bluuebunny/crossref_metadata_2025 huggingface dataset:
Gut proinflammatory bacteria is associated with abnormal functional connectivity of hippocampus in unmedicated patients with major depressive disorder
Authors: Xiao Shu , Yang Zibin , Yan Hong , Chen Guanmao , Zhong Shuming , Chen Pan , Zhong Hui , Yang Hengwen , Jia Yanbin , Yin Zhinan , Gong Jiaying , Huang Li , Wang Ying
Published: July 2024

Accumulating evidence has revealed the gut bacteria dysbiosis and brain hippocampal functional and structural alterations in major depressive disorder (MDD). However, the potential relationship between the gut microbiota and hippocampal function alterations in patients with MDD is still very limited. Data of resting-state functional magnetic resonance imaging were acquired from 44 unmedicated MDD patients and 42 demographically matched healthy controls (HCs). Severn pairs of hippocampus subregions (the bilateral cornu ammonis [CA1-CA3], dentate gyrus (DG), entorhinal cortex, hippocampal–amygdaloid transition area, and subiculum) were selected as the seeds in the functional connectivity (FC) analysis. Additionally, fecal samples of participants were collected and 16S rDNA amplicon sequencing was used to identify the altered relative abundance of gut microbiota. Then, association analysis was conducted to investigate the potential relationships between the abnormal hippocampal subregions FC and microbiome features. Also, the altered hippocampal subregion FC values and gut microbiota levels were used as features separately or together in the support vector machine models distinguishing the MDD patients and HCs. Compared with HCs, patients with MDD exhibited increased FC between the left hippocampus (CA2, CA3 and DG) and right hippocampus (CA2 and CA3), and decreased FC between the right hippocampal CA3 and bilateral posterior cingulate cortex. In addition, we found that the level of proinflammatory bacteria (i.e., Enterobacteriaceae) was significantly increased, whereas the level of short-chain fatty acids producing-bacteria (i.e., Prevotellaceae, Agathobacter and Clostridium) were significantly decreased in MDD patients. Furthermore, FC values of the left hippocampal CA3- right hippocampus (CA2 and CA3) was positively correlated with the relative abundance of Enterobacteriaceae in patients with MDD. Moreover, altered hippocampal FC patterns and gut microbiota level were considered in combination, the best discrimination was obtained (AUC = 0.92). These findings may provide insights into the potential role of gut microbiota in the underlying neuropathology of MDD patients.
NOP2 facilitates EZH2-mediated epithelial–mesenchymal transition by enhancing EZH2 mRNA stability via m5C methylation in lung cancer progression
Authors: Yang Ying , Fan Hongzhao , Liu Hongyang , Lou Xueling , Xiao Nan , Zhang Chenxing , Chen Huanxiang , Chen Shuangshuang , Gu Huihui , Liu Hongchun , Wan Junhu
Published: July 2024

NOP2, a member of the NOL1/NOP2/SUN domain (NSUN) family, is responsible for catalyzing the posttranscriptional modification of RNA through 5-methylcytosine (m5C). Dysregulation of m5C modification has been linked to the pathogenesis of various malignant tumors. Herein, we investigated the expression of NOP2 in lung adenocarcinoma (LUAD) tissues and cells, and found that it was significantly upregulated. Moreover, lentivirus-mediated overexpression of NOP2 in vitro resulted in enhanced migration and invasion capabilities of lung cancer cells, while in vivo experiments demonstrated its ability to promote the growth and metastasis of xenograft tumors. In contrast, knockdown of NOP2 effectively inhibited the growth and metastasis of lung cancer cells. RNA-sequencing was conducted to ascertain the downstream targets of NOP2, and the findings revealed a significant upregulation in EZH2 mRNA expression upon overexpression of NOP2. Subsequent validation experiments demonstrated that NOP2 exerted an m5C-dependent influence on the stability of EZH2 mRNA. Additionally, our investigations revealed a co-regulatory relationship between NOP2 and the m5C reader protein ALYREF in modulating the stability of EZH2 mRNA. Notably, the NOP2/EZH2 axis facilitated the malignant phenotype of lung cancer cells by inducing epithelial–mesenchymal transition (EMT) both in vitro and in vivo. Mechanistically, ChIP analysis proved that EZH2 counteracted the impact of NOP2 on the occupancy capacity of EZH2 and H3K27me3 in the promoter regions of E-cadherin, a gene crucial for regulating EMT. In a word, our research highlights the significant role of NOP2 in LUAD and offers novel mechanistic insights into the NOP2/ALYREF/EZH2 axis, which holds promise as a potential target for lung cancer therapy.
TACSTD2 in gelatinous drop-like corneal dystrophy: variant functional analysis and expression in the cornea after limbal stem cell transplantation
Authors: Skorodumova Liubov O. , Grafskaia Ekaterina N. , Kharlampieva Daria D. , Maltsev Dmitry I. , Petrova Tatiana V. , Kanygina Alexandra V. , Fedoseeva Elena V. , Makarov Pavel V. , Malyugin Boris E.
Published: July 2024

Gelatinous drop-like corneal dystrophy (GDLD) is a rare autosomal recessive eye disease. GDLD is characterized by the loss of barrier function in corneal epithelial cells (CECs) and amyloid deposition due to pathogenic variants in the TACSTD2 gene. Limbal stem cell transplantation (LSCT) has been suggested as an effective therapeutic alternative for patients with GDLD. However, despite LSCT, amyloid deposition recurs in some patients. The pathogenesis of recurrence is poorly studied. We present the case of a patient with GDLD. Genetic analysis revealed a homozygous deletion, NM_002353.3:c.653del, in the TACSTD2 gene. Functional analysis in a cell model system revealed the loss of the transmembrane domain and subcellular protein mislocalization. The patient with GDLD underwent direct allogeneic LSCT with epithelial debridement followed by deep anterior lamellar keratoplasty 10 months later due to amyloid deposition and deterioration of vision. Taken together, the results of transcriptome analysis and immunofluorescence staining of post-LSCT corneal sample with amyloid deposits obtained during keratoplasty demonstrated complete restoration of wild-type TACSTD2 expression, indicating that donor CECs replaced host CECs. Our study provides experimental evidence that amyloid deposition can recur after LSCT despite complete restoration of wild-type TACSTD2 expression.
PRC2-AgeIndex as a universal biomarker of aging and rejuvenation
Authors: Moqri Mahdi , Cipriano Andrea , Simpson Daniel J. , Rasouli Sajede , Murty Tara , de Jong Tineke Anna , Nachun Daniel , de Sena Brandine Guilherme , Ying Kejun , Tarkhov Andrei , Aberg Karolina A. , van den Oord Edwin , Zhou Wanding , Smith Andrew , Mackall Crystal , Gladyshev Vadim N. , Horvath Steve , Snyder Michael P. , Sebastiano Vittorio
Published: July 2024

DNA methylation (DNAm) is one of the most reliable biomarkers of aging across mammalian tissues. While the age-dependent global loss of DNAm has been well characterized, DNAm gain is less characterized. Studies have demonstrated that CpGs which gain methylation with age are enriched in Polycomb Repressive Complex 2 (PRC2) targets. However, whole-genome examination of all PRC2 targets as well as determination of the pan-tissue or tissue-specific nature of these associations is lacking. Here, we show that low-methylated regions (LMRs) which are highly bound by PRC2 in embryonic stem cells (PRC2 LMRs) gain methylation with age in all examined somatic mitotic cells. We estimated that this epigenetic change represents around 90% of the age-dependent DNAm gain genome-wide. Therefore, we propose the “PRC2-AgeIndex,” defined as the average DNAm in PRC2 LMRs, as a universal biomarker of cellular aging in somatic cells which can distinguish the effect of different anti-aging interventions.
Distinct neural mechanisms for heading retrieval and context recognition in the hippocampus during spatial reorientation
Authors: Gagliardi Celia M. , Normandin Marc E. , Keinath Alexandra T. , Julian Joshua B. , Lopez Matthew R. , Ramos-Alvarez Manuel-Miguel , Epstein Russell A. , Muzzio Isabel A.
Published: July 2024

Reorientation, the process of regaining one’s bearings after becoming lost, requires identification of a spatial context (context recognition) and recovery of facing direction within that context (heading retrieval). We previously showed that these processes rely on the use of features and geometry, respectively. Here, we examine reorientation behavior in a task that creates contextual ambiguity over a long timescale to demonstrate that male mice learn to combine both featural and geometric cues to recover heading. At the neural level, most CA1 neurons persistently align to geometry, and this alignment predicts heading behavior. However, a small subset of cells remaps coherently in a context-sensitive manner, which serves to predict context. Efficient heading retrieval and context recognition correlate with rate changes reflecting integration of featural and geometric information in the active ensemble. These data illustrate how context recognition and heading retrieval are coded in CA1 and how these processes change with experience.
scSemiProfiler: Advancing large-scale single-cell studies through semi-profiling with deep generative models and active learning
Authors: Wang Jingtao , Fonseca Gregory J. , Ding Jun
Published: July 2024

Single-cell sequencing is a crucial tool for dissecting the cellular intricacies of complex diseases. Its prohibitive cost, however, hampers its application in expansive biomedical studies. Traditional cellular deconvolution approaches can infer cell type proportions from more affordable bulk sequencing data, yet they fall short in providing the detailed resolution required for single-cell-level analyses. To overcome this challenge, we introduce “scSemiProfiler”, an innovative computational framework that marries deep generative models with active learning strategies. This method adeptly infers single-cell profiles across large cohorts by fusing bulk sequencing data with targeted single-cell sequencing from a few rigorously chosen representatives. Extensive validation across heterogeneous datasets verifies the precision of our semi-profiling approach, aligning closely with true single-cell profiling data and empowering refined cellular analyses. Originally developed for extensive disease cohorts, “scSemiProfiler” is adaptable for broad applications. It provides a scalable, cost-effective solution for single-cell profiling, facilitating in-depth cellular investigation in various biological domains.
Non-volatile magnon transport in a single domain multiferroic
Authors: Husain Sajid , Harris Isaac , Meisenheimer Peter , Mantri Sukriti , Li Xinyan , Ramesh Maya , Behera Piush , Taghinejad Hossein , Kim Jaegyu , Kavle Pravin , Zhou Shiyu , Kim Tae Yeon , Zhang Hongrui , Stevenson Paul , Analytis James G. , Schlom Darrell , Salahuddin Sayeef , Íñiguez-González Jorge , Xu Bin , Martin Lane W. , Caretta Lucas , Han Yimo , Bellaiche Laurent , Yao Zhi , Ramesh Ramamoorthy
Published: July 2024

Antiferromagnets have attracted significant attention in the field of magnonics, as promising candidates for ultralow-energy carriers for information transfer for future computing. The role of crystalline orientation distribution on magnon transport has received very little attention. In multiferroics such as BiFeO3 the coupling between antiferromagnetic and polar order imposes yet another boundary condition on spin transport. Thus, understanding the fundamentals of spin transport in such systems requires a single domain, a single crystal. We show that through Lanthanum (La) substitution, a single ferroelectric domain can be engineered with a stable, single-variant spin cycloid, controllable by an electric field. The spin transport in such a single domain displays a strong anisotropy, arising from the underlying spin cycloid lattice. Our work shows a pathway to understanding the fundamental origins of magnon transport in such a single domain multiferroic.
Revealing the atomic and electronic mechanism of human manganese superoxide dismutase product inhibition
Authors: Azadmanesh Jahaun , Slobodnik Katelyn , Struble Lucas R. , Lutz William E. , Coates Leighton , Weiss Kevin L. , Myles Dean A. A. , Kroll Thomas , Borgstahl Gloria E. O.
Published: July 2024

Human manganese superoxide dismutase (MnSOD) is a crucial oxidoreductase that maintains the vitality of mitochondria by converting superoxide (O2●−) to molecular oxygen (O2) and hydrogen peroxide (H2O2) with proton-coupled electron transfers (PCETs). Human MnSOD has evolved to be highly product inhibited to limit the formation of H2O2, a freely diffusible oxidant and signaling molecule. The product-inhibited complex is thought to be composed of a peroxide (O22−) or hydroperoxide (HO2−) species bound to Mn ion and formed from an unknown PCET mechanism. PCET mechanisms of proteins are typically not known due to difficulties in detecting the protonation states of specific residues that coincide with the electronic state of the redox center. To shed light on the mechanism, we combine neutron diffraction and X-ray absorption spectroscopy of the product-bound, trivalent, and divalent states of the enzyme to reveal the positions of all the atoms, including hydrogen, and the electronic configuration of the metal ion. The data identifies the product-inhibited complex, and a PCET mechanism of inhibition is constructed.
Dual-quartet phosphorescent emission in the open-shell M1Ag13 (M = Pt, Pd) nanoclusters
Authors: Fang Cao , Xu Chang , Zhang Wei , Zhou Meng , Tan Dong , Qian Lixia , Hu Daqiao , Jin Shan , Zhu Manzhou
Published: July 2024

Dual emission (DE) in nanoclusters (NCs) is considerably significant in the research and application of ratiometric sensing, bioimaging, and novel optoelectronic devices. Exploring the DE mechanism in open-shell NCs with doublet or quartet emissions remains challenging because synthesizing open-shell NCs is difficult due to their inherent instability. Here, we synthesize two dual-emissive M1Ag13(PFBT)6(TPP)7 (M = Pt, Pd; PFBT = pentafluorobenzenethiol; TPP = triphenylphosphine) NCs with a 7-electron open-shell configuration to reveal the DE mechanism. Both NCs comprise a crown-like M1Ag11 kernel with Pt or Pd in the center surrounded by five PPh3 ligands and two Ag(SR)3(PPh3) motifs. The combined experimental and theoretical studies revealed the origin of DE in Pt1Ag13 and Pd1Ag13. Specifically, the high-energy visible emission and the low-energy near-infrared emission arise from two distinct quartet excited states: the core-shell charge transfer and core-based states, respectively. Moreover, PFBT ligands are found to play an important role in the existence of DE, as its low-lying π* levels result in energetically accessible core-shell transitions. This novel report on the dual-quartet phosphorescent emission in NCs with an open-shell electronic configuration advances insights into the origin of dual-emissive NCs and promotes their potential application in magnetoluminescence and novel optoelectronic devices.
Controlled human hookworm infection remodels plasmacytoid dendritic cells and regulatory T cells towards profiles seen in natural infections in endemic areas
Authors: Manurung Mikhael D. , Sonnet Friederike , Hoogerwerf Marie-Astrid , Janse Jacqueline J. , Kruize Yvonne , Bes-Roeleveld Laura de , König Marion , Loukas Alex , Dewals Benjamin G. , Supali Taniawati , Jochems Simon P. , Roestenberg Meta , Coppola Mariateresa , Yazdanbakhsh Maria
Published: July 2024

Hookworm infection remains a significant public health concern, particularly in low- and middle-income countries, where mass drug administration has not stopped reinfection. Developing a vaccine is crucial to complement current control measures, which necessitates a thorough understanding of host immune responses. By leveraging controlled human infection models and high-dimensional immunophenotyping, here we investigated the immune remodeling following infection with 50 Necator americanus L3 hookworm larvae in four naïve volunteers over two years of follow-up and compared the profiles with naturally infected populations in endemic areas. Increased plasmacytoid dendritic cell frequency and diminished responsiveness to Toll-like receptor 7/8 ligand were observed in both controlled and natural infection settings. Despite the increased CD45RA+ regulatory T cell (Tregs) frequencies in both settings, markers of Tregs function, including inducible T-cell costimulatory (ICOS), tumor necrosis factor receptor 2 (TNFR2), and latency-associated peptide (LAP), as well as in vitro Tregs suppressive capacity were higher in natural infections. Taken together, this study provides unique insights into the immunological trajectories following a first-in-life hookworm infection compared to natural infections.
Metabolic imaging across scales reveals distinct prostate cancer phenotypes
Authors: Sushentsev Nikita , Hamm Gregory , Flint Lucy , Birtles Daniel , Zakirov Aleksandr , Richings Jack , Ling Stephanie , Tan Jennifer Y. , McLean Mary A. , Ayyappan Vinay , Horvat Menih Ines , Brodie Cara , Miller Jodi L. , Mills Ian G. , Gnanapragasam Vincent J. , Warren Anne Y. , Barry Simon T. , Goodwin Richard J. A. , Barrett Tristan , Gallagher Ferdia A.
Published: July 2024

Hyperpolarised magnetic resonance imaging (HP-13C-MRI) has shown promise as a clinical tool for detecting and characterising prostate cancer. Here we use a range of spatially resolved histological techniques to identify the biological mechanisms underpinning differential [1-13C]lactate labelling between benign and malignant prostate, as well as in tumours containing cribriform and non-cribriform Gleason pattern 4 disease. Here we show that elevated hyperpolarised [1-13C]lactate signal in prostate cancer compared to the benign prostate is primarily driven by increased tumour epithelial cell density and vascularity, rather than differences in epithelial lactate concentration between tumour and normal. We also demonstrate that some tumours of the cribriform subtype may lack [1-13C]lactate labelling, which is explained by lower epithelial lactate dehydrogenase expression, higher mitochondrial pyruvate carrier density, and increased lipid abundance compared to lactate-rich non-cribriform lesions. These findings highlight the potential of combining spatial metabolic imaging tools across scales to identify clinically significant metabolic phenotypes in prostate cancer.
Voltage control of multiferroic magnon torque for reconfigurable logic-in-memory
Authors: Chai Yahong , Liang Yuhan , Xiao Cancheng , Wang Yue , Li Bo , Jiang Dingsong , Pal Pratap , Tang Yongjian , Chen Hetian , Zhang Yuejie , Bai Hao , Xu Teng , Jiang Wanjun , Skowroński Witold , Zhang Qinghua , Gu Lin , Ma Jing , Yu Pu , Tang Jianshi , Lin Yuan-Hua , Yi Di , Ralph Daniel C. , Eom Chang-Beom , Wu Huaqiang , Nan Tianxiang
Published: July 2024

Magnons, bosonic quasiparticles carrying angular momentum, can flow through insulators for information transmission with minimal power dissipation. However, it remains challenging to develop a magnon-based logic due to the lack of efficient electrical manipulation of magnon transport. Here we show the electric excitation and control of multiferroic magnon modes in a spin-source/multiferroic/ferromagnet structure. We demonstrate that the ferroelectric polarization can electrically modulate the magnon-mediated spin-orbit torque by controlling the non-collinear antiferromagnetic structure in multiferroic bismuth ferrite thin films with coupled antiferromagnetic and ferroelectric orders. In this multiferroic magnon torque device, magnon information is encoded to ferromagnetic bits by the magnon-mediated spin torque. By manipulating the two coupled non-volatile state variables—ferroelectric polarization and magnetization—we further present reconfigurable logic operations in a single device. Our findings highlight the potential of multiferroics for controlling magnon information transport and offer a pathway towards room-temperature voltage-controlled, low-power, scalable magnonics for in-memory computing.
Forest carbon stocks increase with higher dominance of ectomycorrhizal trees in high latitude forests
Authors: Yan Guoyong , Fan Chunnan , Zheng Junqiang , Liu Guancheng , Yu Jinghua , Guo Zhongling , Cao Wei , Wang Lihua , Wang Wenjie , Meng Qingfan , Zhang Junhui , Li Yan , Zheng Jinping , Cui Xiaoyang , Wang Xiaochun , Xu Lijian , Sun Yan , Zhang Zhi , Lü Xiao-Tao , Zhang Ying , Shi Rongjiu , Hao Guangyou , Feng Yue , He Jinsheng , Wang Qinggui , Xing Yajuan , Han Shijie
Published: July 2024

Understanding the mechanisms controlling forest carbon accumulation is crucial for predicting and mitigating future climate change. Yet, it remains unclear whether the dominance of ectomycorrhizal (EcM) trees influences the carbon accumulation of entire forests. In this study, we analyzed forest inventory data from over 4000 forest plots across Northeast China. We find that EcM tree dominance consistently exerts a positive effect on tree, soil, and forest carbon stocks. Moreover, we observe that these positive effects are more pronounced during unfavorable climate conditions, at lower tree species richness, and during early successional stages. This underscores the potential of increasing the dominance of native EcM tree species not only to enhance carbon stocks but also to bolster resilience against climate change in high-latitude forests. Here we show that forest managers can make informed decisions to optimize carbon accumulation by considering various factors such as mycorrhizal types, climate, successional stages, and species richness.
CryoET reveals actin filaments within platelet microtubules
Authors: Tsuji Chisato , Bradshaw Marston , Allen Megan F. , Jackson Molly L. , Mantell Judith , Borucu Ufuk , Poole Alastair W. , Verkade Paul , Hers Ingeborg , Paul Danielle M. , Dodding Mark P.
Published: July 2024

Crosstalk between the actin and microtubule cytoskeletons is important for many cellular processes. Recent studies have shown that microtubules and F-actin can assemble to form a composite structure where F-actin occupies the microtubule lumen. Whether these cytoskeletal hybrids exist in physiological settings and how they are formed is unclear. Here, we show that the short-crossover Class I actin filament previously identified inside microtubules in human HAP1 cells is cofilin-bound F-actin. Lumenal F-actin can be reconstituted in vitro, but cofilin is not essential. Moreover, actin filaments with both cofilin-bound and canonical morphologies reside within human platelet microtubules under physiological conditions. We propose that stress placed upon the microtubule network during motor-driven microtubule looping and sliding may facilitate the incorporation of actin into microtubules.
The energy landscape of magnetic materials
Authors: Ponet Louis , Di Lucente Enrico , Marzari Nicola
Published: July 2024

Magnetic materials can display many solutions to the electronic-structure problem, corresponding to different local or global minima of the energy functional. In Hartree-Fock or density-functional theory different single-determinant solutions lead to different magnetizations, ionic oxidation states, hybridizations, and inter-site magnetic couplings. The vast majority of these states can be fingerprinted through their projection on the atomic orbitals of the magnetic ions. We have devised an approach that provides an effective control over these occupation matrices, allowing us to systematically explore the landscape of the potential energy surface. We showcase the emergence of a complex zoology of self-consistent states; even more so when semi-local density-functional theory is augmented - and typically made more accurate - by Hubbard corrections. Such extensive explorations allow to robustly identify the ground state of magnetic systems, and to assess the accuracy (or not) of current functionals and approximations.
Ab initio framework for deciphering trade-off relationships in multi-component alloys
Authors: Moitzi Franco , Romaner Lorenz , Ruban Andrei V. , Hodapp Max , Peil Oleg E.
Published: July 2024

While first-principles methods have been successfully applied to characterize individual properties of multi-principal element alloys (MPEA), their use in searching for optimal trade-offs between competing properties is hampered by high computational demands. In this work, we present a framework to explore Pareto-optimal compositions by integrating advanced ab initio-based techniques into a Bayesian multi-objective optimization workflow, complemented by a simple analytical model providing straightforward analysis of trends. We benchmark the framework by applying it to solid solution strengthening and ductility of refractory MPEAs, with the parameters of the strengthening and ductility models being efficiently computed using a combination of the coherent-potential approximation method, accounting for finite-temperature effects, and actively-learned moment-tensor potentials parameterized with ab initio data. Properties obtained from ab initio calculations are subsequently used to extend predictions of all relevant material properties to a large class of refractory alloys with the help of the analytical model validated by the data and relying on a few element-specific parameters and universal functions that describe bonding between elements. Our findings offer crucial insights into the traditional strength-vs-ductility dilemma of refractory MPEAs. The proposed framework is versatile and can be extended to other materials and properties of interest, enabling a predictive and tractable high-throughput screening of Pareto-optimal MPEAs over the entire composition space.
Systems modeling of oncogenic G-protein and GPCR signaling reveals unexpected differences in downstream pathway activation
Authors: Trogdon Michael , Abbott Kodye , Arang Nadia , Lande Kathryn , Kaur Navneet , Tong Melinda , Bakhoum Mathieu , Gutkind J. Silvio , Stites Edward C.
Published: July 2024

Mathematical models of biochemical reaction networks are an important and emerging tool for the study of cell signaling networks involved in disease processes. One promising potential application of such mathematical models is the study of how disease-causing mutations promote the signaling phenotype that contributes to the disease. It is commonly assumed that one must have a thorough characterization of the network readily available for mathematical modeling to be useful, but we hypothesized that mathematical modeling could be useful when there is incomplete knowledge and that it could be a tool for discovery that opens new areas for further exploration. In the present study, we first develop a mechanistic mathematical model of a G-protein coupled receptor signaling network that is mutated in almost all cases of uveal melanoma and use model-driven explorations to uncover and explore multiple new areas for investigating this disease. Modeling the two major, mutually-exclusive, oncogenic mutations (Gαq/11 and CysLT2R) revealed the potential for previously unknown qualitative differences between seemingly interchangeable disease-promoting mutations, and our experiments confirmed oncogenic CysLT2R was impaired at activating the FAK/YAP/TAZ pathway relative to Gαq/11. This led us to hypothesize that CYSLTR2 mutations in UM must co-occur with other mutations to activate FAK/YAP/TAZ signaling, and our bioinformatic analysis uncovers a role for co-occurring mutations involving the plexin/semaphorin pathway, which has been shown capable of activating this pathway. Overall, this work highlights the power of mechanism-based computational systems biology as a discovery tool that can leverage available information to open new research areas.
A chromosome-level genome assembly for the paramylon-producing microalga Euglena gracilis
Authors: Chen Zixi , Dong Yang , Duan Shengchang , He Jiayi , Qin Huan , Bian Chao , Chen Zhenfan , Liu Chenchen , Zheng Chao , Du Ming , Yao Rao , Li Chao , Jiang Panpan , Wang Yun , Li Shuangfei , Xie Ning , Xu Ying , Shi Qiong , Hu Zhangli , Lei Anping , Zhao Liqing , Wang Jiangxin
Published: July 2024

Euglena gracilis (E. gracilis), pivotal in the study of photosynthesis, endosymbiosis, and chloroplast development, is also an industrial microalga for paramylon production. Despite its importance, E. gracilis genome exploration faces challenges due to its intricate nature. In this study, we achieved a chromosome-level de novo assembly (2.37 Gb) using Illumina, PacBio, Bionano, and Hi-C data. The assembly exhibited a contig N50 of 619 Kb and scaffold N50 of 1.12 Mb, indicating superior continuity. Approximately 99.83% of the genome was anchored to 46 chromosomes, revealing structural insights. Repetitive elements constituted 58.84% of the sequences. Functional annotations were assigned to 39,362 proteins, enhancing interpretative power. BUSCO analysis confirmed assembly completeness at 80.39%. This first high-quality E. gracilis genome offers insights for genetics and genomics studies, overcoming previous limitations. The impact extends to academic and industrial research, providing a foundational resource.
Considerations for protein and amino acids in standardized reference diet for parthenogenetic marbled crayfish Procambarus virginalis model organism
Authors: Das Koushik , Roy Koushik , Mráz Jan , Buřič Miloš , Kouba Antonín
Published: July 2024

The concept of a standardized reference diet (SRD) is used in laboratory model organisms to ensure nutritional control between studies and laboratories. Although models using the genetically identical, all female parthenogenetic marbled crayfish (Procambarus virginalis) are growing in popularity, research into nutrition in this species still has many knowledge gaps. To fast track the development of a SRD in terms of protein and amino acids (SRDprotein) for this species, we first analyzed the composition of its body amino acids to determine the ideal protein concept (IPC) of indispensable amino acids in wild-caught P. virginalis (which had an unusually high preponderance of leucine and arginine). Then, we strategically evaluated three common clusters of types of fish feed: (1) ornamental fish feed (SER) fortified with a naturally occurring alga (Spirulina). This type of feed was protein-high in arginine and leucine (SER + SPI) that fulfils the species’ IPC for iso-protein (~ 40%), iso-phosphorus (~ 0.8%) and near iso-energetic (~ 475 kcal 100 g−1); (2) freeze-dried live feed consisting of chironomid larvae (CHI) fortified with Spirulina (CHI + SPI) that fulfils the IPC for iso-protein (~ 46%), iso-phosphorus (~ 0.7%) and near iso-energetic (~ 405 kcal 100 g−1); and (3) a commercially standardized ‘starter diet’ for carnivorous fish larvae (FISH) and post-larval shrimps (SHRIMP) with iso-protein (~ 56%) and iso-phosphorus (~ 1.6%). A total of six diets, embracing a diverse range of proteinaceous feeds, were used in a 100-day ad libitum feeding and growth trial. The FISH group outperformed all the other groups (p < 0.05) and our exploratory multivariate analysis revealed an ideal demand of > 44% protein (tailored to deliver high arginine 3% and leucine 4%, followed by the usual lysine > 3.5% and methionine 1.2%) but also the lowest carbohydrate level (21%). For SRDprotein, our findings show that the FISH diet is ideal and suggest the possibilities of using a CHI + SPI diet for further optimization (more economic use of protein and phosphorus).
Electrochemical and statistical study of Nickel ion assessment in daily children intake samples relying on magnesium aluminate spinel nanoparticles
Authors: Mostafa Maysa R. , Mohamed Gehad G. , Fouad Omar A.
Published: July 2024

Lately, children's daily consumption of some products, such as cereals and candies, has been rising, which provides a compelling rationale for determining any metallic substances that may be present. Monitoring the concentration of certain metals, like nickel, in these products is necessary due to medical issues in humans when consumed regularly. So, in this work, a novel and highly selective carbon paste as a Ni(II) ion-selective sensor was prepared and investigated using ceramic magnesium aluminum spinel nanoparticles as the ionophore and tritolyl phosphate (TOCP) as a plasticizer. A modified co-precipitation method was used to synthesize the spinel nanoparticles. X-ray diffraction, scanning electron microscope with EDAX, transmission electron microscope, and BET surface area were used to determine the phase composition, microstructure, pores size, particle size, and surface area of the synthesized nanoparticles. The spinel nanoparticle was found to have a nano crystallite size with a cubic crystal system, a particle size ranging from 17.2 to 51.52 nm, mesoporous nature (average pore size = 8.72 nm), and a large surface area (61.75 m2/g). The composition ratio of graphite carbon as a base: TOCP as binder: spinal as ionophore was 67.3:30.0:2.7 (wt%) based on potentiometric detections over concentrations from 5.0 × 10−8 to 1.0 × 10−2 mol L−1 with LOD of 5.0 × 10−8 mol L−1. A measurement of 29.22 ± 0.12 mV decade−1 over pH 2.0–7.0 was made for the Nernstian slope. This sensor demonstrated good repeatability over nine weeks and a rapid response of 8 s. A good selectivity was shown for Ni(II) ions across many interferents, tri-, di-, and monovalent cations. The Ni(II) content in spiked real samples, including cocaine, sweets, coca, chocolate, carbonated drinks, cereals, and packages, were measured. The results obtained indicated no significant difference between the proposed potentiometric method and the officially reported ICP method according to the F- and t-test data. In addition to utilizing ANOVA statistical analysis, validation procedures have been implemented, and the results exceed the ICP-MS methodology.
Deep learning-based cell segmentation for rapid optical cytopathology of thyroid cancer
Authors: Jermain Peter R. , Oswald Martin , Langdun Tenzin , Wright Santana , Khan Ashraf , Stadelmann Thilo , Abdulkadir Ahmed , Yaroslavsky Anna N.
Published: July 2024

Fluorescence polarization (Fpol) imaging of methylene blue (MB) is a promising quantitative approach to thyroid cancer detection. Clinical translation of MB Fpol technology requires reduction of the data analysis time that can be achieved via deep learning-based automated cell segmentation with a 2D U-Net convolutional neural network. The model was trained and tested using images of pathologically diverse human thyroid cells and evaluated by comparing the number of cells selected, segmented areas, and Fpol values obtained using automated (AU) and manual (MA) data processing methods. Overall, the model segmented 15.8% more cells than the human operator. Differences in AU and MA segmented cell areas varied between − 55.2 and + 31.0%, whereas differences in Fpol values varied from − 20.7 and + 10.7%. No statistically significant differences between AU and MA derived Fpol data were observed. The largest differences in Fpol values correlated with greatest discrepancies in AU versus MA segmented cell areas. Time required for auto-processing was reduced to 10 s versus one hour required for MA data processing. Implementation of the automated cell analysis makes quantitative fluorescence polarization-based diagnosis clinically feasible.
Scalable interconnection using a superconducting flux qubit
Authors: Saida Daisuke , Makise Kazumasa , Hidaka Mutsuo
Published: July 2024

Superconducting quantum computers are rapidly reaching scales where bottlenecks to scaling arise from the practical aspects of the fabrication process. To improve quantum computer performance, implementation technology that guarantees the scalability of the number of qubits is essential. Increasing the degrees of freedom in routing by 2.5-dimensional implementation is important for realizing circuit scalability. We report an implementation technology to overcome the scaling bottlenecks using a reliable connection qubit with a demonstration of quantum annealing. The method comprises interconnection based on quantum annealing using a superconducting flux qubit, precise coupling status control, and flip-chip bonding. We perform experiments and simulations with a proof-of-concept demonstration of qubit coupling via interconnection using a flux qubit. The coupling status is strictly controllable by quantum annealing. A low-temperature flip-chip bonding technology is introduced for the 2.5-dimensional interconnection. The superconducting flux qubit, formed across two different chips via bumps, is demonstrated for the first time to show a state transition like that in a conventional qubit. The quantum annealing flux qubit and flip-chip bonding enable new interconnections between qubits. A perspective on the possibility of applying this technology to the connection between gate-type qubits is described.
Lower ionospheric resonance caused by Pekeris wave induced by 2022 Tonga volcanic eruption
Authors: Ohya Hiroyo , Tsuchiya Fuminori , Takamura Tamio , Shinagawa Hiroyuki , Takahashi Yukihiro , Chen Alfred B.
Published: July 2024

The submarine volcano Hunga Tonga–Hunga Ha’apai erupted explosively on January 15, 2022, offering a unique opportunity to investigate interactions between the atmosphere and ionosphere caused by Lamb and Pekeris waves. However, the resonance of Pekeris waves has not been previously detected. In this study, we applied a multi-point monitoring approach focusing on the lower ionosphere and atmospheric electric field. Here we show observed oscillations of 100–200 s in manmade transmitter signals and the magnetic and atmospheric electric fields, which were caused by Pekeris waves. However, no corresponding changes with the period of 100–200 s in atmospheric pressure due to Pekeris waves were observed on the ground. A simulation of neutral wind revealed Pekeris waves oscillating near the mesopause, suggesting resonance. Therefore, the oscillation in atmospheric electric field is interpreted that the resonance in the lower ionosphere was projected onto the Earth's surface via a global electric circuit.
Effectiveness and satisfaction with virtual and donor dissections: A randomized controlled trial
Authors: Yun Young Hyun , Kwon Hyeok Yi , Jeon Su Kyoung , Jon Yu Mi , Park Min Jung , Shin Dong Hoon , Choi Hyung Jin
Published: July 2024

In recent years, human anatomy education has faced challenges with traditional donor dissection, leading to the emergence of virtual dissection as an alternative. This study aims to investigate the academic performance and satisfaction of medical students by comparing the virtual and donor dissections. An open-labeled crossover randomized controlled trial was conducted with 154 first-year medical students in Human Anatomy and Neuroanatomy laboratories, which were divided into three classes. Students were randomly assigned to either the virtual (virtual dissection followed by donor dissection) or donor (donor dissection followed by virtual dissection) groups in each class. A curriculum, incorporating head-mounted displays (HMDs), a life-sized touchscreen, and tablets, was developed. Data was evaluated through quizzes and surveys. In the Human Anatomy laboratory, each class of the donor group conducted heart extraction, dissection and observation. In observation class, the virtual group had a significantly higher mean quiz score than the donor group (p < 0.05). Compared to the donor, satisfaction was significantly higher for the HMD (understanding of concept and immersion), life-size touchscreen (esthetics, understanding of the concept, and spatial ability), and tablet (esthetics, understanding of the concept, spatial ability, and continuous use intention). In the Neuroanatomy laboratory, the virtual group showed significantly higher mean quiz scores than the donor group (p < 0.05), and tablet showed a significantly higher satisfaction than donor in terms of esthetics, understanding of the concept, and spatial ability. These results suggest that virtual dissection has the potential to supplement or replace donor dissection in anatomy education. This study is innovative in that it successfully delivered scenario-based virtual content and validated the efficacy in academic performance and satisfaction when using virtual devices compared to donor.

Trial registration: This research has been registered in the Clinical Research Information Service (CRIS, https://cris.nih.go.kr/cris/search/detailSearch.do?search_lang=E&focus=reset_12&search_page=L&pageSize=10&page=undefined&seq=26002&status=5&seq_group=26002) with registration number "KCT0009075" and registration date "27/12/2023".
Remarkable stability of $$\gamma$$-$$N_2$$ and its prevalence in the nitrogen phase diagram
Authors: Yan Jinwei , Dalladay-Simpson Philip , Conway Lewis J. , Gorelli Federico , Pickard Chris , Liu Xiao-Di , Gregoryanz Eugene
Published: July 2024

Solid nitrogen exhibits a panoply of phenomena ranging from complex molecular crystalline configurations to polymerization and closing band gap at higher densities. Among the elemental molecular solids, nitrogen stands apart for having phases, which can only be stabilized following particular pressure-temperature pathways, indicative of metastability and kinetic barriers. Here, through the combination of Raman spectroscopy and dynamic compression techniques, we find that the appearance of the whole nitrogen phase diagram is determined by the P-T paths taken below 2 GPa. We reveal the existence of the path- and phase-dependent triple point between the $$\beta$$
β
-$$N_2$$

N
2

, $$\delta _{loc}$$

δ

loc

-$$N_2$$

N
2

and $$\gamma$$
γ
- or $$\epsilon$$
ϵ
-$$N_2$$

N
2

. We further show that the $$\beta$$
β
-$$N_2$$

N
2

towards $$\gamma$$
γ
-$$N_2$$

N
2

path below the triple point, that evades $$\delta$$
δ
($$\delta _{loc}$$

δ

loc

)-$$N_2$$

N
2

, results in the formation of $$\gamma$$
γ
-$$N_2$$

N
2

, which in turn becomes a dominant phase. We then demonstrate, that the $$\beta$$
β
-$$N_2$$

N
2

through $$\delta$$
δ
($$\delta _{loc}$$

δ

loc

)-$$N_2$$

N
2

above the triple point path leads to the formation of $$\epsilon$$
ϵ
-$$N_2$$

N
2

and the “well-established” phase diagram. An additional pathway, which by-passes the rotationally inhibited modifications $$\delta$$
δ
($$\delta _{loc}$$

δ

loc

)-$$N_2$$

N
2

, via rapid compression is found to produce $$\gamma$$
γ
-$$N_2$$

N
2

at higher temperatures. We argue that the pathway and phase sensitive triple point and the compression rate dependent phase formation challenge our understanding of this archetypal dense molecular solid.
Quantifying the uncertainty of LLM hallucination spreading in complex adaptive social networks
Authors: Hao Guozhi , Wu Jun , Pan Qianqian , Morello Rosario
Published: July 2024

Large language models (LLMs) are becoming a significant source of content generation in social networks, which is a typical complex adaptive system (CAS). However, due to their hallucinatory nature, LLMs produce false information that can spread through social networks, which will impact the stability of the whole society. The uncertainty of LLMs false information spread within social networks is attributable to the diversity of individual behaviors, intricate interconnectivity, and dynamic network structures. Quantifying the uncertainty of false information spread by LLMs in social networks is beneficial for preemptively devising strategies to defend against threats. To address these challenges, we propose an LLMs hallucination-aware dynamic modeling method via agent-based probability distributions, spread popularity and community affiliation, to quantify the uncertain spreading of LLMs hallucination in social networks. We set up the node attributes and behaviors in the model based on real-world data. For evaluation, we consider the spreaders, informed people, discerning and unwilling non-spreaders as indicators, and quantified the spreading under different LLMs task situations, such as QA, dialogue, and summarization, as well as LLMs versions. Furthermore, we conduct experiments using real-world LLM hallucination data combined with social network features to ensure the validity of the proposed quantifying scheme.
Smartphone usage during walking decreases the positive persistency in gait cycle variability
Authors: Yano Shunpei , Nakamura Akihiro , Suzuki Yasuyuki , Smith Charles E. , Nomura Taishin
Published: July 2024

Gait cycle variability during steady walking, described by the stride interval time series, has been used as a gait-stability-related measure. In particular, the positive persistency in the stride intervals with 1/f-like fluctuation and reduction of the persistency are the well-documented metrics that can characterize gait patterns of healthy young adults and elderly including patients with neurological diseases, respectively. Here, we examined effects of a dual task on gait cycle variability in healthy young adults, based on the mean and standard deviation statistics as well as the positive persistency of the stride intervals during steady walking on a treadmill. Specifically, three gait conditions were examined: control condition, non-cognitive task with holding a smartphone in front of the chest using their dominant hand and looking fixedly at a blank screen of the smartphone, and cognitive motor task with holding a smartphone as in the non-cognitive task and playing a puzzle game displayed on the smartphone by one-thumb operation. We showed that only the positive persistency, not the mean and standard deviation statistics, was affected by the cognitive and motor load of smartphone usage in the cognitive condition. More specifically, the positive persistency exhibited in the control and the non-cognitive conditions was significantly reduced in the cognitive condition. Our results suggest that the decrease in the positive persistency during the cognitive task, which might represent the deterioration of healthy gait pattern, is caused endogenously by the cognitive and motor load, not necessarily by the reduction of visual field as often hypothesized.
The isolation and identification of Bacillus velezensis ZN-S10 from vanilla (V. planifolia), and the microbial distribution after the curing process
Authors: Manyatsi Thabani Sydney , Lin Yu-Hsin , Jou Ying-Tzy
Published: July 2024

The market value of vanilla beans (Vanilla planifolia) is constantly increasing due to their natural aroma and flavor properties that improve after a curing process, where bacteria colonization plays a critical role. However, a few publications suggest that bacteria play a role in the curing process. Hence, this study aimed to isolateBacillussp. that could be used for fermentingV. planifoliawhile analyzing their role in the curing process.Bacillus velezensisZN-S10 identified with 16S rRNA sequencing was isolated from conventionally curedV. planifoliabeans. A bacteria culture solution ofB. velezensisZN-S10 (1 mL of 1 × 107 CFU mL−1) was then coated on 1 kg of non-cured vanilla pods that was found to ferment and colonize vanilla. PCA results revealed distinguished bacterial communities of fermented vanilla and the control group, suggesting colonization of vanilla. Phylogenetic analysis showed that ZN-S10 was the dominantBacillusgenus member and narrowly correlated toB. velezensisEM-1 andB. velezensisPMC206-1, with 78% and 73% similarity, respectively. The bacterial taxonomic profiling of curedV. planifoliahad a significant relative abundance ofFirmicutes, Proteobacteria, Cyanobacteria, Planctomycetes,andBacteroidetesphyla according to the predominance.Firmicutesaccounted for 55% of the total bacterial sequences, suggesting their colonization and effective fermentation roles in curing vanilla.