bluuebunny/crossref_metadata_2025_split huggingface dataset:
Open access repository-scale propagated nearest neighbor suspect spectral library for untargeted metabolomics
Authors: Bittremieux Wout , Avalon Nicole E. , Thomas Sydney P. , Kakhkhorov Sarvar A. , Aksenov Alexander A. , Gomes Paulo Wender P. , Aceves Christine M. , Caraballo-Rodríguez Andrés Mauricio , Gauglitz Julia M. , Gerwick William H. , Huan Tao , Jarmusch Alan K. , Kaddurah-Daouk Rima F. , Kang Kyo Bin , Kim Hyun Woo , Kondić Todor , Mannochio-Russo Helena , Meehan Michael J. , Melnik Alexey V. , Nothias Louis-Felix , O’Donovan Claire , Panitchpakdi Morgan , Petras Daniel , Schmid Robin , Schymanski Emma L. , van der Hooft Justin J. J. , Weldon Kelly C. , Yang Heejung , Xing Shipei , Zemlin Jasmine , Wang Mingxun , Dorrestein Pieter C. 
Published: December 2023

AbstractDespite the increasing availability of tandem mass spectrometry (MS/MS) community spectral libraries for untargeted metabolomics over the past decade, the majority of acquired MS/MS spectra remain uninterpreted. To further aid in interpreting unannotated spectra, we created a nearest neighbor suspect spectral library, consisting of 87,916 annotated MS/MS spectra derived from hundreds of millions of MS/MS spectra originating from published untargeted metabolomics experiments. Entries in this library, or “suspects,” were derived from unannotated spectra that could be linked in a molecular network to an annotated spectrum. Annotations were propagated to unknowns based on structural relationships to reference molecules using MS/MS-based spectrum alignment. We demonstrate the broad relevance of the nearest neighbor suspect spectral library through representative examples of propagation-based annotation of acylcarnitines, bacterial and plant natural products, and drug metabolism. Our results also highlight how the library can help to better understand an Alzheimer’s brain phenotype. The nearest neighbor suspect spectral library is openly available for download or for data analysis through the GNPS platform to help investigators hypothesize candidate structures for unknown MS/MS spectra in untargeted metabolomics data.
Adult stem cell activity in naked mole rats for long-term tissue maintenance
Authors: Montazid Shamir , Bandyopadhyay Sheila , Hart Daniel W. , Gao Nan , Johnson Brian , Thrumurthy Sri G. , Penn Dustin J. , Wernisch Bettina , Bansal Mukesh , Altrock Philipp M. , Rost Fabian , Gazinska Patrycja , Ziolkowski Piotr , Hayee Bu’Hussain , Liu Yue , Han Jiangmeng , Tessitore Annamaria , Koth Jana , Bodmer Walter F. , East James E. , Bennett Nigel C. , Tomlinson Ian , Irshad Shazia 
Published: December 2023

AbstractThe naked mole rat (NMR), Heterocephalus glaber, the longest-living rodent, provides a unique opportunity to explore how evolution has shaped adult stem cell (ASC) activity and tissue function with increasing lifespan. Using cumulative BrdU labelling and a quantitative imaging approach to track intestinal ASCs (Lgr5+) in their native in vivo state, we find an expanded pool of Lgr5+ cells in NMRs, and these cells specifically at the crypt base (Lgr5+CBC) exhibit slower division rates compared to those in short-lived mice but have a similar turnover as human LGR5+CBC cells. Instead of entering quiescence (G0), NMR Lgr5+CBC cells reduce their division rates by prolonging arrest in the G1 and/or G2 phases of the cell cycle. Moreover, we also observe a higher proportion of differentiated cells in NMRs that confer enhanced protection and function to the intestinal mucosa which is able to detect any chemical imbalance in the luminal environment efficiently, triggering a robust pro-apoptotic, anti-proliferative response within the stem/progenitor cell zone.
Common and divergent gene regulatory networks control injury-induced and developmental neurogenesis in zebrafish retina
Authors: Lyu Pin , Iribarne Maria , Serjanov Dmitri , Zhai Yijie , Hoang Thanh , Campbell Leah J. , Boyd Patrick , Palazzo Isabella , Nagashima Mikiko , Silva Nicholas J. , Hitchcock Peter F. , Qian Jiang , Hyde David R. , Blackshaw Seth 
Published: December 2023

AbstractFollowing acute retinal damage, zebrafish possess the ability to regenerate all neuronal subtypes through Müller glia (MG) reprogramming and asymmetric cell division that produces a multipotent Müller glia-derived neuronal progenitor cell (MGPC). This raises three key questions. First, do MG reprogram to a developmental retinal progenitor cell (RPC) state? Second, to what extent does regeneration recapitulate retinal development? And finally, does loss of different retinal cell subtypes induce unique MG regeneration responses? We examined these questions by performing single-nuclear and single-cell RNA-Seq and ATAC-Seq in both developing and regenerating retinas. Here we show that injury induces MG to reprogram to a state similar to late-stage RPCs. However, there are major transcriptional differences between MGPCs and RPCs, as well as major transcriptional differences between activated MG and MGPCs when different retinal cell subtypes are damaged. Validation of candidate genes confirmed that loss of different subtypes induces differences in transcription factor gene expression and regeneration outcomes.
Mtfp1 ablation enhances mitochondrial respiration and protects against hepatic steatosis
Authors: Patitucci Cecilia , Hernández-Camacho Juan Diego , Vimont Elodie , Yde Sonny , Cokelaer Thomas , Chaze Thibault , Giai Gianetto Quentin , Matondo Mariette , Gazi Anastasia , Nemazanyy Ivan , Stroud David A. , Hock Daniella H. , Donnarumma Erminia , Wai Timothy 
Published: December 2023

AbstractHepatic steatosis is the result of imbalanced nutrient delivery and metabolism in the liver and is the first hallmark of Metabolic dysfunction-associated steatotic liver disease (MASLD). MASLD is the most common chronic liver disease and involves the accumulation of excess lipids in hepatocytes, inflammation, and cancer. Mitochondria play central roles in liver metabolism yet the specific mitochondrial functions causally linked to MASLD remain unclear. Here, we identify Mitochondrial Fission Process 1 protein (MTFP1) as a key regulator of mitochondrial and metabolic activity in the liver. Deletion of Mtfp1 in hepatocytes is physiologically benign in mice yet leads to the upregulation of oxidative phosphorylation (OXPHOS) activity and mitochondrial respiration, independently of mitochondrial biogenesis. Consequently, liver-specific knockout mice are protected against high fat diet-induced steatosis and metabolic dysregulation. Additionally, Mtfp1 deletion inhibits mitochondrial permeability transition pore opening in hepatocytes, conferring protection against apoptotic liver damage in vivo and ex vivo. Our work uncovers additional functions of MTFP1 in the liver, positioning this gene as an unexpected regulator of OXPHOS and a therapeutic candidate for MASLD.
Cyclosporine A-resistant CAR-T cells mediate antitumour immunity in the presence of allogeneic cells
Authors: Zhang Yixi , Fang Hongyu , Wang Guocan , Yuan Guangxun , Dong Ruoyu , Luo Jijun , Lyu Yu , Wang Yajie , Li Peng , Zhou Chun , Yin Weiwei , Xiao Haowen , Sun Jie , Zeng Xun 
Published: December 2023

AbstractChimeric antigen receptor (CAR)-T therapy requires autologous T lymphocytes from cancer patients, a process that is both costly and complex. Universal CAR-T cell treatment from allogeneic sources can overcome this limitation but is impeded by graft-versus-host disease (GvHD) and host versus-graft rejection (HvGR). Here, we introduce a mutated calcineurin subunit A (CNA) and a CD19-specific CAR into the T cell receptor α constant (TRAC) locus to generate cells that are resistant to the widely used immunosuppressant, cyclosporine A (CsA). These immunosuppressant-resistant universal (IRU) CAR-T cells display improved effector function in vitro and anti-tumour efficacy in a leukemia xenograft mouse model in the presence of CsA, compared with CAR-T cells carrying wild-type CNA. Moreover, IRU CAR-T cells retain effector function in vitro and in vivo in the presence of both allogeneic T cells and CsA. Lastly, CsA withdrawal restores HvGR, acting as a safety switch that can eliminate IRU CAR-T cells. These findings demonstrate the efficacy of CsA-resistant CAR-T cells as a universal, ‘off-the-shelf’ treatment option.
Metallic micronutrients are associated with the structure and function of the soil microbiome
Authors: Dai Zhongmin , Guo Xu , Lin Jiahui , Wang Xiu , He Dan , Zeng Rujiong , Meng Jun , Luo Jipeng , Delgado-Baquerizo Manuel , Moreno-Jiménez Eduardo , Brookes Philip C. , Xu Jianming 
Published: December 2023

AbstractThe relationship between metallic micronutrients and soil microorganisms, and thereby soil functioning, has been little explored. Here, we investigate the relationship between metallic micronutrients (Fe, Mn, Cu, Zn, Mo and Ni) and the abundance, diversity and function of soil microbiomes. In a survey across 180 sites in China, covering a wide range of soil conditions the structure and function of the soil microbiome are highly correlated with metallic micronutrients, especially Fe, followed by Mn, Cu and Zn. These results are robust to controlling for soil pH, which is often reported as the most important predictor of the soil microbiome. An incubation experiment with Fe and Zn additions for five different soil types also shows that increased micronutrient concentration affects microbial community composition and functional genes. In addition, structural equation models indicate that micronutrients positively contribute to the ecosystem productivity, both directly (micronutrient availability to plants) and, to a lesser extent, indirectly (via affecting the microbiome). Our findings highlight the importance of micronutrients in explaining soil microbiome structure and ecosystem functioning.
Quantitatively assessing early detection strategies for mitigating COVID-19 and future pandemics
Authors: Liu Andrew Bo , Lee Daniel , Jalihal Amogh Prabhav , Hanage William P. , Springer Michael 
Published: December 2023

AbstractResearchers and policymakers have proposed systems to detect novel pathogens earlier than existing surveillance systems by monitoring samples from hospital patients, wastewater, and air travel, in order to mitigate future pandemics. How much benefit would such systems offer? We developed, empirically validated, and mathematically characterized a quantitative model that simulates disease spread and detection time for any given disease and detection system. We find that hospital monitoring could have detected COVID-19 in Wuhan 0.4 weeks earlier than it was actually discovered, at 2,300 cases (standard error: 76 cases) compared to 3,400 (standard error: 161 cases). Wastewater monitoring would not have accelerated COVID-19 detection in Wuhan, but provides benefit in smaller catchments and for asymptomatic or long-incubation diseases like polio or HIV/AIDS. Air travel monitoring does not accelerate outbreak detection in most scenarios we evaluated. In sum, early detection systems can substantially mitigate some future pandemics, but would not have changed the course of COVID-19.
VWCE modulates amino acid-dependent mTOR signaling and coordinates with KICSTOR to recruit GATOR1 to the lysosomes
Authors: Zhao Tianyu , Guan Yuanyuan , Xu Chenchen , Wang Dong , Guan Jialiang , Liu Ying 
Published: December 2023

AbstractThe mechanistic target of rapamycin complex 1 (mTORC1) is a crucial regulator of cell growth. It senses nutrient signals and adjusts cellular metabolism accordingly. Deregulation of mTORC1 has been associated with metabolic diseases, cancer, and aging. Amino acid signals are transduced to mTORC1 through sensor proteins and two protein complexes named GATOR1 and GATOR2. In this study, we identify VWCE (von Willebrand factor C and EGF domains) as a negative regulator of amino acid-dependent mTORC1 signaling. Knockdown of VWCE promotes mTORC1 activity even in the absence of amino acids. VWCE interacts with the KICSTOR complex to facilitate the recruitment of GATOR1 to the lysosomes. Bioinformatic analysis reveals that expression of VWCE is reduced in prostate cancer. More importantly, overexpression of VWCE inhibits the development of prostate cancer. Therefore, VWCE may serve as a potential therapeutic target for the treatment of prostate cancers.
Reconfiguration of the reductive TCA cycle enables high-level succinic acid production by Yarrowia lipolytica
Authors: Cui Zhiyong , Zhong Yutao , Sun Zhijie , Jiang Zhennan , Deng Jingyu , Wang Qian , Nielsen Jens , Hou Jin , Qi Qingsheng 
Published: December 2023

AbstractSuccinic acid (SA) is an important C4-dicarboxylic acid. Microbial production of SA at low pH results in low purification costs and hence good overall process economics. However, redox imbalances limited SA biosynthesis from glucose via the reductive tricarboxylic acid (TCA) cycle in yeast. Here, we engineer the strictly aerobic yeast Yarrowia lipolytica for efficient SA production without pH control. Introduction of the reductive TCA cycle into the cytosol of a succinate dehydrogenase-disrupted yeast strain causes arrested cell growth. Although adaptive laboratory evolution restores cell growth, limited NADH supply restricts SA production. Reconfiguration of the reductive SA biosynthesis pathway in the mitochondria through coupling the oxidative and reductive TCA cycle for NADH regeneration results in improved SA production. In pilot-scale fermentation, the engineered strain produces 111.9 g/L SA with a yield of 0.79 g/g glucose within 62 h. This study paves the way for industrial production of biobased SA.
Multiple independent losses of the biosynthetic pathway for two tropane alkaloids in the Solanaceae family
Authors: Yang Jiao , Wu Ying , Zhang Pan , Ma Jianxiang , Yao Ying Jun , Ma Yan Lin , Zhang Lei , Yang Yongzhi , Zhao Changmin , Wu Jihua , Fang Xiangwen , Liu Jianquan 
Published: December 2023

AbstractHyoscyamine and scopolamine (HS), two valuable tropane alkaloids of significant medicinal importance, are found in multiple distantly related lineages within the Solanaceae family. Here we sequence the genomes of three representative species that produce HS from these lineages, and one species that does not produce HS. Our analysis reveals a shared biosynthetic pathway responsible for HS production in the three HS-producing species. We observe a high level of gene collinearity related to HS synthesis across the family in both types of species. By introducing gain-of-function and loss-of-function mutations at key sites, we confirm the reduced/lost or re-activated functions of critical genes involved in HS synthesis in both types of species, respectively. These findings indicate independent and repeated losses of the HS biosynthesis pathway since its origin in the ancestral lineage. Our results hold promise for potential future applications in the artificial engineering of HS biosynthesis in Solanaceae crops.
A unique sigma/anti-sigma system in the actinomycete Actinoplanes missouriensis
Authors: Tezuka Takeaki , Mitsuyama Kyota , Date Risa , Ohnishi Yasuo 
Published: December 2023

AbstractBacteria of the genus Actinoplanes form sporangia that contain dormant sporangiospores which, upon contact with water, release motile spores (zoospores) through a process called sporangium dehiscence. Here, we set out to study the molecular mechanisms behind sporangium dehiscence in Actinoplanes missouriensis and discover a sigma/anti-sigma system with unique features. Protein σSsdA contains a functional sigma factor domain and an anti-sigma factor antagonist domain, while protein SipA contains an anti-sigma factor domain and an anti-sigma factor antagonist domain. Remarkably, the two proteins interact with each other via the anti-sigma factor antagonist domain of σSsdA and the anti-sigma factor domain of SipA. Although it remains unclear whether the SipA/σSsdA system plays direct roles in sporangium dehiscence, the system seems to modulate oxidative stress responses in zoospores. In addition, we identify a two-component regulatory system (RsdK-RsdR) that represses initiation of sporangium dehiscence.
Storage protein activator controls grain protein accumulation in bread wheat in a nitrogen dependent manner
Authors: Plessis Anne , Ravel Catherine , Risacher Thierry , Duchateau Nathalie , Dardevet Mireille , Merlino Marielle , Torney François , Martre Pierre 
Published: December 2023

AbstractThe expression of cereal grain storage protein (GSP) genes is controlled by a complex network of transcription factors (TFs). Storage protein activator (SPA) is a major TF acting in this network but its specific function in wheat (Triticum aestivum L.) remains to be determined. Here we generated an RNAi line in which expression of the three SPA homoeologs was reduced. In this line and its null segregant we analyzed GSP accumulation and expression of GSP and regulatory TF genes under two regimes of nitrogen availability. We show that down regulation of SPA decreases grain protein concentration at maturity under low but not high nitrogen supply. Under low nitrogen supply, the decrease in SPA expression also caused a reduction in the total quantity of GSP per grain and in the ratio of GSP to albumin-globulins, without significantly affecting GSP composition. The slight reduction in GSP gene expression measured in the SPA RNAi line under low nitrogen supply did not entirely account for the more significant decrease in GSP accumulation, suggesting that SPA regulates additional levels of GSP synthesis. Our results demonstrate a clear role of SPA in the regulation of grain nitrogen metabolism when nitrogen is a limiting resource.
Automated image quality assessment for selecting among multiple magnetic resonance image acquisitions in the German National Cohort study
Authors: Schuppert Christopher , Rospleszcz Susanne , Hirsch Jochen G. , Hoinkiss Daniel C. , Köhn Alexander , von Krüchten Ricarda , Russe Maximilian F. , Keil Thomas , Krist Lilian , Schmidt Börge , Michels Karin B. , Schipf Sabine , Brenner Hermann , Kröncke Thomas J. , Pischon Tobias , Niendorf Thoralf , Schulz-Menger Jeanette , Forsting Michael , Völzke Henry , Hosten Norbert , Bülow Robin , Zaitsev Maxim , Kauczor Hans-Ulrich , Bamberg Fabian , Günther Matthias , Schlett Christopher L. 
Published: December 2023

AbstractIn magnetic resonance imaging (MRI), the perception of substandard image quality may prompt repetition of the respective image acquisition protocol. Subsequently selecting the preferred high-quality image data from a series of acquisitions can be challenging. An automated workflow may facilitate and improve this selection. We therefore aimed to investigate the applicability of an automated image quality assessment for the prediction of the subjectively preferred image acquisition. Our analysis included data from 11,347 participants with whole-body MRI examinations performed as part of the ongoing prospective multi-center German National Cohort (NAKO) study. Trained radiologic technologists repeated any of the twelve examination protocols due to induced setup errors and/or subjectively unsatisfactory image quality and chose a preferred acquisition from the resultant series. Up to 11 quantitative image quality parameters were automatically derived from all acquisitions. Regularized regression and standard estimates of diagnostic accuracy were calculated. Controlling for setup variations in 2342 series of two or more acquisitions, technologists preferred the repetition over the initial acquisition in 1116 of 1396 series in which the initial setup was retained (79.9%, range across protocols: 73–100%). Image quality parameters then commonly showed statistically significant differences between chosen and discarded acquisitions. In regularized regression across all protocols, ‘structured noise maximum’ was the strongest predictor for the technologists’ choice, followed by ‘N/2 ghosting average’. Combinations of the automatically derived parameters provided an area under the ROC curve between 0.51 and 0.74 for the prediction of the technologists’ choice. It is concluded that automated image quality assessment can, despite considerable performance differences between protocols and anatomical regions, contribute substantially to identifying the subjective preference in a series of MRI acquisitions and thus provide effective decision support to readers.
Naïve, adult, captive chimpanzees do not socially learn how to make and use sharp stone tools
Authors: Bandini Elisa , Tennie Claudio 
Published: December 2023

AbstractAlthough once regarded as a unique human feature, tool-use is widespread in the animal kingdom. Some of the most proficient tool-users are our closest living relatives, chimpanzees. These repertoires however consist primarily of tool use, rather than tool manufacture (for later use). Furthermore, most populations of chimpanzees use organic materials, such as sticks and leaves, rather than stones as tools. This distinction may be partly ecological, but it is also important as chimpanzees are often used as models for the evolution of human material culture, the oldest traces of which consist of manufactured sharp stone tools (so-called “flakes”). Thus, examining the conditions (if any) under which chimpanzees may develop flake manufacture and use can provide insight into the drivers of these behaviours in our own lineage. Previous studies on non-human apes’ ability to make and use flakes focused on enculturated apes, giving them full demonstrations of the behaviour immediately, without providing social information on the task in a stepwise manner. Here we tested naïve, captive chimpanzees (N = 4; three potentially enculturated and one unenculturated subject) in a social learning experimental paradigm to investigate whether enculturated and/or unenculturated chimpanzees would develop flake making and use after social information of various degrees (including a human demonstration) was provided in a scaffolded manner. Even though social learning opportunities were provided, neither the unenculturated subject nor any of the potentially enculturated subjects made or used flakes, in stark contrast to previous studies with enculturated apes. These data suggest that flake manufacture and use is outside of our tested group of captive chimpanzees’ individual and social learning repertoires. It also suggests that high levels of enculturation alongside human demonstrations (and/or training) may be required before captive chimpanzees can develop this behaviour.