bluuebunny/crossref_metadata_2025 huggingface dataset:
Adolescent BCG revaccination induces a phenotypic shift in CD4+ T cell responses to Mycobacterium tuberculosis
Authors: Dintwe One B. , Ballweber Fleming Lamar , Voillet Valentin , McNevin John , Seese Aaron , Naidoo Anneta , Omarjee Saleha , Bekker Linda-Gail , Kublin James G. , De Rosa Stephen C. , Newell Evan W. , Fiore-Gartland Andrew , Andersen-Nissen Erica , McElrath M. Juliana
Published: June 2024

A recent clinical trial demonstrated that Bacille Calmette-Guérin (BCG) revaccination of adolescents reduced the risk of sustained infection withMycobacterium tuberculosis(M.tb). In a companion phase 1b trial, HVTN 602/Aeras A-042, we characterize in-depth the cellular responses to BCG revaccination or to a H4:IC31 vaccine boost to identify T cell subsets that could be responsible for the protection observed. High-dimensional clustering analysis of cells profiled using a 26-color flow cytometric panel show marked increases in five effector memory CD4+T cell subpopulations (TEM) after BCG revaccination, two of which are highly polyfunctional. CITE-Seq single-cell analysis shows that the activated subsets include an abundant cluster of Th1 cells with migratory potential. Additionally, a small cluster of Th17 TEMcells induced by BCG revaccination expresses high levels of CD103; these may represent recirculating tissue-resident memory cells that could provide pulmonary immune protection. Together, these results identify unique populations of CD4+T cells with potential to be immune correlates of protection conferred by BCG revaccination.
Faecal microbiota of schoolchildren is associated with nutritional status and markers of inflammation: a double-blinded cluster-randomized controlled trial using multi-micronutrient fortified rice
Authors: Seyoum Yohannes , Greffeuille Valérie , Kouadio Dorgeles Kouakou Dje , Kuong Khov , Turpin Williams , M’Rabt Rachida , Chochois Vincent , Fortin Sonia , Perignon Marlène , Fiorentino Marion , Berger Jacques , Burja Kurt , Ponce Maiza Campos , Chamnan Chhoun , Wieringa Frank T. , Humblot Christèle
Published: June 2024

Faecal microbiota plays a critical role in human health, but its relationship with nutritional status among schoolchildren remains under-explored. Here, in a double-blinded cluster-randomized controlled trial on 380 Cambodian schoolchildren, we characterize the impact of six months consumption of two types of rice fortified with different levels of vitamins and minerals on pre-specified outcomes. We investigate the association between the faecal microbiota (16SrRNA sequencing) and age, sex, nutritional status (underweight, stunting), micronutrient status (iron, zinc and vitamin A deficiencies, anaemia, iron deficient anaemia, hemoglobinopathy), inflammation (systemic, gut), and parasitic infection. We show that the faecal microbiota is characterised by a surprisingly high proportion of Lactobacillaceae. We discover that deficiencies in specific micronutrients, such as iron and vitamin A, correlate with particular microbiota profiles, whereas zinc deficiency shows no such association. The nutritional intervention with the two rice treatments impacts both the composition and functions predicted from compositional analysis in different ways. (ClinicalTrials.gov (Identifier: NCT01706419))
Immuno-protective vesicle-crosslinked hydrogel for allogenic transplantation
Authors: Wang Yuqian , Huang Renqi , Lu Yougong , Liu Mingqi , Mo Ran
Published: June 2024

The longevity of grafts remains a major challenge in allogeneic transplantation due to immune rejection. Systemic immunosuppression can impair graft function and can also cause severe adverse effects. Here, we report a local immuno-protective strategy to enhance post-transplant persistence of allografts using a mesenchymal stem cell membrane-derived vesicle (MMV)-crosslinked hydrogel (MMV-Gel). MMVs are engineered to upregulate expression of Fas ligand (FasL) and programmed death ligand 1 (PD-L1). The MMVs are retained within the hydrogel by crosslinking. The immuno-protective microenvironment of the hydrogel protects allografts by presenting FasL and PD-L1. The binding of these ligands to T effector cells, the dominant contributors to graft destruction and rejection, results in apoptosis of T effector cells and generation of regulatory T cells. We demonstrate that implantation with MMV-Gel prolongs the survival and function of grafts in mouse models of allogeneic pancreatic islet cells and skin transplantation.
Low-coordinated copper facilitates the *CH2CO affinity at enhanced rectifying interface of Cu/Cu2O for efficient CO2-to-multicarbon alcohols conversion
Authors: Zhang Yangyang , Chen Yanxu , Wang Xiaowen , Feng Yafei , Dai Zechuan , Cheng Mingyu , Zhang Genqiang
Published: June 2024

The carbon−carbon coupling at the Cu/Cu2O Schottky interface has been widely recognized as a promising approach for electrocatalytic CO2 conversion into value-added alcohols. However, the limited selectivity of C2+ alcohols persists due to the insufficient control over rectifying interface characteristics required for precise bonding of oxyhydrocarbons. Herein, we present an investigation into the manipulation of the coordination environment of Cu sites through an in-situ electrochemical reconstruction strategy, which indicates that the construction of low-coordinated Cu sites at the Cu/Cu2O interface facilitates the enhanced rectifying interfaces, and induces asymmetric electronic perturbation and faster electron exchange, thereby boosting C-C coupling and bonding oxyhydrocarbons towards the nucleophilic reaction process of *H2CCO-CO. Impressively, the low-coordinated Cu sites at the Cu/Cu2O interface exhibit superior faradic efficiency of 64.15  ±  1.92% and energy efficiency of ~39.32% for C2+ alcohols production, while maintaining stability for over 50 h (faradic efficiency >50%, total current density = 200 mA cm−2) in a flow-cell electrolyzer. Theoretical calculations, operando synchrotron radiation Fourier transform infrared spectroscopy, and Raman experiments decipher that the low-coordinated Cu sites at the Cu/Cu2O interface can enhance the coverage of *CO and adsorption of *CH2CO and CH2CHO, facilitating the formation of C2+ alcohols.
Exponential concentration in quantum kernel methods
Authors: Thanasilp Supanut , Wang Samson , Cerezo M. , Holmes Zoë
Published: June 2024

Kernel methods in Quantum Machine Learning (QML) have recently gained significant attention as a potential candidate for achieving a quantum advantage in data analysis. Among other attractive properties, when training a kernel-based model one is guaranteed to find the optimal model’s parameters due to the convexity of the training landscape. However, this is based on the assumption that the quantum kernel can be efficiently obtained from quantum hardware. In this work we study the performance of quantum kernel models from the perspective of the resources needed to accurately estimate kernel values. We show that, under certain conditions, values of quantum kernels over different input data can be exponentially concentrated (in the number of qubits) towards some fixed value. Thus on training with a polynomial number of measurements, one ends up with a trivial model where the predictions on unseen inputs are independent of the input data. We identify four sources that can lead to concentration including expressivity of data embedding, global measurements, entanglement and noise. For each source, an associated concentration bound of quantum kernels is analytically derived. Lastly, we show that when dealing with classical data, training a parametrized data embedding with a kernel alignment method is also susceptible to exponential concentration. Our results are verified through numerical simulations for several QML tasks. Altogether, we provide guidelines indicating that certain features should be avoided to ensure the efficient evaluation of quantum kernels and so the performance of quantum kernel methods.
Enhanced eMAGE applied to identify genetic factors of nuclear hormone receptor dysfunction via combinatorial gene editing
Authors: Ciaccia Peter N. , Liang Zhuobin , Schweitzer Anabel Y. , Metzner Eli , Isaacs Farren J.
Published: June 2024

Technologies that generate precise combinatorial genome modifications are well suited to dissect the polygenic basis of complex phenotypes and engineer synthetic genomes. Genome modifications with engineered nucleases can lead to undesirable repair outcomes through imprecise homology-directed repair, requiring non-cleavable gene editing strategies. Eukaryotic multiplex genome engineering (eMAGE) generates precise combinatorial genome modifications in Saccharomyces cerevisiae without generating DNA breaks or using engineered nucleases. Here, we systematically optimize eMAGE to achieve 90% editing frequency, reduce workflow time, and extend editing distance to 20 kb. We further engineer an inducible dominant negative mismatch repair system, allowing for high-efficiency editing via eMAGE while suppressing the elevated background mutation rate 17-fold resulting from mismatch repair inactivation. We apply these advances to construct a library of cancer-associated mutations in the ligand-binding domains of human estrogen receptor alpha and progesterone receptor to understand their impact on ligand-independent autoactivation. We validate that this yeast model captures autoactivation mutations characterized in human breast cancer models and further leads to the discovery of several previously uncharacterized autoactivating mutations. This work demonstrates the development and optimization of a cleavage-free method of genome editing well suited for applications requiring efficient multiplex editing with minimal background mutations.
PIP2 modulates TRPC3 activity via TRP helix and S4-S5 linker
Authors: Clarke Amy , Skerjanz Julia , Gsell Mathias A. F. , Wiedner Patrick , Erkan-Candag Hazel , Groschner Klaus , Stockner Thomas , Tiapko Oleksandra
Published: June 2024

The transient receptor potential canonical type 3 (TRPC3) channel plays a pivotal role in regulating neuronal excitability in the brain via its constitutive activity. The channel is intricately regulated by lipids and has previously been demonstrated to be positively modulated by PIP2. Using molecular dynamics simulations and patch clamp techniques, we reveal that PIP2 predominantly interacts with TRPC3 at the L3 lipid binding site, located at the intersection of pre-S1 and S1 helices. We demonstrate that PIP2 sensing involves a multistep mechanism that propagates from L3 to the pore domain via a salt bridge between the TRP helix and S4-S5 linker. Notably, we find that both stimulated and constitutive TRPC3 activity require PIP2. These structural insights into the function of TRPC3 are invaluable for understanding the role of the TRPC subfamily in health and disease, in particular for cardiovascular diseases, in which TRPC3 channels play a major role.
Epistasis mediates the evolution of the receptor binding mode in recent human H3N2 hemagglutinin
Authors: Lei Ruipeng , Liang Weiwen , Ouyang Wenhao O. , Hernandez Garcia Andrea , Kikuchi Chika , Wang Shengyang , McBride Ryan , Tan Timothy J. C. , Sun Yuanxin , Chen Chunke , Graham Claire S. , Rodriguez Lucia A. , Shen Ivana R. , Choi Danbi , Bruzzone Roberto , Paulson James C. , Nair Satish K. , Mok Chris K. P. , Wu Nicholas C.
Published: June 2024

The receptor-binding site of influenza A virus hemagglutinin partially overlaps with major antigenic sites and constantly evolves. In this study, we observe that mutations G186D and D190N in the hemagglutinin receptor-binding site have coevolved in two recent human H3N2 clades. X-ray crystallography results show that these mutations coordinately drive the evolution of the hemagglutinin receptor binding mode. Epistasis between G186D and D190N is further demonstrated by glycan binding and thermostability analyses. Immunization and neutralization experiments using mouse and human samples indicate that the evolution of receptor binding mode is accompanied by a change in antigenicity. Besides, combinatorial mutagenesis reveals that G186D and D190N, along with other natural mutations in recent H3N2 strains, alter the compatibility with a common egg-adaptive mutation in seasonal influenza vaccines. Overall, our findings elucidate the role of epistasis in shaping the recent evolution of human H3N2 hemagglutinin and substantiate the high evolvability of its receptor-binding mode.
Strain to shine: stretching-induced three-dimensional symmetries in nanoparticle-assembled photonic crystals
Authors: An Tong , Jiang Xinyu , Gao Feng , Schäfer Christian , Qiu Junjun , Shi Nan , Song Xiaokun , Zhang Manyao , Finlayson Chris E. , Zheng Xuezhi , Li Xiuhong , Tian Feng , Zhu Bin , Sui Tan , Han Xianhong , Baumberg Jeremy J. , Fan Tongxiang , Zhao Qibin
Published: June 2024

Stretching elastic materials containing nanoparticle lattices is common in research and industrial settings, yet our knowledge of the deformation process remains limited. Understanding how such lattices reconfigure is critically important, as changes in microstructure lead to significant alterations in their performance. This understanding has been extremely difficult to achieve due to a lack of fundamental rules governing the rearrangements. Our study elucidates the physical processes and underlying mechanisms of three-dimensional lattice transformations in a polymeric photonic crystal from 0% to over 200% strain during uniaxial stretching. Corroborated by comprehensive experimental characterizations, we present analytical models that precisely predict both the three-dimensional lattice structures and the macroscale deformations throughout the stretching process. These models reveal how the nanoparticle lattice and matrix polymer jointly determine the resultant structures, which breaks the original structural symmetry and profoundly changes the dispersion of photonic bandgaps. Stretching induces shifting of the main pseudogap structure out from the 1st Brillouin zone and the merging of different symmetry points. Evolutions of multiple photonic bandgaps reveal potential optical singularities shifting with strain. This work sets a new benchmark for the reconfiguration of soft material structures and may lay the groundwork for the study of stretchable three-dimensional topological photonic crystals.
Enhanced stress resilience in potato by deletion of Parakletos
Authors: Zahid Muhammad Awais , Kieu Nam Phuong , Carlsen Frida Meijer , Lenman Marit , Konakalla Naga Charan , Yang Huanjie , Jyakhwa Sunmoon , Mravec Jozef , Vetukuri Ramesh , Petersen Bent Larsen , Resjö Svante , Andreasson Erik
Published: June 2024

Continued climate change impose multiple stressors on crops, including pathogens, salt, and drought, severely impacting agricultural productivity. Innovative solutions are necessary to develop resilient crops. Here, using quantitative potato proteomics, we identify Parakletos, a thylakoid protein that contributes to disease susceptibility. We show that knockout or silencing of Parakletos enhances resistance to oomycete, fungi, bacteria, salt, and drought, whereas its overexpression reduces resistance. In response to biotic stimuli, Parakletos-overexpressing plants exhibit reduced amplitude of reactive oxygen species and Ca2+ signalling, and silencing Parakletos does the opposite. Parakletos homologues have been identified in all major crops. Consecutive years of field trials demonstrate that Parakletos deletion enhances resistance to Phytophthora infestans and increases yield. These findings demark a susceptibility gene, which can be exploited to enhance crop resilience towards abiotic and biotic stresses in a low-input agriculture.
Protein restriction slows the development and progression of pathology in a mouse model of Alzheimer’s disease
Authors: Babygirija Reji , Sonsalla Michelle M. , Mill Jericha , James Isabella , Han Jessica H. , Green Cara L. , Calubag Mariah F. , Wade Gina , Tobon Anna , Michael John , Trautman Michaela M. , Matoska Ryan , Yeh Chung-Yang , Grunow Isaac , Pak Heidi H. , Rigby Michael J. , Baldwin Dominique A. , Niemi Natalie M. , Denu John M. , Puglielli Luigi , Simcox Judith , Lamming Dudley W.
Published: June 2024

Dietary protein is a critical regulator of metabolic health and aging. Low protein diets are associated with healthy aging in humans, and dietary protein restriction extends the lifespan and healthspan of mice. In this study, we examined the effect of protein restriction (PR) on metabolic health and the development and progression of Alzheimer’s disease (AD) in the 3xTg mouse model of AD. Here, we show that PR promotes leanness and glycemic control in 3xTg mice, specifically rescuing the glucose intolerance of 3xTg females. PR induces sex-specific alterations in circulating and brain metabolites, downregulating sphingolipid subclasses in 3xTg females. PR also reduces AD pathology and mTORC1 activity, increases autophagy, and improves the cognition of 3xTg mice. Finally, PR improves the survival of 3xTg mice. Our results suggest that PR or pharmaceutical interventions that mimic the effects of this diet may hold promise as a treatment for AD.
Deep sequencing of Escherichia coli exposes colonisation diversity and impact of antibiotics in Punjab, Pakistan
Authors: Khawaja Tamim , Mäklin Tommi , Kallonen Teemu , Gladstone Rebecca A. , Pöntinen Anna K. , Mero Sointu , Thorpe Harry A. , Samuelsen Ørjan , Parkhill Julian , Izhar Mateen , Akhtar M. Waheed , Corander Jukka , Kantele Anu
Published: June 2024

Multi-drug resistant (MDR) E. coli constitute a major public health burden globally, reaching the highest prevalence in the global south yet frequently flowing with travellers to other regions. However, our comprehension of the entire genetic diversity of E. coli colonising local populations remains limited. We quantified this diversity, its associated antimicrobial resistance (AMR), and assessed the impact of antibiotic use by recruiting 494 outpatients and 423 community dwellers in the Punjab province, Pakistan. Rectal swab and stool samples were cultured on CLED agar and DNA extracted from plate sweeps was sequenced en masse to capture both the genetic and AMR diversity of E. coli. We assembled 5,247 E. coli genomes from 1,411 samples, displaying marked genetic diversity in gut colonisation. Compared with high income countries, the Punjabi population generally showed a markedly different distribution of genetic lineages and AMR determinants, while use of antibiotics elevated the prevalence of well-known globally circulating MDR clinical strains. These findings implicate that longitudinal multi-regional genomics-based surveillance of both colonisation and infections is a prerequisite for developing mechanistic understanding of the interplay between ecology and evolution in the maintenance and dissemination of (MDR) E. coli.
Structural basis for hyperpolarization-dependent opening of human HCN1 channel
Authors: Burtscher Verena , Mount Jonathan , Huang Jian , Cowgill John , Chang Yongchang , Bickel Kathleen , Chen Jianhan , Yuan Peng , Chanda Baron
Published: June 2024

Hyperpolarization and cyclic nucleotide (HCN) activated ion channels are critical for the automaticity of action potentials in pacemaking and rhythmic electrical circuits in the human body. Unlike most voltage-gated ion channels, the HCN and related plant ion channels activate upon membrane hyperpolarization. Although functional studies have identified residues in the interface between the voltage-sensing and pore domain as crucial for inverted electromechanical coupling, the structural mechanisms for this unusual voltage-dependence remain unclear. Here, we present cryo-electron microscopy structures of human HCN1 corresponding to Closed, Open, and a putative Intermediate state. Our structures reveal that the downward motion of the gating charges past the charge transfer center is accompanied by concomitant unwinding of the inner end of the S4 and S5 helices, disrupting the tight gating interface observed in the Closed state structure. This helix-coil transition at the intracellular gating interface accompanies a concerted iris-like dilation of the pore helices and underlies the reversed voltage dependence of HCN channels.
Competing climate feedbacks of ice sheet freshwater discharge in a warming world
Authors: Li Dawei , DeConto Robert M. , Pollard David , Hu Yongyun
Published: June 2024

Freshwater discharge from ice sheets induces surface atmospheric cooling and subsurface ocean warming, which are associated with negative and positive feedbacks respectively. However, uncertainties persist regarding these feedbacks’ relative strength and combined effect. Here we assess associated feedbacks in a coupled ice sheet-climate model, and show that for the Antarctic Ice Sheet the positive feedback dominates in moderate future warming scenarios and in the early stage of ice sheet retreat, but is overwhelmed by the negative feedback in intensive warming scenarios when the West Antarctic Ice Sheet undergoes catastrophic collapse. The Atlantic Meridional Overturning Circulation is affected by freshwater discharge from both the Greenland and the Antarctic ice sheets and, as an interhemispheric teleconnection bridge, exacerbates the opposing ice sheet’s retreat via the Bipolar Seesaw. These results highlight the crucial role of ice sheet-climate interactions via freshwater flux in future ice sheet retreat and associated sea-level rise.
Daily station-level records of air temperature, snow depth, and ground temperature in the Northern Hemisphere
Authors: Tran Vinh Ngoc , Zhou Wenbo , Kim Taeho , Mazepa Valeriy , Valdayskikh Victor , Ivanov Valeriy Y.
Published: June 2024

Air temperature (Ta), snow depth (Sd), and soil temperature (Tg) are crucial variables for studying the above- and below-ground thermal conditions, especially in high latitudes. However,in-situobservations are frequently sparse and inconsistent across various datasets, with a significant amount of missing data. This study has assembled a comprehensive dataset ofin-situobservations of Ta, Sd, and Tg for the Northern Hemisphere (higher than 30°N latitude), spanning 1960–2021. This dataset encompasses metadata and daily data time series for 27,768, 32,417, and 659 gages for Ta, Sd, and Tg, respectively. Using the ERA5-Land reanalysis data product, we applied deep learning methodology to reconstruct the missing data that account for 54.5%, 59.3%, and 74.3% of Ta, Sd, and Tg daily time series, respectively. The obtained high temporal resolution dataset can be used to better understand physical phenomena and relevant mechanisms, such as the dynamics of land-surface-atmosphere energy exchange, snowpack, and permafrost.
Unravelling the effects of nano SiO2, nano TiO2 and their nanocomposites on Zea mays L. growth and soil health
Authors: Kumari Kusum , Rani Neelam , Hooda Vinita
Published: June 2024

Amidst the challenges posed by climate change, exploring advanced technologies like nanotechnology is crucial for enhancing agricultural productivity and food security. Consequently, this study investigated the impact of nano SiO2 (nSiO2), nano TiO2 (nTiO2) and SiO2/TiO2 nanocomposites (NCs) on 30-day-old Zea mays L. plants and soil health at concentrations of 100 and 200 ppm. Results showed that nSiO2 and nTiO2 at 100 ppm and SiO2/TiO2 NCs at both concentrations, positively influenced plant growth, with the best stimulation observed at 200 ppm of SiO2/TiO2 NCs. Improved plant growth was associated with higher chlorophyll content, photosynthetic rate, transpiration rate, stomatal conductance, rhizospheric N-fixing and phosphate solubilizing bacterial population and plant nutrient uptake. Additionally, treated plants exhibited increased cellulose and starch levels. Malondialdehyde (MDA) content was lower or similar to that of the control, except at 200 ppm of nTiO2-treated shoots. Antioxidant enzyme activities fluctuated, indicating physiological adjustments. Overall, 100 ppm of nTiO2 as well as nSiO2 and 100 and 200 ppm of SiO2/TiO2 NCs improved soil fertility and Z. mays growth, suggesting potential benefits for sustainable agriculture. The findings lay the foundation for more comprehensive investigations into the long-term fate of nanomaterials in soil and their intricate molecular-level interactions with Z. mays.
Classification of coal bursting liability of some chinese coals using machine learning methods
Authors: Wang Chao , Liu Yv , Li Yuefeng , Liu Xiaofei , Wang Qiwei
Published: June 2024

The classification of coal bursting liability (CBL) is essential for the mitigation and management of coal bursts in mining operations. This study establishes an index system for CBL classification, incorporating dynamic fracture duration (DT), elastic strain energy index (WET), bursting energy index (KE), and uniaxial compressive strength (RC). Utilizing a dataset comprising 127 CBL measurement groups, the impacts of various optimization algorithms were assessed, and two prominent machine learning techniques, namely the back propagation neural network (BPNN) and the support vector machine (SVM), were employed to develop twelve distinct models. The models’ efficacy was evaluated based on accuracy, F1-score, Kappa coefficient, and sensitivity analysis. Among these, the Levenberg–Marquardt back propagation neural network (LM-BPNN) model was identified as superior, achieving an accuracy of 96.85%, F1-score of 0.9113, and Kappa coefficient of 0.9417. Further validation in Wudong Coal Mine and Yvwu Coal Industry confirmed the model, achieving 100% accuracy. These findings underscore the LM-BPNN model’s potential as a viable tool for enhancing coal burst prevention strategies in coal mining sectors.
Body size predicts ontogenetic nitrogen stable-isotope (δ15N) variation, but has little relationship with trophic level in ectotherm vertebrate predators
Authors: Villamarín Francisco , Jardine Timothy D. , Bunn Stuart E. , Malvasio Adriana , Piña Carlos Ignacio , Jacobi Cristina Mariana , Araújo Diogo Dutra , de Brito Elizângela Silva , de Moraes Carvalho Felipe , da Costa Igor David , Verdade Luciano Martins , Lara Neliton , de Camargo Plínio Barbosa , Miorando Priscila Saikoski , Portelinha Thiago Costa Gonçalves , Marques Thiago Simon , Magnusson William E.
Published: June 2024

Large predators have disproportionate effects on their underlying food webs. Thus, appropriately assigning trophic positions has important conservation implications both for the predators themselves and for their prey. Large-bodied predators are often referred to as apex predators, implying that they are many trophic levels above primary producers. However, theoretical considerations predict both higher and lower trophic position with increasing body size. Nitrogen stable isotope values (δ15N) are increasingly replacing stomach contents or behavioral observations to assess trophic position and it is often assumed that ontogenetic dietary shifts result in higher trophic positions. Intraspecific studies based on δ15N values found a positive relationship between size and inferred trophic position. Here, we use datasets of predatory vertebrate ectotherms (crocodilians, turtles, lizards and fishes) to show that, although there are positive intraspecific relationships between size and δ15N values, relationships between stomach-content-based trophic level (TPdiet) and size are undetectable or negative. As there is usually no single value for 15N trophic discrimination factor (TDF) applicable to a predator species or its prey, estimates of trophic position based on δ15N in ectotherm vertebrates with large size ranges, may be inaccurate and biased. We urge a reconsideration of the sole use of δ15N values to assess trophic position and encourage the combined use of isotopes and stomach contents to assess diet and trophic level.
Use of phase plate cryo-EM reveals conformation diversity of therapeutic IgG with 50 kDa Fab fragment resolved below 6 Å
Authors: Lin Hsin-Hung , Wang Chun-Hsiung , Huang Shih-Hsin , Lin Sung-Yao , Kato Takayuki , Namba Keiichi , Hosogi Naoki , Song Chihong , Murata Kazuyoshi , Yen Ching-Hsuan , Hsu Tsui-Ling , Wong Chi-Huey , Wu Yi-Min , Tu I.-Ping , Chang Wei-Hau
Published: June 2024

While cryogenic electron microscopy (cryo-EM) is fruitfully used for harvesting high-resolution structures of sizable macromolecules, its application to small or flexible proteins composed of small domains like immunoglobulin (IgG) remain challenging. Here, we applied single particle cryo-EM to Rituximab, a therapeutic IgG mediating anti-tumor toxicity, to explore its solution conformations. We found Rituximab molecules exhibited aggregates in cryo-EM specimens contrary to its solution behavior, and utilized a non-ionic detergent to successfully disperse them as isolated particles amenable to single particle analysis. As the detergent adversely reduced the protein-to-solvent contrast, we employed phase plate contrast to mitigate the impaired protein visibility. Assisted by phase plate imaging, we obtained a canonical three-arm IgG structure with other structures displaying variable arm densities co-existing in solution, affirming high flexibility of arm-connecting linkers. Furthermore, we showed phase plate imaging enables reliable structure determination of Fab to sub-nanometer resolution from ab initio, yielding a characteristic two-lobe structure that could be unambiguously docked with crystal structure. Our findings revealed conformation diversity of IgG and demonstrated phase plate was viable for cryo-EM analysis of small proteins without symmetry. This work helps extend cryo-EM boundaries, providing a valuable imaging and structural analysis framework for macromolecules with similar challenging features.
Automated detection of selected tea leaf diseases in Bangladesh with convolutional neural network
Authors: Rahman Hafijur , Ahmad Iftekhar , Jon Parvej Hasan , Salam Abdus , Rabbi Md. Forhad
Published: June 2024

Globally, tea production and its quality fundamentally depend on tea leaves, which are susceptible to invasion by pathogenic organisms. Precise and early-stage identification of plant foliage diseases is a key element in preventing and controlling the spreading of diseases that hinder yield and quality. Image processing techniques are a sophisticated tool that is rapidly gaining traction in the agricultural sector for the detection of a wide range of diseases with excellent accuracy. This study focuses on a pragmatic approach for automatically detecting selected tea foliage diseases based on convolutional neural network (CNN). A large dataset of 3330 images has been created by collecting samples from different regions of Sylhet division, the tea capital of Bangladesh. The proposed CNN model is developed based on tea leaves affected by red rust, brown blight, grey blight, and healthy leaves. Afterward, the model’s prediction was validated with laboratory tests that included microbial culture media and microscopic analysis. The accuracy of this model was found to be 96.65%. Chiefly, the proposed model was developed in the context of the Bangladesh tea industry.
Empowering artificial intelligence in characterizing the human primary pacemaker of the heart at single cell resolution
Authors: Chelu Alexandru , Cartwright Elizabeth J. , Dobrzynski Halina
Published: June 2024

The sinus node (SN) serves as the primary pacemaker of the heart and is the first component of the cardiac conduction system. Due to its anatomical properties and sample scarcity, the cellular composition of the human SN has been historically challenging to study. Here, we employed a novel deep learning deconvolution method, namely Bulk2space, to characterise the cellular heterogeneity of the human SN using existing single-cell datasets of non-human species. As a proof of principle, we used Bulk2Space to profile the cells of the bulk human right atrium using publicly available mouse scRNA-Seq data as a reference. 18 human cell populations were identified, with cardiac myocytes being the most abundant. Each identified cell population correlated to its published experimental counterpart. Subsequently, we applied the deconvolution to the bulk transcriptome of the human SN and identified 11 cell populations, including a population of pacemaker cardiomyocytes expressing pacemaking ion channels (HCN1, HCN4, CACNA1D) and transcription factors (SHOX2 and TBX3). The connective tissue of the SN was characterised by adipocyte and fibroblast populations, as well as key immune cells. Our work unravelled the unique single cell composition of the human SN by leveraging the power of a novel machine learning method.
Identifying clusters of precipitation for the Brazilian Legal Amazon based on magnitude of trends and its correlation with sea surface temperature
Authors: Moreira Rodrigo Martins , dos Santos Bruno César , Biggs Trent , de Sales Fernando , Sieber Stefan
Published: June 2024

Prioritizing watershed management interventions relies on delineating homogeneous precipitation regions. In this study, we identify these regions in the Brazilian Legal Amazon based on the magnitude of Sen’s Slope trends using annual precipitation data from September to August, employing the Google Earth Engine platform. Utilizing the silhouette method, we determine four distinct clusters representing zones of homogeneous precipitation patterns. Cluster 0 exhibits a significant median increase in precipitation of 3.20 mm year−1 over the period from 1981 to 2020. Cluster 1 shows a notable increase of 8.13 mm year−1, while Clusters 2 and 3 demonstrate reductions in precipitation of − 1.61 mm year−1 and − 3.87 mm year−1, respectively, all statistically significant. Notably, the region known as the arc of deforestation falls within Cluster 2, indicating a concerning trend of reduced precipitation. Additionally, our analysis reveals significant correlations between Sea Surface Temperature (SST) in various oceanic regions and precipitation patterns over the Brazilian Legal Amazon. Particularly noteworthy is the strong positive correlation with SST in the South Atlantic, while negative correlations are observed with SST in the South Pacific and North Atlantic. These findings provide valuable insights for enhancing climate adaptation strategies in the Brazilian Legal Amazon region.
Optimization of cross-border E-commerce (CBEC) supply chain management based on fuzzy logic and auction theory
Authors: Gong Zhi
Published: June 2024

People have benefited enormously from e-commerce’s explosive expansion in recent years. E-commerce, in contrast to the traditional business environment, is dynamic and complicated, which poses a number of challenges. The prediction market can create mixed intelligence for sales forecasting, which is essential for e-commerce enterprises, to handle this difficulty. Combining the usage of human analysts and machine learning algorithms can accomplish this. To accurately anticipate retailer volume and allot resources, a novel methodology for optimizing supply chain management at CBEC is proposed in this paper. The framework improves efficiency and profitability by using fuzzy logic and auction theory to make strategic decisions. Thanks to this creative strategy, managers can now make more informed decisions, ultimately enhancing the efficiency of CBEC’s supply chain. The results of this paper reveal that our proposed method is superior to previous comparable methods, with RMSE and MAE values of 22.31 and 18.76, respectively. This approach offers a promising solution to the challenges faced by e-commerce businesses, and can help them achieve greater success in the dynamic and complex world of online commerce.
Paleosedimentary environmental reconstruction and mechanisms of the response to the Toarcian OAE in a lacustrine shale system
Authors: Wang Enze , Guo Tonglou , Li Maowen
Published: June 2024

The Lower Jurassic Ziliujing Formation in China’s Sichuan Basin is a significant shale target for exploration; however, the strong heterogeneity of the properties of organic matter (OM) in shale makes it challenging to identify the target area for exploration, and the mechanism of OM enrichment is still unclear. Furthermore, the mechanisms of the response of the Da’anzhai member to the Toarcian Oceanic Anoxic Event (T-OAE) are controversial. Previous studies have focused on sedimentary facies analysis based on mineralogy and elemental abundances and have provided minimal information about organic geochemistry, which adds to the challenge of deeply understanding the influence of the T-OAE on the molecular geochemical characteristics of the Da’anzhai member. In this study, the Da’anzhai member of the Lower Jurassic Ziliujing Formation in the Langzhong area, Sichuan Basin, is studied via X-ray diffraction, total organic carbon, gas chromatography–mass spectrometry, organic carbon isotope, organic petrographical and pyrolysis analyses. To accurately identify the trend of the paleosedimentary environmental proxies, the Mann‒Kendall test is utilized to identify the trend of the data. Our results show that the Da’anzhai shale was deposited in a dysoxic transitional environment to an intermittent reducing environment with freshwater to brackish conditions. The response to the T-OAE can be identified in the middle and upper parts of the middle submember and the bottom of the upper submember of the Da’anzhai member. The T-OAE influenced the redox conditions, salinity, and OM origins during deposition in the middle of the Da’anzhai member, which resulted in the enrichment of OM. The abnormally high C30 diahopane/C30 hopane (C30D/C30H) ratio can be considered a potential proxy for locating the section of strata that responded to the T-OAE in the Da’anzhai member. In the study area, the mechanism of the response of the Da’anzhai shale to the T-OAE manifested as an improvement in hydrological cycling rather than a marine incursion. Our study provides new information that deepens the understanding of the mechanisms of the response of lacustrine shales to oceanic anoxic events from the perspective of molecular organic geochemistry.
Non-invasive detection of regulatory T cells with Raman spectroscopy
Authors: Pavillon N. , Lim E. L. , Tanaka A. , Hori S. , Sakaguchi S. , Smith N. I.
Published: June 2024

Regulatory T cells (Tregs) are a type of lymphocyte that is key to maintaining immunological self-tolerance, with great potential for therapeutic applications. A long-standing challenge in the study of Tregs is that the only way they can be unambiguously identified is by using invasive intracellular markers. Practically, the purification of live Tregs is often compromised by other cell types since only surrogate surface markers can be used. We present here a non-invasive method based on Raman spectroscopy that can detect live unaltered Tregs by coupling optical detection with machine learning implemented with regularized logistic regression. We demonstrate the validity of this approach first on murine cells expressing a surface Foxp3 reporter, and then on peripheral blood human T cells. By including methods to account for sample purity, we could generate reliable models that can identify Tregs with an accuracy higher than 80%, which is already comparable with typical sorting purities achievable with standard methods that use proxy surface markers. We could also demonstrate that it is possible to reliably detect Tregs in fully independent donors that are not part of the model training, a key milestone for practical applications.
Evaluation of the impact of systemic dexamethasone dosage on docetaxel-induced hand-foot syndrome in patients with breast cancer
Authors: Saito Yoshitaka , Takekuma Yoh , Takahashi Masato , Oshino Tomohiro , Sugawara Mitsuru
Published: June 2024

Hand-foot syndrome (HFS) is a frequently occurring and treatment-requiring adverse effect of docetaxel. We previously reported that systemic dexamethasone (DEX) prevents the other docetaxel-induced adverse inflammatory effects in a dose-dependent manner. This study aimed to evaluate the dose-dependent efficacy of systemic DEX in attenuating HFS in patients with breast cancer receiving docetaxel. Patients with breast cancer receiving docetaxel (75 mg/m2)-containing regimens (n = 111) were divided into 4 and 8 mg/day DEX groups, with each DEX dose administered on days 2–4, and analyzed retrospectively. Development of all-grade HFS in all treatment cycles was significantly lower in the 8 mg group (50.0%) than in the 4 mg group (73.0%, P = 0.03), with primary endpoint accomplishment. Moreover, its development in the first cycle was also lower in the 8 mg group than in the 4 mg group. These results were confirmed in a propensity score-matched population. Logistic regression analysis suggested higher DEX dosage as an independent preventive factor (adjusted odds ratio 0.35; 95% confidence interval 0.14–0.86, P = 0.02 for all cycles; 0.26, 0.11–0.63, P = 0.003 for the first cycle). Our study suggests that systemic DEX prevents the occurrence of docetaxel-induced HFS in patients with breast cancer in a dose-dependent manner in a real-world setting.
Impact of green innovation on carbon reduction in China
Authors: Shan Haiyan , Shao Shangmiao
Published: June 2024

Green innovation directly encompasses the two major concepts of green and innovation in the new development concepts, which provides a powerful driving force to support Chinese-style modernisation. This paper empirically tests the relationship between green innovation and carbon emission intensity using a double fixed effects model. Based on the panel data of 30 provinces in China, the mediation effect model of “green innovation-big data-carbon emission” is constructed. The result shows that green innovation has a noticeable direct negative effect on urban carbon emission intensity. The conclusions are robust after considering measurement errors and endogenous problems. Furthermore, it is found that big data plays a significant role in strengthening the relationship between green innovation and carbon emission intensity. The findings in this study not only advance the study on green innovation and carbon emissions but also provide a new perspective on the role of big data.
Identification of a novel monocyte/macrophage-related gene signature for predicting survival and immune response in acute myeloid leukemia
Authors: Zhan Yun , Ma Sixing , Zhang Tianzhuo , Zhang Luxin , Zhao Peng , Yang Xueying , Liu Min , Cheng Weiwei , Li Ya , Wang Jishi
Published: June 2024

Acute myeloid leukemia (AML) is a heterogeneous hematological tumor with poor immunotherapy effect. This study was to develop a monocyte/macrophage-related prognostic risk score (MMrisk) and identify new therapeutic biomarkers for AML. We utilized differentially expressed genes (DEGs) in combination with single-cell RNA sequencing to identify monocyte/macrophage-related genes (MMGs). Eight genes were selected for the construction of a MMrisk model using univariate Cox regression analysis and LASSO regression analysis. We then validated the MMrisk on two GEO datasets. Lastly, we investigated the immunologic characteristics and advantages of immunotherapy and potential targeted drugs for MMrisk groups. Our study identified that the MMrisk is composed of eight MMGs, including HOPX, CSTB, MAP3K1, LGALS1, CFD, MXD1, CASP1 and BCL2A1. The low MMrisk group survived longer than high MMrisk group (P < 0.001). The high MMrisk group was positively correlated with B cells, plasma cells, CD4 memory cells, Mast cells, CAFs, monocytes, M2 macrophages, Endothelial, tumor mutation, and most immune checkpoints (PD1, Tim-3, CTLA4, LAG3). Furthermore, drug sensitivity analysis showed that AZD.2281, Axitinib, AUY922, ABT.888, and ATRA were effective in high-risk MM patients. Our research shows that MMrisk is a potential biomarker which is helpful to identify the molecular characteristics of AML immunology.
Adiposity in mares induces insulin dysregulation and mitochondrial dysfunction which can be mitigated by nutritional intervention
Authors: Fresa Kyle , Catandi Giovana D. , Whitcomb Luke , Gonzalez-Castro Raul A. , Chicco Adam J. , Carnevale Elaine M.
Published: June 2024

Obesity is a complex disease associated with augmented risk of metabolic disorder development and cellular dysfunction in various species. The goal of the present study was to investigate the impacts of obesity on the metabolic health of old mares as well as test the ability of diet supplementation with either a complex blend of nutrients designed to improve equine metabolism and gastrointestinal health or L-carnitine alone to mitigate negative effects of obesity. Mares (n = 19, 17.9 ± 3.7 years) were placed into one of three group: normal-weight (NW, n = 6), obese (OB, n = 7) or obese fed a complex diet supplement for 12 weeks (OBD, n = 6). After 12 weeks and completion of sample collections, OB mares received L-carnitine alone for an additional 6 weeks. Obesity in mares was significantly associated with insulin dysregulation, reduced muscle mitochondrial function, and decreased skeletal muscle oxidative capacity with greater ROS production when compared to NW. Obese mares fed the complex diet supplement had better insulin sensivity, greater cell lipid metabolism, and higher muscle oxidative capacity with reduced ROS production than OB. L-carnitine supplementation alone did not significantly alter insulin signaling, but improved lipid metabolism and muscle oxidative capacity with reduced ROS. In conclusion, obesity is associated with insulin dysregulation and altered skeletal muscle metabolism in older mares. However, dietary interventions are an effective strategy to improve metabolic status and skeletal muscle mitochondrial function in older mares.
Variant level heritability estimates of type 2 diabetes in African Americans
Authors: Armstrong Nicole D. , Patki Amit , Srinivasasainagendra Vinodh , Ge Tian , Lange Leslie A. , Kottyan Leah , Namjou Bahram , Shah Amy S. , Rasmussen-Torvik Laura J. , Jarvik Gail P. , Meigs James B. , Karlson Elizabeth W. , Limdi Nita A. , Irvin Marguerite R. , Tiwari Hemant K.
Published: June 2024

Type 2 diabetes (T2D) is caused by both genetic and environmental factors and is associated with an increased risk of cardiorenal complications and mortality. Though disproportionately affected by the condition, African Americans (AA) are largely underrepresented in genetic studies of T2D, and few estimates of heritability have been calculated in this race group. Using genome-wide association study (GWAS) data paired with phenotypic data from ~ 19,300 AA participants of the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, Genetics of Hypertension Associated Treatments (GenHAT) study, and the Electronic Medical Records and Genomics (eMERGE) network, we estimated narrow-sense heritability using two methods: Linkage-Disequilibrium Adjusted Kinships (LDAK) and Genome-Wide Complex Trait Analysis (GCTA). Study-level heritability estimates adjusting for age, sex, and genetic ancestry ranged from 18% to 34% across both methods. Overall, the current study narrows the expected range for T2D heritability in this race group compared to prior estimates, while providing new insight into the genetic basis of T2D in AAs for ongoing genetic discovery efforts.