bluuebunny/crossref_metadata_2025 huggingface dataset:
Co-inhibition of glutaminolysis and one-carbon metabolism promotes ROS accumulation leading to enhancement of chemotherapeutic efficacy in anaplastic thyroid cancer
Authors: Hwang Yeseong , Yun Hyeok Jun , Jeong Jae Woong , Kim Minki , Joo Seyeon , Lee Hae-Kyung , Chang Hang-Seok , Kim Seok-Mo , Fang Sungsoon
Published: August 2023

Anaplastic thyroid cancer (ATC) is one of the most aggressive tumors with an extremely poor prognosis. Based on the several biological features related to glutamine metabolism in ATC, we hypothesized glutaminolysis inhibition induces cell death in ATC cells. However, glutamine metabolism inhibition triggered cell growth arrest independent of cell death in ATC, suggesting that other signaling pathways avoid glutamine metabolism inhibition-induced stress exist. To investigate the functional mechanism against glutamine metabolism inhibition, we conducted mRNA and ATAC-Sequencing data analysis and found that glutamine deprivation increased ATF4-mediated one-carbon metabolism. When we inhibited PHGDH, the first rate-limiting enzyme for one-carbon metabolism, cell growth arrest was promoted upon glutamine metabolism inhibition by accumulating intracellular ROS. We next observed that the co-inhibition of glutamine and one-carbon metabolism could augment the anticancer effects of drugs used in patients with ATC. Finally, single-cell RNA sequencing analysis revealed that one-carbon metabolism was strengthened through the evolutionary process from PTC to ATC. Collectively, our data demonstrate that one-carbon metabolism has a potential role of modulation of cell fate in metabolic stress and can be a therapeutic target for enhancing antitumor effects in ATC.
Hypertonic saline induces inflammation in human macrophages through the NLRP1 inflammasome
Authors: Sposito Francesca , Northey Sarah , Charras Amandine , McNamara Paul S. , Hedrich Christian M.
Published: August 2023

Nebulized hypertonic saline (3–7%) is commonly used to increase mucociliary clearance in patients with chronic airway disease and/or virus infections. However, altered salt concentrations may contribute to inflammatory responses. The aim of this study was to investigate whether 500 mM NaCl (3%) triggers inflammation in human macrophages and identify the molecular mechanisms involved. NaCl-induced pyroptosis, IL-1β, IL-18 and ASC speck release were measured in primary human monocyte-derived macrophages. Treatment with the recombinant IL-1 receptor antagonist anakinra or the NLRP3 inhibitor MCC950 did not affect NaCl-mediated inflammasome assembly. Knock-down of NLRP1 expression, but not of NLRP3 and NLRC4, reduced NaCl-induced pyroptosis, pro-inflammatory cytokine and ASC speck release from human THP-1-derived macrophages. Data from this study suggest that 3% NaCl-induced inflammatory responses in human macrophages depend on NLRP1 and inflammasome assembly. Targeting inflammation in addition to inhalation with hypertonic saline may benefit patients with inflammatory airway disease.
Non-interferometric stand-alone single-shot holographic camera using reciprocal diffractive imaging
Authors: Oh Jeonghun , Hugonnet Herve , Park YongKeun
Published: August 2023

An ideal holographic camera measures the amplitude and phase of the light field so that the focus can be numerically adjusted after the acquisition, and depth information about an imaged object can be deduced. The performance of holographic cameras based on reference-assisted holography is significantly limited owing to their vulnerability to vibration and complex optical configurations. Non-interferometric holographic cameras can resolve these issues. However, existing methods require constraints on an object or measurement of multiple-intensity images. In this paper, we present a holographic image sensor that reconstructs the complex amplitude of scattered light from a single-intensity image using reciprocal diffractive imaging. We experimentally demonstrate holographic imaging of three-dimensional diffusive objects and suggest its potential applications by imaging a variety of samples under both static and dynamic conditions.
Identification of a drug binding pocket in TMEM16F calcium-activated ion channel and lipid scramblase
Authors: Feng Shengjie , Puchades Cristina , Ko Juyeon , Wu Hao , Chen Yifei , Figueroa Eric E. , Gu Shuo , Han Tina W. , Ho Brandon , Cheng Tong , Li Junrui , Shoichet Brian , Jan Yuh Nung , Cheng Yifan , Jan Lily Yeh
Published: August 2023

The dual functions of TMEM16F as Ca2+-activated ion channel and lipid scramblase raise intriguing questions regarding their molecular basis. Intrigued by the ability of the FDA-approved drug niclosamide to inhibit TMEM16F-dependent syncytia formation induced by SARS-CoV-2, we examined cryo-EM structures of TMEM16F with or without bound niclosamide or 1PBC, a known blocker of TMEM16A Ca2+-activated Cl- channel. Here, we report evidence for a lipid scrambling pathway along a groove harboring a lipid trail outside the ion permeation pore. This groove contains the binding pocket for niclosamide and 1PBC. Mutations of two residues in this groove specifically affect lipid scrambling. Whereas mutations of some residues in the binding pocket of niclosamide and 1PBC reduce their inhibition of TMEM16F-mediated Ca2+ influx and PS exposure, other mutations preferentially affect the ability of niclosamide and/or 1PBC to inhibit TMEM16F-mediated PS exposure, providing further support for separate pathways for ion permeation and lipid scrambling.
Characterizing cancer metabolism from bulk and single-cell RNA-seq data using METAFlux
Authors: Huang Yuefan , Mohanty Vakul , Dede Merve , Tsai Kyle , Daher May , Li Li , Rezvani Katayoun , Chen Ken
Published: August 2023

Cells often alter metabolic strategies under nutrient-deprived conditions to support their survival and growth. Characterizing metabolic reprogramming in the tumor microenvironment (TME) is of emerging importance in cancer research and patient care. However, recent technologies only measure a subset of metabolites and cannot provide in situ measurements. Computational methods such as flux balance analysis (FBA) have been developed to estimate metabolic flux from bulk RNA-seq data and can potentially be extended to single-cell RNA-seq (scRNA-seq) data. However, it is unclear how reliable current methods are, particularly in TME characterization. Here, we present a computational framework METAFlux (METAbolic Flux balance analysis) to infer metabolic fluxes from bulk or single-cell transcriptomic data. Large-scale experiments using cell-lines, the cancer genome atlas (TCGA), and scRNA-seq data obtained from diverse cancer and immunotherapeutic contexts, including CAR-NK cell therapy, have validated METAFlux’s capability to characterize metabolic heterogeneity and metabolic interaction amongst cell types.
Biosensor Guided Polyketide Synthases Engineering for Optimization of Domain Exchange Boundaries
Authors: Englund Elias , Schmidt Matthias , Nava Alberto A. , Klass Sarah , Keiser Leah , Dan Qingyun , Katz Leonard , Yuzawa Satoshi , Keasling Jay D.
Published: August 2023

Type I modular polyketide synthases (PKSs) are multi-domain enzymes functioning like assembly lines. Many engineering attempts have been made for the last three decades to replace, delete and insert new functional domains into PKSs to produce novel molecules. However, inserting heterologous domains often destabilize PKSs, causing loss of activity and protein misfolding. To address this challenge, here we develop a fluorescence-based solubility biosensor that can quickly identify engineered PKSs variants with minimal structural disruptions. Using this biosensor, we screen a library of acyltransferase (AT)-exchanged PKS hybrids with randomly assigned domain boundaries, and we identify variants that maintain wild type production levels. We then probe each position in the AT linker region to determine how domain boundaries influence structural integrity and identify a set of optimized domain boundaries. Overall, we have successfully developed an experimentally validated, high-throughput method for making hybrid PKSs that produce novel molecules.
Triplet correlations in Cooper pair splitters realized in a two-dimensional electron gas
Authors: Wang Qingzhen , ten Haaf Sebastiaan L. D. , Kulesh Ivan , Xiao Di , Thomas Candice , Manfra Michael J. , Goswami Srijit
Published: August 2023

Cooper pairs occupy the ground state of superconductors and are typically composed of maximally entangled electrons with opposite spin. In order to study the spin and entanglement properties of these electrons, one must separate them spatially via a process known as Cooper pair splitting (CPS). Here we provide the first demonstration of CPS in a semiconductor two-dimensional electron gas (2DEG). By coupling two quantum dots to a superconductor-semiconductor hybrid region we achieve efficient Cooper pair splitting, and clearly distinguish it from other local and non-local processes. When the spin degeneracy of the dots is lifted, they can be operated as spin-filters to obtain information about the spin of the electrons forming the Cooper pair. Not only do we observe a near perfect splitting of Cooper pairs into opposite-spin electrons (i.e. conventional singlet pairing), but also into equal-spin electrons, thus achieving triplet correlations between the quantum dots. Importantly, the exceptionally large spin-orbit interaction in our 2DEGs results in a strong triplet component, comparable in amplitude to the singlet pairing. The demonstration of CPS in a scalable and flexible platform provides a credible route to study on-chip entanglement and topological superconductivity in the form of artificial Kitaev chains.
Stability follows efficiency based on the analysis of a large perovskite solar cells ageing dataset
Authors: Hartono Noor Titan Putri , Köbler Hans , Graniero Paolo , Khenkin Mark , Schlatmann Rutger , Ulbrich Carolin , Abate Antonio
Published: August 2023

While perovskite solar cells have reached competitive efficiency values during the last decade, stability issues remain a critical challenge to be addressed for pushing this technology towards commercialisation. In this study, we analyse a large homogeneous dataset of Maximum Power Point Tracking (MPPT) operational ageing data that we collected with a custom-built High-throughput Ageing System in the past 3 years. In total, 2,245 MPPT ageing curves are analysed which were obtained under controlled conditions (continuous illumination, controlled temperature and atmosphere) from devices comprising various lead-halide perovskite absorbers, charge selective layers, contact layers, and architectures. In a high-level statistical analysis, we find a correlation between the maximum reached power conversion efficiency (PCE) and the relative PCE loss observed after 150-hours of ageing, with more efficient cells statistically also showing higher stability. Additionally, using the unsupervised machine learning method self-organising map, we cluster this dataset based on the degradation curve shapes. We find a correlation between the frequency of particular shapes of degradation curves and the maximum reached PCE.
Deep learning for obstructive sleep apnea diagnosis based on single channel oximetry
Authors: Levy Jeremy , Álvarez Daniel , Del Campo Félix , Behar Joachim A.
Published: August 2023

Obstructive sleep apnea (OSA) is a serious medical condition with a high prevalence, although diagnosis remains a challenge. Existing home sleep tests may provide acceptable diagnosis performance but have shown several limitations. In this retrospective study, we used 12,923 polysomnography recordings from six independent databases to develop and evaluate a deep learning model, called OxiNet, for the estimation of the apnea-hypopnea index from the oximetry signal. We evaluated OxiNet performance across ethnicity, age, sex, and comorbidity. OxiNet missed 0.2% of all test set moderate-to-severe OSA patients against 21% for the best benchmark.
Molecular mechanism underlying regulation of Arabidopsis CLCa transporter by nucleotides and phospholipids
Authors: Yang Zhao , Zhang Xue , Ye Shiwei , Zheng Jingtao , Huang Xiaowei , Yu Fang , Chen Zhenguo , Cai Shiqing , Zhang Peng
Published: August 2023

Chloride channels (CLCs) transport anion across membrane to regulate ion homeostasis and acidification of intracellular organelles, and are divided into anion channels and anion/proton antiporters. Arabidopsis thaliana CLCa (AtCLCa) transporter localizes to the tonoplast which imports NO3− and to a less extent Cl− from cytoplasm. The activity of AtCLCa and many other CLCs is regulated by nucleotides and phospholipids, however, the molecular mechanism remains unclear. Here we determine the cryo-EM structures of AtCLCa bound with NO3− and Cl−, respectively. Both structures are captured in ATP and PI(4,5)P2 bound conformation. Structural and electrophysiological analyses reveal a previously unidentified N-terminal β-hairpin that is stabilized by ATP binding to block the anion transport pathway, thereby inhibiting the AtCLCa activity. While AMP loses the inhibition capacity due to lack of the β/γ- phosphates required for β-hairpin stabilization. This well explains how AtCLCa senses the ATP/AMP status to regulate the physiological nitrogen-carbon balance. Our data further show that PI(4,5)P2 or PI(3,5)P2 binds to the AtCLCa dimer interface and occupies the proton-exit pathway, which may help to understand the inhibition of AtCLCa by phospholipids to facilitate guard cell vacuole acidification and stomatal closure. In a word, our work suggests the regulatory mechanism of AtCLCa by nucleotides and phospholipids under certain physiological scenarios and provides new insights for future study of CLCs.
A lab-based test of the gravitational redshift with a miniature clock network
Authors: Zheng Xin , Dolde Jonathan , Cambria Matthew C. , Lim Hong Ming , Kolkowitz Shimon
Published: August 2023

Einstein’s theory of general relativity predicts that a clock at a higher gravitational potential will tick faster than an otherwise identical clock at a lower potential, an effect known as the gravitational redshift. Here we perform a laboratory-based, blinded test of the gravitational redshift using differential clock comparisons within an evenly spaced array of 5 atomic ensembles spanning a height difference of 1 cm. We measure a fractional frequency gradient of [ − 12.4 ± 0. 7(stat) ± 2. 5(sys)] × 10−19/cm, consistent with the expected redshift gradient of − 10.9 × 10−19/cm. Our results can also be viewed as relativistic gravitational potential difference measurements with sensitivity to mm scale changes in height on the surface of the Earth. These results highlight the potential of local-oscillator-independent differential clock comparisons for emerging applications of optical atomic clocks including geodesy, searches for new physics, gravitational wave detection, and explorations of the interplay between quantum mechanics and gravity.
Self-anticoagulant sponge for whole blood auto-transfusion and its mechanism of coagulation factor inactivation
Authors: Xu Tao , Ji Haifeng , Xu Lin , Cheng Shengjun , Liu Xianda , Li Yupei , Zhong Rui , Zhao Weifeng , Kizhakkedathu Jayachandran N. , Zhao Changsheng
Published: August 2023

Clinical use of intraoperative auto-transfusion requires the removal of platelets and plasma proteins due to pump-based suction and water-soluble anticoagulant administration, which causes dilutional coagulopathy. Herein, we develop a carboxylated and sulfonated heparin-mimetic polymer-modified sponge with spontaneous blood adsorption and instantaneous anticoagulation. We find that intrinsic coagulation factors, especially XI, are inactivated by adsorption to the sponge surface, while inactivation of thrombin in the sponge-treated plasma effectively inhibits the common coagulation pathway. We show whole blood auto-transfusion in trauma-induced hemorrhage, benefiting from the multiple inhibitory effects of the sponge on coagulation enzymes and calcium depletion. We demonstrate that the transfusion of collected blood favors faster recovery of hemostasis compared to traditional heparinized blood in a rabbit model. Our work not only develops a safe and convenient approach for whole blood auto-transfusion, but also provides the mechanism of action of self-anticoagulant heparin-mimetic polymer-modified surfaces.
Fluorescent protein lifetimes report densities and phases of nuclear condensates during embryonic stem-cell differentiation
Authors: Joron Khalil , Viegas Juliane Oliveira , Haas-Neill Liam , Bier Sariel , Drori Paz , Dvir Shani , Lim Patrick Siang Lin , Rauscher Sarah , Meshorer Eran , Lerner Eitan
Published: August 2023

Fluorescent proteins (FP) are frequently used for studying proteins inside cells. In advanced fluorescence microscopy, FPs can report on additional intracellular variables. One variable is the local density near FPs, which can be useful in studying densities within cellular bio-condensates. Here, we show that a reduction in fluorescence lifetimes of common monomeric FPs reports increased levels of local densities. We demonstrate the use of this fluorescence-based variable to report the distribution of local densities within heterochromatin protein 1α (HP1α) in mouse embryonic stem cells (ESCs), before and after early differentiation. We find that local densities within HP1α condensates in pluripotent ESCs are heterogeneous and cannot be explained by a single liquid phase. Early differentiation, however, induces a change towards a more homogeneous distribution of local densities, which can be explained as a liquid-like phase. In conclusion, we provide a fluorescence-based method to report increased local densities and apply it to distinguish between homogeneous and heterogeneous local densities within bio-condensates.
SnapFISH: a computational pipeline to identify chromatin loops from multiplexed DNA FISH data
Authors: Lee Lindsay , Yu Hongyu , Jia Bojing Blair , Jussila Adam , Zhu Chenxu , Chen Jiawen , Xie Liangqi , Hafner Antonina , Mishra Shreya , Wang Duan Dennis , Strambio-De-Castillia Caterina , Boettiger Alistair , Ren Bing , Li Yun , Hu Ming
Published: August 2023

Multiplexed DNA fluorescence in situ hybridization (FISH) imaging technologies have been developed to map the folding of chromatin fibers at tens of nanometers and up to several kilobases in resolution in single cells. However, computational methods to reliably identify chromatin loops from such imaging datasets are still lacking. Here we present a Single-Nucleus Analysis Pipeline for multiplexed DNA FISH (SnapFISH), to process the multiplexed DNA FISH data and identify chromatin loops. SnapFISH can identify known chromatin loops from mouse embryonic stem cells with high sensitivity and accuracy. In addition, SnapFISH obtains comparable results of chromatin loops across datasets generated from diverse imaging technologies. SnapFISH is freely available at https://github.com/HuMingLab/SnapFISH.
Anxious individuals shift emotion control from lateral frontal pole to dorsolateral prefrontal cortex
Authors: Bramson Bob , Meijer Sjoerd , van Nuland Annelies , Toni Ivan , Roelofs Karin
Published: August 2023

Anxious individuals consistently fail in controlling emotional behavior, leading to excessive avoidance, a trait that prevents learning through exposure. Although the origin of this failure is unclear, one candidate system involves control of emotional actions, coordinated through lateral frontopolar cortex (FPl) via amygdala and sensorimotor connections. Using structural, functional, and neurochemical evidence, we show how FPl-based emotional action control fails in highly-anxious individuals. Their FPl is overexcitable, as indexed by GABA/glutamate ratio at rest, and receives stronger amygdalofugal projections than non-anxious male participants. Yet, high-anxious individuals fail to recruit FPl during emotional action control, relying instead on dorsolateral and medial prefrontal areas. This functional anatomical shift is proportional to FPl excitability and amygdalofugal projections strength. The findings characterize circuit-level vulnerabilities in anxious individuals, showing that even mild emotional challenges can saturate FPl neural range, leading to a neural bottleneck in the control of emotional action tendencies.
Social demographics determinants for resistome and microbiome variation of a multiethnic community in Southern Malaysia
Authors: Dwiyanto J. , Huët M. A. L. , Hussain M. H. , Su T. T. , Tan J. B. L. , Toh K. Y. , Lee J. W. J. , Rahman S. , Chong C. W.
Published: August 2023

The prevalence of antibiotic-resistant bacteria in Southeast Asia is a significant concern, yet there is limited research on the gut resistome and its correlation with lifestyle and environmental factors in the region. This study aimed to profile the gut resistome of 200 individuals in Malaysia using shotgun metagenomic sequencing and investigate its association with questionnaire data comprising demographic and lifestyle variables. A total of 1038 antibiotic resistance genes from 26 classes were detected with a mean carriage rate of 1.74 ± 1.18 gene copies per cell per person. Correlation analysis identified 14 environmental factors, including hygiene habits, health parameters, and intestinal colonization, that were significantly associated with the resistome (adjusted multivariate PERMANOVA, p < 0.05). Notably, individuals with positive yeast cultures exhibited a reduced copy number of 15 antibiotic resistance genes. Network analysis highlighted Escherichia coli as a major resistome network hub, with a positive correlation to 36 antibiotic-resistance genes. Our findings suggest that E. coli may play a pivotal role in shaping the resistome dynamics in Segamat, Malaysia, and its abundance is strongly associated with the community’s health and lifestyle habits. Furthermore, the presence of yeast appears to be associated with the suppression of antibiotic-resistance genes.
Aberrant cortico-thalamo-cerebellar network interactions and their association with impaired cognitive functioning in patients with schizophrenia
Authors: Ha Minji , Park Soo Hwan , Park Inkyung , Kim Taekwan , Lee Jungha , Kim Minah , Kwon Jun Soo
Published: August 2023

Evidence indicating abnormal functional connectivity (FC) among the cortex, thalamus, and cerebellum in schizophrenia patients has increased. However, the role of the thalamus and cerebellum when integrated into intrinsic networks and how those integrated networks interact in schizophrenia patients are largely unknown. We generated an integrative network map by merging thalamic and cerebellar network maps, which were parcellated using a winner-take-all approach, onto a cortical network map. Using cognitive networks, the default mode network (DMN), the dorsal attention network (DAN), the salience network (SAL), and the central executive network (CEN) as regions of interest, the FC of 48 schizophrenia patients was compared with that of 57 healthy controls (HCs). The association between abnormal FC and cognitive impairment was also investigated in patients. FC was lower between the SAL-CEN, SAL-DMN, and DMN-CEN and within-CEN in schizophrenia patients than in HCs. Hypoconnectivity between the DMN-CEN was correlated with impaired cognition in schizophrenia patients. Our findings broadly suggest the plausible role of the thalamus and cerebellum in integrative intrinsic networks in patients, which may contribute to the disrupted triple network and cognitive dysmetria in schizophrenia.
Resting-state perfusion in motor and fronto-limbic areas is linked to diminished expression of emotion and speech in schizophrenia
Authors: Gangl Nicole , Conring Frauke , Federspiel Andrea , Wiest Roland , Walther Sebastian , Stegmayer Katharina
Published: August 2023

Negative symptoms (NS) are a core component of schizophrenia affecting community functioning and quality of life. We tested neural correlates of NS considering NS factors and consensus subdomains. We assessed NS using the Clinical Assessment Interview for Negative Symptoms and the Scale for Assessment of Negative Symptoms. Arterial spin labeling was applied to measure resting-state cerebral blood flow (rCBF) in 47 schizophrenia patients and 44 healthy controls. Multiple regression analyses calculated the relationship between rCBF and NS severity. We found an association between diminished expression (DE) and brain perfusion within the cerebellar anterior lobe and vermis, and the pre-, and supplementary motor area. Blunted affect was linked to fusiform gyrus and alogia to fronto-striatal rCBF. In contrast, motivation and pleasure was not associated with rCBF. These results highlight the key role of motor areas for DE. Considering NS factors and consensus subdomains may help identifying specific pathophysiological pathways of NS.
Optimization of an alum-anchored clinical HIV vaccine candidate
Authors: Rodrigues Kristen A. , Cottrell Christopher A. , Steichen Jon M. , Groschel Bettina , Abraham Wuhbet , Suh Heikyung , Agarwal Yash , Ni Kaiyuan , Chang Jason Y. H. , Yousefpour Parisa , Melo Mariane B. , Schief William R. , Irvine Darrell J.
Published: August 2023

In the ongoing effort to develop a vaccine against HIV, vaccine approaches that promote strong germinal center (GC) responses may be critical to enable the selection and affinity maturation of rare B cell clones capable of evolving to produce broadly neutralizing antibodies. We previously demonstrated an approach for enhancing GC responses and overall humoral immunity elicited by alum-adjuvanted protein immunization via the use of phosphoserine (pSer) peptide-tagged immunogens that stably anchor to alum particles via ligand exchange with the alum particle surface. Here, using a clinically relevant stabilized HIV Env trimer termed MD39, we systematically evaluated the impact of several parameters relevant to pSer tag composition and trimer immunogen design to optimize this approach, including phosphate valency, amino acid sequence of the trimer C-terminus used for pSer tag conjugation, and structure of the pSer tag. We also tested the impact of co-administering a potent saponin/monophosphoryl lipid A (MPLA) nanoparticle co-adjuvant with alum-bound trimers. We identified MD39 trimer sequences bearing an optimized positively-charged C-terminal amino acid sequence, which, when conjugated to a pSer tag with four phosphates and a polypeptide spacer, bound very tightly to alum particles while retaining a native Env-like antigenicity profile. This optimized pSer-trimer design elicited robust antigen-specific GC B cell and serum IgG responses in mice. Through this optimization, we present a favorable MD39-pSer immunogen construct for clinical translation.
C5aR+ dendritic cells fine-tune the Peyer’s patch microenvironment to induce antigen-specific CD8+ T cells
Authors: Kim Sae-Hae , Shim Eun-Hyeon , Kim Doo-Jin , Jang Yong-Suk
Published: August 2023

The mucosal delivery route is considered ideal for immunization. However, induction of antigen-specific mucosal immunity is difficult due to the tolerogenic environment. Therefore, developing an immunogenic mucosal dendritic cell (DC)-targeting strategy is required. Herein, we investigated the characteristics and immunogenic potential of Peyer’s patch (PP) DCs as an oral vaccination-targeting strategy. Single-cell RNA sequencing analysis of the PP DCs showed that complement C5a receptor- and lysozyme-expressing DCs exhibit increased expression of genes related to chemotaxis. Administration of the Co1 peptide, a C5aR ligand, increased CD8+ T cell infiltration and response to the co-delivered model antigen in mice. Furthermore, in the SARS-CoV-2 vaccine model, vaccination with Co1 elicited both systemic and mucosal immunity. Collectively, these findings demonstrate that C5aR signaling in mucosal DCs plays a role in regulating adjuvant activity by modulating the tissue microenvironment.
Interferometric imaging of amplitude and phase of spatial biphoton states
Authors: Zia Danilo , Dehghan Nazanin , D’Errico Alessio , Sciarrino Fabio , Karimi Ebrahim
Published: August 2023

High-dimensional biphoton states are promising resources for quantum applications, ranging from high-dimensional quantum communications to quantum imaging. A pivotal task is fully characterizing these states, which is generally time-consuming and not scalable when projective measurement approaches are adopted; however, new advances in coincidence imaging technologies allow for overcoming these limitations by parallelizing multiple measurements. Here we introduce biphoton digital holography, in analogy to off-axis digital holography, where coincidence imaging of the superposition of an unknown state with a reference state is used to perform quantum state tomography. We apply this approach to single photons emitted by spontaneous parametric down-conversion in a nonlinear crystal when the pump photons possess various quantum states. The proposed reconstruction technique allows for a more efficient (three orders of magnitude faster) and reliable (an average fidelity of 87%) characterization of states in arbitrary spatial modes bases, compared with previously performed experiments. Multiphoton digital holography may pave the route toward efficient and accurate computational ghost imaging and high-dimensional quantum information processing.
On reliability of annotations in contextual emotion imagery
Authors: Martínez-Miwa Carlos A. , Castelán Mario
Published: August 2023

We documented the relabeling process for a subset of a renowned database for emotion-in-context recognition, with the aim of promoting reliability in final labels. To this end, emotion categories were organized into eight groups, while a large number of participants was requested for tagging. A strict control strategy was performed along the experiments, whose duration was 13.45 minutes average per day. Annotators were free to participate in any of the daily experiments (the average number of participants was 28), and a Z-Score filtering technique was implemented to keep trustworthiness of annotations. As a result, the value of the agreement parameter Fleiss’ Kapa increasingly varied from slight to almost perfect, revealing a coherent diversity of the experiments. Our results support the hypothesis that a small number of categories and a large number of voters benefit reliability of annotations in contextual emotion imagery.
Effects of plant growth regulators and sucrose on proliferation and quality of embryogenic tissue in Picea pungens
Authors: Gao Fang , Cao Xi , Qin Caiyun , Chen Shigang , Cai Jufeng , Sun Changbin , Kong Lisheng , Tao Jing
Published: August 2023

Embryogenic tissue (ET) is important for genetic modification and plant re-generation. The proliferation ability and vigor of ET are crucial for plant propagation via somatic embryogenesis. In this study, ET was induced from mature zygotic embryos in blue spruce (Picea pungens Engelm.). There were significant differences in ET induction between two provenances, i.e. 78.8 ± 12.5% and 62.50 ± 12.8% respectively. Effects of 2,4-Dichlorophenoxy acetic acid (2,4-D), 6-Benzyl amino-purine (6-BA) and/or sucrose on ET proliferation and somatic embryo (SE) maturation were further investigated with four cell lines. The highest ET proliferation rate reached 1473.7 ± 556.0% biweekly. Concentrations of 2,4-D or 6-BA applied at tissue proliferation stage impacted SE maturation among the cell lines, whereas sucrose showed less effects. The highest rate, 408 ± 230 mature SEs/g FW, was achieved in SE maturation cultures. This research demonstrated that the culture conditions, i.e. the specific concentrations of 2,4-D and BA, at ET proliferation stage affected not only ET growth, but also the quality of ET for SE maturation. This study revealed the necessity and benefit in developing both the general and the genotype-specific protocols for efficient production of mature SEs, or somatic plants in blue spruce.
Both cell autonomous and non-autonomous processes modulate the association between replication timing and mutation rate
Authors: Vardi-Yaacov Oriya , Yaacov Adar , Rosenberg Shai , Simon Itamar
Published: August 2023

Cancer somatic mutations are the product of multiple mutational and repair processes, some of which are tightly associated with DNA replication. Mutation rates (MR) are known to be higher in late replication timing (RT) regions, but different processes can affect this association. Systematic analysis of the mutational landscape of 2787 tumors from 32 tumor types revealed that approximately one third of the tumor samples show weak association between replication timing and mutation rate. Further analyses revealed that those samples have unique mutational signatures and are enriched with mutations in genes involved in DNA replication, DNA repair and chromatin structure. Surprisingly, analysis of differentially expressed genes between weak and strong RT-MR association groups revealed that tumors with weak association are enriched with genes associated with cell–cell communication and the immune system, suggesting a non-autonomous response to DNA damage.
Monthly runoff prediction based on a coupled VMD-SSA-BiLSTM model
Authors: Zhang Xianqi , Wang Xin , Li Haiyang , Sun Shifeng , Liu Fang
Published: August 2023

The accurate prediction of monthly runoff in the lower reaches of the Yellow River is crucial for the rational utilization of regional water resources, optimal allocation, and flood prevention. This study proposes a VMD-SSA-BiLSTM coupled model for monthly runoff volume prediction, which combines the advantages of Variational Modal Decomposition (VMD) for signal decomposition and preprocessing, Sparrow Search Algorithm (SSA) for BiLSTM model parameter optimization, and Bi-directional Long and Short-Term Memory Neural Network (BiLSTM) for exploiting the bi-directional linkage and advanced characteristics of the runoff process. The proposed model was applied to predict monthly runoff at GaoCun hydrological station in the lower Yellow River. The results demonstrate that the VMD-SSA-BiLSTM model outperforms both the BiLSTM model and the VMD-BiLSTM model in terms of prediction accuracy during both the training and validation periods. The Root-mean-square deviation of VMD-SSA-BiLSTM model is 30.6601, which is 242.5124 and 39.9835 lower compared to the BiLSTM model and the VMD-BiLSTM model respectively; the mean absolute percentage error is 5.6832%, which is 35.5937% and 6.3856% lower compared to the other two models, respectively; the mean absolute error was 19.8992, which decreased by 136.7288 and 25.7274 respectively; the square of the correlation coefficient (R2) is 0.93775, which increases by 0.53059 and 0.14739 respectively; the Nash–Sutcliffe efficiency coefficient was 0.9886, which increased by 0.4994 and 0.1122 respectively. In conclusion, the proposed VMD-SSA-BiLSTM model, utilizing the sparrow search algorithm and bidirectional long and short-term memory neural network, enhances the smoothness of the monthly runoff series and improves the accuracy of point predictions. This model holds promise for the effective prediction of monthly runoff in the lower Yellow River.
Ecobiology of Haemagogus leucocelaenus arbovirus vector in the golden lion tamarin translocation area of Rio de Janeiro, Brazil
Authors: Machado Sergio Lisboa , de Mello Cecilia Ferreira , Silva Shayenne Olsson Freitas , Alencar Jeronimo
Published: August 2023

Significant pathogens that have resurfaced in humans originate from transmission from animal to human populations. In the Americas, yellow fever cases in humans are usually associated with spillover from non-human primates via mosquitoes. The present study characterized the prevalence of the yellow fever vector Haemagogus leucocelaenus in Rio de Janeiro, Brazil. The Atlantic Forest fragment chosen is an area of translocation of the golden lion tamarin (Leontopithecus rosalia), where 10 ovitraps were installed to collect mosquito eggs in Fazenda Três Irmãos, at Silva Jardim city, from March 2020 to October 2022. A total of 1514 eggs were collected, of which 1153 were viable; 50% belonged to medically important mosquito species and 24% to the yellow fever vector species, Hg. leucocelaenus. The months of December 2020 (n = 252), November 2021 (n = 188), and January 2022 (n = 252) had the highest densities of this vector. Haemagogus leucocelaenus was positively correlated with temperature (r = 0.303) and humidity (r = 0.48), with eggs hatching up to the 15th immersion with higher abundance of females. Implementing mosquito monitoring for arbovirus activity can help protect both the golden lion tamarin and human populations from the threat of arbovirus transmission.
Micro-mechanical and tribological behavior of Al/SiC/B4C/CNT hybrid nanocomposite
Authors: Nirala A. , Soren S. , Kumar Navneet , Khan Mohammad Amir , Islam Saiful , Khan Nadeem A
Published: August 2023

The aluminum nanocomposite is fabricated through squeeze stir casting method where CNT, SiC/B4C powder has been used as a reinforcement in an aluminum matrix. Squeeze action in stir casting opted due to proper reinforcement of 2 vol% of CNT in the matrix. The boron carbide and silicon carbide have been added by 8 and 12 vol% in the matrix. Uniform distribution of reinforcement and phase analysis has been shown by scanning electron microscopy (SEM) and XRD analysis. The formation of intermetallic compounds like Al3BC and Al4C3, dislocation forests, and the interaction of the reinforcement with the matrix are all confirmed by transmission electron microscopy (TEM). The micro-mechanical behavior of aluminum nanocomposites was investigated using nano indentation. The nano hardness, Vickers hardness, and Young's modulus of 12 vol% B4C compared with 12 vol% of SiC are increased by 12%, 23%, and 16%, respectively, and the same trend has been observed for the 8 vol% B4C reinforced composite. The model analysis for Young's modulus has been done and the experimental value for the modulus of elasticity of the composite are validated and not find such differences significantly. The surface topography was determined, furrow scratches and wear scars, and it was discovered that B4C reinforced composites have reduced stripping pits inside the wear marks, as well as lower wear width and depth. Wear analysis is essential because abrasive encounters result in substantial damage owing to larger pits and bigger wear scars.
Reduced brain connectivity along the autism spectrum controlled for familial confounding by co-twin design
Authors: Neufeld Janina , Maier Simon , Revers Mirian , Reisert Marco , Kuja-Halkola Ralf , Tebartz van Elst Ludger , Bölte Sven
Published: August 2023

Previous studies on brain connectivity correlates of autism have often focused on selective connections and yielded inconsistent results. By applying global fiber tracking and utilizing a within-twin pair design, we aimed to contribute to a more unbiased picture of white matter connectivity in association with clinical autism and autistic traits. Eighty-seven twin pairs (n = 174; 55% monozygotic; 24 with clinical autism) underwent diffusion tensor imaging. Linear regressions assessed within-twin pair associations between structural brain connectivity of anatomically defined brain regions and both clinical autism and autistic traits. These were explicitly adjusted for IQ, other neurodevelopmental/psychiatric conditions and multiple testing, and implicitly for biological sex, age, and all genetic and environmental factors shared by twins. Both clinical autism and autistic traits were associated with reductions in structural connectivity. Twins fulfilling diagnostic criteria for clinical autism had decreased brainstem-cuneus connectivity compared to their co-twins without clinical autism. Further, twins with higher autistic traits had decreased connectivity of the left hippocampus with the left fusiform and parahippocampal areas. These associations were also significant in dizygotic twins alone. Reduced brainstem-cuneus connectivity might point towards alterations in low-level visual processing in clinical autism while higher autistic traits seemed to be more associated with reduced connectivity in networks involving the hippocampus and the fusiform gyrus, crucial especially for processing of faces and other (higher order) visual processing. The observed associations were likely influenced by both genes and environment.
The effects of Selenohomolanthionine supplementation on the rumen eukaryotic diversity of Shaanbei white cashmere wether goats
Authors: Li Longping , Qu Lei , Li Tuo
Published: August 2023

Selenium (Se) is an important microelement for animal health. However, the knowledge about the effects of Se supplementation on rumen eukaryotic community remains less explored. In this study, the ruminal eukaryotic diversity in three months old Shaanbei white cashmere wether goats, with body weight (26.18 ± 2.71) kg, fed a basal diet [0.016 mg/kg Se dry matter (DM), control group (CG)] were compared to those animals given basal diet supplemented with different levels of organic Se in the form of Selenohomolanthionine (SeHLan), namely low Se group (LSE, 0.3 mg/kg DM), medium Se group (MSE, 0.6 mg/kg Se DM) and high Se group (HSE, 1.2 mg/kg DM) using 18S rRNA amplicon sequencing. Illumina sequencing generated 2,623,541 reads corresponding to 3123 operational taxonomic units (OTUs). Taxonomic analysis revealed that Eukaryota (77.95%) and Fungi (14.10%) were the dominant eukaryotic kingdom in all samples. The predominant rumen eukaryotic phylum was found to be Ciliophora (92.14%), while fungal phyla were dominated by Ascomycota (40.77%), Basidiomycota (23.77%), Mucoromycota (18.32%) and unidentified_Fungi (13.89%). The dominant eukaryotic genera were found to be Entodinium (55.44%), Ophryoscolex (10.51%) and Polyplastron (10.19%), while the fungal genera were dominanted by Mucor (15.39%), Pichia (9.88%), Aspergillu (8.24%), Malassezia (7.73%) and unidentified_Neocallimastigaceae (7.72%). The relative abundance of eukaryotic genera Ophryoscolex, Enoploplastron and fungal genus Mucor were found to differ significantly among the four treatment groups (P < 0.05). Moreover, Spearman correlation analysis revealed that the ciliate protozoa and fungi were negatively correlated with each other. The results of this study provided newer information about the effects of Se on rumen eukaryotic diversity patterns using 18s rRNA high-throughput sequencing technology.
99mTc-macroaggregated albumin SPECT/CT predictive dosimetry and dose-response relationship in uveal melanoma liver metastases treated with first-line selective internal radiation therapy
Authors: Tabotta Flavian , Gnesin Silvano , Dunet Vincent , Ponti Alexandre , Digklia Antonia , Boughdad Sarah , Schaefer Niklaus , Prior John O. , Villard Nicolas , Tsoumakidou Georgia , Denys Alban , Duran Rafael
Published: August 2023

First-line selective internal radiation therapy (SIRT) showed promising outcomes in patients with uveal melanoma liver metastases (UMLM). Patient survival depends on liver’s disease control. SIRT planning is essential and little is known about dosimetry. We investigated whether 99mTc-MAA-SPECT/CT dosimetry could predict absorbed doses (AD) evaluated on 90Y-PET/CT and assess the dose–response relationship in UMLM patients treated with first-line SIRT. This IRB-approved, single-center, retrospective analysis (prospectively collected cohort) included 12 patients (median age 63y, range 43–82). Patients underwent MRI/CT, 18F-FDG-PET/CT before and 3–6 months post-SIRT, and 90Y-PET/CT immediately post-SIRT. Thirty-two target lesions were included. AD estimates in tumor and non-tumor liver were obtained from 99mTc-MAA-SPECT/CT and post-SIRT 90Y-PET/CT, and assessed with Lin’s concordance correlation coefficients (ρc and Cb), Pearson’s coefficient correlation (ρ), and Bland–Altman analyses (mean difference ± standard deviation; 95% limits-of-agreement (LOA)). Influence of tumor characteristics and microsphere type on AD was analyzed. Tumor response was assessed according to size-based, enhancement-based and metabolic response criteria. Mean target lesion AD was 349 Gy (range 46–1586 Gy). Concordance between 99mTc-MAA-SPECT/CT and 90Y-PET/CT tumor dosimetry improved upon dose correction for the recovery coefficient (RC) (ρ = 0.725, ρc = 0.703, Cb = 0.969) with good agreement (mean difference: − 4.93 ± 218.3 Gy, 95%LOA: − 432.8–422.9). Without RC correction, concordance was better for resin microspheres (ρ = 0.85, ρc = 0.998, Cb = 0.849) and agreement was very good between predictive 99mTc-MAA-SPECT/CT and 90Y-PET/CT dosimetry (mean difference: − 4.05 ± 55.9 Gy; 95%LOA: − 113.7–105.6). After RC correction, 99mTc-MAA-SPECT/CT dosimetry overestimated AD (− 70.9 ± 158.9 Gy; 95%LOA: − 382.3–240.6). For glass microspheres, concordance markedly improved with RC correction (ρ = 0.790, ρc = 0.713, Cb = 0.903 vs without correction: ρ = 0.395, ρc = 0.244, Cb = 0.617) and 99mTc-MAA-SPECT/CT dosimetry underestimated AD (148.9 ± 267.5 Gy; 95%LOA: − 375.4–673.2). For non-tumor liver, concordance was good between 99mTc-MAA-SPECT/CT and 90Y-PET/CT dosimetry (ρ = 0.942, ρc = 0.852, Cb = 0.904). 99mTc-MAA-SPECT/CT slightly overestimated liver AD for resin (3.4 ± 3.4 Gy) and glass (11.5 ± 13.9 Gy) microspheres. Tumor AD was not correlated with baseline or post-SIRT lesion characteristics and no dose–response threshold could be identified. 99mTc-MAA-SPECT/CT dosimetry provides good estimates of AD to tumor and non-tumor liver in UMLM patients treated with first-line SIRT.
Time derivatives via interconnected waveguides
Authors: Glyn MacDonald Ross , Yakovlev Alex , Pacheco-Peña Victor
Published: August 2023

Electromagnetic wave-based analogue computing has become an interesting computing paradigm demonstrating the potential for high-throughput, low power, and parallel operations. In this work, we propose a technique for the calculation of derivatives of temporal signals by exploiting transmission line techniques. We consider multiple interconnected waveguides (with some of them being closed-ended stubs) forming junctions. The transmission coefficient of the proposed structure is then tailored by controlling the length and number of stubs at the junction, such that the differentiation operation is applied directly onto the envelope of an incident signal sinusoidally modulated in the time domain. The physics behind the proposed structure is explained in detail and a full theoretical description of this operation is presented, demonstrating how this technique can be used to calculate higher order or even fractional temporal derivatives. We envision that these results may enable the development of further time domain wave-based analogue processors by exploiting waveguide junctions, opening new opportunities for wave-based single operators and systems.