bluuebunny/crossref_metadata_2025_split huggingface dataset:
Design principles for energy transfer in the photosystem II supercomplex from kinetic transition networks
Authors: Yang Shiun-Jr , Wales David J. , Woods Esmae J. , Fleming Graham R. 
Published: October 2024

AbstractPhotosystem II (PSII) has the unique ability to perform water-splitting. With light-harvesting complexes, it forms the PSII supercomplex (PSII-SC) which is a functional unit that can perform efficient energy conversion, as well as photoprotection, allowing photosynthetic organisms to adapt to the naturally fluctuating sunlight intensity. Achieving these functions requires a collaborative energy transfer network between all subunits of the PSII-SC. In this work, we perform kinetic analyses and characterise the energy landscape of the PSII-SC with a structure-based energy transfer model. With first passage time analyses and kinetic Monte Carlo simulations, we are able to map out the overall energy transfer network. We also investigate how energy transfer pathways are affected when individual protein complexes are removed from the network, revealing the functional roles of the subunits of the PSII-SC. In addition, we provide a quantitative description of the flat energy landscape of the PSII-SC. We show that it is a unique landscape that produces multiple kinetically relevant pathways, corresponding to a high pathway entropy. These design principles are crucial for balancing efficient energy conversion and photoprotection.
Exploring consumer acceptability of leafy greens in earth and space immersive environments using biometrics
Authors: Gonzalez Viejo Claudia , Harris Natalie , Tongson Eden , Fuentes Sigfredo 
Published: October 2024

AbstractNovel research on food perception is required for long-term space exploration. There is limited research on food/beverage sensory analysis in space and space-simulated conditions, with many studies presenting biases in sensory and statistical methods. This study used univariate and multivariate analysis on data from pick-and-eat leafy greens to assess self-reported and biometric consumer sensory analysis in simulated microgravity using reclining chairs and space-immersive environments. According to ANOVA (p < 0.05), there were significant differences between interaction room × position for head movements; besides, there were non-significant differences in the interaction samples × environment. On the other hand, there were significant differences in the sample×position interaction for all liking attributes. Results from multivariate analysis showed effects on self-reported, physiological, and emotional responses of samples in space-related positions and environments related to sensory perception changes. Non-invasive biometrics could offer a powerful tool for developing digital twins to assess genetically modified plants and plant-based food/beverages for long-term space exploration.
Spatial and functional separation of mTORC1 signalling in response to different amino acid sources
Authors: Fernandes Stephanie A. , Angelidaki Danai-Dimitra , Nüchel Julian , Pan Jiyoung , Gollwitzer Peter , Elkis Yoav , Artoni Filippo , Wilhelm Sabine , Kovacevic-Sarmiento Marija , Demetriades Constantinos 
Published: October 2024

AbstractAmino acid (AA) availability is a robust determinant of cell growth through controlling mechanistic/mammalian target of rapamycin complex 1 (mTORC1) activity. According to the predominant model in the field, AA sufficiency drives the recruitment and activation of mTORC1 on the lysosomal surface by the heterodimeric Rag GTPases, from where it coordinates the majority of cellular processes. Importantly, however, the teleonomy of the proposed lysosomal regulation of mTORC1 and where mTORC1 acts on its effector proteins remain enigmatic. Here, by using multiple pharmacological and genetic means to perturb the lysosomal AA-sensing and protein recycling machineries, we describe the spatial separation of mTORC1 regulation and downstream functions in mammalian cells, with lysosomal and non-lysosomal mTORC1 phosphorylating distinct substrates in response to different AA sources. Moreover, we reveal that a fraction of mTOR localizes at lysosomes owing to basal lysosomal proteolysis that locally supplies new AAs, even in cells grown in the presence of extracellular nutrients, whereas cytoplasmic mTORC1 is regulated by exogenous AAs. Overall, our study substantially expands our knowledge about the topology of mTORC1 regulation by AAs and hints at the existence of distinct, Rag- and lysosome-independent mechanisms that control its activity at other subcellular locations. Given the importance of mTORC1 signalling and AA sensing for human ageing and disease, our findings will probably pave the way towards the identification of function-specific mTORC1 regulators and thus highlight more effective targets for drug discovery against conditions with dysregulated mTORC1 activity in the future.
Diverse anti-defence systems are encoded in the leading region of plasmids
Authors: Samuel Bruria , Mittelman Karin , Croitoru Shirly Ynbal , Ben Haim Maya , Burstein David 
Published: October 2024

AbstractPlasmids are major drivers of gene mobilization by means of horizontal gene transfer and play a key role in spreading antimicrobial resistance among pathogens1,2. Despite various bacterial defence mechanisms such as CRISPR–Cas, restriction–modification systems and SOS-response genes that prevent the invasion of mobile genetic elements3, plasmids robustly transfer within bacterial populations through conjugation4,5. Here we show that the leading region of plasmids, the first to enter recipient cells, is a hotspot for an extensive repertoire of anti-defence systems, encoding anti-CRISPR, anti-restriction, anti-SOS and other counter-defence proteins. We further identified in the leading region a prevalence of promoters known to allow expression from single-stranded DNA6, potentially facilitating rapid protection against bacterial immunity during the early stages of plasmid establishment. We demonstrated experimentally the importance of anti-defence gene localization in the leading region for efficient conjugation. These results indicate that focusing on the leading region of plasmids could lead to the discovery of diverse anti-defence genes. Combined, our findings show a new facet of plasmid dissemination and provide theoretical foundations for developing efficient conjugative delivery systems for natural microbial communities.
Structural basis of mRNA decay by the human exosome–ribosome supercomplex
Authors: Kögel Alexander , Keidel Achim , Loukeri Matina-Jasemi , Kuhn Christopher C. , Langer Lukas M. , Schäfer Ingmar B. , Conti Elena 
Published: October 2024

AbstractThe interplay between translation and mRNA decay is widespread in human cells1–3. In quality-control pathways, exonucleolytic degradation of mRNA associated with translating ribosomes is mediated largely by the cytoplasmic exosome4–9, which includes the exoribonuclease complex EXO10 and the helicase complex SKI238 (refs. 10–16). The helicase can extract mRNA from the ribosome and is expected to transfer it to the exoribonuclease core through a bridging factor, HBS1L3 (also known as SKI7), but the mechanisms of this molecular handover remain unclear7,17,18. Here we reveal how human EXO10 is recruited by HBS1L3 (SKI7) to an active ribosome-bound SKI238 complex. We show that rather than a sequential handover, a direct physical coupling mechanism takes place, which culminates in the formation of a cytoplasmic exosome–ribosome supercomplex. Capturing the structure during active decay reveals a continuous path in which an RNA substrate threads from the 80S ribosome through the SKI2 helicase into the exoribonuclease active site of the cytoplasmic exosome complex. The SKI3 subunit of the complex directly binds to HBS1L3 (SKI7) and also engages a surface of the 40S subunit, establishing a recognition platform in collided disomes. Exosome and ribosome thus work together as a single structural and functional unit in co-translational mRNA decay, coordinating their activities in a transient supercomplex.
Single-neuron representations of odours in the human brain
Authors: Kehl Marcel S. , Mackay Sina , Ohla Kathrin , Schneider Matthias , Borger Valeri , Surges Rainer , Spehr Marc , Mormann Florian 
Published: October 2024

AbstractOlfaction is a fundamental sensory modality that guides animal and human behaviour1,2. However, the underlying neural processes of human olfaction are still poorly understood at the fundamental—that is, the single-neuron—level. Here we report recordings of single-neuron activity in the piriform cortex and medial temporal lobe in awake humans performing an odour rating and identification task. We identified odour-modulated neurons within the piriform cortex, amygdala, entorhinal cortex and hippocampus. In each of these regions, neuronal firing accurately encodes odour identity. Notably, repeated odour presentations reduce response firing rates, demonstrating central repetition suppression and habituation. Different medial temporal lobe regions have distinct roles in odour processing, with amygdala neurons encoding subjective odour valence, and hippocampal neurons predicting behavioural odour identification performance. Whereas piriform neurons preferably encode chemical odour identity, hippocampal activity reflects subjective odour perception. Critically, we identify that piriform cortex neurons reliably encode odour-related images, supporting a multimodal role of the human piriform cortex. We also observe marked cross-modal coding of both odours and images, especially in the amygdala and piriform cortex. Moreover, we identify neurons that respond to semantically coherent odour and image information, demonstrating conceptual coding schemes in olfaction. Our results bridge the long-standing gap between animal models and non-invasive human studies and advance our understanding of odour processing in the human brain by identifying neuronal odour-coding principles, regional functional differences and cross-modal integration.
Overconfidence in climate overshoot
Authors: Schleussner Carl-Friedrich , Ganti Gaurav , Lejeune Quentin , Zhu Biqing , Pfleiderer Peter , Prütz Ruben , Ciais Philippe , Frölicher Thomas L. , Fuss Sabine , Gasser Thomas , Gidden Matthew J. , Kropf Chahan M. , Lacroix Fabrice , Lamboll Robin , Martyr Rosanne , Maussion Fabien , McCaughey Jamie W. , Meinshausen Malte , Mengel Matthias , Nicholls Zebedee , Quilcaille Yann , Sanderson Benjamin , Seneviratne Sonia I. , Sillmann Jana , Smith Christopher J. , Steinert Norman J. , Theokritoff Emily , Warren Rachel , Price Jeff , Rogelj Joeri 
Published: October 2024

AbstractGlobal emission reduction efforts continue to be insufficient to meet the temperature goal of the Paris Agreement1. This makes the systematic exploration of so-called overshoot pathways that temporarily exceed a targeted global warming limit before drawing temperatures back down to safer levels a priority for science and policy2–5. Here we show that global and regional climate change and associated risks after an overshoot are different from a world that avoids it. We find that achieving declining global temperatures can limit long-term climate risks compared with a mere stabilization of global warming, including for sea-level rise and cryosphere changes. However, the possibility that global warming could be reversed many decades into the future might be of limited relevance for adaptation planning today. Temperature reversal could be undercut by strong Earth-system feedbacks resulting in high near-term and continuous long-term warming6,7. To hedge and protect against high-risk outcomes, we identify the geophysical need for a preventive carbon dioxide removal capacity of several hundred gigatonnes. Yet, technical, economic and sustainability considerations may limit the realization of carbon dioxide removal deployment at such scales8,9. Therefore, we cannot be confident that temperature decline after overshoot is achievable within the timescales expected today. Only rapid near-term emission reductions are effective in reducing climate risks.
Dendritic, delayed, stochastic CaMKII activation in behavioural time scale plasticity
Authors: Jain Anant , Nakahata Yoshihisa , Pancani Tristano , Watabe Tetsuya , Rusina Polina , South Kelly , Adachi Kengo , Yan Long , Simorowski Noriko , Furukawa Hiro , Yasuda Ryohei 
Published: October 2024

AbstractBehavioural time scale plasticity (BTSP) is non-Hebbian plasticity induced by integrating presynaptic and postsynaptic components separated by a behaviourally relevant time scale (seconds)1. BTSP in hippocampal CA1 neurons underlies place cell formation. However, the molecular mechanisms that enable synapse-specific plasticity on a behavioural time scale are unknown. Here we show that BTSP can be induced in a single dendritic spine using two-photon glutamate uncaging paired with postsynaptic current injection temporally separated by a behavioural time scale. Using an improved Ca2+/calmodulin-dependent kinase II (CaMKII) sensor, we did not detect CaMKII activation during this BTSP induction. Instead, we observed dendritic, delayed and stochastic CaMKII activation (DDSC) associated with Ca2+ influx and plateau potentials 10–100 s after BTSP induction. DDSC required both presynaptic and postsynaptic activity, which suggests that CaMKII can integrate these two signals. Also, optogenetically blocking CaMKII 15–30 s after the BTSP protocol inhibited synaptic potentiation, which indicated that DDSC is an essential mechanism of BTSP. IP3-dependent intracellular Ca2+ release facilitated both DDSC and BTSP. Thus, our study suggests that non-synapse-specific CaMKII activation provides an instructive signal with an extensive time window over tens of seconds during BTSP.
Quasi-periodic X-ray eruptions years after a nearby tidal disruption event
Authors: Nicholl M. , Pasham D. R. , Mummery A. , Guolo M. , Gendreau K. , Dewangan G. C. , Ferrara E. C. , Remillard R. , Bonnerot C. , Chakraborty J. , Hajela A. , Dhillon V. S. , Gillan A. F. , Greenwood J. , Huber M. E. , Janiuk A. , Salvesen G. , van Velzen S. , Aamer A. , Alexander K. D. , Angus C. R. , Arzoumanian Z. , Auchettl K. , Berger E. , de Boer T. , Cendes Y. , Chambers K. C. , Chen T.-W. , Chornock R. , Fulton M. D. , Gao H. , Gillanders J. H. , Gomez S. , Gompertz B. P. , Fabian A. C. , Herman J. , Ingram A. , Kara E. , Laskar T. , Lawrence A. , Lin C.-C. , Lowe T. B. , Magnier E. A. , Margutti R. , McGee S. L. , Minguez P. , Moore T. , Nathan E. , Oates S. R. , Patra K. C. , Ramsden P. , Ravi V. , Ridley E. J. , Sheng X. , Smartt S. J. , Smith K. W. , Srivastav S. , Stein R. , Stevance H. F. , Turner S. G. D. , Wainscoat R. J. , Weston J. , Wevers T. , Young D. R. 
Published: October 2024

AbstractQuasi-periodic eruptions (QPEs) are luminous bursts of soft X-rays from the nuclei of galaxies, repeating on timescales of hours to weeks1–5. The mechanism behind these rare systems is uncertain, but most theories involve accretion disks around supermassive black holes (SMBHs) undergoing instabilities6–8 or interacting with a stellar object in a close orbit9–11. It has been suggested that this disk could be created when the SMBH disrupts a passing star8,11, implying that many QPEs should be preceded by observable tidal disruption events (TDEs). Two known QPE sources show long-term decays in quiescent luminosity consistent with TDEs4,12 and two observed TDEs have exhibited X-ray flares consistent with individual eruptions13,14. TDEs and QPEs also occur preferentially in similar galaxies15. However, no confirmed repeating QPEs have been associated with a spectroscopically confirmed TDE or an optical TDE observed at peak brightness. Here we report the detection of nine X-ray QPEs with a mean recurrence time of approximately 48 h from AT2019qiz, a nearby and extensively studied optically selected TDE16. We detect and model the X-ray, ultraviolet (UV) and optical emission from the accretion disk and show that an orbiting body colliding with this disk provides a plausible explanation for the QPEs.
Temporally distinct 3D multi-omic dynamics in the developing human brain
Authors: Heffel Matthew G. , Zhou Jingtian , Zhang Yi , Lee Dong-Sung , Hou Kangcheng , Pastor-Alonso Oier , Abuhanna Kevin D. , Galasso Joseph , Kern Colin , Tai Chu-Yi , Garcia-Padilla Carlos , Nafisi Mahsa , Zhou Yi , Schmitt Anthony D. , Li Terence , Haeussler Maximilian , Wick Brittney , Zhang Martin Jinye , Xie Fangming , Ziffra Ryan S. , Mukamel Eran A. , Eskin Eleazar , Nowakowski Tomasz J. , Dixon Jesse R. , Pasaniuc Bogdan , Ecker Joseph R. , Zhu Quan , Bintu Bogdan , Paredes Mercedes F. , Luo Chongyuan 
Published: October 2024

AbstractThe human hippocampus and prefrontal cortex play critical roles in learning and cognition1,2, yet the dynamic molecular characteristics of their development remain enigmatic. Here we investigated the epigenomic and three-dimensional chromatin conformational reorganization during the development of the hippocampus and prefrontal cortex, using more than 53,000 joint single-nucleus profiles of chromatin conformation and DNA methylation generated by single-nucleus methyl-3C sequencing (snm3C-seq3)3. The remodelling of DNA methylation is temporally separated from chromatin conformation dynamics. Using single-cell profiling and multimodal single-molecule imaging approaches, we have found that short-range chromatin interactions are enriched in neurons, whereas long-range interactions are enriched in glial cells and non-brain tissues. We reconstructed the regulatory programs of cell-type development and differentiation, finding putatively causal common variants for schizophrenia strongly overlapping with chromatin loop-connected, cell-type-specific regulatory regions. Our data provide multimodal resources for studying gene regulatory dynamics in brain development and demonstrate that single-cell three-dimensional multi-omics is a powerful approach for dissecting neuropsychiatric risk loci.
One-shot entorhinal maps enable flexible navigation in novel environments
Authors: Wen John H. , Sorscher Ben , Aery Jones Emily A. , Ganguli Surya , Giocomo Lisa M. 
Published: October 2024

AbstractAnimals must navigate changing environments to find food, shelter or mates. In mammals, grid cells in the medial entorhinal cortex construct a neural spatial map of the external environment1–5. However, how grid cell firing patterns rapidly adapt to novel or changing environmental features on a timescale relevant to behaviour remains unknown. Here, by recording over 15,000 grid cells in mice navigating virtual environments, we tracked the real-time state of the grid cell network. This allowed us to observe and predict how altering environmental features influenced grid cell firing patterns on a nearly instantaneous timescale. We found evidence that visual landmarks provide inputs to fixed points in the grid cell network. This resulted in stable grid cell firing patterns in novel and altered environments after a single exposure. Fixed visual landmark inputs also influenced the grid cell network such that altering landmarks induced distortions in grid cell firing patterns. Such distortions could be predicted by a computational model with a fixed landmark to grid cell network architecture. Finally, a medial entorhinal cortex-dependent task revealed that although grid cell firing patterns are distorted by landmark changes, behaviour can adapt via a downstream region implementing behavioural timescale synaptic plasticity6. Overall, our findings reveal how the navigational system of the brain constructs spatial maps that balance rapidity and accuracy. Fixed connections between landmarks and grid cells enable the brain to quickly generate stable spatial maps, essential for navigation in novel or changing environments. Conversely, plasticity in regions downstream from grid cells allows the spatial maps of the brain to more accurately mirror the external spatial environment. More generally, these findings raise the possibility of a broader neural principle: by allocating fixed and plastic connectivity across different networks, the brain can solve problems requiring both rapidity and representational accuracy.
Distinct copy number signatures between residual benign and transformed areas of carcinoma ex pleomorphic adenoma
Authors: Scarini João Figueira , Sabino Wellington Lima , de Lima-Souza Reydson Alcides , Egal Erika Said Abu , Tincani Alfio José , Gondak Rogério , Kowalski Luiz Paulo , Krepischi Ana Cristina Victorino , Altemani Albina , Mariano Fernanda Viviane 
Published: October 2024

AbstractThe mechanisms involved with the pathogenesis of carcinoma ex pleomorphic adenoma (CXPA) seem to be associated with the accumulation of molecular alterations in the pleomorphic adenoma (PA). In this sense, using array-based comparative genomic hybridization (aCGH) a rare series of 27 cases of CXPA and 14 residual PA (rPA) adjacent to the transformation area, we investigated the profile of the copy number alterations (CNAs) comparing benign residual and transformed areas. The main findings were correlated with the histopathological classification by histologic subtype and degree of invasion. The distribution of losses (p = 0.187) and amplifications (p = 0.172) was not statistically different between rPA and CXPA. The number of gains was increased in the transformed areas compared to the benign residual areas (p = 0.005). PLAG1 gain was maintained along the malignant transformation, as it was observed in both residual PA and CXPA samples, likely being an earlier event during transformation. The amplification of GRB7 and ERBB2 may also be an initial step in the malignant transformation of PA to CXPA (salivary duct carcinoma subtype). Furthermore, the amplification of HMGA2 and RPSAP52 were the most prevalent alterations among the studied samples. It was noteworthy that amplified genes in the transformed areas of the tumors were enriched for biological processes related to immune signaling. In conclusion, our results underscored for the first-time crucial CNAs in CXPA, some of them shared with the residual benign area adjacent to the transformation site. These CNAs included PLAG1 gain, as well as amplification of GRB7, ERBB2, HMGA2, and RPSAP52.
Aging affects regrowth of stealthperitoneal dissemination of advanced ovarian cancer: a multicenter retrospective cohort study
Authors: Fujimoto Hiroki , Yoshihara Masato , Ricciardelli Carmela , Tano Sho , Iyoshi Shohei , Miyamoto Emiri , Mogi Kazumasa , Hayashi Maia , Hayakawa Sae , Nomura Satoshi , Kitami Kazuhisa , Uno Kaname , Yoshikawa Nobuhisa , Emoto Ryo , Matsui Shigeyuki , Kajiyama Hiroaki 
Published: October 2024

AbstractOvarian cancer (OvCa) is one of the most lethal gynecological malignancies, and most patients are diagnosed at advanced stage with peritoneal dissemination. Although age at diagnosis is considered an independent prognostic factor, its impact on peritoneal recurrence after combined cytoreductive surgery and chemotherapy is not clear. The objective of this study was to investigate the impact of aging on peritoneal recurrence from stealth dissemination and gain insight of the pathophysiology of OvCa in elderly patients. A total of 243 patients with pT2b-pT3 epithelial ovarian who achieved complete surgery, no-residual tumor at first surgery, were selected to be analyzed the risk of peritoneal seeding and recurrence. We found that age over 65 years was independently associated with an increased risk of peritoneum-specific (PS) recurrence (. Furthermore, pT3 stages and positive ascites cytology also worsen the PS-relapse-free survival. Collectively, our findings suggest that age, especially over 65 years, predicts reduced peritoneum-specific tumor recurrence in patients with advanced ovarian cancer after complete cytoreduction surgery, particularly those with pT3 tumors and positive ascites cytology.