Article
Cell Biology
Shao-Yen Kao, Elena Nikonova, Sabrina Chaabane, Albiona Sabani, Alexandra Martitz, Anja Wittner, Jakob Heemken, Tobias Straub, Maria L. Spletter
Summary: Proper regulation of RNA processing is crucial for muscle development and contractile ability, with RNA binding proteins playing a key role in alternative splicing. Disruption of splicing is associated with muscle diseases and altered by exercise and aging. Drosophila is a valuable model to study the role of RBPs in myogenesis and to investigate the impact of splicing defects on myofibril development.
Article
Cell Biology
Jinghui Liu, Yue Zhao, Daheng He, Katelyn M. Jones, Shan Tang, Derek B. Allison, Yanquan Zhang, Jing Chen, Qiongsi Zhang, Xinyi Wang, Chaohao Li, Chi Wang, Lang Li, Xiaoqi Liu
Summary: Enzalutamide (ENZA), a second-generation androgen receptor antagonist, enhances the efficacy of treatment for metastatic prostate cancer (PCa), but resistance remains a challenge. Through a CRISPR-Cas9 knockout screen, casein kinase 1a (CK1a) has been identified as a therapeutic target to overcome ENZA resistance. Inhibition of CK1a stabilizes ATM and restores DNA-damage response signaling, leading to increased cell death and growth arrest.
CELL REPORTS MEDICINE
(2023)
Article
Chemistry, Multidisciplinary
Laia Miret-Casals, Sander van de Putte, Dorien Aerssens, Julien Diharce, Pascal Bonnet, Annemieke Madder
Summary: In this study, a coiled-coil peptide dimer was used as a model system to investigate the reactivity of furan. Novel cross-link partners of furan warheads for site-specific cross-linking were discovered, and it was demonstrated that the activation of furan could lead to covalently connected coiled-coil motifs. The study also revealed the reaction of the activated furan warhead with cysteine and tyrosine, expanding the versatility of furan cross-link methodology.
FRONTIERS IN CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Bercin K. Cenik, Christie C. Sze, Caila A. Ryan, Siddhartha Das, Kaixiang Cao, Delphine Douillet, Emily J. Rendleman, Didi Zha, Nabiha Haleema Khan, Elizabeth Bartom, Ali Shilatifard
Summary: This study reveals that Set1A/COMPASS and ING5 may play crucial roles in regulating the self-renewal and differentiation status of ESCs.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biology
Jia Li, Xuan Qin, Jie Shi, Xiaoshuang Wang, Tong Li, Mengyao Xu, Xiaosu Chen, Yujia Zhao, Jiahao Han, Yongjun Piao, Wenwen Zhang, Pengpeng Qu, Longlong Wang, Rong Xiang, Yi Shi
Summary: The study identified IL20RA as a key factor in preventing transcoelomic metastasis in ovarian cancer patients through immune signaling, which inhibits the spread of cancer cells.
Review
Genetics & Heredity
Stefano Spada, Brian Luke, Sven Danckwardt
Summary: The integrity of the genome is maintained through a bidirectional coupling between RNA processing and DNA Damage Response, whereby perturbations at one end are compensated by buffering mechanisms at the other end or can even lead to disease initiation.
FRONTIERS IN GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Haiyang Dong, Xi Yang, Lili Wu, Shixin Zhang, Jian Zhang, Pengjuan Guo, Yiwen Du, Changkun Pan, Ying Fu, Lei Li, Jilong Shi, Yanda Zhu, Hongru Ma, Lina Bian, Bingbing Xu, Guo Li, Feng Shi, Jianhua Huang, Haihuai He, Yongfeng Jin
Summary: In this study, the diverse isoforms of Drosophila melanogaster Dscam1 were found to have both redundant and specific roles in neuronal wiring. The self/non-self discrimination of dendrites requires a minimum number of isoforms, while normal axon patterning in certain neurons requires a larger number of isoforms associated with specific clusters or isoforms. The findings suggest a general principle for the role of Dscam1 diversity in neuronal wiring.
Article
Chemistry, Physical
Muhammad Ashfaq, Akbar Ali, Muhammad Nawaz Tahir, Muhammad Khalid, Mohammed A. Assiri, Muhammad Imran, Khurram Shahzad Munawar, Ume Habiba
Summary: Two crystalline schiff bases were synthesized and their crystal structures were confirmed through SC-XRD analysis. Intermolecular interactions were investigated using Hirshfeld surface analysis. DFT calculations provided insights into the geometric parameters, hyper-conjugative transitions, and global reactivity parameters of the compounds. The compounds were found to exhibit excellent non-linear optical properties, making them promising materials for hi-tech optoelectronic applications.
CHEMICAL PHYSICS LETTERS
(2022)
Article
Plant Sciences
Mael Baudin, Eliza C. Martin, Chodon Sass, Jana A. Hassan, Claire Bendix, Rolin Sauceda, Nathan Diplock, Chelsea D. Specht, Andrei J. Petrescu, Jennifer D. Lewis
Summary: The study revealed that naturally occurring polymorphisms in ZAR1 and ZED1 genes can impact Arabidopsis recognition of the P. syringae effector HopZ1a, and that combining natural diversity with functional assays can aid in defining the molecular determinants and interactions necessary to regulate immune induction in response to pathogens.
PLANT CELL AND ENVIRONMENT
(2021)
Article
Cell Biology
Marcus T. Glittenberg, Ilias Kounatidis, Magda Atilano, Petros Ligoxygakis
Summary: Candida infections are being neglected in global public health, and there's a lack of new anti-fungal drugs. Genetic screening of Drosophila genes with human homologues reveals several genes that are crucial for host survival after Candida albicans infection.
DISEASE MODELS & MECHANISMS
(2022)
Article
Immunology
Sandra E. Chaudron, Christine Leemann, Katharina Kusejko, Huyen Nguyen, Nadine Tschumi, Alex Marzel, Michael Huber, Juerg Boeni, Matthieu Perreau, Thomas Klimkait, Sabine Yerly, Alban Ramette, Hans H. Hirsch, Andri Rauch, Alexandra Calmy, Pietro Vernazza, Enos Bernasconi, Matthias Cavassini, Karin J. Metzner, Roger D. Kouyos, Huldrych F. Guenthard
Summary: Studying HIV-1 superinfection is crucial for understanding virus transmission, disease progression, and vaccine development. This study developed a molecular epidemiology screening method using the Swiss HIV Cohort Study, which identified 325 potential HIV-1 superinfections based on phylogenetic reconstruction and distance criteria. Among the tested samples, 52 cases of superinfection were confirmed.
JOURNAL OF INFECTIOUS DISEASES
(2022)
Article
Microbiology
Deeya Saha, Sudip Kundu
Summary: Klebsiella pneumoniae is a major pathogen causing pneumonia and septicemia worldwide, with potential mechanisms of host cell subversion identified in the study. P53 is found to be the most multifunctional host target protein, interacting with other proteins to form a network.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Chemistry, Inorganic & Nuclear
Avishek Majumder, Nityananda Dutta, Sudatta Dey, Priyanka Sow, Asmita Samadder, Gonela Vijaykumar, Krishnan Rangan, Manindranath Bera
Summary: The three discrete [Zn-6] complexes supported by the carboxylate-based multidentate ligand have been successfully synthesized and characterized. Complex 1 showed potential antidiabetic efficacy, while complexes 2 and 3 exhibited promise as chemopreventive drugs against hepatic carcinoma by maintaining hepatic tissue mass and inhibiting DNA damage in hepatic cells.
INORGANIC CHEMISTRY
(2021)
Review
Entomology
Amy Elizabeth Dozier, Edward Alexander Straw, Dara Anne Stanley
Summary: Cuckoo bumblebees are social parasites that depend on host species to complete their life cycle. However, there is still limited knowledge about their fundamental ecology, especially for certain species. Research on cuckoo bumblebees primarily focuses on European species and neglects Asian species. Key research areas such as ecology and behavior have received little attention.
ECOLOGICAL ENTOMOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Yu-Mei Chang, Stephanie Menges, Andreas Westhof, Kerstin Kleinschmidt-Doerr, Christian Brenneis, Andrew A. Pitsillides
Summary: This study found that colony housing of rats may have an impact on OA outcomes, potentially exaggerating pathological changes and strengthening the association between histology and bone micro-CT measures. Additionally, it removes gait differences as a variable in the etiology of OA.
Article
Cell Biology
Dragomir B. Krastev, Shudong Li, Yilun Sun, Andrew Wicks, Gwendoline Hoslett, Daniel Weekes, Luned M. Badder, Eleanor G. Knight, Rebecca Marlow, Mercedes Pardo Calvo, Lu Yu, Tanaji T. Talele, Jiri Bartek, Jyoti Choudhary, Yves Pommier, Stephen J. Pettitt, Andrew Tutt, Kristijan Ramadan, Christopher J. Lord
Summary: The study reveals the regulatory mechanism of trapped PARP1, which is undergoes SUMOylation and ubiquitylation, leading to the recruitment of p97 ATPase for the removal of trapped PARP1 from chromatin and prevention of PARP inhibitor-induced cytotoxicity. Inhibitors targeting p97-complex prolong the trapping of PARP1, enhancing the cytotoxicity of PARP inhibitors in certain types of tumor cells.
NATURE CELL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Jenna Hoersten, Gloria Ruiz-Gomez, Felix Lansing, Teresa Rojo-Romanos, Lukas Theo Schmitt, Jan Sonntag, M. Teresa Pisabarro, Frank Buchholz
Summary: This study discovers that paired mutations targeting residues involved in catalysis can create simple and obligate tyrosine site-specific recombinase (SSR) systems, where catalytic activity is dependent on the binding of all distinct subunits as a heterotetramer. This research improves the recombination specificity of designer-recombinases for therapeutic targets and enhances our understanding of SSR catalysis.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Multidisciplinary Sciences
Felix Lansing, Liliya Mukhametzyanova, Teresa Rojo-Romanos, Kentaro Iwasawa, Masaki Kimura, Maciej Paszkowski-Rogacz, Janet Karpinski, Tobias Grass, Jan Sonntag, Paul Martin Schneider, Ceren Gunes, Jenna Hoersten, Lukas Theo Schmitt, Natalia Rodriguez-Muela, Ralf Knofler, Takanori Takebe, Frank Buchholz
Summary: In this study, a dual designer-recombinase system (RecF8) was developed and shown to efficiently correct the common 140 kb inversion found in patients with severe Hemophilia A.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Sara Vanessa Bernhard, Katarzyna Seget-Trzensiok, Christian Kuffer, Dragomir B. Krastev, Lisa-Marie Stautmeister, Mirko Theis, Kristina Keuper, Jan-Eric Boekenkamp, Maik Kschischo, Frank Buchholz, Zuzana Storchova
Summary: Our study identified 140 genes that when depleted, improved the survival of tetraploid cells. We characterized two of these genes, SPINT2 and USP28, which play roles in regulating CDKN1A transcription and centrosome clustering, respectively. The results suggest that increased mitogenic signaling, establishment of functional bipolar spindles, and reduced DNA damage signaling contribute to the survival of tetraploid cells.
Article
Biochemistry & Molecular Biology
Carla Guillen-Pingarron, Pedro M. Guillem-Gloria, Anjali Soni, Gloria Ruiz-Gomez, Martina Augsburg, Frank Buchholz, Massimiliano Anselmi, M. Teresa Pisabarro
Summary: Protein intrinsically disordered regions (IDRs) play crucial roles in molecular recognition and regulation. By investigating the disordered N-terminal tail of Cre enzyme, the study provides mechanistic insights into the relationship between structural disorder and protein function. The findings offer new understanding of the functional implications of IDRs and their potential applications in biotechnology and genomic medicine.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)
Article
Cell & Tissue Engineering
Pablo Hernandez-Malmierca, Dominik Vonficht, Alexandra Schnell, Hannah J. Uckelmann, Alina Bollhagen, Mohamed A. A. Mahmoud, Sophie-Luise Landua, Elise van der Salm, Christine L. Trautmann, Simon Raffel, Florian Gruenschlaeger, Raphael Lutz, Michael Ghosh, Simon Renders, Nadia Correia, Elisa Donato, Karin O. Dixon, Christoph Hirche, Carolin Andresen, Claudia Robens, Paula S. Werner, Tobias Boch, David Eisel, Wolfram Osen, Franziska Pilz, Adriana Przybylla, Corinna Klein, Frank Buchholz, Michael D. Milsom, Marieke A. G. Essers, Stefan B. Eichmueller, Wolf-Karsten Hofmann, Daniel Nowak, Daniel Huebschmann, Michael Hundemer, Christian Thiede, Lars Bullinger, Carsten Mueller-Tidow, Scott A. Armstrong, Andreas Trumpp, Vijay K. Kuchroo, Simon Haas
Summary: Hematopoietic stem and progenitor cells (HSPCs) can effectively eliminate malignant cells through bidirectional interactions with CD4(+) T cells, thereby preventing the onset of hematological cancers.
Article
Biochemistry & Molecular Biology
Maximilian Clausing, Doreen William, Matthias Preussler, Julia Biedermann, Konrad Gruetzmann, Susan Richter, Frank Buchholz, Achim Temme, Evelin Schroeck, Barbara Klink
Summary: The IDH1(R132H) mutation in glioma leads to the production of the oncometabolite 2-HG and changes in cellular redox balance. The study reveals that targeting the NAD(+) synthesis pathway is a promising therapeutic strategy in IDH mutant gliomas, but the available NAMPT inhibitors are not suitable for this purpose.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Olga Alexandra Sidorova, Shady Sayed, Maciej Paszkowski-Rogacz, Michael Seifert, Aylin Camgoez, Ingo Roeder, Martin Bornhaeuser, Christian Thiede, Frank Buchholz
Summary: DNMT3A mutations are common genetic abnormalities in adult acute myeloid leukemia, and they play a role in leukemic progenitor and stem cell proliferation, as well as AML relapse. Through RNAi screening, we identified MDM4 as a crucial gene for the proliferation of DNMT3A(WT/R882X) AML cells. Inhibition of MDM2/4 using the ALRN-6924 inhibitor can impair the growth of DNMT3A(WT/R882X) primary cells in vitro by inducing cell cycle arrest through upregulation of p53 target genes.
Article
Biology
Li Ding, Lukas Theo Schmitt, Melanie Brux, Duran Sueruen, Martina Augsburg, Felix Lansing, Jovan Mircetic, Mirko Theis, Frank Buchholz
Summary: The expression of promoter-associated sgRNAs and dCas9 fused with KRABd and the transcription repression domain of MeCP2 can lead to long-term gene silencing in mouse embryonic stem cells and human embryonic kidney cells. Surprisingly, this effect is even more pronounced in cells depleted of DNA methyltransferases 3A and 3B.
LIFE SCIENCE ALLIANCE
(2022)
Article
Oncology
Shady Sayed, Olga A. Sidorova, Alexander Hennig, Martina Augsburg, Catherine P. Cortes Vesga, Moustafa Abohawya, Lukas T. Schmitt, Duran Sueruen, Daniel E. Stange, Jovan Mircetic, Frank Buchholz
Summary: In this study, programmable nucleases and base editors were used for targeted therapy of KRAS mutations, and it was found that base editors could more effectively correct KRAS mutations and also repair other cancer-associated mutations. This approach lays the foundation for personalized precision oncology applications.
Article
Oncology
Marta J. Llorca-Cardenosa, Lauren I. Aronson, Dragomir B. Krastev, Jadwiga Nieminuszczy, John Alexander, Feifei Song, Malgorzata Dylewska, Ronan Broderick, Rachel Brough, Astrid Zimmermann, Frank T. Zenke, Bora Gurel, Ruth Riisnaes, Ana Ferreira, Theodoros Roumeliotis, Jyoti Choudhary, Stephen J. Pettitt, Johann de Bono, Andres Cervantes, Syed Haider, Wojciech Niedzwiedz, Christopher J. Lord, Irene Y. Chong
Summary: The study highlights the potential issue of drug resistance in using ATR inhibitors in gastric cancer, particularly with loss-of-function mutations in SMG8 and SMG9, and suggests that targeting these pathways may enhance the overall effectiveness of ATRi.
Article
Multidisciplinary Sciences
Lukas Theo Schmitt, Maciej Paszkowski-Rogacz, Florian Jug, Frank Buchholz
Summary: The authors present RecGen, an algorithm for generating designer-recombinases, which was experimentally validated to predict recombinase sequences. This algorithm can accelerate the development of future designer-recombinases, providing a significant contribution to genome engineering.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Milica Jelicic, Lukas Theo Schmitt, Maciej Paszkowski-Rogacz, Angelika Walder, Nadja Schubert, Jenna Hoersten, Duran Sueruen, Frank Buchholz
Summary: This study develops a systematic computational workflow for annotating putative tyrosine-type site-specific recombinase (Y-SSR) systems and identifies and characterizes eight new naturally occurring Cre-type SSR systems. The activity of these systems is tested in bacterial and mammalian cells, and selectivity profiles are established for both new and established Cre-type SSRs. Potential pseudo-sites and off-targets for Y-SSRs in the human and mouse genome are also identified, providing valuable information for future genome surgery applications.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Oncology
Daniel Martin Klotz, Franziska Maria Schwarz, Anna Dubrovska, Kati Schuster, Mirko Theis, Alexander Krueger, Oliver Kutz, Theresa Link, Pauline Wimberger, Stephan Drukewitz, Frank Buchholz, Juergen Thomale, Jan Dominik Kuhlmann
Summary: We established an in vitro model for PARPi-resistant ovarian cancer and found that PARPi-resistant cells exhibit broad cross-resistance to other PARPis and chemotherapeutic drugs regardless of the BRCA1 status. Co-culture experiments showed that PARPi-resistant cells have a disadvantage in proliferation under drug-free conditions but quickly gain dominance under olaparib selection pressure, which can be blocked by ABC-transporter protein inhibitors. Overall, our well-characterized in vitro model is useful for dissecting mechanisms of PARPi resistance and studying the clonal dynamics of PARPi-resistant cells.
Article
Biotechnology & Applied Microbiology
Lukas Theo Schmitt, Aksana Schneider, Jonas Posorski, Felix Lansing, Milica Jelicic, Manavi Jain, Shady Sayed, Frank Buchholz, Duran Sueruen
Summary: DEQSeq is a nanopore sequencing approach that enables the rational selection of favorable genome editing enzymes from directed molecular evolution experiments. It streamlines the process of identifying valuable variants for further study and application by capturing full-length sequences, editing efficiencies, and specificities from thousands of evolved enzymes simultaneously.
