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71.
Sayantan Bose Carissa M. Heath Priya A. Shah Maher Alayyoubi Theodore S. Jardetzky Robert A. Lamb 《Journal of virology》2013,87(24):13520-13531
Paramyxovirus membrane glycoproteins F (fusion protein) and HN, H, or G (attachment protein) are critical for virus entry, which occurs through fusion of viral and cellular envelopes. The F protein folds into a homotrimeric, metastable prefusion form that can be triggered by the attachment protein to undergo a series of structural rearrangements, ultimately folding into a stable postfusion form. In paramyxovirus-infected cells, the F protein is activated in the Golgi apparatus by cleavage adjacent to a hydrophobic fusion peptide that inserts into the target membrane, eventually bringing the membranes together by F refolding. However, it is not clear how the attachment protein, known as HN in parainfluenza virus 5 (PIV5), interacts with F and triggers F to initiate fusion. To understand the roles of various F protein domains in fusion triggering and metastability, single point mutations were introduced into the PIV5 F protein. By extensive study of F protein cleavage activation, surface expression, and energetics of fusion triggering, we found a role for an immunoglobulin-like (Ig-like) domain, where multiple hydrophobic residues on the PIV5 F protein may mediate F-HN interactions. Additionally, destabilizing mutations of PIV5 F that resulted in HN trigger-independent mutant F proteins were identified in a region along the border of F trimer subunits. The positions of the potential HN-interacting region and the region important for F stability in the lower part of the PIV5 F prefusion structure provide clues to the receptor-binding initiated, HN-mediated F trigger. 相似文献
72.
Jushan Liu Yuguang Bai Eric G. Lamb Dale Simpson Guofang Liu Yongsheng Wei Deli Wang Daniel W. McKenney Pia Papadopol 《PloS one》2013,8(4)
Seed mass is an adaptive trait affecting species distribution, population dynamics and community structure. In widely distributed species, variation in seed mass may reflect both genetic adaptation to local environments and adaptive phenotypic plasticity. Acknowledging the difficulty in separating these two aspects, we examined the causal relationships determining seed mass variation to better understand adaptability and/or plasticity of selected tree species to spatial/climatic variation. A total of 504, 481 and 454 seed collections of black spruce (Picea mariana (Mill.) B.S.P.), white spruce (Picea glauca (Moench) Voss) and jack pine (Pinus banksiana Lamb) across the Canadian Boreal Forest, respectively, were selected. Correlation analyses were used to determine how seed mass vary with latitude, longitude, and altitude. Structural Equation Modeling was used to examine how geographic and climatic variables influence seed mass. Climatic factors explained a large portion of the variation in seed mass (34, 14 and 29%, for black spruce, white spruce and jack pine, respectively), indicating species-specific adaptation to long term climate conditions. Higher annual mean temperature and winter precipitation caused greater seed mass in black spruce, but annual precipitation was the controlling factor for white spruce. The combination of factors such as growing season temperature and evapotranspiration, temperature seasonality and annual precipitation together determined seed mass of jack pine. Overall, sites with higher winter temperatures were correlated with larger seeds. Thus, long-term climatic conditions, at least in part, determined spatial variation in seed mass. Black spruce and Jack pine, species with relatively more specific habitat requirements and less plasticity, had more variation in seed mass explained by climate than did the more plastic species white spruce. As traits such as seed mass are related to seedling growth and survival, they potentially influence forest species composition in a changing climate and should be included in future modeling of vegetation shifts. 相似文献
73.
Controlling the prevalence of Escherichia coli O157 in cattle at the pre-harvest level is critical to reduce outbreaks of this pathogen in humans. Multilayers of factors including the environmental and bacterial factors modulate the colonization and persistence of E. coli O157 in cattle that serve as a reservoir of this pathogen. Here, we report animal factors contributing to the prevalence of E. coli O157 in cattle. We observe the lowest number of E. coli O157 in Brahman breed when compared with other crosses in an Angus-Brahman multibreed herd, and bulls excrete more E. coli O157 than steers in the pens where cattle were housed together. The presence of super-shedders, cattle excreting >105 CFU/rectal anal swab, increases the concentration of E. coli O157 in the pens; thereby super-shedders enhance transmission of this pathogen among cattle. Molecular subtyping analysis reveal only one subtype of E. coli O157 in the multibreed herd, indicating the variance in the levels of E. coli O157 in cattle is influenced by animal factors. Furthermore, strain tracking after relocation of the cattle to a commercial feedlot reveals farm-to-farm transmission of E. coli O157, likely via super-shedders. Our results reveal high risk factors in the prevalence of E. coli O157 in cattle whereby animal genetic and physiological factors influence whether this pathogen can persist in cattle at high concentration, providing insights to intervene this pathogen at the pre-harvest level. 相似文献
74.
Christopher A. Lamb 《Autophagy》2016,12(7):1212-1213
Amino acid withdrawal induces the formation of autophagosomes, which results in dozens of these large double-membrane vesicles appearing in the starved cell within 10–15 min, and the initiation of autophagy. This vesicle-mediated response clearly requires an adequate supply of membrane and a tight molecular regulation creating a substantial challenge for the cell in terms of vesicle trafficking pathways. Several membrane sources, which contribute to autophagosome initiation and formation, have been identified including the ER, Golgi, plasma membrane, mitochondria and recycling endosomes. How contributions from these organelles are regulated is an intensive area of study. Members of several families of membrane traffic regulators, including small GTPases, such as RAB proteins, and their regulators, SNARE proteins and BAR domain-containing proteins, have recently been shown to support autophagosome formation. 相似文献
75.
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77.
Christopher A Lamb Stefanie Nühlen Delphine Judith David Frith Ambrosius P Snijders Christian Behrends Sharon A Tooze 《The EMBO journal》2016,35(3):281-301
Macroautophagy requires membrane trafficking and remodelling to form the autophagosome and deliver its contents to lysosomes for degradation. We have previously identified the TBC domain‐containing protein, TBC1D14, as a negative regulator of autophagy that controls delivery of membranes from RAB11‐positive recycling endosomes to forming autophagosomes. In this study, we identify the TRAPP complex, a multi‐subunit tethering complex and GEF for RAB1, as an interactor of TBC1D14. TBC1D14 binds to the TRAPP complex via an N‐terminal 103 amino acid region, and overexpression of this region inhibits both autophagy and secretory traffic. TRAPPC8, the mammalian orthologue of a yeast autophagy‐specific TRAPP subunit, forms part of a mammalian TRAPPIII‐like complex and both this complex and TBC1D14 are needed for RAB1 activation. TRAPPC8 modulates autophagy and secretory trafficking and is required for TBC1D14 to bind TRAPPIII. Importantly, TBC1D14 and TRAPPIII regulate ATG9 trafficking independently of ULK1. We propose a model whereby TBC1D14 and TRAPPIII regulate a constitutive trafficking step from peripheral recycling endosomes to the early Golgi, maintaining the cycling pool of ATG9 required for initiation of autophagy. 相似文献
78.
Jacob J. Lamb Olivier Bernard Shiplu Sarker Kristian M. Lien Dag Roar Hjelme 《Engineering in Life Science》2019,19(11):759-769
Biogas production is becoming significantly viable as an energy source for replacing fossil‐based fuels. The further development of the biogas production process could lead to significant improvements in its potential. Wastewater treatment currently accounts for 3% of the electrical energy load in developed countries, while it could be developed to provide a source of nitrogen and phosphorus, in addition to energy. The improvement of anaerobic digestion (AD) detection technologies is the cornerstone to reach higher methane productivities and develop fully automatized processes to decrease operational costs. New sensors are requested to automatically obtain a better interpretation of the complex and dynamical internal reactor environment. This will require detailed systematic detection in order to realize a near‐optimal production process. In this review, optical fiber‐based sensors will be discussed to assess their potential for use in AD. There is currently a disparity between the complexity of AD, and online detection. By improving the durability, sensitivity, and cost of dissolved H2 (as well as H2S, acetic acid, ammonia, and methane) sensor technology, further understanding of the AD process may allow the prevention of process failure. The emergence of surface plasmon resonance (SPR) sensing with optical fibers coupled with the H2‐sensitive metal palladium, allows detection of dissolved hydrogen in liquid. By implementing these SPR sensors into AD, improvements to the biogas production process, even at small scales, may be achieved by guiding the process in the optimum direction, avoiding the collapse of the biological process. This review intends to assess the feasibility of online, cost‐effective, rapid, and efficient detection of dissolved H2, as well as briefly assessing H2S, acetic acid, ammonia, and methane in AD by SPR. 相似文献
79.
Philip D. Lamb Ewan Hunter John K. Pinnegar Simon Creer Richard G. Davies Martin I. Taylor 《Molecular ecology》2019,28(2):420-430
Metabarcoding has been used in a range of ecological applications such as taxonomic assignment, dietary analysis and the analysis of environmental DNA. However, after a decade of use in these applications there is little consensus on the extent to which proportions of reads generated corresponds to the original proportions of species in a community. To quantify our current understanding, we conducted a structured review and meta‐analysis. The analysis suggests that a weak quantitative relationship may exist between the biomass and sequences produced (slope = 0.52 ± 0.34, p < 0.01), albeit with a large degree of uncertainty. None of the tested moderators, sequencing platform type, the number of species used in a trial or the source of DNA, were able to explain the variance. Our current understanding of the factors affecting the quantitative performance of metabarcoding is still limited: additional research is required before metabarcoding can be confidently utilized for quantitative applications. Until then, we advocate the inclusion of mock communities when metabarcoding as this facilitates direct assessment of the quantitative ability of any given study. 相似文献
80.
Minich DM Bland JS Katke J Darland G Hall A Lerman RH Lamb J Carroll B Tripp M 《Canadian journal of physiology and pharmacology》2007,85(9):872-883
In this report, we examine the clinical safety and efficacy of NG440, a phytochemical-based antiinflammatory formula consisting of a combination of rho iso-alpha acids from hops, rosemary, and oleanolic acid. In a previous study, we demonstrated that NG440 significantly decreased pain by 50% in patients with osteoarthritis. Consistent with these data, results from a multicentre trial indicate that NG440 reduced pain scores in patients with joint discomfort, as measured by VAS (visual analog scale) methodology. As demonstrated in an ex vivo clinical study, these effects on pain relief may be due to reduced inflammatory cytokine production including lower prostaglandin E2 formation. Finally, strong data exist to suggest that NG440 is a safe formula for human consumption. Animal toxicity data revealed no adverse effects of NG440 at dosages < or =250 mg.kg-1.day-1 for 21 days. Furthermore, human trial data suggest that NG440 does not negatively impact cardiovascular and gastrointestinal markers normally affected by selective COX-2 enzyme inhibitors, including platelet function, blood pressure, blood cell count, or fecal calprotectin, a measure of gastrointestinal injury. In conclusion, NG440 may serve as a safe and efficacious alternative in some areas where specific COX-2 inhibitors have been traditionally used. 相似文献