Article
Multidisciplinary Sciences
Clare Pacini, Joshua M. Dempster, Isabella Boyle, Emanuel Goncalves, Hanna Najgebauer, Emre Karakoc, Dieudonne van der Meer, Andrew Barthorpe, Howard Lightfoot, Patricia Jaaks, James M. McFarland, Mathew J. Garnett, Aviad Tsherniak, Francesco Iorio
Summary: This study integrates two large CRISPR-Cas9 screens to correct biases, provide greater statistical power, identify additional biomarkers, and improve the detection of common essential genes, enhancing cancer-specific analyses.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Martin W. Berchtold, Mads Munk, Katarzyna Kulej, Isabel Porth, Lasse Lorentzen, Svetlana Panina, Triantafyllos Zacharias, Martin R. Larsen, Jonas M. la Cour
Summary: The study reveals how the D130G CaM mutation affects the function of CaMKII and its impact on the beating frequency of cardiomyocyte-like cells.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Keai Sinn Tan, Dongfang Wang, Ziqiang Lu, Yihan Zhang, Sixu Li, Yue Lin, Wen Tan
Summary: This study reveals the role of CNPase in the pathophysiological process of heart failure, demonstrating its protective effects on cardiac health through zebrafish and rat models. By modulating CNPase activity, it can mitigate cardiac hypertrophy and fibrosis, maintain mitochondrial function, and provide new therapeutic approaches for treating heart failure.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Chaya T. L. Yuen, Dawn G. L. Thean, Becky K. C. Chan, Peng Zhou, Cynthia C. S. Kwok, Hoi Yee Chu, Maggie S. H. Cheung, Bei Wang, Yee Man Chan, Silvia Y. L. Mak, Anskar Y. Leung, Gigi C. G. Choi, Zongli Zheng, Alan S. L. Wong
Summary: Researchers have enhanced editing accuracy and reduced off-target edits by re-engineering KKH-SaCas9 with a Y239H mutation and a set of additional mutations, demonstrating the feasibility of multi-domain combinatorial mutagenesis to optimize editing fidelity.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Altea Targa, Katherine E. Larrimore, Cheng Kit Wong, Yu Lin Chong, Ronald Fung, Joseph Lee, Hyungwon Choi, Giulia Rancatil
Summary: This research explores the mechanisms of early physiological adaptation and long-term adaptive evolution in cells under stress by generating hypomorphic alleles of the essential nuclear pore complex gene NUP58. The study demonstrates that early physiological adaptation is linked to transcriptome rewiring and upregulation of interacting genes, while long-term adaptation occurs through focal amplification of NUP58 and restoration of mutant protein expression. These findings suggest a model for mimicking targeted drug therapy and dissecting mechanisms of adaptation in human cells.
Review
Immunology
David W. Vredevoogd, Daniel S. Peeper
Summary: Functional genetic screens have identified tumor-intrinsic nodes of immune resistance, revealing various mechanisms by which tumors evade the immune system. However, limitations in capturing tumor heterogeneity have impacted these analyses. This article provides an overview of the nature and sources of heterogeneity that impact tumor-immune interactions and argues that considering tumor heterogeneity is crucial for discovering novel immune evasion mechanisms.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Caiyan Zhao, Yaya Cheng, Pei Huang, Changrong Wang, Weipeng Wang, Mengjiao Wang, Wenbo Shan, Hongzhang Deng
Summary: X-CC9 system enables selective activation of therapeutic agents at tumor sites through X-ray guidance and remote control, leading to M2-to-M1 repolarization within the tumor microenvironment. This strategy significantly improves antitumor efficacy and induces robust immune responses.
ADVANCED MATERIALS
(2023)
Article
Multidisciplinary Sciences
Honghuang Lin, Alan C. Kwan, Cecilia Castro-Diehl, Meghan I. Short, Vanessa Xanthakis, Ibrahim M. Yola, Gerran Salto, Gary F. Mitchell, Martin G. Larson, Ramachandran S. Vasan, Susan Cheng
Summary: The drivers of sexual dimorphism in heart failure phenotypes are poorly understood. This study aimed to assess the heritability and contributions of genetics and environment to cardiac traits and their inter-relations in a large community-based cohort. The results showed significant heritability for all traits in both men and women, with no significant differences between sexes. However, there were differences in the genetic and environmental correlations between cardiac structure and function, suggesting potential pathways for sex-based divergent heart failure phenotypes.
SCIENTIFIC REPORTS
(2023)
Article
Multidisciplinary Sciences
Vanessa Chenouard, Isabelle Leray, Laurent Tesson, Severine Remy, Alasdair Allan, Daniel Archer, Adam Caulder, Agnes Fortun, Karine Bernardeau, Yacine Cherifi, Lydia Teboul, Laurent David, Ignacio Anegon
Summary: CRISPR-Cas9 cleavage efficacy and accuracy are influenced by the optimal formation of the ribonucleoprotein (RNP) complex. The study shows that an equimolar ratio of Cas9 and guide RNA (gRNA) is optimal for RNP complex formation. Increasing the Cas9/gRNA ratio does not improve knock-in (KI) efficiency, and excess gRNA leads to a decrease in point mutation KI efficiency and an increase in large deletions.
Review
Chemistry, Multidisciplinary
Li Duan, Limei Xu, Xiao Xu, Zhuan Qin, Xiaoying Zhou, Yin Xiao, Yujie Liang, Jiang Xia
Summary: Gene vectors deliver genetic materials or gene editing devices into cells for therapeutic protein production or gene correction, but barriers like cell membrane and degradation necessitate carriers for clinical gene therapy. Exosomes, engineered to encapsulate and deliver nucleic acids, and their fusion with liposomes increase loading capacity and maintain targeting capability, showing promise for future gene delivery applications in therapy.
Review
Engineering, Biomedical
Chao Li, Yawei Du, Tongtong Zhang, Haoran Wang, Zhiyong Hou, Yingze Zhang, Wenguo Cui, Wei Chen
Summary: CRISPR/Cas9 is a revolutionary genome editing technology with numerous advantages and great potential in bone and cartilage repair. This review discusses the research status and development trends of CRISPR/Cas9 in bone and cartilage repair.
BIOACTIVE MATERIALS
(2023)
Article
Multidisciplinary Sciences
Rodrigo M. Florentino, Kazutoyo Morita, Nils Haep, Takashi Motomura, Ricardo Diaz-Aragon, Lanuza A. P. Faccioli, Alexandra Collin de l'Hortet, Zeliha Cetin, Carla Frau, Lawrence Vernetti, Anna-Klara Amler, Alexander Thomas, Tobias Lam, Lutz Kloke, Kazuki Takeishi, D. Lansing Taylor, Ira J. Fox, Alejandro Soto-Gutierrez
Summary: Advancements in cellular engineering and gene therapy allow for the production of human tissues with programmable genetically enhanced functions to model and treat specific diseases. This study successfully fabricated synthetic human liver tissues with programmable functions using CRISPR-Cas9 to control gene expression. The engineered liver tissues demonstrated enhanced functions compared to primary liver cells.
Review
Biochemistry & Molecular Biology
Rosette N. Tamaddondoust, Alicia Wong, Megha Chandrashekhar, Edouard I. Azzam, Tommy Alain, Yi Wang
Summary: The biological impact of ionizing radiation on humans depends on both the physical properties and absorbed dose of radiation, as well as the unique susceptibility of the exposed individual. DNA is a critical target of radiation, and the damage response is important for maintaining genomic integrity. Unrepaired DNA lesions can lead to mutations and adverse health effects. Cellular sensitivity to radiation is correlated with the ability to repair DNA lesions, and recent studies have used whole-genome analysis to identify genes that impact individual sensitivity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Microbiology
Remi Hatinguais, Ian Leaves, Gordon D. Brown, Alistair J. P. Brown, Matthias Brock, Roberta Peres da Silva
Summary: This study develops molecular tools for accurate genetic manipulation in Sporothrix species, addressing the paucity of reliable tools for stable genetic engineering. It is of great importance for studying the virulence determinants of sporotrichosis and their roles in disease establishment.
MICROBIOLOGY SPECTRUM
(2023)
Article
Biotechnology & Applied Microbiology
Malgorzata E. Futyma, Yaojie Guo, Casper Hoeck, Jakob B. Hoof, Charlotte H. Gotfredsen, Uffe H. Mortensen, Thomas O. Larsen
Summary: Demand for naturally derived alternatives to synthetic food colorants is increasing, leading to the discovery of two novel yellow natural products homopyrones A and B produced by Aspergillus homomorphus. These compounds are synthesized using cinnamoyl-CoA as the starter unit and represent a rare case of hybrid phenylpropanoid- and polyketide-derived natural products in filamentous fungi.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2021)
Article
Oncology
Astrid Murumagi, Daniela Ungureanu, Suleiman Khan, Mariliina Arjama, Katja Valimaki, Aleksandr Ianevski, Philipp Ianevski, Rebecka Bergstrom, Alice Dini, Anna Kanerva, Riitta Koivisto-Korander, Johanna Tapper, Heini Lassus, Mikko Loukovaara, Andrus Magi, Akira Hirasawa, Daisuke Aoki, Vilja Pietiainen, Teijo Pellinen, Ralf Butzow, Tero Aittokallio, Olli Kallioniemi
Summary: Efforts are being made to develop new therapies for aggressive high-grade serous ovarian cancers (HGSOCs), but the understanding of treatment options for low-grade (LGSOC) or mucinous (MUCOC) ovarian malignancies is lacking. A functional precision oncology (fPO) strategy combining drug testing, genomic profiling and transcriptomic profiling was used to study epithelial ovarian cancers (EOC). Different drug response profiles were observed among HGSOC, LGSOC, and MUCOC PDCs, with LGSOCs responding better to targeted inhibitors. Specific drug responses were identified for each subtype, with potential for individualized therapies in the future.
BRITISH JOURNAL OF CANCER
(2023)
Review
Oncology
Laszlo Lorenzovici, Laszlo Szilberhorn, Szabolcs Farkas-Raduly, Andrea Ildiko Gasparik, Andreea Mihaela Precup, Adel Gyongyver Nagy, Carsten Utoft Niemann, Tero Aittokallio, Zoltan Kalo, Marcell Csanadi
Summary: This study conducted a systematic literature review to summarize the health economic models related to CLL therapies. The review found that Markov modeling is commonly used to simulate cost effectiveness, but recent studies have added more complexity to the models.
Article
Biochemistry & Molecular Biology
Katri Vaparanta, Anne Jokilammi, Ilkka Paatero, Johannes A. Merilahti, Juho Heliste, Karthik Amudhala Hemanthakumar, Riikka Kivela, Kari Alitalo, Pekka Taimen, Klaus Elenius
Summary: In this study, it is demonstrated that Neuregulin-1 (NRG-1) regulates myocardial growth through the STAT5b pathway. Disruption of the NRG-1/ERBB4 pathway or inhibition of Dynamin-2 reduces STAT5b activation and cardiomyocyte hypertrophy. Activation of Stat5 is also observed in NRG-1-induced myocardial growth in zebrafish embryos, and knockdown of stat5b leads to reduced myocardial growth and cardiac function. Furthermore, the NRG-1/ERBB4/STAT5b pathway is differentially regulated in patients with pathological cardiac hypertrophy.
Article
Biochemistry & Molecular Biology
Swapnil Potdar, Filipp Ianevski, Aleksandr Ianevski, Ziaurrehman Tanoli, Krister Wennerberg, Brinton Seashore-Ludlow, Olli Kallioniemi, Paeivi Ostling, Tero Aittokallio, Jani Saarela
Summary: Functional precision medicine (fPM) simplifies the search for appropriate applications of existing molecules and enhances therapeutic potential. The latest version of Breeze (release 2.0) provides advanced data exploration capabilities and interactive visualization options for accurate interpretation of drug sensitivity and resistance data. It allows integration and cross-comparison of user-uploaded data with publicly available drug response datasets.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemical Research Methods
Anni S. S. Halkola, Kaisa Joki, Tuomas Mirtti, Marko M. M. Maekelae, Tero Aittokallio, Teemu D. D. Laajala
Summary: This paper presents a novel methodology for feature subset selection based on the L-0 pseudonorm, which has advantages in clinical applicability, selection of grouped features, and analysis of high-dimensional transcriptomics data. The methodology is benchmarked against existing regularization methods and shows superior performance.
PLOS COMPUTATIONAL BIOLOGY
(2023)
Article
Biology
Johanna Orling, Katri Kosonen, Jenna Villman, Martin Reichard, Ilkka Paatero
Summary: Impaired wound healing associated with aging has significant impacts on human health and healthcare sector. Deficient angiogenesis may contribute to this process, but the underlying biology is still poorly understood due to complexities and costs in using mammalian aging models. In this study, zebrafish and turquoise killifish fin regeneration models were used to investigate aging-related vascular biology of impaired wound healing. The results showed reduced regeneration in the old individuals of both species, accompanied by changes in angiogenesis, vascular density, and expression levels of angiogenesis biomarker VEGF-A. Anti-angiogenic drug SU5416 further reduced regeneration, suggesting the crucial role of angiogenesis in the regeneration of aging caudal fin despite age-related changes in vasculature. These fish fin regeneration models are therefore suitable for studying aging-related decline in wound healing and associated alterations in aging vasculature.
Article
Oncology
Moritz Otte, Johanna Stachelscheid, Markus Glass, Linus Wahnschaffe, Qu Jiang, Waseem Lone, Aleksandr Ianevski, Tero Aittokallio, Javeed Iqbal, Michael Hallek, Stefan Huettelmaier, Alexandra Schrader, Till Braun, Marco Herling
Summary: T-prolymphocytic leukemia (T-PLL) is a rare and poor-prognostic mature T-cell leukemia. Elevated expression of miR-141/200c cluster in T-PLL cells promotes cell proliferation and alters the expression of genes involved in cell survival and differentiation. Low expression of STAT4, a target gene of miR-141/200c, is associated with an immature phenotype of T-PLL cells and shortened overall survival of T-PLL patients. This study reveals the oncogenic role of miR-141/200c-STAT4 signaling pathway in T-PLL, shedding light on the involvement of non-protein-coding genes in the pathogenesis of this devastating disease.
Article
Biology
Chanchanok Duangsri, Tiina A. Salminen, Marion Alix, Sarawan Kaewmongkol, Nattaphong Akrimajirachoote, Wanthanee Khetkorn, Sathaporn Jittapalapong, Pirkko Maenpaa, Aran Incharoensakdi, Wuttinun Raksajit
Summary: Polyhydroxybutyrate (PHB) is a biocompatible and biodegradable polymer with potential applications as a replacement for fossil-derived polymers. The key enzyme for PHB production in Arthrospira platensis is PHA synthase (PhaC). This study constructed recombinant E. cloni ((R))10G cells carrying the A. platensis phaC gene (rPhaC(Ap)) and characterized the catalytic properties and structure of the overexpressed rPhaC(Ap). The obtained model of PhaC(Ap) revealed its asymmetric dimeric structure and the involvement of specific residues in substrate binding and dimerization.
Article
Biochemistry & Molecular Biology
Verneri Virtanen, Kreetta Paunu, Saana Niva, Maria Sundvall, Ilkka Paatero
Summary: Cancer is a significant medical concern and the search for effective treatments continues. This study focuses on caldesmon as a potential novel target for cancer therapy. By analyzing caldesmon mutations in genetically modified zebrafish embryos, the researchers found that these mutations had mild effects on development but altered behavioral responses to light stimuli. Overall, this suggests that caldesmon may be a reasonably well-tolerated target for cancer therapy.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Review
Oncology
Mona Meng Wang, Sarah E. Coupland, Tero Aittokallio, Carlos R. Figueiredo
Summary: Immune checkpoint therapies can enhance the function of anti-tumour T cells and improve outcomes in cancer patients. However, some patients are refractory to this therapy due to "cold" tumours that do not allow T cell generation or the infiltration of existing anti-tumour T cells. This review explores the mechanisms by which cancer cells induce T cell "desertification" and "exclusion" in these refractory tumours, and highlights the importance of developing immunotherapies that restore T cell generation and tumour trafficking.
BRITISH JOURNAL OF CANCER
(2023)
Article
Cardiac & Cardiovascular Systems
Arghavan Jahandideh, Jenni Virta, Xiang-Guo Li, Heidi Liljenback, Olli Moisio, Jesse Ponkamo, Noora Rajala, Marion Alix, Jukka Lehtonen, Mikko I. Mayranpaa, Tiina A. Salminen, Juhani Knuuti, Sirpa Jalkanen, Antti Saraste, Anne Roivainen
Summary: This study successfully demonstrated the feasibility of using [Ga-68]Ga-DOTA-Siglec-9 PET imaging to detect myocardial lesions in rats with autoimmune myocarditis, suggesting its potential as a novel technique.
JOURNAL OF NUCLEAR CARDIOLOGY
(2023)
Article
Oncology
Oxana V. Denisova, Joni Merisaari, Riikka Huhtaniemi, Xi Qiao, Laxman Yetukuri, Mikael Jumppanen, Amanpreet Kaur, Mirva Paakkonen, Carina von Schantz-Fant, Michael Ohlmeyer, Krister Wennerberg, Otto Kauko, Raphael Koch, Tero Aittokallio, Mikko Taipale, Jukka Westermarck
Summary: Mitochondrial glycolysis and hyperactivity of the AKT pathway are characteristic of brain tumors, but targeting AKT or PDK has shown limited clinical benefits. In this study, a triplet therapy targeting AKT, PDK, and PP2A was effective in inducing apoptosis in brain tumor cells. Reactivating PP2A converted the cytostatic response to cytotoxic apoptosis by shutting down compensatory mitochondrial oxidative phosphorylation. These findings suggest the potential of targeting mitochondrial metabolism to overcome therapy tolerance in brain tumors.
MOLECULAR ONCOLOGY
(2023)
Article
Oncology
Verneri Virtanen, Kreetta Paunu, Antti Kukkula, Saana Niva, Ylva Junila, Mervi Toriseva, Terhi Jokilehto, Sari Makela, Riikka Huhtaniemi, Matti Poutanen, Ilkka Paatero, Maria Sundvall
Summary: The downregulation of l-CaD, regulated by GR, reduces the metastatic potential of PCa, both in vitro and in vivo. CALD1 gene is co-expressed with GR and GR activation upregulates l-CaD expression. This indicates that l-CaD is involved in PCa metastasis and its expression is clinically relevant in the development of antiandrogen resistance.
Article
Multidisciplinary Sciences
Paschalis Athanasiadis, Balaguru Ravikumar, Richard J. R. Elliott, John C. Dawson, Neil O. Carragher, Paul A. Clemons, Timothy Johanssen, Daniel Ebner, Tero Aittokallio
Summary: Designing a targeted screening library of bioactive small molecules is a challenging task due to the complexity of compound-protein interactions. In this study, we developed analytic procedures to design anticancer compound libraries that consider factors such as library size, cellular activity, chemical diversity, and target selectivity. The resulting compound collections cover a wide range of protein targets and biological pathways implicated in various cancers, making them valuable for precision oncology. In a pilot screening study, we identified patient-specific vulnerabilities using a physical library of compounds, highlighting the heterogeneity of phenotypic responses across patients and glioblastoma subtypes.
Article
Cardiac & Cardiovascular Systems
Andrew B. Harvey, Renelyn A. Woltes, Raymond N. Deepe, Hannah G. Tarolli, Jenna R. Drummond, Allison Trouten, Auva Zandi, Jeremy L. Barth, Rupak Mukherjee, Martin J. Romeo, Silvia G. Vaena, Ge Tao, Robin Muise-Helmericks, Paula S. Ramos, Russell A. Norris, Andy Wessels
Summary: This study highlights the importance of SOX9 in the regulation of epicardial cell invasion and emphasizes the role of EPDCs in regulating atrioventricular valve development and homeostasis. It also reports a novel expression profile of Cd109, a gene with previously unknown relevance in heart development.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2024)
Review
Cardiac & Cardiovascular Systems
MariaSanta C. Mangione, Jinhua Wen, Dian J. Cao
Summary: mTOR, a mechanistic target of rapamycin, is an evolutionarily conserved pathway that plays a fundamental role in nutrient sensing, growth, metabolism, lifespan, and aging. Recent studies have highlighted the regulatory role of mTOR in innate immune responses and its involvement in the pathogenesis of cardiovascular diseases, especially in acute inflammation and atherosclerotic cardiovascular disease. This review also discusses mTOR's role in trained immunity, immune senescence, and clonal hematopoiesis, as well as its architecture and regulatory complexes.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2024)
Article
Cardiac & Cardiovascular Systems
Junlin Li, Yajun Gong, Yiren Wang, Huihui Huang, Huan Du, Lianying Cheng, Cui Ma, Yongxiang Cai, Hukui Han, Jianhong Tao, Gang Li, Panke Cheng
Summary: Myocardial ischemia-reperfusion injury is closely related to the final infarct size in acute myocardial infarction. Regulatory T cells play an important role in the inflammatory response after AMI, but different subtypes of Tregs have different effects on the injury.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2024)
Article
Cardiac & Cardiovascular Systems
Yuxin Chu, Yutao Hua, Lihao He, Jin He, Yunxi Chen, Jing Yang, Ismail Mahmoud, Fanfang Zeng, Xiaochang Zeng, Gloria A. Benavides, Victor M. Darley-Usmar, Martin E. Young, Scott W. Ballinger, Sumanth D. Prabhu, Cheng Zhang, Min Xie
Summary: This study demonstrates that administering beta-hydroxybutyrate (beta-OHB) at the time of reperfusion can reduce infarct size and preserve cardiac function by activating autophagy and preserving mitochondrial homeostasis, potentially through mTOR inhibition.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2024)