bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coordination of flux-related leaf and root traits impacts forest community assembly
Authors: Ma Zeqing , Duan Mengcheng , Sack Lawren , Ma Chengen , Li Le , McCormack M. Luke , Lu Mingzhen , Guo Dali 
Published: November 2024

AbstractUnderstanding the functions and coordination of plant traits is critical for predicting how diverse species respond to climate change. According to hydraulic and economic theories, leaves and roots—key organs for resource acquisition—are expected to function in coordination, such that species with faster resource utilization would possess leaf and root traits that facilitate rapid carbon, nutrient, and water uptake and fluxes. However, there has been limited evidence supporting leaf-root trait coordination and a role for that coordination on community structure. Here, we measured 13 leaf and root functional traits for 101 woody species from six tropical and subtropical forests, and assessed coordination and its association with community dominance. Hydraulic traits, such as leaf vein density and root vessel density, were coordinated between organs and showed compensation trade-offs between traits within organs, such as, leaf vein density and diameter. Economic traits relating to composition, such as nitrogen concentration, were coordinated between organs, whereas economic structural traits were decoupled, such as leaf mass per area and specific root length. Overall, hydraulic traits and economics traits were partially independent. The coordination of flux-related leaf and root traits was associated with ectomycorrhizal symbiosis and with dominance within the community. These findings indicate how trait organization within and across organs contributes to optimal whole plant function, with implications for performance in natural communities.
SMAC mimetics induce human macrophages to phagocytose live cancer cells
Authors: Liu Samantha Y. , Hulsman Max , Leyendecker Philipp , Chang Eugena , Donovan Katherine A. , Strobel Fabian , Dougan James , Fischer Eric S. , Dougan Michael , Dougan Stephanie K. , Qiang Li 
Published: November 2024

AbstractMacrophages engulf apoptotic bodies and cellular debris as part of homeostasis, but they can also phagocytose live cells such as aged red blood cells. Pharmacologic reprogramming with the SMAC mimetic LCL161 in combination with T cell-derived cytokines can induce macrophages to phagocytose live cancer cells in mouse models. Here we extend these findings to encompass a wide range of monovalent and bivalent SMAC mimetic compounds, demonstrating that live cell phagocytosis is a class effect of these agents. We demonstrate robust phagocytosis of live pancreatic and breast cancer cells by primary human macrophages across a range of healthy donors. Unlike mouse macrophages where combination of SMAC mimetics with lymphotoxin enhanced phagocytosis, human macrophages were more efficiently polarized to phagocytose live cells by the combination of SMAC mimetics and IFNψ. We profiled phagocytic macrophages by transcriptional and proteomic methodologies, uncovering a positive feedback loop of autocrine TNFα production.
Covert muscle activity reveals dynamic freezing states and prepares the animal for action
Authors: Hobbiss Anna F. , Franco Mariana C. , Medeiros Alexandra M. , Rosher Charlie , Mendes César S. , Moita Marta A. 
Published: November 2024

AbstractWhen an animal detects a threat it must make a split-second choice between fight, flight or freezing (1–3). During freezing, skeletal muscles sustain tension to maintain rigid, sometimes atypical postures, for many minutes at a time (4). Meanwhile the animal must dynamically assess its surroundings to plan future actions and ready its body for movement. The interplay between the neural and somatic systems during freezing remains poorly understood. Here we show that freezingDrosophila melanogasterdisplay a striking novel pattern of leg muscle activation unique to immobility, a rhythmic pulsing in the distal tibia. The muscle, which we show to be a previously undescribed leg accessory heart, displays multiple activity modes and ramps up to movement onset, implying a preparation for movement. The frequency of pulsing is dynamically modulated as the fly integrates external threat or safety cues, and artificially increasing pulse frequency leads to freezing breaks, indicating a causal role in the decision to move. Through the identification of a newDrosophilacardiac organ, this study provides a window into the multiple states which can underlie freezing behaviour, and the physiological changes which the body undergoes to ready the animal to move.
Inhibition of microtubule polymerization and dynein impairs the nuclear localization of the ependymoma-associated ZFTA-RELA fusion protein and NF-κB activation
Authors: Ishii Masaki , Suto Naoki , Katakawa Kazuaki , Makino Kosho , Toma-Fukai Sachiko , Sueki Shunsuke , Anada Masahiro , Kojima Hirotatsu , Ohata Shinya 
Published: November 2024

AbstractEpendymomas are rare and chemotherapy-resistant gliomas. One subclass of supratentorial ependymomas, ST-EPN-ZFTA, expresses a fusion protein consisting of a nuclear protein, zinc finger translocation associated (ZFTA), andv-relreticuloendotheliosis viral oncogene homolog A (RELA), an effector transcription factor of the nuclear factor-κB (NF-κB) pathway (ZFTA-RELA). Constitutive localization of ZFTA-RELA to the nucleus hyperactivates the oncogenic NF-κB signaling pathway, thereby contributing to the pathogenesis of ST-EPN-ZFTA. To identify compounds that inhibit NF-κB activity induced by ZFTA-RELA, we established a high-throughput screening system using the NF-κB-responsive luciferase reporter cell line 6E8, which expresses ZFTA-RELA in a doxycycline-dependent manner. A chemical library of 9600 compounds selected for their structural diversity was screened, and a colchicine derivative was identified. Among colchicine and six of its derivatives, the IC50on ZFTA-RELA-dependent NF-κB-responsive luciferase activity in 6E8 cells was found to be the lowest for colchicine at 90 nM. Interestingly, microtubule polymerization inhibitors (colchicine and vinblastine) and dynein inhibitors (ciliobrevin D and dynarrestin) impaired ZFTA-RELA’s nuclear localization and NF-κB activity in 6E8 cells. These findings indicate that microtubule polymerization and dynein play pivotal roles in activating the NF-κB pathway in ST-EPN-ZFTA by promoting the nuclear localization of ZFTA-RELA. Consequently, inhibition of microtubule polymerization may be a therapeutic strategy for ST-EPN-ZFTA.
The effect of prolonged elbow pain and rTMS on cortical inhibition: A TMS-EEG study
Authors: Chowdhury Nahian S , Chang Wei-Ju , Cheng Donovan , Manivasagan Naveen , Seminowicz David A , Schabrun Siobhan M 
Published: November 2024

AbstractIntroductionRecent studies using combined transcranial magnetic stimulation (TMS) and electroencephalography (EEG) have shown that pain leads to an increase in the N45 peak of the TMS-evoked potential (TEP), which is mediated by GABAergic inhibition. Conversely, 10Hz repetitive TMS (10Hz-rTMS), which provides pain relief, reduces the N45 peak. However, these studies used brief pain stimuli (lasting minutes), limiting their clinical relevance. The present study determined the effect of pain and 10Hz-rTMS on the N45 peak in a prolonged pain model (lasting several days) induced by nerve growth factor (NGF) injection to the elbow muscle.Materials and MethodsExperiment 1: TEPs were measured in 22 healthy participants on Day 0 (pre-NGF), Day 2 (peak pain), and Day 7 (pain resolution).Experiment 2: We examined the effect of 5 days of active (n=16) or sham (n=16) rTMS to the left primary motor cortex (M1) on the N45 peak during prolonged NGF-induced pain, with TEPs measured on Day 0 and Day 4 (post-rTMS).ResultsExperiment 1:While no overall change in the N45 peak was seen, a correlation emerged between higher pain severity on Day 2 and a larger increase in the N45 peak.Experiment 2: Active rTMS reduced the N45 peak on Day 4 vs. Day 0, with no effect in the sham group.ConclusionOur findings suggest that (i) higher pain severity correlates with an increase in the N45 peak, and (ii) rTMS decreases cortical inhibition in a model of prolonged experimental pain. This study extends previous research by demonstrating a link between pain perception and cortical inhibition within a prolonged pain context.
Rhamnogalacturonan-II dimerization deficiency impairs the coordination between growth and adhesion maintenance in plants
Authors: Baba Abu Imran , Lisica Lucija , Atakhani Asal , Aryal Bibek , Bogdziewiez Léa , Erguvan Özer , Heymans Adrien , Jewaria Pawan Kumar , Smith Richard S. , Bhalerao Rishikesh P. , Verger Stéphane 
Published: November 2024

SummaryCell adhesion is a fundamental feature of multicellular organisms. In plants, cell adhesion is mediated by the cell wall, but the control and maintenance of cell adhesion during growth and development remains poorly understood1. Here we uncover the role of a component of the cell wall, rhamnogalacturonan-II (RG-II) and its capacity to crosslink in the presence of Boron2, as a key regulator of plant cell adhesion maintenance. We show that RG-II dimerization deficiency leads to cell adhesion defects. Importantly, the analysis ofmur1mutants with RG-II dimerization defects uncovers a cell adhesion pathway that is distinct from that identified by the analysis of pectin deficient mutants3. We found that mutations in two cell wall integrity sensors, RESISTANCE TO FUSARIUM OXYSPORUM 1 and RECEPTOR-LIKE PROTEIN 44, as well as supplementation with the hormone brassinosteroid can partially rescue the adhesion defects associated with RG-II dimerization deficiency. We also show that adhesion defects associated with RG-II dimerization deficiency are related to increased epidermal tension as well as decreased homogalacturonan levels in the cell wall, which can also be rescued by supplementation with brassinosteroid. Overall, we propose that RG-II dimerization defects alter cell adhesion directly (reduced crosslinks) but also indirectly through cell wall integrity sensing, brassinosteroid signalling, cell wall remodelling and cell layer growth coordination. Thus, our results uncover the involvement of cell wall integrity sensors and hormonal signalling in the coordination between growth and adhesion maintenance in plants, which is a key feature for complex multicellularity.Highlights-RG-II dimerization is required for cell-cell adhesion in plants.-Cell wall integrity sensors and brassinosteroid signalling mediate cell adhesion downstream of RG-II dimerization.-Cell detachments due to defective RG-II dimerization are caused by weakened middle lamella and higher tissue tension.
Cluster nanoarchitecture and structural diversity of PIEZO1 in intact cells
Authors: Verkest Clement , Roettger Lucas , Zeitzschel Nadja , Lechner Stefan G. 
Published: November 2024

AbstractThe mechanically activated ion channel PIEZO1 confers mechanosensitivity to many cell types and is thus essential for numerous physiological processes triggered by mechanical cues1–4. PIEZO1 channels assemble as propeller-shaped trimers5–7, which supposedly undergo a transition from a curved conformational state into a flattened state upon mechanical activation8–11. Whether this gating model also applies to PIEZO1 clusters and to what extent membrane curvature alters PIEZO1 conformation in living cells, is, however, still unclear. Here, we used MINFLUX nanoscopy to resolve the architecture of PIEZO1 clusters and demonstrate that PIEZO1 channels collectively deform the cell membrane into pit-shaped invaginations, which accommodate multiple channels and flatten in response to mechanical stimulation. Moreover, our data suggests that the deformability of the membrane and thus the conformation and sensitivity of PIEZO1 are altered by the architecture and the rigidity of the cytoskeleton. Together, our data provide previously unrecognized structural details about the subcellular distribution and the conformational variability of PIEZO1 in different cellular compartments, which challenge previously proposed hypotheses derived from studies of isolated channels and thus highlight the importance of examining PIEZO1 in its native environment, where additional factors contribute to channel function and structure.
BPMs regulate Arabidopsis seedling development by promoting auxin-independent degradation of the Aux/IAA protein IAA10
Authors: Ban Zhaonan , Hou Yueh-Ju , Ku Ellyse , Zhu YingLin , Hu Yun , Karadanaian Natalie , Zhao Yunde , Estelle Mark 
Published: November 2024

AbstractAfter germination, seedlings undergo etiolated development (skotomorphogenesis), enabling them to grow towards the soil surface. In Arabidopsis, etiolated seedlings exhibit rapid hypocotyl elongation, apical hook formation and closed cotyledons to protect the meristem. In this study, we found that high-order mutants in theBPMgene family displayed defects in seedling development, characterized by a shorter hypocotyl, early apical hook opening, and opened cotyledons in the dark. BPM1, BPM2, BPM4, and BPM5 exhibit distinct expression patterns and subcellular localization in etiolated seedlings. In a hypocotyl segment assay thebpmmutants showed defects in auxin response indicating impaired auxin signaling in the hypocotyl. Expression of the auxin reporterDR5:GFPwas also altered in thebpm1,4,5mutant in various tissues compared to the wild type. Furthermore, we showed that BPM1 and IAA10 interact in yeast two-hybrid, BiFC, and Co-IP assays. Experiments in protoplasts indicated that BPM1 promotes ubiquitylation and degradation of IAA10, and the level of IAA10 protein is greater in thebpm1,4,5mutant. In addition, IAA10 over-expression resulted in phenotypes similar to thebpmmutants. These results indicate that the BPMs target the Aux/IAA proteins for ubiquitylation and degradation. Overall, our findings shed light on the key roles of the BPMs in auxin signaling during seedling development.
Transcriptome of the murine duodenum during recovery after a lethal dose of total body irradiation
Authors: He Ling , Bhat Kruttika , Pajonk Frank 
Published: November 2024

AbstractIn the aftermath of 9/11, the radiobiology community sought novel radiation mitigators capable of preventing death when administered 24 hours or later after exposure to lethal ionizing radiation. The survival and expansion of normal stem cells are crucial for restoring tissue integrity in time to prevent mortality. While FDA-approved drugs for acute radiation syndrome primarily target the hematopoietic system, restoring the integrity of the intestinal lining is equally important for survival. However, the radiation response of the intestinal stem cell (ISC) population and its niche environment is not as well understood as that of the bone marrow. The aim of this study was to explore early transcriptomic changes in the small intestine after a lethal dose of total body irradiation (TBI), and during subsequent recovery.C3H/Sed/Kam mice were irradiated with a TBI dose of 16 Gy, the published LD70/10. The compound 1-[(4-Nitrophenyl)sulfonyl]-4-phenylpiperazine (NSPP) was administered 24 hours post-irradiation. RNAs from the proximal duodenum were extracted at 28, 72, and 96 hours post-irradiation and subjected to RNA-sequencing. Differentially expressed genes were analyzed using gene-set enrichment analysis.Radiation induced significant transcriptomic changes known to precede the death of lymphatic endothelial and epithelial cells. Upregulation ofLgr5+ISC gene signature was observed during recovery. NSPP treatment further amplified the activation of ISC-associated genes and other regenerative markers. Notably, genePsrc1showed strong activation throughout the recovery process, highlighting its potential role in this regenerative response. These findings suggest additional points of intervention for radiation mitigation in the intestines beyond targeting programmed cell death.
Local disorder is associated with enhanced catalysis in an engineered photoswitch
Authors: McCormick James W. , Dinan Jerry C. , Russo Marielle AX , Reynolds Kimberly A. 
Published: November 2024

AbstractTheA. sativaLOV2 domain is commonly harnessed as a source of light-based regulation in engineered optogenetic switches. In prior work, we used LOV2 to create a light-regulated Dihydrofolate Reductase (DHFR) enzyme and showed that structurally disperse mutations in DHFR were able to tune the allosteric response to light. However, it remained unclear how light allosterically activates DHFR, and how disperse mutations modulate the allosteric effect. A mechanistic understanding of these phenomena would improve our ability to rationally design new light-regulated enzymes. We used a combination of Eyring analysis and CD spectroscopy to quantify the relationship between allostery, catalytic activity, and global thermal stability. We found that the DHFR/LOV2 fusion was marginally stable at physiological temperatures. LOV2 photoactivation simultaneously: (1) thermally destabilized the fusion and (2) lowered the catalytic transition free energy of the lit state relative to the dark state. The energetic effect of light activation on the transition state free energy was composed of two opposing forces: a favorable reduction in the enthalpic transition state barrier offset by an entropic penalty. Allostery-tuning mutations in DHFR acted through this tradeoff, either accentuating the enthalpic benefit or minimizing the entropic penalty but never improving both. Many of the allostery tuning mutations showed a negative correlation between the light induced change in thermal stability and catalytic activity, suggesting an activity-stability tradeoff.
Exploring Neural Dynamics in the Auditory Telencephalon of Crows using Functional Ultrasound Imaging
Authors: Liao Diana A. , Schwarzbach Eva , Nieder Andreas 
Published: November 2024

AbstractCrows, known for advanced cognitive abilities and vocal communication, rely on intricate auditory systems. While the neuroanatomy of corvid auditory pathways is partially explored, the underlying neurophysiological mechanisms are largely unknown. This study used functional ultrasound imaging (fUSi) to investigate sound-induced cerebral blood volume (CBV) changes in the field L complex of the crow’s auditory telencephalon, a functional analogue to the mammalian auditory cortex. FUSi revealed frequency-specific CBV responses, showing a tonotopic organization within the field L complex, with low frequencies in the posterior-dorsal region and high frequencies in the anterior-ventral region, similar to neuronal patterns reported in other songbirds. The responses were more robust when the crows were awake compared to when they were anesthetized. Machine learning analyses showed fUSi signals could be used to classify sound types accurately. Shorter stimuli reliably triggered transient CBV increases, while longer sounds resulted in variable responses, including negative deflections. This variability in CBV responses suggests a delineation of subregions within the field L complex with the central region (L2) as the primary processing hub and outer regions (L1, L3) integrating auditory information. These findings highlight the potential of fUSi for providing high-resolution insights into functional systems in corvids, enabling future exploration of task-related cognitive dynamics.
Population-based metaproteomics reveals functional associations between gut microbiota and phenotypes
Authors: Liang Shuang , Sun Yingying , Miao Zelei , Li Bang-yan , Xing Ziyuan , Xie Yuting , Cai Enci , Li Sainan , Liu Pu , Yang Min , Shuai Menglei , Gou Wanglong , Jiang Wenhao , Wang Youming , Gao Huanhuan , Zhang Ke , Yu Jing , Cai Xue , Wang Xingbing , Chen Yu-ming , Zheng Ju-Sheng , Guo Tiannan 
Published: November 2024

SummaryThe association between gut microbiota and physiological disorders underscores the crucial need to understand its largely unexplored biological functions. In this study, we analyzed 86,876 microbial proteins and 1,277 human proteins from 1,967 Chinese stool samples. Our results indicate that metaproteomic data captures the microbial biodiversity of a population more effectively than metagenomic data, displaying greater variability in microbial functions and providing reliable assessments of microbiota stability. We identified crucial functions of core microbes and discovered 10,714 associations between metaproteomic taxon, microbial function, or human proteins with 39 phenotypes, including 1,381 features related to Type 2 Diabetes (T2D). Importantly,Megasphaera elsdenii’s conversion of lactate to butyric acid appears to lower blood glucose levels, suggesting a protective mechanism against T2D. Our study underscores the power of population-based metaproteomics to offer unique functional insights into the gut microbiota.Highlights- The first large-scale population-based metaproteomics landscape.- Metaproteomics efficiently maps microbial functions, exposing individual functional variation.- 10,714 associations between metaproteomic taxa, microbial functions, or human proteins with 39 phenotypes.-Megasphaera elsdeniiprotects against elevated blood glucose levels in the host by degrading lactate to produce butyric acid.
Mycobacterial methionine aminopeptidase type 1c moonlights as an anti-association factor on the 30S ribosomal subunit
Authors: Banerjee Aneek , Srinivasan Krishnamoorthi , Sengupta Jayati 
Published: November 2024

AbstractMethionine aminopeptidase (MetAP), an essential metalloprotease, binds the 70S ribosome near the exit site of peptide tunnel and cleaves the N-terminal methionine from the nascent polypeptide chains. WhileE. coliexpresses a single subclass of type1 MetAP, mycobacteria possesses two subclasses, namely, MetAP1a and MetAP1c, differentiated by the presence of a 40 amino acid long N-terminal tether in the later. Here we reveal a yet unknown moonlighting role of MetAP1c in mycobacteria. We observe stationary phase-specific enhancement of expression and a unique 30S subunit affinity of MetAP1c. A 5Å cryo-EM map ofMycobacterium smegmatis(Msm) MetAP1c-30S subunit complex manifests for the first time the binding of MetAP1c at the inter-subunit side in the vicinity of proteins S13 and S19. MetAP1c binding and resulting conformational changes make the 30S subunit unfit for association with the 50S subunit, thereby conferring an anti-association property on MetAP1c. We further constructed two N-terminal mutants to establish the pivotal role of the N-terminal extension of MetAP1c in its moonlighting function.