On the impact of incomplete taxon sampling on the relative timing of gene transfer events
by Mois ès Bernabeu, Saioa Manzano-Morales, Toni Gabaldón A recent study questioned the use of branch length methods to assess the relative timing of horizontal gene transfers because of the effects of so-called “ghost” lineages. This Formal Comment discusses key considerations regarding the potential effect of missing lineages when assessing relative timing of evolutionary events. (Source: PLoS Biology: Archived Table of Contents)
Source: PLoS Biology: Archived Table of Contents - March 18, 2024 Category: Biology Authors: Mois ès Bernabeu Source Type: research

The evolutionary safety of mutagenic drugs should be assessed before drug approval
by Gabriela Lobinska, Vyacheslav Tretyachenko, Orna Dahan, Martin A. Nowak, Yitzhak Pilpel Some drugs increase the mutation rate of their target pathogen, a potentially concerning mechanism as the pathogen might evolve faster toward an undesired phenotype. We suggest a four-step assessment of evolutionary safety for the approval of such treatments. Some drugs increase the mutation rate of their target pathogen, raising the concern that they might thereby increase the pathogen ’s rate of adaptation. This Perspective article proposes a four-step process to evaluate the evolutionary safety of new treatments, calling on re...
Source: PLoS Biology: Archived Table of Contents - March 15, 2024 Category: Biology Authors: Gabriela Lobinska Source Type: research

Engineering of Cas12a nuclease variants with enhanced genome-editing specificity
by Peng Chen, Jin Zhou, Huan Liu, Erchi Zhou, Boxiao He, Yankang Wu, Hongjian Wang, Zaiqiao Sun, Chonil Paek, Jun Lei, Yongshun Chen, Xinghua Zhang, Lei Yin The clustered regularly interspaced short palindromic repeat (CRISPR)-Cas12a system is a powerful tool in gene editing; however, crRNA-DNA mismatches might induce unwanted cleavage events, especially at the distal end of the PAM. To minimize this limitation, we engineered a hyper fidelity AsCas12a variant carrying the mutations S186A/R301A/T315A/Q1014A/K414A (termed HyperFi-As) by modifying amino acid residues interacting with the target DNA and crRNA strand. HyperFi-...
Source: PLoS Biology: Archived Table of Contents - March 14, 2024 Category: Biology Authors: Peng Chen Source Type: research

Developing inhibitory peptides against SARS-CoV-2 envelope protein
by Ramsey Bekdash, Kazushige Yoshida, Manoj S. Nair, Lauren Qiu, Johnathan Ahdout, Hsiang-Yi Tsai, Kunihiro Uryu, Rajesh K. Soni, Yaoxing Huang, David D. Ho, Masayuki Yazawa Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has affected approximately 800 million people since the start of the Coronavirus Disease 2019 (COVID-19) pandemic. Because of the high rate of mutagenesis in SARS-CoV-2, it is difficult to develop a sustainable approach for prevention and treatment. The Envelope (E) protein is highly conserved among human coronaviruses. Previous studies reported that SARS-CoV-1 E deficiency reduced viral pro...
Source: PLoS Biology: Archived Table of Contents - March 14, 2024 Category: Biology Authors: Ramsey Bekdash Source Type: research

Low-cost, versatile, and highly reproducible microfabrication pipeline to generate 3D-printed customised cell culture devices with complex designs
by Cathleen Hagemann, Matthew C. D. Bailey, Eugenia Carraro, Ksenia S. Stankevich, Valentina Maria Lionello, Noreen Khokhar, Pacharaporn Suklai, Carmen Moreno-Gonzalez, Kelly O ’Toole, George Konstantinou, Christina L. Dix, Sudeep Joshi, Eleonora Giagnorio, Mads S. Bergholt, Christopher D. Spicer, Albane Imbert, Francesco Saverio Tedesco, Andrea Serio Cell culture devices, such as microwells and microfluidic chips, are designed to increase the complexity of cell-based models while retaining control over culture conditions and have become indispensable platforms for biological systems modelling. From microtopography, mic...
Source: PLoS Biology: Archived Table of Contents - March 13, 2024 Category: Biology Authors: Cathleen Hagemann Source Type: research

Neuronal ageing is promoted by the decay of the microtubule cytoskeleton
by Pilar Okenve-Ramos, Rory Gosling, Monika Chojnowska-Monga, Kriti Gupta, Samuel Shields, Haifa Alhadyian, Ceryce Collie, Emilia Gregory, Natalia Sanchez-Soriano Natural ageing is accompanied by a decline in motor, sensory, and cognitive functions, all impacting quality of life. Ageing is also the predominant risk factor for many neurodegenerative diseases, including Parkinson ’s disease and Alzheimer’s disease. We need to therefore gain a better understanding of the cellular and physiological processes underlying age-related neuronal decay. However, gaining this understanding is a slow process due to the large amoun...
Source: PLoS Biology: Archived Table of Contents - March 13, 2024 Category: Biology Authors: Pilar Okenve-Ramos Source Type: research

Specification of distinct cell types in a sensory-adhesive organ important for metamorphosis in tunicate larvae
by Christopher J. Johnson, Florian Razy-Krajka, Fan Zeng, Katarzyna M. Piekarz, Shweta Biliya, Ute Rothb ächer, Alberto Stolfi The papillae of tunicate larvae contribute sensory, adhesive, and metamorphosis-regulating functions that are crucial for the biphasic lifestyle of these marine, non-vertebrate chordates. We have identified additional molecular markers for at least 5 distinct cell types in the papillae of the model tunicateCiona, allowing us to further study the development of these organs. Using tissue-specific CRISPR/Cas9-mediated mutagenesis and other molecular perturbations, we reveal the roles of key transcr...
Source: PLoS Biology: Archived Table of Contents - March 13, 2024 Category: Biology Authors: Christopher J. Johnson Source Type: research

Polyphosphate kinase regulates LPS structure and polymyxin resistance during starvation in < i > E < /i > . < i > coli < /i >
by Kanchi Baijal, Iryna Abramchuk, Carmen M. Herrera, Thien-Fah Mah, M. Stephen Trent, Mathieu Lavall ée-Adam, Michael Downey Polyphosphates (polyP) are chains of inorganic phosphates that can reach over 1,000 residues in length. InEscherichia coli, polyP is produced by the polyP kinase (PPK) and is thought to play a protective role during the response to cellular stress. However, the molecular pathways impacted by PPK activity and polyP accumulation remain poorly characterized. In this work, we used label-free mass spectrometry to study the response of bacteria that cannot produce polyP ( Δppk) during starvation to ide...
Source: PLoS Biology: Archived Table of Contents - March 13, 2024 Category: Biology Authors: Kanchi Baijal Source Type: research

Recommendations for measuring and standardizing light for laboratory mammals to improve welfare and reproducibility in animal research
by Robert J. Lucas, Annette E. Allen, George C. Brainard, Timothy M. Brown, Robert T. Dauchy, Altug Didikoglu, Michael Tri H. Do, Brianna N. Gaskill, Samer Hattar, Penny Hawkins, Roelof A. Hut, Richard J. McDowell, Randy J. Nelson, Jan-Bas Prins, Tiffany M. Schmidt, Joseph S. Takahashi, Vandana Verma, Vootele Voikar, Sara Wells, Stuart N. Peirson Light enables vision and exerts widespread effects on physiology and behavior, including regulating circadian rhythms, sleep, hormone synthesis, affective state, and cognitive processes. Appropriate lighting in animal facilities may support welfare and ensure that animals enter e...
Source: PLoS Biology: Archived Table of Contents - March 12, 2024 Category: Biology Authors: Robert J. Lucas Source Type: research

Synaptic and dendritic architecture of different types of hippocampal somatostatin interneurons
by Vir ág Takács, Zsuzsanna Bardóczi, Áron Orosz, Abel Major, Luca Tar, Péter Berki, Péter Papp, Márton I. Mayer, Hunor Sebők, Luca Zsolt, Katalin E. Sos, Szabolcs Káli, Tamás F. Freund, Gábor Nyiri GABAergic inhibitory neurons fundamentally shape the activity and plasticity of cortical circuits. A major subset of these neurons contains somatostatin (SOM); these cells play crucial roles in neuroplasticity, learning, and memory in many brain areas including the hippocampus, and are implicated in several neuropsychiatric diseases and neurodegenerative disorders. Two main types of SOM-containing cells in area CA1 ...
Source: PLoS Biology: Archived Table of Contents - March 12, 2024 Category: Biology Authors: Vir ág Takács Source Type: research

Noncanonical and reversible cysteine ubiquitination prevents the overubiquitination of PEX5 at the peroxisomal membrane
by T ânia Francisco, Ana G. Pedrosa, Tony A. Rodrigues, Tarad Abalkhail, Hongli Li, Maria J. Ferreira, Gerbrand J. van der Heden van Noort, Marc Fransen, Ewald H. Hettema, Jorge E. Azevedo PEX5, the peroxisomal protein shuttling receptor, binds newly synthesized proteins in the cytosol and transports them to the organelle. During its stay at the peroxisomal protein translocon, PEX5 is monoubiquitinated at its cysteine 11 residue, a mandatory modification for its subsequent ATP-dependent extraction back into the cytosol. The reason why a cysteine and not a lysine residue is the ubiquitin acceptor is unknown. Using an esta...
Source: PLoS Biology: Archived Table of Contents - March 12, 2024 Category: Biology Authors: T ânia Francisco Source Type: research

Attention to audiovisual speech shapes neural processing through feedback-feedforward loops between different nodes of the speech network
by Patrik Wikman, Viljami Salmela, Eetu Sj öblom, Miika Leminen, Matti Laine, Kimmo Alho Selective attention-related top-down modulation plays a significant role in separating relevant speech from irrelevant background speech when vocal attributes separating concurrent speakers are small and continuously evolving. Electrophysiological studies have shown that such top-down modulation enhances neural tracking of attended speech. Yet, the specific cortical regions involved remain unclear due to the limited spatial resolution of most electrophysiological techniques. To overcome such limitations, we collected both electroence...
Source: PLoS Biology: Archived Table of Contents - March 11, 2024 Category: Biology Authors: Patrik Wikman Source Type: research

Widespread prevalence of a methylation-dependent switch to activate an essential DNA damage response in bacteria
by Aditya Kamat, Ngat T. Tran, Mohak Sharda, Neha Sontakke, Tung B. K. Le, Anjana Badrinarayanan DNA methylation plays central roles in diverse cellular processes, ranging from error-correction during replication to regulation of bacterial defense mechanisms. Nevertheless, certain aberrant methylation modifications can have lethal consequences. The mechanisms by which bacteria detect and respond to such damage remain incompletely understood. Here, we discover a highly conserved but previously uncharacterized transcription factor (Cada2), which orchestrates a methylation-dependent adaptive response inCaulobacter. This resp...
Source: PLoS Biology: Archived Table of Contents - March 11, 2024 Category: Biology Authors: Aditya Kamat Source Type: research

Proteasome inhibition triggers tissue-specific immune responses against different pathogens in < i > C < /i > . < i > elegans < /i >
We report here that, in contrast to the previously reported role of SKN-1 in promoting resistance against bacterial infection, loss-of-function mutants inskn-1a and its activating enzymesddi-1 andpng-1 show constitutive expression of immune response programs against natural eukaryotic pathogens ofC.elegans. These programs are the oomycete recognition response (ORR), which promotes resistance against oomycetes that infect through the epidermis, and the intracellular pathogen response (IPR), which promotes resistance against intestine-infecting microsporidia. Consequently,skn-1a mutants show increased resistance to both oomy...
Source: PLoS Biology: Archived Table of Contents - March 11, 2024 Category: Biology Authors: Manish Grover Source Type: research

An ancient bacterial zinc acquisition system identified from a cyanobacterial exoproteome
by Cristina Sarasa-Buisan, Jes ús A. G. Ochoa de Alda, Cristina Velázquez-Suárez, Miguel Ángel Rubio, Guadalupe Gómez-Baena, María F. Fillat, Ignacio Luque Bacteria have developed fine-tuned responses to cope with potential zinc limitation. The Zur protein is a key player in coordinating this response in most species. Comparative proteomics conducted on the cyanobacteriumAnabaena highlighted the more abundant proteins in azur mutant compared to the wild type. Experimental evidence showed that the exoprotein ZepA mediates zinc uptake. Genomic context of thezepA gene and protein structure prediction provided additiona...
Source: PLoS Biology: Archived Table of Contents - March 11, 2024 Category: Biology Authors: Cristina Sarasa-Buisan Source Type: research