iScience. 2024 Oct 18;27(11):111207. doi: 10.1016/j.isci.2024.111207. eCollection 2024 Nov 15.

ABSTRACT

Generative design of promoters has enhanced the efficiency of de novo creation of functional sequences. Though several deep generative models have been employed in biological sequence generation, including variational autoencoder (VAE) or Wasserstein generative adversarial network (WGAN), these models might struggle with mode collapse and low sample diversity. In this study, we introduce the multinomial diffusion model (MDM) for promoter sequence design and propose a structured set of criteria for effectively comparing the performance of generative models. In silico experiments demonstrate that MDM outperforms existing generative AI approaches. MDM demonstrates superior performance in various computational evaluations, remains robust during the training process, and exhibits a strong ability in capturing weak signals. In addition, we experimentally validated that the majority of our model designed promoters have expression activities in vivo, indicating the practicality and potential of MDM for bioengineering.

PMID:39524356 | PMC:PMC11550136 | DOI:10.1016/j.isci.2024.111207

Ecol Evol. 2024 Nov 9;14(11):e70502. doi: 10.1002/ece3.70502. eCollection 2024 Nov.

ABSTRACT

An eco-monitoring program to assess the biodiversity of insects affected by yellow-legged hornet (Vespa velutina) trapping in the north of the Iberian Peninsula (Spain) revealed the first occurrence of the southern giant hornet Vespa soror (Hymenoptera, Vespidae) on the European continent. We present a detailed characterization, combining morphological characteristics and molecular tools for genetic identification, as well as key information on its identification with respect to other hornets found on the Iberian Peninsula. We discuss the most plausible pathways and vectors of introduction, its potential invasiveness, and subsequent impacts on host localities. Our preliminary results raise concerns about the potential threat of V. soror to human health and ecosystem dynamics, as it is a highly predatory species on other insects and even small vertebrates. Finally, this study confirms once again the usefulness of studying insects trapped in such traps for rapid response and early detection of inland invasive species. We also propose a common Spanish name for the species, "avispón sóror".

PMID:39524309 | PMC:PMC11549532 | DOI:10.1002/ece3.70502

Nat Methods. 2024 Nov 11. doi: 10.1038/s41592-024-02504-2. Online ahead of print.

ABSTRACT

Designing proteins with improved functions requires a deep understanding of how sequence and function are related, a vast space that is hard to explore. The ability to efficiently compress this space by identifying functionally important features is extremely valuable. Here we establish a method called EvoScan to comprehensively segment and scan the high-fitness sequence space to obtain anchor points that capture its essential features, especially in high dimensions. Our approach is compatible with any biomolecular function that can be coupled to a transcriptional output. We then develop deep learning and large language models to accurately reconstruct the space from these anchors, allowing computational prediction of novel, highly fit sequences without prior homology-derived or structural information. We apply this hybrid experimental-computational method, which we call EvoAI, to a repressor protein and find that only 82 anchors are sufficient to compress the high-fitness sequence space with a compression ratio of 1048. The extreme compressibility of the space informs both applied biomolecular design and understanding of natural evolution.

PMID:39528677 | DOI:10.1038/s41592-024-02504-2

Nat Commun. 2024 Nov 11;15(1):9139. doi: 10.1038/s41467-024-53163-y.

ABSTRACT

Patient-derived xenografts (PDXs) are tumour fragments engrafted into mice for preclinical studies. PDXs offer clear advantages over simpler in vitro cancer models - such as cancer cell lines (CCLs) and organoids - in terms of structural complexity, heterogeneity, and stromal interactions. Here, we characterise 231 colorectal cancer PDXs at the genomic, transcriptomic, and epigenetic levels, along with their response to cetuximab, an EGFR inhibitor used clinically for metastatic colorectal cancer. After evaluating the PDXs' quality, stability, and molecular concordance with publicly available patient cohorts, we present results from training, interpreting, and validating the integrative ensemble classifier CeSta. This model takes in input the PDXs' multi-omic characterisation and predicts their sensitivity to cetuximab treatment, achieving an area under the receiver operating characteristics curve > 0.88. Our study demonstrates that large PDX collections can be leveraged to train accurate, interpretable drug sensitivity models that: (1) better capture patient-derived therapeutic biomarkers compared to models trained on CCL data, (2) can be robustly validated across independent PDX cohorts, and (3) could contribute to the development of future therapeutic biomarkers.

PMID:39528460 | DOI:10.1038/s41467-024-53163-y

Plant J. 2024 Nov 11. doi: 10.1111/tpj.17101. Online ahead of print.

ABSTRACT

Sorghum bicolor (sorghum) is a vital C4 monocotyledon crop cultivated in arid regions worldwide, valued for its significance in both human and animal nutrition. Despite its agricultural prominence, sorghum research has been hindered by low transformation frequency. In this study, we examined sorghum transformation using the pVS1-VIR2 ternary vector system for Agrobacterium, combined with the morphogenic genes BABY BOOM and WUSCHEL2 and selection using G418. We optimized Agrobacterium-mediated infection, targeting key parameters such as bacterial optical density, co-cultivation time, and temperature. Additionally, an excision-based transformation system enabled us to generate transgenic plants free of morphogenic regulators. The method yielded remarkable transformation frequencies, reaching up to 164.8% based on total isolated plantlets. The same combination of ternary vector, morphogenic genes and geneticin-based selection also resulted in a marked increase in transformation efficiency of the Zea mays (maize) inbred line B104. The potential for genomic editing using this approach positions it as a valuable tool for the development of sorghum and maize varieties that comply with evolving European regulations. Our work marks a significant stride in sorghum biotechnology and holds promise for addressing global food security challenges in a changing climate.

PMID:39527627 | DOI:10.1111/tpj.17101

Adv Biochem Eng Biotechnol. 2024 Nov 12. doi: 10.1007/10_2024_271. Online ahead of print.

ABSTRACT

The fast growth accompanied with high substrate consumption rates and a versatile metabolism paved the way to exploit Vibrio natriegens as unconventional host for biotechnological applications. Meanwhile, a wealth of knowledge on the physiology, the metabolism, and the regulation in this halophilic marine bacterium has been gathered. Sophisticated genetic engineering tools and metabolic models are available and have been applied to engineer production strains and first chassis variants of V. natriegens. In this review, we update the current knowledge on the physiology and the progress in the development of synthetic biology tools and provide an overview of recent advances in metabolic engineering of this promising host. We further discuss future challenges to enhance the application range of V. natriegens.

PMID:39527262 | DOI:10.1007/10_2024_271

Psychiatr Genet. 2024 Dec 1;34(6):124-133. doi: 10.1097/YPG.0000000000000373. Epub 2024 Nov 6.

ABSTRACT

BACKGROUND: Previous studies have shown that genes in brain development pathways may have important roles in affecting risk of suicidal behaviors, with our previous meta-analysis supporting a role of the brain-derived neurotrophic factor (BDNF) gene. NTRK2 is a gene that encodes the neurotrophic receptor tyrosine kinase 2, which is a receptor for BDNF. In the current study, we aim to examine the potential association between NTRK2 single nucleotide polymorphism (SNPs) and suicidal ideation/behaviors.

METHODS: We first conducted a literature search using keywords like 'NTRK2', 'TRKB', and 'suicid*' to identify papers on NTRK2 SNPs and suicidal ideation/behaviors. In addition, we have individual-level genotype data for all the identified SNPs in literature search. We used the R meta package to perform meta-analyses on both the genotype count and the allele count data. Moreover, we performed meta-analyses on specific haplotypes within each haplotype block.

MAIN RESULTS: Following our literature search and meta-analyses on 20 NTRK2 SNPs across up to 8467 samples, we found three SNPs, rs10868235 [N = 5,318, odds ratio (OR) = 1.34, P = 0.02], rs1867283 (N = 5,134, OR = 0.73, P = 0.04), and rs1147198 (N = 5,132, OR = 1.36, P = 0.03) to be nominally associated with suicidal attempts. Those three findings, however, did not survive multiple-testing corrections. Also, none of the haplotype blocks showed significant involvement in suicidality.

CONCLUSION: Our results suggest that the NTRK2 gene may not have a major role in suicidality. Future efforts, however, should explore gene-gene interaction and pathway analyses.

PMID:39527116 | DOI:10.1097/YPG.0000000000000373

Elife. 2024 Nov 11;13:RP94657. doi: 10.7554/eLife.94657.

ABSTRACT

The spatial and temporal linear expression of Hox genes establishes a regional Hox code, which is crucial for the antero-posterior (A-P) patterning, segmentation, and neuronal circuit development of the hindbrain. RNF220, an E3 ubiquitin ligase, is widely involved in neural development via targeting of multiple substrates. Here, we found that the expression of Hox genes in the pons was markedly up-regulated at the late developmental stage (post-embryonic day E15.5) in Rnf220-/- and Rnf220+/- mouse embryos. Single-nucleus RNA sequencing (RNA-seq) analysis revealed different Hox de-repression profiles in different groups of neurons, including the pontine nuclei (PN). The Hox pattern was disrupted and the neural circuits were affected in the PN of Rnf220+/- mice. We showed that this phenomenon was mediated by WDR5, a key component of the TrxG complex, which can be polyubiquitinated and degraded by RNF220. Intrauterine injection of WDR5 inhibitor (WDR5-IN-4) and genetic ablation of Wdr5 in Rnf220+/- mice largely recovered the de-repressed Hox expression pattern in the hindbrain. In P19 embryonal carcinoma cells, the retinoic acid-induced Hox expression was further stimulated by Rnf220 knockdown, which can also be rescued by Wdr5 knockdown. In short, our data suggest a new role of RNF220/WDR5 in Hox pattern maintenance and pons development in mice.

PMID:39526890 | DOI:10.7554/eLife.94657

ACS Nano. 2024 Nov 11. doi: 10.1021/acsnano.4c06024. Online ahead of print.

ABSTRACT

Hierarchical assembly of DNA nanostructures has already led to superstructures of ever-increasing level of complexity. Processing control in building nanostructures hierarchically is desirable but remains underexplored. Here, we present the stepwise assembly of DNA origami nanostructures by a surface-based method. With solid support of magnetic beads or glass slides, we demonstrate hierarchical assembly of preformed DNA origami units to a number of superstructures. The anchoring of DNA constructs on the surface results in better programmability and controllability for DNA self-assembly, suggesting a potential for our surface-based strategy to become a general and standardized assembly methodology of DNA nanostructures and beyond.

PMID:39526834 | DOI:10.1021/acsnano.4c06024

mSystems. 2024 Nov 11:e0100424. doi: 10.1128/msystems.01004-24. Online ahead of print.

ABSTRACT

Legionella pneumophila uses over 300 translocated effector proteins to rewire host cells during infection and create a replicative niche for intracellular growth. To date, several studies have identified L. pneumophila effectors that indirectly and directly regulate the activity of other effectors, providing an additional layer of regulatory complexity. Among these are "metaeffectors," a special class of effectors that regulate the activity of other effectors once inside the host. A defining feature of metaeffectors is direct, physical interaction with a target effector. Metaeffector identification, to date, has depended on phenotypes in heterologous systems and experimental serendipity. Using a multiplexed, recombinant barcode-based yeast two-hybrid technology we screened for protein-protein interactions among all L. pneumophila effectors and 28 components of the Dot/Icm type IV secretion system (>167,000 protein combinations). Of the 52 protein interactions identified by this approach, 44 are novel protein interactions, including 10 novel effector-effector interactions (doubling the number of known effector-effector interactions).

IMPORTANCE: Secreted bacterial effector proteins are typically viewed as modulators of host activity, entering the host cytosol to physically interact with and modify the activity of one or more host proteins in support of infection. A growing body of evidence suggests that a subset of effectors primarily function to modify the activities of other effectors inside the host. These "effectors of effectors" or metaeffectors are often identified through experimental serendipity during the study of canonical effector function against the host. We previously performed the first global effector-wide genetic interaction screen for metaeffectors within the arsenal of Legionella pneumophila, an intracellular bacterial pathogen with over 300 effectors. Here, using a high-throughput, scalable methodology, we present the first global interaction network of physical interactions between L. pneumophila effectors. This data set serves as a complementary resource to identify and understand both the scope and nature of non-canonical effector activity within this important human pathogen.

PMID:39526800 | DOI:10.1128/msystems.01004-24

J Virol. 2024 Nov 11:e0158724. doi: 10.1128/jvi.01587-24. Online ahead of print.

ABSTRACT

Human coronavirus (CoV) HKU1 infection typically causes common cold but can lead to pneumonia in children, older people, and immunosuppressed individuals. Recently, human transmembrane serine protease 2 (hTMPRSS2) was identified as the functional receptor for HKU1, but its region and residues critical for HKU1 S binding remain elusive. In this study, we find that HKU1 could utilize human and hamster, but not rat, mouse, or bat TMPRSS2 for virus entry, displaying a narrow host range. Using human-bat TMPRSS2 chimeras, we show that the serine peptidase (SP) domain of TMPRSS2 is essential for entry of HKU1. Further extensive mutagenesis analyses of the C-terminal regions of SP domains of human and bat TMPRSS2s identify residues 417 and 469 critical for entry of HKU1. Replacement of either D417 or Y469 with asparagine in hTMPRSS2 abolishes its abilities to mediate entry of HKU1 S pseudovirions and cell-cell fusion, whereas substitution of N417 with D or N469 with Y in bat TMPRSS2 (bTMPRSS2) renders it supporting HKU1 entry. Our findings contribute to a deeper understanding of coronavirus-receptor interactions and cross-species transmission.IMPORTANCEThe interactions of coronavirus (CoV) S proteins with their cognate receptors determine the host range and cross-species transmission potential. Recently, human transmembrane serine protease 2 (hTMPRSS2) was found to be the receptor for HKU1. Here, we show that the TMPRSS2 of hamster, but not rat, mouse, or bat, can serve as a functional entry receptor for HKU1. Moreover, swapping the residues at the positions of 417 and 469 of bTMPRSS2 with the corresponding residues of hTMPRSS2 confers it supporting entry of HKU1 S pseudovirions, indicating the critical role of these residues in HKU1 entry. Our study identified the critical residues in hTMPRSS2 responsible for receptor interaction and host range of HKU1.

PMID:39526774 | DOI:10.1128/jvi.01587-24

Elife. 2024 Nov 11;13:RP98169. doi: 10.7554/eLife.98169.

ABSTRACT

Individuals residing in plateau regions are susceptible to pulmonary hypertension (PH) and there is an urgent need for a prediction nomogram to assess the risk of PH in this population. A total of 6603 subjects were randomly divided into a derivation set and a validation set at a ratio of 7:3. Optimal predictive features were identified through the least absolute shrinkage and selection operator regression technique, and nomograms were constructed using multivariate logistic regression. The performance of these nomograms was evaluated and validated using the area under the curve (AUC), calibration curves, the Hosmer-Lemeshow test, and decision curve analysis. Comparisons between nomograms were conducted using the net reclassification improvement (NRI) and integrated discrimination improvement (IDI) indices. NomogramI was established based on independent risk factors, including gender, Tibetan ethnicity, age, incomplete right bundle branch block (IRBBB), atrial fibrillation (AF), sinus tachycardia (ST), and T wave changes (TC). The AUCs for NomogramI were 0.716 in the derivation set and 0.718 in the validation set. NomogramII was established based on independent risk factors, including Tibetan ethnicity, age, right axis deviation, high voltage in the right ventricle, IRBBB, AF, pulmonary P waves, ST, and TC. The AUCs for NomogramII were 0.844 in the derivation set and 0.801 in the validation set. Both nomograms demonstrated satisfactory clinical consistency. The IDI and NRI indices confirmed that NomogramII outperformed NomogramI. Therefore, the online dynamic NomogramII was established to predict the risks of PH in the plateau population.

PMID:39526735 | DOI:10.7554/eLife.98169

Nucleic Acids Res. 2024 Nov 11:gkae1032. doi: 10.1093/nar/gkae1032. Online ahead of print.

ABSTRACT

jPOST (https://jpostdb.org/) comprises jPOSTrepo (https://repository.jpostdb.org/) (over 2000 projects), a repository for proteome mass spectrometry data, the reanalysis of raw proteome data based on a standardised protocol using UniScore, and jPOSTdb (https://globe.jpostdb.org/) (over 600 datasets), a database that integrates the reanalysed data. The jPOST reanalysis protocol rescores MS/MS spectra using a new scale, UniScore, to evaluate the extent to which the spectral peaks correspond to the amino acid sequences identified by search engines. However, the metadata registered in the repository database is insufficient for conducting the reanalysis. To address this issue, the Japanese Proteomics Society launched a data journal, the Journal of Proteome Data and Methods (JPDM), which accepts data descriptor articles detailing metadata that can be reanalysed. Within jPOST, raw proteome data is reanalysed based on the metadata described in the JPDM data descriptor articles, utilising UniScore. The reanalysed data is deposited in jPOSTdb, and a link to the JPDM articles is added to jPOSTrepo. These reanalysis accelerations within the jPOST environment will promote FAIR data principles and open science.

PMID:39526391 | DOI:10.1093/nar/gkae1032

Nucleic Acids Res. 2024 Nov 11:gkae1005. doi: 10.1093/nar/gkae1005. Online ahead of print.

ABSTRACT

Post-translational modifications (PTMs) are essential for modulating protein function and influencing stability, activity and signaling processes. The dbPTM 2025 update significantly expands the database to include over 2.79 million PTM sites, of which 2.243 million are experimentally validated from 48 databases and over 80 000 research articles. This version integrates proteomic data from 13 cancer types, with a particular focus on phosphoproteomic data and kinase activity profiles, allowing the exploration of personalized phosphorylation patterns in tumor samples. Integrating kinase-substrate phosphorylations with E3 ligase-substrate interactions, dbPTM 2025 provides a detailed map of PTM regulatory networks, offering insights into cancer-specific post-translational regulations. This update also includes advanced search capabilities, enabling users to efficiently query PTM data across species, PTM types and modified residues. The platform's new features-interactive visualization tools and streamlined data downloads-allow researchers to access and analyze PTM data easily. dbPTM 2025 also enhances functional annotations, regulatory networks and disease associations, broadening its application for cancer research and the study of disease-associated PTMs. Through these enhancements, dbPTM 2025 is a comprehensive, user-friendly resource, facilitating the study of PTMs and their roles in cancer research. The database is now freely accessible at https://biomics.lab.nycu.edu.tw/dbPTM/.

PMID:39526378 | DOI:10.1093/nar/gkae1005

Front Pharmacol. 2024 Oct 25;15:1481768. doi: 10.3389/fphar.2024.1481768. eCollection 2024.

ABSTRACT

BACKGROUND: Glomerular fibrosis is a tissue damage that occurs within the kidneys of chronic and diabetic kidney disease patients. Effective treatments are lacking, and the mechanism of glomerular damage reversal is poorly understood.

METHODS: A mathematical model suitable for hypothesis-driven systems pharmacology of glomerular fibrosis in diabetes was developed from a previous model of interstitial fibrosis. The adapted model consists of a system of ordinary differential equations that models the complex disease etiology and progression of glomerular fibrosis in diabetes.

RESULTS: Within the scope of the mechanism incorporated, advanced glycation end products (AGE)-matrix proteins that are modified due to high blood glucose-were identified as major contributors to the delay in the recovery from glomerular fibrosis after glucose control. The model predicted that inhibition of AGE production is not an effective approach for accelerating the recovery from glomerular fibrosis. Further, the model predicted that treatment breaking down accumulated AGE is the most productive at reversing glomerular fibrosis. The use of the model led to the identification that glucose control and aminoguanidine are ineffective treatments for reversing advanced glomerular fibrosis because they do not remove accumulated AGE. Additionally, using the model, a potential explanation was generated for the lack of efficacy of alagebrium in treating advanced glomerular fibrosis, which is due to the inability of alagebrium to reduce TGF- β .

IMPACT: Using the mathematical model, a mechanistic understanding of disease etiology and complexity of glomerular fibrosis in diabetes was illuminated, and then hypothesis-driven explanations for the lack of efficacy of different pharmacological agents for treating glomerular fibrosis were provided. This understanding can enable the development of more efficacious therapeutics for treating kidney damage in diabetes.

PMID:39525640 | PMC:PMC11543426 | DOI:10.3389/fphar.2024.1481768

Front Pharmacol. 2024 Oct 25;15:1412593. doi: 10.3389/fphar.2024.1412593. eCollection 2024.

ABSTRACT

OBJECTIVE: The purpose of this study was to predict the four cold-heat patterns in patients who have the subjective symptoms of the cold-heat pattern described in the International Classification of Diseases Traditional Medicine Conditions - Module 1 by applying a machine learning algorithm.

METHODS: Subjects were first-visit Kampo outpatients at six institutions who agreed to participate in this multicenter prospective observational study. The cold pattern model and the heat pattern model were created separately with 148 symptoms, body mass index, blood pressure (systolic and diastolic), age, and sex. Along with a single cold or heat pattern, the tangled heat/cold pattern is defined as being predicted by both cold and heat patterns, while the moderate (heat/cold) pattern is defined as being predicted by neither the cold pattern nor the heat pattern.

RESULTS: We included 622 participants (mean age ±standard deviation, 54.4 ± 16.9; with female 501). The accuracy, macro-recall, precision, and F1-score of a combination of the two prediction models were 96.7%, 93.2%, 85.6%, and 88.5% respectively. The important items were compatible with the definitions of the cold-heat pattern.

CONCLUSION: We developed a prediction model on cold-heat patterns with data from patients whose subjective cold/heat-related symptoms matched the cold-heat pattern diagnosis by the physician.

PMID:39525633 | PMC:PMC11543495 | DOI:10.3389/fphar.2024.1412593

For Res (Fayettev). 2022 Aug 31;2:11. doi: 10.48130/FR-2022-0011. eCollection 2022.

ABSTRACT

Forests are not only the most predominant of the Earth's terrestrial ecosystems, but are also the core supply for essential products for human use. However, global climate change and ongoing population explosion severely threatens the health of the forest ecosystem and aggravtes the deforestation and forest degradation. Forest genomics has great potential of increasing forest productivity and adaptation to the changing climate. In the last two decades, the field of forest genomics has advanced quickly owing to the advent of multiple high-throughput sequencing technologies, single cell RNA-seq, clustered regularly interspaced short palindromic repeats (CRISPR)-mediated genome editing, and spatial transcriptomes, as well as bioinformatics analysis technologies, which have led to the generation of multidimensional, multilayered, and spatiotemporal gene expression data. These technologies, together with basic technologies routinely used in plant biotechnology, enable us to tackle many important or unique issues in forest biology, and provide a panoramic view and an integrative elucidation of molecular regulatory mechanisms underlying phenotypic changes and variations. In this review, we recapitulated the advancement and current status of 12 research branches of forest genomics, and then provided future research directions and focuses for each area. Evidently, a shift from simple biotechnology-based research to advanced and integrative genomics research, and a setup for investigation and interpretation of many spatiotemporal development and differentiation issues in forest genomics have just begun to emerge.

PMID:39525413 | PMC:PMC11524260 | DOI:10.48130/FR-2022-0011

Npj Imaging. 2024;2(1):47. doi: 10.1038/s44303-024-00051-1. Epub 2024 Nov 6.

ABSTRACT

Previous studies have shown that the zinc-responsive MRI probe, GdL1, can distinguish healthy versus malignant prostate tissues based upon differences in zinc content and secretion. In this study, mice were fed chow containing low, normal, or high zinc content for 3 weeks before imaging glucose stimulated zinc secretion (GSZS) by MRI. The distribution of zinc in prostate tissue in these three groups was imaged by synchrotron radiation X-ray fluorescence (SR-XRF). A zinc deficiency caused systemic and organ-level dysregulation, weight loss, and altered zinc bioavailability. Zinc efflux from the prostate increased in parallel to dietary zinc in healthy mice but not in TRAMP mice, consistent with a lowered capacity to store dietary zinc in malignant cells. This differential zinc efflux suggests that a dietary supplement of zinc prior to a GSZS study may enhance image contrast between healthy and malignant prostate tissue, thereby improving the accuracy of prostate cancer detection in man.

PMID:39525279 | PMC:PMC11541085 | DOI:10.1038/s44303-024-00051-1

Genes Dis. 2024 Jul 6;12(1):101373. doi: 10.1016/j.gendis.2024.101373. eCollection 2025 Jan.

NO ABSTRACT

PMID:39524540 | PMC:PMC11549976 | DOI:10.1016/j.gendis.2024.101373

Nat Commun. 2024 Nov 10;15(1):9731. doi: 10.1038/s41467-024-53228-y.

ABSTRACT

The spatial and temporal dynamics of forces in cells coordinate essential behaviors like division, polarization, and migration. While intracellular signaling initiates contractile ring assembly during cell division, how mechanical forces coordinate division and their energetic costs remain unclear. Here, we develop an in vitro model where myosin-induced stress drives division-like shape changes in giant unilamellar vesicles (GUVs, liposomes). Myosin activity is controlled by light patterns globally or locally at the equator. Global activation causes slow, shallow cleavage furrows due to a tug-of-war between the equatorial and polar forces. By contrast, local activation leads to faster, deeper, and symmetric division as equatorial forces dominate. Dissociating the actin cortex at the poles is crucial for inducing significant furrowing. During furrowing, actomyosin flows align actin filaments parallel to the division plane, forming a contractile ring-like structure. Mechanical power is not greatest during contraction, but is maximized just before furrowing. This study reveals the quantitative relationship between force patterning and mechanical energy during division-like shape changes, providing insights into cell division mechanics.

PMID:39523366 | PMC:PMC11551154 | DOI:10.1038/s41467-024-53228-y