bluuebunny/crossref_metadata_2025_split huggingface dataset:
What happens with bacteria in the roots affects what happens with fungi in the leaves
Authors: Fernández-Vargas Rachelle , Tabash-Porras Fabiana , Rojas-Jiménez Keilor 
Published: December 2023

AbstractThe impact of plant-bacteria symbioses in roots on plant-fungus interactions in distant tissues, such as leaves, remains a significant knowledge gap, particularly for tropical ecosystems. We employed amplicon metabarcoding of ITS2 sequences to analyze the endophytic fungal communities of eight tropical Fabaceae tree species to determine variations according to the host’s root nodulation capacity and the host’s subfamily affiliation. Nitrogen-fixing bacteria in root nodules significantly impacted the diversity and composition of fungal endophytes, while subfamily affiliation had a less pronounced effect. In non-nodulating plants, leaves harbored a much larger diversity of fungi, with 25 fungal classes and 72 orders compared to 17 classes and 45 orders in nodulating plants. Notably, 40% of the orders were unique to non-nodulating plants, whereas only 5% were exclusive to nodulating species. This pattern was further reflected in the number of fungal ASVs, with non-nodulating plants averaging 130.5 compared to 42.7 in nodulating plants. Similarly, Shannon diversity was significantly higher in non-nodulating plants. This study demonstrates that interactions between Fabaceae plants and nitrogen-fixing root bacteria significantly influence the richness and diversity of the fungal community present in leaves. Our findings contribute valuable insights into the complex interplay between plants and microorganisms, particularly in the context of tropical Fabaceae tree species and their endophytic fungi.
Exploring the accuracy and limits of algorithms for localizing recombination breakpoints
Authors: Cen Shi , Rasmussen David A. 
Published: December 2023

AbstractPhylogenetic methods are widely used to reconstruct the evolutionary relationships among species and individuals. However, recombination can obscure ancestral relationships as individuals may inherit different regions of their genome from different ancestors. It is therefore often necessary to detect recombination events, locate recombination breakpoints and select recombination-free alignments prior to reconstructing phylogenetic trees. While many earlier studies examined the power of different methods to detect recombination, very few have examined the ability of these methods to accurately locate recombination breakpoints. In this study, we simulated genome sequences based on ancestral recombination graphs and explored the accuracy of three popular recombination detection methods: MaxChi, 3SEQ and GARD. The accuracy of inferred breakpoint locations was evaluated along with the key factors contributing to variation in accuracy across data sets. While many different genomic features contribute to the variation in performance across methods, the number of informative sites consistent with the pattern of inheritance between parent and recombinant child sequences always has the greatest contribution to accuracy. While partitioning sequence alignments based on identified recombination breakpoints can greatly decrease phylogenetic error, the quality of phylogenetic reconstructions depends very little on how breakpoints are chosen to partition the alignment. Our work sheds light on how different features of recombinant genomes affect the performance of recombination detection methods and suggests best practices for reconstructing phylogenies based on recombination-free alignments.
Novel Evolution of the Mineralocorticoid Receptor in Humans compared to Chimpanzees, Gorillas and Orangutans
Authors: Katsu Yoshinao , Zhang Jiawen , Baker Michael E. 
Published: December 2023

AbstractWe identified five distinct full-length human mineralocorticoid receptor (MR) genes containing either 984 amino acids (MR-984) or 988 amino acids (MR-988), which can be distinguished by the presence or absence of Lys, Cys, Ser, Trp (KCSW) in their DNA-binding domain (DBD) and mutations at codons 180 and 241 in their amino terminal domain (NTD). Two human MR-KCSW genes contain either (Val-180, Val-241) or (Ile-180, Val-241) in their NTD and three human MR-984 genes contain either (Ile-180, Ala-241) or (Val-180, Val-241) or (Ile-180, Val-241). Human MR-KCSW with (Ile-180, Ala-241) has not been cloned. In contrast, chimpanzees contain four MRs: two MR-988s with KCSW in their DBD or two MR-984s without KCSW in their DBD. Chimpanzee MRs only contain (Ile180, Val-241) in their NTD. A chimpanzee MR with either (Val-180, Val-241) or (Ile-180, Ala-241) in the NTD has not been cloned. Gorillas and orangutans each contain one MR-988 with KCSW in the DBD and one MR-984 without KCSW, and these MRs only contain (Ile-180, Val-241) in their NTD. A gorilla MR or orangutan MR with either (Val-180, Val-241) or (Ile-180, Ala-241) in the NTD has not been cloned. Together, these data suggest that human MRs with (Val-180, Val-241) or (Ile-180, Ala-241) in the NTD evolved after humans and chimpanzees diverged from their common ancestor. Considering the multiple functions in human development of the MR in kidney, brain, heart, skin, and lungs, as well as MR activity in interaction with the glucocorticoid receptor, we suggest that the evolution of human MRs that are absent in chimpanzees may have been important in the evolution of humans from chimpanzees. Investigation of the physiological responses to corticosteroids mediated by the MR in humans, chimpanzees, gorillas and orangutans may provide insights into the evolution of humans and their closest relatives.
Rendering protein structures inside cells at the atomic level with Unreal Engine
Authors: Chen Muyuan 
Published: December 2023

AbstractWhile the recent development of cryogenic electron tomography (CryoET) makes it possible to identify various macromolecules inside cells and determine their structure at near-atomic resolution, it remains challenging to visualize the complex cellular environment at the atomic level. One of the main hurdles in cell visualization is to render the millions of molecules in real time computationally. Here, using a video game engine, we demonstrate the capability of rendering massive biological macromolecules at the atomic level within their native environment. To facilitate the visualization, we also provide tools that help the interactive navigation inside the cells, as well as software that converts protein structures identified using CryoET to a scene that can be explored with the game engine.Graphical abstract
Stimulus-reward contingencies drive long-lasting alterations in neocortical somatostatin inhibition during learning
Authors: Park Eunsol , Kuljis Dika A. , Zhu Mo , Christian Joseph A. , Barth Alison L. 
Published: December 2023

AbstractLearning involves the association of discrete events in the world to infer causality, likely through a cascade of changes at input- and target-specific synapses. Transient or sustained disinhibition may initiate cortical circuit plasticity important for association learning, but the cellular networks involved have not been well-defined. Here we show that sensory association learning drives a durable, target-specific reduction in inhibition from somatostatin (SST)-expressing GABAergic neurons onto pyramidal (Pyr) neurons in superficial but not deep layers of mouse somatosensory cortex. Critically, SST-output was not altered when stimulus and rewards were unpaired, indicating that these neurons are not modified by sensory input alone. Depression of SST output onto Pyr neurons could be phenocopied by chemogenetic suppression of SST activity outside of the training context. Thus, neocortical SST neuron output is persistently modified by convergent sensory and reinforcement signals to selectively disinhibit superficial layers of sensory neocortex during learning.
The role of mitochondria in sex- and age-specific gene expression in a species without sex chromosomes
Authors: Li Ning , Flanagan Ben A. , Edmands Suzanne 
Published: December 2023

AbstractMitochondria perform an array of functions, many of which involve interactions with gene products encoded by the nucleus. These mitochondrial functions, particularly those involving energy production, can be expected to differ between sexes and across ages. Here we measured mitochondrial effects on sex- and age-specific gene expression in parental and reciprocal F1 hybrids between allopatric populations ofTigriopus californicuswith over 20% mitochondrial DNA divergence. Because the species lacks sex chromosomes, sex-biased mitochondrial effects are not confounded by the effects of sex chromosomes. Using single-individual RNA sequencing, sex differences were found to explain more than 80% of the variance in gene expression. Males had higher expression of mitochondrial genes and mitochondrially targeted proteins (MTPs) involved in oxidative phosphorylation (OXPHOS), while females had elevated expression of non-OXPHOS MTPs, indicating strongly sex-dimorphic energy metabolism at the whole organism level. Comparison of reciprocal F1 hybrids allowed insights into the nature of mito-nuclear interactions, showing both mitochondrial effects on nuclear expression, as well as nuclear effects on mitochondrial expression. Across both sexes, increases in mitochondrial expression with age were associated with longer life. Network analyses identified nuclear components of strong mito-nuclear interactions, and found them to be sexually dimorphic. These results highlight the profound impact of mitochondria and mito-nuclear interactions on sex- and age-specific gene expression.
WRN Inhibition Leads to its Chromatin-Associated Degradation Via the PIAS4-RNF4-p97/VCP Axis
Authors: Pérez Fernando Rodríguez , Natwick Dean , Schiff Lauren , McSwiggen David , Huey Melina , Heckert Alec , Loo Mandy , Miranda Rafael , Morrison Huntly , Ortega Jose , Butler Renee , Cheng Kylie , Filbin John , Zhang Zhengjian , Gonzalez Eric , Miller Rand , Tang Yangzhong , Ho Jaclyn , Anderson Daniel , Bashore Charlene , Basham Steve 
Published: December 2023

AbstractSynthetic lethality, the concept in which the co-occurrence of two genetic events leads to cell death while either single event alone does not, is an attractive strategy for targeted cancer therapies. A recent example of synthetic lethality as a therapeutic paradigm is the observation that cancer cells with high levels of microsatellite instability (MSI-H) are dependent on the Werner (WRN) RecQ helicase for survival. However, the mechanisms that regulate WRN spatiotemporal dynamics are not fully understood. In this study, we used our single molecule tracking (SMT) platform in combination with a recently disclosed WRN inhibitor to gain insights into WRN’s dynamic localization within the nuclei of live cancer cells. We observe that WRN inhibition results in the helicase becoming trapped on chromatin, requiring p97/VCP for extraction and shuttling to the proteasome for degradation. Interestingly, this sequence of events resulting in WRN degradation appears to be MSI-H dependent. Using a phenotypic screen, we identify the PIAS4-RNF4 axis as the pathway responsible for WRN degradation and show that co-inhibition of WRN and SUMOylation has an additive toxic effect in MSI-H cells. Taken together, our work elucidates a novel regulatory mechanism for WRN. Gaining a deeper understanding into this regulatory pathway for WRN can aid in the identification of new high value targets for targeted cancer therapies.
Lactiplantibacillus plantarum K8lysates regulate hypoxia-induced gene expression
Authors: Jeong Jaehyeon , Kang Byeong-Hee , Ju Sangmin , Park Na Yeon , Kim Deukyeong , Dinh Ngoc Thi Bao , Lee Jeongho , Rhee Chang Yun , Cho Dong-Hyung , Kim Hangeun , Chung Dae Kyun , Bunch Heeyoun 
Published: December 2023

ABSTRACTHypoxic responses have been implicated in critical pathologies, including inflammation, immunity, and tumorigenesis. Recently, efforts to identify effective natural remedies and health supplements are increasing. Previous studies have reported that the cell lysates and the cell wall-bound lipoteichoic acids ofLactiplantibacillus plantarum K8(K8) exert anti-inflammatory and immunomodulative effects. However, the effect of K8 on cellular hypoxic responses remains unknown. In this study, we found that K8 lysates had a potent suppressive effect on gene expression under hypoxia. K8 lysates markedly downregulated hypoxia-induced HIF1α accumulation in the human bone marrow and lung cancer cell lines, SH-SY5Y and H460. Consequently, the transcription of known HIF1α target genes, such asp21,GLUT1, andALDOC, was notably suppressed in the K8 lysate supplement and purified lipoteichoic acids of K8, upon hypoxic induction. In addition, K8 lysates decreased the expression of PHD2 and VHL proteins, which are responsible for HIF1α destabilization under normoxic conditions. Overall, our results suggest that K8 lysates desensitize the cells to hypoxic stresses and suppress HIF1α-mediated hypoxic gene activation.
Genome-Wide Profiling of tRNA Using an Unexplored Reverse Transcriptase with High Processivity
Authors: Nakano Yuko , Gamper Howard , McGuigan Henri , Maharjan Sunita , Sun Zhiyi , Krishnan Keerthana , Yigit Erbay , Li Nan-Sheng , Piccirilli Joseph A. , Kleiner Ralph , Nichols Nicole , Hou Ya-Ming 
Published: December 2023

AbstractMonitoring the dynamic changes of cellular tRNA pools is challenging, due to the extensive post-transcriptional modifications of individual species. The most critical component in tRNAseq is a processive reverse transcriptase (RT) that can read through each modification with high efficiency. Here we show that the recently developed group-II intron RT Induro has the processivity and efficiency necessary to profile tRNA dynamics. Using our Induro-tRNAseq, simpler and more comprehensive than the best methods to date, we show that Induro progressively increases readthrough of tRNA over time and that the mechanism of increase is selective removal of RT stops, without altering the misincorporation frequency. We provide a parallel dataset of the misincorporation profile of Induro relative to the related TGIRT RT to facilitate the prediction of non-annotated modifications. We report an unexpected modification profile among human proline isoacceptors, absent from mouse and lower eukaryotes, that indicates new biology of decoding proline codons.
uniLIVER: a Human Liver Cell Atlas for Data-Driven Cellular State Mapping
Authors: Wu Yanhong , Fan Yuhan , Miao Yuxin , Li Yuman , Du Guifang , Chen Zeyu , Diao Jinmei , Chen Yu-Ann , Ye Mingli , You Renke , Chen Amin , Chen Yixin , Li Wenrui , Guo Wenbo , Dong Jiahong , Zhang Xuegong , Wang Yunfang , Gu Jin 
Published: December 2023

AbstractThe liver performs several vital functions such as metabolism, toxin removal and glucose storage through the coordination of various cell types. The cell type compositions and cellular states undergo significant changes in abnormal conditions such as fatty liver, cirrhosis and liver cancer. As the recent breakthrough of the single-cell/single-nucleus RNA-seq (sc/snRNA-seq) techniques, there is a great opportunity to establish a reference cell map of liver at single cell resolution with transcriptome-wise features. In this study, we build a unified liver cell atlas uniLIVER by integrative analyzing a large-scale sc/snRNA-seq data collection of normal human liver with 331,125 cells and 79 samples from 6 datasets. Besides the hierarchical cell type annotations, uniLIVER also proposed a novel data-driven strategy to map any query dataset to the normal reference map by developing a machine learning based framework named LiverCT. Applying LiverCT on the datasets from multiple abnormal conditions (1,867,641 cells and 439 samples from 12 datasets), the alterations of cell type compositions and cellular states were systematically investigated in liver cancer.
Astrocytes regulate neuronal network burst frequency through NMDA receptors species- and donor-specifically
Authors: Räsänen Noora , Tiihonen Jari , Koskuvi Marja , Lehtonen Šárka , Jalkanen Nelli , Karmila Nelli , Weert Isabelle , Vaurio Olli , Ojansuu Ilkka , Lähteenvuo Markku , Pietiläinen Olli , Koistinaho Jari 
Published: December 2023

AbstractBackgroundDevelopment of synaptic activity is a neuronal key characteristic that relies largely on interactions between neurons and astrocytes. Although astrocytes have known roles in regulating synaptic function and malfunction, the use of human or donor-specific astrocytes in disease models is still rare. Rodent astrocytes are routinely used to enhance neuronal activity in cell cultures, but less is known how human astrocytes influence neuronal activity.MethodsWe established human induced pluripotent stem cell (hiPSC)-derived neuron-astrocyte co-cultures and studied their functional development on microelectrode array (MEA). We used cell lines from 5 neurotypical control individuals and 3 pairs of monozygotic twins discordant for schizophrenia. A method combining Ngn2 overexpression and dual SMAD inhibition was used for neuronal differentiation. The neurons were co-cultured with hiPSC-derived astrocytes differentiated from 6-month-old astrospheres or rat astrocytes.ResultsWe found that the hiPSC-derived co-cultures develop complex network bursting activity similarly to neuronal co-cultures with rat astrocytes. However, the effect of NMDA receptors on neuronal network burst frequency (NBF) differed between co-cultures containing human or rat astrocytes. By using co-cultures derived from patients with schizophrenia and unaffected individuals, we found lowered NBF in the affected cells. We continued to demonstrate how astrocytes from an unaffected individual rescue the lowered NBF in the affected neurons by increasing NMDA receptor activity.ConclusionsOur results indicate that astrocytes participate in the regulation of neuronal NBF through a mechanism involving NMDA receptors. These findings shed light on the importance of using human and donor-specific astrocytes in disease modeling.
A novel thermostable and processive reverse transcriptase from a group II intron ofAnoxybacillus flavithermus
Authors: Oscorbin Igor P. , Filipenko Maxim L. 
Published: December 2023

AbstractReverse transcriptases (RTs) are a family of enzymes synthesizing DNA using an RNA template and participating in retrovirus propagation and telomere lengthening. In vitro, RTs are widely applied in various methods, including RNA-seq, RT-PCR and RT-LAMP. Thermostable RTs from bacterial group II introns are promising tools for biotechnology; they showed higher thermostability, fidelity and processivity comparing to commonly using M-MuLV RT and its mutants. However, the diversity of group II intron-encoded RTs is still insufficiently studied. Here, we biochemically characterized a novel RT from a thermophilic bacterium Anoxybacillus flavithermus, isolated from a hot spring in New Zealand with an optimal temperature for growth around 60°C. The cloned RT, named Afl RT, retained around 40% of the specific activity after 45 min incubation at 50°C. Optimal pH was 8.5, temperature — 45-50 °C and Mn2+ions were an optimal cofactor. In a processivity analysis with MS2 phage gRNA (3569 b), Afl RT elongated fully up to 36% of template molecules. In reverse transcription and RT-qLAMP, the enzyme allowed to detect up to 10 copies of MS2 phage genomic RNA per reaction. Thus, Afl RT is a promising enzyme for practical applications requiring thermostable processive RTs.
Recovering short DNA fragments from minerals and marine sediments: a comparative study evaluating lysis and isolation approaches
Authors: Gande Darjan , Hassenrück Christiane , Žure Marina , Richter-Heitmann Tim , Willerslev Eske , Friedrich Michael W. 
Published: December 2023

AbstractMarine sediments as excellent climate archives, contain among other biomolecules substantial amounts of extracellular DNA. Through mechanisms of binding to various minerals, some of the DNA stays protected from degradation and remains preserved. While this pool of DNA represents genomic ecosystem fingerprints spanning over millions of years, the capability of current DNA extraction methods in recovering mineral-bound DNA remains poorly understood. We evaluated current sedimentary DNA extraction approaches and their ability to desorb and extract short DNA fragments from pure clay and quartz minerals as well as from different types of marine sediments. We separately investigated lysis (DNA release) and isolation steps (purification of DNA) comparing five different types of lysis buffers across two commonly used DNA isolation approaches: silica magnetic beads and liquid-phase organic extraction and purification. The choice of lysis buffer significantly impacted the amount of recovered mineral-bound DNA and facilitated selective desorption of DNA fragments. High molarity EDTA and phosphate lysis buffers recovered on average an order of magnitude more DNA from clay than other tested buffers, while both isolation approaches recovered comparable amounts of DNA. However, organic extraction caused an inhibitory effect in subsequent downstream applications (e.g., PCR), across all assessed sediment DNA extracts while silica magnetic beads induced inhibition only in half of the tested DNA extracts. Furthermore, we demonstrate that both, the isolation approach and the lysis buffer play a decisive role in successful library preparation and that lysis buffer choice impacted the final library fragment distribution. With this study, we underscore the critical importance of lysis buffer selection to maximize the recovery of mineral-bound DNA in sedimentary DNA extractions and show its profound impact on recovered fragment lengths, a crucial factor alongside existing isolation approaches in facilitating high-quality DNA extracts for downstream analysis related to ancient environmental (aeDNA) research.
Dynamics of AdultAxin2Cell Lineage Integration in Granule Neurons of the Dentate Gyrus
Authors: Sharifi Khadijeh A. , Farzad Faraz , Soldozy Sauson , Price Richard J. , Kalani M. Yashar S. , Tvrdik Petr 
Published: December 2023

AbstractThe Wnt pathway plays critical roles in neurogenesis. The expression ofAxin2is induced by Wnt/β-catenin signaling, making this gene a sensitive indicator of canonical Wnt activity. We employed pulse-chase genetic lineage tracing with theAxin2-CreERT2allele to follow the fate ofAxin2-positive cells in the adult hippocampal formation. We foundAxin2expressed in astrocytes, neurons and endothelial cells, as well as in the choroid plexus epithelia. Simultaneously with tamoxifen induction ofAxin2fate mapping, the dividing cells were marked with 5-ethynyl-2’-deoxyuridine (EdU). Tamoxifen induction resulted in significant increase of dentate gyrus granule cells three months later; however, none of these neurons contained EdU signal. Conversely, six months after the tamoxifen/EdU pulse-chase labeling, EdU-positive granule neurons were identified in each animal. Our data imply thatAxin2is expressed at several different stages of adult granule neuron differentiation and suggest that the process of integration of the adult-born neurons from certain cell lineages may take longer than previously thought.