HPG axis in a songbird. Specifically, we food‐restricted captive adult male Abert's Towhees Melozone aberti for 2 or 4 weeks during photoinduced reproductive development. A third group (control) received ad libitum food throughout. We measured multiple aspects of the reproductive system including endocrine activity of all three levels of the HPG axis [i.e. hypothalamic gonadotropin‐releasing hormone‐I (GnRH‐I), plasma luteinizing hormone (LH) and testosterone (T)], and gonad morphology. Furthermore, because gonadotropin‐inhibitory hormone (GnIH) and neuropeptide Y (NPY; a potent orexigenic peptide) potentially integrate information on food availability into seasonal reproductive development, we also measured the brain levels of these peptides. 3. At the hypothalamic level, we detected no effect of food restriction on immunoreactive (ir) GnRH‐I, but the duration of food restriction was inversely related to the size of ir‐GnIH perikarya. Furthermore, the number of ir‐NPY cells was higher in food‐restricted than control birds. Food restriction did not influence photoinduced testicular growth, but decreased plasma LH and T, and width of the cloacal protuberance, an androgen‐sensitive secondary sexual characteristic. Returning birds to ad libitum food availability had no effect on plasma LH or T, but caused the cloacal protuberance to rapidly increase in size to that of ad libitum‐fed birds. 4. Our results support the tenet that food availability modulates photoinduced reproductive activation. However, they also suggest that this modulation is complex and depends upon the level of the HPG axis considered. At the hypothalamic level, our results are consistent with a role for the GnIH and NPY systems in integrating information on energetic status. There also appears to be a role for endocrine function at the anterior pituitary gland and testicular levels in modulating reproductive development in the light of energetic status and independently of testicular growth