Article
Biology
Anurag Kumar Sinha, Kristoffer Skovbo Winther
Summary: This study reveals that bacteria synthesize (p)ppGpp to reprogram cell physiology in response to environmental stresses, with proteins of the RSH superfamily playing a key role in hydrolyzing or synthesizing (p)ppGpp. The inactive hydrolase domain of Escherichia coli RelA modulates the activity of the synthetase domain, and mutagenesis studies identify a loop region in the hydrolase domain that acts as a molecular switch to regulate synthetase activity.
COMMUNICATIONS BIOLOGY
(2021)
Article
Chemistry, Physical
Houchao Xu, Jeroen S. Dickschat
Summary: This study investigated the active site of 7-epi-a-eudesmol synthase through site-directed mutagenesis, revealing two key residues that can alter the enzymatic activity of the synthase.
Article
Plant Sciences
Hui Jin, Yong Min Lao, Jin Zhou, Zhong Hua Cai
Summary: A RelA/SpoT homolog, HpRSH, is identified in Haematococcus pluvialis, which is associated with environmental stresses, ppGpp levels and astaxanthin biosynthesis. It is suggested that stringent response may regulate astaxanthin biosynthesis in a light-dependent manner.
FRONTIERS IN PLANT SCIENCE
(2022)
Review
Chemistry, Multidisciplinary
Laleh Solhi, Valentina Guccini, Katja Heise, Iina Solala, Elina Niinivaara, Wenyang Xu, Karl Mihhels, Marcel Kroeger, Zhuojun Meng, Jakob Wohlert, Han Tao, Emily D. Cranston, Eero Kontturi
Summary: Modern technology allows for the extraction of nanocellulose from plant-based fibers, and its application in sustainable materials is a growing trend. While water is typically detrimental to nanocellulose-based materials, it plays an important role in plants, and many nanocellulose applications already incorporate or rely on water. This review presents a comprehensive assessment of the interaction between nanocellulose and water, covering various research areas such as physical chemistry, chemical modification, materials applications, and analytical methods.
News Item
Biochemistry & Molecular Biology
Parjit Kaur
Summary: This study uses deep mutational scanning of a bacterial MDR protein to determine the nature of its drug-binding cavity and understand its function and plasticity. It highlights the major hurdles remaining in understanding the mechanisms of multidrug resistance (MDR) protein efflux.
NATURE CHEMICAL BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Itxaso Anso, Andreas Naegeli, Javier O. Cifuente, Ane Orrantia, Erica Andersson, Olatz Zenarruzabeitia, Alicia Moraleda-Montoya, Mikel Garcia-Alija, Francisco Corzana, Rafael A. Del Orbe, Francisco Borrego, Beatriz Trastoy, Jonathan Sjogren, Marcelo E. Guerin
Summary: Red blood cell antigens are critical in blood transfusion. Researchers have discovered a bacterial enzyme called FucOB that can convert universal O type blood into the rare Bombay type blood. This finding has the potential to facilitate transfusion in recipients with the Bombay phenotype.
NATURE COMMUNICATIONS
(2023)
Editorial Material
Medicine, General & Internal
Peter J. Neumann, Sean R. Tunis
Summary: Recent developments have pushed Medicare to play a bigger role in health technology assessment. Measures such as bolstering the CMS workforce and working with the FDA could enhance the chances of success.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Article
Chemistry, Multidisciplinary
Shuaijun Wang, Maximilian Meixner, Lushuang Yu, Ling Zhuo, Lisa Karmann, Uli Kazmaier, Angelika M. Vollmar, Iris Antes, Stefan Zahler
Summary: The research team discovered derivatives of actin nucleating compounds that exhibit paradoxical inversion of their mode of action, leading to a proposal of a new synthetic method and deciphering the binding mode and mechanism of action of one of these derivatives. This finding opens up the possibility of tuning actin-binding compounds towards either direction and generating new synthetic actin binders with increased functional selectivity.
Article
Biochemistry & Molecular Biology
Antonio Iorio, Celine Brochier-Armanet, Caroline Mas, Fabio Sterpone, Dominique Madern
Summary: This study unveils the intimate relationship between protein dynamics and allostery, and identifies key dynamic mutations in the evolution of allostery. These mutations induce drastic changes in the conformational landscape, allowing access to typical conformers of allosteric proteins. This research is of great importance for understanding the evolution of protein function.
MOLECULAR BIOLOGY AND EVOLUTION
(2022)
Article
Medicine, Research & Experimental
Jonna Tenhunen, Tomas Kucera, Marjo Huovinen, Jenni Kublbeck, Egils Bisenieks, Brigita Vigante, Zaiga Ogle, Gunars Duburs, Martin Dolezal, Ruin Moaddel, Maija Lahtela-Kakkonen, Minna Rahnasto-Rilla
Summary: SIRT6, a member of sirtuin family, plays a role in regulating cellular processes related to aging, metabolism, and cancer development. This study identified novel compounds targeting SIRT6 and discovered both inhibitors and a highly potent activator, demonstrating potential in anticancer therapy for breast cancer. The inhibitors showed a decrease in cell proliferation across various breast cancer cells, while the activator exhibited significant activation and cell cycle arrest in triple negative cells.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Biochemistry & Molecular Biology
Machteld Sillen, Toshio Miyata, Douglas E. Vaughan, Sergei V. Strelkov, Paul J. Declerck
Summary: PAI-1 is a key regulator of the fibrinolytic system, with potential therapeutic significance in various pathological conditions. Small molecule inhibitors like TM5484 may inhibit PAI-1 by binding to the flexible joint region and inducing a substrate to inert form conversion.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Physical
Turgay Tunc, Ahmet Bugra Ortaakarsu, Seda Muhsir Hatipoglu, Ugur Kazanci, Serdar Karabocek, Nevin Karabocek, Necmi Dege, Nurcan Karacan
Summary: 2,6-bis(2-aminophenylthio)pyridine was synthesized and characterized. Its new Schiffbases were tested for their glutathione reductase activities and binding properties. The compound L-4 showed enhanced enzyme activity, while other Schiffbases acted as inhibitors. Molecular docking analysis suggested potential antimalarial properties for 2,6-bis(2-aminophenylthio)pyridine. Computational calculations predicted favorable properties for the synthesized ligands.
JOURNAL OF MOLECULAR STRUCTURE
(2022)
Article
Engineering, Environmental
Fengming Hou, Wei Wei, Yihang Li, Zhipeng Guo, Xiaoke Zhang, Jin Li, Ang Wei
Summary: By target-oriented functionalization, carbon nitride was successfully modified as a round-the-clock antimicrobial photocatalyst for high-efficient water disinfection and bacteriostasis. The modified photocatalyst demonstrated excellent disinfection efficacy against pathogenic microorganisms and continuous inhibition of microbial proliferation.
CHEMICAL ENGINEERING JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Rita Celano, Teresa Docimo, Anna Lisa Piccinelli, Patrizia Gazzerro, Marina Tucci, Rosa Di Sanzo, Sonia Carabetta, Luca Campone, Mariateresa Russo, Luca Rastrelli
Summary: Onion waste, particularly the skins, is rich in bioactive phenolic compounds such as flavonols and anthocyanins, which have antioxidant and anti-diabetic properties. Two traditional onion varieties cultivated in southern Italy, Rossa di Tropea and Ramata di Montoro, were found to be sources of valuable bioactive molecules for various applications, from industrial to nutraceutical and cosmetic sectors.
Review
Oncology
N. E. Donlon, R. Power, C. Hayes, J. Reynolds, J. Lysaght
Summary: Immune checkpoint blockade has significantly changed the treatment of solid tumors, but many patients do not respond. Combining radiation therapy with immunotherapy may have synergistic effects by remodeling the tumor microenvironment, but careful control of dose and fractionation is essential for safety and efficacy. Ongoing efforts to combine radiation, immunotherapy, and DNA damage response inhibitors aim to achieve a beneficial balance between the immunogenic and tolerogenic effects of radiation on the immune microenvironment.
Article
Dermatology
Helen Vaher, Kristiina Kingo, Peep Kolberg, Martin Pook, Liisi Raam, Anet Laanesoo, Anu Remm, Tanel Tenson, Kaur Alasoo, Ulrich Mrowietz, Stephan Weidinger, Kulli Kingo, Ana Rebane
Summary: The study confirms the alteration in expression of IL-1 family cytokines and inflammasome-related genes in the development of atopic dermatitis (AD), and a positive relationship between NLRP1 and IL1B or IL18 mRNA levels. It also demonstrates increased expression of NLRP1 and PYCARD proteins, and increased caspase-1 activity in the skin of AD patients. Additionally, genetic associations with AD and the involvement of various immune cell types are predicted. In keratinocytes, colonization with Staphylococcus aureus results in increased secretion of IL-1b and IL-18, which is inhibited by siRNA silencing of NLRP1. These findings suggest that S. aureus colonization may activate the NLRP1 inflammasome in keratinocytes, leading to the secretion of IL-1b and IL-18, and contributing to the pathogenesis of AD, particularly in the presence of genetic variations in the IL-18 pathway.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2023)
Article
Medicine, Research & Experimental
Kairi Lorenz, Liis Preem, Kadi Sagor, Marta Putrins, Tanel Tenson, Karin Kogermann
Summary: Increasing evidence suggests that chronic wounds are associated with bacterial biofilms. New wound care products are being developed to inhibit biofilm formation and treat existing ones. In order to analyze these new antibacterial drug delivery systems, standardized assays and appropriate tools and models are needed. This study demonstrates that optimized in vitro and ex vivo wound infection and biofilm models provide a convenient approach for testing the antibacterial and antibiofilm properties of novel wound dressings. The results can be used to design more effective wound care products and screen different formulations and active substances.
MOLECULAR PHARMACEUTICS
(2023)
Article
Biochemistry & Molecular Biology
Hedvig Tamman, Karin Ernits, Mohammad Roghanian, Andres Ainelo, Christina Julius, Anthony Perrier, Ariel Talavera, Hanna Ainelo, Remy Dugauquier, Safia Zedek, Aurelien Thureau, Javier Perez, Gipsi Lima-Mendez, Regis Hallez, Gemma C. Atkinson, Vasili Hauryliuk, Abel Garcia-Pino
Summary: Stringent factors regulate bacterial cell reprogramming by increasing the level of (p)ppGpp. This study presents the crystal structure of the hydrolase-only SpoT from Acinetobacter baumannii and reveals the intramolecular regulation mechanism of 'long'-stringent factors. The Core subdomain plays a key role in determining the specialization of long RelA-SpoT homologs towards synthesis or hydrolysis.
NATURE CHEMICAL BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Andres Ainelo, Julien Caballero-Montes, Ondrej Bulvas, Karin Ernits, Kyo Coppieters't Wallant, Hiraku Takada, Sophie Z. Craig, Gabriel Mazzucchelli, Safia Zedek, Iva Pichova, Gemma C. Atkinson, Ariel Talavera, Chloe Martens, Vasili Hauryliuk, Abel Garcia-Pino
Summary: In this study, the crystal structure of the DarB2:RelNTD2 complex was determined to uncover how DarB interacts with the SYNTH domain of Rel to stimulate (p)ppGpp synthesis directly. Binding to c-di-AMP rigidifies DarB, imposing an entropic penalty that precludes DarB-mediated control of Rel during normal growth. These experiments provide insights into the allosteric regulation mechanism of Rel stringent factors independent of amino acid starvation.
Article
Chemistry, Inorganic & Nuclear
Jonathan Bould, Oleg Tok, William Clegg, Michael G. S. Londesborough, Miroslava Litecka, Marcel Ehn
Summary: The diselenaundecaborate anion, [Se2B9H10]- (1), is obtained in 49% yield from a one-pot reaction involving nido-B10H14, Proton Sponge, and selenium. In solution, compound 1 undergoes a fluxional interchange between symmetry-equivalent positions of its two selenium atoms and open-face 'bridging' hydrogen atom, which is resolved through solid-state boron-11 NMR spectroscopy. Treatment of two equivalents of 1 with HgCl2 leads to the formation of the conjoined binary cluster anion [(Se2B9H10)(SeB9H11)]- (2). This metal-mediated linking of selenaborane clusters has the potential to generate new macropolyhedral heteroborane assemblies.
INORGANICA CHIMICA ACTA
(2023)
Article
Biochemistry & Molecular Biology
Marcel Ehn, Dmytro Bavol, Jonathan Bould, Vojtech Strnad, Miroslava Litecka, Kamil Lang, Kaplan Kirakci, William Clegg, Paul G. Waddell, Michael G. S. Londesborough
Summary: The reaction of AlCl3 with room-temperature tetrachloromethane solutions of anti-B18H22 resulted in the formation of fluorescent isomers, 3,3'-Cl-2-B18H20 and 3,4'-Cl-2-B18H20, with 76% yield. These isomers exhibited stable blue light emission under UV excitation. Other dichlorinated and monochlorinated derivatives, as well as trichlorinated species, were also isolated. The molecular structures and photophysical properties of these chlorinated derivatives were investigated, providing valuable insight into the effect of chlorine substitution on the luminescence of anti-B18H22.
Article
Biochemistry & Molecular Biology
Nozomu Obana, Hiraku Takada, Caillan Crowe-McAuliffe, Mizuki Iwamoto, Artyom A. Egorov, Kelvin J. Y. Wu, Shinobu Chiba, Victoriia Murina, Helge Paternoga, Ben I. C. Tresco, Nobuhiko Nomura, Andrew G. Myers, Gemma C. Atkinson, Daniel N. Wilson, Vasili Hauryliuk
Summary: This study investigates genome-encoded antibiotic resistance ABC proteins from different bacteria and discovers their resistance spectrum and mechanisms, which are important for understanding the diversity of intrinsic antibiotic resistance in bacteria.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Engineering, Environmental
Veljo Kisand, Peeter Laas, Kadi Palmik-Das, Kristel Panksep, Helen Tammert, Leena Albreht, Hille Allemann, Lauri Liepkalns, Katri Vooro, Christian Ritz, Vasili Hauryliuk, Tanel Tenson
Summary: Taking advantage of Estonia's small size and population, a wastewater-based epidemiology approach was used to monitor the spread of SARS-CoV-2, with weekly nation-wide updates released. Results showed that the concentration of the virus in wastewater correlated with the number of COVID-19 infections in the population, and the increase in virus concentration preceded the increase in positive cases by approximately 1.25 weeks (9 days). The surveillance system in Estonia helped inform public health policies and interventions during the COVID-19 pandemic.
Article
Biochemistry & Molecular Biology
Taavi Pall, Hannes Luidalepp, Tanel Tenson, Ulo Maivali
Summary: We evaluated the quality of inferential statistics in the field of differential expression profiling using high-throughput sequencing (HT-seq) by analyzing datasets submitted to the NCBI GEO data repository from 2008 to 2020. Our findings indicate widespread bias and unreliability of statistical methods used to analyze HT-seq data. Only a small percentage of experiments resulted in expected p-value distributions, and many experiments showed indications of differential expression despite assumptions that most genes are not differentially expressed. The choice of differential expression analysis program also influenced the observed patterns.
Article
Microbiology
Anna Maria Giuliodori, Riccardo Belardinelli, Melodie Duval, Raffaella Garofalo, Emma Schenckbecher, Vasili Hauryliuk, Eric Ennifar, Stefano Marzi
Summary: Escherichia coli CspA is an RNA binding protein that stimulates translation, including its own, during cold-shock. It specifically promotes the translation of cspA mRNA at low temperature by interacting with the folded conformation less accessible to the ribosome without inducing large structural rearrangements. This interaction allows the progression of ribosomes during the transition from translation initiation to elongation, and a similar mechanism may be responsible for CspA-dependent translation stimulation observed with other probed mRNAs.
FRONTIERS IN MICROBIOLOGY
(2023)
Article
Multidisciplinary Sciences
Janani Durairaj, Andrew M. Waterhouse, Toomas Mets, Tetiana Brodiazhenko, Minhal Abdullah, Gabriel Studer, Gerardo Tauriello, Mehmet Akdel, Antonina Andreeva, Alex Bateman, Tanel Tenson, Vasili Hauryliuk, Torsten Schwede, Joana Pereira
Summary: The AlphaFold database provides millions of predicted protein structures, covering almost all known proteins. By utilizing deep learning techniques, these structures can be accurately predicted, shedding light on the functions and roles of these proteins in biology. This study further explores the discovery of new protein families through these predicted structures.
Article
Biochemical Research Methods
Lucia Dominguez-Molina, Ariel Talavera, Albinas Cepauskas, Tatsuaki Kurata, Dannele Echemendia-Blanco, Vasili Hauryliuk, Abel Garcia-Pino
Summary: This study reports the production, biophysical analysis, and crystallization of the aTfaRel2/faRel2 operon from Coprobacillus sp. D7, which encodes a bicistronic type II toxin-antitoxin module. The structures of the antitoxin ATfaRel2, toxin FaRel2, and the ATfaRel2-FaRel2 complex were determined through crystallography. These findings provide insights into the structure and function of this TA module.
ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Vladimir Motornov, Radek Pohl, Blanka Klepetarova, Petr Beier
Summary: Elusive N-acyl-1,2,3-triazoles formed by direct acylation of NH-1,2,3-triazoles were isolated and characterized. Thermodynamic N2 isomers were found to be preferred. Direct evidence of interconversion between N1- and N2-acyltriazoles confirmed their usefulness in denitrogenative transformations. An efficient synthesis of enamido triflates from NH-triazoles via N2-acyl-1,2,3-triazole intermediates was developed.
CHEMICAL COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
David Kodr, Erika Kuzmova, Radek Pohl, Tomas Kraus, Michal Hocek
Summary: We designed and synthesized lipid-modified dNTPs, which served as substrates for DNA polymerase and could be incorporated simultaneously into the DNA strand. These lipid-ON probes showed enhanced membrane anchoring efficiency and better stability in the cell membrane compared to commonly studied ON analogues. The probes were detected at the cell surface even after 24 hours, indicating their long-lasting effect.
Article
Chemistry, Multidisciplinary
Anna Kovalova, Vit Prouza, Martin Zavrel, Miroslav Hajek, Rastislav Dzijak, Alzbeta Magdolenova, Radek Pohl, Zdenek Voburka, Kamil Parkan, Milan Vrabel
Summary: This study presents a method for identifying lectin-binding ligands with low micromolar affinity by screening synthetic click glycopeptide libraries. The selected glycopeptides showed enhanced binding potency to the target lectins compared to the starting sugar moieties. This approach offers a promising alternative means of discovering ligands for galectins and other carbohydrate-binding proteins.
