| 1. |
- Allison, Timothy M., et al.
(författare)
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Complementing machine learning‐based structure predictions with native mass spectrometry
- 2022
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Ingår i: Protein Science. - : John Wiley & Sons. - 0961-8368 .- 1469-896X. ; 31:6
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Tidskriftsartikel (refereegranskat)abstract
- The advent of machine learning-based structure prediction algorithms such as AlphaFold2 (AF2) and RoseTTa Fold have moved the generation of accurate structural models for the entire cellular protein machinery into the reach of the scientific community. However, structure predictions of protein complexes are based on user-provided input and may require experimental validation. Mass spectrometry (MS) is a versatile, time-effective tool that provides information on post-translational modifications, ligand interactions, conformational changes, and higher-order oligomerization. Using three protein systems, we show that native MS experiments can uncover structural features of ligand interactions, homology models, and point mutations that are undetectable by AF2 alone. We conclude that machine learning can be complemented with MS to yield more accurate structural models on a small and large scale.
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| 2. |
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| 3. |
- Di Saverio, Salomone, et al.
(författare)
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WSES Jerusalem guidelines for diagnosis and treatment of acute appendicitis
- 2016
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Ingår i: World Journal of Emergency Surgery. - : BIOMED CENTRAL LTD. - 1749-7922. ; 11:34
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Forskningsöversikt (refereegranskat)abstract
- Acute appendicitis (AA) is among the most common cause of acute abdominal pain. Diagnosis of AA is challenging; a variable combination of clinical signs and symptoms has been used together with laboratory findings in several scoring systems proposed for suggesting the probability of AA and the possible subsequent management pathway. The role of imaging in the diagnosis of AA is still debated, with variable use of US, CT and MRI in different settings worldwide. Up to date, comprehensive clinical guidelines for diagnosis and management of AA have never been issued. In July 2015, during the 3rd World Congress of the WSES, held in Jerusalem (Israel), a panel of experts including an Organizational Committee and Scientific Committee and Scientific Secretariat, participated to a Consensus Conference where eight panelists presented a number of statements developed for each of the eight main questions about diagnosis and management of AA. The statements were then voted, eventually modified and finally approved by the participants to The Consensus Conference and lately by the board of co-authors. The current paper is reporting the definitive Guidelines Statements on each of the following topics: 1) Diagnostic efficiency of clinical scoring systems, 2) Role of Imaging, 3) Non-operative treatment for uncomplicated appendicitis, 4) Timing of appendectomy and in-hospital delay, 5) Surgical treatment 6) Scoring systems for intra-operative grading of appendicitis and their clinical usefulness 7) Non-surgical treatment for complicated appendicitis: abscess or phlegmon 8) Pre-operative and post-operative antibiotics.
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| 4. |
- Elofsson, Arne, 1966-, et al.
(författare)
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Deep learning insights into the architecture of the mammalian egg-sperm fusion synapse
- 2024
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Ingår i: eLIFE. - 2050-084X. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- A crucial event in sexual reproduction is when haploid sperm and egg fuse to form a new diploid organism at fertilization. In mammals, direct interaction between egg JUNO and sperm IZUMO1 mediates gamete membrane adhesion, yet their role in fusion remains enigmatic. We used AlphaFold to predict the structure of other extracellular proteins essential for fertilization to determine if they could form a complex that may mediate fusion. We first identified TMEM81, whose gene is expressed by mouse and human spermatids, as a protein having structural homologies with both IZUMO1 and another sperm molecule essential for gamete fusion, SPACA6. Using a set of proteins known to be important for fertilization and TMEM81, we then systematically searched for predicted binary interactions using an unguided approach and identified a pentameric complex involving sperm IZUMO1, SPACA6, TMEM81 and egg JUNO, CD9. This complex is structurally consistent with both the expected topology on opposing gamete membranes and the location of predicted N-glycans not modeled by AlphaFold-Multimer, suggesting that its components could organize into a synapse-like assembly at the point of fusion. Finally, the structural modeling approach described here could be more generally useful to gain insights into transient protein complexes difficult to detect experimentally.
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| 5. |
- Levine, Hagai, et al.
(författare)
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Male reproductive health statement (XIIIth international symposium on Spermatology, may 9th-12th 2018, Stockholm, Sweden
- 2018
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Ingår i: Basic and Clinical Andrology. - : Springer Science and Business Media LLC. - 2051-4190. ; 28:1
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Tidskriftsartikel (refereegranskat)abstract
- On the occasion of the XIIIth International Symposium on Spermatology held from 9 to 13 May 2018 in Stockholm (Sweden), participants (guest speakers and audience) collectively felt the need to make a public statement on the general issue of male reproductive health. Our intention is to raise awareness of what we believe is a neglected area of research despite alarming situations around the world. The disclosure strategy desired by the co-authors is to bring it to the attention of the greatest number partly by considering co-publication in the various periodicals dealing with Reproductive Biology and Andrology. BaCA's editorial office accepted this mission and found it natural that our periodical, the official journal of the French Andrology Society (SALF), should carry this message.
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| 6. |
- Nishio, Shunsuke, et al.
(författare)
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ZP2 cleavage blocks polyspermy by modulating the architecture of the egg coat
- 2024
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Ingår i: Cell. - : Elsevier. - 0092-8674 .- 1097-4172. ; 187:6, s. 1440-1459.e24
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Tidskriftsartikel (refereegranskat)abstract
- Following the fertilization of an egg by a single sperm, the egg coat or zona pellucida (ZP) hardens and polyspermy is irreversibly blocked. These events are associated with the cleavage of the N -terminal region (NTR) of glycoprotein ZP2, a major subunit of ZP filaments. ZP2 processing is thought to inactivate sperm binding to the ZP, but its molecular consequences and connection with ZP hardening are unknown. Biochemical and structural studies show that cleavage of ZP2 triggers its oligomerization. Moreover, the structure of a native vertebrate egg coat filament, combined with AlphaFold predictions of human ZP polymers, reveals that two protofilaments consisting of type I (ZP3) and type II (ZP1/ZP2/ZP4) components interlock into a left-handed double helix from which the NTRs of type II subunits protrude. Together, these data suggest that oligomerization of cleaved ZP2 NTRs extensively cross -links ZP filaments, rigidifying the egg coat and making it physically impenetrable to sperm.
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| 7. |
- Stsiapanava, Alena, et al.
(författare)
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Structure of the decoy module of human glycoprotein 2 and uromodulin and its interaction with bacterial adhesin FimH
- 2022
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Ingår i: Nature Structural & Molecular Biology. - : Springer Science and Business Media LLC. - 1545-9993 .- 1545-9985. ; 29:3, s. 190-193
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Tidskriftsartikel (refereegranskat)abstract
- AlphaFold2 predictions, X-ray crystallography and cryo-EM analyses reveal how related human glycoproteins GP2 and uromodulin catch pathogenic bacteria by presenting a high-mannose glycan that acts as a decoy for fimbrial adhesin FimH. Glycoprotein 2 (GP2) and uromodulin (UMOD) filaments protect against gastrointestinal and urinary tract infections by acting as decoys for bacterial fimbrial lectin FimH. By combining AlphaFold2 predictions with X-ray crystallography and cryo-EM, we show that these proteins contain a bipartite decoy module whose new fold presents the high-mannose glycan recognized by FimH. The structure rationalizes UMOD mutations associated with kidney diseases and visualizes a key epitope implicated in cast nephropathy.
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| 8. |
- Thomas, HS, et al.
(författare)
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- 2019
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swepub:Mat__t
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| 9. |
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