Article
Cell Biology
Zhe Feng, Suho Lee, Bowen Jia, Tao Jian, Eunjoon Kim, Mingjie Zhang
Summary: The scaffold protein IRSp53 plays an important role in synapse development and synaptic plasticity. This study reveals that specific interactions between IRSp53 and its binding partners PSD-95 or Shank3 drive phase separation of complexes and promote synaptic enrichment of IRSp53 in mouse cortical neurons. The study also highlights the role of IRSp53 in actin filament formation and synaptic maturation. These findings provide mechanistic insights into the physiological roles of IRSp53 in synapse formation and function.
JOURNAL OF CELL BIOLOGY
(2022)
Article
Microbiology
Alejandro Huerta-Saquero, Itziar Chapartegui-Gonzalez, Sarah Bowser, Nittaya Khakhum, Jacob L. Stockton, Alfredo G. Torres
Summary: This study demonstrates the potential of using P22 viral-like particles as nanocontainers for delivering immunogenic proteins of enterohemorrhagic Escherichia coli (EHEC) and creating effective vaccines against EHEC infections. The EscC-P22 particles were able to induce specific antibodies in mice, enhance phagocytic activity against EHEC, and reduce bacterial adherence to epithelial cells, indicating their functionality. These findings suggest that EscC-P22-based particles could be a promising nanovaccine candidate for immunization against EHEC O157:H7 infections.
MICROBIOLOGY SPECTRUM
(2023)
Article
Microbiology
Lang Peng, Rexford Mawunyo Dumevi, Marco Chitto, Nadja Haarmann, Petya Berger, Gerald Koudelka, Herbert Schmidt, Alexander Mellmann, Ulrich Dobrindt, Michael Berger
Summary: This study proposes a new method for genetic manipulation of enterohemorrhagic Escherichia coli (EHEC) that is more efficient than traditional methods. The method increases recombineering efficiency by 3-4 times in EHEC O157:H7 EDL933 Delta stx1/2, but shows similar efficiency in Escherichia coli K-12 MG1655. Additionally, the study suggests that the inhibition of the RecFOR pathway indirectly blocks phage induction and improves recombineering efficiency.
Article
Biochemistry & Molecular Biology
Natasha S. Clayton, Millie Fox, Jose J. Vicente-Garcia, Courtney M. Schroeder, Trevor D. Littlewood, Jonathon Wilde, Kadalmani Krishnan, Murray J. B. Brown, Claire Crafter, Helen R. Mott, Darerca Owen
Summary: Activated Cdc42-associated kinase (ACK) phosphorylates PI3K regulatory subunits, promoting cell proliferation. ACK interacts with p85 alpha in nuclear-enriched cell fractions, facilitating dimerization of the regulatory subunits.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Review
Gastroenterology & Hepatology
Lingyan Jiang, Wen Yang, Xinlei Jiang, Ting Yao, Lu Wang, Bin Yang
Summary: EHEC O157 carries 177 unique genomic islands, termed O islands, which play a crucial role in its pathogenicity by providing virulence factors, effectors, and regulatory proteins.
Review
Food Science & Technology
Xiaoyan Zhao, Yeting Sun, Yue Ma, Yujia Xu, Hongyang Guan, Dan Wang
Summary: Enterohemorrhagic Escherichia coli (EHEC) is a major bacterial pathogen that can survive in food such as meat and vegetables. Understanding the impact of vegetable characteristics on the adhesion and proliferation processes of EHEC is important for developing control measures. This review discusses the amount, methods, and pathways of adhesion, as well as the proliferation and biofilm formation processes of EHEC during vegetable contamination. Factors such as vegetable types, cultivars, tissue characteristics, and damage levels can affect EHEC adhesion on vegetables.
CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION
(2022)
Article
Veterinary Sciences
Delphine Bibbal, Philippe Ruiz, Panagiotis Sapountzis, Christine Mazuy-Cruchaudet, Estelle Loukiadis, Frederic Auvray, Evelyne Forano, Hubert Brugere
Summary: This study aimed to identify farms with persistent circulation of EHEC O157:H7 in cattle. The results showed that persistent circulation may be due to the presence of a few predominant strains or repeated exposure of cattle to various strains. In addition, differences were found in the fecal microbial communities of shedders and non-shedders, with different bacterial indicators identified.
FRONTIERS IN VETERINARY SCIENCE
(2022)
Article
Multidisciplinary Sciences
Kazuki Kato, Sae Okazaki, Cian Schmitt-Ulms, Kaiyi Jiang, Wenyuan Zhou, Junichiro Ishikawa, Yukari Isayama, Shungo Adachi, Tomohiro Nishizawa, Kira S. Makarova, Eugene V. Koonin, Omar O. Abudayyeh, Jonathan S. Gootenberg, Hiroshi Nishimasu
Summary: The type III-E CRISPR-Cas7-11 effector can catalyze crRNA-guided RNA cleavage by binding crRNA and Csx29, and the binding of tgRNA induces conformational changes in Csx29. Csx29 cleaves Csx30 through a tgRNA-dependent pathway, resulting in the generation of toxic protein fragments and growth arrest, which is regulated by Csx31. Csx30 modulates the cellular response to infection by binding Csx31 and the associated sigma factor RpoE. Additionally, the Cas7-11-Csx29-Csx30 system has been engineered for programmable RNA sensing in mammalian cells.
Article
Microbiology
Joshua L. Cherry
Summary: Enterohemorrhagic E. coli (EHEC) is a major cause of human illness, death, and economic loss. Understanding the genetic changes in EHEC and its source of contamination is crucial for effective mitigation. Through whole-genome sequencing, it was found that EHEC experienced genetic changes mainly in adhesion-related sequences, potentially leading to altered adhesive properties and increased virulence. This pattern of genetic change may help identify other bacteria threatening human health. Additionally, the presence of a mutation affecting arsenic resistance regulation suggests an arsenic-contaminated groundwater as the persistent source of contamination. This observation can aid in locating the reservoir of EHEC.
MICROBIOLOGY SPECTRUM
(2022)
Article
Food Science & Technology
So Young Yang, Ki Sun Yoon
Summary: Listeria monocytogenes and Entero-hemorrhagic Escherichia coli (EHEC) can survive in refrigerated yogurt. The risk of L. monocytogenes and EHEC due to yogurt consumption was estimated using predictive survival models. The results show that the foodborne illness risk from L. monocytogenes and EHEC due to yogurt consumption is very low, but controlling the initial contamination level of EHEC during yogurt manufacture should be emphasized.
Article
Multidisciplinary Sciences
Anthony Davidson, Peter J. Hume, Nicholas P. Greene, Vassilis Koronakis
Summary: Salmonella Typhimurium uses effector proteins to reorganize the actin cytoskeleton and enter non-phagocytic host cells. N-WASP, a host actin regulator, plays a role in bacterial entry. However, the activation of N-WASP by Cdc42 inhibits Salmonella uptake. Later in invasion, the effector SopA interferes with this inhibitory pathway, allowing Salmonella to enter the host cells. This study suggests that the Cdc42-N-WASP signaling pathway may actually be used to limit the entry of multiple pathogens.
Review
Cell Biology
Mehrnaz Mehrabipour, Neda S. Kazemein Jasemi, Radovan Dvorsky, Mohammad R. Ahmadian
Summary: SRC homology 3 (SH3) domains are modular building blocks that facilitate the assembly of protein complexes through interactions with proline-rich/noncanonical motifs. They have been extensively studied across different life kingdoms and viruses, playing roles in various biological processes. Additionally, SH3 domains are implicated in the development of human diseases and are potential drug targets. This review summarizes the classification of SH3 domain functions, their binding specificity, and their significance in disease research.
Article
Cell Biology
Vladimir Baytshtok, Xue Fei, Tsai-Ting Shih, Robert A. Grant, Justin C. Santos, Tania A. Baker, Robert T. Sauer
Summary: At low temperatures, protein degradation by the AAA+ HslUV protease is slow due to residues in the intermediate domain of the HslU(6) unfoldase blocking the axial channel, preventing substrate binding and degradation until heat-induced melting of this autoinhibitory plug activates HslUV proteolysis through a model supported by biochemical experiments with wild-type and mutant enzymes.
Article
Biochemistry & Molecular Biology
Jun-Young Park, Cheorl-Ho Kim, Seung-Hak Cho
Summary: In this study, we developed a FimH inhibitor to prevent adhesion of enterohemorrhagic Escherichia coli on human intestinal epithelium during the early stage of infection. By investigating the ligand binding domain of FimH and analyzing its evolutionary characteristics, we identified a potential drug target and found that glycan-like peptides can serve as initial infection inhibitors.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Food Science & Technology
Yansong Xue, Mei-Jun Zhu
Summary: This article discusses how enterohemorrhagic Escherichia coli (EHEC), specifically E. coli O157:H7, hijacks the host immune system and interferes with host signaling pathways. It also highlights the promising role of bioactive compounds derived from food and probiotics in harnessing host innate immunity and eliminating E. coli O157:H7 infection with multiple strategies.
CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION
(2023)
Article
Virology
Zhe Zhao, Riku Fagerlund, Andreas S. Baur, Kalle Saksela
Summary: The study reveals that HIV-1 Nef protein promotes the loading of TACE into extracellular vesicles by triggering unconventional secretion via activation of the Hck/Raf/mitogen-activated protein kinase (MAPK) cascade. Several pharmaceutical inhibitors of these kinases currently in clinical use for other diseases could potentially suppress this pathogenic deregulation, offering a novel strategy for treating HIV-associated immune activation.
JOURNAL OF VIROLOGY
(2021)
Article
Multidisciplinary Sciences
Rogelio A. Hernandez-Lopez, Wei Yu, Katelyn A. Cabral, Olivia A. Creasey, Maria Del Pilar Lopez Pazmino, Yurie Tonai, Arsenia De Guzman, Anna Makela, Kalle Saksela, Zev J. Gartner, Wendell A. Lim
Summary: The study engineered a two-step positive-feedback circuit that enables human cytotoxic T cells to discriminate targets based on a sigmoidal antigen-density threshold. This circuit involves a low-affinity synthetic Notch receptor controlling the expression of a high-affinity CAR, leading to sharp discrimination between cancer cells and normal cells based on antigen density.
Article
Environmental Sciences
Tareq Hussein, Jakob Londahl, Sara Thuresson, Malin Alsved, Afnan Al-Hunaiti, Kalle Saksela, Hazem Aqel, Heikki Junninen, Alexander Mahura, Markku Kulmala
Summary: The study examined the indoor transmission of the novel coronavirus from an infected person to a susceptible person, assessing the potential inhaled dose rate of particles. Ventilation rates were found to have a significant impact on virus transmission, with higher rates of transmission in poorly ventilated spaces.
INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH
(2021)
Article
Microbiology
Juuso Rusanen, Lauri Kareinen, Leonora Szirovicza, Hasan Ugurlu, Lev Levanov, Anu Jaaskelainen, Maarit Ahava, Satu Kurkela, Kalle Saksela, Klaus Hedman, Olli Vapalahti, Jussi Hepojoki
Summary: The study presented a fast and simple assay principle for antigen detection, which demonstrated high sensitivity and specificity in detecting SARS-CoV-2 antigens in nasopharyngeal swabs. The method is based on time-resolved Forster resonance energy transfer (TR-FRET) for detecting SARS-CoV-2 nucleocapsid protein (NP) and spike protein (SP).
Article
Clinical Neurology
Joni V. Lindbohm, Nina Mars, Keenan A. Walker, Archana Singh-Manoux, Gill Livingston, Eric J. Brunner, Pyry N. Sipila, Kalle Saksela, Jane E. Ferrie, Ruth C. Lovering, Stephen A. Williams, Aroon D. Hingorani, Rebecca F. Gottesman, Henrik Zetterberg, Mika Kivimaki
Summary: This study identified 15 plasma proteins associated with cognitive decline and dementia, which were consistently identified in both cohorts and not explained by known dementia risk factors. Six of these proteins have levels that can be modified by currently approved medications for other conditions in dementia-free individuals.
ALZHEIMERS & DEMENTIA
(2022)
Article
Virology
Ravi Kant, Lauri Kareinen, Teemu Smura, Tobias L. Freitag, Sawan Kumar Jha, Kari Alitalo, Seppo Meri, Tarja Sironen, Kalle Saksela, Tomas Strandin, Anja Kipar, Olli Vapalahti
Summary: Common laboratory mice are not susceptible to wild-type SARS-CoV-2, but can be infected with mouse-adapted virus strains that contain key mutations similar to those found in naturally occurring variants of concern. The SARS-CoV-2 beta variant was shown to be infectious to BALB/c mice, causing pulmonary changes within 2-3 days post infection, indicating that these mice could serve as a suitable model for evaluating COVID-19 countermeasures.
Article
Microbiology
Zhe Zhao, Riku Fagerlund, Helena Tossavainen, Kristina Hopfensperger, Rishikesh Lotke, Smitha Srinivasachar Badarinarayan, Frank Kirchhoff, Perttu Permi, Kei Sato, Daniel Sauter, Kalle Saksela
Summary: The accessory protein Nef of HIV and SIV interacts with cellular protein kinases and signaling proteins through a canonical SH3 binding motif. The study shows that Nef proteins have evolved a structural strategy called the R-clamp to facilitate salt bridge formation. Evolutionarily diverse Nef proteins exhibit different R-clamp designs, indicating a high level of diversity in the evolution of primate lentiviral proteins.
Article
Pharmacology & Pharmacy
Senem Merve Fred, Suvi Kuivanen, Hasan Ugurlu, Plinio Cabrera Casarotto, Lev Levanov, Kalle Saksela, Olli Vapalahti, Eero Castren
Summary: Repurposing currently available drugs is a valuable strategy against the consequences of COVID-19. A study tested the inhibitory effects of various antidepressants and antipsychotic drugs on SARS-CoV-2 and its variants, finding that some of these drugs were effective in inhibiting viral infection with minimal impact on cell viability.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Helena Tossavainen, Hasan Ugurlu, Mikael Karjalainen, Maarit Hellman, Lina Antenucci, Riku Fagerlund, Kalle Saksela, Perttu Permi
Summary: This study reveals the relationship between Class I SH3 domain-binding motifs and specificity, showing the evolutionary mechanism of nsP3 to acquire stronger affinity by comparing and analyzing the structure of SNX9 SH3 with EEEV nsP3.
Article
Immunology
Laura Lahdentausta, Anne Kivimaki, Lotta Oksanen, Marika Tallgren, Sampo Oksanen, Enni Sanmark, Aino Salminen, Ahmed Geneid, Mikko Sairanen, Susanna Paju, Kalle Saksela, Pirkko Pussinen, Milla Pietiainen
Summary: This study examined the usefulness of dried spot blood and saliva samples in analyzing SARS-CoV-2 antibodies. The results showed that the level of exposure was the strongest determinant of all blood antibody classes and saliva IgG. Both blood and saliva IgG levels followed similar trends to the exposures reported in the questionnaires. Self-collected dry blood and saliva spot samples combined with the GSP/DELFIA technique are valuable tools for investigating an individual's immune response to SARS-CoV-2 exposure or vaccination. Saliva IgG has high potential to monitor vaccination response wane.
MEDICAL MICROBIOLOGY AND IMMUNOLOGY
(2022)
Article
Biology
Dovydas Gecys, Arunas Kazlauskas, Emilija Gecyte, Neringa Pauziene, Deimante Kulakauskiene, Indre Lukminaite, Aiste Jekabsone
Summary: This study explores the potential of genetically engineered extracellular vesicles to improve drug delivery in glioblastoma cells. The results show that introducing the RGD ligand significantly increases the internalisation of extracellular vesicles by GBM cells, leading to improved drug delivery efficacy.
Article
Immunology
Tobias L. Freitag, Riku Fagerlund, Nihay Laham Karam, Veli-Matti Leppanen, Hasan Ugurlu, Ravi Kant, Petri Makinen, Ahmed Tawfek, Sawan Kumar Jha, Tomas Strandin, Katarzyna Leskinen, Jussi Hepojoki, Tapio Kesti, Lauri Kareinen, Suvi Kuivanen, Emma Koivulehto, Aino Sormunen, Svetlana Laidinen, Ayman Khattab, Paivi Saavalainen, Seppo Meri, Anja Kipar, Tarja Sironen, Olli Vapalahti, Kari Alitalo, Seppo Yla-Herttuala, Kalle Saksela
Summary: Intranasal administration of adenoviral vector vaccines can induce mucosal immunity and protect mice from SARS-CoV-2 infection, supporting the potential of this approach for preventing transmission of the virus.
Article
Multidisciplinary Sciences
Anna R. Maekelae, Hasan Ugurlu, Liina Hannula, Ravi Kant, Petja Salminen, Riku Fagerlund, Sanna Maeki, Anu Haveri, Tomas Strandin, Lauri Kareinen, Jussi Hepojoki, Suvi Kuivanen, Lev Levanov, Arja Pasternack, Rauno A. Naves, Olli Ritvos, Pamela oesterlund, Tarja Sironen, Olli Vapalahti, Anja Kipar, Juha T. Huiskonen, Ilona Rissanen, Kalle Saksela
Summary: The authors describe a small antibody-like protein, TriSb92, that can prevent infection by diverse SARS-CoV-2 variants. In cell culture and mice, intranasal treatment with TriSb92 before or shortly after exposure to the virus showed protective effects. This highly manufacturable and stable trimeric antibody-mimetic has the potential to be used as a nasal spray for protecting susceptible individuals from SARS-CoV-2 infection.
NATURE COMMUNICATIONS
(2023)
Article
Biochemical Research Methods
Aino Sormunen, Emma Koivulehto, Kari Alitalo, Kalle Saksela, Nihay Laham-Karam, Seppo Ylae-Herttuala
Summary: Traditional Western blotting is commonly used in biological research but has issues with time and reproducibility. Automation, including semi-automated and fully automated systems, offers time-saving and sensitivity advantages. However, the cost of devices and reagents is a downside. Nevertheless, automation can be beneficial for increasing output and facilitating sensitive protein analyses.
METHODS AND PROTOCOLS
(2023)
Article
Endocrinology & Metabolism
Mikael Knip, Anna Parviainen, Maaret Turtinen, Anna But, Taina Harkonen, Jussi Hepojoki, Tarja Sironen, Rommel Iheozor-Ejiofor, Hasan Ugurlu, Kalle Saksela, Johanna Lempainen, Jorma Ilonen, Olli Vapalahti
Summary: An observational cohort study in Finland found that the incidence of type 1 diabetes among children under 15 years old significantly increased during the COVID-19 pandemic. This increase may be attributed to the effects of lockdown and physical distancing, rather than a direct effect of SARS-CoV-2 infection.
LANCET DIABETES & ENDOCRINOLOGY
(2023)