| 1. |
- Luis Vilas, Jose, et al.
(författare)
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MonoRes : Automatic and Accurate Estimation of Local Resolution for Electron Microscopy Maps
- 2018
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Ingår i: Structure. - : Elsevier BV. - 0969-2126 .- 1878-4186. ; 26:2, s. 337-344
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Tidskriftsartikel (refereegranskat)abstract
- Since the beginning of electron microscopy, resolution has been a critical parameter. In this article, we propose a fully automatic, accurate method for determining the local resolution of a 3D map (MonoRes). The foundation of this algorithm is an extension of the concept of analytic signal, termed monogenic signal. The map is filtered at different frequencies and the amplitude of the monogenic signal is calculated, after which a criterion is applied to determine the resolution at each voxel. MonoRes is fully automatic without compulsory user parameters, with great accuracy in all tests, and is computationally more rapid than existing methods in the field. In addition, MonoRes offers the option of local filtering of the original map based on the calculated local resolution.
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| 2. |
- Nowak-Sliwinska, Patrycja, et al.
(författare)
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Consensus guidelines for the use and interpretation of angiogenesis assays
- 2018
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Ingår i: Angiogenesis. - : Springer. - 0969-6970 .- 1573-7209. ; 21:3, s. 425-532
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Forskningsöversikt (refereegranskat)abstract
- The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference.
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| 3. |
- Perez-Gracia, Jose Luis, et al.
(författare)
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Strategies to design clinical studies to identify predictive biomarkers in cancer research
- 2017
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Ingår i: Cancer Treatment Reviews. - : Elsevier BV. - 0305-7372. ; 53, s. 79-97
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Forskningsöversikt (refereegranskat)abstract
- The discovery of reliable biomarkers to predict efficacy and toxicity of anticancer drugs remains one of the key challenges in cancer research. Despite its relevance, no efficient study designs to identify promising candidate biomarkers have been established. This has led to the proliferation of a myriad of exploratory studies using dissimilar strategies, most of which fail to identify any promising targets and are seldom validated. The lack of a proper methodology also determines that many anti-cancer drugs are developed below their potential, due to failure to identify predictive biomarkers. While some drugs will be systematically administered to many patients who will not benefit from them, leading to unnecessary toxicities and costs, others will never reach registration due to our inability to identify the specific patient population in which they are active. Despite these drawbacks, a limited number of outstanding predictive biomarkers have been successfully identified and validated, and have changed the standard practice of oncology. In this manuscript, a multidisciplinary panel reviews how those key biomarkers were identified and, based on those experiences, proposes a methodological framework—the DESIGN guidelines—to standardize the clinical design of biomarker identification studies and to develop future research in this pivotal field.
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| 4. |
- Ukleja, Marta, et al.
(författare)
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Flotillin-mediated stabilization of unfolded proteins in bacterial membrane microdomains
- 2024
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- The function of many bacterial processes depends on the formation of functional membrane microdomains (FMMs), which resemble the lipid rafts of eukaryotic cells. However, the mechanism and the biological function of these membrane microdomains remain unclear. Here, we show that FMMs in the pathogen methicillin-resistant Staphylococcus aureus (MRSA) are dedicated to confining and stabilizing proteins unfolded due to cellular stress. The FMM scaffold protein flotillin forms a clamp-shaped oligomer that holds unfolded proteins, stabilizing them and favoring their correct folding. This process does not impose a direct energy cost on the cell and is crucial to survival of ATP-depleted bacteria, and thus to pathogenesis. Consequently, FMM disassembling causes the accumulation of unfolded proteins, which compromise MRSA viability during infection and cause penicillin re-sensitization due to PBP2a unfolding. Thus, our results indicate that FMMs mediate ATP-independent stabilization of unfolded proteins, which is essential for bacterial viability during infection.
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