| 951. |
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| 952. |
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| 953. |
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| 954. |
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| 955. |
- Nilsson, Ola B., et al.
(författare)
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Cotranslational Protein Folding inside the Ribosome Exit Tunnel
- 2015
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 12:10, s. 1533-1540
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Tidskriftsartikel (refereegranskat)abstract
- At what point during translation do proteins fold? It is well established that proteins can fold cotranslationally outside the ribosome exit tunnel, whereas studies of folding inside the exit tunnel have so far detected only the formation of helical secondary structure and collapsed or partially structured folding intermediates. Here, using a combination of co-translational nascent chain force measurements, inter-subunit fluorescence resonance energy transfer studies on single translating ribosomes, molecular dynamics simulations, and cryoelectron microscopy, we show that a small zinc-finger domain protein can fold deep inside the vestibule of the ribosome exit tunnel. Thus, for small protein domains, the ribosome itself can provide the kind of sheltered folding environment that chaperones provide for larger proteins.
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| 956. |
- O’Brien, D., et al.
(författare)
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Subsidiary management’s horizontal boundary spanning activity as entrepreneurial behaviour
- 2019
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Ingår i: Entrepreneurial Behaviour: Individual, Contextual and Microfoundational Perspectives. - Cham : Palgrave Macmillan. ; , s. 169-202
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- To date, the rich subsidiary literature has largely overlooked the individual entrepreneurial behaviours required by subsidiary managers to build crucial linkages and access vital knowledge. This chapter addresses this issue and takes a microfoundational approach to develop a typology of subsidiary managers’ attentional engagement on key boundary spanning strategic activities. By substantiating middle managers’ strategic activities outside the realm of the direct TMT perspective, the chapter proposes an integrated framework of middle managers’ horizontal boundary spanning activities in multinational corporations (MNCs). Furthermore, this chapter reveals insights on the true levels of strategic coordination required to manage large complex organizations, and how managers focus their attention on different horizontal activities to drive corporate entrepreneurship depending on the specific agenda of their management context.
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| 957. |
- O'Brien, K. M., et al.
(författare)
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Resilience of cardiac performance in Antarctic notothenioid fishes in a warming climate
- 2021
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Ingår i: Journal of Experimental Biology. - : The Company of Biologists. - 0022-0949 .- 1477-9145. ; 224:10
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Tidskriftsartikel (refereegranskat)abstract
- Warming in the region of the Western Antarctic Peninsula is occurring at an unprecedented rate, which may threaten the survival of Antarctic notothenioid fishes. Herein, we review studies characterizing thermal tolerance and cardiac performance in notothenioids - a group that includes both red-blooded species and the white-blooded, haemoglobinless icefishes - as well as the relevant biochemistry associated with cardiac failure during an acute temperature ramp. Because icefishes do not feed in captivity, making long-term acclimation studies unfeasible, we focus only on the responses of red-blooded notothenioids to warm acclimation. With acute warming, hearts of the white-blooded icefish Chaenocephalus aceratus display persistent arrhythmia at a lower temperature (8 degrees C) compared with those of the red-blooded Notothenia coriiceps (14 degrees C). When compared with the icefish, the enhanced cardiac performance of N. coriiceps during warming is associated with greater aerobic capacity, higher ATP levels, less oxidative damage and enhanced membrane integrity. Cardiac performance can be improved in N. coriiceps with warm acclimation to 5 degrees C for 6-9 weeks, accompanied by an increase in the temperature at which cardiac failure occurs. Also, both cardiac mitochondrial and microsomal membranes are remodelled in response to warm acclimation in N. coriiceps, displaying homeoviscous adaptation. Overall, cardiac performance in N. coriiceps is malleable and resilient to warming, yet thermal tolerance and plasticity vary among different species of notothenioid fishes; disruptions to the Antarctic ecosystem driven by climate warming and other anthropogenic activities endanger the survival of notothenioids, warranting greater protection afforded by an expansion of marine protected areas.
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| 958. |
- O'Brien, Kevin P
(författare)
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The role of PDGFB in dermatofibrosarcoma protuberans and giant cell fibroblastoma
- 2000
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Dermatofibrosarcoma protuberans (DFSP) and giant cell fibroblastoma (GCF) are rare invasive tumors of the dermis. GCF is considered the juvenile form of DFSP. Both DFSP and GCF are characterized by the presence of chromosomal aberrations involving chromosomes 17 and 22. Supernumerary ring chromosomes are more common in DFSP, while the translocation t(17;22)(q22;q13) is the most common rearrangement observed in GCF. The aim of this thesis was to determine the molecular events behind these chromosomal aberrations. Chromosomal breakpoints were characterized by FISH walking and Southern blot analysis, which revealed that the platelet derived growth factor B-chain gene (PDGFB proto-oncogene or c-sis) on 22q was rearranged in DFSP/GCF. Using 5' RACE, the collagen type I alpha 1 gene (COL1A1) was demonstrated to be the 17q gene involved in the rearrangement. RT-PCR of the COL1A1/PDGFB fusion genes in 20 tumors, demonstrated that each fusion gene consisted of an exon of the COL1A1 alpha-helical domain fused in-frame to PDGFB exon 2, in all tumors analyzed. This is remarkably similar to Simian sarcoma virus and Parodi-Irgens feline sarcoma virus. These viruses consist of viral genes fused to the exon 2 of a PDGFB gene, thus removing all elements negatively regulated transcription and translation of the PDGFB gene. The COL1A1/PDGFB fusion gene has not been found in any other tumor type and was present in all tumors studied by RT-PCR. This fusion gene may thus be considered diagnostic for DFSP/GCF. Two DFSP case studies were also performed; In one DFSP tumor, quadruplicate copies of the fusion gene were found on a large marker chromosome. In another DFSP case, RT-PCR demonstrated the presence of a fusion gene with a COL1A1 exon 37 to PDGFB exon 2 on the mRNA level, a fusion previously only seen in a GCF tumor. This indicates that the location of the fusion breakpoint in COL1A1 has little effect on tumor type. In order to study the fusion gene in vitro, a COL1A1/PDGFB expressing cell line was constructed by transfection of NIH-3T3 cells with a cosmid containing a tumor-derived fusion gene. These cells were transformed, displaying increased growth, loss of contact inhibition and formation of tumors in nude mice. Using pulse-chase analysis and immunoprecipitations the production of a PDGFB-like protein was demonstrated. It was dimerized, localized and processed in a similar way to normal PDGFB. All COL1A1 segments were removed from the COL1A1/PDGFB protein during this processing. Upon addition of a PDGF receptor tyrosine kinase-specific inhibitor, the transformed COL1A1/PDGFB expressing cells reverted back to a normal phenotype. Thus, in a collagen expressing cell, the presence of a COL1A1/PDGFB gene results in the production of mature PDGF-BB dimers. Since DFSP/GCF cells express both collagen and PDGF receptors, then a similar mechanism is likely to be occurring in these cells. In DFSP/GCF tumor cells, it is likely that COL1A1 acts solely as a production vehicle for PDGFB, the end product of the fusion gene being mature PDGF-BB dimers which stimulate the cell in an autocrine fashion. Interruption of this autocrine stimulation using PDGF receptor inhibitors could be a possible treatment of DFSP/GCF, but is complicated by the presence of other genetic changes which tumor cells have likely undergone.
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| 959. |
- O'Brien, Phoebe A. J., 1995, et al.
(författare)
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Benthic foraminiferal indices and environmental quality assessment of transitional waters: A review of current challenges and future research perspectives
- 2021
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Ingår i: Water. - : MDPI AG. - 2073-4441. ; 13:14
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Forskningsöversikt (refereegranskat)abstract
- Transitional waters straddle the interface between marine and terrestrial biomes and, among others, include fjords, bays, lagoons, and estuaries. These coastal systems are essential for transport and manufacturing industries and suffer extensive anthropogenic exploitation of their ecosystem services for aquaculture and recreational activities. These activities can have negative effects on the local biota, necessitating investigation and regulation. As a result of this, EcoQS (ecological quality status) assessment has garnered great attention as an essential aspect of governmental bodies’ legislative decision-making process. Assessing EcoQS in transitional water ecosystems is problematic because these systems experience high natural variability and organic enrichment and often lack information about their pre-human impact, baseline, or “pristine” reference conditions, knowledge of which is essential to many commonly used assessment methods. Here, foraminifera can be used as environmental sentinels, providing ecological data such as diversity and sensitivity, which can be used as the basis for EcoQS assessment indices. Fossil shells of foraminifera can also provide a temporal aspect to ecosystem assessment, making it possible to obtain reference conditions from the study site itself. These foraminifera-based indices have been shown to correlate not only with various environmental stressors but also with the most common macrofaunal-based indices currently employed by bodies such as the Water Framework Directive (WFD). In this review, we firstly discuss the development of various foraminifera-based indices and address the challenge of how best to implement these synergistically to understand and regulate human environmental impact, particularly in transitional waters, which have historically suffered disproportionate levels of human impact or are difficult to assess with standard EcoQS methods. Further, we present some case studies to exemplify key issues and discuss potential solutions for those. Such key issues include, for example, the disparate performance of multiple indices applied to the same site and a proper assignment of EcoQS class boundaries (threshold values) for each index. Disparate aptitudes of indices to specific geomorphologic and hydrological regimes can be leveraged via the development of a site characteristics catalogue, which would enable the identification of the most appropriate index to apply, and the integration of multiple indices resulting in more representative EcoQS assessment in heterogenous transitional environments. In addition, the difficulty in assigning threshold values to systems without analogous unimpacted reference sites (a common issue among many transitional waters) can be overcome by recording EcoQS as an ecological quality ratio (EQR). Lastly, we evaluate the current status and future potential of an emerging field, genetic biomonitoring, focusing on how these new techniques can be used to increase the accuracy of EcoQS assessment in transitional systems by supplementing more established morphology-based methods.
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| 960. |
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