Natanael Spisak, Marc de Manuel, William Milligan, Guy Sella, Molly Przeworski
The rates at which mutations accumulate across human cell types vary. To identify causes of this variation, mutations are often decomposed into a combination of the single-base substitution (SBS) "signatures" observed in germline, soma, and tumors, with the idea that each signature corresponds to one or a small number of underlying mutagenic processes. Two such signatures turn out to be ubiquitous across cell types: SBS signature 1, which consists primarily of transitions at methylated CpG sites thought to be caused by spontaneous deamination, and the more diffuse SBS signature 5, which is of unknown etiology...
June 17, 2024: PLoS Biology
Charlotte Cordonnier, Msano Mandalasi, Jason Gigley, Elizabeth A Wohlfert, Christopher M West, Ira J Blader
As Toxoplasma gondii disseminates through its host, the parasite must sense and adapt to its environment and scavenge nutrients. Oxygen (O2) is one such environmental factor and cytoplasmic prolyl 4-hydroxylases (PHDs) are evolutionarily conserved O2 cellular sensing proteins that regulate responses to changes in O2 availability. Toxoplasma expresses 2 PHDs. One of them, TgPHYa hydroxylates SKP1, a subunit of the SCF-E3 ubiquitin ligase complex. In vitro, TgPHYa is important for growth at low O2 levels. However, studies have yet to examine the role that TgPHYa or any other pathogen-encoded PHD plays in virulence and disease...
June 10, 2024: PLoS Biology
Laura E Burnett, Peter Koppensteiner, Olga Symonova, Tomás Masson, Tomas Vega-Zuniga, Ximena Contreras, Thomas Rülicke, Ryuichi Shigemoto, Gaia Novarino, Maximilian Joesch
Despite the diverse genetic origins of autism spectrum disorders (ASDs), affected individuals share strikingly similar and correlated behavioural traits that include perceptual and sensory processing challenges. Notably, the severity of these sensory symptoms is often predictive of the expression of other autistic traits. However, the origin of these perceptual deficits remains largely elusive. Here, we show a recurrent impairment in visual threat perception that is similarly impaired in 3 independent mouse models of ASD with different molecular aetiologies...
June 10, 2024: PLoS Biology
Marco A Coelho, Márcia David-Palma, Terrance Shea, Katharine Bowers, Sage McGinley-Smith, Arman W Mohammad, Andreas Gnirke, Andrey M Yurkov, Minou Nowrousian, Sheng Sun, Christina A Cuomo, Joseph Heitman
In exploring the evolutionary trajectories of both pathogenesis and karyotype dynamics in fungi, we conducted a large-scale comparative genomic analysis spanning the Cryptococcus genus, encompassing both global human fungal pathogens and nonpathogenic species, and related species from the sister genus Kwoniella. Chromosome-level genome assemblies were generated for multiple species, covering virtually all known diversity within these genera. Although Cryptococcus and Kwoniella have comparable genome sizes (about 19...
June 6, 2024: PLoS Biology
Frank Hawkins
The potentially catastrophic loss of biodiversity happening around the globe is largely caused by economic activity that is not connected to its environmental impacts. To improve positive and reduce negative outcomes for nature, investment decision-makers in companies, governments, and the finance sector need data on the impacts of economic activity, especially production of food and other commodities, on biodiversity, at fine geographical scales. This Essay argues that the data allowing us to identify the most important factors causing biodiversity loss are already available...
June 4, 2024: PLoS Biology
Che-Yi Lin, Ferdinand Marlétaz, Alberto Pérez-Posada, Pedro Manuel Martínez-García, Siegfried Schloissnig, Paul Peluso, Greg T Conception, Paul Bump, Yi-Chih Chen, Cindy Chou, Ching-Yi Lin, Tzu-Pei Fan, Chang-Tai Tsai, José Luis Gómez Skarmeta, Juan J Tena, Christopher J Lowe, David R Rank, Daniel S Rokhsar, Kai Yu, Yi-Hsien Su
Deuterostomes are a monophyletic group of animals that includes Hemichordata, Echinodermata (together called Ambulacraria), and Chordata. The diversity of deuterostome body plans has made it challenging to reconstruct their ancestral condition and to decipher the genetic changes that drove the diversification of deuterostome lineages. Here, we generate chromosome-level genome assemblies of 2 hemichordate species, Ptychodera flava and Schizocardium californicum, and use comparative genomic approaches to infer the chromosomal architecture of the deuterostome common ancestor and delineate lineage-specific chromosomal modifications...
June 3, 2024: PLoS Biology
Bradley J Edelman, Dominique Siegenthaler, Paulina Wanken, Bethan Jenkins, Bianca Schmid, Andrea Ressle, Nadine Gogolla, Thomas Frank, Emilie Macé
Neuroscientists studying the neural correlates of mouse behavior often lack access to the brain-wide activity patterns elicited during a specific task of interest. Fortunately, large-scale imaging is becoming increasingly accessible thanks to modalities such as Ca2+ imaging and functional ultrasound (fUS). However, these and other techniques often involve challenging cranial window procedures and are difficult to combine with other neuroscience tools. We address this need with an open-source 3D-printable cranial implant-the COMBO (ChrOnic Multimodal imaging and Behavioral Observation) window...
June 3, 2024: PLoS Biology
Dongmei Wang, Yuxiang Cao, Meiyao Meng, Jin Qiu, Chao Ni, Xiaozhen Guo, Yu Li, Shuang Liu, Jian Yu, Mingwei Guo, Jiawen Wang, Bing Du, Wenwei Qiu, Cen Xie, Bing Zhao, Xinran Ma, Xinghua Cheng, Lingyan Xu
Cholesterol metabolism is vital for multiple cancer progression, while how cholesterol affects lung, a low-cholesterol tissue, for cancer metastasis and the underlying mechanism remain unclear. In this study, we found that metastatic lung adenocarcinoma cells acquire cellular dehydrocholesterol and cholesterol by endogenous cholesterol biosynthesis, instead of uptake upon cholesterol treatment. Besides, we demonstrated that exogenous cholesterol functions as signaling molecule to induce FOXA3, a key transcription factor for lipid metabolism via GLI2...
May 28, 2024: PLoS Biology
Irina Kovlyagina, Anna Wierczeiko, Hristo Todorov, Eric Jacobi, Margarita Tevosian, Jakob von Engelhardt, Susanne Gerber, Beat Lutz
Trait anxiety is a major risk factor for stress-induced and anxiety disorders in humans. However, animal models accounting for the interindividual variability in stress vulnerability are largely lacking. Moreover, the pervasive bias of using mostly male animals in preclinical studies poorly reflects the increased prevalence of psychiatric disorders in women. Using the threat imminence continuum theory, we designed and validated an auditory aversive conditioning-based pipeline in both female and male mice. We operationalised trait anxiety by harnessing the naturally occurring variability of defensive freezing responses combined with a model-based clustering strategy...
May 28, 2024: PLoS Biology
Orli Snir, Michael Elgart, Yulia Gnainsky, Moshe Goldsmith, Filippo Ciabrelli, Shlomi Dagan, Iris Aviezer, Elizabeth Stoops, Giacomo Cavalli, Yoav Soen
Despite significant progress in understanding epigenetic reprogramming of cells, the mechanistic basis of "organ reprogramming" by (epi-)gene-environment interactions remained largely obscure. Here, we use the ether-induced haltere-to-wing transformations in Drosophila as a model for epigenetic "reprogramming" at the whole organism level. Our findings support a mechanistic chain of events explaining why and how brief embryonic exposure to ether leads to haltere-to-wing transformations manifested at the larval stage and on...
May 28, 2024: PLoS Biology
Meng-Han Joseph Chung, Rebecca J Fox, Michael D Jennions
When males compete, sexual selection favors reproductive traits that increase their mating or fertilization success (pre- and postcopulatory sexual selection). It is assumed that males face a trade-off between these 2 types of sexual traits because they both draw from the same pool of resources. Consequently, allocation into mate acquisition or ejaculation should create similar trade-offs with other key life history traits. Tests of these assumptions are exceedingly rare. Males only ejaculate after they mate, and the costs of ejaculation are therefore highly confounded with those of mating effort...
May 24, 2024: PLoS Biology
Sofie De Schrijver, Thomas Decramer, Peter Janssen
Neurons responding during action execution and action observation were discovered in the ventral premotor cortex 3 decades ago. However, the visual features that drive the responses of action observation/execution neurons (AOENs) have not been revealed at present. We investigated the neural responses of AOENs in ventral premotor area F5c of 4 macaques during the observation of action videos and crucial control stimuli. The large majority of AOENs showed highly phasic responses during the action videos, with a preference for the moment that the hand made contact with the object...
May 20, 2024: PLoS Biology
Chun-Chih Tseng, Thomas E Woolley, Ting-Xin Jiang, Ping Wu, Philip K Maini, Randall B Widelitz, Chuong Cheng-Ming
Periodic patterning requires coordinated cell-cell interactions at the tissue level. Turing showed, using mathematical modeling, how spatial patterns could arise from the reactions of a diffusive activator-inhibitor pair in an initially homogenous 2D field. Most activators and inhibitors studied in biological systems are proteins, and the roles of cell-cell interaction, ions, bioelectricity, etc. are only now being identified. Gap junctions (GJs) mediate direct exchanges of ions or small molecules between cells, enabling rapid long-distance communications in a cell collective...
May 14, 2024: PLoS Biology
Ryeonghwa Kang, Kyungdeok Kim, Yewon Jung, Sang-Han Choi, Chanhee Lee, Geun Ho Im, Miram Shin, Kwangmin Ryu, Subin Choi, Esther Yang, Wangyong Shin, Seungjoon Lee, Suho Lee, Zachary Papadopoulos, Ji Hoon Ahn, Gou-Young Koh, Jonathan Kipnis, Hyojin Kang, Hyun Kim, Won-Ki Cho, Soochul Park, Seong-Gi Kim, Eunjoon Kim
Autism spectrum disorders (ASD) frequently accompany macrocephaly, which often involves hydrocephalic enlargement of brain ventricles. Katnal2 is a microtubule-regulatory protein strongly linked to ASD, but it remains unclear whether Katnal2 knockout (KO) in mice leads to microtubule- and ASD-related molecular, synaptic, brain, and behavioral phenotypes. We found that Katnal2-KO mice display ASD-like social communication deficits and age-dependent progressive ventricular enlargements. The latter involves increased length and beating frequency of motile cilia on ependymal cells lining ventricles...
May 8, 2024: PLoS Biology
Justin J Quan, Lachezar A Nikolov, Jihui Sha, James A Wohlschlegel, Isabelle Coppens, Peter J Bradley
Toxoplasma gondii resides in its intracellular niche by employing a series of specialized secretory organelles that play roles in invasion, host cell manipulation, and parasite replication. Rab GTPases are major regulators of the parasite's secretory traffic that function as nucleotide-dependent molecular switches to control vesicle trafficking. While many of the Rab proteins have been characterized in T. gondii, precisely how these Rabs are regulated remains poorly understood. To better understand the parasite's secretory traffic, we investigated the entire family of Tre2-Bub2-Cdc16 (TBC) domain-containing proteins, which are known to be involved in vesicle fusion and secretory protein trafficking...
May 7, 2024: PLoS Biology
Parth K Raval, Alexander I MacLeod, Sven B Gould
Algae and plants carry 2 organelles of endosymbiotic origin that have been co-evolving in their host cells for more than a billion years. The biology of plastids and mitochondria can differ significantly across major lineages and organelle changes likely accompanied the adaptation to new ecological niches such as the terrestrial habitat. Based on organelle proteome data and the genomes of 168 phototrophic (Archaeplastida) versus a broad range of 518 non-phototrophic eukaryotes, we screened for changes in plastid and mitochondrial biology across 1 billion years of evolution...
May 7, 2024: PLoS Biology
Kif Liakath-Ali, Rebecca Refaee, Thomas C Südhof
Synaptic adhesion molecules (SAMs) are evolutionarily conserved proteins that play an important role in the form and function of neuronal synapses. Teneurins (Tenms) and latrophilins (Lphns) are well-known cell adhesion molecules that form a transsynaptic complex. Recent studies suggest that Tenm3 and Lphn2 (gene symbol Adgrl2) are involved in hippocampal circuit assembly via their topographical expression. However, it is not known whether other teneurins and latrophilins display similar topographically restricted expression patterns during embryonic and postnatal development...
May 7, 2024: PLoS Biology
Sanjida H Rangwala, Dmitry V Rudnev, Victor V Ananiev, Dong-Ha Oh, Andrea Asztalos, Barrett Benica, Evgeny A Borodin, Nathan Bouk, Vladislav I Evgeniev, Vamsi K Kodali, Vadim Lotov, Eyal Mozes, Marina V Omelchenko, Sofya Savkina, Ekaterina Sukharnikov, Joël Virothaisakun, Terence D Murphy, Kim D Pruitt, Valerie A Schneider
We report a new visualization tool for analysis of whole-genome assembly-assembly alignments, the Comparative Genome Viewer (CGV) ( CGV visualizes pairwise same-species and cross-species alignments provided by National Center for Biotechnology Information (NCBI) using assembly alignment algorithms developed by us and others. Researchers can examine large structural differences spanning chromosomes, such as inversions or translocations. Users can also navigate to regions of interest, where they can detect and analyze smaller-scale deletions and rearrangements within specific chromosome or gene regions...
May 7, 2024: PLoS Biology
Md Hassan Uz-Zaman, Simon D'Alton, Jeffrey E Barrick, Howard Ochman
The phenomenon of de novo gene birth-the emergence of genes from non-genic sequences-has received considerable attention due to the widespread occurrence of genes that are unique to particular species or genomes. Most instances of de novo gene birth have been recognized through comparative analyses of genome sequences in eukaryotes, despite the abundance of novel, lineage-specific genes in bacteria and the relative ease with which bacteria can be studied in an experimental context. Here, we explore the genetic record of the Escherichia coli long-term evolution experiment (LTEE) for changes indicative of "proto-genic" phases of new gene birth in which non-genic sequences evolve stable transcription and/or translation...
May 7, 2024: PLoS Biology
Michalina Kazek, Lenka Chodáková, Katharina Lehr, Lukáš Strych, Pavla Nedbalová, Ellen McMullen, Adam Bajgar, Stanislav Opekar, Petr Šimek, Martin Moos, Tomáš Doležal
Activation of immune cells requires the remodeling of cell metabolism in order to support immune function. We study these metabolic changes through the infection of Drosophila larvae by parasitoid wasp. The parasitoid egg is neutralized by differentiating lamellocytes, which encapsulate the egg. A melanization cascade is initiated, producing toxic molecules to destroy the egg while the capsule also protects the host from the toxic reaction. We combined transcriptomics and metabolomics, including 13C-labeled glucose and trehalose tracing, as well as genetic manipulation of sugar metabolism to study changes in metabolism, specifically in Drosophila hemocytes...
May 7, 2024: PLoS Biology
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