bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutant p53 sustains serine-glycine synthesis and essential amino acids intake promoting breast cancer growth
Authors: Tombari Camilla , Zannini Alessandro , Bertolio Rebecca , Pedretti Silvia , Audano Matteo , Triboli Luca , Cancila Valeria , Vacca Davide , Caputo Manuel , Donzelli Sara , Segatto Ilenia , Vodret Simone , Piazza Silvano , Rustighi Alessandra , Mantovani Fiamma , Belletti Barbara , Baldassarre Gustavo , Blandino Giovanni , Tripodo Claudio , Bicciato Silvio , Mitro Nico , Del Sal Giannino 
Published: October 2023

AbstractReprogramming of amino acid metabolism, sustained by oncogenic signaling, is crucial for cancer cell survival under nutrient limitation. Here we discovered that missense mutant p53 oncoproteins stimulate de novo serine/glycine synthesis and essential amino acids intake, promoting breast cancer growth. Mechanistically, mutant p53, unlike the wild-type counterpart, induces the expression of serine-synthesis-pathway enzymes and L-type amino acid transporter 1 (LAT1)/CD98 heavy chain heterodimer. This effect is exacerbated by amino acid shortage, representing a mutant p53-dependent metabolic adaptive response. When cells suffer amino acids scarcity, mutant p53 protein is stabilized and induces metabolic alterations and an amino acid transcriptional program that sustain cancer cell proliferation. In patient-derived tumor organoids, pharmacological targeting of either serine-synthesis-pathway and LAT1-mediated transport synergizes with amino acid shortage in blunting mutant p53-dependent growth. These findings reveal vulnerabilities potentially exploitable for tackling breast tumors bearing missense TP53 mutations.
Direct biological fixation provides a freshwater sink for N2O
Authors: Si Yueyue , Zhu Yizhu , Sanders Ian , Kinkel Dorothee B. , Purdy Kevin J. , Trimmer Mark 
Published: October 2023

AbstractNitrous oxide (N2O) is a potent climate gas, with its strong warming potential and ozone-depleting properties both focusing research on N2O sources. Although a sink for N2O through biological fixation has been observed in the Pacific, the regulation of N2O-fixation compared to canonical N2-fixation is unknown. Here we show that both N2O and N2 can be fixed by freshwater communities but with distinct seasonalities and temperature dependencies. N2O fixation appears less sensitive to temperature than N2 fixation, driving a strong sink for N2O in colder months. Moreover, by quantifying both N2O and N2 fixation we show that, rather than N2O being first reduced to N2 through denitrification, N2O fixation is direct and could explain the widely reported N2O sinks in natural waters. Analysis of the nitrogenase (nifH) community suggests that while only a subset is potentially capable of fixing N2O they maintain a strong, freshwater sink for N2O that could be eroded by warming.
Visualization of accessible cholesterol using a GRAM domain-based biosensor
Authors: Koh Dylan Hong Zheng , Naito Tomoki , Na Minyoung , Yeap Yee Jie , Rozario Pritisha , Zhong Franklin L. , Lim Kah-Leong , Saheki Yasunori 
Published: October 2023

AbstractCholesterol is important for membrane integrity and cell signaling, and dysregulation of the distribution of cellular cholesterol is associated with numerous diseases, including neurodegenerative disorders. While regulated transport of a specific pool of cholesterol, known as “accessible cholesterol”, contributes to the maintenance of cellular cholesterol distribution and homeostasis, tools to monitor accessible cholesterol in live cells remain limited. Here, we engineer a highly sensitive accessible cholesterol biosensor by taking advantage of the cholesterol-sensing element (the GRAM domain) of an evolutionarily conserved lipid transfer protein, GRAMD1b. Using this cholesterol biosensor, which we call GRAM-W, we successfully visualize in real time the distribution of accessible cholesterol in many different cell types, including human keratinocytes and iPSC-derived neurons, and show differential dependencies on cholesterol biosynthesis and uptake for maintaining levels of accessible cholesterol. Furthermore, we combine GRAM-W with a dimerization-dependent fluorescent protein (ddFP) and establish a strategy for the ultrasensitive detection of accessible plasma membrane cholesterol. These tools will allow us to obtain important insights into the molecular mechanisms by which the distribution of cellular cholesterol is regulated.
GSG1L-containing AMPA receptor complexes are defined by their spatiotemporal expression, native interactome and allosteric sites
Authors: Perozzo Amanda M. , Schwenk Jochen , Kamalova Aichurok , Nakagawa Terunaga , Fakler Bernd , Bowie Derek 
Published: October 2023

AbstractTransmembrane AMPA receptor regulatory proteins (TARPs) and germ cell-specific gene 1-like protein (GSG1L) are claudin-type AMPA receptor (AMPAR) auxiliary subunits that profoundly regulate glutamatergic synapse strength and plasticity. While AMPAR-TARP complexes have been extensively studied, less is known about GSG1L-containing AMPARs. Here, we show that GSG1L’s spatiotemporal expression, native interactome and allosteric sites are distinct. GSG1L generally expresses late during brain development in a region-specific manner, constituting about 5% of all AMPAR complexes in adulthood. While GSG1L can co-assemble with TARPs or cornichons (CNIHs), it also assembles as the sole auxiliary subunit. Unexpectedly, GSG1L acts through two discrete evolutionarily-conserved sites on the agonist-binding domain with a weak allosteric interaction at the TARP/KGK site to slow desensitization, and a stronger interaction at a different site that slows recovery from desensitization. Together, these distinctions help explain GSG1L’s evolutionary past and how it fulfills a unique signaling role within glutamatergic synapses.
Evidence of unconventional superconductivity on the surface of the nodal semimetal CaAg1−xPdxP
Authors: Yano Rikizo , Nagasaka Shota , Matsubara Naoki , Saigusa Kazushige , Tanda Tsuyoshi , Ito Seiichiro , Yamakage Ai , Okamoto Yoshihiko , Takenaka Koshi , Kashiwaya Satoshi 
Published: October 2023

AbstractSurface states of topological materials provide extreme electronic states for unconventional superconducting states. CaAg1−xPdxP is an ideal candidate for a nodal-line Dirac semimetal with drumhead surface states and no additional bulk bands. Here, we report that CaAg1−xPdxP has surface states that exhibit unconventional superconductivity (SC) around 1.5 K. Extremely sharp magnetoresistance, tuned by surface-sensitive gating, determines the surface origin of the ultrahigh-mobility “electrons.” The Pd-doping elevates the Fermi level towards the surface states, and as a result, the critical temperature (Tc) is increased up to 1.7 K from 1.2 K for undoped CaAgP. Furthermore, a soft point-contact study at the surface of Pd-doped CaAgP proved the emergence of unconventional SC on the surface. We observed the bell-shaped conductance spectra, a hallmark of the unconventional SC. Ultrahigh mobility carriers derived from the surface flat bands generate a new class of unconventional SC.
Sialic acid O-acetylation patterns and glycosidic linkage type determination by ion mobility-mass spectrometry
Authors: Vos Gaёl M. , Hooijschuur Kevin C. , Li Zeshi , Fjeldsted John , Klein Christian , de Vries Robert P. , Toraño Javier Sastre , Boons Geert-Jan 
Published: October 2023

AbstractO-acetylation is a common modification of sialic acids that has been implicated in a multitude of biological and disease processes. A lack of analytical methods that can determine exact structures of sialic acid variants is a hurdle to determine roles of distinct O-acetylated sialosides. Here, we describe a drift tube ion mobility-mass spectrometry approach that can elucidate exact O-acetylation patterns as well as glycosidic linkage types of sialosides isolated from complex biological samples. It is based on the use of a library of synthetic O-acetylated sialosides to establish intrinsic collision cross section (CCS) values of diagnostic fragment ions. The CCS values were used to characterize O-acetylated sialosides from mucins and N-linked glycans from biologicals as well as equine tracheal and nasal tissues. It uncovered contrasting sialic acid linkage types of acetylated and non-acetylated sialic acids and provided a rationale for sialic acid binding preferences of equine H7 influenza A viruses.
Artificial photosynthetic cells with biotic–abiotic hybrid energy modules for customized CO2 conversion
Authors: Gao Feng , Liu Guangyu , Chen Aobo , Hu Yangguang , Wang Huihui , Pan Jiangyuan , Feng Jinglei , Zhang Hongwei , Wang Yujie , Min Yuanzeng , Gao Chao , Xiong Yujie 
Published: October 2023

AbstractProgrammable artificial photosynthetic cell is the ultimate goal for mimicking natural photosynthesis, offering tunable product selectivity via reductase selection toward device integration. However, this concept is limited by the capacity of regenerating the multiple cofactors that hold the key to various reductases. Here, we report the design of artificial photosynthetic cells using biotic–abiotic thylakoid–CdTe as hybrid energy modules. The rational integration of thylakoid with CdTe quantum dots substantially enhances the regeneration of bioactive NADPH, NADH and ATP cofactors without external supplements by promoting proton-coupled electron transfer. Particularly, this approach turns thylakoid highly active for NADH regeneration, providing a more versatile platform for programming artificial photosynthetic cells. Such artificial photosynthetic cells can be programmed by coupling with diverse reductases, such as formate dehydrogenase and remodeled nitrogenase for highly selective production of formate or methane, respectively. This work opens an avenue for customizing artificial photosynthetic cells toward multifarious demands for CO2 conversion.
Middle ear innovation in Early Cretaceous eutherian mammals
Authors: Wang Haibing , Wang Yuanqing 
Published: October 2023

AbstractThe middle ear ossicles in modern mammals are repurposed from postdentary bones in non-mammalian cynodonts. Recent discoveries by palaeontological and embryonic studies have developed different models for the middle ear evolution in mammaliaforms. However, little is known about the evolutionary scenario of the middle ear in early therians. Here we report a detached middle ear preserved in a new eutherian mammal from the Early Cretaceous Jehol Biota. The well-preserved articulation of the malleus and incus suggest that the saddle-shaped incudomallear joint is a major apomorphy of Early Cretaceous eutherians. By contrast to the distinct saddle-like incudomallear articulation in therians, differences between the overlapping versus the half-overlapping incudomallear joints in monotremes and stem mammals would be relatively minor. The middle ear belongs to the microtype by definition, indicating its adaptation to high-frequency hearing. Current evidence indicates that significant evolutionary innovations of the middle ear in modern therians evolved in Early Cretaceous.
Geophysical evidence for an enriched molten silicate layer above Mars’s core
Authors: Samuel Henri , Drilleau Mélanie , Rivoldini Attilio , Xu Zongbo , Huang Quancheng , Garcia Raphaël F. , Lekić Vedran , Irving Jessica C. E. , Badro James , Lognonné Philippe H. , Connolly James A. D. , Kawamura Taichi , Gudkova Tamara , Banerdt William B. 
Published: October 2023

AbstractThe detection of deep reflected S waves on Mars inferred a core size of 1,830 ± 40 km (ref. 1), requiring light-element contents that are incompatible with experimental petrological constraints. This estimate assumes a compositionally homogeneous Martian mantle, at odds with recent measurements of anomalously slow propagating P waves diffracted along the core–mantle boundary2. An alternative hypothesis is that Mars’s mantle is heterogeneous as a consequence of an early magma ocean that solidified to form a basal layer enriched in iron and heat-producing elements. Such enrichment results in the formation of a molten silicate layer above the core, overlain by a partially molten layer3. Here we show that this structure is compatible with all geophysical data, notably (1) deep reflected and diffracted mantle seismic phases, (2) weak shear attenuation at seismic frequency and (3) Mars’s dissipative nature at Phobos tides. The core size in this scenario is 1,650 ± 20 km, implying a density of 6.5 g cm−3, 5–8% larger than previous seismic estimates, and can be explained by fewer, and less abundant, alloying light elements than previously required, in amounts compatible with experimental and cosmochemical constraints. Finally, the layered mantle structure requires external sources to generate the magnetic signatures recorded in Mars’s crust.
An ON-type direction-selective ganglion cell in primate retina
Authors: Wang Anna Y. M. , Kulkarni Manoj M. , McLaughlin Amanda J. , Gayet Jacqueline , Smith Benjamin E. , Hauptschein Max , McHugh Cyrus F. , Yao Yvette Y. , Puthussery Teresa 
Published: October 2023

AbstractTo maintain a stable and clear image of the world, our eyes reflexively follow the direction in which a visual scene is moving. Such gaze-stabilization mechanisms reduce image blur as we move in the environment. In non-primate mammals, this behaviour is initiated by retinal output neurons called ON-type direction-selective ganglion cells (ON-DSGCs), which detect the direction of image motion and transmit signals to brainstem nuclei that drive compensatory eye movements1. However, ON-DSGCs have not yet been identified in the retina of primates, raising the possibility that this reflex is mediated by cortical visual areas. Here we mined single-cell RNA transcriptomic data from primate retina to identify a candidate ON-DSGC. We then combined two-photon calcium imaging, molecular identification and morphological analysis to reveal a population of ON-DSGCs in the macaque retina. The morphology, molecular signature and GABA (γ-aminobutyric acid)-dependent mechanisms that underlie direction selectivity in primate ON-DSGCs are highly conserved with those in other mammals. We further identify a candidate ON-DSGC in human retina. The presence of ON-DSGCs in primates highlights the need to examine the contribution of subcortical retinal mechanisms to normal and aberrant gaze stabilization in the developing and mature visual system.
Human-like systematic generalization through a meta-learning neural network
Authors: Lake Brenden M. , Baroni Marco 
Published: October 2023

AbstractThe power of human language and thought arises from systematic compositionality—the algebraic ability to understand and produce novel combinations from known components. Fodor and Pylyshyn1famously argued that artificial neural networks lack this capacity and are therefore not viable models of the mind. Neural networks have advanced considerably in the years since, yet the systematicity challenge persists. Here we successfully address Fodor and Pylyshyn’s challenge by providing evidence that neural networks can achieve human-like systematicity when optimized for their compositional skills. To do so, we introduce the meta-learning for compositionality (MLC) approach for guiding training through a dynamic stream of compositional tasks. To compare humans and machines, we conducted human behavioural experiments using an instruction learning paradigm. After considering seven different models, we found that, in contrast to perfectly systematic but rigid probabilistic symbolic models, and perfectly flexible but unsystematic neural networks, only MLC achieves both the systematicity and flexibility needed for human-like generalization. MLC also advances the compositional skills of machine learning systems in several systematic generalization benchmarks. Our results show how a standard neural network architecture, optimized for its compositional skills, can mimic human systematic generalization in a head-to-head comparison.
Heavy-element production in a compact object merger observed by JWST
Authors: Levan Andrew J. , Gompertz Benjamin P. , Salafia Om Sharan , Bulla Mattia , Burns Eric , Hotokezaka Kenta , Izzo Luca , Lamb Gavin P. , Malesani Daniele B. , Oates Samantha R. , Ravasio Maria Edvige , Rouco Escorial Alicia , Schneider Benjamin , Sarin Nikhil , Schulze Steve , Tanvir Nial R. , Ackley Kendall , Anderson Gemma , Brammer Gabriel B. , Christensen Lise , Dhillon Vikram S. , Evans Phil A. , Fausnaugh Michael , Fong Wen-fai , Fruchter Andrew S. , Fryer Chris , Fynbo Johan P. U. , Gaspari Nicola , Heintz Kasper E. , Hjorth Jens , Kennea Jamie A. , Kennedy Mark R. , Laskar Tanmoy , Leloudas Giorgos , Mandel Ilya , Martin-Carrillo Antonio , Metzger Brian D. , Nicholl Matt , Nugent Anya , Palmerio Jesse T. , Pugliese Giovanna , Rastinejad Jillian , Rhodes Lauren , Rossi Andrea , Saccardi Andrea , Smartt Stephen J. , Stevance Heloise F. , Tohuvavohu Aaron , van der Horst Alexander , Vergani Susanna D. , Watson Darach , Barclay Thomas , Bhirombhakdi Kornpob , Breedt Elmé , Breeveld Alice A. , Brown Alexander J. , Campana Sergio , Chrimes Ashley A. , D’Avanzo Paolo , D’Elia Valerio , De Pasquale Massimiliano , Dyer Martin J. , Galloway Duncan K. , Garbutt James A. , Green Matthew J. , Hartmann Dieter H. , Jakobsson Páll , Kerry Paul , Kouveliotou Chryssa , Langeroodi Danial , Le Floc’h Emeric , Leung James K. , Littlefair Stuart P. , Munday James , O’Brien Paul , Parsons Steven G. , Pelisoli Ingrid , Sahman David I. , Salvaterra Ruben , Sbarufatti Boris , Steeghs Danny , Tagliaferri Gianpiero , Thöne Christina C. , de Ugarte Postigo Antonio , Kann David Alexander 
Published: October 2023

AbstractThe mergers of binary compact objects such as neutron stars and black holes are of central interest to several areas of astrophysics, including as the progenitors of gamma-ray bursts (GRBs)1, sources of high-frequency gravitational waves (GWs)2and likely production sites for heavy-element nucleosynthesis by means of rapid neutron capture (ther-process)3. Here we present observations of the exceptionally bright GRB 230307A. We show that GRB 230307A belongs to the class of long-duration GRBs associated with compact object mergers4–6and contains a kilonova similar to AT2017gfo, associated with the GW merger GW170817 (refs. 7–12). We obtained James Webb Space Telescope (JWST) mid-infrared imaging and spectroscopy 29 and 61 days after the burst. The spectroscopy shows an emission line at 2.15 microns, which we interpret as tellurium (atomic massA = 130) and a very red source, emitting most of its light in the mid-infrared owing to the production of lanthanides. These observations demonstrate that nucleosynthesis in GRBs can creater-process elements across a broad atomic mass range and play a central role in heavy-element nucleosynthesis across the Universe.
Pulsed stimulated Brillouin microscopy enables high-sensitivity mechanical imaging of live and fragile biological specimens
Authors: Yang Fan , Bevilacqua Carlo , Hambura Sebastian , Neves Ana , Gopalan Anusha , Watanabe Koki , Govendir Matt , Bernabeu Maria , Ellenberg Jan , Diz-Muñoz Alba , Köhler Simone , Rapti Georgia , Jechlinger Martin , Prevedel Robert 
Published: October 2023

AbstractBrillouin microscopy is an emerging optical elastography technique capable of assessing mechanical properties of biological samples in a three-dimensional, all-optical and noncontact fashion. The typically weak Brillouin scattering signal can be substantially enhanced via a stimulated Brillouin scattering (SBS) process; however, current implementations require high pump powers, which prohibit applications to photosensitive or live imaging of biological samples. Here we present a pulsed SBS scheme that takes advantage of the nonlinearity of the pump–probe interaction. In particular, we show that the required pump laser power can be decreased ~20-fold without affecting the signal levels or spectral precision. We demonstrate the low phototoxicity and high specificity of our pulsed SBS approach by imaging, with subcellular detail, sensitive single cells, zebrafish larvae, mouse embryos and adult Caenorhabditis elegans. Furthermore, our method permits observing the mechanics of organoids and C. elegans embryos over time, opening up further possibilities for the field of mechanobiology.
Estimating global identifiability using conditional mutual information in a Bayesian framework
Authors: Bhola Sahil , Duraisamy Karthik 
Published: October 2023

AbstractA novel information-theoretic approach is proposed to assess the global practical identifiability of Bayesian statistical models. Based on the concept of conditional mutual information, an estimate of information gained for each model parameter is used to quantify the identifiability with practical considerations. No assumptions are made about the structure of the statistical model or the prior distribution while constructing the estimator. The estimator has the following notable advantages: first, no controlled experiment or data is required to conduct the practical identifiability analysis; second, unlike popular variance-based global sensitivity analysis methods, different forms of uncertainties, such as model-form, parameter, or measurement can be taken into account; third, the identifiability analysis is global, and therefore independent of a realization of the parameters. If an individual parameter has low identifiability, it can belong to an identifiable subset such that parameters within the subset have a functional relationship and thus have a combined effect on the statistical model. The practical identifiability framework is extended to highlight the dependencies between parameter pairs that emerge a posteriori to find identifiable parameter subsets. The applicability of the proposed approach is demonstrated using a linear Gaussian model and a non-linear methane-air reduced kinetics model. It is shown that by examining the information gained for each model parameter along with its dependencies with other parameters, a subset of parameters that can be estimated with high posterior certainty can be found.
Recurrence after postoperative intravesical instillation therapy in Hunner type interstitial cystitis
Authors: Ko Kwang Jin , Koo Michael Jakun , Bang Seokhwan , Byun Hye Jin , Kim Min-Ji , Kim Kyunga , Lee Kyu-Sung 
Published: October 2023

AbstractWe performed a prospective, single-arm study comparing outcomes between transurethral ablation plus postoperative instillation of hyaluronic acid and chondroitin sulfate (HACS group) and transurethral ablation only in patients with Hunner type interstitial cystitis (historical control group). A total of 78 patients were enrolled, and 51 were included in the per-protocol analysis set. The 2-year recurrence rate was 47.1% (95% CI, 32.9–61.5) in the HACS group, which was significantly lower than that in the control group (86.2%; 95% CI, 74.6–93.9, P < 0.001). After instillation therapy, the hazard ratio for recurrence was 0.38 (95% CI, 0.23–0.65, P < 0.001). The HACS group had an increased recurrence-free survival with the median interval not being reached, while it was 11.4 months in the control group (95% CI, 8.8–13.8, P < 0.001). Regardless of the instillation treatment, there were significant improvements in all symptom questionnaire scores and pain compared to the baseline. However, in the instillation group, improvement was stable even after 12 months. In patients with Hunner type interstitial cystitis, intravesical instillation of hyaluronic acid and chondroitin sulfate after transurethral ablation significantly reduced the recurrence rate and maintained symptom improvement for more than 1 year.