bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distinct ancient structural polymorphisms control heterodichogamy in walnuts and hickories
Authors: Groh Jeffrey S. , Vik Diane C. , Stevens Kristian A. , Brown Patrick J. , Langley Charles H. , Coop Graham 
Published: December 2023

AbstractThe maintenance of stable mating type polymorphisms is a classic example of balancing selection, underlying the nearly ubiquitous 50/50 sex ratio in species with separate sexes. One lesser known but intriguing example of a balanced mating polymorphism in angiosperms is heterodichogamy – polymorphism for opposing directions of dichogamy (temporal separation of male and female function in hermaphrodites) within a flowering season. This mating system is common throughout Juglandaceae, the family that includes globally important and iconic nut and timber crops – walnuts (Juglans), as well as pecan and other hickories (Carya). In both genera, heterodichogamy is controlled by a single dominant allele. We fine-map the locus in each genus, and find two ancient (>50 Mya) structural variants involving different genes that both segregate as genus-wide trans-species polymorphisms. TheJuglanslocus maps to a ca. 20 kb structural variant adjacent to a probable trehalose phosphate phosphatase (TPPD-1), homologs of which regulate floral development in model systems.TPPD-1is differentially expressed between morphs in developing male flowers, with increased allele-specific expression of the dominant haplotype copy. Across species, the dominant haplotype contains a tandem array of duplicated sequence motifs, part of which is an inverted copy of theTPPD-13’ UTR. These repeats generate various distinct small RNAs matching sequences within the 3’ UTR and further downstream. In contrast to the single-geneJuglanslocus, theCaryaheterodichogamy locus maps to a ca. 200-450 kb cluster of tightly linked polymorphisms across 20 genes, some of which have known roles in flowering and are differentially expressed between morphs in developing flowers. The dominant haplotype in pecan, which is nearly always heterozygous and appears to rarely recombine, shows markedly reduced genetic diversity and is over twice as long as its recessive counterpart due to accumulation of various types of transposable elements. We did not detect either genetic system in other heterodichogamous genera within Juglandaceae, suggesting that additional genetic systems for heterodichogamy may yet remain undiscovered.
OncogenicPIK3CAcorrupts growth factor signaling specificity
Authors: Madsen R.R. , Le Marois A. , Mruk O. , Voliotis M. , Yin S. , Sufi J. , Qin X. , Zhao S.J. , Gorczynska J. , Morelli D. , Davidson L. , Sahai E. , Korolchuk V.I. , Tape C.J. , Vanhaesebroeck B. 
Published: December 2023

AbstractPathological activation of the PI3K/AKT pathway is among the most frequent defects in human cancer and is also the cause of rare overgrowth disorders. Yet, there is currently no systematic understanding of the quantitative flow of information within PI3K/AKT signaling and how it is perturbed by disease-causing mutations. Here, we develop scalable, single-cell approaches for systematic analyses of signal processing within the PI3K pathway, enabling precise calculations of its information transfer for different growth factors. Using genetically-engineered human cell models with allele dose-dependent expression ofPIK3CAH1047R, we show that this oncogene is not a simple, constitutive pathway activator but a context-dependent modulator of extracellular signal transfer.PIK3CAH1047Rreduces information transmission downstream of IGF1 while selectively enhancing EGF-induced signaling and transcriptional responses. This leads to a gross reduction in signaling specificity, akin to “blurred” signal perception. The associated increase in signaling heterogeneity promotes phenotypic diversity in a human cervical cancer cell line model and in human induced pluripotent stem cells. Collectively, these findings and the accompanying methodological advances lay the foundations for a systematic mapping of the quantitative mechanisms of PI3K/AKT-dependent signal processing and phenotypic control in health and disease.One-sentence summarySingle-cell signaling and information theoretic analyses reveal that oncogenic PI3K/AKT activation leads to a gross reduction in signaling specificity, context-dependent EGF response amplification as well as increased phenotypic heterogeneity.
Multilayer Network Analysis across Cortical Depths in Resting-State 7T fMRI
Authors: Kotlarz Parker , Lankinen Kaisu , Hakonen Maria , Turpin Tori , Polimeni Jonathan R. , Ahveninen Jyrki 
Published: December 2023

AbstractIn graph theory, “multilayer networks” represent systems involving several interconnected topological levels. One example in neuroscience is the stratification of connections between different cortical depths or “laminae”, which is becoming non-invasively accessible in humans using ultra-high-resolution functional MRI (fMRI). Here, we applied multilayer graph theory to examine functional connectivity across different cortical depths in humans, using 7T fMRI (1-mm3voxels; 30 participants). Blood oxygenation level dependent (BOLD) signals were derived from five depths between the white matter and pial surface. We compared networks where the inter-regional connections were limited to a single cortical depth only (“layer-by-layer matrices”) to those considering all possible connections between areas and cortical depths (“multilayer matrix”). We utilized global and local graph theory features that quantitatively characterize network attributes including network composition, nodal centrality, path-based measures, and hub segregation. Detecting functional differences between cortical depths was improved using multilayer connectomics compared to the layer-by-layer versions. Superficial depths of the cortex dominated information transfer and deeper depths drove clustering. These differences were largest in frontotemporal and limbic regions. fMRI functional connectivity across different cortical depths may contain neurophysiologically relevant information; thus, multilayer connectomics could provide a methodological framework for studies on how information flows across this stratification.
PEARL-catalyzed peptide bond formation after chain reversal during the biosynthesis of non-ribosomal peptides
Authors: Yu Yue , van der Donk Wilfred A. 
Published: December 2023

AbstractA subset of nonribosomal peptide synthetases (NRPSs) and polyketide synthases (PKSs) are encoded in their biosynthetic gene clusters (BGCs) with enzymes annotated as lantibiotic dehydratases. The functions of these putative lantibiotic dehydratases remain unknown. Here, we characterize an NRPS-PKS BGC with a putative lantibiotic dehydratase from the bacteriumStackebrandtia nassauensis(sna). Heterologous expression revealed several metabolites produced by the BGC, and the omission of selected biosynthetic enzymes revealed the biosynthetic sequence towards these compounds. The putative lantibiotic dehydratase catalyzes peptide bond formation that extends the peptide scaffold opposite to the NRPS and PKS biosynthetic direction. The condensation domain of the NRPS catalyzes the formation of a ureido group, and bioinformatics analysis revealed distinct active site residues of ureido-generating condensation (UreaC) domains. This work demonstrates that the annotated lantibiotic dehydratase serves as a separate amide bond-forming machinery in addition to the NRPS, and that the lantibiotic dehydratase enzyme family possesses diverse catalytic activities in the biosynthesis of both ribosomal and non-ribosomal natural products.
Automated In Vitro Wound Healing Assay
Authors: Cwycyshyn Jillian , Stansbury Cooper , Meixner Walter , Hoying James B. , Muir Lindsey A. , Rajapakse Indika 
Published: December 2023

AbstractRestoring the epidermal barrier after injury requires spatial and temporal orchestration of migration, proliferation, and signaling across many cell types. The mechanisms that coordinate this complex process are incompletely understood. In vitro wound assays are common model systems for examining these mechanisms in wound healing. In the scratch assay, a cell-free gap is created by mechanical removal of cells from a monolayer, followed by monitoring cell migration into the gap over time. While simple and low-cost, manual scratch assays are limited by low reproducibility and low throughput. Here, we have designed a robotics-assisted automated wound healing (AWH) assay that increases reproducibility and throughput while integrating automated live-cell imaging and analysis. Wounds are designed as computer-aided design (CAD) models and recreated in confluent cell layers by the BioAssemblyBot (BAB) 3D-bioprinting platform. The dynamics of migration and proliferation in individual cells are evaluated over the course of wound closure using live-cell fluorescence microscopy and our high-performance image processing pipeline. The AWH assay outperforms the standard scratch assay with enhanced consistency in wound geometry. Our ability to create diverse wound shapes in any multi-well plate with the BAB not only allows for multiple experimental conditions to be analyzed in parallel but also offers versatility in the design of wound healing experiments. Our method emerges as a valuable tool for the automated completion and analysis of high-throughput, reproducible, and adaptable in vitro wound healing assays.
Spatial genomics of AAVs reveals mechanism of transcriptional crosstalk that enables targeted delivery of large genetic cargo
Authors: Coughlin Gerard M. , Borsos Máté , Appling Nathan , Barcelona Bre’Anna H. , Mayfield Acacia M. H. , Mackey Elisha D. , Eser Rana A. , Chen Xinhong , Kumar Sripriya Ravindra , Gradinaru Viviana 
Published: December 2023

AbstractIntegrating cell type-specific regulatory elements (e.g. enhancers) with recombinant adeno-associated viruses (AAVs) can provide broad and efficient genetic access to specific cell types. However, the packaging capacity of AAVs restricts the size of both the enhancers and the cargo that can be delivered. Transcriptional crosstalk offers a novel paradigm for cell type-specific expression of large cargo, by separating distally-acting regulatory elements into a second AAV genome. Here, we identify and profile transcriptional crosstalk in AAV genomes carrying 11 different enhancers active in mouse brain. To understand transcriptional crosstalk, we develop spatial genomics methods to identify and localize AAV genomes and their concatemeric forms in cultured cells and in tissue. Using these methods, we construct detailed views of the dynamics of AAV transduction and demonstrate that transcriptional crosstalk is dependent upon concatemer formation. Finally, we leverage transcriptional crosstalk to drive expression of a large Cas9 cargo in a cell type-specific manner with systemically-administered engineered AAVs and demonstrate AAV-delivered, minimally-invasive, cell type-specific gene editing in wildtype animals that recapitulates known disease phenotypes.HighlightsTranscriptional crosstalk between enhancers and promoters delivered intransby AAVs is a generalized phenomenon.Spatial genomics techniques, AAV-Zombie and SpECTr, reveal that AAV genome concatemerization facilitates transcriptional crosstalk.Transcriptional crosstalk can be leveraged for minimally-invasive, targeted AAV delivery of large cargo, including machinery for CRISPR-based gene editing and manipulation.Transcriptional crosstalk enables cell-type specific gene disruption in wildtype animals, recapitulating behavioural phenotypes of genetic knockouts.
Substrate complexity buffers negative interactions in a synthetic microbial community of leaf litter degraders
Authors: Abdoli Parmis , Vulin Clément , Lepiz Miriam , Chase Alexander B. , Weihe Claudia , Rodríguez-Verdugo Alejandra 
Published: December 2023

AbstractMicrobes associated with leaf litter, the top layer of soil, collectively decompose organic matter such as plant polysaccharides, and respire carbon dioxide, regulating the land-atmosphere fluxes of carbon. Therefore, it is crucial to understand the processes limiting biopolymer degradation and their influences on soil community properties. For example, it is still unclear how substrate complexity – defined as the structure of the saccharide and the amount of external processing by extracellular enzymes – influences species interactions and species coexistence. Here, we tested the hypothesis that growth on monosaccharides (i.e., xylose) promotes negative interactions through resource competition, and growth on polysaccharides (i.e., xylan) promotes neutral or positive interactions through resource partitioning or synergism among extracellular enzymes. We assembled a three-species community of leaf litter-degrading bacteria isolated from a grassland site in Southern California. In the polysaccharide xylan, pairs of species stably coexisted and grew equally in co-culture and in monoculture. Conversely, in the monosaccharide xylose, competitive exclusion and negative interactions prevailed. These pairwise dynamics remained consistent in a three-species community: all three species coexisted in xylan, while only two species coexisted in xylose. A mathematical model parameterized from single-species growth behaviors showed that in xylose these dynamics could be explained by resource competition. Instead, the resource competition model could not predict the coexistence patterns in xylan. Overall, our study shows that substrate complexity influences species interactions and patterns of coexistence in a synthetic microbial community of leaf litter degraders that can serve as a model for studying carbon cycling and climate change.Graphical Abstract
Concerns on research history overview, distribution patterns, and potentially neglected ecological consequences of the invasive apple snail (Pomacea sp.): A review
Authors: Luo Du , Li Yuefei , Li Jie 
Published: December 2023

ABSTRACTInvasive species pose a threat to global ecosystems and biodiversity, with the apple snail standing out as one kind of the worst invasive species due to its exclusive expansion. In order to draw a conceptual framework of its invasion pattern from an overview, we endeavor to conduct a bibliometric analysis and systematic review to explore the existing knowledge on research history and subjective categorization ofPomacea canaliculataandP. maculata, and to uncover emerging trends of distribution and possible neglected impact on food webs. The research history reveals that the first international research publication was documented in 1958. However, a substantial increase in international publications occurred only after 2000. The adoption and effective implementation of a universally agreed upon management strategy may greatly enhance the progress of research on apple snail invasion. Notably, co-word analysis revealed that the content of each thematic cluster has a shift from basic biology to the monitoring of occurrences and environmental adaptation. Currently, the global distribution of apple snails has expanded to 39 countries primarily as a result of anthropogenic translocation. All infested countries, with the exception of Israel and Singapore, are major paddy rice producers. The northernmost distribution limit is Tyumen in Russia, while the southernmost limit is the Buenos Aires Province in Argentina. Biological control has emerged as a prominent technology for the prevention of apple snail infestations, leading to the identification of 98 non-target enemy species as potential control agents. A taxonomic diversity analysis revealed that these species encompassed a wide range of phylogenetic classifications, including 6 Phyla, 12 Classes, 33 Orders, 55 Families, and 82 Genera. This observation suggests that there is a substantial pool of animals from diverse phylogenetic levels that can prey upon apple snails. Given the high population density and extensive distribution of apple snails, there is a pressing need for further research to explore their potential ecological ramifications. The current understanding of the upward ecological impacts of apple snails remains inadequate. These findings provide valuable insights for future research endeavors and contribute to the effective management of invasive apple snail populations.
Proton transfer from bisphenol-A is required to activate extranuclear-initiated estrogen receptor signaling
Authors: Medina-Gali Regla M. , Martinez-Pinna Juan , Dos Santos Reinaldo S. , Alonso-Magdalena Paloma , Serrano-Maciá Marina , Sempere-Navarro Roberto , Soriano Sergi , Fuentes-Paez Georgina , Pasquali Lorenzo , Mallavia Ricardo , Ciordia Sergio , Grimaldi Marina , Balaguer Patrick , Marroqui Laura , Nadal Angel 
Published: December 2023

ABSTRACTLigand binding to estrogen receptors (ERs), ERα and ERβ, controls the physiology of estrogen-responsive tissues through nuclear and extranuclear initiated pathways. We found that selective ligands activate the extranuclear pathway by a mechanism involving proton transfer. The low affinity ligand and widespread endocrine disruptor Bisphenol-A (BPA) initiated nuclear and extranuclear actions. BPA concentrations similar to the receptor affinity initiated the nuclear pathway, whereas much lower concentrations initiated the extranuclear pathway. Experiments in different cell types using deuterated molecules of BPA (d16-BPA) and the ERβ agonist, diarylpropionitrile (d2-DPN), indicated that a proton transfer from the hydroxyl groups to an amino acid acceptor within the ligand binding domain is required to activate the extranuclear pathway. Activation of the extranuclear pathway by BPA caused a rapid change in the ERβ-associated interactome that did not occur with d16-BPA. To investigate this mechanism in a physiological system, we acutely injected BPA and d16-BPA into male mice. BPA rapidly decreased blood glucose and increased serum C-peptide levels, whereas d16-BPA had no effect. In mouse pancreatic β-cells, acute treatment with BPA closed ATP-dependent K+channels and increased glucose-induced insulin secretion, however d16-BPA was without effect. Contrary to d16-BPA, BPA modified electrical activity and increased apoptosis. RNA sequencing indicated that neither BPA nor d16-BPA significantly altered gene expression. Our findings suggests that the extranuclear actions of ERs are initiated by a mechanism that requires proton transfer from ligands and may have important biological consequences. This mechanism may work for other ligands, nuclear receptors and cell types.One Sentence SummaryProton-transfer from low-affinity ligands activates extranuclear Estrogen Receptor-initiated pathway
Structure and Function Relationships of Mucociliary Clearance in Human and Rat Airways
Authors: Roth Doris , Şahin Ayşe Tuğçe , Ling Feng , Tepho Niels , Senger Christiana N. , Quiroz Erik J. , Calvert Ben A. , van der Does Anne M. , Güney Tankut G. , Glasl Sarah , van Schadewijk Annemarie , von Schledorn Laura , Olmer Ruth , Kanso Eva , Nawroth Janna C. , Ryan Amy L. 
Published: December 2023

ABSTRACTMucociliary clearance is a vital defense mechanism of the human airways, protecting against harmful particles and infections. When this process fails, it contributes to respiratory diseases like chronic obstructive pulmonary disease (COPD) and asthma. While advances in single-cell transcriptomics have revealed the complexity of airway composition, much of what we know about how airway structure impacts clearance relies on animal studies. This limits our ability to create accurate human-based models of airway diseases. Here we show that the airways in female rats and in humans exhibit species-specific differences in the distribution of ciliated and secretory cells as well as in ciliary beat, resulting in significantly higher clearance effectiveness in humans. We further reveal that standard lab-grown cultures exhibit lower clearance effectiveness compared to human airways, and we identify the underlying structural differences. By combining diverse experiments and physics-based modeling, we establish universal benchmarks to assess human airway function, interpret preclinical models, and better understand disease-specific impairments in mucociliary clearance.
ProHap enables proteomic database generation accounting for population diversity
Authors: Vašíček Jakub , Kuznetsova Ksenia G. , Skiadopoulou Dafni , Njølstad Pål R. , Johansson Stefan , Bruckner Stefan , Käll Lukas , Vaudel Marc 
Published: December 2023

AbstractAmid the advances in genomics, the availability of large reference panels of human haplotypes is key to account for human diversity within and across populations. However, mass spectrometry-based proteomics does not benefit from this information. To address this gap, we introduce ProHap, a python-based tool that constructs protein sequence databases from phased genotypes of reference panels. ProHap empowers researchers to account for haplotypic diversity in proteomic searches.
Distractors induce space-specific neural biases in visual working memory
Authors: Raya Deepak V , Gupta Sanchit , Sridharan Devarajan 
Published: December 2023

AbstractInformation held in working memory is remarkably resilient to interference. Yet, distractors containing task-relevant features impact working memory systematically. The neural basis of this interference is poorly understood. Combining behavior with multivariate decoding of human electroencephalography recordings, we show that distractors induce space-specific biases in mnemonic representations. Participants performed a visual working memory task involving grating orientation estimation, with cued and uncued memoranda appearing on opposite visual hemifields. A high-contrast grating distractor, flashed briefly during the delay epoch, biased both behavioral reports and neural representations. Mnemonic representations were biased either towards the distractor’s orientation (attractive) or away from it (repulsive) depending, respectively, on whether the distractor appeared in the same hemifield as the corresponding memorandum, or opposite to it. On the other hand, the magnitude of the bias was much stronger for the uncued than the cued, memorandum, and depended critically on the distractor’s timing, encoding strength and gating efficacy. A two-tier ring attractor model incorporating cross-hemifield competitive inhibition, parsimoniously explained each of these experimental observations. Overall, our results show that prioritization in working memory shields mnemonic representations from distractor interference, and provide a testable computational hypothesis for distractor effects in visual working memory.