1. Postulates for validating TLR4 agonistsRoman Jerala, Mateja Manček Keber, 2015 Povzetek: TLRs play a central role in the innate immune response, recognizing a variety of molecular
structures characteristic of pathogens. Although TLR4, together with its co-receptor
myeloid differentiation-2 (MD-2), recognize bacterial LPS and therefore Gram-negative
bacterial infections, it also plays a key role in many other pathophysiological processes,
including sterile inflammation and viral infection. Specifically, numerous endogenous
agonists of TLR4 of notably diverse nature, ranging from proteins to metal ions, have
been reported. Direct activation of a single receptor by such a range of molecular signals
is very difficult to explain from a structural and mechanistic point of view. It is likely
that only a subset of these directly activate the TLR4–MD-2 complex. We propose three
postulates aimed at distinguishing the direct agonists of TLR4 from indirect activators.
These postulates are as follows: (i) that the agonist requires the TLR4/MD-2 receptor complex;
(ii) that agonist formed synthetically or in situ must activate the receptor complex
in order to eliminate artifacts of contamination by other agonists; and (iii) that a specific
molecular interaction between the agonist and TLR4/MD-2 must be identified. The same
type of postulates can be applied to pattern recognition receptors in general.
Ključne besede: TLR4 agonists, molecular mechanism, ligand recognition
DiRROS - Objavljeno: 26.01.2015; Ogledov: 4307; Prenosov: 336 |
2. Self-assembled structures composed of single polypeptide comprising at least three coiled-coil forming elements : patentRoman Jerala, Ota Fekonja, Jelka Pohar, Helena Gradišar, Mojca Benčina, Iva Hafner Bratkovič, Robert Bremšak, Špela Miklavič, Urška Jelerčič, Anja Lukan, Tibor Doles, Sabina Božič Abram, Marko Verce, Nika Debeljak, Jožica Friedrich, 2014 Ključne besede: self assembled structures, polipeptide chain, nenostructures
DiRROS - Objavljeno: 13.05.2015; Ogledov: 5162; Prenosov: 612
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4. Design principles for rapid folding of knotted DNA nanostructuresRoman Jerala, Jonathan P. K. Doye, Tomaž Pisanski, Nino Bašić, Helena Gradišar, Slavko Čeru, John S. Schreck, Vid Kočar, 2016 Povzetek: Knots are some of the most remarkable topological features in nature. Self-assembly of knotted polymers without breaking or forming covalent bonds is challenging, as the chain needs to be threaded through previously formed loops in an exactly defined order. Here we describe principles to guide the folding of highly knotted single-chain DNA nanostructures as demonstrated on a nano-sized square pyramid. Folding of knots is encoded by the arrangement of modules of different stability based on derived topological and kinetic rules. Among DNA designs composed of the same modules and encoding the same topology, only the one with the folding pathway designed according to the "free-end" rule folds efficiently into the target structure. Besides high folding yield on slow annealing, this design also folds rapidly on temperature quenching and dilution from chemical denaturant. This strategy could be used to design folding of other knotted programmable polymers such as RNA or proteins.
DiRROS - Objavljeno: 13.04.2016; Ogledov: 3696; Prenosov: 1069
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5. Molecular basis of the functional differences between soluble human versus murine MD-2 : role of Val [sup] 135 in transfer of lipopolysaccharide from CD14 to MD-2Jožica Vašl, Alja Oblak, Tina Tinkara Peternelj, Javier Klett, Sonsoles Martín-Santamaría, Theresa L. Gioannini, Jerrold P. Weiss, Roman Jerala, 2016 Ključne besede: MD-2, TLR-4, species specificity, innate immunology
DiRROS - Objavljeno: 10.11.2016; Ogledov: 4174; Prenosov: 832 |
6. Design of coiled-coil protein-origami cages that self-assemble in vitro and in vivoAjasja Ljubetič, Fabio Lapenta, Helena Gradišar, Igor Drobnak, Jana Aupič, Žiga Strmšek, Duško Lainšček, Iva Hafner Bratkovič, Andreja Majerle, Nuša Krivec, Mojca Benčina, Tomaž Pisanski, Tanja Ćirković-Veličković, Adam Round, José María Carazo, Roberto Melero, Roman Jerala, 2017 DiRROS - Objavljeno: 17.04.2018; Ogledov: 3100; Prenosov: 1710
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9. Triangular in vivo self-assembling coiled-coil protein origamiSabina Božič Abram, Helena Gradišar, Jana Aupič, Adam Round, Roman Jerala, 2021 Ključne besede: coiled coil, enzyme clustering, biosynthesis, resveratrol, mevalonate
DiRROS - Objavljeno: 22.03.2021; Ogledov: 842; Prenosov: 487
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10. Robust saliva-based RNA extraction-free one-step nucleic acid amplification test for mass SARS-CoV-2 monitoringMojca Benčina, Roman Jerala, Tatjana Lejko-Zupanc, Gabriele Turel, Viktorija Tomič, Mihaela Zidarn, Žiga Jensterle, Katarina Prosenc, Mojca Milavec, Tina Demšar, Polona Kogovšek, Irena Mlinarič-Raščan, Dunja Urbančič, Alenka Šmid, Petra Sušjan, Arne Praznik, Tina Šket, Eva Rajh, 2021 Povzetek: Early diagnosis with rapid detection of the virus plays a key role in preventing the spread of infection and in treating patients effectively. In order to address the need for a straightforward detection of SARS-CoV-2 infection and assessment of viral spread, we developed rapid, sensitive, extraction-free one-step reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and reverse transcription loop-mediated isothermal amplification (RT-LAMP) tests for detecting SARS-CoV-2 in saliva. We analyzed over 700 matched pairs of saliva and nasopharyngeal swab (NSB) specimens from asymptomatic and symptomatic individuals. Saliva, as either an oral cavity swab or passive drool, was collected in an RNA stabilization buffer. The stabilized saliva specimens were heat-treated and directly analyzed without RNA extraction. The diagnostic sensitivity of saliva-based RT-qPCR was at least 95% in individuals with subclinical infection and outperformed RT-LAMP, which had at least 70% sensitivity when compared to NSBs analyzed with a clinical RT-qPCR test. The diagnostic sensitivity for passive drool saliva was higher than that of oral cavity swab specimens (95% and 87%, respectively). A rapid, sensitive one-step extraction-free RT-qPCR test for detecting SARS-CoV-2 in passive drool saliva is operationally simple and can be easily implemented using existing testing sites, thus allowing high-throughput, rapid, and repeated testing of large populations. Furthermore, saliva testing is adequate to detect individuals in an asymptomatic screening program and can help improve voluntary screening compliance for those individuals averse to various forms of nasal collections.
Ključne besede: SARS-CoV-2, COVID-19, COVID-19 serological testing, real-time polymerase chain reaction, saliva, oral cavity swab, passive drool, pooling
DiRROS - Objavljeno: 09.11.2021; Ogledov: 468; Prenosov: 212
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